Professional Documents
Culture Documents
Encyclopedia of Clinical Pharmacy
Encyclopedia of Clinical Pharmacy
Encyclopedia of Clinical Pharmacy
edited by
Joseph T. DiPiro
Panoz Professor (fPharmacy
University of Georgia College of Pharmacy
Athens, Georgia, U.S.A.
and
Clinical Professor of Surgery
Medical College of Georgia
Augusta, Georgia, U.S.A.
College of
Clinical Pharmacy
*
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Elaine Chiquette I San Anronio Cochrane Center, San Antonio, Taus, U.S.A.
Marie A. Chisholm I University of Georgia College ofI’harmucy, Athens, Georgia, U.S.A.
Thomas P. Christensen 1 North Dakota State University. Furgo, North Dakota, U.S.A.
Robert J. Cipolle I University of Minnesotu, Minneapolis, Minnesota, U.S.A.
Ana Clopes Ilospitul de Iu Stu. Creu i Sant I’au, Burcelona, Spuin
George H. Cocolas I University of North Curolina, Chupel Hill, North Carolina, U.S.A.
Marisue Cody / I4terans Affuirs Medicul Centec North Little Rock, Arkansas, U.S.A.
.Michael R. Cohen I Institute,for Sa& Medication Practices, Huntington Vulley, Pennsylvuniu, U.S.A.
Anthony Compton / St. Joseph k Hospilal of Atlanta, Atlanta, Georgiu, U.S.A.
Rachel Crafts 1 Idaho Drug Injhrmatian Service, Pocatello, Idaho, U.S.A.
Vicki S. Crane 1 Purklund Ilealth and Hospital System, Dullus, Texus, U.S.A.
Jamie Cristy Solvuy Phurmuceuticub, Atlantu, Georgiu, U.S.A.
Diane B. Crutch field I Pharmucy Consulting Cure, Knoxville, Tennessee, U.S.A.
Vaughn L. Culbcrtson 1 Iduho Stute University, Pocatello, Idaho, U.S.A.
Charles E. Daniels 1 Nalional Institutes of Health, Bethesda, Maryland, U.S.A.
Lisa E. Davis I Philudelphia College of Phurmucy, Philudelphia, Pennsylvania, U.S.A.
Robert DeChristoforo Vireo Lab Inc.. Rockville, Maryland, U.S.A.
Joseph H. Deffenhaugh American Society of Health-System Phurmucists, Bethesda, Maryland, U.S.A.
Joseph T. Di Piro University of Georgia College oj’ Pharmacy, Athens, Georgia, U.S.A.
Nfonso Dominguez-Cil I Hospital Univer.sitario de Salamancu, Sulumunca, Spain
Michael Dooley 1 Peter MacCallum Cancer Institute, Victoria, Austrulia
Julie A. Dopheide / University of Southern Culiforniu, Los Angeles, Cali/brnia, U.S.A.
Steven C. Ebert I Meriter IIospitul, Inc., Mudison, Wisconsin, U.S.A.
Eduardo Echarri Arrieta I Sociedud Espuiiolu de Farmucia Hospitalaria, La Coruca, Spain
Robert M. Elenbaas I Americun College of Clinical Pharmacy, Kansas City, Mimouri, U.S.A.
Mary Ensom I BCk Children k di Womenk Hospital, Vancouver, British Columbiu, Cunadu
Susan C. Fagan I University oj’Geo& College of Pharmacy, Athens, Georgiu, U.S.A.
Bi
l
l C. Felkey j‘ Auburn Univer.si& Auburn, Alabama, U.S.A.
Donald J. Filibeck 1 Mt. Carmel IIome Infusion. Columbus, Ohio, U.S.A.
Benet Fit6 Novellas I Pharmaci.st, Barcelona, Spain
Annemieke Floor-Schreudering j’ European Society of Clinical Phurmacy, Leiden, The Netherlands
Brent I. Fox / Auburn Univer,sity,Auburn, Alabama. U.S.A.
George E. Francisco I Univer,sityof Georgia College of Phurmucy, Athens, Georgia, U.S.A.
John A. Cans I American Pharmaceutical Association, Wushington, D.C., U.S.A.
Steven Celone / Temple University, Philudebhiu, Pennsylvunia, U.S.A.
Claire E. Cilmore I Phi1lb.s Group Oncology Communicutions, Philadelphia, Pennsylvania, U.S.A.
Joaquin Giraldez 1 Clinicu Universituriu de Nuvarru, Pamplona, Spain
Ma. Isabel Crespo Gonzalez I Urbanizucibn Monleclaro, Madrid, Spain
Kathryn L. Grant I University of Arizona, Tucson, Arizona, U.S.A.
Rafael Guayta Escolies I General Directorate of Public Heallh, Autonomous Govern of Cutulonia, Catalonia. Spain
Dave Hachey I Idaho State University, Pocutello, Idaho, U.S.A.
Cindy W.Hamilton 1 Hamilton House, Virginiu Beach, Virginia, U.S.A.
David Hawkins 1 Mercer University, Atlantu, Georgiu, U.S.A.
Dean G. Haxby I Oregon State University, Portland, Oregon, U.S.A.
Yechiel Hckstcr 1 University Medical Centre, N i j m e n , The Nelherlands
Mary Hemming I Therapeutic Guidelines Limited, North Melbourne, Austrulia
Catherine A. Heyncman / Idaho State Universily, Pocalello. Idaho, U.S.A.
Teresa J. Hudson I Veterans AJairs Medical Center, North Little Rock, Arkunsrrv, U.S.A.,
Antonio ldoate I Clinica Universitaria de Navarra, Pamplona, Spain
iii
Richard P. Penna / American Association of Co1lege.s of’ PhurmaLy, Alexandria, Virginia, U.S.A.
Carmen Permanyer Mum6 i Pharmaceutical Association of’ Catalonia, Barcelona. Spain
Matthew Pern I11 i University of Georgia College of Pharmacy, Athens. Georgia. U.S.A.
Vanita K. Pindolia / Henly Ford Health .’+stem, Detroit, Michigun, U.S.A.
Stephen C. Piscitclli / Mrco Lab Inc.. Rockville, Maryland, U.S.A.
Sylvie Poirier / Regie Regionale de la Sunte et de.9 Service.s Sociuux Monteregis Quebec, Cunuda
Therese 1. Poirier / Duyucme University, Pittsburgh, Pennsylvuniu, U.S.A.
Samuel M. Poloyac / University of Pittsburgh, Pittsburgh. Pc’c.nsylvuniu, U.S.A.
Jeff Poston I Canudian Pharmacists Association, Ottawa, Onturio. Canada
Leigh Ann Ramsey / Univer.sity of Missi.ssippi. Jackson, Mississippi. U.SA.
Teresa Rcqucna Caturla / Ifospitul “Principede Asturias ”, Madrid, Spain
Renee E Robinson / The Ohio State Univer.sity, Columbus. Ohio, U.SA.
Chip Rohison BeneScript Services, Incc., Norcross, Georgia U.S.A.
David S. Roffman / University qf Maryland. Baltimore, Maryland, U.S.A.
Brendao S. ROSS/ Department of kteruns Affuirs Medical CenteK Juckson, Mississippi, U.S.A.
Simone Rossi / Austrulian Medicines IIundbook Pty Ltd., Adelaide, Austrulia
Myrella T. Roy / The Ottuwu Hospital, Ottawu, Ontario, Cunuda
John RUSSO, Jr. / The Medical Communicutions Resource, Mahwah, New Jersey, U S A .
Melody Ryan / Univer.sity oJ Kentucb, Lexington, Kentucb, U.S.A.
Rosalie Sagraves / University of Illinois, c‘hicugo, Illinois, U.S.A.
Richard T. Scheife / American College of C‘linical Pharmacy. Boston. Massachusetts. U.S.A.
Lauren Schlcssclman / Niantic, Connecticut. U.S.A.
Patricia H. Schoch I Denver VA Mc.dical Center. Denvec Colorado. U.S.A.
Jon C. Schommer / University of Minnesotu. Minneapolis, Minnesotu, U.S.A.
Terry L. Schwinghammer / University of Pittshuqh School qf‘ Phurmucy, Pittsburgh, Pennsylvunia, U.S.A.
Gayle Nicholas Scott / Medical Communications and Consulting, C’he.sapeake, Mrginia. U.S.A.
Leon Shargel / Eon Labs Manujacturing Inc., Jmmdton, New York, (J.S.A.
Marjorie A Shaw Phillips / Medical College of Georgia Hospitab and Clinics, Augusta,
and University of Georgiu College oj‘Pharmacy, Athens, Georgiu. U.S.A.
Kenneth 1. Shine / Institute of Medicine, Wushington. Di.strict ojColumbiu, U.S.A.
Ingrid S. Sketris / Dalhousie University. Hulifiu, Novu Scotiu, Cunudu
Betsy L. Sleath i University of North Curolina, Chupel Hill, North Carolina, U.S.A.
William E. Smith / Virginia Commonweulth University. Richmond, Mrginia, US.A.
Patrick E Smith / 1Jniversity at Bujlizlo, Buffulo. New b r k , U.S.A.
Mary ROSSSouthworth / (Jniver.sityqf Illinois, Chicago, Illinois, U.SA.
Lara E. Storms I M n i a Commonwealth University School of Pharmacy, Richmond. Virginia, U.S.A.
Lynda Sutton / Cato Research Ltd., Durham, North Carolina, U.S.A.
C. Richard Talley 1 American Society of Health-System Pharmacists, Bethesda. Maryland, U.S.A.
Carl E. Trinca / We.stern University, Pomona, Califbrnia, U.S.A.
Patricc Trouillcr / University Hospital of Crenoble, Grenoble, France
Carl J. Tullio 1 Pfizer. Inc., Yorktown, Mrginia, U S A .
Kimbcrly Vcrnachio / Cunton, Georgia. U.S.A.
Peter H. Vlasscs i American Council on Pharmaceutical Education, Chicago, Illinois. U.S.A.
Jeffrey W. Wadclin / American Council on Pharmaceutical Education. Chicago. Il1inoi.s. U.S.A.
Margaret C. Watson / University qf Aberdeen. Aberdeen, U.K.
Timothy Wcbstcr / American Society of Consultant Pharmaci.st.s, Alexandria, Mrginia, U.S.A.
Barbara G. Wclls / Univecsity of Missi.s.sippi, Univer.sity, Missi.ssippi, U.S.A.
Albert 1. Wertheimer / Temple Univemity, Philudelphiu, Pennsylvania. U.S.A.
Roger L. Williams / U.S. Pharmucopeiu, Rockville, Maryland, U.S.A.
Harold H.Wolf / University of Utah. Salt Lake City, Utah, U.S.A.
V
Computer Software for Clinical Pharmacy Services I Bill C. Felkey m d Brent I . Fox . . . .
Crcdentialing in Pharmacy I Richard J . Bertin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Critical Care Pharmacy Practice I Judith Jacobi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Critical Care Pharmacy Services (ACCP) I American College of Clinical Pliarmacy . . . .
Cytochrome P450 I David 1. Mia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Department of Health and Human Scrvices I Lauren Schlesselinan . . . ......................... 251
Diabetes Care, Pharmacy Practice in I Tommy Johnson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Dietary Supplement Health and Education Act I Chyle Nicholas Scott .. ................. 260
Dircctions for Clinical Practice in Pharmacy (Hilton Head Conference) I Mae Kwnng . . . . . . . . . . . . . . . . . . . . 265
Disease Management I Leigh Ann h'amsey and Hrendarz S. Ross . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Doctor of Pharmacy I GeorgP B. Francisco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Drug Enforcement Agency I Claire E. Cilmoi-e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug History I Christi Cuwood Marsh . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug Information Pharmacy Practicc I Patrick M . Malone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug Samples I Nanette C. Sultemeier and D(.an C. Haxby . . . . ........................... 295
Economic Evaluations of Clinical Pharmacy Services (ACCP) / A ollege ($Clinical Pharmarj . . . . . . 301
Electronic Prescribing I Woodie M . Zachry I11 and Edward P . Armstrong . . . . . . . . . ............ 326
Ethical Issues in Clinical Pharmacy I Teresa K ~ ~ q u e nCaturla a .................................... 330
Ethical Issues Related to Clinical Pharmacy Research (ACCP) / American College of Clinical Pharmacy . . . . . . 335
European Society of Clinical Pharmacy I Annemieke Floor-Schreudering and Yechiel Hekster . . . . . . . . . . . . . . 344
Evidence Based Practice I Christine M . Bond and Margaret C. Watson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
I-kllowships in Pharmacy I Joseph 7. DiPiro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
First DataBank, Inc . I Joan Kapusnik-Uner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358
Formulary Systems I J . Russell May . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
Gene Therapy I Daren L. Knoell and Jill M . Kolesar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Generic Drugs and Generic Equivalency I Arthur H . Kibhe . . . . . . . . . . ......................... 379
Government: Clinical Pharmacy Careers in / Stephen C. Piscitelli and Robert DeChristoforo . . . . . . . . . . . . . . . 385
Health Care Systems: Outside the linited States I Albert I . Wertheimer and Sheldon X . Kong . . . . . . . . . . . . . . 389
Health Care Systems: Within the Unitcd States I Henri R . Marzasse, J r. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Hcalth Scrvices Research I Teresa J . Hudson and Marisue Cody . . . . . . . . . . . . . . . .
Hcalth Status Assessment I Kathleen M . Buizcgay . . . . . . . . . . . . . . . . . . . . . . . . . . .
Health-Systems, Clinical Pharmacy Careers in I William E . Smith . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Healthy People 2010: Objectives for Improving Health / Carl J . Tullio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Home Care, Clinical Pharmacy Careers in I Donald J . Filibeck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Home Care Pharmacy Practice (Spain) I Ana Clopes . . . ............... . 439
Hospice and Palliative Care I Arthur G. Lipman . . . . . . ......................... 441
Hospital Pharmacy Practice in Spain I Joaquiiz Ciruldez, Ana Ortega, Antonio Idoate, Azzicena Aldaz
and Carlo.s Lacasa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453
Hyperlipidemia Pharmacy Practicc I Theresa M . Bianco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
Infectious Diseases Specialty Pharmacy Practice I Steven C. Ebert . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
Institute for Safe Medication Practices I Michael R . Cohen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476
Institute for Safe Medication Practices-Spain I Maria-Jose' Otero and Alfonso Dominguez-Gil . . . . . . . . . . . . . 478
Institute of Medicine I Kenneth 1. Shine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
Integrative Medicine I Kathryn I . Grant and William Bendu . . ..... .. ... . 4x2
International Pharmaceutical Abstracts (ASHP) I Carol Wolfe . . ........................... 481
International Society for Pharmacoeconomics and Outcomes Research I Elizabeth Trucie Long . . . . . . . . 488
Janus Commission (AACP) I Richard P . Penna . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
Joint Commission for the Accreditation of Health-Care Organizations I Kathryn T. Andrusko-Furphy . .
Joint Commission of Pharmacy Practitioners (JCPP) I Robert M . Elenhaas . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Long-Term Care, Clinical Pharmacy Careers in / Diane B . Crutchfield . . . . . . . . . . . . . . . . . . . . . . .
Managed Care, Clinical Pharmacy Careers in I Barbara Zarowitz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501
Managed Care Pharmacy Practice I Beverly L. Black . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
Medicaid and Medicare Pharmaceutical Programs / Albert I . Wertheimer and Stephen H . Paul . . . . . . . . . . . . . . 512
Medical Communications, Clinical Pharmacy Careers in / Lara E . Storms and Cindy W. Hamilton . . . . . . . . . . . 519
iX
Role of the Clinical Pharmacist in Clinical Trials (Spain) I Josi-Bruno Montoro-Konsano . , . . . . . . . . . . . . . , . 843
Society of Hospital Pharmacists of Australia, The I Naomi Burgess . . ................... 85 1
Spanish Society of Hospital Pharmacy I Ma. Isabel Crespo Gonznlez . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 854
Therapeutic Guidelines Australia I Mary Hemming . . . . . . . . . . . . . . . . . . . . . . . . . ............. 857
Therapeutic Interchange I Anthony Compton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . 860
Therapeutic Interchange, Guidelines (ACCP) I American College of Clinical Pharmacy . ............ 864
Transplantation Pharmacy Practicc I Onan E. Bajoku and Marwan S. Abouljoud . . . . . . . . . . . . . . . . . . . . . . . 869
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans I Yasmin Khaliq 876
UK Clinical Pharmacy Association I Pat Murray . . ................. ................... 883
1Jnited States Pharrnacopeia I Roger L. Williams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
Universal Precautions and Post-exposure Prophylaxis for HIV I Brent M. Booker, Patrick F. Smith
andGenrD.Morse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 1
Walton, Charlcs I David Huwkins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 899
Weaver, Lawrence I Robert .I. Cipolle ......... ..................................... 902
World Health Organization I Putrice Trouiller . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904
World Health Organization Essential Drug List / Palrice Trouiller . . .........._____.... ...
908
Everyone reading this foreword already knows that clinical pharmacy is evidence-based. Those in the field rely
heavily on therapeutics textbooks, drug information compendia, journal articles, and thc World Wide Web as
critical sources of information and knowledge to guide their patient care and research decisions. So what can
a resource like the Encyclopedia o j Clinical Pharmacy add to the growing (and some might say already over-
crowded) library of professional literature?
This encyclopedia is not intended to be a textbook of therapeutics or a compendium of drug information.
Rather, its goal is to document information about key people, events, publications, legislation, regulations, and the
myriad of things other than therapeutics per se that shape what clinical pharmacists do, why thcy do it, and how
they do it. It was this opportunity that convinced the American College of Clinical Pharmacy and the American
Society of Health-System Pharmacists to partner with Marcel Dekker, Tnc. in this unique project.
Although efforts to publish the Encyclopedia of Clinical Pharmacy began in early 1999, its true origins lie
in the pioneering work of visionary pharmacists like Donald Brodie, Donald Francke, Paul Parker, Harvcy A. K.
Whitney, and others in the 1950s, ' ~ O S ,and '70s. They foresaw the increasing complexity of pharmacotherapy, the
problems or medication-related morbidity and mortality, and the impact that clinically empowered pharmacists
have on assuring safe and effective pharmaceutical care for patients. The Encyclopedia of Clinical Pharmacy-in
print and online-is designed to be a dynamic resource that will expand as future events unfurl and as time allows
a more complete documentation of important past contributions and contributors. Thus, as clinical pharmacy con-
tinues to evolve, so will the Encyclopedia.
Joseph T. DiPiro
Encyclopedia of
Clinical Pharmacy
PROFESSIONAL DEVELOPMENT
pharmacy today are encountering changes in the tenure of higher education from Germany. This research mission
system, a different reward system, and continued evo- requires faculty to generate new knowledge rather than
lution of academic clinical pharmacy. just convey knowledge.[71 Institutions with medical and
health-related profession educational programs
- - also have
practice/patient care as an extension of their service or
Changes in the tenure system
outreach mission.
Unfortunately, by the mid- 1900s the faculty reward
In the early 1900s the tenure system was established so
system, even in institutions with no graduate programs,
that faculty would have the academic freedom to express
had evolved to one in which decisions about faculty
their thoughts without fear of dismissal.[31 Due to sta-
promotions were largely based only on the individuals
tutory repeal of the mandatory retirement age and fi-
research and publication record.[71 The effectiveness of
nancial restrictions in higher education, many institutions
one's teaching was given little, if any consideration at the
are finding tenure limits their flexibility in responding to
time of promotions.
fluctuations in admissions to different degree program^.'^]
In 1990, Boyer called for academia to move beyond this
Advocates believe tenure is necessary since it provides a
problem.[71 He stated that each institution should clearly
healthy environment that encourages new ideas; indivi-
establish its unique missions and measure itself by these
duals can say what they want and be protected from dis-
values rather than the traditional research reputation. To
missal.['] Opponents believe it protects the incompetent
accomplish this, Boyer asserted that higher education
and reduces the flexibility institutions need to be res-
must establish and adopt a new way of defining and
ponsive to new demands such as limited financial re-
rewarding scholarship. Boyer proposed that the term
sources and accountability.
scholarship must take on a broader meaning than just
At most institutions, the tenure system provides new
original research in order to characterize the full scope of
assistant professors a time span of approximately six years
duties an academician is expected to accomplish in today's
in which to demonstrate achievement in teaching, service,
higher-education institutions. He further characterized the
practice. and sch~larship/research.[~] After this window of
scholarship expected among a faculty as encompassing
time, the faculty decides whether to grant tenure. The
four distinct functions: 1) the scholarship of discovery
granting of tenure implies a guaranteed position within
(i.e., original research), 2) the scholarship of application,
the university unless there is financial exigency or the
3) the scholarship of integration, and 4) the scholarship of
faculty member is found guilty of misconduct.
teaching. Glassick and colleagues"] have since facilitated
When contemplating the tenure- versus nontenure-
acceptance of this concept by establishing criteria by
track alternatives, the individual should weigh the benefit
which scholarship can be measured. These criteria have
of academic freedom with the difficulty, stress, and
helped distinguish the difference between achievement of
anxiety that many academicians encounter when trying to
excellence and scholarship. and they are enabling institu-
accomplish promotion and tenure criteria within a six-
tions to place equal value on all four types of schol-
year window. Because clinical pharmacy faculty members
arship.'" Although all four types of scholarship are
have to establish a practice in addition to teaching, scho-
recognized by most institutions, most institutions require
larshiphesearch. and service, these time constraints can be
faculty to excel in only one or two of these four options.
particularly stressful and inflexible.@]To facilitate long-
During the last 11 years, these pivotal reports have led
term success, some institutions are offering clinical fa-
most institutions to reevaluate how faculty members pri-
culty members the opportunity to begin on a nontenure-
oritize their time and the faculty reward system. There-
track and move to the tenure track once their practice and
fore, when contemplating an academic position, an
research abilities are established.
individual should clearly understand the institution's
mission and faculty reward system. The faculty candidate
Changes in the reward system should also ascertain whether the assigned duties can be
accomplished according to the projected allocation of
In the early 1600s when the first colleges were established time and effort and that they are consistent with the
in the United States. the primary college mission of the faculty reward system. Individuals who select either a
faculty was teaching.[71 However, since then our univer- college-based tenure- or nontenure-track position should
sities have added service as a second mission in order to clearly understand that success in academia requires
meet a need of society for practical assistance in everyday achievement of not only excellence in completion of
living, and research as a third mission due to the influence assigned duties, but also s~holarship."~~]
Academia, Clinical Pharmacy Careers in 3
Evolution of clinical pharmacy academicians strategies to ensure that both faculty models are equally
respected and valued, and the relative proportions of each
Similar to the evolution of other clinical disciplines, faculty model that are needed at a pharmacy school in
clinical pharmacy practice grew from the commitment order to achieve the institutional mission."'2~6"01
of a cadre of clinicians who contributed significant time in
practice and teaching."01 Because they had little time for
research and scholarship and often had limited skills in
these areas, early clinical pharmacy academicians were As noted above, a faculty member's roles and specific
sometimes viewed as quasi-faculty members. In the last responsibilities are largely determined by the institution's
30 years, the discipline has overcome this stigma by mission and the assigned duties. Although there are
establishing peer-reviewed discipline-specific journals, differences in the percentage of time that is assigned to
becoming accepted authors to journals of other academic the areas of teaching, practice, scholarship/research, and
disciplines, and developing specialty residency and fel- service, all college-based faculty members are expected to
lowship programs that prepare future clinical pharmacy demonstrate some level of scholarship." 91
faculty members for academic careers. Because faculty members have significant autonomy in
The discipline now also has a cadre of clinical sci- accomplishing university assignments, their responsibil-
entists who are fulfilling the typical academic scientist ities are not always clearly defined. Kennedy[13] has
role; but in order to accomplish this, these individuals concluded that in accepting academic freedom, academi-
have had to focus primarily on teaching and research with cians must also realize their academic duty to the in-
minimal activities in practice. Since the fundamental role stitution. Kennedy further vows that academic duty is
of the discipline is to prepare students for actual practice, accomplished by meeting a set of responsibilities. He
a cadre of clinical faculty whose primary duties are notes that the primary responsibility of academia is to
practice and teaching are therefore also essential. meet the needs of society since it nurtures our existence.
Because a broader definition of scholarship is now Faculty members can help accomplish this by meeting
accepted in higher education and it is realized that fa- specific responsibilities such as: 1) accomplishing all four
culty members cannot effectively accomplish all four missions/responsibilities with excellence, 2 ) demonstrat-
missions, two faculty models are most frequently used ing commitment to students by mentoring and being well-
today. Individuals who assume the practitioner-educator prepared for classes, 3) maintaining high standards of
model are enabled to accomplish either the scholarship individual scholarship, 4) working "collegially" with
of integration. application, and/or teaching because of other faculty members so that all academic missions are
their focus on teaching and practice. Individuals who accomplished, and 5) completing all assignments eth-
fulfill the researcher-educator model are able to pursue ically. It should be emphasized that collegiality requires
the scholarship of discovery because they have minimal the faculty member to be a team member by actively
practice expectations. contributing to the departmental and school/college work
Although clinical pharmacy has established itself in and actively participating in decision-making; collegiality
academia, it is still in its infancy and there are unresolved does not infer that the faculty member is just friendly to
needs. Individuals who are planning for an academic everyone. Kennedy also notes that academicians have a
clinical pharmacy career or who are pursuing an academic responsibility of commitment such that outside activities
position should talk with their mentors and do further (e.g., consulting) do not interfere with one's responsibil-
reading about these needs. For example, fellowship- ities to the university.
training programs are providing fellows with too little
time devoted to development of research abilities and too
much time devoted to teaching and practice."" It has
been proposed that clinical pharmacy training programs at SITES AND SETTINGS
the Ph.D. level may better prepare clinical faculty to
compete for NIH funds and to study the pharmacother- At the present time, there are 84 pharmacy schools in the
apeutic and practice issues that need to be addressed in United States and each has clinical pharmacy faculty
today's healthcare environment."21 Other needs that members. Because the number of new pharmacy schools
pharmacy schools are addressing include development continues to increase and a number of senior faculty
of promotion and tenure guidelines that are equitable and members are likely to retire in upcoming years, it has
consistent with the assigned duties or faculty model, been predicted that we may encounter a shortage of
4 Academia, Clinical Pharmacy Careers in
academic faculty Since the current short- for promotion to the level of associate professor after a
age of pharmacy practitioners is expected to continue in period of 5-7 years.[51At most institutions, this requires
the foreseeable future, the need for new clinical pharmacy demonstration of scholarship/research and excellence in
faculty members will likely persist. accomplishing assigned duties. Most faculty members are
Both public and private institutions serve as the able to achieve the rank of full professor approximately
settings for these pharmacy schools. Therefore, an in- 5-10 years after promotion to the associate professor
dividual pursuing a faculty position should learn about the level. Promotion to this rank usually requires devel-
characteristics of working in each of these settings. Other opment of an established scholarshiph-esearch theme and
considerations when selecting the institutional setting for recognition by peers at a national level.[51The American
your faculty position include whether the institution has Association of Colleges of Pharmacy (AACP) surveys
its own medical center and whether your practice will be pharmacy schools on an annual basis about the salaries of
located at a distant site away from the pharmacy school. each academic rank and publishes the results. Individuals
These factors will greatly impact opportunities for interested in an academic career should review these data
researchkholarship, access to mentors, and ability to to gain insight into the financial aspects of the academic
develop collegial relationships. pharmacy career ladder and growth. These data are
published annually and may be obtained by contacting
either an AACP faculty member or the senior vice
president at AACP.
Once either the associate professor or full professor
rank is achieved, the academician may also opt for an
Today, most academic clinical pharmacy faculty positions academic administration career.[51 An administrative
require a .Pharm.D. degree although individuals with position requires an additional set of knowledge and
another advanced degree may be considered at some skills that emphasize leadership and management. These
institutions. Completion of post-doctoral training pro- attributes may be gained by pursuing postgraduate de-
grams such as specialized residencies and fellowships are grees and, attending workshops and/or fellowships in
also required. Because specialized residencies focus on higher education. Most individuals begin this track by
development of practice skills and teaching, they can serving as a department chair or assistant/associate dean.
appropriately prepare an individual for a tenure-track Success in one of these positions can enable the individual
practitioner-educator or a nontenure-track faculty posi- to become a dean. After several years of experience in any
tion. Individuals who desire a researcher-educator faculty of these positions, an individual may also pursue admi-
position should complete a fellowship that emphasizes nistrative positions in higher education that are outside of
development of research skills. Postgraduate coursework pharmacy schools.
such as biostatistics and research design would also fa-
cilitate success in a researcher-educator position and a
fellowship should provide opportunity to complete such
coursework. Many specialized residency and fellowship
training programs require completion of a general practice Although the need for clinical pharmacy faculty mem-
pharmacy residency as a prerequisite. The requirement for bers will likely continue, the transformation that is oc-
specialty faculty to become board certified is increasing curring in higher education will make the expectations
and individuals planning to enter academic clinical of faculty in the future different than what they have
pharmacy are encouraged to obtain this credential.[l6I been in the past. Individuals contemplating an academic
Some individuals may elect to gain several years of pharmacy career must have a clear understanding about
experience as a practitioner before pursuing either post- the current issues and needs in order to make informed
doctoral training or a faculty position. Although this is not career decisions.
required, the experience can certainly be beneficial.
AR AN
1. Carter, B.L. Chair report of the section of teachers of
Most entry-level faculty positions involve appointments pharmacy practice task force on scholarship definition and
at the level of assistant professor. The successful junior evaluation. Am. J. Pharm. Educ. 1994, 58 ( 2 ) , 220-227.
faculty member usually achieves the criteria established 2. Carter, B.L. Chair report of the AACP section of teachers
Academia, Clinical Pharmacy Careers in 5
of pharmacy practice task force on faculty models. Am. J. New elaborations, new developments. Change 1999, 11
Pharm. Educ. 1992. 56 ( 2 ) , 195 201. 15, SeptemberjQctober.
3. De George, R.T. Academic F r e ~ d u mand Tenure: Ethical 10. Amerson, A.B. The evolution of scholarship in pharmacy
Issues; Iiowman KL Littlefield Publishers, Inc.: Lanham, practice: Examining our direction. Am. J. Pharm. Educ.
Massachusetts, 1997; 1-28. 1992, 56 (4), 421 -424.
4. MeGhan, W.F. Tenure and academic freedom: Vital in- 1 I . Rhoney, D.H.; Brooks, V.G.; Patterson, J.H.; Piper, J.A.
gredients for advancing practice, science, and socicty. Am. Pharmacy fellowship programs in the United States:
J. Pharm. Educ. 1996, 60 (l), 94-97. preceptors. Am. J. Pharm.
5. Heiberger, M.M.; Vick, J.M. Thr Academic Joh Search
Handbook, 2nd Ed.; llniversity of Pennsylvania Press: 12. Cohen, J.L. The need to nurture the clinical pharmaceutical
Philadelphia, Pcnnsylvania, 1996; 161 165.
- sciences. Am. J. Pharm. Educ. 1998, 62 (4), 471.
6. Bradberry, J.C. Some thoughts on promotion and tenure. 13. Kennedy, D. Academic Duty; Harvard University Press:
Am. J. Pharm. Educ. 1990, 54 ( 3 ) , 321-322. Cambridge, Massachusetts. 1997; 1-58.
7. Boyer, E.L. Scholar.ship Reconsidered. Priorities of the 14. Penna, R.P. Academic pharmacy’s own workforce crisis.
Profeswriate; Princeton University Press: Princeton, New Am. J. Phann. Educ. 1999, 63 (4), 453 454.
Iersey, 1990; 1-27. IS. Broedel-Zaugg, K.; Henderson, M.L. Factors utilized by
8. Glassick, C.E.; Huber, M.T.; Maeroff. G I . Scholarship pharmacy faculty in selecting their first academic position.
Assessed: Evolution o i the PI-~Jessoriute;Jossey-Bass: San Am. J. Pharm. Educ. 1999, 61 (4), 384-387.
Francisco, California, 1995; 1-25, 16. Wells, B.G. Board certification and clinical faculty. Am. J.
9. Hutchings, P.; Shulman, L.S. The scholarship of teaching: Pharm. Educ. 1999, 63 (2), 251.
PROFESSIONAL ORGANIZATIONS
“Standards 2000” reflects broad input from the the needs of baccalaureate-degreed practitioners
profession, and sets forth expectations for quality in already in practice.
Doctor of Pharmacy programs offered by colleges and Encourages increased practitioner involvement in
schools of pharmacy. It is expected that colleges and pharmaceutical education as volunteer faculty and
schools of pharmacy maintain a fundamental commitment in the affairs of colleges and schools of pharmacy.
to the preparation of students for the general practice of Places emphasis upon the importance of devel-
pharmacy with provision of the professional competencies oping good problem-solving, decision-making,
necessary to the delivery of pharmaceutical care. For critical-thinking, and communication skills.
these purposes, pharmaceutical care is defined as the Does not distinguish between externships and
responsible provision of drug therapy for the purpose of clerkships; rather, it is expected that experiential
achieving definite outcomes that improve a patient’s education will be incorporated as a curricular
quality of life. These outcomes are: 1) cure of a disease; continuum throughout the professional program,
2 ) elimination or reduction of a patient’s symptomato- as both introductory and advanced practice
logy; 3) arresting or slowing of a disease process; or 4) experiences, and that experiences will begin
preventing a disease or symptomatology. earlier in the educational process.
Pharmaceutical care involves the process through Increases expectations regarding quality control
which a pharmacist cooperates with a patient and other in the pharmacy practice experience component
professionals in designing, implementing, and monitoring of the curriculum (introductory and advanced
a therapeutic plan that will produce specific therapeutic practice experiences).
outcomes for the patient. This in turn involves three major Encourages innovation in the development and
functions: 1) identifying potential and actual drug-related innovation of new tactics for teaching and
problems; 2 ) resolving actual drug-related problems; and learning, with particular emphasis upon increas-
3) preventing drug-related problems. ing student involvement as active learners.
Pharmaceutical care is a necessary element of health- 9. Encourages the development and implementation
care, and should be integrated with other elements. Phar- of new and innovative methods for student
maceutical care is, however, provided for the direct benefit evaluation and assessment which measure learn-
of the patient, and the pharmacist is responsible directly to ing at a variety of levels beyond the memoriza-
the patient for the quality of that care. The fundamental tion and reiteration of facts.
relationship in pharmaceutical care is a mutually bene- 10. Incorporates expectations that the leadership of
ficial exchange in which the patient grants authority to the colleges and schools of pharmacy will undergo
provider, and the provider gives competence and commit- formal evaluations in a regular and systematic
ment (accepts responsibility) to the patient. The funda- manner.
mental goals, processes, and relationships of pharma- 11 Expects that curricular management and editing
ceutical care exist regardless of practice setting. processes will strive to assure that the addition
‘‘Standards 2000” sets forth 18 professional compe- of material will be counterpoised with the eli-
tencies that should be achieved through the college or mination of outdated and/or unnecessary mate-
school of pharmacy’s curriculum. additionally, “Stan- rial, so as to avoid unnecessary and undesirable
dards 2000”: overlap.
12. Incorporates Total Quality Management (TQM)
1. Emphasizes pharmaceutical care, as considered principles throughout the standards and guide-
in the professional literature and as presented in lines.
the Position Paper of the AACP Commission to 13. Expects particular emphasis to be placed upon
Implement Change in Pharmaceutical Education, the professionalization (professional develop-
as a part of the mission statement of a college or ment) of students.
school of pharmacy, and as an organizing prin- 14. Recognizes the broad range of responsibilities of
ciple for curricular development. pharmacy faculty, including teaching, research
2 . Reflects new competencies and outcome expecta- and scholarly activities, professional practice,
tions for the preparation of a generalist practi- service, and administration.
tioner, which are requisite to the rendering of 15. Expects that colleges and schools will develop
pharmaceutical care in a variety of practice and utilize admission criteria, policies, and
settings. procedures that consider not only academic
3 . Encourages the development of non-traditional qualifications but also other factors which may
curricular pathways and innovative program impact upon success in the professional program
delivery modes (e.g., external degrees) to address (e.g., communication skills, etc.).
PHARMACY PRACTICE ISSUES
ori
University of Georgia College of Pharmacy, Athens, Georgia, U.S.A.
-
not a true physiological disease, nonadherence shares
many of the same characteristics as a medical disorder.
For example:
Beliefs, values, attitudes Skills and willingness to perform
Numerous risk factors f o r nonadherence have been
Fig. 1 Patient-centered adherence paradigm. In the patient- identifed. Clearly, nonadherence is a multifactorial
centered adherence paradigm, the pharmacist integrates infor- problem, and a host of contributing social, economic,
mation about a patient's medication use from three perspectives: medical and behavioral factors have been iden-
the patient's knowledge of the medication (comprehension); the [5,&,9,17-191 A
tified. s shown in Table 1, some risk
patient's beliefs and attitudes toward his or her illness and its factors for nonadherence relate to the disease (e.g., a
treatment (beliefs, values, and attitudes); and the patient's
chronic or asymptomatic illness), others relate to the
ability and motivation to follow the regimen (skills and willing-
ness to perform).
patient (forgetfulness, sensory impairment, and eco-
nomic problems), and still others relate to the drug
regimen (concerns about cost, real or perceived ad-
death."39.' For example, an estimated 125,000 deaths verse effects, or dosing schedule).
per year have been attributed to nonadherence to treat- Nonadherence can be assessed and monitored. A
''
ment for cardiovascular disease." Many studies have variety of direct and indirect methods are available to
documented poorer health outcomes due to nonadherence, assess the presence and severity of nonadherence. As
especially in patients with chronic diseases such as hy- pharmacotherapy specialists, pharmacists may be the
pertension, diabetes, and epilepsy.[5,6, 2,1 31 best suited of health providers to evaluate adherence
Finally, nonadherence places a huge burden on the problems on an ongoing basis.
United States' economy. Its direct and indirect costs have Effective interventions are available to treat non-
been estimated to be $100 billion per year in this country adherence. Many cases of nonadherence can be treated
alone."21 Pharmacies also lose revenue because patients with carefully selected interventions. However, other
often fail to refill prescription medications, especially for cases may not be resolvable, despite the best efforts of
chronic disease^."^] According to The Task Force for health care providers.[51
Compliance,"] only 25% of prescriptions for chronic Nonadherence frequently leads to increased morbidi-
conditions are refilled after 1 year. ty and mortality. Just as untreated medical disorders
For pharmacists, the message is clear: To improve often progress to serious complications, nonadherence
adherence to pharmacotherapy, and hence to improve has a well-documented adverse impact on health
[17,20,211
health outcomes, we must assess each patient indivi- outcomes.
dually, then provide targeted interventions that are re- Nonadherence tends to have a variable course. Non-
sponsive to his or her unique risk factors and needs (see adherence is not a stable condition, but tends to prog-
Fig. 1). Research, such as the American Pharmaceu- ress or change over time in a given patient.[71 Just as
tical Association Foundation's Project ImPACT: Hy- most chronic medical conditions require periodic re-
perlipidemia,"51 has clearly documented the value of evaluation and therapeutic adjustments, patients with
pharmacist-led patient care in fostering better adherence adherence problems should also be reassessed on a
and outcomes. regular basis.
RENCE tions, and the conditions for which therapy has been
prescribed. The patient’s health beliefs and the degree
Before effective strategies can be devised to improve of support available from friends and family should also
adherence, pharmacists need to evaluate how well a be asse~sed.‘~’
patient is adhering to pharmacotherapy and identify risk Interviewing patients to detect nonadherence is most
factors that may predispose the individual to nonadher- effective when indirect probes are used. For instance, the
ence. Both direct and indirect methods are available to probe “Most people have trouble remembering to take
assess adherence. their medications. Do you have any trouble remembering
to take yours?” will solicit more reliable information than
asking: “Are you taking your medications as pre-
irect Methods scribed?’ ’ Table 2 gives examples of specific probes that
the pharmacist can use to assess whether a patient has
Direct and objective methods of assessing adherence been or is likely to be adherent.
include blood-level monitoring and urine assay for the
measurement of drug metabolites or marker compounds.
Collecting blood or urine samples can be expensive and
inconvenient for patients and, moreover, only a limited Table 2 Probes pharmacists can use to assess adherence
number of drugs can be monitored in this way. The
bioavailability and completeness of absorption of var- Assessing the patient’s medication knowledge or medication-
ious drugs, as well as the rate of metabolism and ex- taking behavior
cretion, are factors that make it difficult to correlate What is the reason you are taking this drug?
drug levels in blood or urine with adherence. The abi- How do you take this medication?
Are you taking the medication with food or fluid?
lity of direct methods to identify nonadherence also de-
Where did you receive information about this medication?
pends on the accuracy of the test and the degree to which Are you taking nonprescription drugs while on this medica-
the patient was nonadherent before the urine or blood tion?
sample was taken. Do you use any memory aids to help you remember to take
your medication?
Indirect Methods Do you depend on anyone to help you remember to take your
medication or to assist you in taking it?
Assessing attitudes, values, and beliefs regarding medication-
Indirect methods of assessing adherence include patient
taking behaviors
interviews, pill counts, refill records, and measurement of What results do you expect to receive from this medication?
health outcomes. In one study, the use of patient inter- What are the chief problems that you feel your illness has
views identified 80% of nonadherent patients, as verified caused you?
by pill counts.[221The interview method is inexpensive Do you have any concerns about your illness and its
and allows the pharmacist to show concern for the patient treatment?
and provide immediate feedback. A drawback of this Are you satisfied with your current treatment plan?
method is that it can overestimate adherence, and its ac- How well do you usually follow a treatment plan?
curacy depends on the patient’s cognitive abilities and the What is the main concern you have about your medication?
honesty of their replies, as well as the interviewer’s cor- Do you feel comfortable asking your physician or pharmacist
questions about your medications?
rect interpretation of responses. Pill counts provide an
Assessing whether the patient has the proper skills and is
objective measure of the quantity of drug taken over a
motivated or willing to follow through on the therapy plan
given time period. However, this method is time con- Have you encountered any problems with your medication- or
suming and assumes that medication not in the container pill-taking procedure?
was consumed. The refill record provides an objective Are you confident that you can follow your treatment plan?
measure of quantities obtained at given intervals, but What might prevent you from following the recommended
assumes that the patient obtained the medication only treatment plan?
from the recorded source. How likely is it that you will ask your physician or pharmacist
Pharmacists can generally obtain reliable information about your medications?
on medication-taking behaviors from the patient or a Can you explain how you remind yourself to take your
family member or caregiver. The interview should be medication on schedule?
Do you normally write down questions to ask your physician
systematic and include specific questions on forgetful-
or pharmacist before an appointment?
ness, the patient’s understanding of medication instruc-
Adherence to Pharmaceutical Care 13
Pharmacy computerized prescription records provide medication-taking behaviors (e.g., this method would
perhaps the most practical and least intrusive method not detect a patient who was swallowing a sublingual
for assessing adherence. This method allows the phar- tablet or improperly inhaling an asthma medication from
macist to review and monitor prescription records to a metered-dose inhaler).
determine whether the patient is refilling medications in Factors that have a negative or positive influence on
a timely manner. Computer algorithms can be incorpo- medication adherence are shown in Table 3. This table
rated into the pharmacy computer software system as a may be used both to identify factors that contribute to
tool for monitoring adherence and measuring the time- nonadherence and to develop interventions to address
liness of prescription refills.'231This method also has the adherence problems.
potential to flag potential adherence problems that may
develop over the course of several refills. One disad-
vantage of this method is that it does not assess actual DESIGNING PATI~NT-FOCUSE~
INTERVENTIONS FOR NON
comes.“51 Project ImPACT, which stands for Improve such basic questions as: What is the disease? Which
Persistence And Compliance with Therapy, was con- treatments have been prescribed or recommended and
ducted in 26 community-based ambulatory care pharma- why? What is the patient’s role in managing the
cies in 12 states. The program’s objective was to de- disease? Which adverse effects may occur? Perhaps
monstrate that pharmacists, working collaboratively with surprisingly, the amount of factual information that a
patients and physicians, could improve patients’ adher- patient has about his or her medication is not highly
ence to prescribed therapy for dyslipidemia and help them correlated with adherent beha~ior.’~] Instead, the pa-
achieve their National Cholesterol Education Program tient’s functional knowledge-that is, information that
(NCEP) goals. is directly useful and meaningful to the patient-and
Remarkably, over an average of 24.6 months, 93.6% of clear instructions for medication use are more sig-
Project ImPACT patients adhered to their prescribed nificant.[251Opportunities to impart functional know-
therapy and 90.1% persisted with therapy through the ledge begin with the physician andlor nurse at the time
study’s end.[’51 Among patients with existing coronary of the initial prescription, and should be reinforced by
artery disease, 48% attained their NCEP goal, far better the pharmacist when the prescription is filled or
than in any previously published national study of patients refilled.
with hyperlipidemia. The authors stated that collaboration Avoid fear tactics. Scaring patients or giving them dire
between pharmacists, patients, and physicians, using phar- warnings about the consequences of less-than-perfect
macy-based testing for blood lipids and pharmacist-led adherence can backfire and may actually worsen ad-
counseling, could reduce the risk of heart disease and herence.[261A more constructive approach is to help
stroke by one-third. the patient focus on ways to integrate medication tak-
ing into their daily routine. ~ 2 7 1
Help the patient to develop a list of short- and long-
term goals. These goals should be realistic, achievable,
and individualized. The pharmacist can also make
“contractual” agreements with the patient to encour-
Although pharmaceutical care plans should be individua- age development of constructive behaviors, such as
lized, some adherence-promoting strategies tend to be getting more exercise or beginning a smoking ces-
helpful in the majority of patients. Whenever possible, the sation program.
pharmacist should strive to Plan for regular follow-up. The pharmacist should
plan to interact with the patient at regular, usually
8 Promote self-efficacy. Encourage patients to assume brief intervals to reinforce the adherence plan. For
an active role in their own treatment plans. In ge- example, brief appointments can be scheduled when
neral, the more confident people feel about their abi- patients visit the pharmacy for prescription refills.
lity to manage a problem, the more likely they will The plan should be adapted to the patient’s lifestyle
be to take positive action to solve that problem. In- and be reevaluated from time to time to adjust for life
volving patients in decisions about their care is im- changes, such as aging or a change in work or school
portant for promoting self-efficacy. For example, a schedules. If possible, the time for counseling on ad-
study by Nessman and colleagues[241 showed that herence should be separated from the dispensing and
patients with hypertension who were highly involved pick-up functions.
in decisions about their therapy and trained to take their Implement a reward system. Giving prescription cou-
own blood pressure had significantly better health pons or specific product discounts for successfully
outcomes than patients who did not have these char- reaching a goal in the treatment plan can help to
acteristics. The authors attributed the improved out- increase adherence, particularly in patients with low
comes to the patients’ ability to make choices about motivation.
health care decisions and follow through on a moni-
toring plan.
e Empower patients to become informed medication pecial Populations
consumers. A pharmaceutical care plan to enhance
adherence should first focus on educating the pa- Although the problem of nonadherence affects all ethnic
tient and family members or caregivers about the pa- and age groups, some populations are more vulnerable
tient’s disease and medications. Pharmacists should than others. Pharmacists should be especially alert for
provide both written and oral information to address adherence problems in high-risk populations, such as the
Adherence to Pharmaceutical Care 15
certain medications may be eligible for various forms and as many as 50% could not determine whether they
of state or federal aid, or special discounts from phar- were eligible for financial assistance based on their in-
maceutical manufacturers. come and number of children.[351
People with low health literacy may not understand
Pharmacists should also consider how an elderly the health risks associated with errors in medication
patient’s relationship with other health care providers management. Shame or embarrassment about their low
might influence adherence. For example, research shows literacy may deter them from seeking help with med-
that the elderly tend to favor partnership-type relation- ication instructions. Pharmacists can assess health liter-
ships with their physicians and that satisfying patient- acy using nonobtrusive screening tests such as the Test
provider relationships contribute to better adherence.[321 of Functional Health Literacy in Adults (TOFHLA),
However, with the growing number of managed care and which is available in English and Spanish versions.[361
group practices, these relationships are often more dif- This test includes items that assess the patient’s ability to
ficult to develop. A good pharmaceutical care plan can understand labeled prescription vials, blood glucose test
help elderly patients relate more effectively with primary results, clinic appointment slips, and financial informa-
care providers by helping these patients understand the tion forms.
nature of their diseases and how to better communicate On a more practical level, pharmacists also should
their needs to physicians. strive to provide patient educational materials that are
The role of a patient’s caregivers in helping or hin- written at a low literacy level. The National Work Group
dering medication adherence also should be considered. A on Literacy and Health[371 recommends that materials
motivated and well-informed caregiver can be essential should be at the fifth-grade level or lower, yet most
for optimizing adherence in an elderly patient. However, patient education materials are written at the eleventh-
caregivers can sometimes hinder adherence efforts. For grade level. Patient education materials should be short,
example, a caregiver who is having trouble coping with simple, and contain culturally sensitive graphics. Easy-to-
an elderly patient’s behavioral or cognitive problems may read written materials should be combined with verbal
demand medications to sedate the patient. Pharmacists instructions, which ideally should be repeated on several
who serve communities with a large elderly population different occasions to reinforce patient understanding.
may want to hold special classes to teach caregivers about Involving family members in the patient education pro-
medication management, addressing topics such as medi- cess also can promote adherence.
cation administration and how to monitor and report ad- Many literacy organizations recommend that picto-
verse effects. grams and warning stickers be affixed to prescription
bottles and nonprescription product packages. A detailed
Low-literacy patients list of pictograms and a summary of research on their
usefulness for low-literacy populations are available
Patients who read poorly or not at all are at high risk from the United States Pharmacopeia (USP) at www.
for poor adherence. According to the U.S. Department usp.org. In addition, multimedia computer-based edu-
of Education National Adult Literacy Survey,[331 40 cational programs are available that permit patients to
million people in the United States are functionally il- choose to see or hear information about their particular
literate and another 55 million are only marginally medical condition.
literate. Patients with low literacy skills are less likely
to be adherent to their medication regimens and ap- Ethnic minorities
pointments, or to present for care early in the course of
their disease.[341 An extensive literature documents persistent differen-
Inadequate health literacy skills have been shown to ces in health outcomes between ethnic minorities and
adversely affect the management of a number of chronic white Americans. These disparities include differences
diseases, including diabetes and hypertension. For exam- in health care access and utilization as well as health
ple, in a study of hospitalized patients, 49% of patients status and outcomes. W o l i n ~ k y [ ~showed
~] that differ-
with hypertension and 44% of those with diabetes were ences in access and use of health services by various
found to have inadequate health literacy.[351In that study, ethnic groups stems in part from their varying cultural
as many as 50% of patients did not understand how traditions. Pharmacists can assist in closing this gap in
many times a prescription should be refilled. After ex- health outcomes by providing culturally sensitive patient
amining a standard appointment slip, up to 33% could not care. Information about patients’ cultural health care
describe when a follow-up appointment was scheduled, beliefs and practices is essential for devising interven-
Adherence to Pharmaceutical Care 11
essential concepts about the disease and medication. the recommendations can be accessed at www.usp.org/
According to one study, physicians and pharmacists information/programs/children/principles.
htm.
rarely talked with children about medications, yet most
children wanted to know about their medicines and
would ask their physicians or pharmacist if they
coUld.[411Children as young as 5 years of age knew
there was a difference between medications for child-
ren versus those for adults.[411They could grasp the Each chronic disease presents its own constellation of
concept that medications for adults would be “too adherence problems. A brief overview of adherence stra-
powerful for a little body.” Older children perceived tegies for two major public health problems-hyperten-
the risk for adverse reactions better than the younger sion and type 2 diabetes-illustrates disease-specific risk
children did. Older children also could understand the factors for nonadherence and shows how pharmaceutical
“cost-benefit’’ of getting well despite the need to care services can enhance adherence.
take a bad-tasting medicine. These children wanted to
have more personal control and independence in mak- Hypertension
ing decisions about their medication use. Finally, al-
though most children did not know how medications Because hypertension is usually a silent disease, most
worked, they were very much interested in this topic. patients do not experience symptoms that remind them of
Bush and her colleagues[451developed a cognitive the need for taking medications. Without symptoms, it is
developmental model for educating children about more difficult to establish a link in the patient’s mind
medications that is based on Piaget’s cognitive de- between taking the medication and controlling hyperten-
velopment theory. This model recommends teaching sion and its complications. Because patients often do not
children about the therapeutic purpose of their medi- feel or perceive the benefits of their treatment, the first
cations and that medications can be both helpful and step in enhancing adherence is to educate them about
harmful (i.e., good drugs versus bad drugs, or poisons). hypertension and its serious complications, such as coro-
For younger children, learning activities should be in- nary heart disease, stroke, and renal failure.
teractive and fun. For older children, education should Pharmacists who want to maximize adherence to
correct earlier misconceptions and naive theories about pharmaceutical care programs for hypertension should
medications that may have been learned earlier in their first read the Sixth Report of the Joint National Committee
development. Older children may enjoy learning about on Prevention, Detection, Evaluation, and Treatment of
medications through the use of computer games, vi- High Blood Pressure.[461This report encourages a greater
deos, and reading materials. interdisciplinary role for pharmacists in monitoring med-
Relate the need f o r medications to a child’s past ex- ication use and providing patient information. Adherence
periences with the illness. For example, if child is be- to therapy is a key consideration for reaching the 2010
ing recalcitrant about receiving immunization against national goals for blood pressure control.[461Only one-
influenza, the pharmacist might use a probe such as, half of patients with hypertension still take their medi-
“Do you remember the yucky flu you had last year? cations after the first year of treatment, and one-third of
Would you like to avoid that this year?” This ap- them do not take enough medications to keep their blood
proach can help the child remember previous bouts of pressure under control.[71
the flu as an awful-feeling illness. The child then can The primary goals of a pharmaceutical care plan for
understand the need to prevent the illness by receiving hypertension are to improve patient adherence, decrease
the flu vaccination. the risk of developing complications, and reduce the cost
of unnecessary emergency department visits and hospital
Specific guidelines for developing interventions to ad- stays. Simplified dosage regimens, such as once- or twice-
dress adherence problems in children can be found in daily dosing, have been shown to enhance adherence in
the USP’s Ten Guiding Principles for Teaching Clzil- hypertensive patients. In one study, adherence rates were
dren and Adolescents about Medicines. These principles 73% and 70% for once-or twice-daily regimens, respect-
were developed on recommendations from more than ively, versus 52% and 42% for three- and four-times-a-
100 health care professionals, educators. and consumer day regimens.[471 Improving adherence is particularly
representatives who attended the USP’s fall 1996 open important with the newer regimens, because drug con-
conference, Children and Medicines: Information Isn’t centrations may be subtherapeutic when dosing delays or
Just for Grownups. The proceedings of this conference and omissions Common adverse effects of antihy-
Adherence to Pharmaceutical Care 19
pertensive therapy, such as fatigue, impotence, and light- physical inactivity, and an aging population. Studies have
headedness, also can adversely affect adherence. conclusively demonstrated that the complications of
Patients may need advice on how to incorporate type 2 diabetes can be greatly reduced or delayed by
medications and other antihypertensive treatments, such intensive medical management.[511However, it is es-
as exercise recommendations, into their daily activities timated that only 7% of patients with diabetes adhere
and lifestyles. One useful strategy is to help patients fully to all aspects of their regimen.[521Adherence rates
establish cues that will serve as reminders to take med- for insulin-injection regimens range from 20% to SO%,
ication, such as after breakfast, after brushing teeth, or adherence to dietary recommendations is about 6556,
just before bed. and adherence to exercise regimens varies from 19% to
As with other chronic diseases, education of caregivers 30%. Glucose-monitoring adherence rates range from
and family members is crucial. In one study, 70% of 57% to 70%.‘521
patients wanted their family members to know more about Hsiao and Salmon[533 reported that patients’ beliefs
hypertension. The patients reported that negative atti- about the benefits of diabetes therapy are important in
tudes, insufficient family support, and lack of confidence determining whether they obtain and use medication. In
in the management of their blood pressure were contri- general, the more severe the patient’s disease and the
buting factors to their long-term adherence problems.[491 greater the perceived susceptibility to complications, the
Whenever possible, a family member or caregiver should more likely the patient is to be adherent. Patients must be
be included in educational sessions to help the patient convinced of the seriousness of their disease and em-
follow instructions and stay on track over time. powered to monitor themselves for diabetic complica-
Social or group support can also help to boost the tions. Patients with diabetes who were at high risk for
patient’s confidence and sense of self-efficacy. Group nonadherence included older people, men, and those with
social support may be available from a patient advocacy low socioeconomic status.‘531
organization, such as a local chapter of the American Pharmacist-led programs can be extremely effective in
Heart Association. improving adherence to diabetes care, as two independent
To promote adherence to long-term therapeutic inter- pharmacies in Richmond, VA, recently demonstrated in a
ventions, the pharmacist and patient may agree on a year-long program. During the first 6 months of the pro-
“contract” that includes a series of mutually agreed-upon gram, enrolled patients experienced an average decrease
and realistic health goals. Once a target goal has been in their morning glucose values from 178.6 mg/dL to
achieved, the pharmacist can provide the patient with a 159.3 m g / ~ l L . [ ~Remarkably,
~I over the 12-month study
reward, such as a discount on a prescription, a coupon for period, participants had an average adherence rate of 90%
store merchandise, or a colorful certificate announcing for their use of diabetes medications.
successful goal attainment. Rewards should be carefully To help the pharmacists identify medication problems,
staged so they serve as motivators and are not so osten- a prescription record review was performed 6 months
tatious as to overpower the effect of personal satisfaction after the start of the study. In addition, a computerized
from a job well done. The pharmacist and patient also can “diabetes checklist” was generated and given to each
collaboratively develop periodic reports about the pa- patient to complete at every prescription refill. Along with
tient’s progress for the primary care physician. other information, the checklist asked about any medica-
The pharmaceutical care plan should include outcome tion-related problems the patient had experienced since
measures to gauge the success of adherence strategies for the last refill and assessed the patient’s pattern of blood
hypertensive patients. Outcomes might include refill glucose self-monitoring. The program also included a
patterns for patients taking long-term medications and systematic review of appropriate medication dosages, po-
periodic measurement of blood pressure control over tential drug or disease interactions, and potential adverse
time. Quality-of-life measurements and patient satisfac- drug reactions.
tion surveys are also appropriate outcome measures. The At each refill visit, the pharmacist reviewed the
former are useful to monitor the progress or potential plan with the patient and provided reminders about
complications in patients receiving lifelong therapy for the need for other preventive care. such as yearly eye
asymptomatic diseases such as hypertension.[501 exams and proper foot care. When appropriate, the phy-
sician was contacted, with the patient’s consent, regard-
Type 2 Diabetes ing specific treatment recommendations. In summary,
this diabetes monitoring program showed the value of
Type 2 diabetes is reaching epidemic proportions in the combining multiple interventions to improve adherence
United States, largely because of rising rates of obesity, and outcomes.
20 Adherence to Pharmaceutical Care
Considering that pharmacies lose nearly $8 billion yearly Making Time for Adherence Services
from unrefilled prescriptions, improving adherence is well
worth the effort.[’41 Huffman and Jackson[551estimated It can be challenging for pharmacists to find ways to
that by increasing the number of refills by only lo%, a incorporate adherence screening and monitoring into their
pharmacy could increase its annual sales by $55,000 and current organizational structures. Use of pharmacy
net profit by more than $8000. Adherence screening, technicians to perform routine dispensing duties can free
monitoring, and implementation of interventions also take time for the pharmacist to provide cognitive services, such
time, and pharmacists may seek compensation for the as assessment and counseling. Innovative scheduling
hours they spend in those activities. Third-party payers methods may also free up time for patient education and
have begun to realize the value of adherence manage- counseling. For example, there may be a brief overlap of
ment, and some payers may be willing to pay for adher- pharmacist coverage during the times immediately before
ence-related services. Patients also may be willing to pay and after work shifts. Another strategy is to schedule
out of pocket for these services. To increase the likelihood patient appointments during times when the pharmacy
of reimbursement, pharmacists should be sure to docu- workload is lighter.
ment their adherence-related activities, such as patient
assessment, education, and counseling.
Pharmacists also can benefit from building professional
SUMMARY
relationships with a core network of physicians who can
refer patients to the pharmacy for adherence-related ser-
Adherence to pharmacotherapy is essential to optimal
vices. Reimbursement for cognitive services or disease
therapeutic outcomes. The pivotal role of the pharmacist
state management programs is often tied to provider re-
in optimizing adherence encompasses many actions: as-
ferrals. Providers usually make referrals to other specia-
sessing the adherence problem, identifying predisposing
lists based on trust and their expertise and professional
factors, providing comprehensive counseling, and recom-
competence. A physician is more likely to refer a patient to
mending specific adherence strategies targeted to the pa-
a pharmacy when they have confidence in the content of
tient’s needs. Patients who have chronic conditions, phy-
the services and the competence of the pharmacist ad-
sical or cognitive impairments, or cultural backgrounds
ministering the therapeutic plan. Accountability (i.e., hav-
outside the mainstream may have special needs that
ing the name of an individual, rather than an organization,
should be addressed in the adherence plan. Pharmaceut-
responsible for the services rendered) is also important.
ical care plans also should take into account the patient’s
age, stage of life, and literacy level. Although a wide
Space Considerations range of adherence aids and strategies are available, the
key to success is to tailor the intervention to the individual
Assessment of and counseling on adherence is best done
patient and, when necessary, to combine interventions to
face to face. The use of a special counseling area is re-
optimize adherence.
commended, especially when counseling requires more
time or privacy. Although extensive renovation of the
pharmacy is usually not needed, the environment should
be conductive to open communication, with enough pri- REFERENCES
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Hpperlipidemia. J. Am. Pharm. Assoc. 2000, 40; 157- 34. Malveaux, J.O.: Murphy, P.W.; Arnold, C., et al. Im-
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11. Berg, J.S.; Dischler, J.: Wagner, D.J., et al. Medication edge of their chronic disease: A study of patients with
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176. Unsettled issues about compliance. Am. Heart J. 1995,
38. Wolinsky: F.D. Racial differences in illness behavior. J . 1.70 (3). 573-579.
Cornmiin. Health 1982, 8, 87-101. 49. Beckcr. M.H.; Maiman, L.A. Strategies for enhancing
39. Medical Acccss Program (MAP). The Univcrsity of patient compliance. J. Commun. Health 1980, 6 (2), I 13 ~
most widely used causality classifications is based on hypersensitivity reactions (12). Local irritation to the
Naranjo’ s descriptions. These categories include definite gastrointestinal (GI) tract can occur with oral dosages.
(drug is likely the true cause), probable (drug is the For example, toxicity resulting in mouth ulcerations is
apparent cause), possible (drug appears to be associated), associated with antineoplastic drugs. In addition, the use
and remote (drug is not likely to be the cause). The fourth of certain formulations, such as sustained release
classification system is based on degree of injury or preparations, can increase esophageal injury if esopha-
severity of reaction. There are mild reactions (temporary geal transit is delayed. For example, a controlled
discomfort and tolerable), moderate (significant discom- release wax matrix of potassium chloride has been
fort), and severe (potentially life threatening or causing associated with significant esophageal erosions. Factors
permanent disability or death). identified to predispose to esophageal injury include
large film-coated tablets, capsules, large sustained-
release preparations, rapidly dissolving formulations,
and ingestion of solid oral dosage forms before bed rest
with very little water intake (12).
Localized tissue irritation can be seen from the
The frequency of ADRs in the general population is intramuscular (IM) route. This is especially an issue
unknown. However, the reported rates of new occurrences when the formulation pH differs from the pH of the
for ADRs are noted for selected patient populations. A surrounding tissue or when precipitation of poorly soluble
meta-analysis of 39 prospective studies reported an overall drugs occurs (12). Incorrect administration of I M
incidence of serious ADRs in hospitalized patients of 6.7% injections is probably the most important factor that
and of fatal ADRs of 0.32% (8). The fatality rate makes causes local adverse effects. Local skin irritation can also
ADRs the fourth to sixth leading cause of death in the be seen with transdermal delivery systems due to the
United States. Another meta-analysis of 36 studies alcohols, nonionic surfactants, and adhesives.
indicated that approximately 5 % of hospital admissions Hypersensitivity reactions can occur due to the
are due to ADRs (9). The costs of ADRs are estimated to presence of contaminants or excipients in pharmaceutical
be $1.56-$4 billion in direct hospital costs per year in the dosage forms (e.g., outbreaks of eosinophilia-myalgia
United States (10). syndrome associated with oral tryptophan contaminants in
various drugs) (12). Another example is the anaphylactoid
reactions to the surfactant Cremaophor EL, which is used
ISP T RS in paclitaxel (Taxol).
Direct toxicity effects related to use of preservatives
Two major factors predispose to adverse drug reactions: also has been documented. For example, severe
the drug itself and patient factors. Factors related to the metabolic acidosis and death in infants was attributed
drug include its dose, dosage form and delivery system, to the presence of benzyl alcohol. a preservative used in
and interactions between drugs. Patient-related factors bacterostatic normal saline that was used to flush
include age, disease states, genetics, gender, nutrition, catheters (12).
multidrug therapy use, and use of herbal therapies. The use of specific intravenous (IV) delivery devices
also can cause ADRs. For instance, use of plastic infusion
sets for IV administration of nitroglycerin has resulted in
Drug-Related Factors subtherapeutic effects due to diffusion of the drug into the
plastic tubes (12).
Dose
Formulation effects, such as bioavailability differences,
ADRs may be the result of ingestion of increased amounts can cause ADRs when patients are switched to generic
of a drug. Dosing issues are especially likely with narrow products. For example, significant adverse effects
therapeutic index drugs. Examples of these types of drugs have occurred with anticonvulsants and thyroid prep-
include digoxin, anticoagulants, anticonvulsants, antiar- arations (12).
rhythmics, antineoplastic agents, bronchodilators, seda-
Interactions between drugs
tives, and hypnotics (1 1).
It has been estimated that 6.9% of ADRs are due to drug-
Dosage form and delivery system
drug interactions (6). The most likely reason for an adverse
Many of the ADRs related to the dosage form and drug interaction is the pharmacokinetic changes that result
delivery system are the result of local irritation or in altered metabolism or excretion of drugs, or the
Adverse Drug Reactions 25
pharmacodynamic changes that result in synergistic or whether an increased risk for ADRs exists in this group.
additive effects of drugs. However, there is a potential risk for increased ADRs if
appropriate considerations are not taken into account in
view of pharmacokinetic changes (18).
Patient-Related Factors It is important to note that only one-fourth of the drugs
approved by the FDA have indications specific for use in a
Age, disease states, genetics, gender, nutrition, multidrug
pediatric population (17). Medications used in adults are
therapy use, and herbal therapies use are patient-related
often given to children without FDA safety and efficacy
factors that influence the likelihood of adverse drug
data. Compatibility and stability issues with dosage forms
reactions.
intended for adults that have been altered (e.g., dilution or
Age-geriatrics reformulation) can increase risks for ADRs.
Information on pediatric age-related difference in
Age-related alterations in pharmacokinetics and pharma-
neonates, children, and adolescents may aid in prevention
codynamics may affect the response of elderly patients to
certain medications, and may increase the susceptibility for of pediatric ADRs (18) (Table 2). Further studies of drug
use in pediatrics are needed in order to prevent ADRs.
ADRs among elderly patients (13- 15) (Table 1). The risk
of ADRs among elderly patients is probably not due to age Concurrent diseases
alone. ADRs may be related more to the degree of frailty
and medical conditions of the patient (15). On average, Diseases such as hepatic or renal diseases can influence the
older persons have five or more coexisting diseases that incidence of ADRs by altering the pharmacokinetics of
may increase the risk of adverse events. Polypharmacy drugs, such as absorption, distribution, metabolism, or
seems to be more of a common problem among the elderly. excretion (6).
The average elderly patient takes 4.5 chronic medications
Hepatic disease
and fills 13 prescriptions yearly (15). Elderly patients
appear to have a decline in homeostatic mechanisms. The Patients with liver disease have an increased susceptibility
imbalance of homeostatic mechanisms and the decline in to certain drugs due to decreased hepatic clearance for
function reserves may put a patient at greater risk for ADEs drugs metabolized by the liver or due to enhanced
due to decreased tolerance of medications and the ability to sensitivity (6). For example, impaired hepatic metabolism
handle stressful situations (16). can precipitate central nervous system (CNS) toxicity in
patients on theophylline, phenytoin, or lidocaine; or ergot
Age-pediat rics
poisoning on ergotamine (19).
The two factors responsible for increasing risks of ADRs Increased sensitivity to drugs is also encountered in
in children are pharmacokinetic changes and dose liver disease( 19). The use of anticoagulants increases the
delivery issues. Age-related differences in pharmacoki- risk of bleeding due to the reduced absorption of vitamin K
netics in children are documented (17). However, the data or decreased production of vitamin K-dependent clotting
on both efficacy and safety are often limited or not factors. There is an enhanced risk for respiratory
studied at all in this population. Thus, it is unclear depression and hepatic encephalopathy due to morphine
Gastrointestinal absorption Unchanged passive diffusion and no change in bioavailability for most drugs
1 Active transport and T bioavailability for some drugs
1 First-pass effect and 1bioavailability
Distribution 1 Volume of distribution and T concentration of water soluble drugs
T Volume of distribution and half-life for fat soluble drugs
t or 1 free fraction of highly plasma protein-bound drugs
1 Clearance and 1' half-life for some Phase I
Oxidation drugs 1. Clearance and half-life of drugs with high extraction ratio
Renal excretion 1 Clearance and 1 half-life of renally eliminated drugs
= Decreased; 1 = Increased.
26 Adverse Drug Reactions
Table 2 Pediatric age-related risk factors and causes of ADRs Unlike liver disease, use of pharmacokinetic dosing
principles can minimize the risk for adverse effects.
Neonates:
Mechanisms responsible for enhanced ADRs in renal
Placental transfer of drug before birth
disease include delayed drug excretion, decreased protein
Differing drug action
Altered pharmacokinetics binding due to hypoalbuminemia, and increased drug
Increased percutaneous absorption sensitivity (6). Delayed renal excretion is responsible for
Decreased renal/hepatic function enhanced toxicity with drugs such as aminoglycosides,
Decreased plasma protein binding digoxin, vancomycin, chlorpropamide, H2-antagonists,
Use of multiple drugs allopurinol, lithium, insulin, and methotrexate (20). For
Limited information on drug action in critically ill and premature some drugs, the accumulation of a toxic metabolite during
neonates renal failure is responsible for ADRs. This is the case with
Children: meperidine, where a toxic metabolite, normeperidine,
Paradoxical effect of medications (excitability rather than accumulates in renal failure (20).
sedation from antihistamines) Patients with accumulation of uremic toxins have
Excipients of liquid dosage forms increased sensitivity to certain drugs. There may be an
Sugar as sweeteners enhanced response to CNS depressants (such as barbitu-
Propylene glycol as solvent rates and benzodiazepines), hemorrhagic effects from
Large volume intravenous solutions aspirin or warfarin, and other bleeding effects from
Treatment of viral infections with antibiotics antibiotics that inhibit platelet aggregation, such as
Disruption of neurologic and somatic development
carbenicillin, ticarcillin, and piperacillin.
Adolescents:
Autonomy seeking Other diseases
Use and misuse of devices (e.g., tampons) On theoretical grounds, other diseases associated with
Use and misuse of prescription and nonprescription medications
hypoalbuminemia could predispose patients to adverse
Poor compliance with instructions
Use of multiple medications reactions and to altered responses to drugs that are highly
Recreational use of alcohol and illicit drugs protein bound (21) (Table 3).
Effects of changing hormone levels on drugs The presence of other diseases can influence the risk for
ADRs. Many of these adverse effects are related to an
(From Ref. 7.) extension of the pharmacologic effects of the drug in the
presence of certain pathophysiology. Numerous examples
are given in Table 4 (6).
or barbiturates in patients with severe liver disease.
Patients who have had a previous reaction to drugs are
Vigorous use of diuretics can precipitate hepatic coma due
also more likely to experience an ADR (22).Patients with
to potassium loss in liver disease. There is an increased
history of allergic diseases also have an increased risk due
risk of hypoglycemia with sulphonylurea antidiabetic
to a genetically related ability to form immunoglobulin E.
drugs due to decreased glycogenesis in liver disease.
Liver disease can also cause hypoalbuminemia due to Genetic factors
decreased liver synthesis of albumin. For drugs that are
extensively bound to albumin, such as phenytoin, an Genetic factors account for some ADRs due to either
enhanced risk of drug toxicity could occur because of the altered pharmacokinetics or by altering tissue responsive-
increase in free drug concentration. ness. Altered metabolism of drugs occurs due to
There are no useful methods to quantify the degree of
liver disease that can assist in dosage adjustment. A
Table 3 Conditions associated with hypoalbuminemia
practical approach involves checking patients for elevated
prothrombin time, rising bilirubin levels, and/or falling Aging Liver disease
albumin levels. In such instances, drugs that have an Burns Nephrotic syndrome
altered response in liver disease or cause hepatotoxicity Cancer Nutritional deficiency
need to be avoided. Cardiac failure Pregnancy
Protein-losing enteropathy Renal failure
Renal disease Inflammatory diseases Sepsis
Injury Stress
Impaired renal function increases the incidence of ADRs Immobilization Surgery
for drugs that depend on the kidney for their elimination.
5
(D
Ei
Table 4 Influence of diseases on adverse drug reactions
119
F
Disease Drug Adverse reactions
PR
Gastrointestinal E.
Peptic ulcer Aspirin, corticosteroids, nonsteroidal antiinflammatory drugs Risk of bleeding or perforation of ulcer 3
v)
Cardiovascular
Hcart failure P-Blockers Aggravatc or precipitate heart failure
Lidocaine, theophylline Enhanccd toxicity-seizures
Myocardial ischcinia Tricyclic antidepressants Disturbances of cardiac ratc, rhythm, and conduction
Digoxin Arrhythmias
Bradycardia P-Blockers Cardiac standstill
Quinidine
Hypertension Oral contraceptivcs, vasoconstrictors Incrcascd blood pressure
Phcnothiazines, nitrates Decreased blood pressurc
Tricyclic antidcprcssants
Hematologic
Blceding disorders-hemophilia Aspirin Increased risk of hemorrhage
Neurological disorders
Myasthenia gravis Aminoglycosides Aggravate muscle weakness
Quinidinc, quinine Para Iy sis
Epi1epsy Phcnothiazines Lower seimre thrcshold
Tricyclic antidepressants
Cerebrovascular Ergotaminc Ischemic episodes
Rheumatic
Systemic lupus Drugs Increased incidence of drug reactions in general
Hy pcruriccmia Thiazide diuretics. furosemide Gouty attack
Respiratory
Asthin a p-Blockers Acute bronchospasms
Respiratory insufficiency Narcotic analgcsics Hypoventilation, respiratory arrest
Endocrine disorders
Diabetes mellitus Thiazide diuretics, furosemide, corticosteroids, oral contraceptivcs Hyperglycemia; aggravatcs diabetic control
Hypothyroidism Digoxin Enhanced response
Hypcrthyroidism Oral anticoagulants Enhanced response
Digoxin Decreased response
Ocular
Narrow-angle glaucoma Anticholinergics Glaucoma attack
28 Adverse Drug Reactions
differences in hydrolysis. acetylation, and hepatic It has been suggested that the more medications used, the
oxidation of drugs. Altered pharmacodynamic reactions higher the risk for ADRs (27). Consistent drug regimen
could be either an exaggerated response or a qualitative reviews by healthcare providers in order to reduce
response. These types of reactions are unpredictable. polypharmacy may decrease the risk of ADRs.
Examples of altered drug response due to genetic factors
Herbal therapies use
are found in Table 5 (6).
The use of herbal therapies increased dramatically
Gender
during the 1990s. Herbal therapy sales are estimated to
A higher incidence of ADRs has been reported for women be $4 billion a year, with sales increasing at 20% per
in comparison to men (6). One reason for this observation year since the early 1990s ( 2 8 ) . Patients often
is that women take more drugs than men. Yet, no sex- mistakenly believe that since these products are natural,
linked differences in drug pharmacokinetics have been they d o not possess the potential harm as in
documented. Other reports have not supported a higher prescription medications. Since herbal medications are
incidence of ADRs in women as compared to men. Thus, sold and marketed without stringent FDA approval and
sex alone is unlikely to be a major determinant of ADRs. guidelines, limited evidence-based data on efficacy,
adverse effects, and drug interactions exist. Recently,
Nutrition
two review articles examined available data on ADRs
Nutritional factors are also responsible for ADRs. These for the most common herbal medications (28, 29).
factors include the interaction of drugs and nutrients, and Many of these available reports fall short on
altered pharmacokinetics related to nutritional status. documentation of temporal relationship with the specific
One study reported a very low incidence (0.4%) of ADR and the herbal drug.
clinically significant drug-nutrient interactions in a For most conditions, herbal products are not a
teaching hospital (23). Three mechanisms postulated for replacement for proven prescription or nonprescription
drug-nutrient interactions are interference with drug drugs. Patients should be aware that health care
absorption, alteration of drug excretion, and affecting drug practitioners cannot guarantee the safety and consistency
activity. For example, the absorption of tetracycline is of herbal products. Patients should start with the
reduced by chelation with iron, calcium, and magnesium. recommended effective doses and report any unusual
Foods that acidify or alkalinize the urine can affect drug side effects to their health care practitioner. Patients
excretion. Foods that contain a large amount of vitamin K should always consult with their pharmacist for possible
can inhibit the activity of warfarin. A listing of important drug-herbal interactions. Side effects and possible drug
drug-nutrient interactions is found in Table 6 (23). A interactions for the ten most commonly used herbals are
review article on drug-food interactions in clinical listed in Table 7 .
practice is found in Ref. 24.
Drug-nutrient interactions may be more highly
significant in renal failure patients. A review article of
ADVERSE DRUG REACTION
drug-nutrient interactions in renal failure has been
REPORTING SYSTEMS
published (25).
Nutritional status can affect drug pharmacokinetics.
Malnutrition states can cause the following: 1) the liver The WHO, the FDA, the JCAHO, and the Health Care
and kidneys changes affect drug elimination; 2 ) GI system Financing Administration (HCFA) have all addressed
changes affect drug absorption; 3) changes in the heart and mandated the need for health care institutions to
affect blood flow; 4) hormone changes affect metabolic implement an ADE detection and reporting system.
enzymes and drug binding proteins; 5 ) plasma, tissue Detection systems are instrumental in postmarketing
proteins, and body composition changes affect protein surveillance of ADRs. The JCAHO requires all
binding and elimination; 6) mineral and electrolyte accredited health care institutions to have an ongoing
changes affect drug metabolism and protein binding; and drug surveillance program (4). The goals of ADR
7 ) tissue changes affect uptake of drugs and drug-receptor detecting and reporting systems are to aid in
interactions (26). postmarketing surveillance of FDA approved medi-
cations and to identify ways to decrease ADR risks.
Multidrug use
The main focus of all of these reporting systems is to
According to several epidemiological studies, multiple aid in promoting improvements in the medication use
drug use has a strong association in the causality of ADRs. process.
p
a
Table 5 Gcnetic factors and altered drug re5ponscs ;
Genetic mechanism Drug(s) Adverse drug response
Pharmacokinetic
Low plasma pseudocholines- Succinylcholine Prolongcd ncuromuscular blockade lcading to
tcrase apnca
Slow acetylator Isoniarid Increased incidence of peripheral neuropathy;
SLE-like syndrome; and more prone to
phenytoin toxicity
Hydralazinc, procainamide Increased incidence of SLE-like syndrome
Phenelzine, sulfasalaLine More prone to sidc effccts
Rapid acetylator Isoniazid More prone to hepatitis
Deficiency of epoxide hydrolase Phenytoin, carbamaIepine, phenobarbital Life threatening hypcrsensitivity syndrome
due to accumulation of toxic
intermediates
Pharmacodynamic
Glucoac 6-phosphatc Aspirin, BAL (dimercaprol), chloroquinc, Hemolytic anemia
dehydrogenase deficiency (G-6-PD) chloramphenicol, dapsone hydroxychloroquinc,
nalidixic acid, nitrofurantoin, primayuine, probenecid.
yuininc, yuinidinc, sulfonamides
Mcthemoglobin reductase deficiency Acetaminophcn, ancsthctics, topical, benzocaine, Methemoglobi nemi a
chloroquine, dapsone, nitrites, primayuinc,
sul fonamides
Abnormality of calcium regulation Anesthetics, gcneral, (halothanc), muscle relaxants Malignant hyperpyrexia
(succinylcholine)
W
w
30 Adverse Drug Reactions
Echinacea Treatment and prevention of upper Rash, pruritis, dizziness, unclear long-term
respiratory infections, common cold effects on the immune system.
St. John’s wort Mild to moderate depression Gastrointestinal upset, photo-sensitivity.
Mild serotonin syndrome with the following
medications: paroxetine, trazodone, sertraline, and
nefazodone.
May decrease digoxin levels.
May decrease cyclosporine serum concentrations.
Combined oral contraceptives-breakthrough bleeding.
Gingko biloba Dementia Mild gastrointestinal distress, headache, may
affect warfarin (increase INR).
Interaction with aspirin (spontaneous hyphema)
Garlic Hypertension, hypercholesterolemia Gastrointestinal upset, gas, reflux, nausea,
allergic reactions, and antiplatelet effects.
May effect warfarin (increase INR)
Saw palmetto Benign prostatic hyperplasia Uncommon
Ginseng General health promotion, sexual function, High doses may cause diarrhea,
athletic ability, energy, fertility hypertension. insomnia, nervousness, may affect
warfarin (decreased INR)
Goldenseal Upper respiratory infections. common cold Diarrhea, hypertension, vasoconstriction
Aloe Topical application for dermatitis, herpes. May delay wound healing after
wound healing, and psoriasis, orally topical application.
for constipation Diarrhea, and hypokalemia with oral use
Siberian ginseng Similar to ginseng May raise digoxin levels.
May affect warfarin (increased INR)
Valerian Insomnia, anxiety Fatigue, tremor, headache, paradoxical insomnia
(not advised with other sedative-hypnotics)
Studies of therapeutic classes or pediatric patients. These groups of patients are often
excluded in Phase I11 trials. However, a disadvantage of
Observational cohort or case control designs have been
these studies is that they also often use administrative data.
used to determine ADR relationships with specific
These data can warrant risk of problems in determining
therapeutic classes (36, 41). Medical claims data are
causality due to potential confounding variables (38).
often used in these studies and caution should be warranted
due to lack of definite confirmation of drug exposure and
the potential for confounding variables (38). However,
these studies have been beneficial in determining risk of Assessing Adverse Drug
ADRs with specific classes (e.g., NSAIDs and the risk of Reactions
peptic ulcer disease) (42). After detection of a possible ADE, causality assessment
needs to be performed. It is important to be able to rank the
Studies of specific medical
likelihood of an ADR as unlikely, possible. probable, or
syndromes
definite. A major problem with determining causality is that
Observational cohort or case control designs can also be confounding variables can contribute to the complexity of
useful to study possible causality relationships of specific causality assessment (43). In order to determine causality,
medical conditions or syndromes due to drug exposure (36, several important points of data are required. These include
41). These types of studies have been particularly useful in the nature of the adverse event, name of the putative drug,
examining ADRs in a specific population, such as geriatric other potential causes, and the temporal relationship
32 Adverse Drug Reactions
between the drug and adverse event. Potential causes are (predictable) reactions, and thus with quality improvement
obtained by examining the medical history, physical measures, ADRs can be avoided and prevented (46).
examination findings, and directed diagnostic tests. Knowledge of causative factors and an increase in patient
Identification of causality can be performed simply by education may help prevent ADRs. Improvements in the
using a health care provider’s clinical reasoning and judg- documentation of allergic reactions (e.g., via computer
ment. The main disadvantage to this approach is a low inter- tracking), development of tools to enhance compliance,
rater and intra-rater agreement for ADR causality (44.45). and application of tools to improve prescribing and
An ADR causality algorithm addresses the issue of administration of drugs are other preventative approaches
inter-rater and intra-rater reliability with a series of clinical to ADRs.
questions. For example, the Naranjo algorithm consists of In 1994, the ASHP, the American Medical Association
a series of clinical questions that focus on temporal and (AMA), and the American Nurses Association (ANA)
dose-response relationships, consistency of the ADR with generated the following system of recommendations to
previous clinical reports or patient experiences, placebo prevent ADRs in health care systems:
response, drug dechallenge and rechallenge, toxic blood
drug concentrations, alternative causes of the reaction, and 1. Health care systems should establish processes in
whether the event was confirmed by objective evidence which prescribers enter medication orders directly into
(44) (Table 8). Numerous health care institutions and the computer systems.
FDA use some type of causality algorithm to minimize 2 . Health care systems should evaluate the use of
disagreement among different evaluators and improve machine-readable coding (e.g., bar coding) in their
inter-rater and intra-rate agreement. medication use processes.
3. Health care systems should develop better systems for
monitoring and reporting adverse drug events.
4. Health care systems should use unit dose medication
PREVENTING A
distribution and pharmacy-based intravenous medi-
REACTIONS
cation admixture systems.
5 . Health care systems should assign pharmacists to work
ADRs are problematic in that they cause significant in patient care areas in direct collaboration with
morbidity and mortality. Almost 95% of ADRs are Type A prescribers and those administering medications.
Adverse Drug Reactions 33
6. Health care systems should approach medication errors Excess Length of Stay, Extra Costs, and Attributable
as system failures and seek system solutions in Mortality. JAMA 1997, 277, 301-306.
11. Applied Biopharmaceutics and Pharmacokinetics;
preventing them. Shargel, L., Yu. A., Eds.; Appleton and Lange: Stamford,
7. Health care systems should ensure that medication CT, 1999.
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pharmacists, nurses, and other workers seek resolution Concepts 1996, 14 (l), 39-67.
whenever there is any question of safety with respect to 13. Swift, C.G. Pharmacodynamics: Changes in Homeostatic
Mechanisms, Receptor and Target Organ Sensitivity in the
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PROFESSIONAL ORGANIZATIONS
The CERTs legislation has been transferred from clinical practitioners, clinical investigators, educators, and
FDAMA to AHRQ, and is now a permanently authorized others from the pharmacy community.
program. The CERTs network is expected to expand,
both through addition of new Centers as well as estab- Translating Research Into Practice ( T R ~
lishment of collaborations with investigators and practi-
tioners throughout the country. Additional information is One of the most pressing challenges in healthcare is to
available at http:Nwww.certs.hhs.gov. apply the knowledge that is currently available; in other
words, to close the gap between knowledge and practice.
The first round of TRIP initiatives supported devel-
Evidence-Based Practice Centers (EPCs)
opment and implementation of evidence-based tools into
diverse healthcare settings. Translational efforts included
The philosophy of evidence-based practice is widely ac-
cost-effective approaches to implement smoking cessa-
cepted, although operational and implementation issues
tion, chlamydia screening of adolescents, diabetes care
represent major barriers. One of the significant barriers
in medically underserved areas, and treatment of respir-
is a shortage of evidence reports on topics of critical
atory distress syndrome in preterm infants. The second
interest, and the lack of a national infrastructure to pre-
round of TRIP initiatives (funded in 2000) focused on
pare such reports. In response to this need, AHRQ has
continued development of partnerships between resear-
funded 12 Evidence-based Practice Centers to conduct
cher and healthcare systems and organizations (e.g., in-
systematic, comprehensive analyses and syntheses of
tegrated health service delivery systems, academic health
the scientific literature to develop evidence reports and
systems, purchaser groups, managed care programs in-
technology assessments on clinical topics that are com-
cluding health maintenance organizations, practice net-
mon, expensive, and present challenges to decision ma-
works, worksite clinics) to help accelerate and magnify
kers. Since December 1998, l l evidence reports have
the impact of practice-based, patient outcome research in
been released on topics that include sleep apnea, trau-
applied settings.
matic brain injury, alcohol dependence, cervical cytology,
urinary tract infection, depression, dysphasia, sinusitis,
atabases
stable angina, testosterone suppression, and attention
deficit hyperactivity disorder.
AHRQ achieves its mission through a combination of
Pharmacotherapy is a significant interest within the
efforts, described as a “research pipeline.” This pipeline
EPCs, and AHRQ welcomes partners such as specialty
of activities builds the infrastructure, tools, and know-
societies and health systems to submit topics for evidence
ledge for improvements in the American healthcare
reports, participate with the EPC’ s in preparing reports,
system. An important part of that pipeline for pharmacy
and most importantly to use the findings of EPC’s to
is the maintenance of public use databases that can help
develop tools and materials that will improve the quality
identify problems and formulate solutions to improve
of care.
pharmacotherapy. One database of particular interest is
the Medical Expenditure Panel Survey (MEPS) which
National Guidelines Clearinghouse (NGC) provides up-to-date, highly detailed information on how
Americans as a group, as well as segments of the pop-
Developed in partnership with the American Medical ulation, use and pay for healthcare. This ongoing survey
Association and the American Association of Health of about 10,000 households and 24,000 individuals also
Plans, the NGC is a Web-based resource for information studies insurance coverage and other factors related to
on evidence-based clinical practice guidelines. The NGC access to healthcare. AHRQ encourages investigators to
began providing online access to guidelines at http:// write applications that analyze the MEPS data.
www.guideline.gov in 1998. Since becoming fully ope-
rational, the site receives over 100,000 visits each month.
The site provides information to help healthcare profes-
sionals and health system leaders select appropriate
treatment recommendations by providing full text or an Today’s AHRQ has an annual budget of $270 million for
abstract of the recommendations, by comparing and fiscal year 2001, with approximately 80% awarded as
evaluating different recommendations, and by describing grants and contracts to researchers at universities and
how they were developed. Because almost all guidelines other institutions across the country. The remaining 20%
include some consideration of pharmacotherapy, and the is allocated to intramural research and administrative
NGP should be regarded as an invaluable resource to support. The agency is administratively located within the
38 Agency for Healthcare Research and Quality
volvement of clinical pharmacy services in 50 of the grams provides guidance and practical training to phar-
VAMCs’ specialty ambulatory clinics, it was found that macists who are seeking more education and skills to
310 of the 401 (77%) specialty clinics were staffed with provide patient care. These programs are offered in a
a clinical pharmacist and 144 (36%) were managed by variety of work settings from VAMCs and large teach-
pharmacists. These clinics covered a variety of disease ing hospitals to smaller family medicine groups and
states, including congestive heart failure, anticoagula- community pharmacies.
tion, lipid management, geriatrics, diabetes, and thera- Although the majority of ambulatory care pharmacists
peutic drug have chosen the route of the Doctor of Pharmacy degree
The work settings for pharmacists in ambulatory and and residency, it is not the only course to becoming
primary care clinics also vary. More recently, for ex- an ambulatory care pharmacist. Some pharmacists who
ample, pharmacists can be found in private physician have been practicing several years have grown and
offices or large teaching hospitals. Anywhere ambulatory established positions in ambulatory care without res-
care is being provided by physicians, nurse practitioners, idency or fellowship training. However, many institu-
or physician assistants, there is opportunity for phar- tions require that they have continuing education to
macist involvement. practice in an ambulatory care setting with a team or
independently, and one means of continuing education
is through certificate programs. Many certificate pro-
grams that are available will teach specific disease state
EGREE, TRAINING, EXPERIENCE, management such as anticoagulation, diabetes, or asthma
care. However, other certificate programs may be more
inclusive, covering a broader spectrum of ambulatory
Since the push and support for an entry-level Doctor care. [71
of Pharmacy degree by the American Association of Salary range for pharmacists practicing in an am-
Colleges of Pharmacy in 1992, the majority of colleges bulatory care setting varies depending on geographic re-
of pharmacy in the United States have been converting gion, years in the work force, and board certification
from the Bachelor of Science degree. One of the goals status. However, the median salary in 1995 was S53,500
in switching to the Doctor of Pharmacy degree is for (average, $55,861; range, $35,000-$90,000), with a high-
the colleges of pharmacy to produce patient care er salary reflective of more years employed.[61
providers rather than medication dispensers. Because
providing patient care is one of the major activities of
ambulatory care pharmacists, the majority of graduates
have come from an entry-level Doctor of Pharmacy GROWTH AND LONG-TER
program. Others, however, have returned to school for OPPORTUNITIES
additional education to gain the knowledge needed to
move into the clinical setting and manage the diversity Since the 1990s, clinicians in the fields of ambulatory
of disease states. care and primary care have embraced pharmacists as
For many ambulatory care pharmacists. training does colleagues and as an invaluable source of information.
not end at graduation with acceptance of the degree. This acceptance has lead to an increase in demand of
Additional training in residency or fellowship for 1 to 2 pharmacists in the ambulatory care arena in several
years is sometimes completed to obtain more clinical capacities. First, the educational system has experienced
experience in patient care as well as to develop a deeper the need to increase the education of students in this area,
knowledge base. In a 1995 survey of pharmacists prac- thus producing more students that choose paths in
ticing in an ambulatory care setting, 67410 of the 99 res- ambulatory care. Second, pharmacists have been dedicat-
pondents indicated that they had residency training and ing themselves to improving patient outcomes in primary
21% had fellowship training. Forty-six percent of res- and ambulatory care, which has lead to a tremendous
pondents also specified that they had received board growth and need for pharmacists in this area.
certification.[61 As it is evident that this field is growing, the question
New graduates who select a career in ambulatory care arises as to the longevity of these positions. Many
pharmacy may decide to complete a l-year general pharmacists that are practicing in ambulatory care have
pharmacy practice residency program or to choose a created their own positions. Since the mid-1980s and
specialized residency in ambulatory care or primary early 1990s, many of these pharmacists have moved from
care. The invaluable experience gained in residency pro- dispensing to the clinical role. Therefore, pharmacists
Ambulatory Careprimary Care, Clinical Pharmacy Careers in 41
who have been in ambulatory care several years are some cations to become involved in the treatment decisions
of the first to experience this long-term job stability. for patients.
However, as the goals for health care continue to move Retail pharmacy is also making an effort to get phar-
toward more cost-effective ways to administer better macists out from behind the counter by establishing a
health care, pharmacists continue to prove themselves variety of clinics in the retail setting. Some pharmacists
to fit this equation. Thus, pharmacists will most likely are providing pharmaceutical care, such as working in
continue to be in these positions for quite some time. conjunction with physician offices to counsel newly diag-
nosed diabetic patients on the proper use of glucome-
ters and insulin injections, whereas others work more
independently, offering services in durable medical equip-
ment, home infusion, and home oxygen.
The progress in ambulatory care has not always been a
One benefit of practicing as an ambulatory care phar- clear road. Many barriers have risen along the way that
macist is that there are a variety of practice settings. These have prevented pharmacists from being accepted in the
practice sites vary from physician office buildings to clinical community as a patient care provider. Some cli-
physician residency training programs, as well as large nicians still view pharmacists as dispensers of medi-
hospitals and retail pharmacies. cations and believe patient care is not within the scope
One example is that of a private physician’s office. of a pharmacists’ practice. In some cases, this barrier
Studies have been performed to determine the impact of has been surpassed in settings such as VAMCs and
having a pharmacist providing pharmaceutical care in a HMOs, where a capitated health care system is prac-
physician’s office.18] In this scenario, pharmacists usually ticed. Pharmacists have saved these institutions money
have unlimited access to patient information and may as well as improved health outcomes, acting not as dis-
have their own office or exam room to evaluate and pensers of medication, but as clinicians. In addition, the
educate patients. The pharmacist may see these patients pharmacy profession itself has in some respects inhi-
independently of the physician or evaluate the patient for bited its own growth. Large retail pharmacy chains whose
pharmaceutical issues before the physician sees them. salaries are significantly more than that of an ambulato-
Other services may be available at these offices such as ry care pharmacist, absorb a large portion of graduates
a laboratory or radiological services, depending on size that may desire to pursue a career in ambulatory care but
and specialty of the office. are attracted to a higher salary. However, the future
Another model that may be used to integrate phar- for ambulatory care pharmacists appears brighter as le-
macists into ambulatory care settings is that of a uni- gislative change is looking to recognize pharmacists as
versity-based family practice center or residency train- providers and reimburse them for providing pharma-
ing program.[9J In this setting, the pharmacist typically ceutical care.
works at a larger physician training program and teach-
ing clinic. The pharmacist usually has patient care du-
ties such as specialty clinics, medication refill services,
or other consultative services. However, in this environ- CONCLUSION
ment, the pharmacists also have obligations to teach
and evaluate the medical residents in both didactic and As the need for change in the profession of pharmacy
clinical situations. This type of position is sometimes has evolved since the 1990s, pharmacy schools have res-
affiliated with higher academic institutions, and clinical ponded by producing a well-rounded practitioner and
duties may need to be balanced with administrative, re- provider of pharmaceutical care. More graduates are
search, or teaching obligations. choosing to gain patient care skills and training in am-
Other traditional sites are changing the way that bulatory care residency or fellowship programs, allow-
pharmacists see and educate patients. More hospitals are ing them to be focused practitioners and teachers. The
moving to outpatient treatment programs and becom- future for pharmacists in the area of ambulatory care
ing involved in the multidisciplinary approach to ambu- looks bright as pharmacists lobby to be recognized as
latory care patients, and practice sites for pharmacists providers and to be reimbursed for providing phar-
are moving from the central pharmacy to walk-in or maceutical care. Finally, as pharmacists continue to
ambulatory care clinics and even home care teams. demonstrate that their clinical services improve patient
These opportunities have allowed pharmacists who outcomes and decrease overall health care costs, jobs in
traditionally process orders and mix intravenous medi- the ambulatory care setting will continue to expand to
42 Ambulatory Cardl’rimary Care, Clinical Pharmacy Careers in
other venues, allowing pharmacists to accomplish what 4. Reeder, C.E.; Kozma, C.M.; O’Malley, C. ASHP Survey of
they were trained to do. ambulatory care responsibilities of pharmacists in inte-
grated health systems-1997. Am. J. Health-Syst. Pharm.
1998, 55, 35-43.
5. Carter, B.L. Clinical pharmacy in disease specific clinics.
Phamacotherapy 2000, 20 (10 Pt 2), 273s-277s.
6. Anastasio, G.D.; Shaughnessy, A.F. Salary survey of am-
McMullin, S.T.; Hennenfent, J.A.; Rithie, D.J.; Huey, bulatory care clinical pharmacists. Pharmacotherapy 1997,
W.Y.; Lonergan, T.P.; Schaiff, R.A.; Tonn, M.E.; Bailey, 17 (3), 565--568.
T.C. A prospective, randomized trial to assess the cost 7. Jannsen, R.K.; Murphay, C.M.; Kendzierski, Q.L.; Brown,
impact of pharmacist-initiated interventions. Arch. Intern. D.H.; Carter, B.L.; Furmaga, E M . ; Schoen, M.D.; Woker,
Med. 1999, 1 5 Y , 2306- 2309. D.R. Ambulatory care certificate program for pharmacists.
Gattis, W.A.; Hasselblad, V.; Whellan, D.J.; O’Connor, Am. J. Health-Syst. Pharm. 1996, 53, 1018 1023.
~
C.M. Reduction in heart failure events by the addition of a 8. Campbell, R.K.; Sadie, B.A. Providing pharmaceutical
clinical pharmacist to the heart failure management team: care in a physician office. J. Am. Pharm. Assoc. 1998, 38,
Results of the Pharmacist in Heart Failure Assessment 495- 499.
Recommendation and Monitoring (PHARM) Study. Arch. 9. Lilley, S.H.; Cummings, D.M.; Whitley, C.W.; Pippin, H.J.
Intern. Med. 1999, 159, 1939 1945. Intergration of a pharmacotherapy clinic in a university-
Chiquette, E.; Amato, M.G.; Russey, H.T. Comparison of based family practice center. Hosp. Pharm. 1998, 33,
an antiocogulation clinic with usual care. Arch. Intern. 1105-1 110.
Med. 1998, 158, 1641-1647.
PROF ESSl 0NAL ORGAN IZATIO NS
I ershi
The American College of Clinical Pharmacy (ACCP) was As of the end of 2001, ACCP had approximately 7000
founded in 1979 when 29 clinical pharmacists-organized members, located mostly in the United States and Canada.
largely by Donald C. McLeod, M.S.-gathered in Kansas ACCP members can be found in all practice venues,
City, Missouri, with a common goal: to promote the including ambulatory clinics and community pharmacies,
rational use of medications in society by forming an community hospitals, the pharmaceutical industry, phar-
organization dedicated to and focused on advancing the macy and medical school faculties, university hospitals,
cutting-edge of clinical pharmacy practice and research. and VA and military hospitals. More than 80% of ACCP
Those ideals held by ACCP’s founding members still find members hold the Pharm.D. degree, 70% have completed
themselves in the College’s mission: a postgraduate residency, and 25% have complcted a
research fellowship training program. Approximately
ACCP is a professional and scientific society that pro- 25% of ACCP members are certified in one or more of
vides leadership, education, advocacy, and other resources the specialty practice areas recognized by the Board of
enabling clinical pharinacists to achieve excellence in Pharmaceutical Specialties (BPS; i.c., Nuclear Pharmacy,
practice and research. Nutrition Support, Oncology, Pharmacotherapy, Psychi-
atry). Consistent with one of ACCP’s founding tenets-to
promote the rational use of medications in society-
TI College members directly assume responsibility for the
drug therapy of individual patients through collaborative
Only two years after its founding, ACCP created its practice agreements with physicians; regularly consult
Research Institute in 1981 to advance pharmacotherapy with and advise physicians, other health professionals,
through support and promotion of research, training, and and patients regarding drug therapy; serve on key insti-
educational programs. Through 2000, this has largely tutional or other committees that oversee the medication
taken the form of a number of Research Awards that use process; and teach pharmacy or other hcalth profes-
support specific research projects conducted by College sion students. In addition, many ACCP members are
members in a variety of therapeutic areas, and Fellow- responsible for conducting basic, clinical, health services,
ships that provide for the stipends of postgraduate clinical economic, or other applied research. This research, for
pharmacists in an intensive research training experience. example, may involve clinical trials of new drug entities,
Both types of programs are available to ACCP members pharmacokinctic and pharmacodynamic studies in normal
on a competitive basis. volunteers and patients, pharmacoeconomic evaluations
Also in 1981. Russcll R. Miller, Ph.D., founded the of drug therapies, and health services research to ex-
journal Phurmucotherupy as a publication dedicated to amine the impact of pharmacy services.
human pharmacology and drug therapy. When first esta- The practice and research interests of ACCP members
blished, Pharmucotherupy was not affiliated with any span the broad array of pharmacothcrapy. As one way to
medical or pharmacy associations. In 1988, ACCP adopted provide for the unique needs of clinical pharmacists with
Pharinucotherupy as its official journal, and in 1994, diverse interests, ACCP currently includes approximately
ACCP acquired the journal. Now a monthly publication, 20 Practice and Research Networks (PRNs). The PRNs
Phurmucotherupy publishes a complementary array of ori- form special interest groups within the College jn areas
ginal clinical research and evidcnce-based reviews in the ranging from Ambulatory Care to Infectious Diseases to
broad field of pharmacotherapy and clinical pharmacology. Women’s Wealth.
program. Certificate programs are designed to instill, structure of ACPE assures the integrity of the accredita-
expand, or enhance practice competencies through the tion program through responsive, responsible, and inde-
systematic acquisition of specified knowledge, skills, pendent operation. The Board of Directors has authority
attitudes, and behaviors. In June 1999, Standards and for management of corporate affairs and is responsible for
Quality Assurance Procedures for Providers Offering establishing policies and procedures, setting standards for
Certificate Programs in Pharmacy were adopted. As of accreditation of professional programs of colleges and
Fall 2000, 30 providers had been accredited to provider schools of pharmacy, establishing standards for accre-
certificate programs. The symbol used by the ACPE to ditation of providers of continuing education, including
designate that a certificate training program is provided certificate programs in pharmacy, and taking actions
by an accredited provider is concerning accreditation. A Public Interest Panel serves in
an advisory capacity. The ACE appointee and the Public
mACPE
Interest Panel assure a public perspective in policy- and
decision-making processes.
Of note, the standards originally developed for the Dr. Daniel A. Nona served as the Executive Director
accreditation of providers of continuing pharmaceutical from 1975-2000. Dr. Peter H. Vlasses assumed the Exe-
education were revalidated during development of the cutive Director position effective January 1, 2000.
standards pertaining to providers of certificate programs.
In addition, the new term “statements of credit” should
be when documenting completion of a continuing edu- MISSION
cation activity provided by an ACPE-accredited provider.
The term “certificates of credit” should be reserved for ACPE is organized for the purpose of promoting and
use in conjunction with ACPE-accredited certificate pro- encouraging educational, research, and scientific activi-
grams only. ties. The ACPE formulates educational, research, and
Annually, or more frequently if necessary, the ACPE scientific standards which an accredited professional pro-
publishes the Directory of Accredited Doctor of Pharmacy gram of a college or school of pharmacy or an accredited
Programs of Colleges and Schools of Pharmacy and the provider of continuing education will be expected to meet
Directory of Accredited Providers of Continuing Phar- and maintain. The essential purpose of the professional
maceutical Education. degree program accreditation process is to provide a
The Pharmacists’ Learning Assistance Network professional judgment of the quality of a college or school
(P.L.A.N?) is an information service developed by the of pharmacy’s professional program(s) and to encourage
ACPE to allow pharmacists to access information on continued improvement thereof. Accreditation concerns
continuing education programs. The P.L.A.N. service, itself with quality assurance and quality enhancement.
which is operated by ACPE, maintains a database on all The responsibilities of the ACPE’ s professional degree
continuing pharmaceutical education programs offered by accreditation program are as follows:
ACPE-approved providers. Pharmacists may request a
computer search of continuing pharmaceutical education To advance the standards of pharmaceutical education
programs to suit their learning needs or conduct their own in the United States and associated commonwealths.
search on ACPE’s web site. To formulate the educational, scientific, and professio-
nal principles and standards for professional programs
in pharmacy which a college or school of pharmacy is
ORGANIZATIONAL STRUCTURE expected to meet and maintain for accreditation of its
AND GOVERNANCE programs, and to revise these principles and standards
when deemed necessary or advisable.
The Council is an autonomous and independent agency To formulate policies and procedures for the accred-
whose 10-member Board of Directors is derived through itation process.
the American Association of Colleges of Pharmacy, the To evaluate the professional program(s) of any college
American Pharmaceutical Association, the National As- or school of pharmacy within or beyond its national
sociation of Boards of Pharmacy (three appointments geographic scope that requests accreditation of its
each), and the American Council on Education (one program( s) .
appointment). These organizations are not members of the To publish a directory of accredited professional
ACPE, and appointees to the Board of Directors are not programs of colleges and schools of pharmacy for
delegates of these organizations. The organizational the use of state boards of pharmacy or appropriate
A ~ e ~ Council
~ c a on
~ ~ a r ~ a c Education
e ~ ~ ~ ~ ~ l 47
the AJHP and Clinical Pharmacy staff was able to reduce In 1997 some components of AJHP began appearing on
production costs dramatically. That enabled ASHP to ASHP’s Web Gte. Starting in September 1999, the full
merge Clinical Pharmacy into AJHP in 1994, creating text of AJHP was posted. Members and other subscribers
pharmacy’s only peer-reviewed scientific journal to be can now read and print type-quality copies of AJHP con-
published 24 times each year. AJHP has published more tent about 10 days before an issue is mailed. Furthermore,
than 2000 pages annually for the past 20 years. important scientific findings that affect patient safely can
AJHP (Codcn: AHSPEK; ISSN: 1079-2082) is pub- be conveyed to the public and the media the instant they
lished by the American Society of Health-System Phar- have finished undergoing the traditional peer-rcview,
macists twice a month, on the 1 st and 15th. Circulation in editing, and composition steps, saving weeks or months
2001 was 37,870; the 2001 subscription rate was $195 of delay in many cases. No other pharmacy organization
for nonmembers (USA). A subscription is included as in the world is currently doing this.
a benefit to ASHP members. Editorial offices are located Enhancements of AJHP’s Web-based distribution are
at 7272 Wisconsin Avenue, Rcthesda, Maryland 201 84, in the works. The scarchability of past issues is bcing
U.S.A. (Telephone: 301-657-3000, ext. 1200; Fax: 301- improved, and new procedures and mechanisms for
664-8857; E-mail: ajhp@ashp.org). authors and reviewers to use in electronically submit-
AJHP is abstracted and indexed by all the major ting manuscripts, letters, and other communications are
secondary sources (e.g., International Pharmaceutical being developed.
Abstracts, Biological Abstracts, Chemical Abstracts,
Cumulative Index to Nursing and Allied Health Literut-
ure, Current Contents: Clinical Medicine, Current Y
Contents: L f e Sciences, Excerptu Medica, Index Medicus,
and the Iowa Drug Information Service. www.ashp.org.
PROFESSIONAL K E S O I J R C E S
review services in the nation’s nursing facilities improve le 2 Percentage of ASCP pharmacists that provide
the frequency of optimal drug therapy outcomes by 43% services to the following sites
~ ~
and save as much as S3.6 billion annually in costs as- Nursing homes 76%
sociated with medication-related problems.[ ’] In Fleet- Counseling to long-term care facilities (LTCF) 70%
wood Phase 11, the Fleetwood model was developed and Dispensing to LTCF 54%
tested for feasibility. The Fleetwood model includes Administrative responsibility to LTCF 42%
prospective drug regimen review, direct communication Residential 41%
with prescribers to resolve therapeutic issues, patient Subacute 31%
assessment, and formalized pharmaceutical care planning Hospice 30%
for geriatric patients at highest risk for medication-related Mental health 28%
Home care 25 %
problems. The results of the Phase 11 pilot study were
Retail dispensing 19%
published in the October 2000 issue of The Consultant
Acute care 15%
Pharmacist. The Fleetwood model will be further refined Correctional facilities 11%
in Fleetwood Phase 111. currently underway, by identify- Hospital LTCF 8%
ing and validating “pharmacist-sensitive outcomes”-
those clinical outcomes most sensitive to pharmacist
intervention for older patients at high risk for medication- The Executive Director of ASCP is Tim Webster;
related problems. elected leadership consists of President (Mark Sey),
President-elect (Stephen Feldman), Vice President (Ross
Buckley), Secretary/Treasurer (Herb Langsam), and the
Immediate Past President and Chairman of the Board.
These officers and ten directors comprise the Board of
Directors. The Board of Directors has full administrative
authority in all Society matters, except as otherwise pro-
The ASCP was founded in 1969 to represent the interests vided in ASCP bylaws.
of its members and promote safe and effective medication ASCP has chapters in 20 states and Canada, 30 state
therapy for the residents of nursing facilities-mostly frail affiliates, over 600 pharmacy student members, and
elderly patients. The term “consultant pharmacists” is hundreds of international members in 18 countries. As
rooted in federal regulations, which requires a pharmacist consultant pharmacists’ practice activities expand and di-
to provide drug regimen reviews for nursing facility versify, so does their need for innovative programs, infor-
residents. The organization has grown dramatically over mation, and resources. ASCP is strongly committed to
the past quarter century and its membership continues to meeting these needs.
diversify and expand their services to people who need
them the most-America’ s seniors, wherever they reside
cati
(Tables 1 and 2).
ASCP offers many opportunities for ACPE-accredited
continuing education at its annual meeting, midyear con-
Table 1 Percentage of ASCP members that provide the ference. and other regional and chapter-sponsored meet-
following services ings, seminars, and workshops. ASCP also enables phar-
macists to gain geriatric pharmacy knowledge thought its
Drug regimen review 64%
IV therapy 34% web-based education sites, which include geriatricphar-
Drug utilization review 34% macyreview.com and scoup.net. (SCOUP is the acronym
Pharmacokinetic monitoring 27 7c for Senior Care Online University for Professionals.)
Drug formulary management 23% The ASCP Research and Education Foundation also
Pain management 20% funds, coordinates, and conducts a wide range of trainee-
Drug research and studies 20% ships and research programs in long-term care and ge-
Nutrition 18% riatric healthcare.
Compliance packaging 15%
Home care 13%
DMEhrgical appliances 11%
Services for fees 7%
ASCP protects the interests of consultant pharmacists and
Laboratory testing 5%
their patients in lobbying and congressional testimony on
American Society of Consultant Pharmacists 55
Capitol Hill, with fcderal regulatory agencies, and with nical Consult, continuing education newsletter, providing
state legislatures. The Society tracks and analyzes in-depth information on a wide range of clinical topics.
hundreds of legislative and regulatory developments na-
tionwide, and maintains an effective political presence
through the ASCP-PAC (political action committee) and
the Capitol Fund, a legislative lobbying fund.
ASCP is the international professional association that
ractic provides leadership, education, advocacy, and resourccs
enabling senior care pharmacists to enhance quality of
To help consultant pharmacists succeed in a demanding care and quality of life for older individuals through the
and changing healthcare environment, ASCP offers a provision of pharmaceutical care and the promotion of
broad array of manuals, tcxts, videotapes, and software healthy aging.
programs. These include the widely used texts: Drug ASCP’s vision include:
Regimen Review: A Process Guide j o r Pharmacists,
100% Immunization Campaign Resource Manual, The e The senior population realiLes improved quality of
Medication Policy and Procedure Manual for Assisted care and quality of life through the provision of
Living, and Nursing Home Survey Procedures and pharmaceutical care.
Interpretive Guidelines: A Resource f o r the Consultant e Senior care pharmacists are recognized and valued for
Pharmacist. A multitude of resource directories arc also their care of patients.
available at ascp.com, which includc Medication-Related e Senior care pharmacists are professionals, essential in
Problems in Older Adults, Geriatrics Resource Page, and healthcare systems.
Fact Sheet on Medication Use in Nursing Facilities. Other 0 ASCP is the acknowledged leader in Senior Carc
ASCP-related web sites include ccgp.com, immunizese- Pharmacy practice.
niors.org, ascpfoundation.org, geriatricpharmacyrcview.
com, and scoup.net. For more information, contact the American Society of
Consultant Pharmacists, 1321 Duke Street, Alexandria,
Virginia 22314-3563; Tcl: 703-739-1 300; Fax: 703-739-
1321 ; e-mail: info@ascp.com; www.ascp.com.
ASCP members rcceive several publications including
The Consultant Pharmacist, the Society’s award-winning
monthly journal presenting peer-reviewcd clinical re- REFERENCE
search, news, and practice management information;
ASCP Update, a monthly newsletter focusing on pharma- I. Bootman, J.L.; Harrison, D.L.; Cox, E. The healthcare cost
cy news, ASCP programs and initiatives, and state and of’ drug-related morbidity and mortality in nursing fa-
federal legislative and regulatory developments; and Cli- cilities. Arch. Intern. Med. 1997, 157 (18), 2089-2096.
PKOFESSIONAL ORGANIZATIONS
c. Talley
American Soc iety of Hedth-Sy5tem Pharmacists
Befhesda, Maryland, U.S.A
to the Practitioner Recognition Program. National and ASHP’s Government Affairs Division staff provides
international recognition can be achieved through author- substantial advocacy for public policy on behalf of ASHP
ship in AJHP and through presentations at ASHP’s members before the U S . Congress, federal agencies
educational meetings. Members qualify for financial (e.g., FDA and HCFA), state legislators, and boards
benefits through ASHP’s MemberCard program, available of pharmacy.
at low rates and with no annual fee. There is also an ASHP The ASHP Section of Clinical Specialists focuses on
Member loan program, and members are eligible for “bringing science to practice” through 17 specialty net-
insurance benefits, including group insurance plans for works, dedicated Web-site content, and section-specific
family term life, short-term medical. catastrophic major electronic listservs and an online membership directory
medical, accident, and disability income protection and in- available only to section members.
hospital care. The ASHP Section of Home Care Practitioners
provides home infusion providers in alternative sites with
special programming at the Midyear Clinical Meeting,
advocacy on reimbursement and JCAHO issues, dedi-
cated Web-site content, section-specific listserv news
services, and an online membership directory available
ASHP is the leading publisher of pharmacy information. only to section members.
The best-known products include: ASHP’ s Center on Pharmacy Practice Management
monitors, analyzes, and reports on trends in pharmacy
e American Journal of Health-System Pharmacy. practice management. It conducts and publishes an annual
9 AHFS Drug Information, the print product; AHFS national survey of pharmacy practice in health systems,
first, the electronic database. and eBookman, the conducts a leadership conference on pharmacy practice
hand-held multimedia content player version. management, and coordinates other educational sessions
9 International Pharmaceutical Abstracts. at ASHP meetings.
8 Handbook on Injectable Drugs. ASHP’s Center on Managed Care Pharmacy monitors,
Clinical Skills Programs, for acute care and ambulat- analyzes, and reports on trends in managed care phar-
ory care. macy, creates specialized programming at ASHP’ s
9 Medication Teaching Manual, the print product; national meetings, conducts conferences and workshops,
MedTeach, the customizable electronic database; and conducts surveys, monitors and influences quality-related
safemedication.com, the Web-based consumer medi- measures, and coordinates networking opportunities.
cation guide. ASHP’s Center on Patient Safety helps pharmacists
lead implementation of proven medication-use safety
Over several decades, ASHP has worked with mem- practices, fosters best practices, identifies training oppor-
bers to develop Best Practices f o r Health-System Phar- tunities, promotes pharmacy’s role, facilitates alliances,
macy, a compilation of statements, guidelines, therapeutic and collaborates with the ASHP Research and Education
position statements, and residency accreditation stan- Foundation to achieve its goals.
dards. In addition to its ongoing creation of practice To better support the success of its members, ASHP
standards, the Office of Professional Practice and Scien- works with other pharmacy organizations, such as the Joint
tific Affairs at ASHP monitors professional practice Commission of Pharmacy Practitioners, the Pharmacy
needs, works with other major health organizations, works Technician Certification Board, the Board of Pharmaceu-
toward the prevention of medication misadventures, and tical Specialties, the Institute for Safe Medication Prac-
communicates with federal and state regulatory bodies tices, and the International Pharmaceutical Federation.
that define pharmacy practice in hospitals and other com- On a broader scale, ASHP’s Public Relations Division
ponents of health systems. works to influence the image of pharmacy with the U.S.
ASHP is the sole accrediting body for postgraduate Congress and regulatory bodies, other healthcare associa-
residency training programs and pharmacy technician tions, hospital and health-system organizations, groups
training programs. In 2001 there were 536 ASHP-ac- concerned with scientific issues, accrediting and licensing
credited programs for pharmacists and 83 ASHP- bodies, groups concerned with consumer and patient
accredited programs for technicians throughout the safety issues, key health-system decision-makers, and the
United States. news media.
PHARMACY PRACTICE ISSUES
Steve e
Temple University, Philadelphi,i, Penn5ylvania, U.S.A.
c3
Farm Formulary
4 environmental isolates. Organisms need to be able to be
Biomass stratified based on site of infection, location within the
hospital, and whether they are community or nosocomi-
Fig. 1 Variables involved in antimicrobial resistance. ally acquired. As has been outlined above, antimicrobial
agents are only one of the variables related to anti-
to be able to draw any conclusions about the success or microbial resistance, and antibiotic rotation should be
failure of antibiotic rotation. seen as one of several modalities that will achieve
antibiotic stewardship. A stable and effective infection
The impact of such a system will be measured in large
control program must be in place, as well as a mechanism
part based on the changes in bacterial susceptibility, so
to optimize antimicrobial prescribing and track all
antimicrobial use. This needs to include the ability to
type organisms, identify genetic markers of resistance,
entiation between nosocomial and community isolates, of the study, these agents were restricted, and other
there was no specific infection control documentation, antibiotics (including other beta-lactams with or without
nonaminoglycoside antimicrobial use was not monitored, an aminoglycoside) were utilized. The authors noted a
and clinical outcomes were not assessed. significant reduction in all VAP, but an increase in VAP
Various investigators have conducted several other caused by methicillin-sensitive Staphylococcus aureus.
studies involving switches within the same class or a ces- Susceptibility patterns for Pseudoinonas aeruginosa and
sation of the use of one agent within a class." 91 Most have Burkholderia cepacia were evaluated and showed im-
demonstrated improved antimicrobial susceptibility that provements over the baseline period.
was maintained as long as the original agent with which Raymond et al. reported on a rotation study in a sur-
poor susceptibility had been seen, was not reintroduced gical intensive care unit with a different twist."31 Patients
into the environment. A recent study by Seppala et al. in were stratified as either having sepsis/peritonitis or pneu-
Finland showed that by reducing the use of erythromycin, monia, and empiric therapy was cycled every 3 months by
the susceptibility of Group A streptococci to macrolides syndrome. Fourteen hundred fifty-six admissions and 540
significantly improved.["] Unfortunately, as newer ma- infections were treated over a 2-year period.
crolides penetrated the marketplace in Finland and began severity of illness during the before and after periods
to be utilized, this trend was quickly reversed (Fig. 3)."n1 (mean APACHE I1 = 19), the authors demonstrated a re-
Kollef et al. conducted a single switch study where duction of length of stay from a mean of 62 days to 39
they treated patients in a cardiothoracic intensive care unit days, a reduction of vancomycin-resistant enterococcal
empirically for 6 months with ceftazidime and then in the and methicillin-resistant staphylococcal infection from 14
second 6-month period, treated patients with ciproflox- per 100 admissions to 8 per 100 admissions and death due
acin."'] They showed a significant reduction in vent- to any cause dropped from 25 in the before period to 18 in
ilator-associated pneumonia (VAP), mostly due to a de- the rotation period. Antimicrobial susceptibility and seve-
crease in the number of patients infected with resistant ral other key parameters needed to evaluate the effec-
Gram-negative bacteria. This study did not employ true tiveness of chis program were not reported.
rotation in that a second 6-month rotation of each therapy Gelone et al. conducted a 3-year prospective study of
was not conducted and. as outlined above. did not meet antimicrobial rotation in three intensive care units at
most of the criteria for an ideal rotation program. Temple University (the START trial)."41 This study,
Gruson et al. conducted a study in a 16-bed medical like those described above, used a before and after ap-
intensive care unit in patients mechanically ventilated for proach. Daily rounds were performed, and the follow-
greater than 2 days."21 During the first phase of the study, ing were assessed on every patient: I ) demographics;
ciprofloxacin and ceftazidime were used empirically to 2) antibiotic regimen and dosing; 3) the presence of
treat Gram-negative infections. During the second phase infection (based on predefined criteria); and 4) organ-
ism susceptibility. All definitions were developed antibiotic control, definitive evidence of its impact in a
prospectively. Criteria for bloodstream, skin and skin- variety of health care settings is lacking. The available
structure, and urinary tract infection were defined based evidence does suggest that antibiotic rotation is associat-
on modified Center's for Diseases Control and Pre- ed with improvements in bacterial susceptibility and a
vention (CDC) criteria. Pneumonia was defined using the decrease in- the incidence of resistant infections. Many
American Thoracic Society's criteria. Resistant organ- questions remain unanswered, including which agents to
ismslinfections were defined as resistance to two or more rotate, how long to rotate, and what settings would most
antibiotics typically used to empirically treat the above benefit from this strategy.
infection in these units (including aminoglycosides, The development of new or novel agents active
ceftazidime, ciprofloxacin, imipenem-cilastatin, and against resistant pathogens is time consuming and at
piperacillin). Baseline data were collected for a 1-year times lags behind new microbial threats. Strategies that
period, and subsequently, a 2-year rotation period was enable the use of currently available agents for extended
carried out. Four regimens for empiric therapy of Gram- periods of time are exciting and necessary. Although
negative infection were rotated on a monthly basis (cefe- antibiotic rotation is promising, there are currently gaps
pime, imipenem-cilastatin, piperacillin- tazobactam, and in knowledge regarding this method of antibiotic control.
ciprofloxacin). The addition of an aminoglycoside was In addition, the data generated to date may not be
left to the discretion of the primary care physician. generalizable across various health care settings. Caution
Susceptibility to studied antimicrobials improved sig- should be exercised in establishing such a program. Indi-
nificantly for Klebsiella pneumoniae, Enterobacter spe- viduals are encouraged to apply as many of the essential
cies, Pseudomonas aeruginosa, and Enterococcus spe- elements noted above in an effort to assess the impact of
cies. Susceptibility remained stable for Staphylococcus this strategy. Documentation of results (both positive and
aureus. Susceptibility significantly decreased for Acine- negative) is essential to define the ultimate role of anti-
tobacter species to imipenem-cialstatin. Resistant blood- biotic rotation.
stream infection decreased significantly (11% versus 4%)
as did resistant pneumonias (15% versus 5.4%). Overall,
antimicrobial expenditures remained stable comparing
before and after periods ($1.5 before and $1.3 million REFERENCES
dollars after). Significant increases were seen in piper-
acillin -tazobactam (23%), imipenem -cilastatin (21%), 1. John, J.F., Jr.; Rice, L.B. The microbial genetics of anti-
and ciprofloxacin (18%) use, while cefepime use de- biotic cycling. Infect. Control Hosp. Epidemiol. 2000, 21,
creased by 34%. Review of crude mortality rates for S22-S31.
bloodstream infections and pneumonia cases showed no 2. Shales, D.M.; Gerding, D.N.; John, J.F., Jr.; Craig, W.A.;
Bornstein, D.L.; Duncan, R.A.; Eckman, M.R.; Farrer,
significant differences.
W.E.; Greene, W.H.; Lorian, V.; Levy, S.; McGowan, J.E.,
The CDC has funded a 2-'12 year, three-center study Jr.; Paul, S.M.; Ruskin, J.; Tenover, F.C.; Watanakuna-
to evaluate antimicrobial rotation in adult intensive care korn, C. Society for Hospital Epidemiology of America
units."51 This trial will utilize 4-month cycles of the and the Infectious Diseases Society of America joint
following drugs: cefepime, a fluoroquinolones, imipe- committee on the prevention of antibiotic resistnace:
nem-cilastatin or meropenem, and piperacillin- tazo- Guidelines for the prevention of antibiotic resistance in
bactam. Investigators will evaluate the acquisition of hospitals. Clin. Infect. Dis. 1997, 25, 584-599.
antibiotic-resistant Gram-negative organisms as gastro- 3. John, J.F., Jr.; Fishman, N.O. Programmatic role of the
intestinal tract colonizers, those associated with clinical infectious diseases physician in controlling antibiotic costs
infection, changes in organism susceptibility over time, in hospitals. Clin. Infect. Dis. 1997. 24, 471-485.
and adverse events and death. At the time of this 4. O'Donnell, J.A.; Gelone, S.P.; Levison, M.E. Antibiotic
Control Systems. In Saunders Infection Control Reference
publication, this project was just underway, and results
Sewice, 2nd Ed.; Abrutyn, E., Ed.; W.B. Saunders Co.,
were unavailable. Orlando, 2000; 52-58.
5. McGowan, J.E., Jr., Unpublished.
6. McGowan, J.E., Jr. Strategies for the study of the role of
cycling on antibiotic use 2nd resistance. Infect. Control
ROLE OF ANTIBIOTIC ROTATION Hosp. Epidemiol. 2000, 21, S36-S43.
7. Gerding, D.N.; Larson, T.A.; Hughes, R.A.; Weiler, M.;
As stated above, antibiotic rotation should be viewed as Shanholtzer, C.; Peterson, L.R. Aminoglysocide resistance
one method of antibiotic control. As with most methods of and aminoglycoside use: Ten years of experience in one
62 Antibiotic Rotation
hospital. Antimicrob. Agents Chemother. 1991, 35, 12. Gruson, D.; Hilbert, G.; Vargas, F.; Valentino, R.; Bebear,
1284-1290. C; Allery, A,; Bebear, C.; Gbikpi-Benissan, G.; Cardinaud,
8. McGowan, J.E., Jr. Minimizing antibiotic resistance in J.P. Rotation and restricted use of antibiotics in a medical
hospital bacteria: Can switching or cycling drugs help? intensive care unit. Impact on the incidence of ventilator-
Infect. Control Hosp. Epidcmiol. 1986, 7, 573-576. associated pneumonia caused by antibiotic-resistant gram-
9. Bonhoeffer, S.; Lipsitch, M.; Levin, B.R. Evaluation of negative bacteria. Am. J. Respir. Crit. Care Med. 2000, 162
treatment protocols to prevent antibiotic resistance. Proc. (3 Pt. l), 837 843.
Natl. Acad. Sci. U. S. A. 1997, 94, 12106-12111. 13. Raymond, D.P.; Pelletier, S.J.; Crabtree, T.G.; Gleason,
10. Seppala, H.; Klankka, T.; Vuopio-Vakila, J.; Muotiala, A.; T.G.; Hamm, L.L.; Pruett, T.L.; Sawyer, R.G. Impact of a
Helenius. H.; Lager, K.; Huovinen, P. The effect of rotating empiric antibiotic schedule on infectious mortality
changes in consumption macrolide antibiotics on erythro- in an intensive care unit. Crit. Care Mcd. 2001, 29, 1101-~
mycin resistance in Findland. N. Engl. J. Med. 1997, 337, 1108.
441 -446. 14. Gelone. S.P.; Lorber, B.; St. John, K.; Badelino, M.;
11. Kollef, M.H.; Vlasnik, J.; Sharpless, L.; Pasque, C.; Axelrod, P.; Crincr, G. Prospective evaluation of antibiotic
Murphy, D.; Frascr, V. Schedule changes of antibiotic rotation on three intensive care units at a tertiary care uni-
classes: A strategy to decrease the incidence of ventilator versity hospital. Pharmacotherapy 2000, 20, abstract #107.
associated pneumonia. Am. J. Respir. Crit. Care Med. 15. Centers for Disease Control and Prevention Program
1997, 156 (4 Pt. I ) , 1040- 1048. Announcement #99149.
PROFESSIONAL DEVELOPMENT
showed how unstandardized PT tests could lead to community pharmacy-based clinics. In a year 2000
significant error and misjudgment."'] The adoption of survey, approximately 20% of the 250 National Health
the INR is considered one of the most significant ad- Service hospitals had a pharmacist-led anticoagulation
vances in anticoagulation therapy. clinic; these anticoagulation clinics are now working
together to develop a master protocol for the initiation of
DVT treatment, management of anticoagulation treatment
CY O TUNlTl in outpatients, training of anticoagulation personnel, and
research opportunities.[411 Pharmacists have also been
ulatisn Clinics in the Unite involved in a pharmacist-led outpatient DVT clinic.[381At
Neath General Hospital, it was determined that there was
There have been many articles published concerning a potential savings of 268 inpatient-bed days annually by
pharmacist involvement with anticoagulation clinics. Ty- employing the outpatient DVT clinic.[3s1A former senior
pically, such anticoagulation clinics are in hospital- general practitioner at Downfield surgery in Dundee
based, outpatient settings. In the United States, the ma- explained how working with a team, specifically with
jority of these clinics are in the outpatient units of the pharmacists, led to improved patient care, innovation, and
Department of Veterans Affairs Medical Centers development.[421He noted that pharmacists are playing a
(VAMC) and other teaching hospital^.[^^^,^,^,'^-^'' These major role in implementing national evidence-based
anticoagulation clinics are usually responsible for the guidelines to improve the quality of patient care.[421
management and coordination of warfarin therapy. The
first report of a pharmacist-managed anticoagulant clinic
was published in 1979.'21This report described a pharma-
cist-managed anticoagulation clinic at McGuire VAMC There may not be such a thing as a typical anticoagulation
in Richmond, VA, that began in the Department of Car- clinic. Generally, however, a physician will serve as a
diology. Although the majority of anticoagulation clinics director or consultant for the clinic. The physician may
exist in VAMC or university-affiliated teaching hospitals, directly oversee each plan the pharmacist formulates, or
there have been descriptions of an outpatient anticoagula- the pharmacist may follow some type of protocol without
tion clinic in a private community hospital[281and in man- being directly supervised by the physician. In many
aged-care setting^.[^^-^'] There is a growing network of clinics, the pharmacist has responsibility for designing an
private practice-based, for-profit clinics.[321Anticoagula- appropriate anticoagulant regime for the patient. The
tion clinics can also be found in the inpatient ~ e t t i n g . [ ~ ~ - ~ pharmacist
~] is normally responsible for the day-to-day
operations of the clinic. Pharmacists are also responsible
Outpatient Trea for enrolling patients in the anticoagulation clinic by
~ h r ~ m b s swit is obtaining medication and medical histories, and by
assessing factors that may affect the control of the
With the advent of LMWH, anticoagulation clinics are therapy. The pharmacist is responsible for counseling
now using LMWH, by use of which patients can avoid patients about the signs and symptoms of bleeding and
being admitted into a hospital or shorten the length clotting, compliance with medications and follow-up
of h o s p i t a l i ~ a t i o n . [ ~ ~Patients
- ~ ~ ~ ~ ~can
~ ~ have their in- appointments, drug interactions, food interactions, and
jections done at home. Patients with a confirmed di- how health status affects warfarin. Generally, the patient
agnosis of deep vein thrombosis (DVT) are evaluated to presents for a blood draw either via venous puncture or
determine eligibility to receive LMWH via outpatient. via point-of-care testing. Point-of-care testing is currently
Once the patient is eligible, a nurse typically administers being used in a few clinic sites and is done via portable
the first dose, and the pharmacist begins the counseling machine. It measures the INR from a fingerstick sample
and evaluates the patient's ability to self-inject. The of whole blood and provides results within minutes. If the
anticoagulation clinic then follows up with the patient patient has blood drawn from a venous puncture, the
until determining that anticoagulation therapy is no patient will have to wait for results, or some clinics will
longer required. call or mail them to the patient. With modern technology,
an efficient lab can provide INR results within 15 minutes
linics in the Unite of a blood draw. If blood is drawn from a finger stick, the
patient will receive the results immediately and will be
In the United Kingdom, pharmacists have also managed given instructions on dosing of warfarin and follow-up
anticoagulation They can be found in instructions for returning to the clinic. Regardless of the
hospital clinics, general practitioner surgery clinics, and means of testing, patients are assessed for compliance
Anticoagulation Clinical Pharmacy Practice 65
with the anticoagulant, signs or symptoms of bleeding or have been estimated between $860 and $4072 per pa-
clotting, recent changes in diet, appetite, medications, tient per year of therapy for patients on oral antico-
alcohol consumption, and illnesses. Based on the patient's agulation Anticoagulation clinics that
INR and assessment of the previous factors, the anti- have used LMWH for DVT treatment in the outpatient
coagulant may be continued or adjusted. A follow-up setting have estimated cost-avoidance savings between
appointment is then made. $1800 and $2470 per patient These savings
not only reflect improved anticoagulation management,
Safety but also reflect pharmacists identifying and intervening
with other medical conditions. Chiquette et al. described
Table 1 summarizes nonrandomized, mainly retrospective $300 savings per patient per year in regards to other
studies that compare frequency of hemorrhage and interventions besides anticoagulation management.[l7I
thromboembolism prior to being enrolled into a phar-
macy-managed anticoagulation clinic and after enroll- ysician Sati~fact~on
ment. These studies demonstrate a decrease in adverse
events when patients are followed in a pharmacist- Three surveys have been published on patients' per-
managed anticoagulation clinic. Many of these reports ceptions of a pharmacy-managed anticoagulation cli-
compare adverse events before there was an anticoagu- nic.[19,2"'291 Ge nerally, patients found pharmacists to be
lation clinic versus after an anticoagulation clinic was caring and ~ o m p e t e n t . " ~Patients
] perceived that they were
instituted. The study by Chiquette et al. was unique in at a decreased risk of having problems with warfarin and
that it compared results with three different inception blood clotting due to pharmacist involvement, and they
groups."71 All the patients were newly started on war- believed that frequent monitoring of their warfarin would
farin, two groups were in a pharmacy-managed anticoa- mean less chance of bleeding or clotting.[251 Overall,
gulation clinic, and one group was managed by routine patients were highly satisfied with the care they received
medical care."71 from a pharmacist-managed anticoagulation clinic.[291A
survey of physicians published in the United States elic-
ited 21 out of 41 responses and showed that physicians
were positive about the care their patients were receiving
The cost effectiveness of pharmacy-managed anticoagu- from a pharmacy-managed anticoagulation clinic.[291
lation clinics has been addressed in a few s t ~ d i e s . " ~ , ' ~ , ' ~ ]
Usually the benefits are determined from decreased ad- uture
verse events and decreased hospitalization and emergen-
cy visits. In one study, hospitalizations and emergency The future for anticoagulation clinics is bright. Every year
room visits were reduced by 50 to 80%."'] Savings there is evidence of increased interest in this area. The
Table 1 Frequency of hemorrhage and thromboembolism with routine medical care versus pharmacist-managed
anticoagulation clinics
Type of No. of Patient Major Minor
Studyb care patients years hemorrhage' hemorrhage' Thromboembolis~'
biggest problem facing anticoagulation clinics today is through a multidisciplinary national certification process
reimbursement. Pharmacists currently can only bill for a for registered nurses, advanced practice nurses, pharma-
minimal visit, whereas other practitioners such as nurse cists, physician’s assistants, or physicians. Any creden-
practitioners and physician’s assistants can charge three tialed individual who is a Certified Anticoagulant Care
to five times as much per visit due to their provider sta- Provider (CACP) should possess advanced antithrombo-
tus. Oral anticoagulation monitoring may become more tic/anticoagulant knowledge. Practitioners are required to
common in the community setting as pharmacists learn submit evidence of their practice experience and obtain a
more about anticoagulation and as more states allow passing score on a comprehensive examination. CACP
pharmacists to adjust medications. Patients may find it providers must possess a valid US.professional license,
to be more convenient due to proximity of local phar- as well as the knowledge and skills to provide high-
macies, and with the availability of portable point-of- quality care to patients. The certification and examination
care testing, patients can receive results Many began in 1999; as of the spring of 2000, there were 68
patients may ultimately perform testing at home with CACP providers, 44 of these being pharmacists.[461 (To
portable machines.[441Home testing can be performed in obtain more information, contact the NCBAP through
a couple of ways. Either the patient tests the blood at www.acforum.org or write to NCBAP, c/o Anticoagula-
home and calls in the results to the anticoagulation clinic, tion Forum, Boston University Medical Center, Room E-
or the patient follows a protocol to adjust the warfarin 113, 88 E. Newton Street, Boston, Massachusetts 02118-
dosage at home.[441There will always be some patients 2395, phone 716-638-7265.) The National Institute for
not capable of performing their own testing. Even if Standards in Pharmacists Credentialing (NISPC) was
the patient is monitoring his or her blood at home, formed in 1998 by the American Pharmaceutical Asso-
pharmacists will still need to be involved by providing ciation, the National Association of Boards of Phar-
education and making dosage change recommendations, macy, the National Association of Chain Drug Stores,
especially when confounding factors exist, such as drug and the National Community Pharmacists Association.
interactions and illnesses. Currently, the disadvantages The NISPC provides a nationally recognized credential-
of the portable machines are that they are expensive ing process that establishes appropriate standards of care
and that follow-up management is not billable. Re- and facilitates recognition of the value of disease state
cently, Roche Diagnostics withdrew its point-of-care management services such as anticoagulation provided
testing machine for patient’s home use due to insurance by pharmacists. (To obtain more information, contact the
companies. hospitals, and clinics not willing to pay for NISPC Testing Center through www.nispcnet.org, or
such machines. Results of portable machine monitors write to NISPC Testing Center, 700 Busse Highway, Park
versus routine lab results may diverge at high INRs; Ridge, Illinois 60068-2402, phone 847-698-6227.)
however, this also can occur between two different rou-
tine laboratories. Two studies reported that the portable raini
monitor was more reliable, less variable, more repro-
ducible, and less likely to give clinically misleading and The Anticoagulant Therapy Management Certificate Pro-
erroneously high INR results than the laboratory of a gram is an internet-delivered program developed by the
major medical center.[451 University of Southern Indiana, School of Nursing and
Health Professionals. This program is a collaborative ef-
fort among regional health care providers. members of
the NCBAP, and the University of Southern Indiana
School of Nursing and Health Professionals. Their goal
is to prepare health professionals for monitoring and
managing outpatient anticoagulation therapy. This pro-
gram will also prepare health professionals for the
Pharmacists in anticoagulation clinics should be able to National Certified Anticoagulation Care Provider Exam-
demonstrate advanced knowledge of anticoagulation. ination. (For information, visit the web site at http://
More recently, the importance of credentialing anti- healthusi.edu or call 1-877-874-4584.)
coagulation providers has come to the forefront. This The American Society of Health-Systems Pharmacist
may become more important in the future for pharmacy (ASHP) Foundation provides a 5-day, experience-based
practitioners who want reimbursement for their services. certificate program called the Anticoagulation Manage-
The National Certification Board for Anticoagulation ment Service Traineeship Program. This program is
Providers (NCBAP) has a mission to optimize patient care designed to train pharmacy practitioners to establish and
Anticoagulation Clinical Pharmacy Practice 67
maintain specialized services for the management of pa- * Advanced knowledge of the pathophysiology of
tients undergoing long-term anticoagulant therapy. The thromboembolic disease states.
program is intended to provide individualized, intensive * Experience with physical assessment and interviewing
didactic and clinical training for selected candidates. patients.
Trainees will observe and participate in the activities of * Experience preparing and providing in-service edu-
an established anticoagulation management service. This cation to other health care professionals and patients.
program provides 35 hours of continuing education. * A working knowledge of basic hospital and clinic
(Applications and additional information may be obtained policies and quality assurance practices.[”]
by calling the ASHP Fax-on-demand system at 301-664-
8888 and requesting documents 702 and 703, or by These requirements were met through reading review
logging on to their web site at www.ashpfoundation.org.) and research articles, observing patient interviews and
The American College of Clinical Pharmacy (ACCP) conducting patient interviews under direct observation of
Research Institute, University of Texas (UT), and Antic- a privileged anticoagulation clinic pharmacist, presenting
oagulation Clinics of North America (ACNA) provides a an in-service, and passing a credentialing examination.[211
minimum 4-week, intensive traineeship that includes a
structured didactic component. extensive clinical experi-
ence in several ACNA practice sites in San Antonio, TX, RESOURCES
and surrounding communities; and participation in on-
going clinic research. The program is targeted primarily There are a few critical papers or publications that a
to PharmD students in their final year of professional practitioner should have available in the clinic:
study, but pharmacy residents and fellows as well as prac-
ticing pharmacists are encouraged. Applicants have also * Consensus Conferences on Antithrombotic Therapy
come from other countries. Arrangements can be made sponsored by the American College of Chest Physi-
with ACNA/UT faculty for students to receive academic ~ians.[~’] This provides a comprehensive review and
credit from their home institution for the experience. recommendations performed by international experts
(Applications can be obtained through www.accp.com/ on antithrombotic therapy.
ClinNet/Research.html or by calling 816-53 1-2177.) * British Committee for Standards in Haematology
The University of Illinois at Chicago offers an Anti- Guidelines.[491This document tends to be the guideline
thrombosis Management Service Certificate Program via used in Europe. It contains information on indications
the Internet. It is a 9-week certificate program and offers for oral anticoagulation and management of an anti-
40 contact hours. This program covers a wide array of coagulation service.
topics, including pharmacotherapy, patient assessment, * The Consensus Guidelines f o r Coordinated Outpatient
protocol development, and business planning. (Applica- Oral Anticoagulation Therapy This
tions can be obtained through conted@uic.edu or by guideline contains information on the organization
calling 866-742-7623.) and management of anticoagulation clinics.
* Managing Oral Anticoagulation Therapy, Clinical
Credentialing and Operational Guidelines.[” Written by a multi-
disciplinary group of health care providers. This is an
A 1996 survey conducted nationwide in the United States excellent resource that covers the development and
elicited 110 responses out of 177 pharmacist-managed implementation of an anticoagulation management ser-
anticoagulation clinics ~ontacted.‘~’]As per the results, vice and management of patients receiving oral anti-
23% offered some type of anticoagulation training pro- coagulants. The chapters contain examples of actual
gram and 29% had at least one pharmacist who completed policies, procedures, guidelines, algorithms, charts,
the ASHP Research and Education Foundation’s Anti- and flow sheets used in anticoagulation clinics across
coagulation Service T r a i n e e ~ h i p . ~At~ ~the
] McClellan the United States.
Memorial VAMC in Little Rock, Arkansas, the anti- * The NCBAP puts forth competency statements for
coagulation clinic has specific guidelines on how their certified anticoagulation care providers. There are
pharmacists should be trained and credentialed.[211 five domains:
Pharmacists are required to have the following:
* Applied physiology and pathophysiology of throm-
* Advanced knowledge of the pharmacology and phar- boembolic disease.
macokinetics of anticoagulants. * Patient assessment and management.
68 Anticoagulation Clinical Pharmacy Practice
ASHP Foundation provides an example of an anti- Although important, only limited information is available
coagulation clinic protocol. in the literature concerning the legal issues of operating an
0 Drug-use evaluation criteria that have been put anticoagulation clinic. Legal issues are mentioned briefly
forth by ASHP.[511These criteria serve as guide- in the 2001 Chest supplement.[541It describes strength in
lines for quality assurance. unanimity among anticoagulation clinics.[541As the num-
ber of anticoagulation clinics increases and as more
0 The web site of the Anticoagulation Forum (www. studies show that anticoagulation clinics improve patient
acforum.org) has links to continuing education, news care, anticoagulation clinics are becoming the standard of
and events, newsletters, and clinic locations.[521 care. Other means of managing anticoagulated patients
0 The Department of Health in the United Kingdom may have to demonstrate services that are equal or sup-
provides an anticoagulant booklet, which provides pa- erior to an anticoagulation
tients with information on anticoagulation [obtained Another issue that may impact pharmacist-managed
from DHSS Stores, No. 2 site, Manchester Road, Hey- anticoagulation clinics will be collaborative drug therapy
wood, Lancashire OLlO 2PZ, or SHHD (Div. IIID), management (CDTM) based on legislated statute. Anti-
Room 9, St. Andrews House, Edinburgh EH1 3DE].[491 coagulation clinics are a good example of CDTM.[551It
is officially recognized in 25 states and by the federal
government (i.e., U S . armed forces, VAMCs, Indian
PROFESSIONAL NETWORKING Health Service).[551 Typically, the physician delegates
OPPORTUNITIES management authority to the pharmacist with the terms
of a formal agreement.[551It allows pharmacists to order
The Anticoagulation Forum, founded in 1991, is an laboratory tests, assess patients, initiate and modify drug
excellent avenue for professional networking. It brings therapy, monitor patients, and administer medications.[551
together three health care disciplines-medicine, nursing, States without CDTM may limit the pharmacist’s role in
and pharmacy. This organization has global membership an anticoagulation clinic.[551To avoid litigation, pharma-
and is interested in anticoagulation management in the cists should be well trained, act within protocol frame-
setting of a coordinated anticoagulation management work, document thoroughly, and always be sure patients
service. It is supported by the pharmaceutical and are aware that a pharmacist is providing
diagnostics industry. Currently, the organization’s web
site contains information about news and events, articles,
meetings, and continuing education.[521It can be accessed REFERENCES
through the following web site address: www.acforum.
~rg.[~ There
~ I are currently more than 2300 members Davis, F.B.; Estruch, M.T.; Samson-Corvera, E.B.; Voigt,
representing 25 countries and more than 800 antic- G.C.; Tobin, J.D. Management of anticoagulation in
oagulation clinics.[521These countries include the United outpatients: Experience with an anticoagulation service in
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Brazil, Slovenia, Denmark, Holland, Sweden, Switzer- (2): 197-202.
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16. Lee, Y.-P.; Schommmer. J.C. Effect of a pharmacist- 33. Chenella, F.C.; Klotz, T.A.; Gill, M.A.; Kern, J.W.;
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admissions. Am. J. Health-Syst. Pharm. 1996, 53 (13), Cheetham, T.C.; Noguchi, J.K.; McGehee, W.G. Compar-
1580-1583. ison of physician and pharmacist management of anti-
17. Chiquette, E.; Amato, M.G.; Bussey, H.I. Comparison of coagulant therapy of inpatients. Am. J. Hosp. Pharm. 1983,
an anticoagulant clinic with usual medical care. Arch. 40 (10); 1642-1645.
Intern. Med. 1998, 158 (15), 1641-1647. 34. Ellis, R.F.; Stephens, M.A.; Sharp, G.B. Evaluation of a
18. Kroner, B.A. Anticoagulation clinic in the VA Pittsburgh pharmacy-managed warfarin-monitoring service to coordi-
healthcare system. Pharm. Pract. Manage. Q. 1998, 18 (3), nated inpatient and outpatient therapy. Am. J. Hosp.
17-33. Pharm. 1992, 49 ( 2 ) , 387-394.
A n t ~ c ( ~ ~ ~ u 1Clinical
a ~ i o n Pharmacy Practice
35. Mamdani, M.M.; Racine, E.; McCreadie, S . ; Zimmerman, Clark, G.M. A statistical and clinical evaluation of
C.: O'Sullivan, T.L.; Jensen, G.; Kagatzki, P.; Stevenson, fingerstick and routine laboratory prothrombin time mea-
J.G. Clinical and economic effectiveness of an inpatient surements. Pharmacothcrapy 1997. 17 ( 5 ) , 861-866.
anticoagulation service. Pharmacothcrapy 1999. I 9 (9), 46. Certified Anticoagulant Care Providcr (CACP) exam.
I Oh4 1074.
~
Anticoagulation Forum Newsl. 2000. 5 (1).
36. Radley, A.S.; Hall, J.; Farrow, M.; Carey, P.J. Evaluation 47. Mehlbcrg, J.; Wittowsky, A.K.; Possidente, C. National
of anticoagulant control in a pharmacist operated anti- survey of training and credentialing methods in phar-
coagulant clinic. J. Clin. Pathol. 1995, 48 (6), 545-547. macist-managed anticoagulation clinics. Am. J. Health-
37. Macgregor, S.H.; Hamley, J.G.: Dunbar, J.A.; Dodd. Syst. Pharm. 1998. 55 (lo), 1033- 1036.
T.R.P.; Cromarty, J.A. Evaluation of a primary care 48. Sixth ACCP Consensus ConPerence on Antithrombotic
anticoagulant clinic managed by a pharmacist. BMJ Therapy. Dalen, J.E., Hirsh, J., Bds.; Chest, 2001; 119 (1);
1996, 312 (7030), 560. IS-370S, (SUPPI.).
38. Hughes, E.C.; John, N.R.; Swithenbank, P.J. Setting up 49. Baglin, T.P.: Rose, P.E.; Walker. I.D.; Machin, S . ; Baglin,
and evaluating a pharmacist-led outpatient DVT clinic. T.P.; Barrowcliffe, T.W.; Colvin. B.T.; Greavcs, M.;
Pharm. J. 1999, 263 (7063), R66-R67. I d l a m , C.A.; Mackie, I.J.; Preston, F.E.; Rose, P.E.
39. Leach, R.H.; Calvcrt, P.S. Service developments at har- Guidelines on oral anticoagulation: Third edition. Brit. J .
rogate district hospital. Hosp. Pharm. 2000. 7 ( I ) , 20 23. Haem. 1998, 101, 374 387.
40. Radley, A.S.; Dixon, N.; Hall, J. Primary care group 50. Ansell, J.E.; Buttaro, M.L.; Thomas. O.V.: Knowlton. C.H.
anticoagulant clinics. Prim. Care Pharm. 2000, 1 , 70- 72. Anticoagulation guidelines task force. Conscnsus guide-
41. Davc.Roberts~uhw-tr.walcs.nhs.uk, e-mail, September lines for coordinated outpatient oral anticoagulation
25, 2000. therapy management. Ann. Pharmacother. 1997. 31 (9,
42. Macgregor, S. A general practitioner pcrspcctivc. Prim. 1604 1615.
Care Pharni. 1999. 1 (l), 18-19. 51. Hiatt, J . ; Zabloeki, C.I.; Wittowski, A.K. Criteria for use of
43. McCurdy, M. Oral anticoagulation monitoring in a com- warfarin in adult inpatients and outpatients. Clin. Pharm.
munity pharmacy. Am. Pharm. 1993, NSi.7 (1 0), 6 I 70. 1993, 12 (4); 307 3 13.
44. Ansell, J.E.; Hughes, R. Evolving models or warfarin 52. www.acforum.org (accessed September 2000).
management: Anticoagulation clinics, patient self-moni- 53. Barbara.Ganick@bmc.org, e-mail, September 26, 2000.
toring, and patient self-management. Am. Heart J. 1996, 54. Mclnlyre, K. Medicolegal implications 01 the consensus
132 ( 5 ) , 1095- 1100. confcrcnce. Chest 2001, I1 9 (1). 3378-343s. (Suppl.).
45. Busscy, H.I.; Chiyuette, E.; Rianco, T.M.; Loweder- 55. Koch, K.E. Trends in collaborative drug therapy manage-
Bender, K.; Kraynak, M A . ; l h n , W.D.; Farnett, L.; ment. Drug Benefit Trends 2000, 12 (I), 45-54.
P KOF ESSI0NA L 0R G A N IZ AT I(1N S
0 To roster and promote progress in pharmaceutical The Association convenes an annual conference in late
education and research. May or June of each year. The Executive and Council also
hold a mid-year meeting 111 February with the primary ton, AB T6C 2W8;Phone. (780) 492-0202: Fax: (780)
purposc of conducting intcrnal b u m c \ \ and meeting with 492-1 21 7. E-mail: jbachyn\ky@pharinacy u a l b e r t a a
external pharmacy and related organvations.
Dr. Yvotztze Shrvchuk (2003), College of Pharmacy and
Nutrition, University of Saskatchewan, 1 I0 Science
lace; Saskatoon, S S7N 5C9; Phone: (306) 966-
6330; Fax: (306) 966-6377; E-mail: shevchuk@duke.
usask.ca
Dr. John Bachynsky (2001), Faculty of Pharmacy and As\oci'ition of Faculties of Pharmacy o f Canada; w w w d p c .
Pharmaceutical Sciences, University of Alberta, Edmon- info.
PHARMACY PRACTICE ISSUES
Although ADRAC clearly encourages reporting of all service is provided in a very timely fashion, with the
suspected adverse drug reactions in Australia (including turnaround time for the feedback of information routinely
those to alternative medicines, including herbal and ho- less than 24 hours.
meopathic products), the committee has provided guid- In addition to providing access to the information
ance in relation to reactions of particular interest. Reac- stored in the database, ADRAC also utilizes the infor-
tions that result in death, danger to life, admission to mation received in reports for a range of other purposes.
hospital, prolongation of hospitaliration, absence from The ADRAC bulletin is published four times each year
productive activity, or increased investigational or treat- and is widely distributed to medical practitioners and
ment costs have been identified as priority areas for pharmacists free of charge. The bulletin, which is also
ADRAC. In addition lo these reports, the committee also available on the Internet (www.health.gov.au/tgddocs/
requests the reporting of all suspected drug interactions, html/aadrbidx.htm), summarizes details of common or
as well as all reactions thought to have been implicated important drug reactions and interactiocs and in this
as a cause of birth defects. Naturally, reaction reports are way serves an important educative function. Information
also sought for drugs that have been newly released onto from ADR reports is also summarized into reports that
the Australian market. are published up to three times a year in the Medical
Journal of Australia. ADR data from ADRAC are also
forwarded to the Collaborating Centre for International
Drug Monitoring of the World Health Organization in
Uppsala, Sweden.
The Australian Medicines Handbook (AMH) is a com- ‘The concept of a “national formulary” modeled on thc
pendium of drug and therapeutic information. It was BNF was recommended in 1991 following a meeting
developed to provide pharmacists, doctors, other health convened by the Australian Society of Clinical and Ex-
professionals, and their students with concise, independ- pcrimental Pharmacologists and Toxicologists (ASCEPT)
ent and comparative information about drugs and quality and the Consumers’ Health Forum. In June 1995, money
drug use in Australia. was granted by the Australian Government to develop a
drug information database suitable for publishing printed
and electronic versions of an Australian Medicines
Handbook. The publishing phase was not initially funded.
First staff were appointed in Dccember 1995.
In May 1998, the first edition, AMH 1998, was
A compendium of drug and therapeutic information, the published. The sccond cdition, AMH 2000, was published
AMH is an initiative of Australia’s National Health Policy in February 2000. CD-ROM and lnternct products, based
in response to professional, consumer, and government on second edition content, were released in May 2000,
concerns about the lack or independent drug inlormation with upgrades relcased in April 2001. A set of third
resources in Australia. AMH was developed to providc edition products is planned for release in early 2003.
pharmacists, doctors, other health professionals, and their Australian Medicines Handbook Ply Ltd., the
students with indcpcndent and comparative information business entity that owns thc content and publishes
about drugs. the products, was established with Australian govern-
AMH was initially modeled on the British National ment funding. It received its final funding in March
Formulary (BNF), and evolved to incorporate further 1999, and now operates on a fully commercial basis.
comparativc and therapeutic information. The best The three shareholders of the company are the Royai
available evidence is uscd to support rccommcndations, Australian College o€ General Practitioners, the Phar-
thus discouraging drug use where evidence is lacking maceutical Society of Australia, and the Australasian
or poor. Society for Clinical and Expcrimental Pharmacologists
AMH publications are designed as practice, teaching, and Toxicologists.
and learning tools, and aim to promote Quality Use of
Medicines (QUM) by providing readily accessible, con-
cise, up-to-date, clinically relevant information that h-
cilitatcs effective, rational, safe, and economical pres-
cribing and dispensing.
AMH complcrnents other independent Australian The first edition was available only in print version
publications about drugs and therapeutics including (book) and sold approximately 9500 copies. The second
Australian Prescriber, the Therapeutic Guideline series, edition, AMH 2000, is cxpected to at least match this
and National Prescribing Scrvice publications. It providcs figure in print version sales. CD-ROM and Internet
a different focus to drug information compendia bascd versions based on the sccond edition have made a signi-
on government-approved Product Information. ficant impact on uptake.
Uptake by community and hospital pharmacists and children, and the elderly are included. AMH documents
undergraduate pharmacy training is very high. Most frequently include .‘Practice points,” which include brief
medical students in Australia now use AMH. In teaching information, advice, and tips that are important for the
hospitals, uptake by nurses and doctors is moderate to safe and effective use of a particular drug or drug class.
high but varies by state. Although uptake in general General principles of drug use for groups of drugs,
practice is moderate (about 10 to 20%), it appears to be such as anti-infectives, antineoplastics, and ocular drugs,
steadily increasing (1). are also provided.
BENEFITS
In Australia, the most commonly utilized and accessible Although passive provision of this high-quality targeted
information sources about prescription drugs are based on information alone is unlikely to change prescribing be-
a drug‘s Product Information, the document approved by havior and improve health outcomes, access to impartial
Australia‘s drug regulation authority, the Therapeutic drug information is recognized as a component of the
Goods Administration (TGA). WHO/INRUD drug use indicators ( 2 ) and is an identified
AMH content is written after consideration of best strategy in the implementation plan of Australia’s Na-
available scientific evidence, the Product Information, tional Prescribing Service.
standard international reference sources, and Australian The perceived benefits of AMH are:
evidence-based and consensus guidelines from govern-
ment and nongovernment agencies. Information is concise It is a good starting point for drug-related questions,
and clinically relevant for Australian practice, providing and can save time by providing reliable up-to-date
comparisons between drugs and between drug classes, information in a user-friendly format.
with a focus on comparative efficacy, safety, and cost. 0 It provides practical knowledge and advice that is
Key advice for patients about how to use medicines safely independent of government and acts as a balance to
and effectively is included. promotional information provided by the phannaceu-
tical industry.
Types of Information Presented It is written in minimally technical language and can
be used as an aid to patient consultations.
Information in the AMH is organized into 20 chapters, * It is suited to both hospital and community use.
according to organ-system (e.g., neurological drugs).
Each chapter contains brief disease treatment summaries AMH has been credentialed by key health professional
(e.g., hypertension), which incorporate discussion of organizations such as the Australian Medical Association
various treatments, including nondrug and complement- Council of General Practice, the Society of Hospital
ary therapies, and comparison of different classes of Pharmacists of Australia, the Australian Divisions of
drugs. Treatment summaries also include advice for ap- General Practice, and the National Prescribing Service.
propriate management for specific groups of patients or Consumer groups such as Consumers Health Forum and
stages of disease. government advisory groups such as the Pharmaceutical
Drug profiles are arranged by generic drug name and Health and Rational Use of Medicines committee and the
Iisted under drug class profiles (e.g., ACE inhibitors); this Australian Pharmaceutical Advisory Committee have also
allows for comparison across a class to be made, and given support.
minimizes repetition of information common to all
members of the class. Indications listed in monographs
are generally those that are approved by TGA. Additional CONTENT
accepted clinical uses such as minor indications for which
there are few or no other alternative drugs and there is Creation
evidence to support such use are also included. Dosage
information is clear and concise; interactions information AMH content is derived in-house by a small team of
is limited to those likely to be important clinically, highly skilled and experienced editors, most of whom are
together with advice on management. Information and pharmacists. Editors possess postgraduate training and
recommendations regarding use of a particular drug in experience in areas such as drug information and critical
pregnancy, breastfeeding, renal or hepatic impairment, appraisal, pharmacoepidemiology, pharmacoeconomics,
and editing. Work experiences are broad and include the tioners (urban and rural). and allied hcalth workers when
pharmaceutical industry, academic detailing, hospital- relevant (e.g., diabetes and asthma nurses and educators).
based clinical pharmacy, and medical writing. In addition, These reviewers arc not remunerated, but they receive a
a small number ol‘ paid external contributing writers hclp compliineiitary copy or AMH, and their contribution I\
expand and update specific parts of the content. In acknowledged in the publications.
addition to regular surveillance of published pharma-
cotherapeutics literature, spontaneous feedback rrom
readers assists in developing and refining content.
The Editorial Advisory Board contains academics and
practitioners in pharmacy, clinical pharmacology, and
general practice. Some members have substantial experi-
The review process for the scientific aspects or the
ence in medical editing and publishing. They are asked to
content involves four steps. After initial drarting or
declare any potential contlicts or interest.
updating by an AMH editor or external contributor, a
As well as assisting in the review process, the Editorial
second AMN editor will review material for adherence to
Advisory Board helps set editorial policy and approve
house style and for scientific content. Content is modified
plans for new content or major update.
based on this review. The draft matcrial is then sent out in
parallel to members of the Editorial Advisory Board, and
a Review Panel (external reviewers) who are spccifically
recruited to look at particular sections. Inrormation
regarding drug use in renal impairment and pregnancy
or breastfeeding is reviewed by external specialist clinical Although a traditional publishing process was used in the
pharmacists. AIter consideration of all reviewers’ com- creation or the first two editions o f AMH books, the need
ments, a final draft is created and sent to the Editorial to provide users with multiple formats has required the
Advisory Board for approval. work environment to be re-engineered and editors now
In this way, a combination of experts and end-users work in an SGML environment. This allows production
review AMW content. At present, a team of about 150 of reports such as a print-ready file (from which the
external reviewers assist in the Review Panel process. book is published); an HTML version that serves as the
They include general practitioners and specialist physi- current CD-ROM and web-based products; and poten-
cians and surgeons, academics and researchers, hospital tially other formats or subsets of AMH data, from one
and community pharmacists, specialist nurses, and set of source files.
educators from organizations that support consumers with Future developments include adding a production
chronic illnesses. Each Review Panel contains expert pathway to allow a personal digital assistant version of
specialist clinicians, a clinical pharmacologist with an AMK to be produced, and incorporation or an XML
interest in the specific area, hospital-based clinical database into the work environment, which will allow for
pharmacists, community pharmacists, general practi- complex queries to be performed on the data set.
PROFESSIONAL RESOURCES
aKge
Eon Lnh, M,mufacturing, In(., Laurelton, New York, U.S.A.
Manufacturing considerations
Production methodology and technology Cost
Quality control/quality assurance Stability testing
Specification of raw materials
Patient considerations Compliance, labeling. and product acceptance Cost
w
00
84 Biopharmaceutics
Fig. 1 Scheme demonstrating the dynamic relationships among the drug, the product, and pharmacologic effect. (From Ref. 1.)
by intramuscular injection include, local irritation, drug process of drug disintegration, dissolution, and absorption,
dissolution, and drug absorption from the injection site. the rate at which drug reaches the circulatory system is
Biopharmaceutic studies may be performed using determined by the slowest step in the sequence.
in vitro or in vivo methods (Table 3). In vitro methods are The slowest step in a kinetic process is the rate-limiting
useful (2-6) to understand the physico-chemical proper- step. Except for controlled release products, disintegration
ties of the drug and drug product and to evaluate the of a solid oral drug product is usually more rapid than drug
quality of the manufacturing process. Ultimately, the drug dissolution and drug absorption. For drugs that have very
must be studied in vivo, in humans to assess drug efficacy, poor aqueous solubility, the rate at which the drug
including the pharmacodynamic, pharmacokinetic, thera- dissolves (dissolution) is often the slowest step, and
peutic and toxic profiles. Drug dissolution, absorption, therefore exerts a rate-limiting effect on drug bioavail-
metabolism, and potential interaction with food and other ability. In contrast, for a drug that has a high aqueous
components in the GI tract are major biopharmaceutic solubility, the dissolution rate is rapid and the rate at which
topics for research and regulatory considerations in drug the drug crosses or permeates cell membranes is the
development. slowest or rate-limiting step.
A drug given by intravenous administration is
considered complete or 100% bioavailable because the
drug is placed directly into the systemic circulation. By
carefully choosing the route of drug administration and DRUG A ~ S O R P T ~ O N
proper design of the drug product, drug bioavailability
can be varied from rapid and complete systemic drug
absorption to a slow, sustained rate of absorption or assage of Drugs
even virtually no absorption, depending on the For systemic absorption, a drug must pass from the
therapeutic objective. Once the drug is systemically absorption site through or around one or more layers of
absorbed, normal physiologic processes for distribution cells to gain access into the general circulation.
and elimination occur, which usually is not influenced The permeability of a drug at the absorption site into
by the specific formulation of the drug. The rate of the systemic circulation is intimately related to the
drug release from the product, and the rate of drug molecular structure of the drug and the physical and
absorption, are important in determining the onset, biochemical properties of the cell membranes. For
intensity, and duration of drug action of the drug. absorption into the cell, a drug must traverse the cell
membrane. Transcellular absorption is the process of a
drug movement across a cell. Some polar molecules may
not be able to traverse the cell membrane, but instead, go
KING STEPS IN ORAL DRUG
through gaps or “tight junctions” between cells, a process
ABSORPTION
known as paracellular drug absorption. Some drugs are
probably absorbed by a mixed mechanism involving one
Systemic drug absorption from a drug product consists of a or more processes.
succession of rate processes (Fig. 2). For solid oral,
Passive diffusion
immediate release drug products (e.g., tablet, capsule), the
rate processes include 1) disintegration of the drug product Passive diffusion is the process by which molecules
and subsequent release of the drug; 2) dissolution of the spontaneously diffuse from a region of higher concen-
drug in an aqueous environment; and 3) absorption across tration to a region of lower concentration. This process is
cell membranes into the systemic circulation. In the passive because no external energy is expended. Drug
Parenteral routes
Intravenous Complete ( 100%) systemic drug Drug is given for immediate effect. Increased chance for adverse reaction. Possible
bolus (IV) absorption. Rate of bioavailability anaphylaxis.
considered instantaneous.
Intravenous infusion Complete (1 00%) systemic drug Plasma drug levels more precisely controlled. Requires slcill in insertion of infusion set.
(1V inn absorption. May inject large fluid volumes.
Rate of drug absorption controlled by May use drugs with poor lipid solubility and/or Tissue damage at site of injection (infiltration,
infusion pump. irritating drugs. necrosis, or sterile abscess).
Intramuscular Rapid from aqueous solution. Easier to inject than intravenous injection. Irritating drugs may be very painful.
injection (IM)
Slow absorption from nonayueous (oil) Larger volumes may be used compared to Different rates of absorption depending upon
solutions. subcutaneous solution. muscle group injected and blood flow.
Subcutaneous Prompt from aqueous solution. Generally, used for insulin injection. Rate of drug absorption depends upon blood
injection (SC) flow
and injection volume.
Slow absorption from repository
formulations.
Enteral Routes
Buccal or sublingual Rapid absorption from lipid-soluble No “first-pass” effects. Some drug may be swallowed. Not for
(SL) drugs. most drugs or drugs with high doses.
Oral (PQ) Absorption may vary. Generally Safest and easiest route of drug administration Some drugs may have erratic absorption,
slower absorption rate cornpared May use immediate-release and modified-release be unstable in the gastointestinal tract, or be
to IV bolus or IM injection. drug product\ metabolized by liver prior to systemic
absorption.
Rectal (PR) Absorption may vary from suppository. Uscful when patient cannot swallow medication. Absorption may be erratic. Suppository may
migrate to different position.
More reliable absorption from enema Used for local and systemic effects. Some patient discomfort.
(solution).
Other route5
Transdermal Slow absorption, rate may \ ary , Transdermal delivery system (patch) Some irritation by patch or drug. Permeability of
is easy to use. skin variable with condition, anatomic site,
age, and gender.
Increased absorption with occlusive Used for lipid-soluble drugs with low dose Type of cream or ointment base affects drug
dressing. and low MW. release and absorption.
Inhalation Rapid absorption. Total dose absorbed May bc used for local or systemic effects. Particle size of drug determines anatomic
is variable. placement in respiratory tract.
May stimulate cough reflex. Some drug may be
s w a1I owed. m
00
(Proin IW. 1 )
86 Biopharmaceutics
Biopharmaceutic studies (in vivo) Bioavailability study Measurement of drug in plasma, urine or other
tissues
Acute pharmacologic effect Measurement of a pharmacodynamic effect,
e.g.. FEVl, blood pressure, heart rate, skin
blanching
Clinical study Measurement of drug efficacy
Biopharmaceutic studies (in vitro) Drug release/dissolution Measurement of the rate of drug dissolved
under specified conditions
Drug permeability Use of CAC02 cells (an isolated colon cell line)
are grown into membranes to study the intestinal
permeability and gut metabolism of drugs.
Drug biotransformation (metabolism) Use of liver cells, homogenates or isolated
cytochrome P450 isozymes to drug study
biotransformation.
molecules move randomly forward and back across a molecules in other directions would not result in
membrane (Fig. 3). If the two regions have the same drug concentration changes because of the limitation of the
concentration, forward-moving drug molecules will be container wall.
balanced by molecules moving back, resulting in no net Passive diffusion is the major transmembrane process
transfer of drug. For a region that has a higher drug for most drugs. The driving force for passive diffusion
concentration, the number of forward-moving drug is the difference in drug concentrations on either side
molecules will be higher than the number of backward- of the cell membrane. According to Fick’s Law
moving molecules, resulting in a transfer of molecules to of Diffusion, drug molecules diffuse from a region of
the region with the lower drug concentration, as indicated high drug concentration to a region of low drug
by the big arrow. Flux is the rate of drug transfer and is concentration
represented by a vector to show its direction. Molecules
tend to move randomly in all directions because
molecules possess kinetic energy and constantly collide
with each another in space. Only left and right molecule where dQldt = rate of diffusion; D = diffusion
movements are shown in Fig. 3, because movement of coefficient; K = partition coefficient; A = surface area
$%+ I / s #+
( +
) #%$
Fig. 2 Summary of processes involved following the oral administration of a drug in tablet or capsule form. (From Blanchard, J.
Gastrointestinal absorption. 11. Formulation factors affecting bioavailability. Am. J. Pharm. 1978, 150, 132- 151.)
Biopharmaceutics 87
Oral cavity Saliva, pH 7, contains ptyalin (salivary amylase), Buccal and sublingual absorption occurs for lipid-
digests starches. Mucin, a glycoprotein, lubricates soluble drugs.
food and may interact with drugs.
Esophagus The esophagus connects the pharynx and the cardiac Tablets or capsules may lodge in this area, causing
orifice of the stomach. The pH is 5-6. The lower part local irritation. Very little drug dissolution occurs
of the esophagus ends with the esophageal sphincter, in the esophagus.
which prevents acid reflux from the stomach.
Stomach The fasting stomach pH is about 2 to 6. In the fed state, Drugs are not efficiently absorbed in the stomach.
the stomach pH is about 1.5 to 2 , due to hydrochloric Basic drugs are solubilized rapidly in acid. Stomach
acid secreted by parietal cells. Stomach acid secretion emptying influences the time for drug reaching the
is stimulated by gastrin and histamine. Mixing is small intestine. The food content and osmolality
intense and pressurized in the antral part of the influenced by stomach emptying. Fatty acids delay
stomach, a process of breaking down large food gastric emptying. High-density foods generally are
particles described as antral milling. Food and liquid emptied more slowly from the stomach.
are emptied by opening the pyloric sphincter into the
duodenum.
Duodenum A common duct from the pancreas and gall bladder The main site for drug absorption. An immense
enters the duodenum. Duodenal pH is 6 to 6.5 due surface area for the passive diffusion of drug to
to the presence of bicarbonate that neutralizes the due to the presence of villi and microvilli forming a
acidic chyme emptied from the stomach. The pH brush border. A high blood perfusion maintains a
is optimum for enzymatic digestion of protein and drug concentration gradient from the intestinal
peptide food. Pancreatic juice containing enzymes lumen and plasma circulation. The complex fluid
is secreted into the duodenum from the bile duct. medium in the duodenum dissolves many drugs
Trypsin, chymotrypsin, and carboxypeptidase are with limited aqueous solubility. Ester prodrugs are
involved in the hydrolysis of proteins into amino hydrolyzed during absorption. Proteolytic enzymes
acids. Amylase is involved in the digestion of degrade many protein drugs in the duodenum,
carbohydrates. Pancreatic lipase secretion preventing adequate absorption. Acid drugs dissolve
hydrolyzes fats into fatty acids. in the alkaline pH. Bile secretion helps to dissolve
fats and hydrophobic drugs
Jejunum The jejunum is the middle portion of the small Drugs generally absorbed by passive diffusion.
intestine in between the duodenum and the ileum.
Digestion of protein and carbohydrates continues
after receiving pancreatic juice and bile in the
duodenum, this portion of the small intestine
generally has less contraction than the duodenum
and is preferred for in vivo drug absorption studies.
Ileum The ileum, pH about 7, with the distal part as high Drugs generally absorbed by passive diffusion.
as 8, is the terminal part of the small intestine
and has fewer contractions than the duodenum.
The ileocecal valve separates the small intestine
with the colon.
Colon The colon, pH 5.5-7, is lined with much functioning Very limited drug absorption due to the lack of
as lubricant and protectant. The colon contains both microvilli and the more viscous and semisolid
aerobic and anaerobic micro-organisms that may nature of the lumen contents. A few drugs such
metabolize some drugs. Crohn’s disease affects the as theophylline and metoprolol are absorbed in
colon and thickens the bowel wall. The microflora this region. Drugs that are absorbed well in this
may also become more anaerobic. Absorption of region are good candidates for an oral sustained-
clindamycin and propranolol are increased, whereas release dosage form.
other drugs have reduced absorption with this disease
(Rubinstein et al. 1988). (Continued)
Biopharmaceutics 91
Rectum The rectum is about 15 cm long, ending at the anus. Drug absorption may be variable depending upon the
In the absence of fecal material, the rectum has a placement of the suppository or drug solution within
small amount of fluid, (about 2 m) with a pH about 7. the rectum. A portion of the drug dose may be
The rectum is perfused by the superior, middle, and absorbed via the lower hemorrhoidal veins, from
inferior hemorrhoidal veins. The inferior hemorrhoidal which the drug feeds directly into the systemic
vein (closest to the anal sphincter) and the middle circulation; some drug may be absorbed via the
hemorrhoidal vein feed into the vena cava and back to superior hemorrhoidal veins, which feeds into the
the heart. The superior hemorrhoidal vein joins the mesenteric veins to the hepatic portal vein to the
mesenteric circulation, which feeds into the hepatic liver, and metabolized prior to systemic absorption.
portal vein and then to the liver.
Some drugs may be absorbed into the lymphatic The drug dosage form may also be affected by food. For
circulation through the lacteal or lymphatic vessels under example, enteric-coated tablets may stay in the stomach
the microvilli. Absorption of drugs through the lymphatic for a longer period of time because food delays stomach
system bypasses the first-pass effect due to liver emptying. If the enteric-coated tablet does not reach the
metabolism, because drug absorption through the hepatic duodenum rapidly, drug release and subsequent systemic
portal vein is avoided. The lymphatics are important in the drug absorption are delayed. In contrast. enteric-coated
absorption of dietary lipids and may be partially beads or microparticles disperse in the stomach, are less
responsible for the absorption for some lipophilic drugs affected by food, and demonstrate more consistent drug
such as bleomycin or aclarubicin which may dissolve in absorption from the duodenum.
chylomicrons and be systemically absorbed via the Food may also affect the integrity of the dosage form,
lymphatic system. causing an alteration in the release rate of the drug.
For example, theophylline bioavailability from Theo-24
controlled-release tablets is much more rapid (7)
Effect of food and other factors
when given to a subject in the fed rather than fasted
on GI drug absorption
state (Fig. 6).
Digested foods may affect intestinal pH and solubility of Some drugs, such as ranitidine, cimetidine, and
drugs. Food effects are not always predictable. The dipyridamole, after oral administration produce a blood
absorption of some antibiotics (e.g., penicillin, tetra- concentration curve consisting of two peaks. This
cycline) is decreased with food, whereas other drugs (e.g., double-peak phenomenon is generally observed after
griseofulvin) are better absorbed when given with food the administration of a single dose to fasted patients. The
containing a high fat content. Food in the GI lumen rationale for the double-peak phenomenon has been
stimulates the flow of bile. Bile contains bile acids. Bile attributed to variability in stomach emptying, variable
acids are surfactants are involved in the digestion and intestinal motility, presence of food, enterohepatic
solubilization of fats, and increases the solubility of fat- recycling, or failure of a tablet dosage form. For a
soluble drugs through micelle formation. For some basic drug with high water solubility, dissolution of the drug
drugs (e.g., cinnarizine) with limited aqueous solubility, occurs in the stomach, and partial emptying of the drug
the presence of food in the stomach stimulates into the duodenum will result in the first absorption peak.
hydrochloric acid secretion, which lowers the pH, causing A delay in stomach emptying results in a second
more rapid dissolution of the drug and better absorption. absorption peak as the remainder of the dose is emptied
Generally, the bioavailability of drugs is better in into the duodenum.
patients in the fasted state and with a large volume of water Diseases such as Crohn’s disease that alter GI
(Fig. 5). However, to reduce GI mucosal irritation, drugs physiology and corrective surgery involving peptic ulcer,
such as erythromycin, iron salts, aspirin, and nonsteroidal antrectomy with gastroduodenostomy and selective
anti-inflammatory agents (NSAIDs) are given with food. vagotomy may potentially affect drug absorption. Drug
The rate of absorption for these drugs may be reduced absorption may be unpredictable in many disease
in the presence of food, but the extent of absorption may be conditions. Drugs or nutrients or both may also affect
the same. the absorption of other drugs. For example, propantheline
92 Biopharmaceutics
54
34
r- .4
&L
!4
‘4
4
! . 5 6 ’ 4 ’ !
‘4
= 6
r-
? % !
4
4 ! . 5 6 ’ 4 ’ !
Fig. 5 Mean plasma or serum drug levels in healthy, fasting human volunteers ( n = 6 in each case) who received single oral doses of
aspirin (650 mg) tablets, erythromycin stearate (500 mg) tablets, amoxicillin (500 mg) capsules, and theophylline (260 mg) tablets,
together with large. (From Welling P.G.; Drug Bioavailability and Its Clinical Significance. Progress in Drug Metabolism, Vol. 4;
Bridges K.W.; Chassea, VD LF. Eds.; Wiley; London, 1980.)
bromide is an anticholinergic drug that slows stomach suspension, suppository), 2 ) the nature of the excipients
emptying and motility of the small intestine and may in the drug product, 3) the physicochemical properties
reduce stomach acid secretion. Grapefruit juice was found of the drug molecule, and 4) the route of drug
to increase the plasma level of many drugs due to administration.
inhibition of their metabolism in the liver.
Disintegration
Immediate release, solid oral drug products must rapidly
disintegrate into small particles and release the drug. The
United States Pharmacopoeia (USP) describes an official
tablet disintegration test. The process of disintegration
Biopharmaceutic considerations in the design and does not imply complete dissolution of the tablet and/or
manufacture of a drug product to deliver the active the drug. Complete disintegration is defined by the USP as
drug with the desired bioavailability characteristics “that state in which any residue of the tablet, except
include: 1) the type of drug product (e.g., solution, fragments of insoluble coating, remaining on the screen of
Biopharmaceutics 93
’‘3t I
# 8 9
I
of the rate of drug diffusion from the surface to the bulk of
the solution. In general, drug concentration at the surface
is assumed to be the highest possible, i.e., the solubility of
the drug in the dissolution medium. The drug concen-
tration C is the homogeneous concentration in the bulk
solution which is generally lower than that in the stagnant
layer immediate to the surface of the solid. The decrease in
concentration across the stagnant layer is called the
diffusion gradient
dCldt = DA(CS - C)h
where, dCldt = rate of drug dissolution, D = diffusion rate
4 6 ‘5 !, &! ,4 ,6 35 54
constant, A = surface area of the particle, CS = drug
concentration in the stagnant layer, C = drug concen-
Fig. 6 Theophylline serum concentration in an individual tration in the bulk solvent, and h = thickness of the
subject after a single 1500 mg dose of Theo-24 taken during stagnant layer.
fasting, period during which this patient experienced nausea, The rate of dissolution, (dCldt) X (UA), is the amount
repeated vomiting, or severe throbbing headache. The pattern of
of drug dissolved per unit area per time (e.g., g/cm2 per
drug release during the food regimen is consistent with “dose-
dumping.” (From Ref. 7.) min).
The Noyes-Whitney equation shows that dissolution
rate is influenced by the physicochemical characteristics of
the test apparatus in the soft mass have no palpably firm the drug, the formulation, and the solvent. In addition, the
core.” The USP provides specifications for uncoated temperature of the medium also affects drug solubility and
tablets, plain coated tablets, enteric tablets, buccal tablets, dissolution rate.
and sublingual tablets. Exempted from USP disintegration
tests are troches, tablets which are intended to be chewed,
and drug products intended for sustained release or
prolonged or repeat action.
Disintegration tests allow for precise measurement of
the formation of fragments, granules, or aggregates from ~iubility,pH, an
solid dosage forms, but do not provide information on the
The natural pH environment of the GI tract varies from
dissolution rate of the active drug. The disintegration test
acidic in the stomach to slightly alkaline in the small
serves as a component in the overall quality control of
intestine. Drug solubility may be improved with the
tablet manufacture.
addition of acidic or basic excipients. Solubilization of
aspirin, for example, may be increased by the addition of
Dissolution an alkaline buffer. Controlled release drug products are
nondisintegrating dosage forms. Buffering agents may be
Dissolution is the process by which a chemical or drug
added to slow or modify the release rate of a fast-
becomes dissolved in a solvent. In biologic systems, drug
dissolving drug in the formulation of a controlled release
dissolution in an aqueous medium is an important prior
drug product. The buffering agent is released slowly rather
condition of systemic absorption. The rate at which drugs
than rapidly so that the drug does not dissolve immediately
with poor aqueous solubility dissolve from an intact or
in the surrounding GI fluid. Intravenous drug solutions are
disintegrated solid dosage form in the GI tract often
difficult to prepare with drugs that have poor aqueous
controls the rate of systemic absorption of the drug. Thus,
solubility. Drugs that are physically or chemically unstable
dissolution tests are discriminating of formulation factors
may require special excipients, coating or manufacturing
that may affect drug bioavailability.
process to protect the drug from degradation.
As the drug particle dissolves, a saturated solution
(stagnant layer) is formed at the immediate surface around
the particle. The dissolved drug in the saturated solution
Stability, pH, and Dru rptio
gradually diffuses to the surrounding regions. The overall
rate of drug dissolution may be described by the Noyes- The pH-stability profile is a plot of reaction rate constant
Whitney equation which models drug dissolution in terms for drug degradation versus pH and may help to predict if
94 Biopharmaceutics
Particle
h
.
The effective surface area of the drug is increased
enormously by a reduction in the particle size. Because
drug dissolution is thought to take place at the surface of Fig. 7 Comparison of mean blood serum levels obtained with
the solute, the greater the surface area, the more rapid the chloramphenicol palmitate suspensions containing varying ratios
rate of drug dissolution. The geometric shape of the drug of 01 and p polymorphs, following single oral dose equivalent.
particle also affects the surface area, and during (From Ref. 9.)
dissolution the surface is constantly changing. In
dissolution calculations, the solute particle is usually
change in crystal structure of the drug may cause cracking
assumed to have retained its geometric shape.
in a tablet or even prevent a granulation to be compressed
Particle size and particle size distribution studies are
into a tablet requiring reformulation of the product. Some
important for drugs that have low water solubility. Particle
drugs interact with solvent during preparation to form a
size reduction by milling to a micronized form increased
crystal called solvate. Water may form a special crystal
the absorption of low aqueous solubility drugs such as
with drugs called hydrates, for example, erythromycin
griseofulvin, nitrofurantoin, and many steroids. Smaller
forms different hydrates (8) which may have quite different
particle size results in an increase in the total surface area
solubility compared to the anhydrous form of the drug
of the particles, enhances water penetration into the
(Fig. 8). Ampicillin trihydrate, for example, was reported
particles, and increases the dissolution rates. With poorly
soluble drugs, a disintegrant may be added to the
formulation to ensure rapid disintegration of the tablet
and release of the particles.
T
Table 5 Common excipients used in solid drug products Table 6 Common excipients used in oral liquid drug products
-
"This may be concentration and drug dependent.
1= Increase, = decrease, - = no effect. k , = absorption rate constant, t,,,
drug concentration time curve.
= time for peak drug concentration in plasma, AUC = area under the plasma
suspending agents increase the viscosity of the drug the drug and thus decrease the dissolution rate. High
vehicle, but may decrease the drug dissolution rate from tablet compression without sufficient disintegrant may
the suspension. An excessive quantity of magnesium cause poor disintegration in vivo of a compressed
stearate (a hydrophobic lubricant) in the formulation tablet.
may retard drug dissolution and slow the rate of drug
absorption. The total amount of drug absorbed may also
be reduced. To prevent this problem, the lubricant level
should be decreased or a different lubricant selected.
Sometimes, increasing the amount of disintegrant may
A dissolution test in vitro measures the rate and extent of
overcome the retarding effect of lubricants on
dissolution. However, with some poorly soluble drugs dissolution of the drug in an aqueous medium in the
an increase in disintegrant level has little or no effect presence of one or more excipients contained in the drug
product. A potential bioavailability problem may be
on drug dissolution because the fine drug particles are
uncovered by a suitable dissolution method. The optimum
not wetted. The general influence of some common
dissolution testing conditions differ with each drug
excipients on drug bioavailability parameters for typical
formulation. Different agitation rates, different medium
oral drug products is summarized in Table 7.
(including different pH), and different dissolution
Excipients may enhance or diminish the rate and
extent of systemic drug absorption. Excipients that apparatus should be tried to distinguish which dissolution
increase the aqueous solubility of the drug generally method is optimum for the drug product and discriminat-
ing for drug formulation changes. The appropriate
increase the rate of drug dissolution and absorption. For
dissolution test condition for the drug product is then
example, sodium bicarbonate in the formulation may
change the pH of the medium surrounding the active used to determine acceptable dissolution specifications.
The size and shape of the dissolution vessel may
drug substance. Aspirin, a weak acid, in an alkaline
affect the rate and extent of dissolution. For example, the
medium will form a water-soluble salt in which the drug
rapidly dissolves. This process is known as dissolution in vessel may range in size from several milliliters to
several liters. The shape may be round-bottomed or flat,
a reactive medium. The solid drug dissolves rapidly in
so that the tablet might lie in a different position in
the reactive solvent surrounding the solid particle. As the
different experiments. The amount of agitation and the
dissolved drug molecules diffuse outward into the bulk
solvent, the drug may precipitate out of solution with a nature of the stirrer affect the dissolution rate. Stirring
rates must be controlled, and specifications differ
very fine particle size. The small particles have
between drug products. Low stirring rates (SO- 100 rpm)
enormous collective surface area and disperse and
are more discriminating of formulation factors affecting
redissolve readily for more rapid absorption on contact
dissolution than higher stirring rates. The temperature of
with the mucosal surface.
the dissolution medium must be controlled and variations
Excipients may interact directly with the drug to form a
in temperature must be avoided. Most dissolution tests
water-soluble or water-insoluble complex. If tetracycline
are performed at 37°C.
is formulated with calcium carbonate, an insoluble
complex of calcium tetracycline is formed that has a The nature of the dissolution medium, the solubility of
the drug and the amount of drug in the dosage form will
slow rate of dissolution and poor absorption.
affect the dissolution test. The dissolution medium should
Excipients may increase the retention time of the
not be saturated by the drug. Usually, a volume of medium
drug in the GI tract and therefore increase the amount
of drug absorbed. Excipients may act as carriers to larger than the amount of solvent needed to completely
increase drug diffusion across the intestinal wall. The dissolve the drug is used in such tests. The usual volume of
addition of surface-active agents may increase wetting the medium is 500- 1000 ml. Drugs that are not very water
as well as solubility of drugs. In contrast, many soluble may require use of a very-large-capacity vessel
excipients may retard drug dissolution and thus reduce (up to 2000 ml) to observe significant dissolution. Sink
drug absorption. conditions is a term referring to an excess volume of
Shellac used as a tablet coating, upon aging, can medium that allows the solid drug to continuously
slow the drug dissolution rate. Surfactants may affect dissolve. If the drug solution becomes saturated, no
drug dissolution in an unpredictable fashion. Low further net drug dissolution will take place. According to
concentrations of surfactants lower the surface tension the USP, “the quantity of medium used should be not less
and increase the rate of drug dissolution, whereas higher than three times that required to form a saturated solution
concentrations of surfactants tend to form micelles with of the drug substance.”
Biopharmaceutics 97
Which medium is best is a matter of considerable drug formulation proposed for marketing. Essential
controversy. The preferred dissolution medium in USP pharmacokinetic parameters of the active drug ingredient
dissolution tests is deaerated water or if substantiated by or therapeutic moiety is also characterized. Essential
the solubility characteristics of the drug or formulation, a pharmacokinetic parameters include the rate and extent of
buffered aqueous solution (typically pH 4-8) or dilute systemic absorption, elimination half-life, and rates of
HCl may be used. The significance of dearation of the excretion and metabolism should be established after
medium should be determined. Various investigators have single- and multiple-dose administration. Data from these
used 0.1 N HCl, 0.01 N HCl, phosphate buffer, simulated in vivo bioavailability studies are important to establish
gastric juice, water, and simulated intestinal juice, recommended dosage regimens and to support drug
depending on the nature of the drug product and the labeling.
location in the GI tract where the drug is expected to In vivo bioavailability studies are performed also for
dissolve. No single apparatus and test can be used for all new formulations of active drug ingredients or therapeutic
drug products. Each drug product must be tested moieties that have full NDA approval and are approved for
individually with the dissolution test that best correlates marketing. The purpose of these studies is to determine the
to in vivo bioavailability. bioavailability and characterize the pharmacokinetics of
The dissolution test usually states that a certain the new formulation, new dosage form, or new salt or ester
percentage of the labeled amount of drug in the drug relative to a reference formulation. After the bioavail-
product must dissolve within a specified period of time. In ability and essential pharmacokinetic parameters of the
practice, the absolute amount of drug in the drug product active ingredient or therapeutic moiety are established,
may vary from tablet to tablet. Therefore, a number of dosage regimens may be recommended in support of drug
tablets from each lot are usually tested to get a labeling.
representative dissolution rate for the product. The USP
provides several official (compendia) methods for carrying
out dissolution tests of tablets, capsules and other special
products such as transdermal preparations. The selection Bioequivalent drug products are pharmaceutical equiva-
of a particular method for a drug is usually specified in the lents whose bioavailability (i.e., rate and extent of
monograph for a particular drug product. systemic drug absorption) does not show a significant
difference when administered at the same molar dose of
the therapeutic moiety under similar experimental
conditions, either single or multiple dose. Some pharma-
BIOAVAILABILITY
ceutical equivalents or may be equivalent in the extent of
BlQEQUWALE NCE
their absorption but not in their rate of absorption and yet
may be considered bioequivalent because such differences
Bioavailability and bioequivalence may be determined in the rate of absorption are intentional and are reflected in
directly using plasma drug concentration vs. time profiles, the labeling, are not essential to the attainment of effective
urinary drug excretion studies, measurements of an acute body drug concentrations on chronic use, or are considered
pharmacologic effect, clinical studies, or in vitro studies. medically insignificant for the particular drug product
Bioavailability studies are performed for both approved studied [21 CFR 320.l(e)].
active drug ingredients or therapeutic moieties not yet
approved for marketing by the FDA. New formulations of
active drug ingredients or therapeutic moieties must be
approved, prior to marketing, by the FDA. In approving a A generic drug product is considered bioequivalent to
drug product for marketing, the FDA must ensure that the the reference listed drug product (generally the currently
drug product is safe and effective for its labeled marketed, brand-name product with a full (NDA)
indications for use. To ensure that the drug product approved by the FDA) if both products are pharmaceu-
meets all applicable standards of identity, strength, quality, tical equivalents and its rate and extent of systemic drug
and purity, the FDA requires bioavailability/pharmacoki- absorption (bioavailability) do not show a statistically
netic studies and where necessary bioequivalence studies significant difference when administered in the same
for all drug products. dose of the active ingredient, in the same chemical form,
For unmarketed drugs which do not have full New in a similar dosage form, by the same route of
Drug Application (NDA) approval by the FDA, in vivo administration, and under the same experimental
bioavailability studies must be performed on the conditions.
98 Biopharmaceutics
Pharmaceutical equivalents are drug products that clinical efficacy and safety profile of these drug
contain the same therapeutically active drug ingredient(s), products are assumed to be similar and may be
same salt, ester, or chemical form; are of the same dosage substituted for each other.
form; and are identical in strength and concentration and
route of administration. Pharmaceutical equivalents may
differ in characteristics such as shape. scoring configur-
ation. release mechanisms, packaging, and excipients MEASURE OF
(including colors, flavoring, preservatives).
Therapeutic equivalent drug products are pharmaceu-
tical equivalents that can be expected to have the same
The best measure of a drug product’s performance is to
clinical effect and safety profile when administered to
give the drug product to human volunteers or patients and
patients under the same conditions specified in the
then determine the in vivo bioavailability of the drug using
labeling. Therapeutic equivalent drug products have the
a pharmacokinetic or clinical study. For some well
following criteria: 1) The products are safe and effective;
characterized drug products and for certain drug products
2 ) The products are pharmaceutical equivalents contain-
where bioavailability is self-evident (e.g., sterile solutions
ing the same active drug ingredient in the same dosage
for injection), in vivo bioavailability studies may be
form, given by the same route of administration, meet
unnecessary. In these cases, the performance of the drug
compendia or other applicable standards of strength,
product in vitro is used as a surrogate to predict the in vivo
quality, purity, and identity and meet an acceptable in
drug bioavailability. Because these products have
vitro standard; 3) The drug products are bioequivalent in
predictable in vivo performance as judged by the in vitro
that they do not present a known potential problem and
characterization of the drug and drug product, the FDA
are shown to meet an appropriate bioequivalence
may waive the requirement for performing an in vivo
standard: 4) The drug products are adequately labeled;
bioavailability study (Table 8).
5) The drug products are manufactured in compliance
with current good manufacturing practice (GMP)
regulations. Drug Products for w ich BioavailabiIity
The generic drug product requires an abbreviated new
drug application (ANDA) for approval by the FDA and
may be marketed after patent expiration of the reference Drug bioavailability from a true solution is generally
listed drug product. The generic drug product must be a considered self-evident. Thus, sterile solutions, lyophi-
therapeutic equivalent to the Reference drug product but lized powders for reconstitution, opthalmic solutions do
may differ in certain characteristics including shape, not need bioequivalence studies but still must be
scoring configuration, packaging, and excipients (includes manufactured according to current GMPs. However,
colors, flavors, preservatives. expiration date, and minor highly viscous solutions may have bioavailability
aspects of labeling). problems due to slow diffusion of the active drug.
Pharmaceutical alternatives are drug products that
contain same therapeutic moiety but are different salts,
esters or complexes (e.g., tetracycline hydrochloride
In Vitro-in Vivo orrelation ( I V I V ~ )
versus tetracycline phosphate) or are different dosage In vitro bioavailability data may be used to predict the
forms (e.g., tablet versus capsule: immediate release performance of a dosage provided that the dissolution
dosage form versus controlled release dosage form) or method selected is appropriate for the solid oral dosage
strengths. form and prior information has been collected showing
In summary, clinical studies are useful in determin- that the dissolution method will result in optimum drug
ing the safety and efficacy of the drug product. absorption from the drug product. In general, IVIVC is
Bioavailability studies are used to define the affect of best for well absorbed drugs for which the dissolution
changes in the physic0 chemical properties of the drug rate is the rate-limiting step. Some drugs are poorly
substance and the affect of the drug product (dosage absorbed and dissolution is not predictive of absorption
form) on the pharmacokinetics of the drug; whereas, (1). The objectives of IVIVC are to use rate of
bioequivalence studies are used to compare the dissolution as a discriminating (i.e., sensitive to changes
bioavailability of the same drug (same salt or ester) in formulation or manufacturing process), as an aid in
from various drug products. If the drug products are setting dissolution specifications. When properly
bioequivalent and therapeutically equivalent, then the applied, IVIVC may be used to facilitate the evaluation
Biopharmaceutics 99
Table 8 Examples of drug products for which in vivo bioavailability studies may be waived
Drug products for which Drug solution (e.g., parented Drug bioavailability from a true solution is
bioavailability is self-evident ophthalmic, oral solutions) considered self-evident. However, highly viscous
solutions may have bioavailability problems.
In vivo-in vitro correlation Modified release drug products The dissolution of the drug from the drug product
(IVIVC) in vitro must be highly correlated to the in vivo
bioavailability of the drug.
Biopharmaceutic classification Immediate release solid oral Drug must be a highly soluble and highly
(BCS) system drug products permeable substance that is in a rapidly
dissolving dosage form.
Biowaiver Drug product containing a Drug product is in the same dosage form, but
lower dose strength lower strength and is proportionally similar in
its active and inactive ingredients.
Condition Comments
Solubility A drug substance is considered highly soluble when the highest dose strength is soluble in 250 ml or less of water over
a pH range of 1-8.
Dissolution An immediate release (IR) drug product is considered rapidly dissolving when not less than 85% of the label amount
of the drug substance dissolves within 30 min using the USP apparatus I at 100 rpm (or apparatus I1 at 50 rpm) in a
volume of 900 ml or less.'
Permeability A drug substance is considered highly permeable when the extent of absorption in humans is to be >90% of an
administered dose based on mass balance determination.
"Media include: acidic media (e.g., 0.1 N HCI) or simulated gastric fluid, USP without enzymes, pH 4.5 buffer and pH 6.8 buffer of simulated intestinal
fluid, USP without enzymes (From FDA Draft Guidance, Jan, 1999.)
Level 1 Deletion or partial deletion of Level 1 changes are those that are unlikely to have any detectable
an ingredient to affect the color impact on formulation quality and performance.
or flavor of the drug product
Level 2 Quantitative change in excipients Level 2 changes are those that could have a significant impact on
greater that allowed in a Level 1 change. formulation quality and performance
Level 3 Qualitative change in excipients Level 3 changes are those that are likely to have a significant impact
on formulation quality and performance. A Level 3 change may
require in vivo bioequivalence testing.
Biopharmaceutics 101
FER s
In Vivo Bioequivalence Documentation, FDA Guidance for 16. Shah, V.P.; Skelly, J.P.; Barr, W.H.: Malinowski, H.;
Industry, Nov. 1995. Amidon, G.H. Scale-up of Controlled Release Products -
I 1. FDA Regulatory Guidances FDA Website for Kcgulatory Preliminary Considerations. Pharmaceutical Technology
(iuidances. www.fda.gov/ccler/guidance/indes.htm). 1992, I6 ( 5 ) , 35-40.
12. Amidon, G.L.; Ixnncrnas, H.; Shah, V.P.; Crison, J.R. A 17. Skelly, J.P. Rcport of Workshop on In Vitro and In Vivo
Theoretical Basis For a Biopharmaceutic Drug Classifi- Testing and Correlation for Oral Controlled/Modified-
cation: The Correlation of I n Vitro Drug Product Release Dosage Forms. Journal of Pharmaceutical Sciences
Dissolution and In Vivo Bioavailability. Pharniaceutical 1990, 79 (9), 849-854.
Research 1995, 12, 413-420. 18. Cadwallader, D.E. Biophnrmnceutics rind D rug Inter-
13. Skelly, J.P.; Amidon. G.L.; Barr, W.H.; Benet, L.Z.; actions; Raven Press: New York; 1983.
Carter, J.E.; Robinson, J.R.; Shah, V.P.; Yacobi, A. InVitro 19. Cibaldi, M. Biopham~acruticsand Cinical Pharmacoki-
and In Vivo Testing and Correlation for Oral Controlled/ netics; Lea & Febiger: Philadelphia, 1984.
Modified-Release Dosage Forms. Pharmaceutical Research 20. Cibaldi, M.; Perrier, D. Pharmacokinetirs; Marcel Dekker,
1990, 7, 975-982. Inc.: New York, 1982.
14. In Vitro-In Vivo Correlation for Estcnded Release Oral 21. McGinity, J.W.; Stavchansky, S.A.; Martin, A . Bioavail-
Dosage Forms, Pharmacopeial Forum Stimuli Article. ability in Tablet Technology. Pharmacrutical Dosage
United States Pharmacopeial Convention. Inc.: July 1988; Forms: Tablets; Lieberman, H.A., Lachman, L., Eds.;
4160-4 161. Marcel Dckker, Inc.: New York, 1981; 2.
15. In Vitro In Vivo Evaluation of Dosage Forms, U.S.P. 22. Rowland, M.; Tozer, T.N. Clinical Pliavmacokinelics.
XXIV< I088> United States Pharmacopeial Convention, Concepts and Applications; Lea & Febiger: Philadelphia,
Inc. 2051-2056. 1995.
PROFESSIONAL OKGANIZATIONS
viability; and 6) communicating the value of specializa- adventure\ in a treatment area where novel and expcri-
tion and specialty certification in pharmacy. mental drug therapies arc lrcquently employed.
BPS has recognized five spccialty practice areas. They arc Added Qualifications is the mechanism used by BPS to
I ) nuclear pharmacy (1978); 2) nutrition support phar- recognize further differentiation within a specialty which
macy (1 988); 3) pharmacothcrapy (1988); 4) psychiatric thc Board has already recognized. This distinction may be
pharmacy (1992); and 5) oncology pharmacy (1 996). granted to a BPS-certified specialist on the basis of a
Nuclear pharmacy seeks to improve and promotc pub- structured portfolio rcvicw process, administered by the
lic hcalth through the safe and effectivc L I S of
~ radioactive Specialty Council responsiblc for the specialty. Thc first
drugs for diagnosis and therapy. A nuclear pharmacist, as petition for Added Qualifications was i n Infectious
a member of the nuclear medicine team, specializes in Diseases and was approved by the Pharmacotherapy
procurcmcnt, compounding, quality assurancc, dispens- Spcciaity Council and BPS in 1999. The first candidates
ing, distribution, and developmcnt of radiopharmaceuti- were conferred the “Added Qualifications in Infectious
cals. In addition, thc nuclear pharmacist monitors paticnt Diseases” crcdcntial in 2000. A petition for Added
outcomes and providcs information and consultation rc- Qualifications in Cardiology was approved in 2000, and
garding hcalth and safety issues. the first candidates were conferred the .Added Qualifica-
Nutrition support pharmacy addrcsscs the care of pa- tions in Cardiology Pharmacotherapy credcntial in 200 1.
tients receiving specialized parenteral or enteral nutrition.
The nutrition support pharmacist is responsible for pro-
moting restoration and maintenance of optimal nutritional
status and designing and modifying treatment in accord-
ance with paticnt needs. These specialists havc rcspon- When a group of interested pharmacists wishes to have a
sibility for direct patient care and often function as mem- ncw spccialty considered for recognition by the BPS, they
bers of niultidisciplinary nutrition support teams. submit a petition to the Board. The petition is evaluated
Pharmacotherapy is thc specialty responsible for en- against seven criteria: 1) need of the profession and the
suring the safe, appropriate, and economical usc of drugs public for specifically traincd practitioncrs in thc spccialty
in paticnt carc. The pharinacotherapy specialist has practice area to fulfill the responsibilities of the profession
responsibility for dircct patient care and often functions in improving the health and welfare of the public; 2) clear,
as a member of a multidisciplinary treatment team. Thcsc significant demand for thc spccialty by the public and
spccialists may conduct clinical research and arc frcqucnt- health carc system; 3) presence of a reasonable number of
ly primary sources of drug information for other health pharmacist specialists practicing in and devoting signifi-
care professional s. cant time in the specialty area; 4) spccialicd knowledge
Psychiatric pharmacy addresses the pharmaceutical of pharmaceutical sciences required by thosc practicing in
care of paticnts with psychiatric disorders. As a mcmbcr the specialty arca; 5) spccializcd functions provided by
oP a multidisciplinary treatment tcam, thc psychiatric pharmacists in the specialty practice area that require
pharmacist specialist is often responsible for optimizing education and training beyond thc basic level attained by
drug treatment and paticnt care by conducting patient licensed pharmacists; 6) education and training in the
asscssmcnts; rccommending appropriate treatment plans; specialty arca provided by pharmacy colleges and other
monitoring patient response; and preventing, identifying, organizations; and 7) transmission of knowledge in the
and correcting drug-relatcd problems. specialty practice area occurring through books, journals,
Oncology pharmacy addrcsscs the pharmaceutical care symposia, professional meetings, and othcr media.
of patients with canccr. The oncology pharmacist spe- After a new specialty is recognized by BPS, a Spe-
cialist promotes optimal care of patients with various ma- cialty Council of contcnt cxpcrts is appointed to work
lignant diseases and their complications. These specialists with the RPS and a professional testing firm to develop a
are closely involvcd in recognition, management, and psychometrically sound and legally defensible certifica-
prevention of uniquc morbidities associated with cancer tion process. Thc Spccialty Council is composed of six
and canccr trcatmcnt; recognition of the balance bctwccn pharmacists practicing in the specialty area and three
improved survival and quality of lifc as primary outcome othcr pharmacists. Certification examinations consisting
indicators; and provision of safeguards against drug mis- of 200 multiple choice questions are administered an-
Board of ~ ~ ~ r ~ ~Specialties
c ~ u t i c ~ ~ ~ 105
nually at designated sites throughout the United States certification. Sornc pharmacist specialists have also re-
and in other countries. Each BPS-certified specialist must ported increased salaries or one-time bonuses upon at-
recertify every scven years. Approved professional de- taining BPS certification.
vclopment programs are availablc as an alternative to BPS certification has been formally recognized by the
sitting for a 100-item recertification cxamination in nuc- American Association of Colleges of Pharmacy, the Ame-
lear pharmacy and pharmacotherapy. BPS continually rican College of Clinical Pharmacy, the American Phar-
evaluates and updates its certification and recertification maceutical Association, the American Socicty for Pa-
processes. Approximately every five years, a new role rcntcral and Entcral Nutrition, the American Society of
delincation study is conducted for each specialty, and Health-System Pharmacists, the Ordre des Pharinaciens du
cxainination specifications are modified accordingly. Quebec, the Society of Infcctious Discases Pharmacists,
and the Society of Hospital Pharmacists of Australia.
BPS-certificd pharmacist specialists are recognized for
thcir advanced lcvcl of knowledge, skills, and achievc-
ment by many government agencies and health care
organizations. The following are examples of specific
benefits that may bc realized by BPS-certified pharmacist
Spccialty certification in pharmacy olfers numerous po- specialists:
tential benefits of significant value to patients, other health
professionals, employers. health care systems, and the U.S. Nuclear Rcgulatory Commission: specialists may
public. Specialty certilication denotes that specialists are be licensed as Radiation Safety Officers and/or
highly trained and skilled and havc demonstrated the recognized as Authorized Users.
ability to identify, resolve, and prevent drug therapy prob- U.S. Department of Defense: specialists may receive
lems. They havc taken the initiative to seek additional bonus pay.
education and expcricnce in a spccialized pharmacy field U.S. Department of Veterans Affairs: specialists may
and exhibit a high lcvcl of comtnitmcnt to patients and thc serve at higher pay steps.
profession. Certified pharmacist specialists function as U.S. Public Health Scrvicc: specialists may receive
valued members of treatment tcams, optimizing and in- bonus pay.
dividualizing drug therapy. Employers can feel assurcd Ncw Mexico State Board of Pharmacy: specialists may
that the knowledge and skills of certified pharmacist spe- apply for specified prescribing privileges.
cialists have been testcd through a rigorous, objectivc, and At least seven Colleges of Pharmacy may exempt
peer-determined process. BPS-certified specialists from some didactic courses in
Ccrtification also provides a personal reward for phar- postbaccalaureate or nontraditional Pharm.D. pro-
macist specialists. Specialty certification communicates grams. Other Colleges award advanced placement on
to others that thc specialist’s educational and practice an individual case basis and may recognize BPS
accomplishments differentiate the specialist from col- certification in this process.
leagues. Many specialists feel that thcy have a competi-
tive edge in applying for positions, and some have re- Many other national, regional, or local employers of
ceived reimburscment from third-party payers, because RPS-certified pharmacists also recognize BPS ccrtifica-
their skills and knowledge have been validated through lion in thcir hiring, salary, or privileging policies.
PHARMACY PRACTICE ISSUES
anita la
Hcnry Ford Health Syslem, Iletroit, Michigan, U.S.A.
options for patient care, and developing research proto- Because the patient’s immune system is compromised
cols to advance patient care. Therefore, in addition to a for several months to several years secondary to the slow
solid knowledge base in hematology-oncology, immuno- process of complete bone marrow recovery and/or long-
logy, infectious diseases, fluid/electrolyte balance, and term usage of immunosuppresives, the patient is vul-
pain management, it is imperative for a bone marrow nerable to numerous life-threatening infectious disease
transplant pharmacist to possess excellent communication processes. In addition, the allogeneic bone marrow trans-
and people skills. plant patient always carries a certain risk (highest per-
centage if the donated bone marrow is from an un- There is a definite need for both an inpatient and
related individual without a 6/6 Human Lymphocyte outpatient bone marrow transplant pharmacist. Due to the
Antigen match) for developing acute and/or chronic patient’s initial prolonged inpatient stay and high prob-
graft-versus-host disease (GVHD). If the patient devel- ability of multiple readmissions during the first several
ops GVHD, the immune system is even further com- months post-bone marrow transplant, the distinction be-
promised by not only the intense immunosuppressive tween an inpatient and outpatient bone marrow transplant
agents needed for treatment, but also by the GVHD pharmacist role becomes unclear. To help maintain con-
itself. Thus, an allogeneic bone marrow transplant pa- tinuity of care, usually one pharmacist (labeled as the
tient may have numerous hospital readmissions for inpatient pharmacist) will manage a patient’s pharmaceut-
treatment of infectious disease processes, aggressive ical needs both during the initial hospitalization and
treatment, and close monitoring of moderate-to-severe during the first several months of outpatient care. Once a
GVHD or bone marrow failure (i.e., tumor relapse, bone patient’s ambulatory visits decrease to at least once every
marrow engraftment lost). The majority of patients are 2 weeks, the outpatient pharmacist will attend to the
at highest risk for readmission during the first 100 days patient’s medication needs. If the institution predomi-
post-transplant. Bone marrow transplant recipients of nantly performs autologous bone marrow transplants or if
mismatched or unrelated donors require more intense the number of bone marrow transplants (autologous
bone marrow immunosuppression for a longer period of combined with allogeneic) performed is low, then one
time than their counterparts who receive matched or pharmacist is sufficient to play both the inpatient and
related bone marrow, thereby increasing their risk for outpatient role.
hospital readmissions for a period greater than 100 days. The type and level of care provided by the pharmacist
Because the patient’s medical needs can change dras- depends on the stability of the patient’s health (Table 1).
tically from day to day, the pharmacist needs to stay Generally, the patient is most unstable during the
abreast of all new medication regimens required for transplant and for the first several months post-transplant.
patient care. It is imperative that the pharmacist has a
good working relationship with the patient and patient’s
caregivers to ensure appropriate adherence to the evolv-
ing medication regimen.
Recently, there has been a surge of bone marrow
The type of work a bone marrow transplant pharmacist
transplant centers shifting inpatient care to the outpatient
performs on a daily basis depends on the goal of the
setting early in transplant (post bone marrow/peripheral
employer. A pharmacist can be predominantly research
blood stem cell infusion). The incentive for this trend has
based or clinically based.
been to decrease the cost of bone marrow transplant and
improve the patient’s quality of life. Stringent, institution-
specific criteria have been developed for patients to be
outpatient bone marrow transplant candidates. The pri-
mary basis behind the criteria rely on the patient and a Most of the bone marrow transplant pharmacist positions
dedicated caregiver to be attentive to all their medical with research emphasis are tenure-tracked or tenured with
needs, including comprehension of appropriate medica- a teaching hospital. These pharmacists have minimal to
tion administration guidelines. The patients are respons- no direct patient care duties assigned to them. Pharmacists
ible for self-administration of scheduled and as needed are responsible for the following:
oral, subcutaneous, and intravenous medications. By
placing this level of responsibility on the patient and 1. Developing research protocols
caregiver, the patient can be overcome with anxiety. A 2. Applying for grants to fund the protocols
pharmacist plays a dominant role in alleviating any con- 3. Screening and enrolling patients into study (when
fusion or misunderstanding on medication self-adminis- applicable)
tration. The bone marrow transplant pharmacist will 4. Developing/running various assays
need to thoroughly educate both the patient and caregiver 5 . Publishing research results
on all the medications daily. Although the patient maybe 6. Didactic, experiential university-based teaching
medically stable in the outpatient setting, the initial
amount of time the pharmacist needs to spend with the The majority of pharmacists will participate in
patient is equivalent to a complicated hospitalized bone pharmacy doctoral or postdoctoral programs or develop
marrow transplant patient. bone marrow transplant fellowships to attain reliable,
Bone Marrow Transplant Pharmacy Practice 109
poictic stem cell to form the three lineages. It is impor- Ilnfortunately, a pharmacy conference/meeting spe-
tant to understand the rclevancc of immunomodulators cializing or subspecializing in bone marrow transplant
at each step of cell maturation. ecausc ex-vivo cyto- has not been identified. There is a rising interest in
kines are very expensive and many of them carry high forming a bone marrow transplant pharmacy network
toxicity profiles, it is important for a pharmacist to group; perhaps modclcd after the infectious disease
know which stem cell maturation step(s) will be influ- pharmacy group (Society of Infectious Disease Phar-
cnccd by the cytokine(s). macy meet annually at their medical counterpart con-
ference, Interscience Conference on Antimicrobial Agents
and Chemotherapy).
ACCP Oncology pm mainly targets the hematology/
Currently, there are no published documents providing oncology pharmacists and ACCP Transplant prn mainly
guidelines or consensus statements on how medications largets the solid organ transplant pharmacists. Thus,
should be administered during and following a bone bone marrow transplant pharmacist members of ACGP
marrow transplant. ‘There are numerous review articles arc not strongly committed to any particular ACCP
available on bone marrow transplant preparative regi- pm group.
mens, prevention and treatment of graft versus host
disease, infectious disease topics related to bonc mar-
row transplant, and pain management. The chemothcr-
apy/radiothcrapy used as the preparative regimen for a
bone marrow transplant varies from center to center,
depending on the hematologist’s past experience with I. http:/IIBMTK.org/sitemap/sitcmap/html (acccsscd Scptcm-
thc various regimens, the patient’s eligibility for drug ber, 2000).
2. Bailey, E.M.; Pindolia, V.K. How to obtain funding for
study enrollment, the patient’s past chemotherapy/radio-
clinical research. Am. J. Hosp. Pharm. 1994, 51, 2858~-
therapy history, and the patient’s past medical history.
2860.
Thc medications and medication doses used to prevent 3. Weeks, F.M.; Yee, G.C.; Bartfield, A.A.; Wingard, J.R.
D and to treat other bone marrow trans- The true cost of bone marrow transplantation. Am. J. Med.
plant related complications is also dependent on the phy- 97, 3’14 (2), 101 112.
sician’s preference, patient’s cligibility for drug study 4. Waters, T.M.; Bcnnctt, C.L.; Pajeau, T.S.; Sobocinski,
enrollment, and patient’s medical history. K.A.; Klein, J.P.; Rowlings, PA.; Horowitx, M.M. Eco-
nomic analyses of bone marrow and blood stem cell
transplantation for leukemias and lymphoma: What do we
know? Bone Marrow Transplant. 1998, 21, 641 650.
5. Bennett, C.L.; Waters, T.M.; Stinson, T.J.; Almagor, 0.;
Pavletic, Z.S.; Tarantolo, S.K.; Bishop, M.R. Valuing
clinical stratcgics early in development: A cost analyses of
Thcrc are numerous bone marrow transplant web sites allogeneic periphcral blood stem cell transplanlation. Bone
Marrow Transplant. 1999, 24, 555-560.
available; however, they arc oncology center initiated to
6. Rixzo, J.D.; Vogelsang, G.B.; Krumm, S.; Frink, B.; Mock,
increase patient relerral base or patient initiated to pro-
V.; Bass, E.B. Outpatient-based bone marrow transplanta-
vide personal advice to other bone marrow transplant tion for hematologic malignancies: Cost savings or cost
patients. The networking opportunities available for bone shifting? J. Clin. Oncol. 1999; 17 (9), 281 1 2818.
marrow transplant pharmacists are primarily in the fol- I. Barr, K.; Furlong, W.; Henwood, J.; Feeny, D.; Wegener,
lowing medical conferences/mcctings: J.; Walker, 1.;Brain, M. Economic evaluation of allogeneic
hone marrow transplantation: A rudimentary model to
I . American Society of Hematology (ASH) generate estimates for the tinicly formulation o f clinical
2. American Society of Clinical Oncology (ASCO) policy. J. Clin. Oncol. 1996, 14, 1413 - 1440.
PROFESSIONAL ORGANIZATIONS
aton
Univenity of Toronto, Toronlo, Onhrio, Canadi
The mission of the Canadian Hospital Pharmacy Re- The Canadian Hospital Pharmacy Rcsidency Board was
sidency Board is to establish and apply standards for established in the early 1960s. The assessmcnt of the re-
accreditation of pharmacy practice residency programs sidency training programs was done following review of
and to promote excellence in hospital pharmacy residcncy written documentation submitted to the Board. The on-
programs and practice. The key objectives are as follows: site accreditation process and survcy did not begin until
the early 19XOs, however. At the present time, the Board
1 To gain cxternal recognition dnd support tor phdr- accredits residency training programs in pharmacy
macy residency program\ practice. Currently, there are 30 programs in Canada
2 To provide \upport to residency program partici- with 104 positions for prospective rcsidents. The Board is
pants i n their role through educdtion, skill de- not currently involvcd in thc accrcditation of specialty
velopment and practice tools programs or pharmacy technician training programs.
3 To foster an environment that facilitates the growth
and development of ph'irmacy reiidency progrdinc
sto
Canadian Pharmacists Association, Ottawa, Ontario, Canada
trate
2. To promote and facilitate the evolution of the care until January 2002. With the passage of the
pharmacy profession toward an expanded role in legislation, CPhA participated in a working group with
health care. six national health provider and consumer associations
3. To foster public recognition of pharmacists as drug to examine the issue of privacy protection in Canada.
experts and as members of the health care team. The report of the Privacy Working Group focuses on
4. To secure appropriate reimbursement for pharma- the challenges of developing and implementing princi-
cists’ professional services. ples for privacy protection. lt highlights the lack of
5 . To effectively analyze and respond to the impact consensus and the tension on this issue due to the dis-
of advances in information technology on phar- parate perspectives of the many stakeholders involved.
macy practice. CPhA continues to seek effective remedies to the shor-
6. To align resources to the key result areas. comings in the legislation, including presentations to
federal officials.
Privac i~lation
A major reengineering of the CPhA web site is underway.
CPhA was pivotal in securing an amendment to the This revitalized site will offer Web services to benefit our
Personal Information Protection and Electronic Docu- members (e.g., electronic membership and order transac-
ments ActL2] which delayed its application to health tions, chat rooms, e-mentoring, e-broadcast).
I I4 Canadian Pharmacists AssociationlAssociation des Pharmaciens d~ Canada
EF ES
CPhA, through its publishing program, provides pharma- I. A Situational Analysis of Human Resource Issues i n the
cists in every practice setting with accurate, current drug Pharmacy Profession in Canada. http://www.cdnpharm.ca
information and resource materials. However, on-line (accessed Junc 25, 2001).
of our drug information presents new chal- 2. Personal Information Protection and Electronic Docu-
lcngc. Work is underway on the CPS so that this pub- ments Act. http://www.privcom.gc.ca (accessed June 22,
lication can be easily accessible Tor print and electronic 2001).
3. National e-Claims Standard Initiative. http://www.cihi.ca/
publishing. The CI’S and our other publications are being
eclaims/intro.shtml (accessed June 25, 200 I ).
rcpurposed for use on new e-media platforms.
PROFESSIONAL DEVELOPMENT
is clear that a real opportunity exists for the pharmacist to provided 3.1 consultations per 14-hour call period. Ninety
influence those efforts related both to the improvement of percent of these consultations were completely followed
drug use policies, and to the creation of quality im- by the recipient physician^."^] Clinical pharmacy services
provement and feedback processes that can identify and involving a pediatric subspecialty emergency practice has
improve hospital resuscitative efforts. Despite the as- been described in which a pharmacist is a member of a
sumption that hospitals function as self-contained emer- pediatric trauma team consisting of a pediatric surgeon,
gency medical services (EMS) systems with respect to neurosurgeon, emergency physician, intensivist, radiology
their management of cardiac arrest based on their technician, and an intensive care unit nurse.1181
abundance of health care providers in a defined environ- Opportunities for clinical pharmacy service in the
ment, the Bethesda Conference report stated, "the process emergency department may expand because of the con-
of improving resuscitation in the hospital remains in its siderable effects resulting from changes in health in-
infancy." Such an assessment presents a unique oppor- surance provision in the United States focused on re-
tunity for pharmacy to establish itself as a necessary ducing the number of hospital admissions. Perhaps the
component of a process that has become a part of required most prominent example of clinical pharmacy services in
standards of hospital care. the emergency department setting is related to the man-
agement of asthma. The number of asthma-related deaths
in the United States is increasing, especially among
MERGENCY MEDICAL SERVl children. One potential cause for this increase may be
inappropriate early discharge of patients from emergency
Pharmacists have provided clinical services in emergency departments. Pharmacists have participated in inter-
medicine-related areas of hospitals since the late disciplinary efforts to maximize the urgent care of asth-
1960s."*] Documentation of clinical pharmacy services ma patients in a number of environments, including the
relate primarily to the provision of services in hospital emergency department. In a university-affiliated urban
emergency departments. Services vary from those pro- teaching hospital, the number of emergency department
vided fundamentally as support to the emergency de- visits for a group of asthma patients was significantly
partment staff, to those provided directly to patients in reduced after institution of a comprehensive program of
specific disease management program^."^ 14' In a report asthma management."']
of follow-up observations on 3787 pharmacotherapy con- Finally, a number of nontraditional practice sites have
sultations provided in an emergency department in a uni- been described in which pharmacist have participated in
versity hospital, 33% involved patients with pulmonary natural disaster relief or as part of a humanitarian effort
disease, 22% involved toxicology cases, 17% involved relief team. These nontraditional practices have included
patients with seizure disorders. 11% involved cardiac a pharmacy consultative service for wilderness emer-
cases, 7% were pharmacokinetic consultations, and 8% gency drug planning, pharmacy involvement in emer-
were miscellaneous consultations."'] Consultations aver- gency preparednesslresponse, the provision of phar-
aged 100 minutes each, and serum drug concentration maceutical services at a medical site after Hurricane
determinations primarily involved theophylline, pheny- Andrew in Florida, and the experience of several phar-
toin, phenobarbital, and acetaminophen. An early ques- macists providing service in B o s n i a - H e r z e g ~ v i n a . ~ ~ ~ - ~ ~ ~
tionnaire of the value of clinical pharmacy services in a In conclusion, there are numerous current emergency
medical center emergency department setting reported practice opportunities in which pharmacists play a
that clinical pharmacy services added benefit to both significant role. Although the number of pharmacists
patient care and to educational programs in the depart- who provide clinical services in these settings is relatively
ment.[16] Eighty-seven percent of the responding phy- small, the critical nature of drug use in such setting
sicians reported the pharmacist capable of providing suggests that the potential for direct pharmacotherapeutic
primary care to specific patients once a physician-based intervention is large. Well-designed outcome evaluation
diagnosis was established. Ninety-five percent of respon- of such service is sorely needed.
ders believed that clinical pharmacy services could be
transferred to other emergency departments, and 83%
were willing to have their patients charged for clinical
services provided by the pharmacist. A more recent eval-
uation of the utility of clinical pharmacy services in the 1. Edwards, G.A.: Samuels, T.M. The role of the hospital
emergency department revealed that provision of a 24- pharmacist in emergency situations. Am. J. Hosp. Pharm.
hour consultative service by clinical pharmacy residents 1968, 25, 128-133.
I18 Cardiac Arrestmmergency Pharmacy Services
2. Shimp, L.A.; Mason, N.A.; Tocdter, N.M.: Atwater, C.B.; 14. Powell, M.F.; Solomon, D.K.; McEachen, R.A. Twenty-
Corenflow, D.W. Pharmacist participation in cardiopul- four hour emergency pharamaceutical services. Am. J.
monary resuscitation. Am. J. Health-Syst. Pharm. 1995, 52 Hosp. Pharm. 1985, 42 (4), 831-835.
(9). 980-984. 15. Berry: N.S.; Folstad, J.E.; Bauman, J.L.; Leikin, J.B.
Bond. C.A.; Raehl, C.L.; Pitterle, M.E. 1992 National Follow-up observations on 24-hour pharmacotherapy
clinical pharmacy services survey. Pharmacotherapy 199 services in the emergency department. Ann. Pharmacother.
14 ( 3 ) , 282-304. 1992, 26 (4), 476 480.
Bond, C.A.: Raehl, C.L.; Pittcrlc, M.E. 1992 National 16. Elenbaas, R.M.; Waeckerle, J.F.; McNabney, W.K. The
clinical pharmacy services survey. Pharmacotherapy 1998, clinical pharmacist in emergency medicine. Am. J. Hosp.
18 (2), 302 326. Pharm. 1977, 34 (X), 843 846.
Bond, C.A.; Raehl, C.L.; Pitterle, M.E. 1992 National 17. Kasuya, A.; Bauman, J.L.; Curtis, R.A.; Duarte, B.;
clinical pharmacy services survey. Pharmacotherapy 2000, Hutchinson, R.A. Clinical pharmacy on-call program in
20 (4), 436-460. the emergency department. Am. J. Emerg. Med. 1986, 4
Elcnbaas, R. Pharmacist on resuscitation team. N. Engl. J. ( 5 ) ; 464-461.
Med. 1972, 287 ( 3 ) , 151. 18. Vernon, D.D.; Furnival, R.A.; Hansen, K.W.; Dillcr, E.M.;
Bond, C.A.; Rcahl, C.L. Pharmacists’ attitudes toward the Bolte, R.G.; Johnson, D.G.; Dcan, J.M. Effect of a
use of cardiopulmonary resuscitation training received in pediatric trauma response tcam on emergency departmcnt
pharmacy school. Am. J. Hosp. Pharm. 1989, 46 (7), treatment time and mortality of pediatric trauma victims.
1392- 1394. Pediatrics 1999, 103 (l), 20 24.
~
X. White, R.D.; Asplin, B.R.; Bugliosi, T.F.; Hankins, D.G. 19. Pauuley, T.R.: Magee, M.J.; Cury, J.D. Pharmacist-
High discharge survival rate after out-of-hospital ventricu- managed, physician-directed asthma management program
lar fibrillation with rapid defibrillation by police and reduces emergency department visits. Ann. Pharmacother.
paramedics. Ann. Emerg. Med. 1996, 28, 480-485. 1995. 29 (l), 5-9.
9. White, R.D.; Hankins, D.G.; Bugliosi, T.F. Seven years’ 20. Closson, R.G. The pharmacist as consultant for wilderness
experience with early defibrillation by police and para- emergency drug planning. J. Am. Pharm. Assoc. 1977, 17
medics in an emergency medical services system. Resus- (12), 746-749.
citation 1998, 39, 145 -151. 21. Moore, S.R. Pharmacy involvement in emergency pre-
10. Comprehensive Accreditation Manual ,for Hospitals: The parednessiresponse. J. R. Soc. Health 1998. 118 (l), 28-
Official Handbook ( C A M H J ,Joint Commission Resources, 30.
Inc. 22. Nestor, A,; Aviles, A.I.; Kummerle, D.R.; Barclay, L.P.;
I I. Ewy, G.A.; Ornato, J.P. 3 I st Bethesda conference. Rcy, J.A. Pharmaceutical services at a medical site after
Emergency cardiac care. Task force 1: Cardiac arrest. J. hurricane andrew. Am. J. Hosp. Pharm. 1993, 50 (9),
Am. Coll. Cardiol. 2000, 35 (4). 832 846. 1896-1898.
12. Edwards, G.A.; Samuels. T.M. The role o l the hospital 23. Bussieres, J.F.; St-Arnaud. C.: Schunck, C.; Lamarre, D.;
pharmacist in emergency situations. Am. J. Hosp. Pharm. Jouberton, F. The role of the pharmacist in humanitarian
1968. 25 ( 3 ) , 128 133.
~ aid in Bosnia-Herzegovina: The experience of pharma-
13. Culbertson, V.; Anderson, R.J. Pharmacist involvement in ciens sans frontiers. Ann. Pharmacothcr. 2
emergency room services. Contemp. Pharm. Pract. 1981, 4 112-118.
( 3 ) ; 167- 176.
PROFESSIONAL DEVELOPMENT
comes (clinical and economic) associated with clinical ute to health care costs in numerous ways, including in-
pharmacy practice in cardiology settings. These are sum- creases in lengths of stay, medication, and laboratory
marized in the following sections. One will find that the costs. Medications used in acute cardiac settings tend to
role of pharmacists providing services to targeted areas have narrow therapeutic windows with substantial risk for
(e.g., lipid clinic, anticoagulation clinic, smoking cessa- toxicity and require close monitoring to optimize therapy
tion) in ambulatory settings is much more frequently (e.g., antithrombotics, antiarrythmic agents, intravenous
studied than the role of the pharmacist practicing in an inotropes, nitroprusside). Drug-drug interactions (also
acute care, inpatient setting where the clinical functions quite common with cardiac regimens), inappropriate dos-
are more broad. ing, and inappropriate drug selection are just a few ex-
amples of common ADEs where pharmacy intervention
could have a tremendous impact. An important study by
ACUTE CARE CARDIOL Leape et al. noted that the inclusion of a clinical phar-
macist on a multidisciplinary team rounding in an in-
tensive care setting reduced ADEs by 66%, through order
Twenty-five percent of Americans discharged from hos- clarification, provision of drug information, and recom-
pitals have a primary diagnosis of cardiovascular (CV) mendations of alternative therapy.[31
disease.”] The pharmacist practicing in an acute care A unique responsibility of a cardiology specialty phar-
setting helps manage common cardiac disease states, in- macist is the management of drug therapy of ACS,
cluding the spectrum of acute coronary syndromes (ACS), particularly those involving unstable angina and cardiac
hypertensive emergencies and urgencies, acute heart fail- catheterization-associated procedures. Low-molecular-
ure, and cardiac arrhythmias, along with comorbid con- weight heparins and glycoprotein IIb/IIIa receptor anta-
ditions. Decisions regarding optimal medication use in gonists are newer treatment modalities, but are consid-
such patients are complex. Beginning with the initial erably more expensive than older medications used for
choice of medication to treat a patient acutely, and through ACS. Newer thrombolytics used in treatment of acute
selection of appropriate chronic therapy and proper titra- myocardial infarction are easier to administer (in one or
tion and monitoring, the acute care pharmacist is a vital two bolus doses versus an infusion), yet are more expen-
component in the system of health care provision. sive. Therefore, there is a need to develop cost-effective
As part of the health care team, the acute care phar- treatment strategies that encompass these newer agents.
macist works with attending physicians, physicians-in- These strategies must take into account critical literature
training nurses, and other health care professionals to pro- evaluation (i.e., are there superior outcomes between
vide patient care. Daily activities are often centered around studies involving the newer agents?) and knowledge of
medical rounds, where the team reviews each inpatient’s patient characteristics (i.e., determining if the patient has
progress over the last day. Here, drug therapy decisions are an appropriate indication for use of a new therapy, iden-
made within the constructs of a team approach. Informa- tifying appropriate dosage adjustments in the face of renal
tion shared during rounds includes results of lab tests, insufficiency) when formulating guidelines. The cardio-
physical exams, diagnostic and therapeutic procedures, logy specialty pharmacist may play a significant role in
and symptomatology. Using this information, a pharmacist developing such guidelines for the institution, selecting
assists in evaluating patient response to medications, in- individual patients for therapy, and selecting which
cluding assessing dose, route, and monitoring of each drug therapy to use in particular ACS scenarios.
that the patient is receiving. When prospectively adding a It is common to find a pharmacist as a member of the
medication to the patient’s orders, the pharmacist recom- hospital cardiopulmonary resuscitation (CPR) team, which
mends appropriate agents based on the clinical indication, responds to emergent situations that may require imme-
dosing (initial and “target”), and both efficacy and safety diate patient care. These scenarios usually involve a pa-
monitoring parameters. In providing such information, the tient who suddenly becomes nonresponsive, ceases spon-
pharmacist becomes a primary source of education re- taneous respirations, and/or experiences a life-threatening
garding optimal medication use for all the members of the cardiac arrhythmia. The CPR team responds to such pa-
health care team. Other tasks the pharmacists might per- tients by implementing advanced cardiac life support
form include obtaining medication histories from patients (ACLS), which involves quick provision of an airway and
admitted to the hospital, patient medication education, and electrical (defibrillation) and/or pharmacologic interven-
discharge counseling for patients discharged from the tions to sustain cardiac function. The pharmacist’s role on
hospital on a new medication regimen. such a team involves the preparation of intravenous infu-
An important role for the pharmacist is prevention of sions needed in an emergent situation, dose calculations,
adverse drug events (ADEs), which significantly contrib- and consultation regarding appropriate medication use.
Cardiology, Clinical Pharmacy Practice in 121
Participation by a pharmacist on a CPR team was asso- therapy. In addition, a pharmacist can provide patient
ciated with significantly lower hospital mortality rates in a education regarding the importance of compliance, ad-
study by Bond and colleagues.[41 verse effects, and goals of therapy, thereby increasing the
likelihood of successful control of patients' disease states.
Dyslipidemia
SPECIALTY PRACTICE
Dyslipidemia is a major risk factor for several CV dis-
In the outpatient setting. cardiology pharmacists frequent- eases, including myocardial infarction, stable and un-
ly provide services in a wide array of clinic types, in- stable angina, and stroke. Control of cholesterol levels is
cluding general cardiology clinics, primary care/family important in reducing risk of both primary and secondary
medicine clinics, and disease management clinics. The CV events. High cholesterol levels may be treated by
impact of a cardiology pharmacist in these settings has altering diet and through pharmacologic intervention.
been clearly documented in the medical literature. Gen- Outpatient dyslipidemia clinic models that include in-
erally, a pharmacist's knowledge of CV disease state tervention by a clinical pharmacist have demonstrated
pathophysiology , presentation, and course, coupled with larger reductions in total cholesterol level, greater like-
extensive knowledge of drug therapy options and moni- lihood for achieving National Cholesterol Education Pro-
toring are invaluable insofar as enhancing comprehensive gram"] low-density lipoprotein goals, and better medica-
patient care. The following is a description of types of tion compliance."0-'21
specialty care that a pharmacist might provide. The decision to start cholesterol-lowering therapy can
be complex and should involve patient assessment for
concurrent risk factors (hypertension, diabetes), concom-
Hypertension
itant medications, diet, and social history (alcohol and
cigarette use). The pharmacist can recommend and coun-
Some of the earliest published reports on the effects of
sel regarding nonpharmacologic interventions such as re-
provision of pharmaceutical care provided insight into the
duction in body weight, dietary alterations, exercise, and
effects of a pharmacy program in the care of patients with
cessation of cigarette smoking. It is also important to en-
hypertension. In an early study by McKenney and col-
sure that comorbid disease states (diabetes, hypertension)
leagues, the effects of clinical pharmacy services in a
are adequately treated and monitored. If the decision is
group of hypertensive patients were d e ~ c r i b e d . ~Those
~]
made to start a cholesterol-lowering agent, the pharmacist
patients who received pharmacy services in addition to
must ensure that the appropriate agent is selected because
standard care by their physician demonstrated an im-
each agent may have a distinct effect on each lipoprotein
provement in self-knowledge of their disease state, im-
component (low density, high density, triglycerides) of
proved compliance. and better blood pressure control.
the lipid profile. In addition, prospective identification
Subsequent investigations have demonstrated a positive
and avoidance of drug interactions when using choles-
effect of pharmacy services on cost and quality of life in
terol-lowering therapy is a salient pharmacist responsibil-
patients treated for h y p e r t e n ~ i o n . ' ~ ~ ~ ]
ity. For example, IlMG CoA reductase inhibitors (some of
In this largely asymptomatic yet morbid disease, early
the most commonly used cholesterol-reducing medica-
identification and treatment are the mainstays for ex-
tions) are agents that inhibit a major metabolizing enzyme
cellent patient care. The proper management of a hyper-
in the liver and may be a source of clinically significant
tensive patient begins with selecting an appropriate goal
drug interactions, including the occurrence of myositis,
blood pressure, recognizing other risk factors for CV di-
rhabdomyolysis, or renal dysfunction. Recommendation
sease, noting concomitant disease states, and selecting
of pertinent monitoring parameters and patient education
appropriate drug therapy for the patient. When selecting
are additional contributions that the clinical pharmacist
such therapy it is important to bear in mind compelling
can make when caring for the dyslipidemic patient.
indications (as defined in the Sixth Report for the Joint
National Committee on the Detection, Evaluation, and
Treatment of High Blood Pressure,"] which is the con- Chronic Heart Failure
sensus guidelines for the treatment of hypertension), con-
traindications or cautions for using certain classes of There are many drug therapy-specific tasks unique to the
medications, patient compliance, and cost. As a drug ex- care of a heart failure patient. A thorough review of the
pert, pharmacists are in an ideal position to enhance care medication profile of a patient with heart failure should
through the selection and monitoring of antihypertensive include ensuring the presence of appropriate medications
I22 Cardiology, Clinical Pharmacy Practice in
(ACE inhibitors, beta blockers) for reducing mortality interactions. Guidance is also provided to other health care
related to this devastating disease. Cardiology pharina- providers regarding appropriate dosage changes and
cists can optimizc therapy by identifying and achieving monitoring parameters.
goal doses (those doses achieved in clinical trials of heart Numerous siudies have described clinic models and
failure) for each of these mcdications, depending on outcomes related to pharmacist-managed antithrombosis
patient tolerability. Of equal importance is a check for clinics. Chiquettc and colleagues demonstrated fewer in-
mcdications that may potentially exacerbate heart Failure cidences of supratherapeutic levels of anticoagulation,
or cause toxicity when given in conjunction with existing more consistent maintenance of appropriate levels of anti-
heart failure therapy. coagulation, lower rates of bleeding complications, and
Numerous trials document that many patients do not thromboembolic events in a group o f patients managed in
always rcccivc drugs shown to decrease mortality in heart a pharmacist-managed clinic versus those managed by
Failure (c.g., ACE inhibitors) or do not rcccivc the proper usual medical care.' '" These investigators also showed
("goal") doses (see studics by Smith et al."" and Roe lower rates of hospital admissions and emergency dcpart-
et a1."41). Clearly, cardiology pharmacists have an impact inent visits due to warfarin therapy in those patients man-
on outcomes related to the use of these medications by aged in the clinic. Similar superior care was noted in in-
ensuring appropriate dosing parameters. Such respons- vestigations published by Wilt and colleagues who also
ibilities may include recognition of an appropriate patient demonstrated a 20-fold increase in events (warfarin-rc-
for ACE inhibitor or beta blocker therapy, proper uptit- lated hospitalization, hemorrhagic or thrombotic events) in
ration of each agent, management of advcrsc effects re- patients cared for in a family practice setting versus a
lated to therapy, and identification of true ACE or beta pharmacist-managed clinic.' 17' Both of these invcstiga-
blocker intolerance. lions translated these reduced event rates into significant
Gatlis and colleagues demonstrated the valuable con- cost savings; Chiquette estimated annual health care
tributions made by a clinical pharmacist in the care of costs would be reduced by more than $130,000 per 100
patients with heart failure.' ''I In this study, pharmacists patients, whereas Wilt attributed a $4000 cost avoidance
made therapy recommendations (including ensuring at- per person-year of follow-up for those patients managed
tainment of goal doses of heart failure medications, by a pharmacist.
avoidance of contraindicated medications), provided pa- Other antithrombotic therapies that arc managed by
tient education regarding medical therapy, and monitored pharmacists include the oral antiplatclct agents ticlopidine
for adverse drug events. By providing intensive pharmacy and clopidigrel, which are used for therapy for ischemic
services, the investigators were able to demonstrate a stroke and postcoronary stent placement. As with war-
reduction in all cause mortality, attainment of higher ACE farin, therapy with these medications requires specific
inhibitor dose, and greater use of alternate vasodilators in monitoring (especially of blood counts) and patient edu-
those patients intolerant to ACE inhibitors. cation. Another potential role for an antithrombosis phar-
macist is management of patients on low-molecular-
weight heparin (c.g., enoxaparin). As the use of these
agents has expanded to the outpatient setting, particularly
Antithrombotic therapy is used in myriad CV diseases as a transition to oral anticoagulant therapy, the need
such as atrial fibrillation, heart failure, valve replacement, exists for a skilled clinical pharmacist to maintain cffcc-
peripheral vascular disease, and stroke. This presents an tive and safe treatment with the agents. Dedden and col-
ideal setting for a pharmacist-managed antithrombosis leaugcs published a report on a pharmacist-managed pro-
clinic. Today, inany institutions have antithrombosis cli- gram to treat proximal deep vein thrombosis."" Patients
nics managed by clinical pharmacists; this trend continues were treated at home with enoxaparin and warfarin until
to grow. the patient's TNR was therapeutic; all therapeutic mon-
In such a clinic, a pharmacist is responsible for the itoring was done by pharmacists. In treating 55 patients, a
careful, periodic monitoring of prothrombin time (or in- total of 294 patient hospital days were avoided, which
ternational norrnalizcd ratio [INRI) to ensurc safe and could be translated into significant cost savings.
efllcacious therapy with oral anticoagulants such as war-
farin. In addition, the pharmacist emphasizes patient edu- es
ation regarding adverse effects, vitamin K-containing
diets, and potentially interacting drugs. The patient's drug Given the many clinical conditions related to or caused by
profile should be reviewed at every visit (for prescription cardiac conditions combined with the numerous medica-
and over-the-counter medication) to prevent possible drug tions used to treat such conditions, it is clear that the po-
Cardiology, Clinical Pharmacy Practice in 123
tential for pharmacist collaboration in the care of car- larly matters. Presentations of the results of major clinical
diology patients is endless. Other clinic types described in trials that will influence the daily practice of clinicians
the literature include pharmacist-managed smoking ces- compel many to attend major medical cardiology meet-
sation clinics' - 221 amiodarone monitoring clinics,[231 ings, such as the annual meetings of the American Heart
and cardiac medication assistance programsi241(for those Association or the American College of Cardiology, and
who cannot afford these medications). follow cardiology specialty journals such as Circulation,
Journal of the American College of Cardiology, American
Journal of Cardiology, and American Heart Journal,
NET TUNlTl among others. However, the primary forum for network-
ing of cardiology clinical pharmacists is through the
Many cardiology clinical pharmacists collaborate closely Cardiology PRN of the ACCP. This group meets at the
with their physician colleagues in patient care and scho- annual meeting of ACCP, and maintains a useful and ac-
Clinical Trials
*Kinetics/Dynamics
.Drug information
4htcomeslEconomi
i-\
HMOIMCO
*CHF
*HTN
*Lipids
.Smoking Cessation
*Anti-thrombosis
~Amiodarone *MI/ACS
.CHF
*HTN
*Arrhythmias
-ACLS
Fig. 1 Representation of the spectrum of cardiology clinical pharmacy practice. Clinical pharmacists may use their skills and knowledge
of the drug treatment of heart disease in a variety of sites (large circles) such as the pharmaceutical industry, health care systems,
ambulatory care, or inpatient settings. Specific duties are listed inside the large circles: they may include the direct care of patients
(inpatient and ambulatory practice) or more global responsibilities for drug use (health care systems and industry), and overlap to some
degree. The smaller circles represent more specific practice sites for each of the respective areas. Abbreviations: HMO, health
maintenance organization; MCO, managed care organization: GPO, group purchasing organization; AHC, academic health center;
Comm, community; Pharm, pharmacy or pharmaceutical; CICU, cardiac intensive care unit; CHF, congestive heart failure; HTN,
hypertension; MI/ACS, myocardial infarctiodacute coronary syndromes; ACLS, advanced cardiac life support (i.e., cardiac arrest team).
124 Cardiology, Clinical Pharmacy Practice in
tive listserv for discussion on therapeutic problems or is- ing, cardiology clinical pharmacists can find opportunities
sues in clinical pharmacy practice. in managing disease state-specific clinics such as the ones
previously reviewed (e.g., antithrombosis, smoking ces-
sation, heart failure lipid management). Indeed, it has
become very common (if not standard of care) for health
care systems to employ cardiology pharmacists to manage
There are numerous opportunities for cardiology clinical outpatient antithrombosis treatment (e.g., warfarin, low-
pharmacists, and these opportunities appear to be expand- molecular-weight heparin). Usually, this is accomplished
ing (Fig. 1). Traditionally, positions with a predominantly by establishing approved treatment protocols and collab-
clinical practice focus were concentrated in academic orative drug therapy agreements with physician collea-
medical centers, often those affiliated with a college of gues. It should be noted that a growing number of states
pharmacy. Here, clinicians would practice-either colla- have passed legislation to allow collaborative drug man-
boratively (particularly in an inpatient setting) within a agement by pharmacists (i.e., prescriptive authority under
health care team on cardiology units or independently approved protocols and/or agreements with physicians).
(particularly in an ambulatory setting)-to manage spe- The next frontier is cardiology clinical practice in
cialized clinics. Typically, this type of clinician has community pharmacy settings. It is hoped that the progress
teaching duties and some scholarly duties, in addition to made in ambulatory practice can be extrapolated into these
clinical responsibilities. These roles have expanded to environments. This possibility has been fueled by demon-
some degree into community hospitals as the clinical stration projects where pharmacists receive financial pay-
pharmacy movement grew. Further, because of the shift to ments for cognitive services. Noteworthy is that some of
managed health care, some clinical pharmacists with skills these initial disease state management efforts (e.g., man-
in cardiology may take responsibility for the drug use in a agement of hypertension, lipid disorders, and thrombosis)
health care system, managing formularies and developing require practice skills and specialized knowledge in car-
systemwide treatment guidelines and drug-use policies. diovascular pharmacotherapy .
Here, cardiology clinical pharmacists use their skills and
knowledge to effect drug use in populations of patients
with heart disease rather than select individuals.
For positions with a research focus, cardiology clinical
pharmacists (usually with research fellowship training)
have opportunities as clinical science faculty at research-
intensive universities (colleges of pharmacy and/or medi-
cine) or in the pharmaceutical industry. In industry po-
sitions, cardiology clinical pharmacists may coordinate General
clinical trials (phase III and IV) or work in drug dispo-
sition and pharmacokinetics. These types of positions American Heart Association web site: www.american-
remain, but other opportunities have arisen more recently. heart .org .
For instance, opportunities in the pharmaceutical indus-
try for “medical service managers’ ’ or medical liaisons Acute coronary syndromes
have expanded. These individuals may coordinate some
smaller. single-site research projects (e.g., phase IV), Ryan TJ; Antman EM; Brooks NH; Califf RM; Hillis
have educational responsibilities to physicians and phar- LD: Hiratzka LF; Rapaport E; Riegel B; Russell RO;
macists. and also have a minor sales component within Smith EE 111; Weaver WD. 1999 update: ACC/AHA
their duties (or combinations of all of the above, depending guidelines for the management of patients with acute
on the specific company). The industry is seeking sophis- myocardial infarction: executive summary and recom-
ticated health care professionals who can represent the mendations: a report of the American College of Car-
company and their products on a sophisticated level; thus, diology/American Heart Association Task Force on
the cardiology clinical pharmacist seems well suited for Practice Guidelines (Committee on Management of
such positions. Acute Myocardial Infarction). Circulation. 1999, 100,
Last, there has been an expansion of cardiology cli- 1016- 1030.
nical pharmacy into ambulatory settings. Due in part to Braunwald E; Antman EM; Beasley JW; Califf RM;
prospective and fixed payment systems and the growing Cheitlin MD; Hochman JS; Jones RH; Kereiakes D;
sophistication of pharmacists in therapeutic decision mak- Kupersmith J; Levin TN; Pepin CJ; Schaeffer JW;
Cardiology, Clinical Pharmacy Practice in 125
* Gibbons R9; Chatterjee K; Daley J: et al. ACC/AHA/ Advanced cardiac life support
ACP-ASIM guidelines for the management of ptients
with chronic stable angina: executive summary and * The American Heart Association in Collaboration with
recommendations: a report of the American College of the International Liaison Committee on Resuscitation
Cardiology/American Heart Association Task Force (ILCOR). Guidelines 2000 for Cardiopulmonary
on Practice Guidelines (Committee on Management of Resuscitation and Emergency Cardiovascular Care.
Patients With Chronic Stable Angina). Circulation. Circulation 2000, 102 (suppl I), 1-1-1-384.
Hypertension EF s
e The Sixth Report for the Joint National Committee on 1. The American College of Clinical Pharmacy Cardiology
the Detection, Evaluation, and Treatment of High Blood Practice and Research Network. Executive Summary: Peti-
Pressure. Arch Intern Med 1 97, 157, 2413-2446. tion for Added Qualifications in Cardiology for Board
Certified Pharmacotherapy Specialists; 2000.
yslipidemia 2. American Heart Association Web Page, www.american-
heart.org, accessed November 2000.
0 Executive Summary of the Third Report of the Na- 3. Leape. L.L.; Cullen, D.J.; Clapp, M.D.; Burdick, E.;
tional Cholesterol Education Program (NCEP) Expert Demonaco, H.J.; Erickson, J.I.; Bates, D.W. Pharmacist
Panel on Detection. Evaluation, and Treatment of High participation on physician rounds and adverse drug events
in the intensive care unit. JAMA 1999, 282. 267-270.
Blood Cholesterol in Adults (Adult Treatment Panel
4. Bond, C.A.; Raehl, C.L.: Franke, T. Clinical pharmacy
. 285, 2486-2497. services and hospital mortality rates. Pharmacotherapy
1999, 19: 556-564.
Anti t hrombotic therapy 5. McKennep. J.M.; Slining, J.S.: Henderson, H.R.; Devins,
D.; Barr, M. The effect of a clinical pharmacy services on
* Sixth ACCP Consensus conference on antithrombotic patients with essential hypertension. Circulation 1973, 48,
01, 119 (suppl), 1§-370S. 1104-1 11 1.
6. Forstrom, M.J.; Ried, L.D.; Stergachis, A.S.: Corliss, D.A.
Atrial fibrillation Effect of a clinical pharmacist program on the cost of
hypertension treatment in an HMO family practice clinic.
0 Fuster V, Ryden LE, Asinger RW. Cannom DS, Crijns DICP 1990, 24>304-309.
HJ. Frye RL. Halperin JL, Kay GN, Klein WW, Levy 7. Erickson, S.R.; Slaughter, R.; Halapy, H. Pharmacists
ability to influence outcomes of hypertensive therapy.
S, McNamara RL. Prystowsky EN, Wann LS, Wyse
Pharmacotherapy 1997, 17, 140- 147.
DG. ACC/AHA/ESC guidelines for the management 8. The sixth report for the Joint National Committee on the
of patients with atrial fibrillation: a report of the detection, evaluation, and treatment of high blood pressure.
American College of Cardiology/American Heart Arch. Intern. Med. 1997. 157, 2413-2446.
Association Task Force on Practice Guidelines and 9. National cholesterol education program. Second report of
Policy Conferences (Committee to Develop Guide- the expert panel on detection, evaluation. and treatment of
lines for the Management of Patients With Atrial high blood cholesterol in adults. Circulation 199
Fibrillation). J. Am Coll Cardiol 20 1333-1445.
I26 Cardiology, Clinical P h ~ r ~ Practice
a c ~ in
10. Bogden, P.L.; Koontz, L.M.; Williainson, P.; Abbott, R.D. a pharmacist inanaged anticoagulation service. Pharma-
The physician and pharinacist teain: An effective approach cotherapy 1995, 15; 732 739.
to cholesterol reduction. I . Gcn. Intern. Mcd. 1997, 12, 18. Dedden, P.; Chang: €3.; Nagel, 1).Pharmacy managed pro-
158 164. gram for home trcatmcnt of deep venous thrombosis with
1 1 . Shaffer, 1.; Wexlcr, I>.F.Reducing low-density lipoprotein enoxaparin. Am. J. Health-Syst. Pharm. 1997, 54, 1968-
cholesterol in an ambulatory care system. Results of a 1972.
multidisciplinary collaborative practice lipid clinic c o n - 19. Tommasello, T. Two pharmacy-practice models [or im-
pared with traditional physician-based care. Arch. Intern. plementing the AHCPR smoking cessation guideline. Tob.
Med. 1995. 155, 2330-233s. Control 1997, h (Suppl. l), S36- S 3 8 .
12. Furrnaga, E M . Pharmacist management of a hyperlipide- 20. Crealey, G.E.; McElnay, .I.(:.; Maguire, T.A.; O’Neill. C.
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13. Smith, N.;Psaty. R.M.; Pitt, B.; Garg, I<.; Gottdiener, bascd smoking cessation programme. Pharmacoeconornics
J.S.; Hcckbert, S.R. Tcrnporal patterns in the medical 1998, 14. 323 333.
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converting enzyme inhibitors in oldcr adults. I989 Winfield, A.J.; Donnan, P.T. Training pharmacists and
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14. Roc, C.M.; Motheral, B.R.; Tcitclbaum, F.; Rich. M.W. Tob. Control 1998. 7, 253 261.
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C.M. Reduction in heart failure events by the addition of a 23. Carmichael, J.M.; O’Conncll, M.B.; Devine, B.: Kelly, W.;
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Arch. Intern. Med. 1999. 159, 1939- 1945. statement: Collaborative drug therapy management by
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an anticoagulation clinic with usual medical care: Anti- 24. Schocn, M.D.; DiDornenico, R.S.; Connor, S.E.; Ilischler,
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17. Wilt, V.M.; Gums, J.G.; Ahrned, 0.1. Outcome analysis of Pharinacotherapy 2001, 21, 1455 1463.
Pt 1ARMACY PRACTICE ISSUES
Allen Cato
C&o R ~ ~ r Ltd.,
c h San D i c y ~California,
, U.S.A.
the causal relationship of the AEs to the drug under studied; 3) preliminary pharmacology and toxicology of
development. the drug (specific study objectives and designs); 4) the
The physician’s involvement in clinical research does methods and materials to be used in the study;
not end with the completion of the clinical study. Medical 5 ) information regarding drug packaging, labeling, dosage
reports, clinical study reports, and sections of NDAs must forms, and decoding procedures; 6) overdose manage-
be written. Interactions with regulatory agencies that ment; 7) patient discontinuation procedures; 8) expla-
require the physician’s input may occur frequently. nation of informed consent and provisions regarding
Physicians in clinical research may also be called upon institutional review board approval; and 9) any relevant
to promote new drugs in a scientific environment by references and appendices. The CRFs are the forms on
organizing symposia and workshops and by reviewing which individual patient data are recorded during a clinical
journal advertisements and promotional material for trial. From these data, clinical and statistical analyses are
medical validity and accuracy. performed. All the information that is stipulated in the
The role of the physician in a clinical drug development study protocol must be collected on the CRFs.
program has expanded and has been refined in the last 40 In conjunction with nonscientific personnel, scientists
years. Physicians increasingly contribute clinical and are responsible for ensuring that the CRFs will capture the
scientific expertise and administrative skills. Many appropriate information for each study subject according
physicians on drug development teams today spend most to the objectives, tests, and evaluations stipulated in the
of their time designing and implementing studies and protocol. Careful attention must be given to the
interpreting and reporting data rather than being in direct administration of special tests or collection of samples so
contact with patients. An experienced clinician is an that the timing of the assessments or sample collections do
important member of any drug development team. not conflict.
Experience in basic research enables the scientist to
function as an important link between the basic research
Scientists
labs within the company and the drug development team.
While a drug development team may have only one Departments specializing in drug metabolism, micro-
primary physician, it may have multiple scientists. biology, pharmacology, and toxicology need feedback
Pharmacokineticists, pharmacologists, toxicologists, and from early human safety and pharmacokinetic studies so
pharmaceutical scientists are all involved in the clinical they can continue to plan and conduct appropriate long-
development of drugs. The contributions of scientists to a term animal studies. Thus, communication between the
drug development project are derived from their clinical scientist and the basic scientist is important
experience in both scientific methodology and basic throughout the progress of the drug development
research (1). program.
Although physicians are trained in patient care, Because clinical research has become increasingly
scientists are trained in problem-solving skills related to more scientific, experts in the methodology of science are
scientific research. To obtain a doctoral degree, a necessary for a complete research program. The drug
scientist must conduct research and write a dissertation development team’s scientists may account for much of
that covers a topic of sufficient scope and depth. During the scientific expertise, but the roles of the research team
this process, the scientist learns how to solve problems overlap to form a scientifically sound, medically astute
from different perspectives. The scientist also collects cohesive group. In addition to scientific expertise, use of
extensive data and performs data analyses, thereby the scientist’s administrative talents, such as organi-
gaining valuable insight into the considerations neces- zational skills and familiarity with personnel practices,
sary to determine the feasibility of collecting data in a enables effective drug development. Thus, scientists with
clinical trial. Also, some scientists, such as pharmaco- these skills are often employed in management positions in
kineticists with a pharmacy background, may receive many organizations.
some clinical experience during their training as a
scientist.
armacists
Scientists help design major portions of study protocols
and clinical case report forms (CRFs). The study protocol The pharmacist’s role on the drug development team has
is the overall plan that the study follows, and it must greatly expanded the professional opportunities of
contain certain types of information, including the individuals with backgrounds in pharmacy. Pharmacists
following: 1) background data on the targeted disease; can provide valuable therapeutic insight into medical
2) the empirical and structural formula of the drug being research. Training of pharmacists as clinical scientists with
130 Clinical Evaluation of Drugs
both clinical skills and scientific research skills continues report that could support all of the different research
to be an emphasis at many pharmacy schools. Several documents that are generated by drug research teams.
programs have been devised for the education and With such a variable report, common information need not
development of the pharmacist as clinical scientist ( 2 ) . be recreated each time another document is generated.
Pharmacists have a broad knowledge in both clinical Excellent communication skills may be the most
medicine and pharmaceutics, and therefore are able to important quality for individuals working in drug
bridge the gap between the clinic and the laboratory. development, even for those with strong medical back-
Pharmacists’ training focuses on drug therapies in grounds. Clinical research requires extensive interactions
disease states, whereas physicians’ training focuses on the with personnel within the organization and with outside
diagnosis of disease states. Studies regarding drug vendors or clinical sites. The information flow must be
interaction, positive control, or drug comparison involve both efficient and accurate. For example, marketing
drugs that have been studied and marketed. Pharmacists departments must communicate frequently with medical
can help in the design of such trials because of their departments so that marketing studies, advertising. and
knowledge of marketed drugs. package inserts can be planned and evaluated. Individuals
Additional roles of pharmacists appear in the areas of who lack strong science backgrounds but who have
drug information and education and training. Pharma- excellent communication skills often act as liaisons in
cists have the appropriate expertise in drug therapy to these situations.
answer inquiries from physicians (and other health One aspect of clinical research that requires extensive
professionals) concerning both marketed and investiga- contribution by the drug development team personnel is
tional drug products. Similarly, the clinic/laboratory study monitoring. Study monitors oversee the planning,
bridge that the pharmacist builds makes this team initiation, conduct. and data processing of clinical studies
member especially well suited to educate and train new (3). While monitoring studies, monitors must commu-
employees in drug development. By offering both nicate frequently with investigators and help ensure the
general and special skills, the research pharmacist data are being collected properly, FDA regulations are
blends clinical medicine with pharmaceutical science being followed, and any administrative problems are
and is well qualified as an educator and drug information resolved as quickly as possible. Although monitors
specialist. traditionally have had a nonscientific background, many
monitors today have training in the basic sciences, and
some even have advanced degrees, which allows them to
better understand the scientific aspects of the project.
Drug development includes many tasks that may not Effective study monitors have a wide range of talents.
require the specialized expertise of a physician or a The many facets of a clinical research program afford
scientist. Administrative skills, creativity, and excellent individuals with varying types of training, education, and
communication abilities, which are qualities not neces- experience, the opportunity to contribute to the drug
sarily emphasized within traditional medical and scientific development process. Although some tasks clearly require
educational curricula, may be required for many of these the clinical or scientific expertise of a physician or a
tasks. scientist, other tasks are better suited to those individuals
The administrative skills necessary for drug develop- with less specialized and more general capabilities.
ment include incorporating seemingly disparate hut vitally
linked concepts into a single overall plan. Integration
planning may mean organizing study files into a logical
sequence or helping to assemble the various parts of an
NDA. In the first example, files must be set up in a way
that can facilitate internal quality assurance audits and Before clinical drug development can begin, many years
FDA inspections. In the second example, knowledge of the of preclinical development occur, millions of dollars are
FDA’s regulations and good abstracting capabilities are spent, and countless decisions are made. Basic research
required. teams consisting of chemists. pharmacologists, hiol-
Creativity is a quality that cannot be developed through ogists, and biochemists first identify promising thera-
formal training. Creativity requires bold conjecture and it peutic categories and classes of compounds. One or
expresses itself in newer, better ways to accomplish the more compounds are selected for secondary pharma-
same goals. An example of creativity in clinical drug cology evaluations and for both acute and subchronic
research might involve the development of a variable toxicology testing in animal models. A compound that is
Clinical ~ ~ a ~ u a t of
i oDrugs
n 131
pharmacologically active and safe in at least two is the determination of acute safety in humans, the
nonhuman species may then be selected for study in studies are designed to collect meaningful pharmacoki-
humans. Before the drug can be tested in humans, an netic information. Efficacy information or surrogate
Investigational New Drug (IND) application, which efficacy measurements also may be collected. However,
contains supporting preclinical information and the because a multitude of clinical measurements and tests
proposed clinical study designs, must be filed with an must be performed to assess safety, measurements of
appropriate regulatory agency. efficacy parameters must not compromise the collection
Clinical drug development follows a sequential of safety and pharmacokinetic data.
process. By convention. development of a new drug in Appropriate biological samples for pharmacokinetic
humans is divided into four phases: preapproval segments assessment, typically blood and urine. should be
(Phases 1 through 3j and a postapproval segment (Phase 4) collected at discrete time intervals based upon extrapola-
(1-4). The definitions of the three preapproval phases tions from the pharmacokinetics of the drug in animals.
have relatively clear separations. However, the different Depending on the assay sensitivity, the half-life and
phases refer to different types of studies rather than a other pharmacokinetic parameters in healthy volunteers
specific time course of studies. For example. bioequiva- should be able to be evaluated, particularly at the higher
lence studies and drug-drug interaction studies are doses. The degree of exposure of the drug is an
both Phase 1 studies, but they may be conducted after important factor in understanding the toxicologic results
Phase 3 studies have been initiated. The generalized of the study. Pharmacokinetic linearity (dose linearity) or
sequence of studies may be tailored to each new drug nonlinearity will be an important factor in the design of
during development. future studies.
Once the initial dose has been determined, a placebo-
controlled, double-blind, escalating single-dose study is
ase
initiated. Generally, healthy male volunteers are
After the appropriate regulatory agency has approved a recruited, although patients sometimes are used (e.g.,
potential drug for testing in humans, Phase 1 of the clinical when testing a potential anticancer drug that may be too
program begins. The primary goal of Phase 1 studies is to toxic to administer to healthy volunteers). These studies
demonstrate safety in humans and to collect sufficient may include two or three cohorts, with six or eight
pharmacokinetic and pharmacological information to subjects receiving the active drug and two subjects
permit the determination of the dose strength and regimen receiving placebo. The groups may receive alternating
for Phase 2 studies. dose levels, which allow assessment of dose linearity,
Phase 1 studies are closely monitored, are typically intrasubject variability of pharmacokinetics, and dose-
conducted in healthy adult subjects, and are designed to response (i.e., adverse events) relationship within
meet the primary goal (i.e., to obtain information on the individual subjects.
safety, pharmacokinetics, and pharmacologic effects of the Participants in the first study are usually hospitalized or
drug). In addition. the metabolic profile, adverse events enrolled in a clinic so that clinical measurements can be
associated with increasing dosages, and evidence of performed under controlled conditions and any medical
efficacy may be obtained. Because most compounds are emergency can be handled in the most expeditious
available for initial studies as an oral formulation, the manner. This study is usually placebo-controlled and
initial pharm-acokinetic profile usually includes infor- double-blinded so that the drug effects, such as drug-
mation about absorption. Additional studies, such as induced ataxia, can be distinguished from the nondrug
drug-drug interactions. assessment of bioequivalence of effects, such as ataxia secondary to viral infection. The
various formulations, or other studies that involve normal first study in humans is usually not considered successfully
subjects, are included in Phase 1. completed until an MTD has been reached. An MTD must
Generally, the first study in humans is a rising, be reached because the relationship between a clinical
single-dose tolerance study. The initial dose may be event (e.g., emesis) and a particular dose level observed
based on animal pharmacology or toxicology data, such under controlled conditions can provide information that
as 10% of the no-effect dose. Doses are increased will be extremely useful when designing future trials.
gradually according to a predetermined scheme, often Also, the dose range and route of administration should be
some modification of the Fibonacci dose escalation established during Phase 1 studies.
scheme ( 5 ) , until an adverse event is observed that A multiple-dose safety study typically is initiated once
satisfies the predetermined criteria of a maximum the first study in humans is completed. The primary goal
tolerated dose (MTD). Although the primary objective of the second study is to define an MTD with multiple
132 Clinical Evaluation of Drugs
dosing before to initiating well-controlled efficacy testing. patients. These studies are designed to obtain information
The study design of the multiple-dose safety study should on the efficacy and pharmacologic effects of the drug, in
simulate actual clinical conditions in as many ways as addition to the pharmacokinetics. Additional pharmacoki-
possible; however, scientific and statistical validity must netic and pharmacologic information collected in Phase 2
be maintained. The inclusion of a placebo group is studies may help to optimize the dose strength and
essential to allow the determination of drug-related versus regimen and may provide additional information on the
nondrug-related events. The dosing schedule, which drug’s safety profile (e.g., determine potential drug-drug
includes dosages, frequency, dose escalations, and dose interactions).
tapering, should simulate the regimen to be followed in Efficacy trials should not to be initiated until the MTD
efficacy testing. has been defined. In addition, the availability of
Typically, dosing in the second study lasts for 2 weeks. pharmacokinetic information in healthy volunteers is key
The length of the study may be increased depending on the to the design of successful efficacy trials. The clinical
pharmacokinetics of the drug so that both drug and pharmacokineticist assists in the design and execution of
metabolite concentrations reach steady state. Also, if the these trials and analyzes the plasma drug concentration
drug is to be used to treat a chronic condition, a 4-week data upon completion of the efficacy studies.
study duration may be appropriate. To obtain information During the planning stage of an efficacy trial, the focus
for six dose levels with six subjects receiving active drug is on the dosage regimen and its relationship to efficacy
and two receiving placebo for each of two cohorts, a measurements. Plasma drug concentrations for various
minimum enrollment of 24 subjects should be anticipated. dosages can be simulated based upon the data collected in
Similar to the first study in humans, these subjects would the first two studies in humans. The disease or
be hospitalized for the duration of the study. physiological states of the test patients (e.g., organ
Also similar to the first study, pharmacokinetic data dysfunction as a function of age), concurrent medications
must be obtained. These data will be used to help determine (e.g., enzyme inducers or inhibitors), and the safety data
dosage in future efficacy trials. The new pharmacokinetic obtained earlier must be considered when choosing an
information that can be gathered includes the following: optimal dosage regimen for the study. In addition, if the
1) determination regarding whether the pharmacokinetic targeted site of the drug is in a tissue compartment,
parameters obtained in the previous acute safety study theoretical drug levels in this compartment can be
accurately predicted the multiple dose pharmacokinetic simulated, which may help scientists determine the
behavior of the drug; 2) verification of pharmacokinetic appropriate times for efficacy measurements.
linearity (i.e., dose proportionality of C,, and AUC) On completion of the efficacy trial, a therapeutic
observed in the acute study; 3) determination regarding window for plasma drug concentrations can be defined by
whether the drug is subject to autoinduction of clearance reviewing the correlation between plasma drug concen-
upon multidosing; and 4) determination of the existence trations and key safety and efficacy parameters. The goal is
and accumulation of metabolites that could not be detected to improve efficacy and safety of the drug by
in the previous single-dose study. A number of individualizing the dosage based upon previous plasma
experimental approaches can be used to gather this drug concentration profiles in the same patient.
information, and all require frequent collection of blood
and urine samples. The challenge to the clinical
Phase 3
pharmacokineticist is to design an appropriate blood
sample collection schedule that will maximize the If the earlier clinical studies establish a drug’s therapeutic,
pharmacokinetic information, yet can be gathered without clinical pharmacologic, and toxicologic properties and if it
biasing the primary objective-determination of clinical is still considered to be a promising dmg-Phase 3 clinical
safety parameters. trials will be initiated. Phase 3 studies enroll many more
patients and may be conducted both in a hospital or
controlled setting and in general practice settings. The
goals of Phase 3 studies are to confirm the therapeutic
After the initial introduction of a new drug into humans, effect, establish dosage range and interval, and assess
Phase 2 studies are conducted. The focus of these Phase 2 long-term safety and toxicity. Less common side effects
studies is on efficacy, while the pharmacokinetic and AEs that develop latently may be identified. In
information obtained in Phase 1 studies is used to addition, studies targeted to evaluate and quantify specific
optimize the dosage regimen. Phase 2 studies are not as effects of the drug, such as drowsiness or impaired
closely monitored as Phase 1 studies and are conducted in coordination, are conducted during this phase.
Clinical Evaluation of Drugs 133
Regulatory agencies frequently require the pivotal Compared with a crossover study. more patients may be
Phase 3 studies, which will be used to support an NDA, to required for a parallel study so that statistical significance can
be placebo-controlled studies. Placebo medication should be established between the study groups. In a parallel study,
be as similar as possible to the drug being investigated recruiting the required larger numbers of patients who fit the
(e.g., same color. taste. and shape). No statistically study criteria takes longer, but the duration of that study is
significant difference in response between this group and usually shorter than the duration of a crossover study.
the subjects taking the investigational drug is evidence Crossover designs span greater periods of time because
against that drug having any real effectiveness. each group must sequentially take an active and a control
Similar to the placebo considerations, active medi- medication over a period that is long enough to allow a
cation taken by the control group also should be as similar treatment effect to emerge. When washout periods are added,
as possible to the drug being investigated (e.g.. same color, the time required to conduct these studies becomes longer
taste, and shape). If the formulations cannot be made with still, and more study subjects may drop out. These difficulties
similar appearances (e.g., tablet, suspension. etc.), a are often outweighed by the fact that statistical significance
placebo of each formulation could be made so subjects can be achieved with fewer patients in crossover studies.
would take one active formulation and the placebo of the Once the study design has been chosen, there are many
other formulation to maintain the blind. No statistically other issues to consider when developing and writing
significant difference in response in this group relative to clinical protocols. Among the topics to be considered are
the subjects taking the investigational drug is evidence that criteria for patient eligibility, efficacy and safety para-
active medication has no advantage therapeutically over meters. timing of the events, packaging and dispensing of
the existing therapy. However. a higher incidence of AEs the clinical trial material, and the informed consent form.
in the control group and an equal rate of efficacy relative to Also, to be determined is how the study will be blinded. For
the subjects taking the investigational drug are evidence of most well-controlled studies, subjects are assigned to the
the new drug’s advantage over the existing therapy. various groups by using a randomization process so that
In addition to determining the types and number of biased selection is eliminated, the overall collection of the
control groups that should be included in a study, the drug subjects’ variables is comparable in each group, and
development team must decide between a parallel and a statistical power is guaranteed (9). In these double-blind
crossover design. For example, in a placebo-controlled studies. neither the subject nor the investigating scientists
clinical trial, a parallel design is one in which each study know to which group the subject has been assigned. Thus,
group takes the same medication (i.e., either placebo or extensive input from the drug development team is required
active drug) throughout the study. With a crossover when designing studies and writing protocols.
design. each study group eventually receives both placebo
and active drug (e.g., one group may take placebo for a
6-week period and then cross over to receive active drug
for the following 6-week period).
An adbantage of the crossover design is that it allows
each group to be its own control, thereby allowing a Most drugs are tested in humans to treat a specific disease
demonstration of efficacy to occur during the treatment entity or some adverse clinical condition. Because the
with the drug. A disadvantage of the crossover design is pathogenesis of diseases and the exact mechanisms of
that residual effects from one treatment period may carry action of drugs are often poorly understood, the process of
over into the other treatment period. Absolute determi- evaluating a drug’s efficacy can be complicated. Upon
nation of efficacy and safety of the different treatments is treatment, a patient’s adverse clinical condition may
difficult and sometimes impossible. One way to avoid the improve; however, for many diseases this occurrence can
problem of residual effects on crossover studies is to liave only be evaluated indirectly by clinical assessments (e.g.,
washout periods between the different treatment phases. via blood pressure measurements in the treatment of
During the washout period, the patient is either given a hypertension). However, a drug‘s characteristics can also
placebo or no treatment for several days or weeks so that be measured directly. For example, measurement of blood
any possible metabolite or effect of the drug is “washed concentrations of the drug enabling calculation of
out” of the patient before the next treatment phase begins. pharmacokinetic parameters is a direct evaluation of the
An advantage of the parallel design is that it avoids the drug.
problems associated with possible residual effects of one Similar to efficacy assessments, evaluation of the safety
treatment period influencing the other treatment period(s) of a drug may also involve indirect measurements. One of
because each treatment group is only exposed to one drug. the primary methods of obtaining safety information in a
Clinical Evaluation of Drugs 135
clinical trial is through a patient’s rcporting of AEs. symbiotic, rather than antagonistic, relation\hip.
Although the exact biochemical mechanisms responsible an effective scientific and clinical research team often
for many AEs cannot be evaluated directly, the indirect designs and executes experiments and clinical trials that
evaluation of the drug’s adverse cffect can be seen involve costly overhead expenses, it is essential for
clinically. Because clinical assessmcnts are indirect marketing decisions to bc geared toward company
measures, AE reporting leads to scveral complex questions. profitability bcing made allow the company profitable so
The degree of drug-relatedness or causality, the cffect of these expcnses can be met. Therefore, both medical and
concomitant medication, thc severity of the AE, the marketing input arc necc ry if a pharmaceutical
complications of the disease state, and the effects of other company is to be successful.
clinical conditions or diseases are usually difficult to By gathering data on all facets of the needs in the
determine, particularly early in the drug development marketplace from clinicians and by maintaining a profile
program. Also, all reports of AEs in a clinical drug research awareness of new products under development by
program are recorded, tabulated, and cross-referenced to competitors, markeiing personnel are in an excellent
form a safety database, regardless of whether the AE is position to advise thcir colleagues in the research arena
determined to bc drug related. The information contained in who arc responsible for the drug development program.
this database is used to generate the package insert. Also, a marketing expert can help identify the problems
Although the clinical effect of a drug is perhaps the other companies are having in selling their product and
primary concern of drug development, an understanding of thereby avoid the same difficulties. For instance, sales
the drug’s biochemical and physicochemical properties and problems may be related to ineffective advertising or
mechanism of action is also desired. These direct measures faulty packaging; therefore, they do not concern clinical
are of equal concern in drug development as are the indirect research. However, problems in sales can also be related to
evaluations of a drug’s clinical effects. The primary tool a drug’s undesirable effects. An effective drug that does
used to study the intrinsic physicochemical properties of a not lead to the AEs associated with an already approved
drug is pharmacokinetics, which is a branch of biopharma- drug would have a marketing advantage. Someone in
ceutics. Pharmacokinetics describcs the relationship markcting research may suggest conducting clinical
between the processes of drug absorption, distribution, studies that would evaluate the relative incidence of the
metabolism (biotransformation), and excretion (collec- AE with the hope that the data could be uscd to support
tively abbreviated ADME) and the time coursc of effective advcrtising.
thcrapcutic or adverse cffects of drugs (10). Efficacy is Thus, research and marketing are mutually benefical in
determined by the drug concentration at the sitc of action, a successful pharmaceutical company. Marketing groups
which gcnerally is correlated with the drug concentration in help clinical research teams by supplying them with
the blood. The ultimate goal of pharmacokinetics is to information about competing products, the needs of the
charactcrize the sources of variability in the conccntration- marketplace, and suggestions for new formulations.
time profile, which may be correlated with variability in Clinical research teains provide the data to support
efficacy and adverse events. therapeutic and marketing claims and act as chief advisors
Pharmacokinetics can be used to guide dosage regimen to marketing personiicl conccrning drug research studies
selection and thereby optimize pharmacologic effects and and promotional claims.
minimim toxicologic effects when a drug is administered to
an individual patient. Thus, although thc basic pharmaco-
kinetic properties of a drug are identified during the earlicst
stage of clinical drug development, the many factors
afkcting the phamacokinetics in the patient population
must be identified throughout the drug dcvelopmcnt process Because drugs are frequently marketcd worldwide and the
to enable proper dose selection for individuals. Thus, both clinical devclopment of drugs may involve studies that are
indirect and direct measurcs arc used to evaluate a drug. conducted internationally erfcctive global planning can
present its own difficulties. Obviously, medical practice,
regulatory guidelines, and the cultural environment may
be different in various countries, but also the manncr in
which research is conceived can differ vastly between
countries. Mcdical researchers in some countries may be
A successful pharmaceutical company ha\ an appro- more conservative than researchers in other countries,
priate blend of both rcscarch and marketing to enable a which could potentially lead to the underdosing of drugs.
136 Clinical Evaluation of Drugs
These differences in research approaches actually stem International Conference on Harmonisation (ICH) of
from differences in ethical standards. Technical Requirements for Registration of Pharmaceu-
Another reason that international planning may be ticals for Human Use. ICH has focused on achieving
difficult in drug research concerns the way in which harmonization of technical requirements in three major
various countries view early clinical trials and drug safety. regions of the world: the United States, the European
Some countries view volunteer subjects and patients Union, and Japan. Some of the earliest ICH guidelines
differently from a regulatory perspective, making it easier addressed the format and content of the Investigator’s
to recruit and enroll Subjects for Phase 1 studies than it is Brochure (12), stability testing (1 3), and genotoxicity
to recruit and enroll patients for Phase 2 or Phase 3 testing (14). The FDA also works with the World Health
studies. In the United States. both patients and volunteers Organization and other international organizations to set
are viewed in the same way, and studies with patients and standards for health care products (1 1).
volunteers cannot be initiated until the FDA has Clinical drug research is a complicated, multidisciplin-
authorized an IND. ary task that may be conducted internationally. In fact,
In addition to regulatory guidelines, the regulatory many pharmaceutical companies are multinational, with
process is still another aspect of clinical drug development locations in several countries. Planning and coordination
that can differ widely between countries. In England, become even more complex for such global drug
sponsoring research firms do not interact very much with development programs. Despite the differences among
the British drug regulatory agency the Committee on countries in medical practice, regulation, and culture,
Safety of Medicines. This lack of direct interaction stems international drug development and marketing are vital
from the desire to keep commercial influence away from parts of many organizations. The successful multinational
the objective evaluation of a pharmaceutical company’s pharmaceutical company will plan its clinical research
study data. This lack of communication results in British strategy according to any differences among nations before
companies treating government guidelines for conducting to implementing its international development plans.
clinical research as a routine checklist rather than an aid in
forming the most appropriate development strategy.
In the United States, federal guidelines (Code of
CONSIDE S
Federal Regulations, CFR) have been established by the
FDA to help sponsoring research firms conduct good,
consistent clinical studies. However, some of the items No topic in clinical drug development is more con-
in these guidelines may not be appropriate for all clinical troversial and emotionally charged than the myriad ethical
studies, and some items that may be appropriate to dilemmas that face physicians and scientists involved in
include in a clinical study may not have been clinical research. Given that clinical research has generally
incorporated into the federal guidelines. These variations proved to have moral consequences through its direct and
occur because each drug and disease state is unique, and indirect influence on alleviating suffering, steps must be
complete guidelines cannot be established for all cases. taken to ensure that abuses do not occur during the course
For these reasons, several meetings are held between of drug development. Therefore, guidelines for the
clinical research teams and the FDA before an NDA protection of human subjects have been developed,
submission to ensure that all appropriate methodology proposed, and accepted worldwide (15).
and experimentation is being incorporated into the Because of the atrocities committed by Nazi medical
overall drug development project. researchers in the 1930s, the Nuremberg Code (16) was
Beginning in the early 1990s, the FDA participated in a written, and highlighted the importance of obtaining all
collaborative effort to harmonize the technical procedures research subjects’ voluntary consent to their participation
for development and regulatory approval of human in clinical studies. The Declaration of Helsinki (17), which
pharmaceuticals internationally. Forces that led the agency was published by the World Medical Association in 1964
in this direction included increased trade, the multinational and has been updated several times since, takes the
nature of the pharmaceutical industry, trade agreements informed consent issue one step further by giving only
such as the North American Free Trade Agreement and the qualified medical scientists and physicians the right to
General Agreement on Tariffs and Trade by the World conduct clinical research. However, similar concerns go
Trade Organization, European activism, and pressures on back at least to the 1830s, when Dr. William Beaumont
the industry to control costs (1 1). These pressures included developed a contract with a patient, and in the late 1800s,
intense competition and health care reimbursement when a leprosy worker experimented on a patient without
controls. This harmonization effort is the work of the her consent (18).
Clinical Evaluation of Drugs 137
Legislation that ensures the protection of human One defense for conducting placebo-controlled clinical
research subjects in the United States includes the 1979 trials is that the subjects chosen for the placebo group are
publication of the Belmont Report on the Ethical randomly chosen, so that no malicious withholding occurs.
Principles and Guidelines for the Protection of Human Also. many study protocols have provisions of study
Subjects of Research (19). This report concerns the fine extension that guarantee subjects in placebo groups have
line between biomedical research and the routine practice the opportunity to take the drug as an extension of the
of medicine and explores the criteria that determine the study after they complete the original part, or they are
risk-benefit ratio in the consideration of conducting offered the chance to receive alternative therapy. Study
clinical research. It also addresses basic guidelines for subjects may be given monetary compensation for their
the proper selection of human research subjects and further participation in studies, in addition to free, thorough
defines the elements of informed consent. physical exams, lab work, and physician visits.
Other important legisiation in the United States Interestingly, experimental drugs have unknown side
includes the FDA’s Guidance for Institutional Review effects that can cause serious biochemical and physiologic
Boards (IRBs) (20) for further guarantees of protection for problems, whereas placebo medication does not. This fact
human research subjects. IRBs are independent commit- makes possible the contrary argument and objection, on
tees that review proposed clinical research projects before purely ethical grounds, to giving study subjects
the commencement of the research. These committees experimental and hence unproven drugs. Of course,
decide whether the risk to research subjects outweighs the informed consent and careful monitoring by trained
potential benefit of the research; they can suggest medical personnel help to alleviate the ethical problems
modifications in the research proposal or disapprove the associated with giving subjects an active, investigational
project altogether. IKBs must consist of both men and drug. The most important aspect of all studies is that the
women of varying professions. At least one member must patient be completely informed of all study procedures and
have his or her primary concern in a nonscientific area agree to willingly participate in the study.
(e.g., a lawyer or clergyperson), and at least one member The most recent pressing ethical dilemma facing the
must not be affiliated with the institution at which the clinical research scientist surrounds the increasing amount
research will be conducted. of research that is being conducted in biotechnical and
Closely related to the rights of human research subjects genetic engineering. Ethical issues will continue to play
are the rights of routine patients involved in nonresearch important parts in the medical and legal worlds. Whereas
medical matters. In 1973, the American Hospital pure science is value-neutral, its application is always
Association published the Patient’s Bill of Rights (21), open to debate. Undesirable extremes are likely to exist at
which requires that the acting physician give his patients both ends of the spectrum.
complete information concerning their diagnosis, treat-
ment, and prognosis; that the patient be given respectful
care; that the patient be given the opportunity to refuse
CON NS
treatment; and that the patient’s records, condition, and
medical care be treated confidentially.
Another ethical issue facing clinical research scientists To conduct a clinical study for the evaluation of a new
concerns study design, in particular, the placebo- drug, a vast array of personnel is required. Physicians are
controlled clinical trial. The reason placebo-controlled largely used because of their knowledge of clinical
clinical trials are conducted is quite compelling from a medicine and patient care, whereas scientists are used
scientific standpoint: to ensure that the evidence support- because of their knowledge of the methodology and the
ing the efficacy of an experimental drug is actually due to science. Pharmacists serve a bridging function due to their
the properties of the drug and not to the psychologic unique training in therapeutics and the pharmaceutical
properties of the study subjects. In other words, if a sciences. Nonscientific personnel are indispensable
placebo effect from the experimental drug occurs rather because of their ability to coordinate the many facets of
than a true therapeutic effect, then a comparison of the a drug development project.
drug group with the placebo group will show statistically The clinical evaluation of drugs involves many
similar response rates. It is a way to help separate actual different levels of scrutiny before a drug product can be
drug responses from placebo responses, especially in marketed. These levels include Phase 1 for safety testing,
studies investigating psychiatric compounds, but also in Phase 2 for evaluating efficacy and determining the
other therapeutic areas with a clearer “physiologic” or correct therapeutic dose, Phase 3 for large-scale studies
“biochemical” basis. and determination of drug interactions, and Phase 4 for
138 Clinical Evaluation of Drugs
postmarketing surveillance. Phase 1 studies are typically 6. Bertz, R.J.; Granneman, G.R. Use of In Vitro and In Vivo
conducted in healthy volunteers, and Phase 2 through 4 Data to Estimate the Likelihood of Metabolic Pharmaco-
kinetic Interations. Clin. Pharmacokinet. 19
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evaluation of drugs. A clinical study cannot be conducted Protocol. Concepts and Strategies in New Drug
without specifically outlined objectives and a definitive Development; Praeger Publishers: New York, 1983; 82-87.
plan, which are vital components around which the study 8. Spilker, B. Part 11: Developing and Writing Clinical
protocol is constructed. The use of placebo or active drug Protocols. Guide to Clinical Trials; Lippincott-Raven:
Philadelphia, 1996; 145-272.
control groups in the study, and whether the design should 9. Friedman, L.M.; Furberg, C.D. Basic Study Design.
be open, parallel, or crossover, must be determined. In most Fundamentals of Clinical Trials; PSG Publishing Co.,
studies, patients are assigned to study groups randomly. Inc.: Littleton, MA, 1985; 35-38.
The developmental objectives facing the clinical 10. Gibaldi, M.; Levy, 6 . Pharmacokinetics in Clinical Practice
research team include indirect evaluations of a drug’s I. Concepts. JAMA 1976,235, 1864-1867.
safety and efficacy, such as effects on vital signs or 11. Horton, L.R. Harmonization, Regulation, and Trade: Where
Do We Go from Here? [editorial]. PDA J. Pharm. Sci.
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properties, such as its pharmacokinetics and mode of 12. Cocchetto, D.M. The Investigator’s Brochure: A Compari-
action. Also, the marketing-medical liaison is important if son of the Draft International Conference on Harmonisation
research is to support future sales plans and advertising is Guideline with Current Food and Drug Administration
to reflect study results. Finally, effective global planning is Requirements. Qual. Assur. 1995, 4, 240-246.
13. Haase, M. Stability Testing Requirements for Vaccines:
necessary because drugs are more frequently developed
Draft Guidelines of the International Conference on
and marketed worldwide, and therefore involve differing Harmonization. Dev. Biol. Stand. 1996, 87, 309-318.
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ICH guidelines have helped to standardize regulations Genotoxicity Testing: Current Practices and Strategies
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15. Levine, R.J. Ethics and Regulation of Clinical Research;
affect much of the legislation that currently regulates the
Urban & Schwarzenberg: Baltimore, 1981.
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research is to develop effective pharmacotherapy for 17. World Medical Association Declaration of Helsinki:
mankind’s ailments, and regulatory agencies have enacted Recommendations Guiding Physicians in Biomedical
legislation to prevent unethical research. Research Involving Human Subjects, Adopted by the 18th
Although traditional medicines continue to be dis- World Medical Assembly, Helsinki, Finland, June 1964
and Amended by the 29th World Medical Assembly,
covered and developed, the fields of biotechnology and
Tokyo, Japan, October 1975, the 35th World Medical
gene therapy continue to advance. In addition, new Assembly, Venice, Italy, October 1983, the 41st World
methods to collect and evaluate clinical data on a real-time Medical Assembly, Hong Kong, September 1989. and the
basis will help to speed the development process. 48th General Assembly, Somerset West, Republic of South
Africa, October 1996.
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Belmont Report. Ethical Principles and Guidlines for the
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PKOFESSIONAL RESOURCES
CLIA 1988 significantly increased the scope of federal tests are required to register but are exempt from
laboratory regulation both in terms of the number of la- most quality standards. The exception raised concerns
boratories regulated and quality standards.[’] Under CLIA with regard to accuracy and interpretation of results in
1988, any facility that examines or tests material derived these settings.
from the human body for patient care purposes is subject
to federal regulation. Furthermore, the law provides for
personnel, patient test management, quality control and
quality assurance standards. as well as proficiency testing
to identify poorly performing laboratories. Although relatively few pharmacies engaged in laboratory
The legislation came under immediate criticism.[71Ini- activities when CLIA 1988 was passed, the issues and
tial criticism called the need for more comprehensive concerns raised with the passage of CLIA 1988 are ex-
regulation into question. The Wall Street Journal articles tremely important to pharmacist^."^] There is an increas-
that precipitated the legislation focused on “errors’ ’ that ing need for timely, accurate laboratory values in modern
resulted in missed or delayed diagnosis of carcinoma of pharmacy practice. Objective laboratory measures help
the uterine cervix. The problems described did exist to in determining dosages, evaluating medication efficacy,
some degree but the articles were considered by many to assessing for adverse drug reactions or toxicity, and mo-
be sensationalistic and misrepresentative. Furthermore, nitoring adherence to therapy. Furthermore, in-pharmacy
neither the Wall Street Journal article nor congressional laboratory testing allows for the provision of screening
testimony revealed that the CLIA 1967 regulations al- services, a valuable public service in the detection of un-
ready applied to cytology and that all cited instances of recognized disease.
unacceptable laboratory practice had been subject to en- Pharmacists share in the concerns about underregu-
forcement under existing regulations. lated laboratories. especially with regard to accuracy and
Continuing criticism focused on the extent of the re- interpretation of results.“’] Since the results of pharma-
gulation.[12-141Manjr laboratory professionals expressed cist-conducted laboratory tests are used in making clinical
concern that certain portions of the CLIA regulations decisions. the values must be accurate. Additionally,
were overly prescriptive and burdensome. While labo- pharmacists must be knowledgeable about interpretations
ratory management welcomed the decreased stringency of laboratory results. the variables that can affect them,
in personnel requirements as providing greater flexibi- and their clinical implications. Finally. these concerns
lity in staffing, laboratory professionals expressed con- require that equipment be maintained and operated in full
cern that personnel changes were a dangerous weaken- accordance with the manufacturer’s instructions.
ing of standards.
Physicians operating office laboratories were also
concerned. Much of the concern focused on the intru-
siveness of quality standards, especially proficiency
testing.[141A chief criticism of proficiency testing was Given the importance of laboratory data to pharmacy
that the proficiency testing process is highly artificial practice, pharmacists should be familiar with the regu-
with many operational, technical, and clerical variables latory framework of CLIA 1988. A major aim of ex-
that are absent from routine patient testing. Physicians panding the reach of CLIA 1988 to virtually all clinical
argued that in an office setting significant inaccura- laboratories was to ensure that laboratory tests varied only
cies were likely to be detected by the physician. Requir- by differences in methodology, equipment used, and
ing physicians to comply with burdensome regulations training required for test performance.“6 17] In other
might cause many physicians to eliminate office-based words. the type of regulatory standards applied to a phar-
laboratory services. They argued quicker and more ac- macy, physician’s office. or some other previously un-
cessible results were more important for immediate regulated site would be determined only by the tests
patient care than highly accurate results after the patient performed. This regulatory framework is known as a
has gone home. “complexity model.”
In contrast to the concerns about overregulation were Under the complexity model there are three categories
concerns about underregulation of persons engaged in of tests on which regulatory standards are based: waived
relatively simple laboratory activities such as health tests, tests of moderate complexity (including a pro\ ider-
screenings.“‘] Under the CLIA 1988 regulations, per- performed microscopy subcategory), and tests of high
sons collecting human specimens for patient care pur- complexity. The complexity of tests performed within the
poses using specified, relatively simple equipment and laboratory determine which personnel, proficiency test-
Clinical Laboratory Improvement Amendments of 1988 141
ing, patient management, and quality control and quality in performing tests. While proficiency testing, quality
assurance standards will apply to the laboratory. control, and personnel standards are not required, persons
performing waived tests should adhere to basic tenets of
quality control and quality assurance.[16]
Table 1 Tests granted waived status under CLIA used in drug monitoring
Test name Manufacturer Use
Glucose monitoring devices cleared Various Monitoring of blood glucose levels
by the FDA for home use
Bayer DCA 2000 Bayer Measures the percent concentration
Metrika DRx HbAlc Metrika, Inc. of hemoglobin Alc in blood for
monitoring long-term diabetic control
LXN Fructosamine Test System LXN Corp. Measures glucose/fructosamine to
LXN Duet Glucose Control evaluate diabetic control over a 2-3
Monitoring System week period
LXN IN CHARGE Diabetes
Control System
ChemTrack AccuMeter ChemTrak Cholesterol monitoring
Advance Care Johnson &Johnson
Accu-Check Instant Plus Cholesterol Boehringer Mannheim Corp.
ENA.C.T Total Cholesterol Test ActiMed Laboratories
Lifestream Technologies Lifestream Technologies
Cholesterol Monitor
MTM Bioscanner 1000 (for OTC use) Polymer Technology Systems, Inc.
PTS Bioscanner Test Strips Cholesterol Polymer Technology Systems, Inc.
Cholestech LDX Cholestech Measures total cholesterol, HDL
cholesterol, triglycerides, and
glucose levels
PTS Bioscanner (for OTC use)-for HDL Polymer Technology Systems, Inc. Measures HDL cholesterol in
whole blood
PTS Bioscanner 2000 for Triglycerides Polymer Technology Systems, Inc. Measures triglycerides in whole
blood
ITC Protime Microcoagulation System International Technidyne Corp. Evaluation of heparin, coumarin,
CoaguChek PST Boehringer Mannheim Corp. or warfarin effect
AvoSure Pro Avocet Medical, Inc.
Roche Diagnostics CoaguChek S Roche Diagnostics Corp.
Systems Test
142 Clinical Laboratory Improvement Amendments of 1988
specialized tests (for example, cytogenetics, histopathol- quality control standards by following manufacturer's
ogy, histocompatibility, cytology, and other highly spe- instructions when using a device cleared by the FDA as
cialized tests) have been classified as high complexity.['61 meeting CLIA requirements for quality control.[261 For
The categorization of tests enables a laboratory to deter- other tests of moderate and high complexity, the re-
mine easily what level of regulation it will follow.[21.221 gulations state specific quality control standards.
The intent is that testing environments not eligible for a
certificate of waiver, and which do not conduct highly
specialized testing, will be certified to perform moderate-
complexity testing. The personnel, proficiency testing, Finally, laboratories performing moderate-complexity or
patient test management, and quality control and assurance high-complexity testing must establish and follow written
standards for moderate- and high-complexity tests are policies and procedures for a comprehensive quality as-
outlined below. surance program that is designed to monitor and evaluate
the ongoing and overall quality of the total testing pro-
nnei ~ e s s . [The
~ ~ laboratory's
] quality assurance program must
evaluate the effectiveness of its policies and procedures;
Personnel standards are a significant differentiating ele- identify and correct problems; assure the accurate, re-
ment in the regulation of moderate- and high-complexity liable. and prompt reporting of tests results; and assure the
testing l a b ~ r a t o r i e s . ' ~Both
~ ] types of laboratories require adequacy and competency of the staff.
a laboratory director, a technical consultant, a clinical
consultant. and testing personnel. However, the educa-
tion, training, and experience required for these positions CLU
differ. In addition, high-complexity laboratories are re-
quired to maintain technical supervisor and general su- Currently, most pharmacy-based testing falls within the
pervisor positions. waived category and is exempt from extensive quality
standards. However, given the importance of timely and
accurate laboratory data in the provision of pharmaceut-
ical care, it is likely that pharmacy-based laboratory
Each laboratory performing tests of moderate and high testing will expand in breadth and scope.[281Therefore,
complexity must enroll in an approved proficiency testing pharmacists need to be aware of the quality issues raised
program for each specialty or subspecialty for which it and addressed by CLIA 1988.
seeks certification.[241In general, proficiency testing re- Although the detail is beyond the scope of this
quires five challenges per testing and three testing events monograph, pharmacists should also be aware of other
per year. Failure to attain an overall testing event score of laws and regulations impacting pharmacy-based labo-
at least 80% is unsatisfactory performance. Proficiency ratory testing. Many states have their own laws regulating
testing samples must be tested with the laboratory's re- laboratory quality and professional competency.['51 In
gular patient workload, using routine testing methods, and addition, there are Occupational Safety and Health Ad-
by personnel who routinely perform testing. ministration (OSHA) standards pertaining to laboratory
operations.'293301Before engaging in laboratory testing
t Tes ement pharmacists should be thoroughly familiar with all la-
boratory regulations.
Laboratories performing moderate-complexity or high-
complexity testing must also employ and maintain a system
that provides for proper patient preparation and proper
specimen collection, identification, preservation, and pro- EN
cessing.[251This system must assure optimum patient spe-
cimen integrity and positive identification throughout the 1. Clinical Laboratory Improvement Amendments of 1988
(CLIA). Pub. L. NO. 100-578, 42 USC 201 (1988).
pretesting, testing, and posttesting processes and must meet
2. Laboratory Requirements. In 42 Code of Federal Regula-
the standards as they apply to the testing performed.
tions Parts 430 to End; Revised as of October 1, 1999;
8 19-941.
3. Bluml, B.M.: McKenney, J.M.; Cziraky, M.J. Pharmaceut-
ical care services and results in project ImPACT: Hyper-
After December 3 1, 2000, laboratories performing either lidemia. J. Am. Pharm. Assoc. 2000. 40, 157- 165.
moderate- or high-complexity tests may, in general, meet 4. Bluml, B.M.: McKenney, J.M.; Cziraky, M.J.; Elswick,
143
R.K., Jr. Interim report from Project ImPACT: Hyperlide- Federal Rc,gulations Section 493.15; Revised as of October
niia. J. Am. Pharm. Assoc. I 1, 1999; 828.
5. Gore. M.J. Pharmacy-based laboratory testing: Adding 20. Test Categorization. In 42 Code of Federul liegiilutions
cal care. J. Am. Pharm. Section 493. / 7: Revised as of October 1 , 1999; 828-830.
21. Laboratories Performing Tests of Moderate Complexity. In
6. tunitics and rcsponsibil- 42 Code of I.Pderul Reg~i1utioiz.vSection 493.20; Keviscd
ities in pharmaceutical care. Am. 1. Hosp. Pharm. 199 as of October 1, 1999: 831.
533-542. 22. Laboratories Performing Tests o f High Complexity. Tn 42
7. Bachner, P.; Hamiin, W. Federal regulation o f clinical Code of Federal Regulutioizs Sectioiz 493.15: Revised as of
labOrdtorieS and the Clinical 1,aboratory Iinprovcment October I , 1990; 831.
Amendments of 1988-Part 1. Clin. Lab. Mcd. 1993. 13; 23. Subpart M-Personnel for Moderate Complexity (Includ-
739-752. ing thc Subcategory) and High Complexity Tcsting. In 42
8. Rachner, P.; Hamlin, W. Federal regulation of clinical Code o f Fedrral Kegul~itiniis Section 493.1351 to
laboratories and the Clinical Laboratory Improvement 493.1495: Revised as of October I , 1999; 900-925.
Amendments of 1988-Part TI. Clin. Lab. Med. 1993, 13, 24. Subpart I-I-Participation i n Proficiency Testing for
987- 994. IAoratories Performing Tests of Moderatc Complexity
9. Clinical Laboratory Tmprovemcnt Act of 1967 (CLIA), (Tncluding the Subcategory), High Complexity, or Any
Pub. L. No. 90- 174, 42 USC 2 I6 (1967). Combination of These Tcsts. I n 42 Coix'c. of Fedeml
10. Bogdanich, W. Medical labs; trusted as largely error-free, R~~gulatiorzsSeclioi~493.801 to 493.825; Revised as of
arc far from infallibl October 1, 1999; 853-856.
11. Bogdanich, Mi. Thc 2s. Subpart J-Patient Test Management for Moderate
through labs' crrors. Complexity (Including the Subcategory), High Complex-
12. Neff, J.C.: Speichcr, ity. or Any Combination of These Tests. In 42 C,'ode ol
gulation, or a promise of quality. Arch. Pathol. Lab. Med. Federal Rrgulationv Section 493.1101 to 493.1 I 1 I ; Re-
1992. 116, 679-680. vised as of October 1, 1999; 881-883.
13. Hurst, J.; Nickel, K.; Hilborne, L.H. Are physicians' office 26. Subpart K-Quality Control for Tests of Moderate
laboratory results of comparablc quality to those produced Complexity (Including the Subcategory), High Complex-
i n other laboratory settings? JAMA, J. Am. Med. Assoc. ity. or Any Combination of These Tests. l n 42 Code of
Federal Regulritiorzs Section 493.1201 /o 493.1203;
14. Rachner. P. Is it time to tu Kevised as of Octobcr 1. 1999: 883-885.
JAMA. J. Am. Mcd. Assoc. 27. Subpart P-Quality Assurance for Moderate Complexity
IS. Koscnthal, W.M. Establishi (Including the Subcategory) or High Complexity Testing,
ratory service. J. Am, Pharm or Any Cornbination o f These Teats. In 42 Codr uf Federal
16. Medicare, Medicaid and CLIA Programs: Regulations Kegidatioti.~Section 493.1 701 io 493. I71 7; Revised as of
Irnplcmenting the Clinical 1,aboratory Iinprovemcnt October 1, 1999: 925-927.
Amendments o f 1988 (CLIA). Fed. Regist. 1992. 57; 28. Magarian, E.O.: Peterson, C.D.; McCullagh. M E : Kuzel,
7002-7186. R.J. Role model ambulatory care clinical training site in a
17. Stull, T.M.; Nearn, T.L.: Hancock, J.S.; Handsfield, .I.H.: community-based pharmacy. Aim J. Pharm. Ed. 1993, 57,
Collins, C.L. Variation i n proficiency testing performance 1 ~ ~ 9 .
by testing aitc. IAMA, J. Am. Med. Assoc. 1998, 279, 29. Blood-borne Pathogens. In 29 Code cf Federul Regu-
463 -467. lations Section IOI0.1030: Revi\ed as of July I . 1999;
18. Subpart B-Certificate of Waiver. In 42 Code of Fede- 26 1 -274.
ral Regulutioizs Secli(177 493.35 lo 493.30; Revised as of 30. Occupational Exposure to Hazardous Chemicals i n the
October 1. 1999; 831-833. Laboratory. In 20 Code o$ Federal lieg~ilationsS e r ~ i o n
19. Laboratories Performing Waived Tests. In 42 Code u/ 1910.1450; Revised as of July 1, 1999; 484-538.
PHARMACY PRACTICE ISSUES
WiCa
Kansas City, Missouri, U.S.A.
-
145
*. 9
b
. DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
i
9,
1
Food and Drug Administration
Rockville MD 20857
MAY I 0 1983
Fig. 1 1983 Response letter from the FDA addressing participation of clinical pharmacists as PIS
experience needed to assume the significant responsibil- nistered by telephone to a small number of pharmaceu-
ities of PI.'^] tical companies. Information was obtained from five
companies and suggests that most companies do not have
specific policies that exclude pharmacists from function-
ECTlVE ing as PIS. However, the general consensus was that
pharmacists were used primarily for pharmacokinetic
To better understand current industry policies regarding studies and not for other types of clinical trials. In most
pharmacists as PIS, a short, informal survey was admi- instances, the program manager or study team leader
146 Clinical Pharmacist as Principal Investigator (ACCP)
.
."
*9
6
. DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
?,
*,
Food and Drug Administration
Original dated: April 3 , 1990 Rockville MD 20857
At the June 1, 1989 Division Director's Policy Meeting, one of the topics was FDA
policy on qualifications of principal investigators. It was agreed that FDA policy
should continue to be as stated in the July 16, 1980 memorandum from Dr. Finkel, but
that the memo should be updated to reflect the wording of the IND Rewrite as
follows:
Clinical Investisators
Qualified individuals who are not M.D.'s can participate in clinical trials
either as principal investigators or sub-investigators provided that an M.D.
or D.O., (or D.O.S. depending upon the study) is either a sub-investigator or
is listed in the IND as an individual who will be responsible for drug
administration and evaluation of patient safety.
Clinical Monitors
Qualified individuals who are not M.D.'s can serve as monitors of clinical
trials provided that an M.D., D.O., or D.O.S. is involved in the review and
evaluation of the ensuing clinical data and the adverse reactions.
Please remind division staff of the above policy.
-d
James Bilstad, M.D.
Fig. 2 1989 and 1990 Response letters from the FDA reiterating that clinical pharmacists can serve as PIS in clinical trials (Continued).
makes the decision regarding which investigators to If the contact at a particular company states that a
approach as PIS based on their overall qualifications. If pharmacist may not serve as a PI, it may be worth
a pharmacist can demonstrate their expertise in a inquiring about this policy. It could be that the decision
therapeutic area (as outlined later), and their ability to maker is unaware of FDA's policy regarding pharma-
enroll the required number of qualified subjects into the cists as PIS. Such information could influence the
clinical trial within an established time period, it would decision of the study manager, especially if there is no
appear that most pharmaceutical companies will allow a company policy that precludes pharmacists from func-
pharmacist to serve as the PI for a study. tioning as PIS.
148 Clinical Pharmacist as Principal Investigator (ACCP)
Given the importance of investigator experience and Investigators are defined in the GCP guidance as the
qualifications to their designation as PI, the remainder persons responsible for the conduct of a clinical trial at a
of this article centers on the capabilities and responsi- given site. If that trial is conducted by a team of indi-
bilities (including FDA regulations) needed to serve in viduals, the PI is the responsible team leader. Subinves-
this capacity. tigators are individual team members designated and
supervised by the PI to perform critical trial-related pro-
cedures and/or make important study-related decisions. In
the same document, a clinical trial or study is defined as
any investigation in human subjects intended to discover
or verify the clinical, pharmacological, and/or pharmaco-
F il ities dynamic effects of an investigational product.
list of qualified persons to whom the investigator has primary physician about their participation in the trial.
delegated significant trial-related duties. A qualified PI The investigator should make every effort to determine
must show familiarity with the compound to be studied the reason for subject withdrawal from the trial, while
and demonstrate adequate resources to conduct the trial. being respectful of the subject’s rights to withdraw with-
This includes being able to recruit in a timely manner an out explanation.
adequate number of subjects that meet protocol-defined During the performance of the study, the investigator
entry criteria, have an adequate number of qualified staff, must maintain adequate documentation of study acti-
and have necessary facilities available for the anticipated vities and must promptly report any deviations from the
duration of the trial. The PI is responsible for assuring that protocol to both the IRB and study sponsor. Any chang-
all staff assisting in the trial are well informed about the es to the protocol, all adverse drug reactions that are
protocol, the investigational drug, and their duties with both serious and unexpected, and any new information
regard to the trial. that may affect adversely the safety of the subjects or
their willingness to participate in the clinical trial must
be promptly reported to the IRB. Substantive changes to
the protocol must receive IRB approval. Investigators
must also submit progress reports to the IRB at least
enera annually; sponsors will usually request more frequent
progress reports.
A PI is responsible for the conduct of a scientific
investigation in accordance with study methodology, a
signed investigator agreement or contract with the spon-
sor (if applicable), and any federal or state rules and The PI is responsible for maintaining records associated
regulations regarding performance of a study using human with the clinical study. These include case histories
subjects. The underlying premise is to protect the rights, designed to record all observations or other pertinent data
safety, and welfare of subjects under the investigator’s on each enrolled subject, independent of whether the
care and to control the distribution and use of drugs un- subject received active treatment. Data for each trial sub-
der study. ject is normally recorded on a case report form provided
As mentioned, prior to initiation of the trial, the in- by the sponsor. The sponsor may also require study data
vestigator needs IRB approval, an approved subject in- to be recorded in a source document (patient chart). It is
formed consent form, and approved subject recruitment the responsibility of the PI to assure that the forms are
procedures. The investigator must provide the IRB with filled out with the correct information and according to
current copies of the Investigator’s Brochure for each guidelines established by the sponsor.
investigational drug before beginning the trial, and must Study drugs, whether investigational or commercially
provide updated copies if the Investigator’s Brochure is available, must be controlled and accounted for, and may
revised during the conduct of the study. The PI is ac- only be administered to study subjects who have provided
countable for obtaining written informed consent from all informed consent and who are under the supervised care
subjects. In life-threatening situations necessitating the of a trial investigator. Accordingly, a drug accountability
use of the study drug, the IRB may approve other methods log must be kept up to date and accurate. The log should
of obtaining informed consent. Regardless, an investigator record the disposition of the drug, including dates, quan-
may only obtain consent after a subject or their legally tity, and use by subjects. Study drugs must be secured in
authorized representative has had sufficient opportunity to a locked storage area until destroyed, properly disposed
consider the risks and benefits of participation without of, or returned to the study sponsor.
coercion or unreasonable influence. Case histories, drug accountability logs, and all cor-
During the clinical study, a qualified physician or respondence associated with the study must be secured
dentist, as appropriate, who is at least a subinvestigator and kept for 2 years after the marketing application is
must be responsible for all trial-related medical (or dental) approved by the FDA. If no such application is filed, or if
decisions. The PI and the institution must ensure that the application is not approved by FDA, these records
adequate medical care is provided to subjects for any must be retained for 2 years after the investigation is
adverse events related to the trial. Intercurrent illnesses discontinued and the FDA is notified. It is advisable that
that are detected during the course of the study must be records from clinical trials supported by grants from
noted and the subject informed. If agreeable to the study academic, government, or voluntary health organizations
subject, the PI is also responsible for informing their also be maintained for this same time period, unless
150
otherwise specified by the agcncy. If the study is part of be allowed to copy documents with patient identifiers
an international clinical trial, or if speciricd b y the omitted and must be provided sufficient timc to verify
sponsor, the PI may be required to keep a patient list with records associated with the conduct of the study. Inves-
igninents for 15 years after the conclusion tigators are not requircd to provide the names of subjects
of the trial. unless the records or a specific individual require more
In the case of premature termination or swpension of intensive examination related to an adverse event, or there
thc trial, the investigator must promptly inform trial is suspicion that the records are falsified. Frequent or
sub.jects, assure appropri follow up and treatment if dcliberatc falsification of records may lead to disquali-
required, and inform the B and regulatory authorities fication of a PI to conduct futurc clinical studies, as wcll
as appropriate. Similarly, when a trial is completed un- as potential criminal or civil prosccution.
dcr normal conditions, the investigator must file final
reports with the sponsor and inform the institution, the
IRB, and regulatory authorities (as appropriate) that the
trial is complctcd.
Finally, all records must be available on request from Before agreeing to participate in a sponsored clinical
the FDA or study sponsor within a reasonable time. The study. the P11 should answer a number of questions about
authorized representativc lrom the sponsor or FDA must the logistics of conducting thc protocol at their site and
y Logistics: A § ~ ~and
~ Plan
s ~ e ~ ~
I. Administrative Plan
a. Institutional approvals
* Determine if contract and investigator agreement regarding responsibilities, intellectual property, confidentiality,
indemnification, data ownership, and publication rights are acceptable to your institution.
* Is approval needed from other institutional regulatory committees? 'This might include radiation safety or biohaLards
committees,
I l t h e investigator is receiving funding for the study, how will these monies be handled Mithin the institution?
How much time is nccdcd by the institution to set up the payment infrastructure?
Docs the institution havc an overhcad charge for government, voluntary organizations, or corporate studies?
Will the PI have access to these excess monies after the study is complete'?
b. IRB 1,ogistics
I4ow oftcn does the I N 3 meet?
0 What are the requirements for submission of an IRB study packet?
Take time to talk with the R B personnel to understand the complete review process before submission.
0
_.
1 his will save time and prevent anxiety.
[I. Opcrational Plan
a. Physical Kcsources
Where will the study be conducted?
Docs the study require an ambulatory care clinic, a clinical research center, or will patients need to be hospitalizd?
Usc of tliesc facilities will need to be negotiated with the institution.
0 What types of tests are necessary? Laboratory testing, radiography, nuclear medicine, physical therapy, or other
scrviccs should be contacted about the proper method of sending samplcs, ordering tests, and paying for services.
Some inslitutions may offer research discounts for tests.
lHow will the test data bc collected? If study data are recorded in patient's charts or institution computers, will the
invcstigator havc accesb to these charts after the paticnt is discharged or thc study is complete? Verification of
records may occur several years after a study is complctc: thercfore, access to records must be confirmed prior
to starting the study.
b. Human Resources
Determine need Ibr coinvestigator(s) and outline their roles.
0 Determine need for study coordinator and responsibilities.
Assign responsibilities and esldblish deadlines and milestones for all personnel closely related to the study
(e.g.>study coordinator, coinvestigators, research fel lows).
e Visit with the nursing staffofthe faculty to avoid unnecessarq delays in starting the protocol.
Fig. 3 Kccoininended guidclinci for assessment and planning of study logistics before conducting a study protocol
Clinical Pharmacist as Principal Investigator (ACCP)
should create a sound plan for study implementation. To comprehensive budget and provide accurate estimates on
do so, the PI must understand the structure that governs all institutional costs. If such an office does not exist. one
research support and funding within their institution to can contact the campus grants and contract office or a peer
avoid technical or financial problems during or after the group with experience in conducting clinical studies in the
study. Addressing the issues and questions identified in investigator’s setting. Many times, the sponsor will ge-
Fig. 3 before starting the protocol will help in conducting nerate a proposed budget for a trial based on usual and
a timely and successful study. customary costs. These budgets are typically very com-
Once the PI agrees to participate in a clinical study, its plete, although they can be modified through negotiation
successful initiation requires that the PI have the fol- with the sponsor if the increased costs can be justified.
lowing: 1) regulatory approval from the sponsor and FDA The investigator must remember that most clinical trial
[if the study requires an Investigational New Drug ap- budgets derived in academic settings must conform to the
plication (IND)] through submission of FDA Form 1572; Health Care Finance Administration’s corporate compli-
2) legal approval by the investigator’s institution of their ance regulations. The regulations state that federal health
contract and agreement with the study sponsor that details care payers are responsible for covering only those re-
the scope of work, data ownership, intellectual property, sources that are medically necessary for the care of a
publication rights, indemnification, and confidentiality; 3) patient. Taxpayer dollars (e.g., Medicare) cannot be used
budget approval from the institution’s grants and con- to subsidize purely research activities, or for experimental
tracts office; and 4) IRB approval of the study protocol or unproven medical therapies.
and informed consent procedure. Investigators are en- Research-related costs are derived from the investiga-
couraged to complete this process within 45 days to be tor’s hospital or clinic, laboratory testing or analysis, or
competitive with other research service providers. Two through contractual arrangements with other laboratories.
major pitfalls of which investigators must be aware In addition, there may be patient recruitment costs such as
involve budgetary planning and ownership of data. Poor advertising, patient expense reimbursement (parking and
planning in either regard can jeopardize the PI’s ability to transportation), and participation honoraria. Research
complete the project and disseminate new scholarly in- resources usually include equipment, supplies, and salary
formation (data ownership and publication). support for the PI and associated personnel. Salary
support for the PI and other study personnel generally
Budget has the greatest flexibility and provides an opportunity to
generate residual funds to support the PI’s overall
An essential component to any clinical trial is a well- research program.
planned budget that accounts for all resources and project From a financial perspective, the PI’s primary ob-
costs. In many instances, the investigator will be com- jective when entering into a research contract is to com-
peting with other sites for the research contract. Therefore, plete the study successfully at or below the requested
the budget must cover costs. provide a reasonable incen- budget. The residual funds that result are often placed into
tive to the investigative team, and be Competitive in the a development fund on behalf of the PI and can be used at
marketplace. All direct and indirect costs must be iden- the investigator’s discretion to support other research
tified and negotiated among the PI, their institution, and projects. Although this objective is perfectly reasonable,
the sponsor before initiating the study. In doing so, the PI study expenditures and allocation of funds must be
will assure that the study can be completed and that useful thoroughly documented throughout the course of the
information will be provided to all parties. The most com- investigation. Accurate records are often requested by the
monly made error on the part of the PI is to underestimate sponsor, and occasionally by outside auditing agencies,
study costs because of failure to identify all resources re- and are essential to maintaining a productive clinical re-
quired to complete the study or to underestimate their true search program.
costs. As a result, the study may not be comp2eted andlor
the investigator‘s research program will not benefit from Publication Rights
residual funds remaining in the contract budget after study
completion. These monies can usually be used to sustain A clear understanding of study responsibilities and
the infrastructure of the clinical facility or laboratory. publication rights should be negotiated among the PI,
To avoid these problems. it is recommended that the PI their collaborators, the study sponsor, and the investiga-
consult with internal support staff knowledgeable in bud- tor’s institution prior to initiating the trial. It is best to
get design and institutional overhead. Most academic cen- involve all parties as early as possible and to negotiate all
ters have a clinical trials office that can help construct a aspects before agreeing to the study contract. In this
152 Clinical Pharmacist as Principal Investigator (ACCP)
rcgard, most academic institutions have a liaison within investigator must establish thcir qualifications and
their research officc for business and industry contracts credentials before they can reasonably expect an industry
that can assist the investigator to organize and expedite sponsor to trust them to serve as PI.
this process. It should be thc mission of the PI and liaison
to ensure the investigator’s freedom to publish the re-
search findings. This includes the right to publish negative
results. In doing so, the investigator has ownership of the A PI typically evolves from a subinvestigator. Although
data, materials, and documentation, but the sponsor re- we may consider our research trainees ready to assume a
ceives copies and is given the right to use the materials for career as an independent scientist on completion of thcir
certain purposes. In general, sponsoring companies are program, 2-3 years of postdoctoral research training may
aware of the research mission of academic institutions and not realistically provide them with sufficient experience.
are flexible in the negotiation process. For example, a qualified PI should have relevant clinical
Any terms and conditions that restrict the publication experience in the proposed study population, usually
rights of the investigator are usually reserved for the gained from several years of experience in patient care.
protection of the sponsor’s patent rights that may arise However, this patient care experience alone does not
from the contracted work. In this situation, the sponsor is automatically qualify someone as an investigator. Under-
granted a specified period of time (e.g., 30 days) to review standing and demonstrating competence in clinical re-
the proposed publication before its submission and is search practices, demonstrated compliance with research
provided the right to withhold publication for a specified regulations and data management, and the ability to cre-
time period (preferably no more than 90 days), pending ate and manage an investigational plan through task de-
submission of a patent application. It is always important legation must also be considered.
to identify in the contract that the investigator and
supporting institution will not allow any publication
restriction in such a way as to impede the academic
progress of a graduate student or research fellow if these
individuals were integrally involved with the study. If any The PI must demonstrate that they have acceptable and
publication restrictions are accepted on behalf of the PI adcquatc resources available to manage the trial, includ-
and students, they should be agreed to in contractual form ing access to or control over clinical space such as beds
before initiating the trial. and clinics, if needed. The facilities must have appropriate
Finally, in single-ccnter trials, the order in which staff and othcr resourccs to conduct the research and to
authors are listed on the publication is usually the res- protect the subjects. Specialized testing equipment needcd
ponsibility of the investigators involved with the study. for the experiments must be available, either in the form
Therefore, choose collaborators wisely. In multicenter of general testing purchased from the health system or in
trials, the publication rights of individual investigators the PI’S own laboratory.
and thc expcditious publication of results become more
complex. In this case, the investigator must accept the risk arc s
of sacrificing both ownership and timely publication of
research findings despite a priori agreements with the The PI must be knowledgeable about the multiple
study sponsor. Many sponsors choose authors for multi- processes needed to manage a clinical study, including
center studies based on the reputation of those authors in the medical records system, investigational drug phar-
the area of study or based on the number of sub.jects that macy, clinical laboratory, other clinical departments ne-
their site enrolled in thc trial. Thus, younger investigators, cessary to support the project, the institutional review and
or investigators from smaller study sites, may find them- approval processes, budget and financial management,
selves excluded from the publication process. and contract initiation.
eric
Kansas City, Missouri, U.S.A.
Step 1.
al of the insti~utionor
Review the performance a p ~ ~ a i sre~uir~ments Guidelines or other
loyee evaluations should be incorpora~edinto th
Step 2.
Review the criteria within ach section of the template an delete or add criteria as necessary to reflect
activities performed the practice site. ?he template can be tailored to an individual p h a ~ ~ a c ~ s ~ ’ s
activities or to the ~ a ~ i care
en~ activities of the entire clinical staff.
Determine the standar s (thresholds) for each criterion. These can reflect un~versal~tandards
established for the inst~~ution’s
clin ions of an individual clinical pharmacist. The
standards establis the extent to which the individual performs
each criterion. Th expressed clearly. Some sites may decide
not to use standar ever, they should be cautioned that ~ b j e c t ~ vevaluation
e may be difficult
without standards.
Step 4.
Review the assessment me~hodsfor each criterion and tailor them to the practice site, the eva~~ator,
and matter who complet he performance assess
met nted, and understood he evaluator and the per
eva and direct observatio e time consuming but yi
info~mation.
Meets
Criteria Assessment Method Standard Criteria Comments
Provides drug education and counsels Review of selected patient-
patients on approp~iatedrug use monitoring forms or chart
and storage. notations
Provides written information for Review of selected patient-
a p p ~ o ~ ~drug
i a ~ p~oduc~s.
e monitoring forms or chart
notations
Provides educational pr~sen~ations to Review of inservice
pharmacy staff, students, and other presentations, evaluations,
health care ~ ~ ~ f e s s i o n a l s . and/or scores on post-test
evaluat~ons
Meets
Criteria sessment M e t ~ o d tandard Criteria Comments
ete and accurate rvisor review; recipient
uation
ion ~ u ~ e r v ireview;
~ o r pie pi en^
e~alua~ion
Clinical Pharmacist, Evaluation of a (ACCP) 159
Comments
a
This template may be photocopied and used for evaluating clinical pharmacists,
I60 harmacist, ~ v a ~ u a t of
i o a~ (ACCP)
(0.9 +. 5.2%)). carbarnampine (0.6 t 3.4%), valproic acid up) were provided i n 778 (70%) of hospitals survcyed,
*
(0.5 3.0%), procainamidc or N-acetylprocainamide compared with only 54% in 1992. According to the
(0.2 t 0.9%), phenobarbital (0.2 f 0.8%), caffeine (0.1 * 1995 survey, provision of pharmacokinetic consultations
*
0.7%), quiiiidine (0.1 0.6%), cyclosporine (0.1 t 0.4%), no longer varied by hospital ownership or geographic
ethosuximide (0.02 ? 0.1%I), and methotrexate (0.02 f 0.1). location as they did in 1992. Those hospitals with
Pharmacokinctics services were paid primarily through greater involvement in pharmacokinetic consultations
the pharmacy budget (74.5 *43.6%), although 1 5 . 8 t included large hospitals, pharmacy teaching hospitals,
36.5% billed the patien( for the consultation via a phar- hospitals in which the pharmacy director had a PharmD
macy number. A disappointingly high number [i.e., 60 degree, and hospitals with dccentrali,xd pharmacists.
(61.2%1)]of institutions providing pharmacokinetic con- Pharmacokinetic consultation was among the three ser-
sultations did not counsel patients receiving the service, vices (the other two being adverse drug reaction man-
although 12 (12.2%) provided educational materials to agement and drug history) that were more common in
patients and 30 (30.6%) provided patients with individual hospitals with a pharmaceutical care program than in
instruction by the pharmacist or other health care pro- those without one. In addition, pharmacokinetic consul-
fessional. The survey showed that pharmacists, mostly tations and drug therapy protocol management were
staff pharmacists, spent on average of 19 hours per week the clinical services that experienced the most consis-
providing pharmacokinetics services.’?’ tent and greatest growth since the first national survey
Responses of 20 survey statements on attitudes toward in 1989. In hospitals providing pharmacokinetic consult-
pharmacokinctics serviccs were all on the agreement side *
ations, 80.4 30.3% of inpatients on aminoglycosidc
of neutral, with ihe exception of “Pharmacokinetic therapy for greater than 48 hours had a measured serum
software is so sophisticated that very little judgment is aminoglycoside concentration. In the hospitals offering
needed for pharmacokinetic evaluation” (2.4 ? 1.6 on a pharmacokinetic consultations, 74% routinely provided
scale of I = strongly disagree and 7 = strongly agrcc, rz = documentation in patient medical
92). Notably, the statements whose average responses Detailed teaching affiliation data were available for
were >6 included: “Pharmacokinetic reviews and/or con- 1 102 of the 1109 surveyed hospitals in the 1995 national
sultations should be integrated into the duties of every clinical pharmacy services Hospitals affiliated
hospital pharmacist” (6.3 ? 1.3, n = 94); “Provision of with both PharmD and BS degree-granting Colleges of
pharmacokinetic services is an important component of Pharmacy provided pharinacokinetic consultation as a
*
hospital pharmacy practice” (6.2 0.9, i z = 94); and “Our core clinical service (defined as being offered in 50% or
pharmacokinetic services are very successful in terms more of hospitals). However, the percentage was sig-
of acceptance and use by prescribers” (6.1 t I .O, n = 93). nificantly grcater for PharmD-affiliated hospitals [ 85%
However, only about 6% of respondents indicated a (PharmD), 66% (BS Pharmacy), 63% (nonpharmacy
potential for increased pharmacokinetic consultations or teaching), and 57% (nonteaching), p < 0.001].L71
reviews in the future. The authors surmised that as the In 1999, Ringold et al.“’ published the results of thc
profession embraces the concept of pharmaceutical care, 1998 ASHP national survcy of pharmacy practice in acute
pharmacokinetic consultations are being integrated into care settings, which pcrtaincd to prescribing and tran-
the pharmaceutical care process, with the pharma- scribing practices. Of 1058 general and children’s me-
cokinctics specialist in larger institutions acting as a dical -surgical hospitals surveyed in the United States,
consultant to the nonspecialists. Because the survcy 548 (51.8%) responded. Of the 536 hospitals or health
revealed that only a minority of pharmacokinctics scr- systems for which information was available, 432 (80.6%)
vice providers interact directly with patients or thcir provided pharmacokinetic consultations. On average,
advocates (12?22% of patients), the authors also en- 435.5 t 943.2 consultations were provided per year
couraged grcater direct involvement of pharmacists (12 = 362 hospitals or health systems). Of 4 1 1 total respon-
with patients.’” dents, 7 1.2% indicated a >80% adoption rate for pharma-
In 1998, Raehl et aLr6’ published the results of the cokinctic recommendations.’*’
1995 National Clinical Pharmacy Services study that aehl et al.“” published the results of the 1998
determined the extent of hospital-based clinical pharmacy National Clinical Pharmacy Services study that deter-
services in 1109 U.S. acute care, general, medical- mined the extent of hospital-based clinical pharmacy ser-
surgical, and pediatric hospitals with SO or more licensed vices in 950 U.S. a c u k care, general, medical-surgical,
beds. Pharmacokinetic consultations (ix., pharmacist rc- and pediatric hospitals with 50 or more licensed beds.
view of the serum drug concentration data and paticnt Eighty percent of hospitals offered pharmacokinetic con-
medical record with appropriate verbal or written follow sultations compared with 70% in 1995, 54% in 1992, and
Clinical Pharmacokinetics Specialty Practice 163
only 40% in 1989. Again, pharmacokinetic consultations kinetics service^[^-^] to assume the following res-
and drug therapy protocol management were the clinical ponsibilities, as delineated in the “ASHP Statement on
services that experienced the most consistent and greatest the Pharmacist’s Role in Clinical Pharmacokinetic Mon-
growth since the first national survey in 1989. According itoring”: 1) design and conduct of clinical pharmacoki-
to the 1998 survey, those hospitals with greater involve- netiddynamic research, explore concentration-response
ment in pharmacokinetic consultations included phar- relationships for specific drugs, and evaluate and expand
macy teaching hospitals. hospitals in which the pharmacy clinical pharmacokinetic monitoring as an integral part
director had a PharmD degree, hospitals with decentra- of pharmaceutical care; 2) develop and apply computer
lized pharmacists, and those in the Pacific region. In programs and point-of-care information systems; and 3)
hospitals providing pharmacokinetic consultations, 68.9 f serve as an expert consultant to pharmacists with a general
37.8% of inpatients on aminoglycoside therapy for great- background in clinical pharmacokinetic monitoring.“]
er than 48 hours had a measured serum aminoglycoside Aside from being directors and consultants of clinical
concentration. In the hospitals offering pharmacokinetic pharmacokinetics services, clinical pharmacokinetic spe-
consultations. 79% routinely provided documentation in cialists also have professional practice opportunities as
patient medical records.”] preceptors of pharmacokinetic residency and/or fellowship
Clinicians in general agree that pharmacokinetic programs. The American College of Clinical Pharmacy’s
software cannot replace clinical judgment. Nevertheless, (ACCP’ s) 2000 Directoiy of Residencies and Fellowships
judicious use of software programs can facilitate optim- lists two residency preceptors (with a total of three
ization of patients’ drug therapy. The USC*PACK PC positions) whose programs have “pharmacokinetics” as
program (University of Southern California Laboratory of their primary specialty.“01At least one of these residencies
Applied Pharmacokinetics, Los Angeles, CA, USA) is a is accredited by ASHP.“ol Using the search engine
software package developed by investigators at the “Yahoo” and the search terms ‘‘Clinical Pharmacokine-
University of Southern California. Within the package, tic Service” and “Pharmacokinetic Practice,” two more
individual drug programs enable the clinicians to fit a residencies in pharmacokinetics were identified.‘””’] All
patient’s dosing history and drug concentrations to a these residencies are designed to prepare the resident for a
population model. This Bayseian approach has been career in clinical practice or teaching with a focus on
shown to provide good prediction of concentrations and pharmacokinetics. The same directory lists 7 fellowship
dosage regimens. Seminar courses regarding the scope preceptors (with a total of 11 fellow positions) whose
and use of the USC”PACK PC programs are scheduled programs have ‘‘pharmacokinetics” as their primary
each year. DataKinetics (ASHP, Bethesda, MD, USA) is specialty.“’] Of these 7 fellowship programs, 4 are ACCP
another dosing program based on one-compartment recognized. These fellowship programs seek to provide
modeling. Most of the commonly monitored drugs are fellows with clinical pharmacokinetic/dynamic research
included in the program. With animation and drawing experience that involves, but is not limited to, study design,
features, STELLA (High Performance Systems, Lyme, research methodology, study conduct, analytical methodo-
NH, USA) is a useful program for teaching. Programs logy, data analysis, and scientific writing and research.“’]
primarily for analysis of pharmacokinetic data include Compared with the 1990s, the current numbers of
PCNonlin (Scientific Consulting, Inc., Cary, NC, USA), specialized clinical pharmacokinetics pharmacy practices
RSTRIP (MicroMath. Salt Lake City, UT, USA), and and fellowships are small. This likely reflects the general
NONMEM (University of California, San Francisco, CA, trend of integration of clinical pharmacokinetics into the
USA). Modeling of pharmacodynamic data is available concept of pharmaceutical care provided by pharmacists.
with P-PHARM (Simed, Creteil, France) and MKMO- In addition, concentration measurement is only an in-
DEL (Biosoft, Ferguson, MO, USA), an National Ins- termediate endpoint for optimal patient care. However,
titutes of Health and Prevention (N1H)-supported PRO- outside the traditional realm of therapeutic drug monitor-
PHET program. A list of pharmacokinetic programs and ing, there are other opportunities for pharmacists with
other resources is also available on the world wide web at indepth knowledge of clinical pharmacokinetics. This
http://www.boomer.org/pkin/.“ includes drug evaluation and regulatory review at the Food
Clinical pharmacokinetics specialists have opportun- and Drug Administration (FDA), clinical research or drug
ities as directors and/or consultants of clinical pharmaco- development at pharmaceutical companies, the potential
role of pharmacokinetic and monitoring for the increasing
trend of home/community-based parenteral antibiotic
“See the section on Professional Networking Opportunities later in therapy, and the relatively untested disciplines of toxico-
this article. kinetics and clinical toxicology. Toxicokinetic studies are
164 Clinical Pharmacokinetics Specialty I’rracticc
not confined to preclinical drug development, and clinical also are reviewed at least thrice weekly for all patients
toxicology presents a challenging opportunity for evalu- o n “noncovered” services to identify any patients who
ating the adverse effects of drugs and poisons, as well as are prescribed “monitorablc” drugs for which no serum
characterizing altered pharmacokinctics and response in drug concentrations have been ordered. Any physician
overdose situations. Even within the current redefined also may request a pharmacist to provide a clinical
practice of therapeutic drug monitoring, opportunities still pharmacokinetic evaluation by verbal or written com-
exist. One good example is oplimizing the use of once- munication.’13’
daily aminoglycosidc dosing. ‘The TDM Laboratory notifies the primary pharmacist
of any “supratherapeutic’ ’ drug concentrations, between
OX00 and 1700 during the week; after 1700 and on
weekends and holidays, the pharmacy resident on-call is
notified. The TDM Laboratory also notifies the Clinical
Pharmacokinetics Service of any supratherapeutic levels
Following is a description of a model clinical practice in for any “noncovered” service. All other TDM issues are
the specialty area of pharmacokinctics practice. This is directed to the Director of the Clinical Pharmacokine-
an actual practice setting at the University of Kentucky tics Scrvicc.Li’31
Medical Center. For every patient with a serum drug concentration or-
The mandate of the Clinical Pharmacokinetics Service dered, the primary pharmacist writes a “Clinical Phar-
at the University of Kentucky Medical Center is to ensure macokinetics” note in the progress notes section of the
safe and efficacious dosage regimens through the appli- patient’s chart within 24 hours for normal or “subthc-
cation of pharmacokinetic/dynamic principles and the rapcutic” concentrations, For ”supratherapeutic” drug
determination of serum drug concentrations.’”’ The Gli- concentrations, the medical teain is notified immediately
nical Pharmacokinetics Service Policy and Procedure if clinically warranted and a chart note written within 12
Manual outlines standard dosing and monitoring guide- hours after the concentration was reported. The chart
lines (for aminoglycosides, carhamazepinc, digoxin, fo- note contains all relevant patient information and phar-
sphenytoin, lidocaine, lithium, phenobarbital, phcnytoin, macokinetic parameters necessary to provide dosing and
procainamide, quinidinc, thcophylline, valproic acid, and monitoring rccommcndations.’”’
vancomycin) when providing clinical pharmacokinetic At the University of Kentucky Medical Center, an
monitoring.’ 14’ In addition, the Clinical Pharmacokinc- average of approximately 800 serum drug conccntra-
tics Service provides warfarin monitoring for patients tions are assessed every month, of which about 300
on services or teams that do not have an assigned clini- are directly evaluated through the Clinical Pharmacoki-
cal pharmacist.“31 nctics Service. On average, thc Clinical Pharmacoki-
At the University of Kentucky Medical Center, the netics Service provides direct consultations for 100 to
primary pharmacist or pharmacy resident who attends 125 patients monthly.’
rounds or precepts pharmacy students on a primary me- Several other examples of clinical pharmacokinetics
dical team is responsible for clinical pharmacokinetic services arc described in the literature. Briefly, Shcvchuk
monitoring of all patients on that team. The Clinical and Poulinilsl described a pharmacist training program
Pharmacokinetics Service oversees the pharmacokinctic at Regina General Hospital, a 485-bed acute care facility
monitoring process for all patients Li.e., those on teams in Saskatchewan, Canada, for an aminoglycoside moni-
with assigned pharmacists (“covered”)], as well as those toring service and a quality assurance program involving
who arc on teams that do not have an pharmacist certification. Amcnt and McGuircL16’ dcs-
pharmacist or resident (‘ ‘noncovered”). The Clinical cribed a pharmacokinetic dosing service at Latrobe Area
Pharmacokinetics Service consists of a faculty mcmbcr Hospital, a 300-bed teaching-community hospital in
who serves a s the director and of pharmacy practice rc- Pennsylvania, wherein the pharmacist initiates and ad-
sidcnts and senior pharmacy students during their clini- justs aminoglycosidc and vancomycin regimens, and
cal pharmacokinctic rotations.’ 1 3 ’ schedules serum drug concentration measurements and
Patients with serum drug concentrations on “non- renal function lab tests without contacting a physician
covered” services are identified by two daily printouts for verbal approval. Williams”71 also described a phar-
provided by the Therapeutic Drug Monitoring (TDM) macokinetic consult service at York Hospital, a 565-bed
IAoratory (in thc hospital’s clinical laboratory, which community teaching hospital i n Pennyslvania, that cx-
analyzes all serum drug concentrations), Drug profiles pandcd to include other clinical activities.
Clinical Pharmacokinetics Specialty Practice 165
be higher (p=O.O15) than that of generalists with respect Associated Terminal and Enabling Objectives include
to recommendations based on pharmacokinetic~.[~~] sections on practice foundation skills, direct patient care,
In a study that determined associations among hospital drug information, drug policy development, and practice
characteristics, mortality rates, and staffing levels for management .Is4’
professional health care workers in 3763 U S . hospitals.
Bond et al.rsO1found that increased numbers of pharma-
cists in a hospital were associated with lower mortality
rates. Although the reasons for this were unknown, the
authors speculated that providing clinical pharmacy
services such as pharmacokinetic dosing services, pre- A number of network opportunities are available within
venting and detecting adverse drug reactions, and admis- professional organizations. These include, but are not
sion drug histories may be responsible for improving limited to. the following:
patient care outcomes.[j01 American Society of Health-System Pharmacists
Performing simple regression analysis on data from the Section of Clinical Specialists Pharmacokinetics Spe-
1992 National Clinical Pharmacy Services study,[”] Bond cialty Network:[”] The Pharmacokinetics Specialty Net-
et al. found a significant ( p =0.001) association between work is available as one of 19 networking assemblies of
provision of pharmacokinetic consultations and lower ASHP’s Section of Clinical Specialists, each of which is
mortality rates. Further multiple regression analysis did led by a facilitator. Modes of networking among phar-
not reveal a significant association ( p = 0.544).[521Subse- macokinetic specialists are via the listserv as well as at
quently, Bond et aI.[j3]evaluated direct relationships and networking assemblies conducted during ASNP Midyear
associations among clinical pharmacy services, phar- Clinical Meetings.
macist staffing, and total cost of care in 1016 U.S. hos-
pitals. Pharmacokinetic consultations were among seven American College of Clinical Pharmacy Pharmacoki-
clinical pharmacy services that were associated with lo- netics/Dynamics Practice Research Network (PRN):[s61
wer cost of care ( p = O.OOOl), based on simple regression The Pharmacokinetics/DynamicsPRN provides a mech-
analysis. Further multiple regression analysis did not anism for networking and collaboration, educational
reveal a significant association ( p = 0.436).[531 programming, and a forum in which ACCP members
with similar interests can discuss pharmacokinetic and
pharmacodynamic methods and research.
Pharmacokinetics services in Ikpartiiient of Veterans side dose and cost of hospitali,mion. Thcr. Drug Monit.
Affairs mcdical centers. Am. J. Hosp. Pharin.
1672 1675. 21. Dcstachc, C.J.: Meyer, S.K.; Rowlcy; K.M. Docs accepting
Santcll: J.P. ASHP national survey of hospital-based pharmacokinetic recommendations impact hospitalization?
pharmaceutical services-I 994. A m . J. Health-Syst. A cost-benefit analysis. Thcr. Drug Monit. 19990, / 2 (j),
Pharm. 1995. 52, 1179- 1198. 427 433.
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I8 (21, 302-326. patients treated with aminoglycosides for grain-negative
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12 (2). 173-181. services and hospital mortality rates. Pharmacotherapy
39. Klamerus, K.J.; Munger, M.A. Effect of clinical phar- 1999, 19 ( 5 ) , 556-564.
macy services on appropriateness of serum digoxin con- 53. Bond, C.A.; Raehl, C.L.; Franke, T. Clinical pharmacy
centration monitoring. Am. J. Hosp. Pharm. 1988, 45. services, pharmacy staffing and the total cost of care in
1887-1893. United States hospitals. Pharmacotherapy 2000, 20 (6),
40. Kraus; D.M.: Calligaro, I.L.S.; Hatoum, H.T. Multilevel 609-621.
model to assess appropriateness of pediatric serum drug 54. American Society of Health-System Pharmacists. ASHP
concentrations. Am. J. Dis. Child. 1991, 145 (10): 1171- Supplemental Standard and Learning Objectives for
1175. Residency Training in Clinical Pharmacokinetics Practice;
41. Jorgenson, J.A.: Rewers, R.F. Justification and evaluation Available from URL: http://www.ashp,org/public/trp/
of an aminoglycoside pharmacokinetic dosing service. PKSUPPST.htm1 (accessed July 2000).
Hosp. Pharm. (Saskatoon, Sask.) 1991. 26, 605,609- 55. Beringer, P.M.: American Society of Health-System
611.615. Pharmacists. Pharmacokinetics. Available from URL:
42. Cook, C.R.: Bush, N.D. Cost-saving impact of pharmacist- http://www.ashp.org/public/news/newsletters/specialist/
calculated IV aminophylline dosing schedules. Hosp. 1999/summer99/NewsBytes/pharmaco.html (accessed July
Formul. 1989, 24 (12). 716-721. 2000).
43. Wade. W.E.; McCall. C.Y. Educational effort and CQI 56. American College of Clinical Pharmacy. ACCP Practice
program improves ordering of serum drug levels. Hosp. and Research Networks-Pharmacokinetics/Dynamics;
Formul. 1994, 29 (9), 657-659. Available from URL: http://www.accp.com/ClinNet/
44. Wing, D.S.; Duff, H.J. Evaluation of therapeutic drug prnkenetics.htm1 (accessed Aug. 2000).
monitoring program for theophylline in a teaching hospital. 57. American Association of Pharmaceutical Scientists. Phar-
Drug Intell. Clin. Pharm. 1987. 21; 702-706. macokinetics, Pharmacodynamics and Drug Metabolism
45. Relling, M.V.; Fairclough, D.; Ayers, D.: Crom, W.R.; Section (PPDM); Available from URL: http://www.aaps.
Rodman, J.H.; Pui, C.-H.; Evans, W.E. Patient character- org/sections/ppdm/ (accessed Aug. 2000).
istics associated with high-risk methotrexate concentra- 58. American Association of Pharmaceutical Scientists. Popu-
tions and toxicity. J. Clin. Oncol. 1994, 12 (8), 1667- lation Pharmacokinetics and Pharmacodynamics FOCUS
1612. Group; Available from URL: http://www,aaps.org/focus/
46. Masson; E.; Zamboni, W.C. Pharmacokinetic optimisation poppk.htm1 (accessed Aug. 2000).
of cancer chemotherapy: Effect on outcomes. Clin. Phar- 59. American Society for Clinical Pharmacology and Ther-
macokinet. 1997, 32 (4), 324-343. apeutics Pharmacokinetics and Drug Metabolism Section,
47. Chin, J.M.W.: Muller, R.J.: Lucarelli. C.D. A pharmacy Available from URL: http://www.ascpt.org/members/lists.
intervention program: Recognizing pharmacy's contri- 60. Bourne, D.W.A. Pharmacokinetic and pharmacodynamic
bution to improving patient care. Hosp. Pharm. (Saskatoon, resources, Available from URL: http://www.boomer.org/
Sask.) 1995, 30 ( 2 ) , 120, 123-126, 129-130. pkin/ (accessed Aug. 2000).
PROFESSIONAL RESOUKCES
Encyclopedia of Clinic~ilPhLiinzcqJ
DOl: 10.1081iE-ECPI20006367
Copyright ((32003 b y Marcel Dekker, Inc. All rights rescrved.
Clinical Pharmacy Practice Guidelines (Society of Hospital Pharmacists of Australia) 171
Leading on from this definition is a section that management or therapy.” By definition, the change must
outlines the extent and operation of a clinical pharmacy have occurred rather than have been merely proposed, and
service. Components that are discussed include the issue non-drug-related changes that impacted on patient man-
of the frequency of monitoring of patients’ drug therapy. agement are included.
Clinical pharmacists need to be involved in activities
that could improve patient clinical outcomes but are not
necessarily focused on individual patients, for example,
drug usage evaluations and the formulation of care
plans. Research was addressed specifically by statements These guidelines have been utilized in policy devel-
that involvement is an essential component of contem- opment at local and federal government levels. in the
porary clinical pharmacy practice and should include a accreditation of provision of clinical pharmacy services,
focus on optimizing drug therapy as well as research as a key standard for undergraduate and postgraduate
on the practice of clinical pharmacy. Education is also teaching, and as a benchmark for practice.
affirmed as a key core activity of clinical pharmacy The SHPA Standards of Practice for Clinical Pharmacy
practice. Specific details are not included in the docu- was one of the reference documents used in the for-
ment but rather motherhood statements that emphasize mulation of the national guidelines to ensure continuity of
the need for involvement in undergraduate and post- medication management through hospital admission and
graduate clinical teaching. treatment and postdischarge.“61 These guidelines were
The third major section of the guidelines is the prepared by the Australian Pharmaceutical Advisory
classification of clinical pharmacy services as a number Council (APAC), which advises the Commonwealth
of discrete activities. A goal for each activity is stated and Government of Australia on a wide range of pharmaceut-
then a recommended procedure outlines the major generic ical policy issues. The council includes representatives of
components of the activity. The activities were presented major professional, industry, consumer, and media orga-
in an order that is somewhat reflective of the provision of nizations as well as government members. The council
these services. The Standard provides direction on which published the guidelines in 1998, and they consist of
activities should be performed routinely. This is reflected broad principles on which standard procedures for
in statements relating to medication history interview, individual institutions can be based, with the aim of
the monitoring of drug therapy, and the provision of ensuring continuity of medication management through
medication counseling. hospital admission, treatment and postdischarge.
The guidelines provide direction to the various re- In another initiative by APAC, an integrated best-
sources recommended for the efficient provision of a practice model for medication management in residential
clinical pharmacy service. There is limited detail as the aged care facilities was devel~ped.“’~One of the re-
primary aim was to briefly describe some selected commendations was that residents’ medication be re-
components that should be considered rather than an viewed with cooperation between the prescriber and
attempt to quantify. accredited pharmacists. Incorporated in the APAC model
During the formulation and ratification of the guide- are guidelines for the performance of comprehensive
lines, overwhelming input from members of the Society medication review developed from the SHPA Standards
requested that the committee formulate a guide to of Practice for Clinical Pharmacy. Following on from
staffing structure for the provision of a clinical service this, the Commonwealth government agreed to reimburse
to particular clinical subspecialties. The document incor- accredited pharmacists to perform medication review
porates a guide to the ratio of pharmacists to patient bed services for nursing homes. Pharmacists can obtain
numbers. These figures have not been substantiated by accreditation through a number of mechanisms, including
any objective measure or structured benchmarking study, SHPA and also the Australian Association of Consultant
but are based purely on consensus of the members of Pharmacy (AACP). The AACP practice guidelines for the
the Society. comprehensive medication review in residential care faci-
Documentation of clinical service is featured and lities utilize the Standard.
focuses on the very broad requirements of documenting The SHPA Standards of Practice for Clinical
actual activities performed as well as clinician docu- Pharmacy are used as a reference point for benchmark-
mentation in the patient medical record. One of the key ing the provision of clinical pharmacy services in
issues addressed is the defining of an intervention. The hospitals in Australia. An independent not-for-profit
definition states that an intervention is “any action by a organization, the Australian Council of Healthcare
pharmacist that directly results in a change in patient Standards (ACHS), accredits healthcare organizations
172 Clinical Pharmacy Practice Guidelines (Society of Hospital Pharmacists of Australia)
12. The Society of Hospital Pharmacists of Australia Corn- 16. Australian Pharmaceutical Advisory Council. National
mittee of Specialty Practice i n Oncology. SHPA Standards Guidelines to Achieve the Continuum of QualiQ Use of
of Practice for the Oncology Pharmacist. In Practicc, Medicines Between Hospital and Comnzunity, ISBN
Standurd.s uncl Definitions; Johnstone. J.M., Vienet, M.D., 0642272646; Commonwealth Department of Health and
Eds.; The Society of Hospital Pharmacists of Australia: Family Services Canberra, Australia 1998; 1- 11.
Melbourne, 1996. 17. Australian Pharmaceutical Advisory Council. Integrated
13. The Society of Hospital Pharmacists of Australia C o n - Best Practice Model f o r Medication Management in
mittee of Specialty Practicc in Drug Usage Evaluation. Residential Aged Care Facilities, ISBN 06424 15390;
SHPA Standards of Practice for Drug Usage Evaluation in Coininonwealth Department of Health and Aged Care.
Australian Hospitals. In Practice Standcuds and De57zi- Canberra, Australia 2000; 1 - 17.
tions: Johnstone, J.M.; Vienet, M.D., Eds.; The Society of 18. 1Cll-10-AM Tabular List of Proredures (MBS-Extendd).
Hospital Pharmacists o f Australia: Melbourne, 1996. National Center ,for Classijication in Health. Sydney,
14. The Society of Hospital Pharmacists of Australia Code of Australia; Faculty of Health Sciences, University of
Ethics. Pructicp Standard.s and Dq5nition.s; Johnstone, Sydney: Australia, 19%.
J.M., Vienet, M.D., Eds.; The Society of Hospital Phar- 19. Dooley, M.J.; Galbraith, K.; Burgess, N.; McLennan, D.N.
macists of Australia: Melbourne, 1996. Multicentre pilot study of a standard approach to document
15. National Medicines Policy 2000, ISBN 0642415684; clinical pharmacy activity. Aust. J. Hosp. Pharm. 2000,
Cornmonwcalth Department of Health and Aged Care 30, 150- 156.
Canberra: Australia, 2000; 1-7.
PIIOFESSIONAL DEVELOPMENT
Fig. 1 This figure represents the continuum of research endeavors within the pharmaceutical sciences. The shaded areas represent the
research areas encompassed by the definition of a CPS. The arrows indicate the potential movement from one sphere of research to
another. The overlap with genetics, discovery, drug delivery, and animal mechanistic studies represent areas of translational research that
provide the critical link between research theory and human application. Abbreviation: PWPD, pharmacokineticdpharmacodynamics.
based research as a means of gaining mechanistic or evolved. Common to most current CPS programs is the
theoretical insight. Other clinical pharmaceutical scien- requirement for training in clinical pharmacotherapeutics.
tists began their careers in the research laboratory and Stated in this way, clinically trained health care profes-
extended their research into normal volunteer and patient sionals other than pharmacists have the potential to
studies; these were often individuals with PhD degrees. become CPSs, given that they have an interest in de-
Both career paths resulted in the generation of a CPS, and veloping research careers within the clinical pharmaceut-
both were essentially “bootstrap” methods of becoming a ical sciences. It is the nature and scope of research and not
clinical scientist. professional background that serves as the foundation for
The initial formal CPS training programs emerged in the definition of the CPS.
the 1980s. These programs required that the trainees As stated in the definition, a CPS is an independent
conduct related patient-oriented and laboratory research. investigator with education and training in pharmaco-
Historically, most of these programs were fellowships, therapeutics who utilizes contemporav research ap-
although a few clinically oriented MS and PhD programs proaches to generate new knowledge relevant to drug
also emerged. Although most educational and training behavior in humans, to therapeutic interventions, and/or
programs were in schools of pharmacy, some excellent to patient outcomes.
fellowships are found in research institutes and health CPS training options that have been developed
care organizations. since the mid-1970s are summarized in Table 2 . Each
CPS training option has unique advantages and dis-
advantages, some of which have been debated pre-
v i o u ~ l y . [91~ Despite
*~ the differing opinions on the best
method of training, the goal of these training programs
is to develop individuals with the skills and confid-
Like the definition of the CPS, the background education ence to conduct clinical research within their chosen
and training options for becoming a CPS have also career path.
176 Clinical Pharmacy Scientist
Fellowship programs have provided advanced practice ded an additional 1 to 2 years of training or sought men-
experience for clinicians for decades and have prepared tors who provided a large research component to their
them for board certification in areas of specialty in core experiences. In the early 1980s and the 1990s, a
pharmacy and medicine."01 Those individuals who desire small number of institutions developed postdoctoral gra-
a research component to their experience have either ad- duate programs in the clinical pharmaceutical sciences.
Some of these programs conferred an MS degree (e.g., ican Association of Colleges of Pharmacy emphasized
University of Iowa, University of Minnesota), where- the demand for ‘‘scientists (who) possess excellent verbal
as others conferred a PhD (University of Pittsburgh, and written communication skills, team-building apti-
Virginia Commonwealth University, University of Ken- tudes, critical thinking. problem-solving skills. leadership
tucky). The core content of fellowship, MS, and PhD ability, and scientific integrity.’”’]
programs is similar, with the primary difference being The primary goal of CPS training programs is to
the greater breadth and depth of experience associated develop critical thinking, clinical acumen, and technical
with the PhD programs, which is paralleled by the skills in a specialty research field, so as to develop the
greater duration of training. individual’s ability to contribute to the knowledge that
Certificate programs in clinical pharmaceutical re- serves as the basis of clinical pharmaceutical science. It
search have only emerged more recently. These are has been stated that “for the most part, graduate edu-
usually offered as a 1-year or less training option. Many cation has produced technical proficiency and mastery of
of these programs provide graduate academic courses in a specific discipline.”“]
which the individual can develop the skills to conduct The common denominator for all training options, as
clinically oriented research. Typically, these programs are well as for each research sphere (clinical, outcomes, and
very focused on human clinical interventional or obser- preclinical). is the skill set that one must acquire to suc-
vational studies. Independent research skills are limited cessfully establish a clinical or translational research
due to the short training period. program. These skill sets can be grouped into six major
The purpose of an educational program is to provide categories. These categories include, but are not limited
the optimal experience that will develop the skills for to, literature tracking and evaluation, critical scientific
that individual to succeed within this chosen career. thinking and creativity, behavioral development, commu-
However, success is predicated not only on training, but nication skills, technical proficiency, and research ethics
also on the innate motivation and talents of the indi- and integrity. Mechanisms of attaining these skills vary
viduals, as well as their commitment to lifelong learning with the different training options; however, the majority
and perseverance in research after the formal training of these skills are attained via combination of graduate-
is complete. Each of the training options identified has level courses and mentored research experiences. Note
resulted in successful CPSs. The decision as to the that the role of advising and mentoring young scientists is
“best” training option is highly individualized and de- viewed as sufficiently important that the National Aca-
pendent on a multitude of factors, including the given demy of Sciences, National Academy of Engineering, and
student’s career goals and aspirations. It is important for Institute of Medicine convened a committee that pub-
interested students to evaluate each training option ex- lished a document regarding advising in 1997.[12]
tensively, realizing that the degree of development and
the ability to conduct independent research increases
directly with the duration and intensity of the various
training options. The core of scientific research is based on the ability to
review large volumes of published literature. To effec-
tively pursue these research endeavors, the CPS must
develop the ability to find, interpret, and critique the
scientific literature. The trainee must become adept at
The world in which science is conducted has changed, and using the existing body of information as the foundation
so have the skills necessary for scientists to function for well-planned research. Once the research direction has
effectively. In a report published in 1995, essential skills been set, continual tracking of the literature is critical to
and characteristics of scientists were addressed by The maintaining currency and a successful research program.
Committee on Science, Engineering, and Public Policy
(COSEPUP). which was a joint committee of the National ritical ~ ~ i e n tThinkin
~~ic
Academy of Science, National Academy of Engineering,
and the Institute of Medicine.[”’ The COSEPUP report The development of critical and independent scientific
states that “a world of work that has become more in- thinking is paramount to the success of building a re-
terdisciplinary, collaborative, and global requires young search program within each CPS research sphere. Using
people who are adaptable, flexible, as well as technically published literature as the foundation, scientists must be
proficient.”‘”’ Subsequently, the 1996 report of the able to identify the next frontier for scientific exploration.
Research and Graduate Affairs Committee of the Amer- They must also integrate the results of their own expe-
118 Clinical Pharmacy Scientist
riments with relevant existing literature in an iterative Frequent oral presentations to peer and mixed au-
process of literature tracking, assimilation, and creativity diences develops verbal communication skills. Large- and
to form the basis of new research ideas. develop new small-group teaching and research presentation skills each
hypotheses, and design methods to test their validity. It require different talents that should be developed during
is this creative process that requires critical scientific the training period. Furthermore, the ability to verbally
thinking that leads to new scientific discoveries. Implicit defend one’s research ideas and results must be developed
in hypothesis generation and study design is the ability irrespective of the clinical pharmaceutical training path
to use accepted methods or develop new technology that has been chosen. Mastery of the ability to verbally
to quantify study endpoints. defend one’s research occurs only after the trainee has
Like most skills, this skill is best honed by practice. fully developed multiple other skill sets including critical
Through exposure to the ongoing work of several scien- thinking, hypothesis derivation, literature mastery, and
tists and peers, the development of these skills and cha- technical proficiency.
racteristics can be enhanced.
As discussed previously, the CPS is a clinically trained Concordant with hypothesis generation and study design
individual capable of conducting independent research. development are the processes associated with method
The combined clinical and research educational back- establishment and/or development, data generation, and
ground ideally facilitates interactions of the CPS with data analysis, all collectively referred to as technical pro-
both researcher and clinician colleagues, thereby devel- ficiency. Establishing a method for generating data using
oping a collaborative and interdisciplinary team approach previously established methods allows for general tech-
to develop and test research hypotheses. For the CPS to nical skill development, as do data analysis and inter-
develop both independent and collaborative research, it pretation. These skills are generally obtained using an
is critical to develop decision-making, problem-solving, apprenticeship technique, which involves learning from
team building, and leadership skills. These skills are not someone already working in the laboratory. However, it
only important for collaborative development, but also is important for the individual to develop technical
for the development of leadership and managerial skills mastery of the methods used within the mentor‘s labo-
that will be necessary for the CPS to effectively super- ratory, as well as be able to identify, establish, and va-
vise research assistants, graduate students, and postdoc- lidate valuable methods described in the literature. This
toral students, and to lead a team of investigators. For develops confidence to develop de novo techniques,
CPSs or any other scientist to develop these traits, trai- which can move the entire discipline forward. Similarly,
nees should ideally be exposed to diverse research en- to complete the process, the appropriate statistical com-
vironments where scientists exhibit these traits.[’] parisons must be planned and applied to interpret the
results of the tested hypotheses.
~ommunicationSkills
Research Ethics and lnt@~rity
CPSs must develop the ability to effectively communicate
their ideas to colleagues, collaborators, and students, as Ethics and integrity associated with the conduct of re-
well as granting agencies, regulatory agencies, and peer- search is important in the development of every scien-
reviewed publication. Frequent writing experiences en- tist. However, the direct human impact of the research
hance written skills. Venues including the preparation of adds a layer of complexity to the training of a CPS.
Institutional Review Board and Institutional Animal Care Federal regulations mandate that study protocols be
and Use Committee proposals, grant applications, and carefully evaluated for subject/patient safety by the in-
manuscripts are essential components of the training vestigator and the local Institutional Review Board. Re-
experience. Peer review of manuscripts for journals and gulations also mandate that all scientists funded by the
report preparation are also vehicles for enhancing written National Institutes of Health (NIH) provide certification
communications skills. Frequent written communication of training in the protection of human subjects. This
is essential. All written materials should be viewed as training can be obtained either locally or through the
vehicles for enhancing communications skills, providing NIH Office of Human Subjects Research, which main-
that a mentor gives feedback. tains a web site for computer-based training on the
Clinical Pharmacy Scientist 179
“Protection of Human Research Subjects.” The URL intensive institutions and those that are expanding their
for this site is http://ohsr.od.nih.gov/cbt/. research focus.
Concerns regarding confidentiality of patient informa- Similarly, these individuals are capable of functioning
tion have heightened, particularly with the advent of in the preclinical or clinical areas of drug development
human genetic research. There are also ethical issues that within the pharmaceutical industry. In particular, the CPS
relate to accuracy of data collected and its security in a has unique talents to contribute to the decision-making
database, which relates to either technical proficiency in process and study design at the preclinical/clinical in-
database management or the knowledge that a database terface, which is a critical juncture of the drug deve-
manager needs to be part of the investigative team. lopment process. In addition to the traditional pharma-
ceutical industry, contract research organizations and site
management organizations have become essential con-
tributors to the drug, biological, and device development
process. Many CPSs who have experience within the
The demand for researchers who focus on the clinical pharmaceutical industry have guided the growth and
pharmaceutical sciences has exceeded the supply. Indi- development of this industry. It is not surprising that the
viduals graduating from CPS programs have secured design, monitoring, analysis, and evaluation functions
successful careers within academic, industrial, and go- provided by these organizations draw heavily on the
vernmental institutions (Fig. 2). Academic institutions are strengths of the CPS.
major employers of CPSs within the clinical or basic CPSs are prime candidates for positions in govern-
science divisions in the various health-related schools. mental and regulatory agencies. The CPSs’ critical think-
The CPSs’ unique blend of clinical and research skills ing and analysis skills, plus their practical experience in
allow these individuals to develop interdisciplinary col- conducting clinical investigations, are highly desirable
laborations and thus are aggressively sought by research attributes for individuals entrusted with the evaluation of
Pharmaceutical
Industry Academia
Translational Science
Biotechnology
Industry Academia
CROs
@
Clinical Sciences
0 SMOs
Fig. 2 This figure represents the career options for individuals interested in the clinical pharmaceutical sciences. Abbreviations:
PhaRMA, Pharmaceutical Research Manufacturers; CROs, Contract Research Organizations; SMOs, Site Management Organizations;
NIH, National Institutes of Health; CDC, Center for Disease Control and Prevention; HCFA, Health Care Financing Administration;
FDA, Food and Drug Administration; EPA, Environmental Protection Agency; CDER, Center for Drug Evaluation Research; CBER,
Center for Biological Evaluation Research.
180 Clinical ~ ~ a r Scientist
~ a ~ y
the ellicacy and saPety of new drugs, biologicals, and 5. Juhl, K.P.; Kroboth, P.D. Conceptual issues in designing a
devices in agencies such as thc Ccntcr Lor Drug Eva- clinical scientist program. Drug Intell. Clin. Pharm. 1987,
luation Research, Ccntcr lor Biological Evaluation Re- 21, 103 -106.
search, Environmental Protection Agency, and so on. 6. Schwartz, M.A. Are academic pharmacists meeting the
clinical scicntist role'? Drug Tntcll. Clin. Pharm. 1987, 21,
Governmental health policy decisions arc often bascd
114- 117.
on critical review of scientific and economic evidence,
7. Blouin, K.A.; Cloyd, J.C.; Luddcn, T.M.; Krohoth, P.D.
along with a prqjection of their impact on the health Central issues relevant to clinical pharmaceutical scicntist
care system. T h e CPS is similarly wcll suitcd to ciigagc training programs. Pharmacothcrapy
in this critical policy decision-making process at the 8. Juhl, K.P. Training of Clinical Pharmaceutical Scientists.
national or local lcvcl. In Americun Collegc~ of Clinical Pl~armacy Reporl;
Burckart, G.J., Ed.; ACCP: 1987; Vol. 6 (7), S24.
9. Rorchardt. R.T. Chair report of the Research and Graduate
Affairs Committee. Am. J. Pharm. E ~ L K1996, . 60. 18%
22s.
10. Directory oj' Rcsidenc-ics and Fellowships; American
Pharmacists Lor the Future. In '/%a Report uf' the Study Collcgc of' Clinical Pharmacy: Kansas City, Missouri,
Commission on Pharmacy; Health Administration Press: 200 1 : I -274.
Ann Arbor, Michigan, 1975; 123- 125. 1 I . Reshaping the Graduate Education or Scientists and
Smith, R.V.; Cohen, J.L.; Kenyon, J.L.; Powell, J.R.; /Snginerr.y; Committee on Science, Engineering and Public
Rutledge, C.O.; Svarstad, U.L. Am. J. Pharm. Educ. 1984. Policy; National Academy Prcss: Washington, DC, 1997.
48, 439. 12. AdviscJr, Teacher, Role Model, Friend: On Being a Mentor
Evans, W.E. Training of Clinical Pharmaceutical Scicn- to Students in Science and Ilngineering; National Academy
'
. In Atnerican Cd/agr of Clifziral Pharmacy T<?port; o f Science, National Academy of Engineering, and Ins-
.kart, G.J., Ed.; ACCP: 1987; Vol. 6 (7), S22-S24. titute of Medicine; National Academy Press: Washing-
Smith, R.V. Lhdoprnent of clinical scientists. Drug Intell. ton, DC, 1997; Available online at http://www.nap.cdu/
rcadingroom/books/mcntor/.
PROFESSIONAL RESOURCES
Encyclopedia of C l i i ~ i ~Phcii.mucj
c~l
DOI: 10.1081/E-ECP 120006288
Copyright C 2003 by Marcel Dckker, Inc. All rights rcservcd.
182 Cochrane Library, The
Brazilian, Canadian. Chinese. Dutch, French, German, healthcare (Table 1). The groups' core function is to pre-
Italian. Nordic, North American, South African, South pare systematic reviews that are evidence-based, inter-
American, Spanish, and United Kingdom. Each center has nationally developed, quality controlled, and clinically
general responsibilities, such as helping to maintain a useful. Creating a Cochrane review involves the system-
directory of contributors to the Collaboration, offering atic assembly, critical appraisal, and synthesis of all rele-
training in the process of producing a Cochrane review, vant studies that address a specific clinical question. Re-
and coordinating handsearches for healthcare journals. viewers use strategies that limit bias and random error.[41
The centers are not responsible for preparing and/or These strategies include a comprehensive search for po-
maintaining systematic reviews. This is the role of the tentially relevant articles and selection of relevant articles,
Collaborative Review Groups. using explicit, reproducible criteria. Reviewers critically
appraise research designs and study characteristics during
synthesis and interpretation of results. When appropriate,
they integrate the results using meta-analysis. The unique
A review group is formed by researchers, healthcare pro- value of Cochrane reviews is the commitment to regular
fessionals, consumers, and others who share a common updating. Reviews published in journals are often out-of-
interest in a particular health problem. As of November date by the time they are published. By updating reviews
2000, about 50 review groups cover the major areas of as new evidence becomes available, Cochrane Colla-
\
f Status: 10COCHRANE
i
COCHRANE CENTERS FIELDSiNETWORK
Status: 15 centers around the world fieldsiNetwork
Roles: Maintain a directory of contributors Roles: Ensure review groups consider their fields'
Foster international collaboration perspective while conducting reviews
Provide training workshops Compile specialized databases of reviews
Coordinate handsearches of health care journals Coordinate activities with external agencies
Help developimaintain Collaboration's tools Comment on systematic reviews relating to
Help translate and disseminate the Collaboration's mission an their particular area.
accomplishments URL:
URL: www.cochrane.org/cochrane/crgs.htm#CENTRES , www. coch rane.org/cochrane/crg s. htm#FI ELDLIST
COCHRANE REVIEWS
Status: more than 1,200 reviews
Access: Cochrane Library (Subscription)
OVI D (Subscription)
MEDLINE (Citations only, not full text)
borative Review Groups seek to provide the current best that Collaborative Review Groups address their issues
evidence for healthcare decision makers. and concerns, 3) compile a specialized database of re-
To create a comprehensive review on a given topic, views relevant to elder healthcare, and 4) establish in-
Cochrane reviewers need access to all relevant random- A] Cochrane Pharma-
ternal and external p ~ t n e r s h i p s . [ ~
ized controlled trials. To assist the reviewers in this ceuticals Field is being considered.
process, each Collaborative Review Group maintains a
specialized registry of all (English and non-English; pub-
lished and unpublished) randomized controlled trials Cochrane Methods Groups
pertinent to its particular focus. Trials are identified se-
veral ways: 1) electronic and manual searching of bib- The Collaborative Review Groups are further assisted by
liographic databases, 2) contacting the pharmaceutical in- Cochrane Methods Groups, which develop tools and
dustry for unpublished trials, 3) handsearching hundreds assess new methodologies to improve the validity and
of medical journals. accuracy of systematic reviews. For example, the in-
Three other Cochrane entities have much broader formatics methods group played an important role in the
interests and focus on other dimensions other than specific development of the review manager software (REV-
healthcare problems. These are fields, methods groups, MAN).[61The Cochrane review manager software assists
and networks. Cochrane reviewers in conducting reviews (submitting
review protocol, entering data for analysis, and writing
results) in the structured format for publication in the
Cochrane Fields
Cochrane Library.
Fields serve to ensure that Collaborative Review Groups
consider healthcare issues other than interventions, e.g., Consumer Network
healthcare settings, types of consumers, and types of
providers. For example. the field devoted to the health- Consumers, users of the healthcare system, participate
care of elderly people does the following: 1) assist in the throughout most entities of the collaboration. Consumers’
handsearching activity of specialist journals, 2 ) ensure input and feedback helps identify clinical questions that
The traditional system of providing drug therapy to pa- The ACCP advocates the role of qualified pharmacists
ticnts. in which only certain health care profession'1' 1.s are as capable collaborative drug therapy managers. Further-
authoriLed to initiate drug therapy, is under attack at many more, ACCP supports the pharmacists' role in collab-
levels. The processes of drug prescribing, dispensing, orative drug thcrapy management to improve patient
administration, monitoring, and dosage adjustment, as outcomes and increase ef€iciencies in the health care sys-
practiced in this traditional system, occur in a disjointed tem. To participate in collaborative drug therapy manage-
fashion that frequently results in avoidable drug-related ment, pharmacists must have access to patients and patient
problems that contribute significantly to poor patient health information, conduct patient assessments, docu-
outcomes and increased medical costs." ' ment activities, and undergo quality assurance programs
Collaborative drug therapy management, characterized on these activities. Scope of practice statements, identify-
by an interdisciplinary approach to patient care, is emcrg- ing pharmacists' professional authority and responsibility,
ing as a solution that can maximiie the patient's health- will be based on the pharmacist's credentials and the na-
relaled quality of life, reduce the frequency or avoidable ture of the collaborative arrangement within the health
drug-related problems, and improve societal benefits from care environment or system.
phannaceuticals. In this approach to care, drug therapy
decision making and management are coordinated
collaboratively by pharmacists, physicians, other health
care professionals. and the patient.
Many pharmacists with sufficient clinical training have
or arc willing to assume this level of responsibility for the Regulation of pharmacist prescribing in the modern health
patients they serve. When participating in collaborative care system of the United States can be traced to passage
drug therapy management. pharmacists share the respons- of the Federal Food. Drug, and Cosmetic (FDC) Act of
ibility for patient outcomes, not just by providing basic 1938. This act was introduced to address concerns sur-
dispensing functions and drug information services, but rounding the availability of a growing therapeutic arma-
by solving patient- aud medication-related problems and mentarium of antimicrobial agents. led by introduction of
by making decisions regarding drug prescribing, monitor- the sulfonamides in 1935. Following a disaster in which
ing, and drug regimen ad,justments. 107 people died from consuming a toxic base used to
This statement represents the position of the Ame- compound a sulfanilamide elixir, Congress passed the
rican College of Clinical Pharmacy (ACCP) on the role FDC Act of 1938. The Food and Drug Administration
of pharmacists in collaborative drug therapy manage- (FDA) then issued regulations to enforce this legislation.
ment. Furthermore, a model for collaborative manage- The 1938 act deemcd as misbranded any drug that failed
ment of drug therapy is described and endorsed as a to carry adequate directions for use or failed to warn
way to enhance the quality of patient care within health patients about potential lack of sai'ety. Any drug could be
care systems. exempt from the requirement of adequate directions for
use if, because of its potential for toxicity or misuse, it In 1972, individual states began exploring the issue of
was to be used under the supervision of a physician. Re- pharmacist prescribing, heralded by the Health Man-
gulations mandated these exempted agents carry the power Experimental Act of 1972, a unique experiment in
wording, “Caution: to be used only by or on the pres- California. Health Manpower Pilot Projects were created
cription of a physician, dentist, or veterinarian.” Another with the purpose of training students of the allied health
provision was the working, “Warning-may be habit professions in areas that were then beyond their legal
forming,” required on certain narcotic and hypnotic drugs. scope of practice. To include prescribing by pharmacists,
These regulations became the forerunner to our present- nurses, and physician assistants in these pilot projects,
day system for designating prescription drugs and con- the California Assembly Bill 717 was introduced in
trolled substances. Until this time, pharmacists had been 1977, with a provision for sunsetting in 1983. The bill
able to prescribe medications legally. authorized prescriptive authority only to those directly
The activity of pharmacists refilling, and thereby con- involved with the pilot projects. The project was so suc-
tinuing, a patient’s medications without authorization cessful in saving health care dollars[61that the California
from the patient’s physician was a secondary issue in the Pharmacists Association, with assistance from the Cali-
1938 FDC debates. Although not defined as unlawful in fornia Society of Hospital Pharmacists, introduced legis-
1938, the practice of pharmacists providing refills of lation in 1981 to enable prescribing by all pharmacists
medications directly to patients was not favored by the in the state. This legislation allowed registered pharma-
FDA. No definition had differentiated a prescription drug cists functioning in licensed acute and intermediate
from a nonlegend, over-the-counter. drug. The two classes health care facilities to adjust the dosage of a patient’s
of drugs were not legally differentiated until passage of drug regimen pursuant to a prescriber’s authorization,
the Durham-Humphrey Amendment in 1951. At that order laboratory tests, perform physical assessments, and
time, it became illegal for pharmacists to refill legend administer medications. This law has been expanded
drugs without authorization from the patient’s physi- twice since then and now enables pharmacists to initiate
~ i a n . [ ~Thus,
, ~ ] the practice of physician prescribing and drug therapy (1983) and expands the types of practice
pharmacist dispensing became law. Many regulations sites to include clinics and systems licensed as health
endorsed by today’s state boards of pharmacy are re- care service plans (e.g., managed care organizations;
sultant attempts to define these distinctions clearly. 1994). The specific duties outlined by each protocol are
During this same period, the preparation of medica- site- and practice-specific. Traditionally, they have ranged
tions was increasingly assumed by pharmaceutical ma- from pharmacist-managed nutritional support prescrib-
nufacturing companies, thereby lessening the role of in- ing in the inpatient setting to antihypertensive medica-
dividual pharmacists in production manufacturing. Thus, tion management in the outpatient
pharmacists were no longer taking an active role in ini- Eventually, pharmacists have gained recognition as
tiating or continuing prescription drug therapy, and were drug therapy experts at the national level. In 1974, the
also spending less time in the final preparation of the Department of Health, Education, and Welfare enacted a
pharmaceutical product. drug regimen review regulation for nursing homes in an
In the 1960s and 1970s, pharmacists began to assume attempt to improve the quality of drug prescribing in that
roles as direct patient care providers in rural settings health care setting. In 1984, Thompson and associates
within the Indian Health Service. The activity of phar- published the results of a study of clinical pharmacists
macist prescribing was first documented in this setting. who prescribed under physician protocol in a skilled
As early as 1977, Brands described pharmacist practi- nursing facility.“ The findings of this controlled study
tioners in the Indian Health Service who were trained to indicated that patients in the prescribing clinical pharma-
diagnose and treat acute, self-limiting diseases and chro- cists’ group had significantly fewer deaths, more patients
nic diseases in ambulatory patient^.'^] A 1-year review of discharged to lower levels of care, and fewer drugs per
patients cared for by this arrangement found that 70% of patient than the patients in the traditional care group. The
the patients in this group were cared for solely by estimated health care savings due to clinical pharmacists
pharmacists. Quality of care was satisfactory and patient prescribing in a skilled nursing facility were $70,000
acceptance was excellent. In a similar fashion, Erickson annually (in 1984 dollars) for every 100 beds.
described a program in the same Indian Health Service Legislation enabling pharmacists to prescribe under
setting that demonstrated pharmacists were able to pro- protocol was first passed in the state of Washington in
vide patient monitoring between physician visits and 1979. Since then, it has been amended several times to
were also able to extend the interval between physician clarify or expand the types and numbers of protocols.
Currently, the Washington State Board of Pharmacy has
190 Collaborative Drug Therapy Management by Pharmacists (ACCP)
Other Aspects Completion Administering No pregnant Changing Physical Pharmacist must Initiating and
Addressed of course injections; or nursing duration of assessment; record the name modifying
approved by patient women; therapy, drug ordering clinical of the drug therapy
Board of assessment; only drug strengths. tests; initiating, delegating MD or
Pharmacy laboratory supplies for dosage forms, continuing, or DO on
enables tests; initia- less than 34 d: frequencies stopping drug the prescription
pharmacist ting and no refills or routes of therapy; drug
to administer adjusting administration: modification and
certain drug stopping and monitoring;
medications. regimens adding drugs therapeutic
including interchange
immunizations
and vaccinations,
to patients age
18 yr or older
Collaborative Drug Therapy Management by Pharmacists (ACCP) 191
Table 1 Attributes of state and federal regulations governing pharmacist prescribing (Continued)
Nevada New Mexico North Dakota Oregon South Dakota Texas Washington Federal government
Licensed .411 settings Institutional All settings All settings All settings All settings All settings
medical settings
facilities (hospitals,
(hospitals, skilled
hospices, nursing
managed care facilities,
settings, home swing bed
health care. facilities)
skilled nursing
facilities)
No additional Additional No additional No additional No additional Specific No additional MS degree,
training equiv- clinical PharmD degree,
alent to that continuing accredited
of a physician education residency,
assistant specialty board
(60 hr of certification, or
physical 2 yr of clinical
assessment; experience
9 mo of
clinical
experience
or MD
preceptorship)
Initiating, Monitoring Pharmacist Further Administering, Written Initiating and No protocol
modifying, drug therapy; must notify rulings initiating, and protocol modifying drug or cosignature
and monitoring ordering physician expected modifying defined as therapy; required within
drug therapy laboratory when they in 1997 drug a physician's protocols must scope of practice;
tests; patient initiate or therapy; order, standing be renewed policies required
assessment; modify drug research order, standing every 2 yr to assure practice
prescribing therapy investigators delegation is within
and modifying order, or identified scope
drug therapy other protocol of practice
192 Collaborative Drug Therapy Management by Pharmacists (ACCP)
over 70 protocols on file, conducted by over 425 phar- the pharmacist’s role in collaborative drug therapy man-
macists practicing in 60 locations throughout the state. agement. States are continuing to enact or pursue le-
Although the protocols were initially used in institutions, gislation to enable pharmacists to prescribe as part of
most are now used in managed care and community collaborative drug therapy management agreements. Cur-
settings. In clinic settings, these protocols have been rently, 14 states and the federal government have enacted
found to create efficiencies in prescribing antimicrobial legislation allowing some form of collaborative prescrib-
and anticoagulation In the community ing for pharmacists. Table 1 provides some specific at-
pharmacy setting, protocols are used for prescribing refills tributes of these laws.
and for monitoring drug therapy of chronic disease states.
The third state to provide prescriptive authority to
pharmacists was Florida. Taking a different approach,
the Florida legislature created a third class of drugs in
1986. In contrast to the California and Washington pro-
visions for prescribing under protocol, Florida pharma-
cists enjoy independent prescribing from within a limited
formulary. Certain drugs within the following categories Since the late 1970s, many studies have been published
are included in this formulary: oral, urinary, and otic that document the success of pharmacists’ management of
analgesics; hemorrhoid medications; antinausea prepara- specific types of patients, drugs, disease states, and speci-
tions; antihistamines and decongestants; anthelmintics; fic patient problems and issues. Outcomes measured have
topical antifungals and antimicrobials; topical antiinflam- included increased patient safety and satisfaction, reduced
matory preparations; otic antifungals and antimicrobials; health care costs, and improved e f f i c i e n c i e ~ . [ ’ ~ - ~ ~ ~
keratolytics; vitamins with fluoride; lindane shampoos; Recently, a summary and critique of 104 studies that
antidiarrheals; smoking cessation products; and ophthal- assessed the economic outcomes of clinical pharmacy
mics. The formulary is subject to specific conditions services from 1988- 1995 was published.[231The clinical
spelled out in the state’s pharmacy practice act. The pharmacy services evaluated could be classified into four
legislation has been amended freq~ently.”~] main categories-disease state management (4%), general
In 1995, the Veterans Health Administration (VHA) pharmacotherapeutic monitoring (36%), pharmacokinetic
updated the granting of prescribing authority for practi- monitoring (13%), and targeted drug programs (47%).
tioners in the Veterans Affairs (VA) system. “General The services were provided in a variety of health care
guidelines for establishing medication prescribing author- settings, including university, community, and govern-
ity for clinical nurse specialists, nurse practitioners, ment hospitals; health maintenance organizations; and
clinical pharmacy specialists, and physician assistants,’ ’ community pharmacies.
VHA Directive 10-95-019, reviews and clarifies the pre- Outcomes, or consequences, of the services described
scribing role of these practitioners within the VA health were considered in all 104 papers. Nineteen (18%) of the
care system. Clinical pharmacy specialists are defined as papers were found to be full economic analyses because
those with Master of Science or Doctor of Pharmacy they considered two or more alternatives to care and
degrees, pharmacists who have completed an accredited measured both input costs and outcomes. The most com-
residency, specialty board-certified pharmacists, or phar- mon outcomes measured were drug costs avoided, length
macists with equivalent experience. The scope of practice of hospital stay, use of nonpharmaceutical resources,
for each type of practitioner is determined by the practice rates of adverse drug reactions, frequency of pharmacist-
site. The scope of practice statement identifies each driven therapeutic interventions, and qualitative changes
individual’s prescriptive authority and describes routine in prescribing patterns. In 93 (89%) of the papers, bene-
and nonroutine professional duties and general areas of ficial financial impacts of clinical pharmacy services
responsibility. Prescriptions written by authorized practi- were described.
tioners within their approved scope of practice do not In seven papers, the study design was sufficiently
require a physician cosignature. Because states cannot rigorous to allow the results to be expressed as a benefit-
regulate the activities of the federal government or its to-cost ratio. The calculated benefit-to-cost ratios for
employees when acting within the scope of their em- these seven studies ranged from 1.08:1 to 75.84:l (mean
ployment, state laws and regulations related to medication 16.7:l). In other words, for every dollar invested in cli-
orders and prescriptions do not affect scope of practice nical pharmacy services, on average, $16.70 of benefit
statements in the VA system. was realized. Overall, the body of literature contains a
With early models in place and numerous studies do- wealth of information pertinent to the value of the clinical
cumenting success, momentum has mounted to support practice of pharmacy.
Collaborative Drug Therapy Management by Pharmacists (ACCP) 193
optimally, but are prohibited by some state pharmacy therapy that achieves the defined outcomes that improve a
statutes and regulations. patient’s quality of life. The process of prescribing is
more appropriately described by a broad set of activities
that include selecting, initiating, monitoring, continuing,
VQ VI G modifying, and administering drug therapy. Table 4
provides definitions of these prescribing activities. To
efini select, initiate, and monitor drug therapy, the practitioner
must be able to order and interpret laboratory tests, and
Today, prescribing is no longer the act of writing perform patient assessments related to drug therapy
medication instructions. Prescribing encompasses mul- management. This set of prescribing activities suggests
tiple complex tasks, and as a term, it inadequately des- that the focus of a practitioner’s responsibility is on drug
cribes the numerous activities needed to provide drug therapy management to improve patient outcomes.
Table 5 Areas and content of core pharmacy curriculum adopted in 1997 by the American Council on Pharmaceutical Education
Biomedical Science, Anatomy, physiology, pathophysiology, microbiology, immunology, biochcmistry,
molecular biology, bioatatistics
Pharmaceutical Scicnco Medicinal chemistry, pharmacognosy, pharmacology, toxicology, pharmaceutics,
biopharmaceutics, pharmacokinetics
Bchavioral, social, and Health carc economics, pharmacoeconomics, practice management, communications,
administrativc pharmacy sciences pharmacy history, ethics, social and behavioral applications and laws of practice
Pharmacy practice Dispensing, drug administration, epidemiology, pediatrics, geriatrics, gerontology,
nutrition, health promotion and discasc prcvenlion, physical assessment, emergency
first carc, clinical laboratory medicine, clinical pharmacokinetics, paticnt cvaluation
and ordering medications, pharmacothcrapcutics, disease state management,
outcomes documentation, sclf care and nonprcscription drugs, drug inPormalion
and literature evaluation
Profewonal experience Introductory and advanccd practice cxperienccs throughout the curriculum as a
continuum, in a variety of practice settings
(Adaptcd from Ref. [301.)
Prescribing activities:121
Select: When pharmacotherapy is necessary, and after
This article examines how the practice of pharmacy review of an individual patient’s history, mcdical
can be improved by the legal and institutional recog- status, presenting symptoms, and current drug re-
nition of Collaborative Drug Therapy Management gimen, the clinician chooses thc best drug regimen
(CDTM). Further, the development of Collaborative among availablc therapeutic options.
Practice Agreements or defining a specific Scope of Initiate: After selecting the best drug therapy for an
Practice that allows the pharmacist and other health individual patient, the clinician determines the most
professionals to focus more on integration and colla- appropriate initial dose and dosage schedule and writes
boration is discussed. an order or prescription.
Monitor: Once drug therapy is initiated, the clinician
evaluates response, adverse effects, therapeutic out-
DEFlNIT1 comes, and adhcrence to dcterrnine if the drug, dose,
or dosage schedule can be continued or nccds to be
Pharmaceutical care: The responsible provision of drug modified.
therapy for the purpo\c or achieving a definite outcome Continue: After monitoring the current drug therapy
that improves the patient’s quality of life.“’ for a patient, the clinician renews or continues the
same drug, dose, and dosage schedule.
Collaborutive Drug Therapy Management (CDTM): The Mod&: After monitoring a patient’s drug thcrapy,
provision of pharmaceutical care in a collaborativc and the clinician makes an adjustment in dose and/or dos-
supportive practicc cnvironment that allows the qualified age schedule, or adds, discontinues, or changes drug
pharmacist legal, regulatory, and ethical responsibility to therapy.
solve drug related problcms when discovered. Administer: Regardless of who initiates a patient’s
drug therapy, the clinician gives the drug directly to
Scope of practice: The boundaries within which a health the patient, including all routcs of administration.
professional may practice. For pharmacists, the scope of
practice is gencrally approved by the board, agency, or
committee that regulates the profession in a given state
or organization. PRACTICE E N V I R O ~ M ~ N T
Credentialiizg: The process by which an organization or As the volume and potency of prcscription medications
institution obtains, verifies, and assesses a pharmacist’s have increased. the nation’s attention has become focused
qualifications to provide patient care services. on the staggering human and economic cost of medication
errors. Drug-related morbidity and mortality in the United
Privileging: The process by which a healthcare organi- States has a vast cconomic impact on the healthcare
zation, having reviewcd an individual healthcare provi- system. The nation was stunned in 1999 when the Institute
der’s credentials and performance and having found them of Medicine (IOM) issued a report that concluded that
satisfactory, authorizes that individual to perform a spe- medical errors account for bctween 44,000 and 98,000
cific scope of patient care service within that organization. deaths annually.”’ The IOM report noted that “[blecause
quirements might also be very different depending on the frequencies by appropriate boards, individuals, and
environment of care and the tasks the pharmacist wishes committees.[20.211An example of a CPA for primary care
to perform. To confirm that all core requirements are met, pharmacists is shown in Fig. 1.
most health systems require .‘privileging” or approval
by a health system committee. During this process a
healthcare organization, having reviewed an individual
healthcare provider’s credentials“’] and performance and
found them satisfactory, authorizes that individual to
perform a specific scope of patient care service within the
organization. Credentialing and privileging are processes CPAs can be written as process specific, or disease-state
fundamental to CDTM. specific, or both. Process documents describe the routine
Even though many pharmacists possess all of the duties of the pharmacist in global terms; e.g., write
core requirements, the widespread implementation of prescriptions, order laboratory tests needed to monitor
CDTM has not yet occurred. Although progress is being medication, order certain radiological tests, take medica-
made in many environments, integrated health systems tion histories, record information in the medical record,
are among the fastest moving. Perhaps this is because order consults, etc. Disease specific CPAs give examples
these systems are rapidly incorporating the factors that of the specific patient populations the pharmacist will see,
support pharmaceutical care. Five enabling factors and may include protocols for patient management. These
have been identified as features of a system or infra- CPAs may describe comprehensive, interim-care, and
structure that would likely facilitate CDTM or phar- unscheduled or acute-care practice models.
maceutical care: Provision of longitudinal comprehensive pharmuceut-
ical cure using CPAs involves evaluation of patients’
0 Presence of an integrated electronic medical records drug-related problems during an ongoing relationship
system. with other care providers. One example of a pharmacist’s
0 Availability of an automated dispensing system for role in CDTM programs focuses on identification of drug-
ambulatory care prescriptions. related problems in the comprehensive review of a
Q Pharmacist participation on multidisciplinary care patient’s medical record and by interviews with the
teams. patient. This review can be conducted when the patient is
Q Support from medical staff. admitted to a general inpatient facility or is in an out-
0 Support from senior management. patient, primary-care clinic. In this model, the pharmacist
uses a problem-based approach to determine the presence
These trends in ambulatory care pharmacy have been of medication-therapy problems and composes a problem
studied by two surveys of the ASHP Managed Care list considering and incorporating disease state, adverse
and Ambulatory Care Pharmacy in Integrated Health effects, cost, and compliance issues. The pharmacist then
~ystems.”~”~] establishes treatment goals, monitoring parameters, and
plans patient follow-up. Documentation in the medical
chart of these actions is a critical component of any
CDTM model. Interventions using this comprehensive
model have been described.‘221
The document describing the specific routine and non- Interim cure is defined as frequent care for specified
routine professional duties to be performed (the bound- patient populations and close patient monitoring between
aries of practice) and the general areas of responsibility visits to the primary provider. Interim care models
for each pharmacist practitioner is called a Scope of follow a similar process for delivering care as do com-
Practice. When this scope of practice has concurrence by prehensive pharmaceutical care models, but on a disease-
the physician(s) or other collaborating practitioners in the state specific basis. Many examples of this exist in the
patient care/program area in which the pharmacist CDTM model. Examples of interim-care CDTM models
functions, it is called a Collaborative Practice Agreement include: anticoagulation/heparin clinics and clinics to
(CPA). The health system will generally have written treat asthma, seizures, pain. hypertension, diabetes, HIV,
policies to address all aspects of scope of practice issues dyslipidemia, congestive heart failure, and other chronic-
for pharmacists including medication prescribing author- disease conditions.
ity, quality assurance, and peer review. In addition, a Pharmacists working within unscheduled acute cure or
process of credentialing and privileging will be outlined urgent cure models handle patient issues that require
in policy, and CPAs will be reviewed at predetermined immediate attention between scheduled visits. Some
202 Collaborative Practice Agreements (Collaborative Ikug Therapy M a n a ~ e m c n ~ )
-
I am educationally competent and physically capable of performing the activities that I have rcqucstcd. Whcrc
indicated below, it is fully understood that my scope is defined by approved protocols/procedures.
RECOMMEND APPROVAL/DISAPPROVAL
Granted on:
To be reviewed on or before: -
Rclkrenceu
\‘I IA Dircctivc 10-95-019 - (icncrdl (iuidclinc for Furnishing Medication Prcsci-ihing Authority for (’linical NUI-scSpeciali?tu, kurse 1’1-actitionel-s,Clinical I’hnrinacy
Specialisis and Physician Assistants, dated March 3 , I995
V l l A L)irccii\c 96-034 -Scope ofl’ractice tix (‘linical Pharmacy Spccialials. dated May 7, lY96
To identify scope of practice privileges for the clinical pharmacy specialist (CPS) at the VA Medical
Center, and to define criteria for the qualifications for these privileges. The CPS will be qualified and
authoriLed to perform specific clinical duties to assure high quality health care and appropriate
pharmaceutical care is provided to the veterans.
POLICY:
Scope of practice guidelines for CPS shall be dclineated in writing and will follow established protocols.
OUALIFICATIONS:
The CPS is trained in clinical pharmacy, clinical pharmacokinetics and clinical pharmacology. Hc/shc is
a Masters or Pharm. D. graduate, has completed an accredited pharmacy residency, is a specialty board
certified pharmacist, or has equivalent education, training and experience functioning as a clinical
pharmacist.
K E Y FUNCTIONS:
Conduct comprehensive appraisals of patients’ health status by taking health histories, drug histories
and performing physical examinations necessary to assess drug therapy
Document relevant findings of a patients’ health status in the patients’ medical record
Evaluate drug therapy through direct patient care involvement, with clinical assessment, subjective
and objective findings relating to patient’s responses to drug therapy and communicating and
documenting those findings and recommendations to appropriate individuals and in appropriate
records (i.e., patient’s medical record)
Develop, document and execute therapeutic plans utilizing the most effective, least toxic, and most
economical medication treatments as per national or VA guidelines or VTSW protocol or established
local protocol
Provide ongoing primary care for chronic stable or minor acute health problems as delineated in
protocols/procedurcs
Provide patient and health care professional education and medication information
Evaluate and document paticnts’ and caregivers ability to understand medication instructions and
provide oral and written counseling on their medications
Refer patients by consult to specialty clinics, order appropriate laboratory tests and other diagnostic
studies necessary to monitor and support thc patient’s drug therapy
Perform venipuncture or finger sticks for the purpose of withdrawing blood for clinical laboratory
test
Prescribe medications, including initiation, continuation, discontinuation, and altering therapy, based
upon established formulary or protocols
Conduct and coordinate research drug investigations and research under FDA guidelines and
regulations and approval by appropriate local officials
e Analyze laboratory and diagnostic test data so as to modiry drug therapy and dosing as necessary.
Perform physical measurement necessary to assure the patients responses to drug therapy
Implement protocols approved by the Pharmacy and Therapeutics Committee or other Medical
Center Committees regarding drug therapy
Assist i n the management of medical emergencies, advcrse drug rcactions, and acutc and chronic
disease states
Administer medication according to preestablished protocol when rcquested by physicians
Identify and take specific corrective action for drug-induccd problems
Serve as clinical managers of drug and drug-related program5 in clinics and wards in conjunction
with the attending physician
A. The ability to prcscribc non-controllcd medications has bcen out1ined in the General Guideline fbr
Furnishing Medication Prescribing Authority for Clinical Nurse Specialists, Nursc Practitioners,
Clinical Pharmacy Specialists and Physician Assistants in VHA Directive 10-95-019. CPS will
initiate, continue, modi ry a i d monitor medication therapy as outliiicd in approved treatment
protocols listed below or in policies and procedures of the Medical Ccnter. The CPS will prescribe
all drugs except narcotics.
€3. Equipment and non-medication supplies issued by Phai macy and Prosthetics/Matei ials Management
Serviccs may be ordcred without co-signature of a physician.
SUPERVISION:
A collegial relationship with mutual consultation and referral exists with the physicians and the CPS.
Consultation with the physician or referring practitioner is outlined and co-signature is required for
practice outside approved procedures/protocols. The CPS will provide patient care as a Non-Physician
Clinician (NPC). A physician is available at all times by telephone or in person for consultation.
Periodic chart and peer reviews, and annual evaluations provide ongoing medication use evaluation.
The CPS prescribing practices are includcd in the medication use evaluation process.
1 he following is a list ofclinical conditions that the CPS at the VA Mzdical Center would commonly be
referred for evaluation and rnanagemcnt. Thc most reccnt version of the protocols listed will be the
working copy ofthe CPS protocols.
e ~ ~ e ~ t e TQV C
No Ycs No Yes No Ucs
Anticoagulation Clinic n u n u u u
Medication Renewal Clinic 0 0 0 0 U Q
Fig. P Example of a CPA for primary care pharmacists (Continued).
Collaborative Practice Agreements (Collaborative Drug Therapy Management) 205
Approved with
Reauested Approved Supervision
Yes No Yes No Yes No
HIViAIDS Antiretroviral Therapy n o 0 0 0 0
Other Clinical Conditions (specify):
Approved with
Requested Approved Supervision
Yes No Yes No Yes No
n o 0 0 o n
n o o n n o
-
committees and officers on professional and administra- practice, education, and research and to optimize the
tive matters. health of individuals affected by psychiatric and neuro-
CPNP committees function in an advisory capacity to logic disorders.
thc Board of Directors, developing and implementing Objectives include the following:
programs and policies authorized by the Board in the
major areas of interest to which it is assigned. * Facilitate dissemination of information regarding psy-
The following are standing committees of CPNP: chotherapeutic pharmacotherapy, patient care, and
Communication and Information-responsi ble for pub- community support.
lishing the CPNP Newsletter and maintaining the web Endorse the Psychiatric Pharmacy Certification Exam
site cpnp.org; Community Resource-acts as a liaison process and support programs for the preparation of
to extramural groups and organimtions on issues rela- candidates for the exam.
ting to psychiatry and neurology; Program-responsible 0 Facilitate programming in the areas of psychiatric and
for planning the annual meeting as well as other neurologic pharmacy at national meetings and with
continuing education programs; and Membership-res- organizations that support our intercsts.
ponsible for the recruitment and retention of members Improve patient care.
of CPNP. e Promote research in patient care.
CPNP officers since its founding are summarized:
1998-President: Gary Levin; president-elect: Alex
Cardoni; Secretary: Cherry Jackson; and Treasurer: James
Wilson. 1999-President: Alex Cardoni; president-elect:
Roger Sommi; Immediate Past-Prcsidcnt: Gary Levin; The Board of Director5 has identified Eeveral priority
Secretary: Cherry Jackson; and Treasurer: James Wilson; initiatives in 2000:
and 2000-President: Roger Sommi; president-elect:
Cherry Jackson; Immediate Past-President: Alex Cardoni; Further develop and refine “cpnp.org” web site.
Sccretary: Judith Curtis; and Treasurer: James Wilson. Retain the services of a management consultant to
The following members were elected as Directors-at- assume rcsponsibility for routine administrative opera-
Large: 1998-2000-Lawrence Cohen; 1998-2001- tions of the organization.
Sally Guthrie; and 2000-2002-Charles Caley. Implement and facilitate a board recertification pro-
cess for board certified psychiatric pharmacists by
working with existing professional organizations.
Initiatc strategic planning for the organization that will
set goals and objectivcs and a budget for the next
As of fall 2000, the College of Psychiatric and Neurologic several years.
Pharmacists has a membership of approximately 300 Stimulate development of pharmaceutical care
individuals. In a survey of CPNP membership conducted psychiatric and neurologic clinical services by es-
in 1999, the following profile emerged: tablishing a competitive “visiting expert” grant
program.
60% between ages of 3 1-50, Stimulate development and growth of regional affi-
52% female. liatcs to facilitate attainment of CPNP goals and
4.5% based in hospitals. objectives.
57% in practice less than 10 years.
50% with psychlneuro specialty residency training.
20% with fellowship training.
70% working in psychiatric pharmacy; 10% in neu-
rologic pharmacy. CPNP holds its annual meeting in the spring, usually late
SS% board certified in psychiatric pharmacy. March or early April. The site of the meeting changes to
include East Coast, mid-America, and West Coast. The
meeting is 2-2 112 days in length and includes sessions
which focus on contemporary clinical and research topics
in psychiatric and neurologic pharmacy. A poster session
The mission of the College of Psychiatric and Neurologic allows for presentation of research and clinical practice
Pharmacists is to advance neuropsychiatric pharmacy activities of members.
College of Psychiatric and Neurologic ~ h ~ r ~ a c i s t s 209
CPNP tncmbers also traditionally participate in the Regional programming for CPNP members and
annual NCDEU meeting sponsored by the National Ins- other psychiatric and ncurologic pharmacists is provi-
titutes of Mental Health. This meeting is held in the dcd by local “chapters” of CPNP throughout the
spring as well, usually in late May or carly June. The country. Annual pharmacotherapy updates are held in
location has been (with few exceptions) in Boca Raton, the Northeast region (fall), Georgia-Southeast (winter),
Florida. Cutting-edge programming characterizes this Midwest region ([all), Texas (fall), Arizona-Southwest
meeting, with presentations from leading NTH re- (winter), and in Montana-Northwest (spring). These
searchers as well as others in thc United States and sessions bring high-quality programming to members
abroad. A poster session also facilitates reporting of re- and nonmembers who may not be ablc to attend the
search findings. annual meeting.
PROFESSIONAL ORGANIZATIONS
arol
University of Utah, S d t Lake City, Utah, U.S.A.
function as professionals and informed citizens in pharmaceutical care. And they must be able to do this at a
a changing health care system. It does this by maintaining level commensurate with the evolving mission of phar-
a dynamic, challenging, and comprehensive curriculum. macy practice (see above).
It is also responsible for generating and disseminating Based on this assumption, the Commission outlined
new knowledge about drugs and about pharmaceutical
the major practice functions that comprise pharmaceut-
care systems.
ical care as rendered at the entry level and offered re-
commendations for the educational outcomes and com-
Pharmaceutical education inculcates students with the
petencies that are necessary to perform pharmaceutical
values necessary to serve society as caring. ethical,
learning professionals and enlightened citizens. It pro- care functions.
vides students with scientific fundamentals and fosters The practice functions identified were:
attitudes necessary to adapt their careers to changes in
health care over a lifetime. It also encourages students e Participate in the drug use, decision-making process.
prior to and after graduation to take active roles in a Select the appropriate dosage form, formulation, ad-
shaping policies, practices, and future directions of the ministration, and delivery system of specific drug
profession. entities.
e Select the drug product source of supply.
Pharmaceutical education promotes advances in phar- e Determine the dose and dosage schedule.
maceutical care by fostering postgraduate residencies and 0 Prepare medication for patient use.
fellowships in the clinical sciences and differentiated a Provide drug products to patients.
areas of pharmacy practice. It provides structured 0 Counsel patients.
postgraduate education and training through which a Monitor patients to maximize compliance.
practitioners maintain their competence and acquire new
competencies to serve the changing needs of society.
a Monitor patients’ progress with regard to therapeutic
objectives.
Pharmaceutical education is responsible to the profession
e Monitor patients to prevent adverse drug reactions and
and to society for generating new knowledge about drugs, drug interactions.
drug products. drug therapy, and drug use through the
conduct of basic and applied research. It promotes the Several general outcomes and competencies were
pharmaceutical sciences by fostering graduate education described that underlie the education of a professional
and research within its schools and colleges. Pharmaceu- person and citizen. These included:
tical education is responsible for both professional edu-
cation and graduate education for research. The latter Thinking abilities involving scientific comprehension
focuses on preparing students to discover new knowledge, and critical thinking.
primarily by use of the scientific method. The goal is to
Communication abilities involving communication
prepare scholars to perform independent, creative re-
competence and aesthetic sensitivity.
search that addresses important questions related to the
discovery and use of drugs. Facility with values and ethical principles involving
professional ethics.
Pharmaceutical education continually evaluates its mis- Personal awareness and social responsibility involving
sion, objectives, goals, and outcomes and determines and contextual competence and professional identity.
implements necessary changes in the nature and scope of Self-learning abilities and habits involving adaptive
education and research performed within the purview of competence, scholarly concern for improvement, and
pharmaceutical education (p. 376). motivation for continued learning.
Social interaction and citizenship including effective,
Perhaps the most substantive portion of the Commis- interpersonal, and intergroup behaviors as well as
sion’s work resides in its second position paper (Back- leadership competence.
ground Paper 11) which dealt with issues of entry level,
curricular outcomes, curricular content, and educational Additional professional outcomes and competencies
process.[21 In considering what is “entry level,” the were identified as essential to perform the functions that
Commission embraced the view that while a system of support practice. These included the broad skills ne-
pharmaceutical care requires the participation of both cessary to solve problems and make decisions; manage;
generalists and specialists, students prepared at the entry learn; communicate, teach, and collaborate; and particip-
level are general practitioners who coordinate and render ate in policy formulation and professional governance.
212 Commission to Implement Change in Pharmacy Education, AACP
The Commission than proceeded to describe a core cur- The Commission was reappointed in 1995 by AACP
riculum to serve as a guide for pharmacy faculty at in- President Mary Anne Koda-Kimble to analyze and as-
dividual schools and colleges to design the content of a sess how a range of rapid and extensive changes in
specific curriculum felt likely to engender the com- health care delivery, education, and research might alter
petencies and outcomes necessary to render pharmaceu- its original observations and recommendations. The Com-
tical care. mission met twice, reaffirmed the contemporary value of
A major portion of the Commission’s efforts in the its original views, and, in 1996, encouraged all schools
area of curriculum was devoted to recommendations re- and colleges of pharmacy to accelerate their plans for
lating to the educational process. Particular suggestions curricular reform based on recommendations made in its
were offered to assist faculty in teaching problem sol- previous reports.[’]
ving. fundamental information, communication skills, While history will judge the overall impact of the
and practice skills. Commission’s work, there is little doubt that the effort
Certainly the most controversial issues examined by was a catalyst for major change in pharmaceutical edu-
the Commission were those contained in its position paper cation.r61Subsequent to the release of the Commission’s
dealing with the standards of educational quality neces- reports and adoption of most of its recommendations by
sary for the entry-level curriculum, the length of that AACP in 1992, major, nationwide energies were, and
curriculum, and the title of the ensuing degree.r31The continue to be, directed toward changes both in cur-
Commission concluded that AACP must advocate the ricular structure based on educational outcomes as well
outcomes, competencies, content, and processes con- as in the process of teaching within the curriculum.
tained in Background Paper I1 before the American Moreover, there occurred a substantial increase in the
Council on Pharmaceutical Education (ACPE) for incorp- number of schools offering the Pharm.D. as the sole
oration into the revised entry-level program accreditation professional degree. At the time the Commission’s re-
standards that the Council was then developing. It commendations were adopted, 19% of pharmacy schools
emphasized that this should be done for all programs, offered the Pharm.D as the sole professional degree. As
including existing Pharm.D. offerings. The Commission of fall 1995, 37% of schools were admitting students into
went on to say that at least one additional year of pro- all Pharm.D. programs. In fall 1996, that percentage
fessional education (beyond the 5-year entry-level pro- increased to over 50%. Finally, as a result of the Accre-
grams commonly in place) was needed to accomplish the ditation Stacdards and Guidelines for the Professional
educational objectives previously described, and thus, Program in Pharmacy Leading to the Doctor of Phar-
proposed that AACP endorse an entry-level program that macy Degree adopted June 14, 1997 by the American
is at the doctoral level, is at least four professional, aca- Council on Pharmaceutical Education,[71 all schools of
demic years in length, and follows preprofessional ins- pharmacy will only admit students into a Pharm.D.
truction of sufficient quality and length (2-year minimum) program by 2002. Thus, an issue that had been hotly
to prepare applicants for doctoral level education. Finally. debated within and outside of AACP for some 42 years
the Commission proposed that AACP support the doctor is finally resolved.
of pharmacy (PharmD.) degree as the sole degree for
entry into pharmacy practice and offered several recom-
mendations to overcome the barriers that could impede
the process of implementing such needed changes in phar-
maceutical education. 1. Wolf. H.H.; Walton, C.A.; Hepler, C.D.; Koda-Kimble,
The balance of the Commission‘s efforts related to M.A.; Knapp, D.A.; Miller, K.W.; Nahata, M.C.; Rutledge,
discussions surrounding faculty scholarship, graduate edu- C.D.; Smith, W.E.; Vandel, J.H. Background paper I: What
cation, fellowships, and postgraduate professional edu- is the mission of pharmaceutical education? Am. J. Pharm.
cation.[41Particular attention was focused on issues of fos- Educ. 1993, 57 (4), 374-376.
2. Wolf, H.H.; Walton, C.A.; Hepler, C.D.; Koda-Kimble,
tering scholarship, assessing graduate programs, preparing
M.A.; Knapp, D.A.; Miller, K.W.; Nahata, M.C.; Rutledge,
clinical scholars. developing mid-career residencies, and C.D.: Smith, W.E.; Vandel, J.H. Background paper 11:
considering the role of distance learning in sustaining up- Entry level, curricular outcomes, curricular content and
to-date competence. Numerous recommendations were educational process. Am. J. Pharm. Educ. 1993. 57 (4),
advanced. with the intent that these profound responsi- 377-385.
bilities of the enterprise of pharmaceutical education re- 3. Wolf, H.H.; Walton, C.A.; Hepler, C.D.; Koda-Kimble,
ceive the attention necessary to catalyze required change. M.A.; Knapp, D.A.; Miller, K.W.; Nahata, M.C.; Rutledge,
Commission to Implement Change in Pharmacy Education, AACP 213
C.D.; Smith, W.E.; Vandel, J.H. Entry-level education in W.E.; Vandel, J.H.; Yanchick, V.A. Maintaining our com-
pharmacy: Commitment to change. Am. J. Pharm. Educ. mitment to change. Am. J. Pharm. Educ. 1996, 60 (4),
1993, 57 (4). 366-374. 378-384.
Wolf, H.H.: Hepler, C.D.; Koda-Kimble, M.A.; Knapp, 6. Buerki. R.A. In search of excellence: The first century of
D.A.: Miller, K.W.; Nahata. M.C.: Rutledge, C.D.: Smith. the American Association of Colleges of Pharmacy. Am. J.
W.E.; Vandel, J.H.; Yanchick, V.A. The responsibility of Pharm. Educ. 1999, 63, 181-184. (Fall Suppl.).
pharmaceutical education for scholarship, graduate edu- 7. Accreditation Standards and Guidelines for the Projes-
cation, fellowships, and postgraduate professional edu- sional Program in Pharmacy Leading to the Doctor of
cation and training. Am. J. Pharm. Educ. 1993, 57 (4), Pharmacy Degree Adopted June 14, 1997; American
386-399. Council On Pharmaceutical Education: Chicago, Illinois,
Wolf, H.H.; Hepler, C.D.; Koda-Kimble, M.A.: Knapp, 1997; 1-51.
D.A.; Miller, K.W.: Nahata, M.C.; Rutledge, C.D.; Smith,
PHARMACY PRACTICE ISSUES
Identification of value-added features and enhance- sidered fully in any purchase decision. PalmPilots and
ments that discriminate one choice from other other compatible devices now comprise over 80 percent of
solutions. the PDA market. Wireless versions using a variety of
Vendor ability to personalize the solution for a health bandwidths and frequencies are making it possible to
system’s specific needs. provide connectivity to devices that easily fit- within the
Determination of quality assurance and safety features. shirt pocket, lab coat pocket, and purse. As memory
Satisfaction that security features are adequate and increases in these PDA devices, it is now possible to have
responsive to the organizational structure. complete medication references as well as network access,
Identification of the frequency of significant system a bar-code scanner, a pager, a digital voice recorder, and a
upgrades. cellular telephone combined into a single device.
Determination of the assistance available for data One must also consider the functional specifications of
migration and the system rollout planning. workstation hardware. While we’re waiting for the per-
Strategic and tactical consideration for how the phar- fectly integrated system to be realized, it will be necessary
macy software solution matches up with the clinical to consider terminal emulation as a first step in com-
information systems, Internet solutions, health resource municating with diverse systems. Previously, “dumb”
planning, access management, decision support, home terminals, which consisted of a keyboard and monitor
care, managed care, and infrastructure applications. connected to a server, dominated the workstations used in
most pharmacies. Now a combination of terminal emu-
These considerations are primarily enterprise-wide in lation running on microcomputers and Internet thin client
scope. With integration being of primary importance to workstations are beginning to proliferate. With the use of
healthcare in general, it is still necessary to obtain best-of- terminal emulation it is possible to have three or more
class software solutions for specific pharmacy activities. patient sessions running on a taskbar of a Microsoft
Recommendations that will help select appropriate Windows workstations and, through multitasking, access
applications and technologies that are backed by reliable Internet-based and information applications simulta-
implementation, support, and services will be the focus of neously. Due to the volume of data that must be trans-
the remainder of this chapter. Refer to Tables 1 and 2 mitted, some functions still tend to run better offline
(used with permission from GomputeuTalk) as you read during peak network congestion times in an organization.
this chapter. These figures contain an extensive evaluation As bandwidth increases, this problem may diminish.
of the current information systems market. The importance of integration between systems is quite
high. Historically, pharmacy departments purchased
point-to-point interfaces at a cost of $1500 to $15,000
T each. Interfaces are now more popular and often are more
cost-effective for an organization. So important is the
Decision-makers now have an interesting array of hard- functioning of these interfaces that many pharmacists
ware options with which to manage the data processing for wear pagers that alert them when an interface has gone
pharmacy operations. Clientherver architecture is still the down. This occurs automatically as pages are sent from
dominant means of configuration, but Application Service the information technology systems as problems are
Providers (ASPS) are expected to be utilized more as both identified. Another interface consideration is the ability to
information technology (IT) professionals and corporate remotely address problems such as these. Programs that
executives begin to understand what these services offer. allow system access and control from any computer in the
As pharmacists have moved from the central pharmacy world are becoming normal. Of course, firewall protec-
into satellite pharmacies, home care, and other modalities tion from unwanted intruders is necessary in all aspects of
that demand a mobile solution, other hardware must be data management, including remote access.
considered for a total solution. Initially, pharmacists em- Telecommuting presents unique opportunities and
ployed the use of notebook computers that operated offline challenges for the health system and the pharmacy
for data storage and retrieval. These devices were limited department, especially. As the pharmacist shortage con-
because they did not provide real-time access to the health tinues, with one pharmacy chain reportedly building
system’s information system. Then, progressive hospitals enough stores to hire every pharmacy school graduate for
began to develop the necessary infrastructure and to con- the next ten years, new approaches to practice must be
nect these devices wirelessly. More recently, however, explored. Telecommuting will be one response to this
enough resources have been developed in the PDA (per- shortage, bringing the work to the worker. When work can
sonal digital assistant) market to have this platform con- be brought to the worker instead of bringing workers to the
216 Computer Software for Clinical Pharmacy Services
162 Pharmex i -
I I I I I I
Computer Software for Clinical Pharmacy Services 217
Footnotes
- ! - 1 F r i a based 01 transactic-s
2 1n:Iudes scff;+;rs ana succort
17
includes conrsrsicn
a,
Computer Software for Clinical Pharmacy Services 219
work, new and unique hardware challenges will be pre- of simply ignoring them. System oversight for monitoring
sented. Bandwidth to the home represents one of the great- the potential of medication error should occur throughout
est challenges for telecommuting. Services such as DSL the process, beginning with point-of-prescribing through
and cable modems offer potential solutions to this band- point-of-administration. Bar codes and other technologies
width problem. Productivity gains as high as 30 percent will be needed to facilitate this process.
are reported as an incentive for investigation of this area.
DOCUMENTATION
If one asks the question. “What is my computer supposed It has been said, “If you didn’t document it, you didn’t
to be doing when I’m providing pharmaceutical care?” do it.” In the litigious environment in which we live,
the answer will not only describe the appropriate hardware documentation is paramount to professional survival.
or device that matches the needs of the professional Without documentation, reimbursement can be chal-
providing the care, but should also describe the optimal lenged. Personnel reductions are almost assured without
software that will support the provision of pharmaceutical documentation to demonstrate the impact of clinical
care. We define the point-of-care as the place where a services. Without documentation, unnecessary redund-
pharmacist provides pharmaceutical care to a patient or ancies and events will be exacerbated.
assists a colleague (pharmacist, physician, or nurse) in the Ideally, documentation should occur as a natural by-
provision of care. Many kinds of software available on the product of rendering care to patients. In these times where
market today focus solely on transaction processing, with the integration of care (care management) is being sought,
minimal decision support available through prospective the ability of clinical software to access and populate a
drug utilization review (DUR) modules. clinical data repository is a key evaluation criterion.
Because the clinical environment demands real-time or Increasingly, integration with clinical practice protocols
near-real-time decisions, a different kind of computer is facilitating more effective and more comprehensive
support is required. Pharmacy is like other healthcare delivery of care. A major question is, “Will the patient and
disciplines in that we face the problem of having large the profession of pharmacy be best served by accessing,
volumes of information but a lack of information services on a read/write basis, an electronic medical record that is
that are able to translate this information into better out- seen by all other disciplines, or should pharmacists to
comes for patients.r21A clinical practitioner requiring de- continue to have a pharmacy-specific software solution?”
cision support wants this support to be presented in a It may be mission critical to the profession for phar-
succinct manner that facilitates a timely response to the macists to gain or maintain read/write privileges where
problems routinely encountered in his or her practice. all pharmaceutical care contributions can be viewed by
Specific characteristics of successful decision-support all caregivers. Additionally. pharmacists will need to be
systems include the provision of patient-specific recom- able to access diagnosis, laboratory, and other charted in-
mendations, delivery of measurable time savings, and formation such as demographics on a common medical
seamless integration into the daily work activities of the record. Thus, at a minimum, it will be necessary for all
clinical ~ e t t i n g . ‘ ~
Documentation
] should occur as a by- pharmacy software to be able to be integrated into the
product of the interactions between clinical practitioners electronic medical records as they emerge.
and their patients or clients. Access to patient records Orthopedics has recognized the importance of meas-
should not only be provided instantaneously through uring outcomes in terms of quality-adjusted life-years in-
electronic means, but the ability to customize the infor- stead of length of implant survival.‘21Similarly, pharmacy
mation provided into a format desired by the individual must implement software documentation solutions that
practitioner should be allowed. When pharmacokinetic facilitate outcomes monitoring beyond cost savings.
calculations are required, known demographic values Software is needed with the ability to calculate, in a cost-
such as body weight or serum creatinine levels should be benefit analysis, the clinical impact of pharmacist inter-
prepopulated into calculation variables. ventions as they affect therapeutic, financial, and hu-
Clinicians will often desire to examine historical data or manistic outcomes. The current array of products could be
use relevant references, or primary or secondary literature better integrated into documentation software to facilitate
sources. The software design should include these aspects tabulation of these data. With the power of the Internet to
at a minimum. When prospective drug utilization review manipulate data in a dynamic database, it would even be
flags are presented, false positive warnings should be possible for hospitals to compare their outcomes on a local,
minimal to prevent practitioners from getting in the habit regional, or national basis. Furthermore, the database could
Computer Software for Clinical Pharmacy Services 221
be utilized to gain new insights into additional interven- Thus far we have only focused on patient care clinical
tions that could be implemented by clinical personnel. software. An increasingly important alternative focus
would include population-based patient management.
Some health systems call this care management, and it is
largely a nursing-involved activity. Because pharmacists
use automation to a greater degree than other healthcare
disciplines, it is possible to generate a clinical data repo-
Distribution software has had many years to evolve and sitory revolving around drug-related problems in a timelier
improve. Software that supports the provision of phar- manner than is possible with a total system approach. Data
maceutical care is still maturing. The provision of mining of this repository can yield significant manage-
pharmaceutical care is a process. Whether this provision ment information resources on both a strategic and tactical
occurs in a community, health system, long-term care fa- level. Selection of clinical software should never ignore
cility, or other pharmacy practice setting, there is a pro- this population-based aspect of data analysis. Although
cess that underlies each practice. The practice of phar- pharmacist involvement in this area is currently not as
maceutical care begins with the appraisal of the patient. widespread as it could be, there are many opportunities
Based on the findings of that appraisal, the pharmacist available for expansion.
will perform one or several interventions. Having do-
cumented an intervention, the pharmacist will then need
to evaluate the outcomes of these interventions. Once
the desired outcomes have been achieved and documen-
ted, a suitable follow-up and monitoring schedule should
be established. There are several complementary computer applications
Software that supports this process to the highest degree that deserve mention. Part of the difficulty associated with
should be sought, identified, evaluated, purchased, and the increased documentation necessary from pharmacy can
through user feedback, enhanced continually. The best-of- be alleviated, in part, through the use of continuous speech
class clinical software available helps pharmacists assure recognition applications. This chapter was authored using a
that an efficient, comprehensive, and cost-effective ren- speech recognition program, which allowed the authors to
dering of pharmaceutical care is provided. Excellent phar- speak at 160 words per minute with about 99 percent
maceutical care software will be evidence-based in all accuracy. It recognizes medical vocabulary and will allow
aspects of support, including practice protocols and de- the user, after only a five-minute training session, to speak
cision support tools. Due to the importance of financial directly into any Windows-based program.
outcomes, multiple aspects of care provision would be Other applications that should be considered for in-
covered by these applications, including n;edications, tegration involve access to tertiary literature sources
nondrug therapies, steps for prevention, lifestyle issues, directly from the clinical application. The purpose of
and alternative medicine. The software would also include information is to reduce uncertainty. The ability for the
suggested outcomes to be measured and appropriate pharmacist to access and validate decisions based on
scheduling considerations. evidence found in the literature is an important skill and
Ideally. clinical software should help prompt practi- a necessary requirement for clinical software support.
tioners through the provision of the care process. Au- This kind of support can be provided in palm-top form,
tomatic to-do lists will assure consistency in care provision. from network resources, and as intranet applications.
Integration with all other aspects of the management and A movement is underway in medicine and nursing that
distribution side of pharmacy practice must be assured so will allow a concept known as just-in-time continuing
that the coordination of care within a pharmacy operation is education to become mainstream. When pharmacists need
assured. Prospective drug utilization review assets and to access reference information while solving a clinical
succinct decision-support resources should be internalized problem, it is appropriate that this activity be accredited
within the software to minimize the necessity of using as continuing education. When pharmacists accumulate
multiple applications for every problem-solving exercise. one hour of this continuing education activity, a posttest
Again, measurement of the potential impact for phar- would be offered at a convenient time. A score of 75
maceutical care interventions should be done as a by- percent would result in 0.1 CEUs being awarded.
product of rendering care. This means that as a pharmacist Currently. WebMD is providing credit to physicians
uses clinical software the application deductively calcu- who use its Web site to keep up with current issues in
lates potential calamities that were averted and dollar medicine. Pharmacists will be the focus of a similar effort
savings that were attained. if funding permits.
222 Computer Software for Clinical Pharmacy Services
replies, “Oh, you must have seen our demo.” One of the
first recommendations we make is, during an evaluation
of a piece of software, stop allowing the salesperson to
Even though patients distrust the implications surrounding show you the “power path” way their software can solve
their medical records being available electronically, the all of your problems. Each salesperson knows the best set
benefits for this movement should outweigh the potential of circumstances to show off all of the unique features
risks. There are currently 14 layers of technology to help available from an application.
ensure privacy, security, and confidentiality of the medi- We recommend, instead, that you build a matrix
cal records of patients. Encryption, user tracking, bio- whereby you will place competing systems in rows on the
metric authentication. and other measures make it pos- matrix and place all of the features and benefits offered by
sible, beyond a reasonable certainty, to give patients the each system in the columns of the matrix. Next, devise a
assurance necessary for them to sign an informed consent rating system where 3 would equal excellent, 2 would
document allowing their records to be online. The basis equal moderately available, 1 would equal minimally
for moving forward in this effort will be founded on the available, and 0 would equal missing. A simple priority
trust relationship between individual practitioners and system can help weight each feature by a priority to the
individual patients. pharmacy operation. A calculation using feature score and
Research based on widespread use of electronic feature weight would help create a selection of the most
medical records in three British hospitals has demon- powerful application, with the greatest score identifying
strated that these records can be practical while ensuring the most suitable system from those compared. Subject-
patient privacy. The first step taken was to develop an ive assessments of user-friendliness, screen designs, and
access control list to identify which individual caregivers number of keystrokes necessary to perform the most
are responsible for a patient, and therefore, can access his/ common tasks can be similarly evaluated.
her records. The system also documents all occasions In clinical applications, the best recommendation for
when a record is accessed, whether or not information in it testing available applications would be to use a case-
was modified. As not all caregivers will be acknowledged based methodology. We recommend that five or six
as providing care to a particular patient, certain users are complicated cases, which would represent a cross section
given override privileges that allow them to access of the patient population served by the pharmacy, be used
records when the system is not aware that they are, to test the application. In this way, the clinician will see
indeed, providing care to this patient. The user is warned how the application performs throughout an entire care
that his actions are being documented when this override process and avoid the power path demonstration. In this
procedure is used. The ability to collate enterprise-wide information age, selecting clinical software is an ex-
clinical data has posed a problem in this system. When tremely important task. The explosion of capabilities of-
caregivers want to gather data on a specific condition, fered by the Internet can make the selection process both
they are only able to gather information on those patients exciting and confusing. A careful analysis of options will
under their care. This is an acknowledged limitation of usually be rewarded by better results, but wary buyers
this current system. It is important to note that in the five need to prepare themselves to revisit the marketplace
years this system has been in use, no patients have more frequently than they might have in the past to iden-
requested a report of all accesses of their record.[41Again, tify innovative alternatives.
trust in caregivers translates into trust for the electronic
medical record.
EN
The purpose of this paper is to create a common frame of “Credentialing in Pharmacy” has been created by the
reference and understanding for discussions concerning Council on Credentialing in Pharmacy (CCP), a coalition
pharmacist credentialing. It begins with definitions of se- of 1 1 national pharmacy organizations founded in 1999 to
veral terms that are essential to any discussion of cre- provide leadership, standards, public information, and
dcntialing. This is followed by a short section highlighting coordination for professional voluntary credcntialing
thc importance of credentialing to pharmacists. The next programs in pharmacy. Founding members of the CCP
three sections, which form the body of the paper, discuss include the following organizations:
in detail the thrcc types of credentials that pharmacists
may earn: e Academy of Managed Care Pharmacy.
American Association of Colleges of Pharmacy.
Credentials needed to prepare for practice (ix., aca- 0 American College of Apothecaries.
demic degrees). American Collcge of Clinical Pharmacy.
Credentials needed to enter practice (i.e., licensurc) e American Council on Pharinaceutical Education.
and to update professional knowledge and skills (i.e., 0 American Pharmaceutical Association.
relicensure) under statc law. 0 American Society of- Consultant Pharmacists.
Credentials that pharmacists voluntarily earn to American Society of Health-System Pharmacists.
document their specialized or advanced knowledge 0 Board of Pharmaceutical Specialties.
and skills (i.e., postgraduate degrees, certificates, 8 Commission for Certification in Geriatric Pharmacy.
certification). 0 Pharmacy Technician Certification Board.
standings, one must first distinguish between processes specialized, area of the total discipline. Certification
(e.g., credentialing) and titles (a credential). Distinctions usually requires initial assessment and periodic reas-
must also be made between processes that focus on indi- sessments of the individual’s qualifications.
viduals (e.g., credentialing and certification) and those
that focus on organizations (accreditation). Finally, it is
essential to understand that for practicing pharmacists,
some credentials are required (e.g.. an academic degree
or a state license), while others are earned voluntarily
(e.g., certification). “Credential’ ‘ and “credentialing,” like the words
Beyond these distinctions, it is also necessary to “creed” and “credence,” derike from the Latin verb
understand the definitions of the words that commonly credere, which means “to trust,” “to entrust,” or “to
come up in discussions of credentialing and to be able to believe.” A pharmacist’s credentials are indicators that he
distinguish the sometimes subtle differences among them. or she holds the qualifications needed to practice the
A comprehensive glossary of such words and their de- profession of pharmacy and is therefore worthy of the
finitions appears in Appendix A. The following defini- trust of patients, of other health care professionals, and of
tions are provided here, because an understanding of these society as a whole.
terms is a prerequisite to any meaningful discussion of In the profession of pharmacy, the interest in creden-
credentialing in pharmacy. tials has been catalyzed in recent years by several factors.
First among them is the pace of change and the increasing
A credential is documented evidence of a pharmacist’s complexity of health care. A second factor is the pharma-
qualifications. Pharmacist credentials include dip- cist’s expanding clinical role. Interest in credentialing has
lomas, licenses, certificates, and certifications. These likewise been stimulated by the growing trend toward spe-
credentials are reflected in a variety of abbrevia- cialization in pharmacy practice and by the need to do-
tions that pharmacists place after their names (e.g., cument the pharmacist’s ability to provide specialty care.
Pharm.D. for ”doctor of pharmacy,” an earned aca- Another contributing factor has been the need to help
demic degree; R.Ph. for “registered pharmacist.” ensure lifelong competence in a rapidly changing, tech-
which indicates state licensure; and acronyms such as nologically complex field. The need to provide a means of
BCNSP for “Board-Certified Nutrition Support Phar- standardization of practice has also had a role. Such a
macist,” which indicates that an individual has de- motivation was key, for example, to the development of
monstrated advanced knowledge or skill in a spe- the Federal Credentialing Program. which is creating a
cialized area of pharmacy). national database of health professionals that will in-
Credeiztialing is the process by which an organization clude pharmacists.
or institution obtains. verifies, and assesses a pharma- Finally, economic realities enter the picture. Pharma-
cist’s qualifications to provide patient care services. cists who are providing cognitive services or specialized
Accreditatiori is the process by which a private asso- care need to be reimbursed for the services they provide.
ciation. organization, or government agency, after ini- Payers rightfully demand validation that pharmacists are
tial and periodic evaluations, grants recognition to an qualified to provide such services. Credentials, and in
organization that has met certain established criteria. many cases, more specifically, certification, can help
A certificate is a document issued to a pharmacist provide the documentation that Medicare and Medicaid,
upon successful completion of the predetermined level managed care organizations, and other third-party payers
of performance of a certificate training program or of a require of pharmacists today and in the future.
pharmacy residency or fellowship.
A statement of continuing education credit is a do-
cument issued to a pharmacist upon participation in an
accredited continuing education program.
Certification is a voluntary process by which a nongov-
ernmental agency or an association grants recognition Pharmacist credentials may be divided into three fun-
to a pharmacist who has met certain predetermined damental types:
qualifications specified by that organization. This for-
mal recognition is granted to designate to the public a The first type-college and university degrees-is
that this pharmacist has attained the requisite level of awarded to mark the successful completion of a
knowledge, skill, or experience in a well-defined, often pharmacist’s academic training and education.
Credentialing in Pharmacy 225
a The second type-licensure and relicensure-is an a Credential awarded by: School or college of phar-
indication that the pharmacist has met minimum re- macy.
quirements set by the state in which he or she intends Accreditation body f o r professional progrums in phar-
to practice. macy: American Council on Pharmaceutical Educa-
0 The third type of credential-which may include ad- tion (ACPE). The U S . Department of Education has
vanced degrees and certificates-is awarded to phar- recognized the ACPE accreditation of the professional
macy practitioners who have completed programs of degree program in pharmacy.
various types that are intended to develop and enhance
their knowledge and skills, or who have successfully Until July 1, 2000, an individual who wished to be-
documented an advanced level of knowledge and skill come a pharmacist could enroll in a program of study that
through an assessment process. would lead to one of two degrees: a bachelor of science
degree in pharmacy (B.S.Pharm. or Pharm.B.S.) or a
These three paths to pharmacist credentialing are il- doctor of pharmacy (Pharm.D.) degree.
lustrated in Fig. l . The sections that follow provide in- As of 1998, two-thirds of all students studying in
formation on each of the credentials offered in pharmacy, professional programs in pharmacy were enrolled in
the credentialing or accreditation body involved, whether Pharm.D. programs. The Pharm.D. degree became the
the credential is mandatory or voluntary, and other rela- sole degree accredited by ACPE for pharmacists'
ted information. entry into practice in the United States, as of July 1,
2000, with the institution of new ACPE professional
program accreditation standards. Pharm.D. programs
typically take six years to complete and generally
0 Credential earned: Bachelor of Science degree in involve two years of preprofessional coursework and
Pharmacy; Doctor of Pharmacy degree. four years of professional education. A few programs
ractic
Pharmacists Relicensure
(State Boards and NABP)
Continuing Education programs (ACPE*)
Doctor of Pharmacy
(Pharm.D.) Degree (ACPE*) Licensure
Usual Format: Education (Optional)
(State Boards of Additional Education &Training (optional)
2 yr pre-pharmacy
4 yr pharmacy Pharmacy and Advanced degrees
NABP*) M.S.
Non-traditional option for BS Ph.D.
graduates Training
Residency (ASHP)
Traineeship (ASHP*)
Fellowship (ACCP' AACP")
Certificate programs (ACPE*)
Continuing Education programs (ACPE*)
Certification (optional)
Specialty (BPS*)
Non-specialty (CCGP*)
Disease management (NISPC')
Multidisciplinary(various*)
Technicians
EducationiTraining
(ASHP*)
Fig. 1 U.S. pharmacy credentials and oversight bodies. (*Oversight bodies are described in text.)
226 Credentialing in Pharmacy
offer the professional education over three years of full- forcing uniform standards for the purpose of protecting
time education. the public health. The NAPLEX and MPJE examina-
B.S. level pharmacists who have been in the workforce tions are administered by appointment, daily, through-
may also return to a college or school of pharmacy to earn out the year, at a system of test centers located in all
the Pharm.D. degree. These programs, which are tailored 50 states.
to the individual’s background and experience, may fol- In addition to the NAPLEX and MPJE, some states
low “nontraditional” pathways; however, they must pro- require a laboratory examination or an oral examination
duce the same educational outcomes as does the entry- before licensure is conferred. All state boards also require
level Pharm.D. degree. that candidates complete an internship before being li-
State boards of pharmacy require a Pharm.D. or B.S. censed. The internship may be completed during the can-
degree from a program approved by the boards (almost didate’s academic training or after graduation, depending
always an ACPE-accredited program) for a candidate to upon state requirements.
be eligible to take the state licensing examination. A list- State licensure is an indication that the individual has
ing of accredited professional programs offered by col- attained the basic degree of competence necessary to
leges and schools of pharmacy is published annually by ensure the public health and welfare will be reasonably
the ACPE, and is available on the ACPE web site (www. well protected. The names of individuals who have
acpe-accredit.org) . received a license may use the abbreviation “R.Ph.” (for
“registered pharmacist”) after their names.
Nearly all state boards of pharmacy also require that
Entering Practice and Updating Professional registered pharmacists complete a certain number of
Knowledge and Skills continuing education units (CEUs) before they can renew
their licenses. The CEUs must be earned through par-
4 Crederztials earrzed: Licensure as registered pharma- ticipation in a continuing education (CE) program whose
cist (R.Ph.); relicensure. provider has been approved by the American Council on
e Credential awarded by: State board of pharmacy. Pharmaceutical Education (ACPE). The symbol used by
0 Licensure process overseen by: State regulatory the American Council on Pharmaceutical Education to
authorities. designate that the continuing education provider is ap-
postgraduate education and training opportunities. They A fellowship is an individualized postgraduate pro-
include the following: gram that prepares the participant to become an inde-
pendent researcher. Fellowship programs, like residencies,
Academic postgraduate education and training usually last one to two years. The programs are developed
by colleges of pharmacy, academic health centers, col-
Pharmacists who wish to pursue a certain field of study leges and universities, and pharmaceutical manufacturers.
in depth may enroll in postgraduate master‘s or doctor There is no official accreditation body for fellowship
of philosophy (Ph.D.) programs. Common fields of programs; however, the American Association of Col-
study for master’s candidates include business admin- leges of Pharmacy and American College of Clinical
istration, clinical pharmacy, and public health. Common Pharmacy have issued guidelines that are followed by
fields for Ph.D. studies include pharmacology. pharma- many fellowship program directors.
ceutics, pharmacy practice, and social and administra-
tive sciences. Certificate Training Programs
Role delineation. The first step is to define the area in Pharmacists who wish to retain BPS certification must
which certification is to be offered. This is done be recertified every seven years.
through a process called role delineation or “task The recognition of each specialty is the result of a
analysis.” An expert panel of individuals in the pro- collaborative process between the Board and one or
posed subject area develops a survey instrument to more pharmacy organizations, which develop a petition
assess how practitioners working in the area rate the to support and justify recognition of the specialty.
importance, frequency, and criticality of specific ac- This petition must meet written criteria established by
tivities in that practice. The instrument is then sent to a the BPS.
sample of pharmacists who are practicing in that field. The BPS is directed by a nine-member board that
Development of content outline. On the basis of re- includes six pharmacists, two health professionals who
sponses to the survey, a content outline for the certi- are not pharmacists, and one publickonsumer member. A
fication program is developed. specialty council of six specialist members and three
Preparation of examination. The written examination pharmacists not in the specialty direct the certification
component of the certification program is developed process for each specialty.
on the basis of the content outline. BPS examinations are administered with the assistance
Other activities. Appropriate measures are taken to of an educational testing firm, resulting in a process that is
ensure that security and confidentially of the testing psychometrically sound and legally defensible. Each of
process are maintained, that the examination and eli- the five specialties has its own eligibility criteria, exa-
gibility criteria are appropriate, and that the knowledge mination specifications, and recertification processes. All
Credentialing in Pharmacy 229
five examinations are given on a single day once a year in ease-specific examinations as the consistent and objective
approximately 25 sites in the United States and elsewhere. means of documenting the ability of pharmacists to pro-
In 1997, BPS introduced a method designed to re- vide disease state management services.”
cognize focused areas within pharmacy specialties. A NISPC offers certification in the management of di-
designation of “Added Qualifications’ ’ denotes that an abetes, asthma, dyslipidemia, and anticoagulation ther-
individual has demonstrated an enhanced level of training apy. At the time of its founding, the organization’s im-
and experience in one segment of a BPS-recognized spe- mediate objective was to design a process that would
cialty. Added qualifications are conferred on the basis of a document the competence of pharmacists providing care
portfolio review to qualified individuals who already hold for patients with these disease states. The NISPC cre-
BPS certification. The first added qualification to receive ential was first recognized in the state of Mississippi,
BPS approval was infectious diseases, within the pharma- where it was used to enable pharmacists to qualify for
cotherapy specialty. Medicaid reimbursement as part of a pilot project in that
state. The NABP developed the competency assessment
Commission for Certification in Geriatric Pharmacy examinations and oversees their administration. As of
(CCGP). In 1997, the American Society of Consultant June 2002, 1340 pharmacists hold NISPC certification:
Pharmacists (ASCP) Board of Directors voted to create 771 in diabetes, 314 in asthma, 120 in dysiipidemia, and
the CCGP to oversee a certification program in geriatric 135 in anticoagulation therapy.
pharmacy practice. CCGP is a nonprofit corporation that The NISPC tests are administered nationally as com-
is autonomous from ASCP. It has its own governing puterized examinations and are available throughout
Board of Commissioners. The CCGP Board of Commis- the year.
sioners includes five pharmacist members, one physician
member, one payer/employer member, one publickon- Multidisciplinary certification programs
sumer member, and one liaison member from the ASCP
Board of Directors. Some certification programs are available to professionals
Pharmacists who meet CCGP’s requirements are from many health disciplines, including pharmacists.
entitled to use the designation Certified Geriatric Phar- Areas in which such certification programs are available
macist, or CGP. As of June 2002, approximately 800 include diabetes education, anticoagulation therapy, pain
pharmacists have earned the CGP credential. Pharma- management, and asthma education. Some of these pro-
cists who wish to retain their CGP credential must re- grams are still in the early stages of development. Several
certify every five years by successfully completing a writ- of these providers are listed in Appendix B; however, the
ten examination. information is not intended to be exhaustive.
CCGP contracts with a professional testing firm to
assist in conducting the role delineation or task analysis
and in developing and administering the examination. The e
resulting process is psychometrically sound and legally
defensible; it also meets nationally recognized standards. A pharmacy technician is an individual who assists in
The CGP certification exams are administered twice a pharmacy activities that do not require the professional
year at multiple locations in the United States, Canada, judgment of a pharmacist. For example, pharmacy tech-
and Australia. CCGP publishes a candidate handbook that nicians may accept orders from patients, prepare labels,
includes the content outline for the examination, eligib- enter drug information into the pharmacy’s computer sys-
ility criteria for taking the examination, and the policies tem, and retrieve medications from inventory. As phar-
and procedures of the certification program. macists assume an increasing number of clinical roles,
pharmacy technicians are taking more and more re-
National Institute for Standards in Pharmacist Creden- sponsibility for distributive functions in pharmacies in
tiding (NZSPC). The NISPC was founded in 1998 by all settings.
the American Pharmaceutical Association, the National The exact functions and responsibilities of pharmacy
Association of Boards of Pharmacy (NABP), the National technicians are defined by state laws and regulations and
Association of Chain Drug Stores, and the National are also determined by the willingness of pharmacists to
Community Pharmacists Association. The purpose of delegate the nonjudgmental activities of their practice.
NISPC is to “promote the value and encourage the adop- Pharmacy technicians always work under the supervision
tion of National Association of Boards of Pharmacy dis- of a licensed pharmacist.
230 Credentialing in Pharmacy
Competency: A distinct skill, ability, or attitude that Scope of practice: The boundaries within which a
is essential to the practice of a profession. Individual health professional may practice. For pharmacists, the
competencies for pharmacists include, for example, scope of practice is generally established by the board
mastery of aseptic technique and achievement of a or agency that regulates the profession in a given state
thought process that enables one to identify therapeutic or organization.
duplications. Pharmacists must master a variety of
~ t ~ t e ~ of
e ncontinuing
t education credit: A doc-
competencies in order to gain competence in a profession.
ument issued to a pharmacist upon completion of a
Continuing education: Organized learning experi- continuing education program provided by an organiza-
ences and activities in which pharmacists engage after tion approved by the American Council on Pharmaceuti-
they have completed their entry-level academic education cal Education.
and training. These experiences are designed to promote
Traineeship: A short, intensive, clinical, and didac-
the continuous development of the skills, attitudes, and
tic postgraduate educational program intended to provide
knowledge needed to maintain proficiency, provide
the pharmacist with knowledge and skills needed to pro-
quality service or products, respond to patient needs,
vide a high level of care to patients with specific diseases
and keep abreast of change.
or conditions.
Credential: Documented evidence of professional
qualifications. For pharmacists, academic degrees, state
licensure, and Board certification are all examples
of credentials.
Gredentialing: 1) The process by which an organ-
ization or institution obtains, verifies, and assesses a phar-
macist’s qualifications to provide patient care services;
Pharmacy organizations
2) The process of granting a credential (a designation
that indicates qualifications in a subject or an area.)
Academy of Managed Care Pharmacy (AMCP)
Fellowship: A directed, highly individualized post- 100 North Pitt Street, Suite 400; Alexandria, Virginia
graduate program designed to prepare a pharmacist to 22314; (800) 827-2627
become an independent researcher. www .amcp.org
License: A credential issued by a state or fede- American Association of Colleges of Pharmacy
ral body that indicates that the holder is in compli- (AACP)
ance with minimum mandatory governmental require- 1426 Prince Street; Alexandria, Virginia 223 14-2841;
ments necessary to practice in a particular profession (703) 836-8982
or occupation. www .aacp.org
Pharmacists have contributed to our understanding of error rate was 3.3% (187 of 5744 observations), which is
the needs of the critically ill patient through descriptive lower than previously reported. The majority of the
reports characterizing patterns of drug utilization. In errors caused no harm, but some required additional
surgical and trauma patients, an average total of 7.6 and patient monitoring or intervention. Other errors were
9.1 medications per patient were reported, respective- related to omission of doses or administration at an in-
ly.[4951These data reaffirm reports that a growing number correct time. Critical care pharmacists observed these
of medications are used in ICU patients, from an average medication errors during their routine daily activities.
of 4.2 to 7 rt 4.6 drugs per patient in general I C U S . [ ~ In
,~] The presence of these trained specialists may have in-
1988, the pharmacoeconomic impact of the large number fluenced the number and type of errors. The process in
of medications used in surgical ICU patients was sig- this report differs from prior observational studies where
nificant, averaging 13.6% of total hospital charges.['] a trained observer recorded medication administration
Hazards of these complex drug therapy regimens are practices and recorded errors. However, calculation of
becoming well documented. Concern with medication er- infusion rates was identified as an area for potential
rors is a frequent topic in the medical and lay literature."] quality improvement.
A general adult ICU reported that a medication error was
made in more than 50% of the patients, but the overall
error rate was low, detected in 2.2% of the doses dis-
pensed or administered."'] However, this unit reported a
generous 1:1 nurse-to-patient ratio and relied on a retro- Pharmacists have developed specialty practices in every
spective medical record review to detect errors. Current facet of critical care and emergency medicine. These in-
staffing patterns with 1:2 or 1:3 nurse-to-patient ratios are clude burn, cardiac care, cardiovascular surgery, medical,
becoming more common and may adversely affect error neurological, neurosurgical, renal, respiratory, surgical,
frequency. Higher rates have been detected in other stu- trauma, and pediatric and neonatal critical care. Pediatric
dies, due to differences in the definition of an error and specialty units in the same areas may also have pharma-
the method of detection. New therapies and technologies cists dedicated to those units. Descriptive reports of their
may increase the risk of critical errors.["] The ability of contributions to these units have been p ~ b l i s h e d . [ ' ~ - ~ ~ ]
the pharmacist to reduce medication errors and adverse Although many of these practitioners work for larger
drug events has been reported.[12' Pharmacists participat- hospitals or have academic appointments, there is a grow-
ing on physician rounds on a part-time basis were shown ing number of pharmacists focusing on critical care pa-
to decrease all adverse drug events and, in particular, to tients in smaller hospitals. In 1989, a survey of hospitals
decrease preventable adverse drug events by 66%."'] The with >lo0 beds demonstrated that 34% of medium-size
pharmacist primarily detected prescribing errors such as hospitals had pharmacy satellites, as did 61% of large
incomplete orders, incorrect doses or frequency, and the- hospitals.[241 The majority (76%) of pharmacists who
rapy duplication; however, the pharmacist also avoided staffed these satellites held BS degrees. However, one-
inappropriate drug selection. Alternative therapies were third of the pharmacists spent more than 50% of their
recommended that were safer (avoided a drug interaction day providing clinical services. Hopefully, this level of
or allergy) or less expensive. Participation of a pharmacist pharmacist involvement has been maintained or has
in the medication ordering process in a teaching hospital grown since the early 1990s. Although not a complete
appears to be essential to avoid prescribing errors. measure, the number of critical care pharmacists who are
Pharmacists have used avoidance of medication errors members of SCCM has grown progressively from approx-
to justify expanding services. A pediatric critical care sa- imately 80 in the early 1990s to the current number of
tellite was opened to reduce the rate of errors from a total more than 450 pharmacist members. It is hoped that this
of 17.4% in an intensive care nursery and 38% in a pe- reflects a larger number of specialty practitioners in cri-
diatric ICU."31 A large number of the errors (86.5%) oc- tical care.
curred with medications possessing a high potential for The majority (63.2%), of critically ill patients are cared
serious adverse consequences. for in hospitals without full-time or consultative intensi-
Avoidance of medication administration errors is ano- vi~ts.''~]Patients are more likely to be cared for by their
ther potential contribution of critical care pharmacists. A primary physician or a single or multiple consultants
multicenter analysis of medication errors from five ICUs (pulmonary or cardiology), although hospitalists are be-
revealed that medication errors occurred most commonly coming more available to care for ICU patients (internal
with vasoactive agents and ~edative-analgesics.['~~ Incor- medicine specialists who care for hospitalized patients
rect infusion rate was the most common error. The overall full-time). An intensivist is a physician who is board
Critical Care Pharmacy Practice 235
certified in critical care but may have received their initial difficult to accomplish in complex patients where nume-
medical training in medicine, surgery, anesthesia, or pe- rous factors can influence outcome, but is essential to the
diatrics. Board certification is achieved through the integration of novel therapies and improved utilization of
subspecialty organizations after completion of a written existing agents.
examination. The SCCM model of critical care is that of Critical care pharmacists have also been active in the
an intensivist-led multidisciplinary team. An organized area of collaborative disease-state management and qua-
critical care team has been a predictor of improved patient lity improvement projects, and have documented the im-
care.[261Despite the apparent benefit of the intensivist-led pact of these on patient outcome. Pharmacists often take a
team, workforce projections predict a significant man- leadership role in these efforts. Examples of the impact of
power shortfall by 2020, due to a relatively constant these programs include reductions in the use of laboratory
supply but an increasing demand for critical care ser- cost saving through improved antibiotic uti-
v i c e ~ . [Critical
~ ~ ] care pharmacists may have increasing lization,"sl improved utilization of sedative and neuro-
opportunities to affect the care of these patients as a result muscular blocking a g e n t ~ , [ ~ limproved
-~~I monitoring of
of this imbalance. sedation, and avoidance of adverse drug
Training in critical care research is available through
fellowships cosponsored by the pharmaceutical industry
CH IN C R I ~ I C A LCARE through organizations such as SCCM and ACCP, as well
as through a number of clinical training centers.
There are many challenges to performing research in a
critically ill patient. Informed consent may be difficult to
obtain if there is a narrow window for therapy initiation. K ~ O W L ~ D
BASE
~ E
The ICU population may have numerous other injuries or
organ dysfunction that would disqualify the patient. Fi- Although critical care is considered a specialty area, there
nally, an adequate number of patients may be difficult to is a challenge to define the body of knowledge encom-
recruit. As a result, animal research models have been used passed by this field. Critical care patients as a whole are a
by critical care pharmacists to develop the framework for very heterogeneous group. As a result, many institutions
clinical trials and control the large number of patient va- provide care for a more homogenous group of patients in
riables present in a critically ill patient. geographically distinct units. Whether these patients are in
Numerous avenues exist for critical care research.
Critical care pharmacists have contributed to the under-
standing of pharmacotherapy of multiple disease states
Table 1 Important components of critical care pharmacist
and organ systems. Evaluation of pharmacokinetics and
knowledge base for adult and pediatric patients
pharmacodynamics in the critically ill patient has faci-
litated the design of therapeutic regimens in these com- Pharmacokinetic alterations in the critically ill
plicated patients. For example, the variations in hepatic Analgesia, sedation, neuromuscular blockade
metabolic rate following head trauma or hemorrhagic Cardiovascular pathology and therapeutics
shock have been c h a r a c t e r i ~ e d However,
. ~ ~ ~ ~ ~ much
~ ~ ad- Endocrine pathology and therapeutics
ditional research is needed to further characterize the im- Gastrointestinal pathology and therapeutics
Hemodynamic monitoring/manipulation
pact of changes in organ function on phannacokinetics in
Hepatic pathology and therapeutics
this complex and heterogeneous population.
Hematologic pathology and therapeutics
Clinical case reports of unusual treatments or response Infection control/antimicrobial therapy
to therapy have presented a plethora of questions that Inflammatory injury/multiple organ system dysfunction
remain to be answered. Case series and descriptions of Neurological pathology and therapeutics
experience with treatment protocols or the impact of Nutritional support
pharmacist interventions are useful contributions to the Patienthentilator interface
literature. Evaluation of economics and outcomes has Psychiatric therapeutics
been an important area of research in critical care. The Renal pathology and therapeutics
critically ill patient patient typically receives a large Respiratory pathology and therapeutics
number of different and often expensive medications, and Resuscitation therapeutics
Shock and related problems
is monitored with expensive devices. Pharmacists have
Thrombosis/hemostasis and therapeutics
characterized various aspects of the cost of care, although
Toxicologic therapeutics
comprehensive pharmacoeconomic outcome research is
236 Critical Care Pharmacy Practice
a specialty unit or a general ICU, the critical care prac- standing the cardiovascular system and therapeutics is
titioner must focus on a variety of complex patient prob- another fundamental portion of a critical care pharma-
lems and therapeutic areas (Table I). cists' knowledge base. In addition, expertise in the resus-
Understanding the potential pharmacokinetic changes citation of patients experiencing an acute cardiac or res-
experienced by critically ill patients is essential for the piratory event is an important skill and knowledge set.
optimal dosing and monitoring of drug therapy in the Pharmacist knowledge of the current guidelines and par-
critically ill patient.[341 Altered organ blood flow, dys- ticipation in cardiopulmonary resuscitation teams is a cli-
function of drug-eliminating organs, and changes in fluid nical pharmacy service shown to be associated with re-
compartment volumes often dictate the need for indivi- duced hospital
dualized approaches to drug d o ~ i n g . [ ~ Pharmacists
~-~~] Disease-specific therapies and other fundamental com-
are ideally trained to provide comprehensive therapeutic ponents of the knowledge-base required to practice as a
drug monitoring and optimize expenditures for serum critical care specialist is outlined in the ASHP require-
drug concentration^.'^^] ments for critical care residency training.[441In addition to
Universal concern with the comfort of the patient re- direct patient care, the critical care resident should receive
quires knowledge of analgesics and sedatives. Guidelines training or experience in drug information and drug policy
have been published to guide the optimal use of these development, practice management. and participate in the
agents.'391These therapies must be prescribed in a manner management of drug distribution systems in the critical
that does not adversely affect the respiratory status of the care setting.
patient and, in many cases, is used to facilitate adequate There are currently 21 critical care residencies listed in
ventilation of patients with acute lung injury. An under- the ACCP 2001 Guide to Residencies and Fellowships.
standing of lung injury and mechanical ventilation is es- Eight of these residencies are accredited by the ASHP. In
sential. Use of pharmacologic agents to induce paralysis addition, 11 critical care fellowships are available.[451
may be an essential part of this care for some patients.[401
Prevention of common adverse events such as stress-rela-
ted gastrointestinal bleeding and deep venous thrombosis I ClSTS
requires knowledge of the gastrointestinal and coagulation
systems and therapeutics. Nutrition support consultation Critical care pharmacists have demonstrated numerous
is also provided by critical care pharmacists in many set- contributions to the cost-effective care of ICU patients.
tings. Critically ill patients may be highly catabolic and Pharmacist initiated interventions in a 1200-bed teaching
optimal provision of macro- and micronutrients may en- hospital were demonstrated to lower the drug costs by
hance their recovery. Proper application of immune-en- 41% compared with a control group (mean $73.75 vs.
hancing nutrients has added complexity to the nutritional $43.40: p < 0.001).'461Approximately, fifty percent of the
support of critically ill patients. 259 patients were in critical care units. The majority
Critically ill patients are at high risk for a variety of (79%) of the interventions over the 30-day trial period
nosocomial infections. Knowledge of infection control were aimed at improving the quality of care, whereas the
techniques, as well as proper use of prophylactic and remaining 2 1% were to provide equivalent care at a lower
empiric antibiotics, is an important component of critical cost. There was no impact on length of stay or readmis-
care pharmacy practice. Inappropriate antibiotic use can sion rates, but there was a trend toward lower hospital
lead to antimicrobial resistance and outbreaks of nosoco- mortality in the intervention group.
mial infection that are difficult to treat with conventional Similarly, a multidisciplinary performance improve-
therapies. Critical care pharmacists work with infection ment team that included a pharmacist established a series
control staff and infectious disease pharmacists to opti- of patient care protocols and tested the impact on the costs
mize the use of antimicrobial therapies. of care and outcome.[301 Protocols were developed that
The hemodynamic stability of patients is another uni- eliminated many standing orders for laboratory tests,
versal concern for critical care pharmacists. Patients with electrocardiograms, and chest x-ray films. Other protocols
cardiac diseases or postcardiac surgery are obvious candi- were directed toward the use of sedatives, analgesics,
dates for inotropic and vasoactive therapy (vasopressors neuromuscular blocking agents, and ventilator weaning.
and vasodilators). However, patients of all ages with se- The outcome and costs from a baseline evaluation of 72
vere injury. sepsis, or the systemic inflammatory response patients were compared with 85 patients in the follow-up
syndrome require vigorous resuscitation with fluids and phase. Application of the guidelines reduced costs for
vasoactive agents. Guidelines have been written to guide laboratory tests by 65%, and the number of chest x-rays
the management of these challenging patients.[411Under- were reduced by 56%. The cost of neuromuscular block-
Critical Care Pharmacy Practice 237
ers was reduced by 75%. In addition, the length of ICU Table 2 Selected critical care pharmacist activities
stay and duration of mechanical ventilation were reduced.
Fundamental
There was no change in mortality. If these results can be Dedicated ICU pharmacist providing pharmaceutical care
extrapolated to a larger population and maintained, signi- Order evaluation and intervention
ficant economic and outcome benefits could be realized. Adverse drug event and medication error management
Another publication from this same group focused on the and prevention
impact of guidelines for the use of analgesics, sedatives, Documentation of impact
and neuromuscular blocking agents in the same popu- Medication use policy implementation and support
lati~n.‘~’]The pharmacist was involved in protocol
development, education and implementation, and ongoing Desirable
intervention when practice did not meet guidelines. A Rounding with the critical care team
Medication history review
reduction of direct drug costs, ventilator time, and length
Resuscitation response
of stay were accomplished by using the protocol. Phar-
Education of pharmacy students and residents
macists have demonstrated similar results using sedation Implements and evaluates drug therapy protocols or pathways
protocols elsewhere.[481 Participates in clinical research
Others have shown a positive impact of critical care
pharmacists. A clinical pharmacist working part-time (dai- Optimal
ly rounds, average 10 hours per week) in a medical ICU Formal and informal education of the critical care team
over 8 weeks demonstrated a net benefit of $101 per Advanced cardiac life support education
day, considering cost avoidance, cost savings, increased Residency or fellowship development
drug costs, and the pharmacist’s salary.[491Although the Conducts research and presents and publishes findings
medical ICU was unable to increase staffing levels to (From Ref. 1511.)
maintain this service, they redistributed pharmacist and
technician workloads to perpetuate the clinical activities.
Similarly, a clinical pharmacist with 50% teaching res-
ponsibility was assigned to participate in daily work participation in quality improvement activity. At a higher
rounds with the (medical-surgical patients) critical care level of practice, the desirable activities additionally in-
team for 13 weeks.[501 A cost saving using drug costs clude critical care-specific pharmacotherapeutic services.
only (no personnel costs) was $69.11 per patient day. Additional desirable activities may include rounding with
Inclusion of personnel costs, for an average of 3 hours a critical care team, review of medication histories, par-
per day, did not negate the cost benefit. High-cost drugs ticipation in resuscitation events, student and resident
were targeted, so it may be difficult to maintain this education, protocol development, participation in re-
level of cost savings once the prescribing habits are mo- search, and outcome analysis. At the highest level, the
dified or as protocols are implemented. optimal activities of a critical care pharmacy specialist
include provision of education to families, pharmacists,
and physicians, development of research protocols, new
pharmacy services, and publication of the results of these
ONGOING ~ H A L L E N ~ E S programs. A single pharmacist cannot provide all these
services, but rather should function within a team to meet
A focal point for critical care pharmacists and hospitals these goals.
with critical care units is a position paper on critical care A similar model is used to present the recommended
pharmacy services jointly developed and published by levels of service and personnel from a pharmacy depart-
ACCP and SCCM.[”j This paper identifies and describes ment and hospital per~pective.[~” Fundamental service
the fundamental, desirable, and optimal activities that includes the use of patient profiles, provision of ‘‘ready to
define the scope of practice of the critical care pharmacist administer” medications and parenterals, and adequate
(Table 2 ). Fundamental activities are deemed vital to the quality improvement programs. Desirable pharmacy ser-
safe provision of pharmaceutical care to the critically ill vices include computerized information management sys-
patient. The fundamental responsibilities of critical care tems and an ICU satellite. Optimal pharmacy department
pharmacists include a full-time commitment to critical services include a 24-hour satellite, physician order entry,
care patients, evaluation of all drug therapy, identification and continuous availability of pharmaceutical care ser-
of adverse events, individualized drug dosing, provision vices. This document challenges practitioners and ins-
of drug information, documentation of activities, and titutions to measure their progress and strive for the deli-
238 Critical Care Pharmacy Practice
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17. Herfindal, E.T.; Bernstein, L.R.; Kishi, D.T. Impact of
clinical pharmacy services on prescribing on a cardiotho-
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t't IARMACY PRACTICE ISSlJ ES
merica
I<ans,,s City, Mmouri, U.S.A.
creased responsibility for monitoring patient outcomes as macist as clinician, educator, researcher, and
well as supervising drug distribution service^.'^] manager.
Pharmacists have demonstrated a role in the manage- 2. To recommend levels of service and personnel
ment of drug costs and reductions in morbidity and mor- requirements for the provision of pharmaceutical
t a l i t ~ . [ ~19]
, ~Clinical
,~- pharmacy services such as clinical care to critically ill patients. The levels will be
research, provision of drug information, drug admission defined as fundamental, desirable, or optimal.
histories, and participation on a cardiopulmonary resusci-
tation (CPR) team have been associated with reduced
mortality." 'I Prospective, controlled trials demonstrated METHODS
that when pharmacists assume responsibility for pharma-
cotherapy as part of a multidisciplinary health care team, The Task Force on Critical Care Pharmacy Services con-
significant reductions in adverse drug events (ADEs) and sisted of members from the Clinical Pharmacy and
length of stay are realized."2-'61 Many of these findings Pharmacology Section of the Society of Critical Care
have been documented in specialized critical care popu- Medicine and the Critical Care Practice and Research
lations."4-201 The ACCP estimates that a benefit of Network of the ACCP. Members of the task force were
$16.70 is realized for every $1.00 invested in clinical from institutions of various sizes and they provide critical
pharmacy program^."^] A landmark study involving cri- care services within a variety of pharmacy practice mod-
tical care pharmacists confirmed that pharmacist rounding els. Practitioners from both community-based and aca-
in the ICU with the multidisciplinary team reduces pre- demic practice settings were included.
ventable ADEs and associated costs caused primarily by The formulation of these recommendations, including
prescribing errors."61 Pharmacist intervention during pre- discussion and development of consensus, took place be-
scribing decreased the rate of preventable ADEs by 66% tween October 1997 and September 1999. Task force
from 10.4 to 3.5/1000 patient-days ( p < 0.001). Pharma- members were charged with developing graded para-
cist involvement was categorized as drug order clarifica- meters within six domains: clinical activities, drug distri-
tion (45%), provision of drug information (25%), and re- bution, education, research, documentation, and admin-
commendations for alternative therapy (12%). Based on an istration. This article was organized into pharmacist
estimated cost of $4685/preventable ADE, the annualized activities and pharmacy services. Drafts were reviewed
financial impact in the unit studied would be $270,000 and evaluated by all members of the task force, and a
(1995 dollars). consensus was reached. When differences in opinion were
Despite the growing evidence supporting the critical expressed, they were resolved using a modified Delphi
care pharmacist's contribution to patient care, many ICUs method.[211The document was reviewed externally by
have not taken full advantage of this vital resource."'] A three established leaders in critical care pharmacy and by
description of pharmacy services and pharmacist activities 18 pharmacy and hospital administrators for appropriate-
in a critical care setting will assist practitioners and ad- ness of categorization of pharmacy activities and services.
ministrators in establishing or advancing these specialized The article was further reviewed by select members and
pharmacy services. This article may be used to educate the governance of both the Clinical Pharmacy and Phar-
other health care providers, administrators, and devel- macology Section of the Society of Critical Care Medi-
opers of health care policy on the role of pharmacists and cine and the Critical Care Practice and Research Network
pharmacy services in the care of the critically ill. Fur- of the ACCP. Before organizational endorsement, the
thermore, the application of the elements in this article will article underwent internal review by both the Council of
allow researchers to further document the effect of critical the Society of Critical Care Medicine and the Board of
care pharmacy services on improving patient outcomes. Regents of the ACCP.
Existing guidelines and literature for pharmacy prac-
tice and drug use processes were reviewed and adapted for
the critical care ~ e t t i n g . [ ~ The
, ~ ~needs
- ~ ~ ]of hospitals with
comprehensive resources as well as those with more li-
This article identifies and describes the scope of phar- mited resources were considered. The task force created
macy practice of the critical care pharmacist and critical three gradations of pharmacist responsibilities and depart-
care pharmacy services. Specifically, the aims of the Task mental services as fundamental, desirable, and optimal.
Force on Critical Care Pharmacy Services were: Classification of the elements into each category was the
result of the consensus process. For the purposes of this
1. To define the level of clinical practice and spe- article, the following definitions were used. Fundamental
cialized skills characterizing the critical care phar- activities are vital to the safe provision of pharmaceutical
242 Critical Care Pharmacy Services (ACCP)
care to the critically ill patient. Desirable activities include hospitals of varying resources to optimize the delivery of
fundamental activities and critical care-specific pharma- pharmaceutical care to the critically ill. It is expected that
cotherapeutic services. Optimal activities encompass the these recommendations will continue to be reviewed at
range of fundamental to desirable services and, addition- intervals of approximately 5 years as critical care phar-
ally, reflect an integrated. specialized, and dedicated mod- macy services, clinical pharmacy, and critical care medi-
el of critical care that aims to optimize pharmacothera- cine evolve.
peutic outcomes through the highest level of teaching,
research; and pharmacotherapy practice. Fundamental ser-
vices should not be interpreted as an acceptable minimum
level of service. Each institution and practitioner continu-
ally should strive for the highest level of service possible.
A single pharmacist cannot perform all the funda-
mental activities on all patients every day. Rather, these 1. The pharmacist’s time is dedicated to critical care
critical care pharmacy activities will require varying lev- patients, with few commitments outside the ICU
els of involvement from multiple pharmacists and trained area.
technicians acting as a team, along with support from 2. The pharmacist prospectively evaluates all drug
pharmacy and hospital administrators, and other person- therapy for appropriate indications, dosage, drug
nel. The exact allocation of labor and the pharmacist-to- interactions, and drug allergies; monitors the
patient ratio will vary by institution and depend on the patient’s pharmacotherapeutic regimen for effec-
level of care, the acuity of patients, and the degree of tiveness and ADEs; and intervenes as needed.
specialization of the institution. 3. In conjunction with the clinical dietitian, the
“The pharmacist,” as used herein, refers to the team pharmacist evaluates all orders for parenteral nu-
of licensed pharmacy practitioners with specialized trition and recommends modifications as indi-
training or practice experience focusing on the unique cated to optimize the nutritional regimen.
characteristics and needs of critically ill patients. Al- 4. The pharmacist identifies ADEs and assists in
though various practice models exist, the pharmacist their management and prevention, and develops
practices within the framework of a multidisciplinary process improvements to reduce drug errors and
team. In collaboration with other members of the patient preventable ADEs.
care team. pharmacists share the responsibility for patient 5 . The pharmacist uses the medical record as one
care outcomes, not just by providing basic dispensing means to communicate with other health care
functions and drug information services, but by solving professionals and to document specific pharma-
patient- and drug-related problems and by making de- cotherapeutic recommendations.
cisions regarding drug prescribing, monitoring, and drug 6. The pharmacist provides pharmacokinetic mon-
regimen adjustment^."^' The pharmacist’s practice may itoring when a targeted dmg is prescribed.
integrate varying elements of patient care, teaching, and 7 . The pharmacist provides drug information and
research activities, depending on the nature of the ins- intravenous compatibility information to the ICU
titution and the pharmacist’s training. team and uses the regional poison information
The task force recognizes the varied educational back- center when indicated.
grounds of practicing critical care pharmacists. Having 8. The pharmacist maintains current tertiary drug
the qualifications and competence necessary to provide references.
pharmaceutical care in the ICU is essential and may be 9. The pharmacist provides drug therapy-related
achieved by a variety of means including advanced de- education to ICU team members.
grees: residencies, fellowships or other specialized prac- 10. The pharmacist participates in reporting ADEs to
tice experiences. institutional committees and to the Food and
The term pharmacy and hospital services refers to Drug Administration’s MedWatch program.
departmental and institutionaUorganizationa1 components 11. The pharmacist documents clinical activities that
of the infrastructure that support the pharmacist’s activi- include, but are not limited to, disease state man-
ties. They consist of systems, operations, and personnel agement, general pharmacotherapeutic monitor-
who facilitate and support the provision of patient care, ing, pharmacokinetic monitoring, ADEs, educa-
teaching, and research to optimize safe and effective tion, and other patient care activities.
pharmaceutical care of the critically ill. 12. The pharmacist acts as a liaison between phar-
This article is not intended to be a standard of practice; macy, nursing, and the medical staff to edu-
however, we envision that it will serve as a guideline for cate health professionals regarding current drug-
Critical Care Pharmacy Services (ACCP) 243
related procedures. policies, guidelines, and 7 . The pharmacist participates in training pharmacy
pathways. students, residents, and fellows through expe-
13. The pharmacist contributes to the hospital news- riential critical care rotations, where applicable.
letters and drug monographs on issues related to 8. The pharmacist coordinates the development and
drug use in the ICU. implementation of drug therapy protocols andlor
14. The pharmacist implements and maintains de- critical care pathways to maximize benefits of
partmental policies and procedures related to safe drug therapy.
and effective use of drugs in the ICU. 9. The pharmacist uses a documentation program
15. The pharmacist collaborates with nursing, medi- that attaches both a clinical significance and an
cal staff, and hospital administration to prepare economic value to clinical interventions.
the ICU for the Joint Commission on the Accre- 10. The pharmacist is actively involved in critical
ditation of Healthcare Organizations (JCAHO) care pharmacotherapy research by assisting in the
survey and responds to any deficiencies identified. screening and enrollment of patients and by
16. The pharmacist provides consultation to hospital serving as a study coordinator or contact person,
committees, such as Pharmacy and Therapeutics, where applicable.
when critical care pharmacotherapy issues are 11. The pharmacist participates in research design
discussed. and data analysis, where applicable.
17. The pharmacist identifies how drug costs may be 12. The pharmacist contributes to the pharmacy and
minimized through appropriate use of drugs in medical literature, e.g., case reports, letters to
the ICU and through implementation of cost- the editor, and therapeutic, pharmacokinetic, and
containment measures. pharmacoeconomic reports.
18. The pharmacist participates in quality assurance 13. The pharmacist is involved in nonpatient care
programs to enhance pharmaceutical care. activities including multidisciplinary committees
and educational in-services.
Desirable Activities
Optimal Activities
1. The pharmacist regularly makes rounds as a
member of the multidisciplinary critical care team 1. The pharmacist assists physicians in discussions
(if available) to provide pharmacotherapeutic with patients andlor family members to help
management for all ICU patients. make informed decisions regarding treatment
2. The pharmacist maintains knowledge of current options.
primary references pertinent to critical care phar- 2. The pharmacist provides formal accredited edu-
macotherapy. cational sessions, such as medical grand rounds
3. The pharmacist reviews a patient’s drug history or intensive care rounds, for medical staff, stu-
to determine which maintenance drugs should be dents, and residents.
continued during the acute illness. 3. The pharmacist participates in teaching advanced
a. The pharmacist clarifies previously effective cardiac life support.
dosages and dosage regimens. 4. The pharmacist develops residencies and/or
b. For all suspected drug-related ICU admis- fellowships in critical care pharmacy practice.
sions, the pharmacist assesses the patient 5. The pharmacist develops and implements phar-
drug history for causality and documents in macist and pharmacy technician training pro-
the medical record any findings that will grams for personnel working in the ICU.
impact patient management. 6. The pharmacist identifies and educates lay
4. In collaboration with the clinical dietitian, the groups and medical personnel in the community
pharmacist provides formal nutrition consultation about the role of pharmacists as part of the mul-
on request and responds within 24 hours. tidisciplinary health care team in the ICU.
5 . The advanced cardiac life support-certified (or 7. The pharmacist independently investigates or
pediatric advanced life support-certified) phar- collaborates with other critical care practitioners
macist responds to all resuscitation events in the to evaluate the impact of guidelines and/or pro-
hospital 7 dayslweek, 24 hourslday. tocols used in the ICU for drug administration
6. The pharmacist provides didactic lectures to and management of common disease states.
health professional students in critical care phar- 8. The pharmacist uses pharmacoeconomic analyses
macology and therapeutics, where applicable. to prospectively evaluate existing or new phar-
244 Critical Care Pharmacy Services (ACCP)
Task force members were Maria I. Rudis, Pharm.D., 9. Bond, C.A.; Raehl, C.L.; Pittele, M.E., et al. Health care
University of Southern California, LOS Angeles, CA professional staffing, hospital characteristics, and hospital
(Chair); Henry Cohen, Pharm.D., Long Island University, mortality rates. Pharmacotherapy 1999, 19, 130- 138.
10. Chuang, L.C.; Suttan, J.D.; Henderson, J.P. Impact of the
New York, NY; Bradley E. Cooper, Pharm.D., Hamot
clinical pharmacist on cost saving and cost avoidance in
Medical Center, Erie, PA; Luis S. Gonzalez, 111,
drug therapy in an intensive care unit. Hosp. Pharm. 1994,
Pharm.D., Conemaugh Medical Center, Erie, PA; Erkan 29, 215-221.
Hassan, Pharm.D., FCCM, University of Maryland, 11. Bond, C.A.; Raehl, C.L.; Franke, T. Clinical pharmacy
Baltimore, MD; Christian Klem, Pharm.D., Tampa services and hospital mortality rates. Pharmacotherapy
General Healthcare, Tampa, EL; Vanessa L. Kluth-Land, 1999, 19, 556-564.
Pharm.D., SmithKline Beecham Pharmaceuticals, HQW 12. Bjornson, D.C.; Hiner, W.O.; Potyk, R.P., et al. Effect of
ton, TX; Katherine M. Kramer, Pharm.D., University of pharmacists on health care outcomes in hospitalized pa-
New Mexico, Las Cruces, NM; Angela M. Swerlein, tients. Am. J. Hosp. Pharm. 1993. 50, 1875-1884.
Pharm.D., GrantRiverside Methodist Hospitals, Colum- 13. Boyko, W.L.; Yurkowski, P.J.; Ivey, M.F., et al. Phar-
bus, OH; Julie Ann Whippel, Pharm.D., Waukesha macist influence on economic and morbidity outcomes in a
tertiary care teaching hospital. Am. J. Health-Syst. Pharm.
Memorial Hospital, Waukesha WI. At the time of manu-
1997, 54, 1591-1595.
script preparation, Dr. Kluth-Land was at Hermann HQS-
14. Kelly, W.N.; Meyer, J.D.; Flatley, C.J. Cost analysis of a
pital, Houston, TX. satellite pharmacy. Am. J. Hosp. Pharm. 1986. 43, 1927-
1930.
15. Smythe, M.A.; Shah, P.P.: Spiteri, T.L.. et al. Pharmaceut-
ical care in medical progressive care patients. Ann. Phar-
macother. 1998, 32, 294-299.
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and personnel: Recommendations based on a system of in the intensive care unit. JAMA 1999. 282, 267-270.
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1999. 27, 422-426. evaluations of clinical pharmacy services-1988- 1995.
2. Dasta, J.F.; Jacobi, J. The critical care pharmacist: What Pharmacotherapy 1996, 16, 1188- 1208.
you get is more than what you see. Crit. Care Med. 1994, 18. Matuszewski, K.A.; Vlasses, P.H. Survey results from
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standard and learning objectives for residency training in ventions on drug therapy costs in a surgical intensive care
critical care pharmacy practice. Am. J. Hosp. Pharm. 1990, unit. Am. J. Hosp. Pharm. 1986, 43, 3008-3113.
47, 609-612. 21. Dalkey, N.C. The Delphi Method: An Experimental Study
5. Society of Critical Care Medicine. Directory of Critical of Group Opinion; Rand Corporation: Santa Monica,
Care Residencies and Fellowships. In Clinical Pharmacy California, 1969.
and Pharmacology Section; Society of Critical Care 22. Joint Commission on the Accreditation of Healthcare
Medicine: Anaheim, California, 2000. Organizations. Standards for Hospitals; JCAHO: Chicago,
6. American College of Clinical Pharmacy. Directov of Illinois, 1998.
Residencies and Fellowships; American College of Clin- 23. American Pharmaceutical Association. Pharmacy Practice
ical Pharmacy: Kansas City, Missouri, 2000. Activity Classification; APhA: Washington, DC, 1998.
7. American College of Clinical Pharmacy Practice Affairs 24. Anonymous. Over-reliance on pharmacy computer sys-
Committee. Practice guidelines for pharmacotherapy spe- tems may place patients at great risk. ISMP Med. Saf.
cialists. Pharmacotherapy 200 Alert. 1999, 4. 1, Available from: http:/,’www.ismp.org/
8. Hatoum, H.T.; Hutchinson, R.A.; Witte, K.W., et al. MSArticles/Computer.html.
Evaluation of the contribution of clinical pharmacists: 25 American College of Clinical Pharmacy. Collaborative
I
Inpatient care and cost reduction. Drug Intell. Clin. Pharm. drug therapy management by pharmacists. Pharmacothe-
1988, 22, 252-259. rapy 1997, 17, 1050-1061.
PHARMACY PRACTICE ISSUES
avi
Universily of Iowa, Iowa City, Iowa, U.S.A
Table 1 Major CYP enzymes, their substrates, inducers, inhibitors, and phenotype markers
Representative
Enzyme substrates Known inducer Inhibitor Polymorphism Noninvasive test marker
"There are no conclusive evidences between genotype and phenotype, although some phenotype or genotype differences are detected in the population.
same medication. Many factors involve this inter- and levels, and therapeutic response in an individual patient is
intrapatient variability of drug response. The recom- largely determined by the catalytic activity of single
mended dose of each therapeutic agent is determined enzyme, CYP2D6. For example, patients with the poor
based on clinical study results from a small number of metabolizer phenotype for CYP2D6 demonstrate sig-
patients who meet a narrowly defined criteria. However, nificantly high area under the plasma concentration time
the optimal daily dose in clinical practice can vary widely curve for metoprolol, compared with extensive meta-
among patients because of factors such as age, size of the bolizers of CYP2D6.[12] As a result, poor metabolizers
patient, gender, ethnicity, concurrent drug therapy, food generally attain therapeutic effects from these drugs at
intake, and the patient's own disease conditions (i.e., renal significantly reduced daily doses. If the same dose as a
function o r liver function)."'] It should be noticed that rapid metabolizer is given, the patients will develop se-
each individual patient has his or her own optimal dose of vere toxicity.
drug therapy in a specific clinical condition. Because the The activity of CYP3A varies at least 10-fold among
CYP is an important enzyme system for various drug patients, and the activity level in a given patient appears
classes, large differences in the activities of the CYP to be related to the dosing requirements of a certain
among individuals explain some of this wide variability in substrate metabolized by CYP3A.['32'41It has been shown
the dosing requirements of various drugs."'] that the liver activity of CYP3A largely predicts blood
Most drugs are metabolized by multiple metabolic levels of cyclosporine in patients receiving the drug for
pathways, which is necessary because this may protect the treatment of psoriasis;['31 that is, patients with higher
body from the toxic effects of drugs in case one metabolic CYP3A activity have lower blood levels of cyclosporine
pathway is shut down. However, in certain cases, single at any given daily dose of the d r ~ g . " ~ . ' ~ ]
enzyme activity largely determines drug response. For There are significant differences in CYP enzyme
example, the therapeutic effect of the drug may be activities in the general population. which are mainly
correlated with the blood levels of the parent drug, and determined by genetics, although some environmental
this may depend largely on the rate of metabolism of factors such as enzyme inducers or inhibitors are
the drug catalyzed by a single CYP. Although it is not involved. One of the best known CYP enzyme inducer
always true, there are now at least several important is cigarette smoking, which generally induces CYPlA2
examples in which the relation between drug dose, blood and other CYP enzyme^.['^,^^] In a certain population,
248 Cytochrome P450
there is genetically a lack of CYP genes (i.e., CYP2C19, induced or inhibited by, and involved in the oxidation of,
CYP2D6), and these populations may develop significant a number of currently used drugs, they are likely to be
toxicity if the standard dose of a drug with a narrow responsible for numerous drug interactions in humans.12]
therapeutic index is given. Because CYP3A4 metabolizes more than 50% of all
therapeutic agents, its inhibitors and inducers have
significant impact. Clinically important CYP3A4 inhibi-
YP tors include ketoconazole, itraconazole, erythromycin,
clarithromycin, nefazodone, ritonavir, and grapefruit
jUiCe.[23241
The CYP is present not only in the liver, but also in the Torsades de pointes, a life-threatening ventricular
intestine. It appears that the CYP is located mainly at the arrhythmia associated with QT prolongation, can occur
apex of the mature enterocytes, lying in a band just below when these inhibitors are coadministered with terfena-
the microvillous border.['s1 In humans, the major dine, astemizole, or cisapride because they inhibit these
enterocyte CYP appears to be the CYP3A4, which agents from converting the parent compound into
accounts for more than 70% of CYP activity in the nontoxic, pharmacologically active metabolite^.[^^-^^]
intestine. Interestingly, CYP3A4 is located along with P- As a result, the proarrhythmic parent compound ac-
glycoprotein, a cell membrane efflux pump."'] This may cumulates in the body, which causes toxic effects.
indicate that CYP3A4 along with P-glycoprotein are Because of this serious drug interactions, these drugs
intended to prevent the environmental toxins, or xeno- have to be withdrawn from the market. Cyclosporine, an
biotics such as drugs, from entering the body. The important immunosuppressant, has clinically been
intestinal metabolism of many lipophilic drugs metabo- shown to be involved in multiple drug interactions.[231
lized by CYP3A4 is estimated to be as much as one-half Because cyclosporine is extensively metabolized in
of the administered dose.[201 Previously, many CYP human liver and enterocytes by CYP3A4, any inducer
inhibitors were thought to act only on liver CYP enzymes, of CYP3A4 (e.g., ripampin) should cause a decrease in
but it was found that they affect on both liver and cyclosporine levels, whereas any substrate or inhibitor
intestinal CYP.['93201 For example, ketoconazole, which is (e.g., ketoconazole) of this CYP should elicit the
a potent inhibitor of CYP3A4, increases area under the opposite effect. Indeed, this has been clearly demon-
curve of cyclosporine not only by inhibiting hepatic strated clinically[2s1 as well as in an experimental
CYP3A4, resulting in reducing metabolism of cyclospor- model. [291
ine, but also inhibiting intestinal CYP3A4, subsequently Some drugs with multiple metabolic pathways are
increasing bioavailability of cyclosporine.[211Some food affected by many different inhibitors. For example, co-
components such as grapefruit juice inhibit CYP3A in the deine is metabolized by CYP2D6 and CYP3A4, which act
intestine and, when oral felodipine is given with on different sites of action.[301 The 0-demethylation of
grapefruit juice, its AUC and Cmax are increased by codeine is catalyzed by CYP2D6 and N-demethylation is
250% and 150%,[221respectively. However, when intra- catalyzed by CYP3A4.[311The substrates of CYP2D6,
venous felodipine is given with grapefruit juice, there is such as thioridazine, amitriptyline, and metoprolol inhibit
no significant difference.[221 the 0-demethylation of codeine preferentially,[301whereas
substrates of CYP3A4, such as ketoconazole, are strong
inhibitors of the N-demethylation of codeine.[311
Not all predicted drug interactions are expected to
be clinically significant. For example, nifedipine and
cyclosporine are both CYP3A4 substrates, but there is
Drug interactions constitute a major problem in chronic no clinically important drug interaction noticed.[231 To
multiple drug therapy.[231Although interactions affecting predict the drug interaction, several parameters are
the pharmacodynamics of a drug can be reasonably pre- expected to be important. These include notably:[321
dicted (i.e., additive effect or synergistic effect), those 1) relative affinity of CYP enzyme on both drugs (km);
affecting its pharmacokinetics are difficult to predict. 2) dose and local concentration of each drug either in
These might result from various contributions involving enterocytes or hepatocytes; 3) duration of concurrent
absorption, transportation, distribution, metabolism, and therapy; and 4) CYP enzyme in the liver or intestine
excretion.[231Among these, metabolism in liver as well as of the patient. The level of CYP3A is highly variable
intestine appears to represent the major source of drug- in each individual. It is possible that, in one patient
drug interactions. Because CYP enzymes are known to be with a low CYP3A level, all the cytochrome would
Cytochrome P450 249
be saturated by the coadministered drugs, but not in activity.[411In the near future, genotyping information
another with higher CYP3A level: the consequence is regarding individual CYP will be readily available,
that the interaction should occur in the former but not which may better explain individual variability of drug
the latter. pharmacokinetics and pharmacodynamics.
test as a predictor of cyclosporine blood levels. Clin. 29. Wang, R.W.; Newton, D.J.; Liu, N.; Athns, W.M.; Lu,
Pharmacol. Ther. 1990, 48, 120-129. A.Y.H. Human cytochrome P-450 3A4: in vitro drug-drug
15. Turgeon, D.K.; Normolle, D.P.; Leichtman, A.B.; Annes- interaction patterns are substrate-dependent. Drug Metab.
ley, T.M.; Smith, D.E.; Watkins, P.B. Erythromycin breath Dispos. 2000, 28 (3), 360-366.
test predicts oral clearance of cyclosporine in kidney 30. Dayer, P.; Desmeules, J.; Leemann, T.; Striberni, R.
transplant recipients. Clin. Pharmacol. Ther. 1992, 52, Bioactivation of the narcotic drug codeine in human liver
471 -478. is mediated by the polymorphic monooxygenase catalyzing
16. Nakachi, K.; Imai, K.; Hayashi, S.-I.; Watanabe, J.; debrisoquine 4-hydroxylation of debrisoquine. Biochem.
Kawajiri, K. Genetic susceptibility to squamous cell car- Biophys. Res. Commun. 1988, 152, 411-416: 30.
cinoma of the lung in relation to cigarette dose. Cancer 31. Pellinen, P.; Honkakoski, P.; Stenback, F.; Niemitz, M.;
Res. 1991, 51, 5177-5180. Alhava, E.; Pelkonen, 0.;Lang, M.: Pasanen, M. Codeine
17. Nebert, D.W. Role of genetics and drug metabolism in N-demethylation and the metabolism-related hepatotoxi-
human cancer risk. Mutat. Res. 1991, 247, 267-281. city can be prevented by cytochrome P450 3A inhibitors.
18. Kolars, J.C.; Schmiedlin-Ren, P.: Dobbins, W.O.; Schuetz, Eur. J. Pharmacol., Environ. Toxicol. Pharmacol. Sect.
J.: Wrighton, S.A.; Watkins, P.B. Heterogeneity of 1994, 270, 35-43.
cytochrome P450IIIA expression in rat gut epithelia. 32. De Waziers, I.; Cugnenc, P.H.; Yang, C.S.; Leroux, J.P.;
Gastroenterology 1991, 102. 1186- 1198. Beaune, P.H. Cytochrome P450 isoenzymes epoxide
19. Wacher, V.J.; Wu, C.-Y.; Benet, L.Z. Overlapping hydrolase and glutathione transferases in rat and human
substrate specificities and tissue distribution of cytochrome heaptic and extrahepatic tissues. J. Pharmacol. Exp. Ther.
P450 3A and P-glycoprotein: Implications for drug 1990, 253, 387-394.
delivery and activity in cancer chemotherapy. Molecular 33. Watkins, P.B. Noninvasive tests of CYP3A enzymes.
Carcinogenesis. 1995, 13, 129-134. Pharmacogenetics 1994, 4, 171- 184.
20. Wu, C.-Y.; Benet, L.Z.; Hebert, M.F.; Gupta, S.K.; 34. Lown, K.; Kolars, J.; Turgeon, K.; Merion, R.; Writhton,
Rowland, M.; Gomez, D.Y.; Wacher, V.J. Differentiation S.A.; Watkins, P.B. The erythromycin breath test selec-
of absorption and first-pass gut and hepatic metabolism in tively measures P450IIIA in patients with severe liver
humans: Studies with cyclosporine. Clin. Pharmacol. Ther. disease. Clin. Pharmacol. Ther. 1992, 51; 229-238.
1995, 58, 492-497. 35. Thummel, K.E.; Shen, D.D.; Podoll, T.D.; Kunze, K.L.;
21. Gomez, D.Y.; Wacher, V.J.; Tomlanovich, S.J.; Hebert, Trager, W.F.; Hartwell, P.S.; Raisys, V.A.; Marsh, C.L.;
M.F.; Benet, L.Z. The effects of ketoconazole on the in- McVicar, J.P.; Barr, D.M. Use of midazolam as a human
testinal metabolism and bioavailability of cyclosporine. cytochrome P450 3A probe: I. In vitro-in vivo correla-
Clin. Pharmacol. Ther. 1995, 58. 15-19. tions in liver transplant patients. J. Pharmacol. Ther. 1994,
22. Baily, D.G.; Arnold, M.O.; Munoz, C.; Spence, J.D. 271 (l), 549-556.
Grapefruit juice-felodipine interaction: Mechanism, pre- 36. Lown, K.; Thummel, K.E.; Benedict, P.E.; Shen, D.D.;
dictability, and effect of naringin. Clin. Pharmacol. Ther. Turgeon, D.K.: Berent, S.; Watkins, P.B. The erythromy-
1993, 53, 637-642. cin breath test predicts the clearance of midazolam. Clin.
23. Yee, G.C.: McGuire, T.R. Pharmacokinetc drug interac- Pharmacol. Ther. 1995, 57, 16-24.
tions with cyclosporine. Clin. Pharmacokinet. 1990, 19, 37. Watkins, P.B. Erythromycin breath test and clinical
319-332 and 400-415. transplantation. Ther. Drug Monit. 1996, 18, 368-371.
24. Ku, Y.; Min, D.I.; Flanigan, M. Effect of grapefruit juice 38. Kronbach, T.; Mathys, D.; Umeno, M.; Gonzalez, F.J.;
on microemulsion cyclosporine and its metabolites, M1 Meyer, U.A. Oxidation of midazolam and tnazolam by
and M17 pharmacokinetics in healthy volunteers. J. Clin. human liver cytochrome P450IIIA4. Mol. Pharmacol.
Pharmacol. 1998, 38, 959-965. 1989, 36, 89-96.
25. Honig, P.K.; Worthan, D.C.; Zamani, K.; Conner, D.P.; 39. Krivoruk, Y.; Kinirons, M.T.; Wood, A.J.; Wood, M.
Mullin, J.C.; Cantilena, L.R. Terfenadine-ketoconazole Metabolism of cytochrome P4503A substrates in vivo
interaction: Pharmacokinetic and electrocardiographic administered by the same route: Lack of correlation
consequences. JAMA, J. Am. Med. Assoc. 1993, 269, between alfentanil clearance and erythromycin breath test.
1513-1518. Clin. Pharmacol. Ther. 1994, 56, 608-614.
26. Zechnich, A.D.; Hedges, J.R.; Eiselt-Proteau, D.; Haxby, 40. Kinirons, M.T.; O’Shea, D.; Downing, T.E.; Fitzwilliam,
D. Possible interactions with terfenadine or astemizole. A.T.; Joellenbeck, L.; Groopman, J.D.; Wilkinson, G.R.;
West. J. Med. 1994, 160 (4). 321-325. Wood, A.J. Absence of correlations among three putative
27. Chan-Tompkins, N.H.; Babinchak, T.J. Cardiac arrhyth- in vivo probes of human cytochrome P4503A activity in
mias associated with coadministration of azole compounds young healthy men. Clin. Pharmacol. Ther. 1993, 54,
and cisapride. Clin. Infect. Dis. 1997, 24 (6), 1285-1313. 621 -629.
28. Jensen, C.W.B.; Flechner, S.M.; Van Buren, C.T.; Frazier, 41. Min, D.I.; Ku, Y.; Vichiendilokkul, A,; Fleckenstein, L. A
O.H.; Cooley, D.A.; Lorber, M.I.; Kahan, B.D. Exacer- urine metabolic ratio of dextromethorphan and 3-metho-
bation of cyclosporine toxicity by concomitant adminis- xymorphinan as a probe for CYP3A415 activity and
tration of erythromycin. Transplantation 1987, 43 (2), prediction of cyclosporine clearance in healthy volunteers.
263-269. Phannacotherapy 1999, 19, 753-759.
PROFESSIONAL ORGANIZATIONS
eSSe
Niantic, Connecticut, U.S.A.
maceuticals, biological products, and medical devices.[41 mitted by manufacturers to ensure the claim meets with
This authority to monitor medications and foods was first significant scientific agreement.
granted by Congress with the Food and Drug Act in
1906.r5.61Assuring compliance with this important act re- Centers for Diseas
mains a key function of the FDA.
Since 1906, various amendments to the Food and Drug
Act have greatly influenced the practice of Pharmacy. The roots of the CDC, the agency responsible for
The Sherley Amendment of 1912 was the first legislation protecting health, are traced back to World War 11. At
to regulate the labeling of medications. The amendment that time the Malaria Control in War Areas (MCWA)
mandated a guarantee against adulteration and misbrand- attempted to control the spread of malaria among ser-
ing from manufacturers. vicemen, along with preventing the introduction of the
The Delaney Clause, named for Congressman James disease into the civilian population.[*] After the war, the
Delaney, remains an important part of the 1958 Food Ad- importance of continued monitoring of infectious diseases
ditives Amendment and the 1960 Color Additive Amend- prompted the conversion of MCWA to the Communica-
ments to the Food, Drug, and Cosmetic Act. The clause ble Disease Center in 1946, the predecessor of the mo-
states that “no additive shall be deemed to be safe if it is dern CDC. Today, the CDC monitors disease trends,
found to induce cancer when ingested by man or ani- investigates outbreaks and health risks, fosters healthy
mal’ 151 at any dose. The clause also recognizes and ac- environments, and implements illness prevention mea-
cepts that evidence of carcinogenicity in animals is suf- sures and standards. The research performed by the CDC
ficient to correlate to a risk in man. Examples of the FDA is primarily field research, as compared with the labo-
invoking the Delaney Clause include the removal of ratory research that is performed by the NIH. More than
cyclamates, aminotriazole, and DDT from human food. 7500 employees and $3 billion per year are necessary to
Modernization of the act, to allow for a negligible risk accomplish these goals.
standard, rather than the current zero risk, is currently
being pursued. ealth Services (IHS)
The Kefauver-Harris Amendments of 1962 gave the
FDA control over prescription drug advertising. Accord- Although federally funded health services for Native
ing to the amendment, all advertisements and printed Americans began in the early 19th century, the Transfer
matter issued by a manufacturer must include the medi- Act of 1954 propelled Native American health toward
cation name, strength, side effects, contraindications, and its modern form. This law transferred responsibility for
information on effectiveness. Another major change to the health care of Native American and Alaska Natives to
the act was the requirement that all medications must be the PHS. Soon after the transfer the PHS was directed by
shown to be effective, as well as safe. After this amend- Congress to conduct health surveys of Native American
ment, all new drug applications submitted to the FDA populations. The first study was the Trachoma Study. This
must contain research proving the effectiveness of the study found a widespread trachoma epidemic, along with
product. At that time, control over investigational me- increased incidence of other infectious diseases, includ-
dications and the inspection of factories was also trans- ing tuberculosis, among this population. These results
ferred to the FDA. prompted moves to improve sanitary living conditions
Another amendment to the Food, Drug, and Cosmetic and expand the provision of health care available to
Act is the Nutrition Labeling Health and Education Act Native Americans.
(NLHEA) of 1990. NLHEA is intended to provide Another PHS survey, the Meriam Report, also pushed
consumers with information to help maintain healthy for advances in Native American health care. Among
dietary practices and to protect consumers from unfoun- the Meriam Report findings were that 1 out of 10 Na-
ded health claims. NLHEA provides information to con- tive Americans had tuberculosis and over one-third of
sumers by requiring nutrition labeling on all foods and all Native American deaths were children under 3 years
dietary supplements. These nutrition labels must include of age. These findings prompted moves for stronger
the serving size, and number of servings per package, health program supervision with more qualified staff
along with the amount of calories, fat, saturated fat, and the establishment of health clinics on Native Amer-
cholesterol, sodium, carbohydrates, sugars, dietary fiber, ican reservations.
and total protein per serving. NLHEA also ensures the The findings of all the PHS surveys led to the for-
validity of nutrition claims by reviewing research sub- mation of the current Indian Health Services as the fed-
Department of Health and Human Services 253
era1 agency responsible for providing health services to home health services, hospice care, counseling services,
Native American and Alaska Natives. These services are and housing and transportation assistance. Title 2 of the
currently provided to nearly 1.5 million persons in more CARE Act provides grants to states, Washington, DC,
than 550 federally recognized tribes in 35 states[71with Puerto Rico, and other United States territories to pro-
the goal to assure that comprehensive, yet culturally vide health care to individuals living with HIV and
acceptable, personal and health services are available AIDS. Title 2 is aimed at prolonging life and preventing
and accessible. The IHS currently maintains 36 hos- hospitalization, particularly through assistance with ob-
pitals, 58 health centers, 4 school health centers, and 44 taining medications through the AIDS Drug Assistance
health stations. With the health care provided by the Program. With more than $150 million in funding from
IHS, the Native American life expectancy has increased the CARE Act, the AIDS Drug Assistance Program al-
12 years since 1973,[71with decreased infant and ma- lows states to establish programs to purchase and distri-
ternal pneumonia and influenza, tuberculosis, and gas- bute antiretroviral therapy for low-income individuals.
trointestinal mortality. Despite these advances, IHS The third section of the act, Title 3, provides funds to
continues to work to reduce deaths due to alcoholism, public and nonprofit organizations to support early inter-
accidents, diabetes mellitus, homicide, and suicide. The vention services for low-income, medically underserved
rates of death due to these causes remain significantly people at risk for HIV. These services are designed to
higher in the Native American population than the rest slow the spread of HIV through education, counseling,
of the U.S. population. testing, and early treatment. Title 4 provides grants to
establish services for children, women, and families. In
Health Resources and 1996, Part F was added to the CARE Act to combine
Services Administration (HRSA) other existing AIDS programs under the HRSA umbrel-
la. Included in Part F are AIDS Education and Training
HRSA provides the leadership necessary to achieve in- Centers that train health care providers about the ne-
tegration of service delivery to meet the health needs of cessity of early intervention and appropriate treatment,
Americans. This is done through the provision of per- Dental Reimbursement Programs that provide grants to
sonnel, educational, physical, and financial resources. dental schools to assist in covering costs incurred in
Part of HRSA’s S4.8 billion budget funds more than 3000 providing treatment to HIV patients, and the Special Pro-
health clinics to provide medical care to more than 9 jects of National Significance Program that provides
million individuals in underserved communities each grants to develop models for providing care to persons
year. HRSA also administers the Migrant Health Program, with HIV in special populations.
which provides grants to communities to support cultu-
rally based medical services to migrant and seasonal Substance Abuse and Mental Health
farmworkers and their families. Services Administration (SAMHSA)
Although HRSA administers many diverse programs,
one of the major programs is the Ryan White Compre- Although the Narcotics Division of the PHS (later re-
hensive AIDS Resources Emergency (CARE) Act, named the Mental Hygiene Division) was created in
Public Law 101-381.’s1 The Ryan White CARE Act is 1929 to treat and study addiction, the National Mental
named in memory of an Indiana teenager who increased Health Act of 1946 was the first legislation to authorize
awareness about the needs of people with AIDS while research and aid for mental health services. Starting in
suffering from the disease himself. This act helps states, 1973, this act was administered by the Alcohol, Drug
communities, and families to ease the burden of the Abuse and Mental Health Administration (ADAMHA)
AIDS epidemic. HRSA estimates 500,000 individuals through the National Institute of Mental Health (NIMH),
with HIV and AIDS receive assistance through this act the National Institute of Alcohol and Abuse and Al-
each year.[’] coholism, and the National Institute on Drug Abuse. The
The Ryan White CARE Act is divided into multiple current SAMHSA did not replace ADAMHA until 1992.
parts with each part providing support to different seg- SAMHSA continues ADAMHA’s work to improve the
ment of the AIDS community. The first part of the CARE quality and availability of substance abuse prevention,
Act, Title 1, provides grants to cities and large numbers addiction treatment, and mental health services. The goal
of low-income, underinsured, or uninsured individuals of SAMHSA is to reduce illness, disability, and death,
with HIV and AIDS. These grants are intended to pro- along with the cost to society, which result from sub-
vide outpatient health care, prescription medications, stance abuse and mental illness. SAMHSA is able to
254 Department of Health and Human Services
an Services (0s)
Tom Son
Univrrvly of Georgia College of P h x m x y , Athens, Georgi,j, U.S.A.
form basic nutrition assessments, or educate pa- counseling about some aspect of diabetes. Clinics for
tients on carbohydrate counting and the exchange indigent patients are becoming more common with the
systems of meal planning. They may discuss me- number of working poor increasing. Pharmacists may be
dication adjustments, specifically increases or involved with collaborative practice arrangements with
decreases in insulin dosage, based on blood glucose physicians where medication changes are made based on
readings and the carbohydrate content of the next the pharmacist assessment in some cases. This type of
meal. In-depth discussions about the cause, pre- setting tends to give the pharmacist flexibility to p e r f o m
vention, and treatment of complications of diabetes diabetes education and management services.
may be part of the education provided to patients.
Pharmacists may provide these services by them-
selves or hire a nurse or dietitian to work with them ICIA FIC
through the pharmacy. The creation of educational
rooms where individual and group sessions can Physicians are being overburdened by patient visits and
occur are often created to give the pharmacist, the necessity to follow the Health Plan Employer Data
educators, and patients privacy. By having a nurse and Information Set (HEDIS) and other practice guide-
and dietitians on staff as part- or full-time employ- lines. Pharmacists can perform chart reviews to see if
ees, pharmacists can apply to become American patients with diabetes have received regularly scheduled
Diabetes Association Recognized Outpatient Edu- test for A l C , urinary microalbumin, lipid measurements,
cation Providers and to be subsequently reimbursed referral for dilated eye exams, foot assessment and foot
by medicare for their educational services. care, and blood pressure measurements.
Pharmacists can assist the physician by assessing
clinical outcomes of diabetes, hypertension, thyroid dis-
ACY orders, and lipids, and making recommendations to the
physician about the potential need for adjustments in
Pharmacists can provide diabetes care in the hospital set- medications. Pharmacists can also educate individuals and
ting in several ways. One way is to perform in-services to groups of the physician’s patients on diabetes within the
the nursing and hospital staff on medication used in office setting.
treating diabetes and comorbidities. Which blood pressure
medication should be used in patients with microalbumi-
nuria, and why? Which medications when used in patients TE E
with diabetes can cause an increase or decrease in blood
sugar levels? What contraindications should they look out Some pharmacists are confident in their counseling and
for in patients in the hospital with diabetes? Another way business skills to where they develop their own private
is to actively participate in patient education of inpatients practice. However, in the United States, this is not com-
or outpatients. mon for pharmacists to do and heavily relies on individual
In most instances, pharmacists are relegated to the state’s reimbursement for diabetes education and man-
medication or blood glucose monitor counseling aspect agement services. Services are provided in clinic-type
only. In some hospital programs, pharmacists are the settings, in other pharmacist’s practices, and even over the
diabetes coordinators and perform all areas of adminis- Internet and phone. This area will expand when reim-
tration and patient education. Preparing IVs for patients bursement improves for the provision of these services.
with diabetes undergoing surgery, those admitted with Examples of a few of these services are The Diabetes
diabetic ketoacidosis (DKA), or newly diagnosed patients Center in Connecticut, and Diabetes In Control, which is
are common areas of pharmacist involvement in hospitals. an Internet business.
CLINIC
identification of the signslsymptoms, causes, and treat- outcomes. Pharmacists working for managed care orga-
ments of high and low blood glucose is a basic training nizations may be in decision-making positions that de-
skill that all staff should know, but few do. A written termine the frequency and type of diabetes education that
protocol should be available and accessible to staff. In- particular insurance companies will provide to their card-
services, including medications, blood sugar reading as- holders. Pharmacists that have been involved in diabetes
sessments, and foot and skin care, should be covered care know of the importance of individual assessment and
quarterly with staff and even more frequently in some periodic follow-up to assess maintenance of optimal
homes due to the high turnover rate of staff. It should be therapeutic and personal outcomes. Pharmacists without
included in all new hire training. this background may only look at products and edu-
cational services as a current cost without taking long-
term benefits into consideration.
Comprehensive diabetes management programs that
have showed positive clinical and financial outcomes ex-
tend past the examples of the Asheville Pharmacy Project,
Pharmacists that work for pharmaceutical companies may the Mississippi Medicaid Project, and the South Carolina
be involved in diabetes care either as salesmen, clinical Pharmacists Diabetes Management Programs. The degree
education consultants, or researchers. The number of pro- of reimbursement for diabetes education services often
ducts used in the treatment of diabetes is expanding as we differs by state.
learn more about the underlying causes of the disease.
Since the late 1990s, more than five new oral agents and
three new insulins have come into the marketplace.
Pharmacists have played an integral part in educating
physicians, other pharmacists, and other health care per- Pharmacists can be involved in a variety of areas of dia-
sonnel on actions and uses of these new products. Clinical betes care. These areas can range from direct, with per-
education consultants or medical liaisons for pharmaceu- sonal intervention and counseling, to indirect by deciding
tical companies take this education a step further by what services and products a patient may obtain. With
providing continuing education and clinical assistance to any pharmacist practice, the environment, financial con-
the physicians in the treatment of their patients with dia- straints, time limitations, desire, and competence of the
betes. It is evident with the development of the alpha pharmacist each play a role as to the involvement a
glucosidase inhibitors, meglitinides, thiazolidinediones, pharmacist has with a person with diabetes. With the
and new insulin formulations such as lispro and glargine number of cases of diabetes expected to increase, phar-
that researchers have been trying to develop products that macists can and should play a more prominent role in
improve the outcomes of these patients. The number of assisting patients with diabetes.
products used for patients to check their blood sugar Resources for information about diabetes products and
has mushroomed since the early 1990s. Blood glucose management are abundant. Below are some of the many
monitor technology has allowed patients to perform informative web sites available to patients and pharma-
these tests with minimal invasion. The development of cists that will enable them to increase their knowledge
truly noninvasive blood glucose monitoring; testing de- about diabetes.
vices for home use for blood pressure, cholesterol, and
A l c ; and other diabetes-related devices will require sales
personnel with more technical and medical knowledge
that those used in the past.
Forms to document patient assessments and educational
session content are abundant. Individual practices can
modify these forms to meet their specific locations needs.
Examples of these forms are often included in certificate
programs such as those offered by the National Com-
With passage and implementation of national medicare munity Pharmacist Association, American Pharmaceu-
prescription drug coverage, pharmacists will need to take tical Association, American Association of Diabetes
a more active role in the development of reasonable, Educators, and state pharmacy organizations. These
effective formularies of medications used to treat diabetes forms are also found on the different web sites, such as
and the supplies necessary for patients to achieve optimal www .bd.com, www .novo.dk, and www .humulinpen.com.
Diabetes Care, Pharmacy Practice in 259
www.diabetesincontrol.com
www.kunkelrx.com
www.aadcnet.org www.edu-centcr.com
www.pharminfo.com/disease/immun/#iddm
www.ezdiabetes.com/
www.afpafitness.com/FACTINDX.HTM
http://medicine.ucsf.edu/resources/guidelines/
guidcdm.htm1 Coast-Senior, E.A.; Kroner B.A.; Kelley C.L.; Trilli L.E.
www.pfim-.com/main.html Management of patients with Type 2 diabetes by pharmacists
www .cdc.gov/di abeteslindex. htm in primary care clinics. Annals of Pharmacothcrapy 1998
Jun, 32 (6), 636-641.
www.diabetes.org/
McDcrmott, J.H.; Christensen D.B. Provision of pharmaceutical
www.avandia.com care services in North Carolina: A 1999 survey. Journal of
www.actos.com/ the American Pharmaceutical Association 2002 Jan-Feb,
www .novo.dk/health/dwk/in fo/ydww/index.asp 42 (l), 26 35.
http://diabetes.lilly.com Monroe, W.P.; Kunz, K.; Dalmady-Israel, C.; Potter, L.;
www.eatright.org/ Schonfield, W. Economic evaluation of pharmacist involve-
www.diabetesmonitor.com/tx-tin2/sld~Ol .htm ment in disease management in a community setting. Clinical
www.joslin.harvard.edu/edue~~tion/library/oha.html Ther. 1997, IY, I13 -123.
www.lifescan.com Schapansky, L.M.; Johnson J.A. Pharmacists' attitudes toward
www.intelihealth.comIH/ihtl H?t=2 1054 diabetes. Journal of the American Pharmaceutical Associa-
www.niddk.nih.gov/health/diahetes/diabetes.htm tion 2000 May-Jun, 40 (3), 371 377.
Sctter, S.M.; Corbett C.F.; Cook D. Johnson SB exploring the
www.cdc.gov/nccdphp/cdnr.htm
clinical pharmacist's role in improving home care for
www.aace.com/indexnojava.htm patients with diabetes. Home Care Provid. 2000 Oct, 5 ( 5 ) ,
www.bms.com/products/index.html 18 5 192.
~~
e as Sc
Medical Communirationi and Consulting, Chesapeake, Virginia, U.S.A.
gulations and legal decisions by which the FDA had removed from the market unless the FDA can prove that it
prohibited dietary supplements as unapproved food is unsafe for its labeled
additives.“.8391
Section 4 of the DSHEA establishes adulteration pro-
visions for dietary supplements. The DSHEA sets con- ANATOMY OF THE DSHEA:
siderably less stringent safety standards for dietary sup- MARKETING AND LABELING OF DlETA
plements than those required for drugs or food additives. SUPPLEMENTS (SECTIONS 5-7)
The FDA safety standard for drugs and food additives is a
“reasonable certainty” that a substance is not harmful. In Section 5 of the DSHEA addresses dietary supplement
contrast, the DSHEA requires a “reasonable expectation’’ claims and marketing. Unlike drugs for which any ad-
of safety for dietary supplements. Manufacturers are not vertising, informational, or promotional material is con-
required to submit safety data f o v most products to the sidered labeling by law and is subject to FDA review
FDA prior to marketing dietary supplements; the product before distribution, dietary supplement literature is not
is presumed safe. The burden of proof to show that a deemed labeling. .‘A publication, including an article, a
dietary supplement is adulterated or unsafe is the res- chapter in a book, or an official abstract of a peer-re-
ponsibility of the FDA. Additionally, the DSHEA defines viewed scientific publication that appears in an article and
a dietary supplement as adulterated if an ingredient pre- was prepared by the author or editors of the publication,
sents “a significant or unreasonable risk of illness or which is reprinted in its entirety” is not considered la-
injury” when used as directed on the label. The adul- beling under the provisions of the DSHEA. The DSHEA
teration definition for dietary supplements focuses on the requires that the information presented must not be false
toxicity for a labeled use, unlike standards for drugs and or misleading, cannot promote a specific supplement
food additives which focus on the toxicity of product brand. must be displayed with other similar materials to
itself, regardless of labeled use. For example, a dietary present a balanced view, must be displayed separate from
supplement that is used as a substance of abuse cannot be supplements, and must not have other information at-
262 Dietary Supplement Health and Education Act
tached, such as product promotional information. The contains botanical ingredients, the label must state the
DSHEA relies on good faith marketing by the manufac- part of the plant used in the supplement. Listing of inert
turer to adhere to these requirement^."^'^.'^^'^^ ingredients is not required. Supplements that claim to
Section 6 of the DSHEA amends the Nutrition La- conform to the standards of an official compendium, such
beling and Education Act to allow four types of label as the U.S. Pharmacopeia (USP) or National Formulary
claims on dietary supplements without obtaining pre- (NF), must meet the specifications of the compendium to
marketing approval by the FDA. A product may claim a avoid misbranding.il.’O.’
benefit related to a classical nutrient deficiency, as long as Dietary supplement labels must also include nutrition
the U S . disease prevalence is disclosed. The label may labeling. Ingredients for which the FDA has established
also describe the role of a nutrient or dietary ingredient Reference Daily Intake (RDI) or Daily Reference Value
that is intended to affect the structure or function of the (RDV) are listed first, followed by ingredients with no
human body (so-called structure and function claim), or daily intake recommendations. If an ingredient is listed in
characterize the documented mechanism by which a the nutrition labeling, it does not have to be included
nutrient or dietary ingredient acts to maintain such struc- again in the list of ingredients. Dietary ingredients that
ture or function. The label may also include a statement are not present in significant amounts do not need to
about general well-being from consumption of a nutrient be listed. Significant amounts are not defined by the
or dietary ingredient. If any of these claims is made, the DSHEA. The label must state a suggested quantity (dose)
product must also include the following statement: “This ’
per serving.[ O.’ ‘1
9’
Tyler’s Herbs of Choice; The Therapeutic Use of Phytomedicinals. James E. Robbers and Varro E. Tyler. Binghampton, NY:
Hawthorn Herbal Press, 1999.
The Review of Natural Products. Ara DerMarderosian, ed. St. Louis, MO: Facts and Comparisons, Inc. (published monthly).
The Cochrane Library, 2002. Oxford: Update Software. Online at www.update-software.com (updated quarterly).
Herbal Medicine: Expanded Commission E Monograph. Mark Blumenthal, ed. Newton, MA: Integrative Medicine
Communications, 2000.
commendations for dietary supplement label claims. The $15.7 billion in 2000. Nearly half of Americans surveyed
Commission submitted its findings to the president and report using vitamins, herbal products, or other supple-
Congress in 1997.[121 ments. The DSHEA exempts dietary supplements, most of
The last section of DSHEA, Section 13, establishes an which are nonpatentable, from the multimillion dollar
Office of Dietary Supplements (ODS) within the National FDA drug approval process and simultaneously shifts the
Institutes of Health (NIH). The purpose of ODS is to burden of proof of safety from the manufacturer to the
conduct and coordinate scientific study within NIH re- FDA. The DSHEA allows marketing of substances with
lating to supplements in maintaining health and prevent- safety standards that predate the Food, Dmg, and Cos-
ing disease and to collect and compile scientific research, metic Act of 1938.12-43111
including data from foreign sources and the NIH Office of Pharmacists should be aware of the differences in
Alternative Medicine. The OCS is also responsible for safety standards and regulatory control between drugs and
serving as the principal advisor to other government dietary supplements (Table 1). When counseling people
agencies on issues relating to dietary supplements, com- about dietary products, pharmacists must be aware that
piling a database on scientific research on dietary sup- the DSHEA allows the promotion of substances that may
plements and individual nutrients, and coordinating NIH have variable potency, unidentified components, unpro-
funding relating to dietary supplement^.""^^ ven efficacy, and unknown adverse effects. The DSHEA
The FDA Center for Food Safety and Applied Nut- does not require warnings about drug interactions or me-
rition published a 10-year plan for fully implementing the dical conditions under which a dietary supplement should
DSHEA. The goal of the plan is, “By the year 2010, have not be used. In view of the liberal labeling provisions of
a science-based regulatory program that fully implements the DSHEA, pharmacists cannot trust dietary supplement
the Dietary Supplement Health and Education Act of company literature and should consult reliable informa-
1994, thereby providing consumers with a high level of tion sources (Table 2).[1,171
confidence in the safety, composition, and labeling of
dietary supplement products.” In the plan, the FDA de-
tails strategy to improve safety and labeling; clarify struc-
ture and function claims, and differences among dietary
supplements and foods and drugs; improve enforcement Although the passage of DSHEA was hailed as a victory
of the DSHEA provisions; enhance science and research for consumer access to dietary supplements and a defeat
capabilities; and improve communication with the pub- of government overregulation, the DSHEA has been
lic. Pharmacists should be familiar with the DSHEA and widely criticized by medical, legal. and public groups as
FDA rules concerning dietary supplement products to be being deficient in safety provisions and requirements for
effective conveyors of consumer information.[201 scientifically proven claims. Citing reports of serious tox-
icity caused by substances regulated as dietary supple-
ments, critics point out that Congress passed the Food,
I TS Drug, and Cosmetic Act of 1938 as a consequence of
poisoning by sulfanilamide elixir and the Kefauver-
Dietary supplement sales have grown from $8.8 billion Harris Amendments in 1962 in reaction to the thalidomide
since the passage of the DSHEA in 1994 to a projected tragedy in Europe. Barring public outcry for congres-
264 ealth and Education Act
sional action over a disastrous toxic effect, the slow pro- 8. Burdock. G.A. Dietary supplements and lessons to be
cess of FDA rulc-making and litigation between the FDA learned from GRAS. Regul. Toxicol. Pharmacol. 2000, 3 / ,
and the dietary supplement industry will define the broad- 68-76.
based language of the DSHEA. By counseling consumers 9. Young, A.L.; Bass, 1,s.The Dietary Supplcmcnt Health
and Education Act. Food Ilrug Law J. 1995, 50, 285-
about possible lax manufacturing standards and potential
292.
drug interactions and adverse effects of dietary supple-
10. Anon. Dic~tarjSupplement H(,dth and Education A c t qf
ments, pharmacists can circumvent some of the inad- 1994; U.S. Food and Drug Administration, December 1,
equate saLe'eguai-ds or the DSHEA.'L.4'8~'0"" 17' 1995: http://vm/cfsan.fda.gov/-dms/di~~tsupp.html.
(accessed September, 2000).
11. Commission on Dietary Supplement Labels. Mqjor 1s.sLie.s
and Recommendutioiis Relcitad to Laheling qf 1jietar.y
Supplements; http://www.healtli.gov/dietsupp/ch3.lltm (ac-
1. Ilietaiy Supplement Health and Education Act o j 1994; cessed September, 2000).
http://thomas.loc.gov/cgi-bin/yuery/D?c 1 03 : h : ./temp/ 12. Commission on Dietary Supplement Labels. http://web.
-c I03705yih:e 13550. (accessed September, 2000). heaJth.gov/dietsupp (accessed September, 2000).
2. The Washington Post. Healrli Concc.riis Grow 0vc.t- Ilerlxd 13. Office of Dietary Supplemcnts. http://odp.od.nih.gov/ods/
Aids: March 19, 2000. http://washingtonpost.com/wp-dyn/ dcfault.htm1 (accessed Octobcr, 2000).
articles/A32685~2000Marl7.html. (accessed September, 14. Kessler, D.A. Cancer and Herbs. NEJM 2000, 342; 1742--
2000). 1743.
3. KicsLak, S.M.; Philen, R.M.; Mulinare, J. IS. Quackwatch. "Haw the Dietury Supplemmf Health and
Vitamin and mineral suppleinent use in the Unitcd States. Education Act qf 1994 Weukened the FDA" by Stephen
Results from the third National Health and Nutrition Barrett, M D ; http://www.quackwatch.com/02Consumer-
Examination Survey. Arch. Fain. Med. 2000, 9, 258 262. Protection/dshea.html (accessed September. 2000).
4. KacLka, K.A. From herbal P r o a c to Mark McGwirc's 16. Anon. Herbal roulette. Consumer Reports 1995, 698-705,
tonic: How the Dietary Supplcinent Hcalth and Education November.
Act changed the regulatory landscape for health products. 17. Hasegawa, G.R. Uncertain quality of dietary supple-
J. Contcmp. Hcalth Law Policy 2000; 16; 463 499. ments: History repeated. Am. J. Health-Syst. Pharm.
5 . Simmons, C.; Simmons, M. Drugs and dictary supple- 2000, 57, 951.
ments: Ramifications ofthe Food Drug and Cosmetic Act 18. Regulations on statements madc for dietary supplements
and the Dietary Supplement Health and Education Act. concerning the effect of the product on the structure or
W. Va. J. Law Tech. 1998. 2. (February 14. 1998) http:// function of the body; final rule. Federal Register 2000, 65,
www.wvjolt.wvu.edu/v2i I/simmons.htm. (accessed Sep- 999- 1050. http://vm.cfsan.fda.gov/-lrd/fr[)OO 106.html
tember, 2000). (accessed October, 2000).
6. Food, Drug, Cosmetic, and Devicc. Enforcetneizf Amend- 19. FDA FinaliLes Claims for Claims on Dietary Supplements.
menls of 1091 (H.R. 2507, 102nd Congress); http:// In FDA 7hlk Puper TOO-]; Ian 5 , 2000. http://vm.cfsan.
thomas.loc.gov/cgi-bin/query/z?cI 02:H.R.2597. (accessed fda.gov/-lrd/tpdsclm.html (acccssed October, 2000).
Septembcr, 2000). 20. U S . Food and Drug Administration: Center for Food
7. Nutrition Cool-dirzating Act of 1991 (H.R. 1662, 102nd Salety and Applied Nutrition. FDA Dirrnrj Siipplwnmt
Congre.s.s); http://thonias.loc.go~~/cgi-hin/query/~'~cl02: Strutrgj ( l e n Y w r Plan); http://vm.cfsan.fda.gov/-dins/
H.K. 1662. (accessed September, 2000). ds-strat.html (accessed October, 2000).
PHARMACY PRACTICE ISSUES
ac
Mae Kwong
American Society o f Health-System Pharmacists,
Bethesda, Maryland, U.S.A.
agreed that practicing clinical pharmacy had become sibilities; and that educational programs should be deve-
easier within the past few years, mostly because of loped to train pharmacists to manage clinical services.
increased recognition by other healthcare professionals William A. Miller, Pharm.D., presented the final ple-
of the pharmacist’s role in patient care. The workshop nary session on building pharmacy’s image. According to
groups produced 37 consensus statements on barriers to Miller, building pharmacy’s image as a clinical profession
clinical practice. According to the statements receiving would occur simply by providing clinical services. Phar-
the highest consensus, pharmacy directors are unable to macy would be advanced as a clinical profession by es-
provide effective leadership to their staff, a widely ag- tablishing goals for pharmaceutical services; creating
reed-upon philosophy of pharmacy practice is lacking, standards for pharmacy practice; planning, implementing,
there is no concurrence on what the standard of prac- and managing pharmaceutical service, education, and
tice in pharmacy should be, consumer demand for cli- research programs; providing financial management; and
nical pharmacy services is weak because the public has a assessing the quality of pharmaceutical services and drug
poor understanding of the services pharmacists can offer, use within the institution. The workshop groups sought to
and the value of clinical pharmacy services has not been characterize the type of relationship pharmacy should
adequately demonstrated. establish with medicine, nursing, hospital administration,
To discuss the symbiosis of clinical practice and edu- and the public. Eight consensus statements were written.
cation, Charles A. Walton, Ph.D., presented the educator’s The major consensus statement was that pharmacy should
perspective and Marianne F. Ivey presented the practitio- establish a public image of advocacy in all matters related
ner’s perspective. The presenters believed that both to the use of drugs. Other statements expressed that phar-
pharmacy practitioners and educators should share in ad- macist input should be a required component of the drug-
vancing the profession through the establishment and use process, that pharmacy should be viewed as a clinical
provision of clinical pharmacy services, through edu- service, and that pharmacy is a colleague with nursing and
cation and training of pharmacy students and pharmacists, medicine in patient care.
and through clinical research. The objectives for the
workshop groups were: 1) to identify steps for making
more effective use of clinical pharmacy faculty in im-
proving the level and quality of clinical pharmacy ser-
vices and 2) to use pharmacy staff more effectively in
clinical education. A total of 33 consensus statements The Hilton Head Conference affirmed that pharmacy is a
were developed for objective 1 and 18 for objective 2. clinical profession committed to clinical practice and the
With respect to using clinical pharmacy faculty. it was patient. Pharmacy is fundamentally a healthcare profes-
agreed that there is a need to clearly define a shared sion with a responsibility for safe and effective drug use
philosophy between clinical faculty members and phar- in society.
maceutical services staff. the clinical service responsi- The conference provided a forum for pharmacists to
bilities of clinical faculty, and the clinical education discuss the past, present, and future of clinical pharmacy.
missions of both the college and the pharmacy depart- Even though the conference occurred in 1985, many of
ment. In addition, orienting deans and other academics to the conclusions reached still apply to practice today. For
the roles of clinical faculty would provide a basis for instance, some of the barriers identified with respect to
balancing teaching, research, and service responsibilities leadership and substantiation of the value of clinical
and would help acknowledge the scholarly activity and pharmacy services still exist. Also, there continues to be a
clinical research that occur in clinical practice. need to educate the public and gain the support of other
With respect to using pharmacy staff more effectively healthcare professionals for clinical pharmacy practice.
in clinical education, the major statements identified that
staff should be recognized for their teaching activities;
that staff involved in clinical instruction should partici- CE
pate in the evaluation of students; that hospital admi-
nistrators, pharmacy directors, and staff should recognize 1. Proceedings from the conference were published in the
their respective roles in pharmacy education and have a American Journal of Hospital Pharmacy 1985, 42, 1287-
thorough understanding of the clinical faculty’s respon- 1342.
PHAKMACY PRACTICE ISSUES
Leig SeY
Univer.sity o f Mi.sissippi, lackson, Mississippi, U.S.A.
adapted to local conditions from established national per year during the project. Pharmacy disease manage-
practice guidelines.["] The care is fleshed out by edu- ment favorably impacted both direct and indirect medical
cating patients as to the pathogenesis of asthma, the signs costs. The majority of employees were highly satisfied
and symptoms of airway decompensation, and the with their care. as they reported improvements in
pharmacology underlying medication options. Both functional status and quality of life.
short-term goals, lifestyle modifications such as smoking A critical review of pharmacy disease management
cessation and allergen avoidance, and long-term goals, programs is hindered by the lack of statistical design rigor
such as decreased rates of school or work absenteeism, are and robust cost analyses found in many published reports.
set and reviewed. In concord with the physician-su- The heterogeneity of studies with regard to clearly de-
pervised protocol, an individualized asthma action plan is fined and widely accepted outcome measures also ham-
developed for each referred patient. Pharmacists train pers systematic assessment. The authors of a review of 55
patients to use peak flow meters and to monitor and self- comparative studies representing 50 programs in which
adjust drug therapy. Pharmaceutical care is intended to pharmacists provided support for ambulatory care provi-
supplement regularly scheduled physician appointments, ders in outpatient clinics and community pharmacies
to identify and respond to intervening pathophysiology, found that prescription monitoring led to a general trend
and to mitigate the need for urgent medical attention. toward cost savings. enhanced timeliness of care, and
Outcome analysis reveals that the Asthma Care Clinic improved clinical outcomes.i151 However, this review
at the University of Mississippi is achieving its stated noted no consistent improvement in disease knowledge
goals."21 Utilizing enrolled patients as historical controls, or patient satisfaction and little improvement in quality
this disease-management intervention resulted in fewer of life among pharmaceutical care enrollees. The Nation-
emergency room visits or hospitalizations for asthma de- al Institutes of Health (NIH) through the Agency for
compensation. An annualized cost saving of approximate- Healthcare Research and Quality (AHRQ) is funding
ly 60 percent for these hospital services has been realized. studies to address these deficiencies in the evidence
Cost savings are sustained even though additional clinical base."61 This federal interest in data documenting the
funds are expended on pharmaceutical care. As a result costs and benefits associated with disease management
of these salutary findings. all patients presenting for the bodes well for the acceptance of pharmaceutical care into
emergency treatment of asthma-related bronchospasm at the medical mainstream.
the University Medical Center are subsequently consi-
dered for disease-management assessment.
Similarly encouraging results of collaborative drug CREQENTIALING AND CERTIFICATI
therapy are reported in the medical literature for a number
of economically burdensome chronic diseases. Project As pharmacy embraces disease management, the profes-
ImPACT (Improve Persistence and Compliance with The- sion must reassure skeptics that pharmacists possess the
rapy): Hyperlipidemia assessed the contributions of necessary knowledge and skills to provide these services.
community pharmacists to the care of patients with lipid For pharmacists desiring to broaden their scope of
disorders requiring pharmacologic interventi~n."~] During practice, training beyond that required to obtain a phar-
this three-year project, the observed rate for compliance macy degree or license may be necessary. Although cre-
with lipid-lowering medication therapy improved to ap- dentialing is a controversial topic, it is increasingly evi-
proximately 90 percent. The impact of these Virginia dent that a nationally recognized process is necessary to
pharmacists was significant, as nearly two-thirds of parti- bolster the professional stature of pharmacists and to
cipants achieved and maintained nationally recognized identify clinical specialists who are capable of providing
treatment goals. The City of Asheville, North Carolina, reimbursable pharmaceutical care.
and the largest private employer in western North Caro- Credentialing is defined in a medical context as the
lina, the Mission St. Joseph Health System, contracted process by which an organization or institution obtains,
with trained community pharmacists to manage the drug verifies, and assesses an applicant's qualifications to pro-
therapy of their employees with d i a b e t e ~ . " ~Patient
] inter- vide a particular patient-care service. The Council on
action with providers increased with the advent of phar- Credentialing in Pharmacy (CCP), a coalition of 11 na-
maceutical care, while metabolic indices of disease tional organizations founded in 1999 as a coordinating
control improved. Moreover, payer expenditures for the body for credentialing programs, delineates three avenues
total cost of ambulatory and inpatient diabetes care for credentialing in pharmacy: 1) credentials required to
decreased. When absentee rates were compared to prior enter the profession-academic degrees, 2 ) credentials
years, participants worked an average of 6.5 days more required to enter practice-licenses, and 3) optional cre-
Disease Management 269
dentials documenting specialized knowledge and skills- years of experience in the field being tested prior to ap-
advanced academic degrees or certificate^."^] Certifica- plying for examination. States may require that prere-
tion involves granting a credential to a pharmacist who quisites, such as a training program, be completed before
has demonstrated a level of competence in a specific and permission for testing is granted. The NISPC-sanctioned
relatively narrow area of practice. Postlicensure certifica- examinations are graded as either pass or fail; a score of
tion usually requires an initial assessment and periodic 75% or greater yields a passing grade. Pharmacists re-
reassessments of a grantee’s qualifications. There are ceiving a passing score are eligible for this recognition
three agencies that offer certification to pharmacists: the to be listed on the NABP’s Pharmacist and Pharmacy
Board of Pharmaceutical Specialties (BPS), the Commis- Achievement and Discipline (PPAD) Web site database
sion for Certification in Geriatric Pharmacy (CCGP), and (Table 1).
the National Institute for Standards in Pharmacist Cre- Since 1998, NISPC has awarded credentials to over
dentialing (NISPC). BPS was established by the American 1,200 pharmacists in the United States. In 2001, NISPC
Pharmaceutical Association (APhA) in 1976 and certifies adopted the designation of Certified Disease Manager
pharmacists in five practice concentrations: nuclear phar- (CDM) for those pharmacists successfully completing one
macy, nutrition support pharmacy, oncology pharmacy, of the disease-management exams. NISPC hopes the CDM
psychiatric pharmacy, and pharmacotherapy. An “Added credential will gain national recognition by both patients
Qualifications” in either infectious diseases or cardiovas- and payers. NISPC certification must be renewed every 3
cular pharmacy is available for pharmacists certified in years. For pharmacists awarded a CDM credential in 2000
pharmacotherapy . The CCGP was established by the or later, 30 hours of American Council on Pharmaceutical
American Society of Consultant Pharmacists (ASCP) in Education (ACPE)-approved continuing education in the
1997 and supervises the certification program in geriatric credentialed disease state must be documented within the
pharmacy practice. NISPC was founded in 1998 to over- 3-year recertification period. Ten of the required 30 hours
see pharmacist credentialing in disease management. must be obtained during the third year.
NISPC is composed of four member organizations: the The availability of a cadre of pharmacists certified in
APhA, the National Association of Boards of Pharmacy disease management does not assure reimbursement for
(NABP), the National Association of Chain Drug Stores pharmaceutical care. NISPC formed a Standards Board
(NACDS), and the National Community Pharmacy Asso- and a Payer Advisory Panel to ensure public trust in the
ciation (NCPA).“’] NISPC was charged with coordi- care provided through collaborative drug therapy by cre-
nating the development of a nationally recognized testing dentialed pharmacists. The Standards Board has identified
program to credential pharmacists in disease-specific a need to improve the communication skills of pharma-
pharmaceutical care. NISPC utilized NCPA’s National cists so that their collaborative work is enhanced, to train
Institute for Pharmacist Care Outcomes (NIPCO) model pharmacists regarding the benefits of nonpharmacologic
as a resource for constructing examinations to test di- therapies, and to adopt a regular review and modification
sease-management competencies. An expert panel drawn process for disease-management competencies. The Payer
from community practitioners, academicians, pharmacy Advisory Panel was tasked with advising NISPC on the
benefits managers, and state board of pharmacy members needs of the payer community as pharmaceutical care
develops the standards and objectives for each disease- penetrates the marketplace. The Panel has stressed the
management examination. Panel members ensure that the need to clearly define the package of clinical services
content of the examinations reflects the knowledge base credentialed pharmacists provide, to involve other allied
expected of pharmacists providing care at an advanced health professionals in collaborative management, to de-
practice level. velop standard outcome measures, and to establish an
The first pharmacy disease-management examinations accessible databank for credentialed pharmacists. The
were offered in 1998 as pencil-and-paper tests in the work of the Standards Board and Payer Advisory Panel
states of Arkansas, North Dakota, and Mississippi.[191 should significantly contribute to the stature of pharma-
Certification was offered in four disease states: asthma, ceutical care.
dyslipidemia, diabetes, and anticoagulation therapy. Since
that time, the examinations have been adapted for com-
puter administration at multiple test sites any time of the
year. However, non-electronic testing is offered annually REIMBURSEMENT
at the APhA national meeting. Due to the specialized
funds of knowledge required for successful certification, In 1998, Mississippi became the first state to secure
pharmacists are strongly encouraged to have at least 2 government reimbursement for pharmaceutical care.[201
270 Disease Management
Indust?-) Linisons
Disease Management Association of America DMAA www.dmaa.org 202-861- 1490
Disease Management Purchasing Consortium and Advisory Council DMC [*I www.dismgmt.com 781-237-7208
(Adapted from Ref. [17].)
The Health Care Financing Administration (HCFA) practicing at that site for use by all their referred patients.
approved payment through the Mississippi Division of In the community setting, a separate protocol from each
Medicaid to pharmacists for disease-management ser- referring physician must be completed for each patient.
vices provided to patients enrolled in the Medicaid pro- Pharmacists are paid a flat fee for each 15- to 30-minute
gram. The components of a reimbursable service are patient encounter. Currently, pharmacists can be reim-
patient evaluation, patient or caregiver education, drug bursed for up to 12 visits per year per patient for all
therapy review and compliance assessment, and disease disease states managed. These pharmaceutical care visits
management under protocol according to clinical practice are in addition to the annual allotment of reimbursed
guidelines. NISPC credentialing is currently required physician visits provided by Mississippi Medicaid. No
for pharmacists to apply for a Mississippi Medicaid pro- restrictions exist as to the number of patients a pharmacist
vider number, which in turn is necessary to bill for phar- can manage.
maceutical care under the Other Licensed Practitio- Mississippi is not alone in explicitly recognizing the
ner designation. important contributions of pharmacists to disease man-
In addition to obtaining a Medicaid provider number, a agement with state funding. In 2000, the Iowa Division of
pharmacist must produce two other documents prior to Medicaid initiated a reimbursement program for phar-
providing pharmaceutical care in Mississippi: a written maceutical case management.[211During this 2-year pilot
evaluation and treatment protocol and a referral from a project, patients who are candidates for pharmaceutical
physician. The protocol must define the collaborative care are identified and participating pharmacists are
agreement between the pharmacist and the referring notified of their eligibility. The pharmacist performs an
physician and be on file with the State Board of initial disease assessment and develops an individualized
Pharmacy. The nature of protocol requirements differs therapeutic plan for each patient, which is subsequently
among practice sites. Within an institution, one protocol reviewed by a physician collaborator. Pharmacists must
agreement may be submitted for all the physicians meet criteria outlined by the project’s advisory commit-
Disease Management 271
tee, and complete a training program approved by the systems in place in most community pharmacies are often
Iowa Department of Human Services. New Mexico also inadequate to respond to the additional demands of di-
has a demonstration project that allows for pharmaceut- sease management.[291 These administrative concerns
ical care under physician-supervised protocol.[221Assess- compound the stresses placed on pharmacists by the high
ments of the medical and cost outcomes of these projects volume of medication dispensing and the need for tech-
will determine the future of these initiatives. nician supervision characteristic of retail pharmacy prac-
State support for pharmaceutical care is bolstered by tice. These issues will need urgent attention so that the
managed care imperatives. States are increasingly willing willingness of the public and payers to support pharma-
to fund programs that maintain the health of their insured ceutical care is not hindered.
populations, if this care can be proven to be efficacious
and to control medical costs. States are confronting the
same financial challenges faced by private health plan
leaders such as Humana and Kaiser Permanente, who
were early adopters of disease management. Health Laws pertaining to disease management differ from state
Maintenance Organizations (HMOs) employ pharmaceut- to state. Most states provide the Board of Pharmacy with
ical care to improve the health of their enrollees and thus statutory authority to regulate pharmaceutical care. Thir-
limit the need for costly medical interventions.[231HMOs ty-three states currently allow pharmacists to initiate or
have invested considerable time and effort into devel- modify drug therapy pursuant to a collaborative practice
oping multidisciplinary treatment pathways and algo- agreement or protocol; other states are in the process of
rithms for many pharmacy-intensive disorders and di- amending their practice acts to incorporate pharmaceut-
s e a s e ~ . [ By
~ ~ 'standardizing processes of care, providers ical care services (Table 2). Pharmacists must adhere to
become accountable for fully implementing therapies the restrictions imposed by state practice agreements or
proven to favorably impact patient outcomes. The de- they assume a greater risk of liability. Exposure to admi-
dication of organized pharmacy to disease management is nistrative or criminal penalties can be diminished if phar-
likely to lead states to commit greater resources to phar- macists fully acquaint themselves with the boundaries
maceutical care. limiting pharmaceutical care in their state.
As Medicare becomes structured to support health One legislative initiative is worthy of note. North Ca-
maintenance, federal interest in disease management is rolina allows a pharmacist who provides disease manage-
coming full circle. The Indian Health Service was a ment to be designated as a Clinical Pharmacy Practi-
pioneer in pharmaceutical care. and the U.S. Armed ti~ner.'~']Pathways to attain this professional recognition
Forces and Veterans Affairs healthcare sectors are now are available to either bachelor or doctorate degree-
leaders in collaborative drug therapy.r251In 1999, HCFA holding pharmacists. Applicants for this designation must
recognized the provider status of nonfederally employed submit a collaborative practice agreement that delineates
pharmacists to participate in diabetes management.r261 the dimensions of their pharmaceutical care proposal for
Congress and the Medicare Trust administrators are formal review. Approval is granted after appraisal by both
actively weighing the benefits of extending coverage to the Board of Pharmacy and State Medical Board. Many in
include disease management by pharmacists. Pharmacists organized medicine have joined pharmacy in endorsing a
are likely to be accorded enhanced provider status given grant of proscribed prescriptive authority to pharmacists
the developing affirmative body of research and patient through such novel state provisions. However, the Ame-
willingness to embrace pharmaceutical care. Indeed, a rican Medical Association (AMA) opposes nonphysician
recent patient survey indicated that a majority would pay groups that seek independent prescribing rights as they
for disease management by pharmacists, if accredited believe this will further fragment h e a l t h ~ a r e . ~A~ more
services were widely available.[271 recent Position Paper outlining the stance of the American
Although reimbursement is often cited by pharmacists College of Physicians-American Society of Internal Me-
as the paramount barrier to the widespread dissemination dicine (ACP-ASIM) with regard to the increasing scope of
of disease management, other troublesome yet surmount- pharmacy practice endorses further research on phar-
able obstacles exist.[2s1 Even when reimbursement is maceutical care programs, yet opposes independent phar-
assured, the requirements accompanying billing can be macist prescriptive privileges and the initiation of drug
time-consuming and costly. As in other medical fields, the therapy.[321
paperwork required to document encounters and apply for Some within the pharmacy profession also question
pharmacy service reimbursement from various payers in whether direct patient care is a proper role for phar-
different practice settings is not uniform. The information m a c i s t ~ . [They
~ ~ ] argue that disease management requires
292 Disease Management
proficiency in differential diagnosis, analytical thinking, right of patients to inform and to govern their own
and patient interaction skills that are not within the healthcare decisions. However, pharmacists practicing in
purview of pharmacists. They believe that pharmacy collaborative arrangements have ethical duties to each
should retain its traditional focus on quality assurance in party to the agreement, to both patients and physicians.
medication delivery and cede responsibility for patient Conflicts can arise as patients may provide information to
care to physicians rather than join the ranks of other mid- a pharmacist that they are unwilling to share with their
level practitioners. These concerns are being addressed in physician.[391A pharmacist may be faced with the moral
undergraduate and postgraduate pharmacy education. dilemma of disclosing information provided in confid-
Pharmacy schools are moving away from passive teaching ence or withholding data pertinent to medical decision
models to active curricula founded on problem-based making. In a purely consultant relationship, the primary
learning and from didactic lectures to clinical pharmacy duty of the consultant is owed to the party requesting the
preceptorships in practice environments. Pharmacy lead- consultation and professional standards hold that full
ers are also addressing the lack of readily available disclosure is warranted. Disease management is an effort
advanced clinical training for commuiiity pharmacists. by both pharmacists and physicians on the behalf of pa-
Pharmaceutical care is not without its extramural critics tients and thus the desires of patients for confidential
as well. Consumer advocates question whether disease interactions may be ethically problematic. The import-
management is a sound public health policy.[341According ance of these ethical principles is reflected in recent fe-
to these critics, such programs concentrate healthcare ex- deral legislation; the Health Insurance Portability and
penditures on high-risk patients to control short-term costs Accountability Act requires the establishment of health
and thus redirect scarce resources needed for health pro- privacy regulations to protect the confidential information
motion and disease prevention. They believe that disease yielded by patients.[401Pharmaceutical care is more co-
management has been promoted by the pharmaceutical venant than contract; when the inevitable conflicts arise,
industry as a way to augment drug sales. Drug manu- pharmacists must recognize that resolution may require
facturers are accused of organizing disease-management choices based upon individual patient values rather than
programs to gain access to restricted formularies and to on a reflexive recourse to an objective standard. As di-
ensure control over medication demands rather than to sease management takes hold, comprehensive pharmacy
improve patient The research community also education will need to encompass legal and ethical
raises ethical concerns, as it objects to the lack of public training so that pharmacists retain the good will of the
reporting of the outcomes from commercial pharmaceut- public they currently enjoy.
ical care programs.[361 It cautions that while exclusive
access to proprietary information may be necessary to
preserve a company’s competitive advantage, it may hin- Y NGLU
der medical progress. Pharmacists must be wary of un-
critically adopting pharmaceutical care protocols deve- National surveys estimate that one-third of adults in the
loped by the for-profit sector and be vigilant to unethical United States suffers from a chronic disease, yet most fail
inducements to prescribe unnecessary or inappropriate to achieve treatment goals promulgated by consensus
medication therapies. care guidelines; fewer than one half of hypertensives
Public regard for the honesty and ethical character of have well-controlled blood pressure and less than one-
pharmacists is greater than for either physicians or the quarter of patients with coronary artery disease have lipid
clergy.[371 Pharmacy must guard against a decline in levels within optimal limits.[411 The current healthcare
consumer confidence as it expands its spectrum of ser- model is geared to acute disorders, rather than tooled for
vices. Professional codes are being challenged by the new the systematic care of chronic diseases. Pharmacy disease
relationships developing between pharmacists and those management is the multidisciplinary process of selecting
they serve. As pharmacists become more involved in appropriate drug therapy and continually monitoring pa-
direct patient care, their ethical obligations extend beyond tient outcomes to that therapy. It is a response to the
professional dictates to maintain knowledge and skills to demands of health-conscious consumers and cost-con-
uphold the welfare of patients. Of significant patient scious payers. The value of pharmaceutical care can be
concern are the related issues of privacy and confidenti- promoted by ensuring the knowledge and judgment of
ality. Therapeutic relationships are built on a foundation practitioners through training and credentialing and by
of trust. Clinicians are entrusted with sensitive, personal measuring their impact on health outcomes through ri-
information by patients and they are expected to hold gorously designed clinical trials. Healthcare is in tran-
these private communications in strict confidence by the sition, and new models of delivery will likely be ac-
canons of medical ethics.[381Additionally, respect for the companied by a broader pharmacoeconomic perspective,
dignity of patients entails promoting their autonomy: the one that does not isolate drug costs, but views the cost of
274 Disease Management
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care. Pharmacy is favorably situated to contribute to di- 0007.
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69-76.
18. Credentialing in pharmacy: No simple matter. Am. J.
Health-Syst. Pharm. 2000, 33 ( 2 ) , 84-85.
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PROFESSIONAL DEVELOPMENT
mended that the baccalaureate curriculum in pharmacy be licensure. In July 1978, the AACP’s House of Delegates
extended to 5 years, and in 1965, the 5 year degree voted on the entry-level degree issue. By an almost two-
became the minimum standard.‘21Pharmacy schools were to-one majority, the delegates voted to retain both the
now able to offer a baccalaureate or a Pharm.D. degree as baccalaureate and Pharm.D. dual-degree structure.
their entry-level degree into the profession. They could In an article published in 1987 titled, “The Third
also offer the PharmD as a postbaccalaureate degree. a Wave in Pharmaceutical Education: The Clinical Move-
1- to 3-year program after completion of the B.S. degree. ment,” pharmacy educator Dr. Charles D. Helper
A third option was the “track in” PharmD, whereby all described his vision of pharmacy education and prac-
students began as baccalaureate students, and a few t i ~ e . ‘ ~He
] described clinical pharmacy as adding new
students were allowed to enter the Pham.D. curriculum knowledge for the patient’s welfare. This knowledge had
after completing a certain number of their baccalaureate limitations because it was provided to other health care
courses. For the next 25 years, debates raged over the providers for the patient’s benefit, instead of being
length of study and titles of pharmacy degrees. provided directly to the patient. Hepler wrote:
The 1960s through the 1980s witnessed the slow
transformation of pharmacists’ roles from solely dispens- As pharmacy further clarifies its clinical role. it should
ing to more patient and information centered. During the underscore its acceptance of as much responsibility for
early 1960s, a few pharmacists-including Donald Brodie drug use control as its social authority (under law) will
support. This ideal can be called pharmaceutical care: a
of the University of California-San Francisco, Donald
covenantal relationship between a patient and a phar-
Francke of the University of Michigan, and Paul Parker of macist in which the pharmacist performs drug use control
the University of Kentucky-envisioned new roles for functions (with appropriate knowledge and skill) gov-
pharmacists. They saw the pharmacist working side by erned by awareness of and commitment to the patient’s
side with physicians to provide information about the interest. The term is intended to invoke analogies with the
potent new drugs that were being manufactured. Thus ideals of medical care and nursing care.
began the clinical pharmacy movement. By 1967, the first
journal devoted to clinical pharmacy, Drug Intelligence It was this concept of pharmaceutical care that
and Clinical Pharmacy, was published. In 1972, two rekindled the discussion of pharmacy curricula, degrees,
therapeutics textbooks that were centered around clinical and practice.
pharmacy were published. By the mid-l970s, the U.S. By 1989, over 50% of all U.S. pharmacy schools still
government began to recognize the clinical contributions offered only the baccalaureate degree as their entry-level
of pharmacists and passed legislation that required degree, 14% offered only the Pharm.D. degree. and 30%
monthly reviews of drug regimens for patients residing offered both degrees.”] AACP President William Miller
in skilled nursing facilitie~.’~] appointed a task force (which was termed the Commis-
By the early 1970s. debates over pharmacy manpower, sion to Implement Change in Pharmaceutical Education)
pharmacists’ roles, and pharmacy education were heigh- to develop recommendations to guide pharmaceutical
tened. In 1972, AACP President Arthur Schwarting education to meet the changing demands of the profes-
recommended the formation of a “Commission on sion, the health care system, and society. During the next
Pharmacy” to study the scope of pharmacy services in 2 years, the task force addressed the educational stan-
health care and to project the educational requirements dards necessary for the entry-level curriculum for phar-
needed to train pharmacists to provide these services. The macy students, the length of the curriculum, and the title
commission was chaired by John S. Millis, President of of the degree granted for completing the curriculum. The
the National Fund for Medical Education. The Millis commission’s recommendations were published as a two-
Commission’s report, “Pharmacists for the Future,” was part series in 1991 .””’ The recommendations included
published in 1975.[2.31The report contained 14 recom- ‘‘an entry-level educational program for pharmacy prac-
mendations for pharmacy practice and education. Among tice that is at the doctoral level, is a least four pro-
these were continued movement of pharmacy as a fessional, academic years in length, and follows pre-
knowledge-based clinical profession, increased devel- professional instruction of sufficient quality and length
opment of clinical practice sites for pharmacy school (two-year minimum) to prepare applicants for doctoral
faculty, and development of a national board licensing level education.” Furthermore, the task force recom-
exam for pharmacists. mended the Pharm.D. degree as the sole degree for entry
As a result of the Millis Commission’s report, many into pharmacy practice. In addition, schools and colleges
pharmacy educators believed the time was right to adopt that currently offered Pharm.D. programs were urged to
the Pharm.D. degree as the sole degree leading to examine, analyze, and revise their curricula to ensure
278 Doctor of Pharmacy
that they were based on and reflected the philosophy of to become generalist practitioners of pharmacy.18’ Spe-
pharmaceutical care. cifically stated in the accreditation standards,
In late 1989: the ACPE, in its regular periodic review
of accreditation standards and guidelines, issued a The goals and objectives of the curriculum in pharmacy
“declaration of intent.”[’] In this declaration, ACPE should embrace the scope of contemporary practice
stated that its intent was to accredit only Pharm.D. degree responsibilities as well as emerging roles that ensure the
programs as the entry-level degree into the profession and rational use of drugs in the individualized care of patients
suggested the year 2000 as a probable target date. This as well as in patient populations. The organized program
of study should provide students with a core of
declaration fueled much discourse among pharmacy
knowledge, skills, abilities, attitudes, and values that are
educators. practitioners, and organizations. Educators
necessary to the provision of pharmaceutical care and
were skeptical of obtaining adequate resources to add should provide opportunity for selection by students of
another year to their curricula. Practitioners were fearful courses and professional experiences in keeping with
that baccalaureate practitioners would be disenfranchised particular interests and goals. The need for life-long
if pharmacy schools and colleges produced only doctoral- learning should be reflected as an integral theme of
level graduates. Various pharmacy organizations were the curriculum.
wary of the economic and political ramifications of such
a decision. The Pharm.D. degree requirements include postse-
During the next 3 years, a number of meetings were condary preprofessional courses and requirements, as
held and articles written regarding the future of pharmacy well as a minimum of 4 academic years to achieve
education, particularly with respect to the Pharm.D. professional competencies. Most pharmacy schools and
degree. A joint statement by the American Pharmaceu- colleges require a minimum of 6 academic years to
tical Association, the American Society of Hospital complete all the degree requirements. The preprofes-
Pharmacists (now the American Society of Health-System sional requirements include basic sciences (e.g., general
Pharmacists), and NARD (now the National Community chemistry, organic chemistry, biological sciences. math-
Pharmacists Association) supported a new Pharm.D. ematics, computer technology. physical sciences). In
degree as the entry-level degree for practice in the addition, the student should have adequate preparation
profession of pharmacy and outlined methods of degree in general education requirements such as humanities,
equivalence for current practitioners. In defining the new behavioral sciences, social sciences, and communica-
degree, the joint statement stressed, “It is the respon- tion skills.
sibility of pharmaceutical education to provide a graduate The professional courses in the Pharm.D. curriculum
prepared for immediate licensure and commencement of consist of didactic material, laboratory courses, and
a career in any area of pharmacy practice.” Therefore, practical experiences in patient care environments. The
the joint statement urged that the degree requirements pre- overall curriculum is structured to provide instruction
pare pharmacists for entry into the practice rather than for in the following core areas: biomedical sciences (in-
specialty practice.[71 cluding anatomy, physiology. pathophysiology, micro-
Debates about the PharmD as the entry-level degree biology, immunology, biochemistry, molecular biology,
had continued for more than half a century, but the issue and biostatistics); pharmaceutical sciences (including
was finally resolved in July 1992, in Washington, D.C., at medicinal chemistry, pharmacognosy, pharmacology,
the annual meeting of the AACP. With every school and toxicology, and pharmaceutics); behavioral, social, and
college of pharmacy casting one administrative and one administrative pharmacy sciences (including health care
faculty vote each, the delegates voted overwhelmingly to economics, pharmacoeconomics. practice management,
endorse the Pharm.D. degree as the sole degree leading communications applicable to pharmacy, the history of
into the practice of pharmacy. It was then up to the ACPE pharmacy, ethical foundations to practice. and social and
to finalize the accreditation standards and up to the behavioral applications and laws pertaining to prac-
individual colleges and schools of pharmacy to revise tice); pharmacy practice (including prescription proces-
their respective curricula. sing, compounding and preparation of dosage forms,
drug distribution, drug administration, epidemiology,
pediatrics, geriatrics, gerontology, nutrition, health pro-
T motion and disease preention, physical assessment,
emergency first care, clinical laboratory medicine, cli-
As defined in the ACPE’s standards for accreditation, the nical pharmacokinetics, patient evaluation and ordering
purpose of the Pharm.D. curriculum is to prepare students medications, pharmacotherapeutics, disease state man-
Doctor of Pharmacy 279
2 /
Fillldispense the
Monitor for efficacy
medication (including
and safety
patient counseling)
Administer the
medication
professional curriculum. Experiences that are taught graduates are employed in traditional community and
earlier in the curriculum are usually brief in nature and hospital pharmacies. Many pharmacists, however, seek
are designed to introduce students to the healthcare sys- employment in other patient care areas, including nutri-
tem in general, to the pharmacy profession, or to various tional support, ambulatory care, primary care, pharmaco-
aspects of patient care through a combination of obser- kinetics, pediatrics, and a variety of medical subspecialty
vation and participation. The later experiences consist of areas (e.g., oncology, nephrology, pulmonology, hema-
rotations of several weeks in length through various tology, critical care, infectious disease, emergency med-
aspects of pharmacy practice in which students spend all icine, gastroenterology, psychiatry, cardiology). Phar-
their time learning to manage the practice setting, in- macists may work in areas of less direct patient care,
teracting with other healthcare professionals, and pro- such as nuclear medicine, drug information, or medical
viding direct care to patients. Each rotation may ty- writing. They may be employed in all aspects of managed
pically last several weeks and include experiences in care, including pharmacy benefits management or for-
outpatient and inpatient settings, managed care organiza- mulary development and control, as well as in patient care
tions, pharmacy associations, or the pharmaceutical in- areas. Pharmaceutical companies employ pharmacists to
dustry. These advanced rotations are considered capstone manage clinical trials, serve as medical liaisons to phy-
courses in which students, through direct practice ex- sicians and other healthcare providers. or work in phar-
perience, develop their competence and confidence to maceutical sales. There are also careers in academic fields
practice pharmacy. to teach pharmacy students and students in other health
disciplines and to conduct research or serve as role mod-
els in providing healthcare to patients.
CAREER OPPORTU NIT!ES Some career opportunities require additional training
or credentialing through residencies, fellowships, certifi-
There are literally hundreds of different career op- cate programs, and credentialing examinations. Residen-
portunities for pharmacy graduates. The majority of cies provide intense 1- to 2-year learning opportunities for
Doctor of Pharmacy 281
continued development of patient care and managerial L.M., Ed.; PAS Pharmacy/Association Services: Athens,
skills. Fellowships develop pharmacists’ research skills Georgia, I 992: 15 -22.
to prepare them for careers i n the pharmaceutical indus- 4. Hepler, C.D. The third wave in pharmaceutical education:
The clinical movement. Am. J. Pharm. Educ. 1987, 51,
try or academia. Credentialing and certification provide
369-385.
specialized training in distinct areas such as nuclear phar-
5. Wolf, H.H.; Walton, C.A.; Hepler, C.D.; Koda-Kimble,
macy and disease management, and may b e beneficial to M.A.; Knapp, D.A.; Miller, K.W.; Nahata, M.C.; Rutledge,
the pharmacist to receive reimbursement for providing C.O.; Smith, W.E.; Vandel, J.H. Commission to implement
thesc specialized services. change in pharmaceutical education: A position paper.
AACP News NQV. 1991, 1-13.
6. Wolf, H.H.; Walton, C.A.; Hepler, C.D.; Koda-Kimble,
M.A.; Knapp, D.A.; Miller, K.W.; Nahata, M.C.; Rutledge,
EFE C.O.; Smith, W.E.; Vandel, J.H. Commission to implement
change in pharmaceutical education: Background paper 11.
1. Kremers, E. Kremers and Urdang ‘ s History oJ’ Pharmacy; Mar. 1991. 1-10.
1,ippincott: Philadelphia, 1976; 221 -280. 7. Joint statement on the entry-level Doctor of pharmacy
2. Buerki, R. In search of excellence: The first century of the degree. Am. J. Hosp. Pharm. 1992, 49, 244-251.
American Association of Colleges of Pharmacy. Am. J. 8. Accreditation Standards and Guidelines f o r f h e Profes-
Pharm. Educ. 1999, 63 (Suppl.). 1-210. sionul Program in Pharmacy Leading to the Doctor qf
3. Posey, L.M. Pharmaceutical Care: The Reprofessionaliza- Pharmacy Degree; American Council on Pharmaeutical
tion of Pharmacy. In Pharmucy Cadence 1992; Posey, Education; ACPE: Chicago, 1997; 12-20.
PKOFESSIONAL ORGANIZATIONS
Claire E. ore
Phillips Groiip Oncology Corninunications, PhiLidrlphin, Pennsylvania, U.S.A.
rogram
trafficking organuation Another operation, Operation records accountability arc required of these groups.
Green Air, uccesstully halted marijuana trarficking acti- Clinical pharmacists should be aware of the potential for
vities of an organimtion that exclusively used a com- drug diversion and be alert to the various ways in-
mercial \hipment company, FedEx, to tran4port the drug dividuals divert controlled substances. Examples of drug
Two additional problems tor which the DEA is respons- diversion schemes includc physicians who sell pres-
ible are the diversion of controlled phnrmaceuticals and criptions to drug dealers or abusers, pharmacists or
the diverwin of controlled chemicals nurses who falsify records to steal drugs to scll, em-
ployees who steals narcotics from inventory, prescription
forgers, patients who obtain controllcd substances from
multiple physicians, and individuals who Falsify narcotic
k orders to hide illicit sales. Research studies involv-
ing controlled substances or investigational controlled
substances are subject to strict accountability per
Although intended for legitimate medical use, narcotics, DEA regulations.
stimulants, and depressants are frequently abused;
therefore, controls have becn established b y the DEA
to prevent their illegal distribution. Registration with the
DEA is required of all health professionals entitled to
dispense, administer, or prescribe controlled substances
and of all pharmacies dispcnsing controlled substances. Briefs and Backgrounds: Inside the DEA. Drug Enforcement
Strict regulatory standards relating to drug security and Agency Website. www.dea.gov.
PHARMACY PRACTICE ISSUES
These data are measurable or can be observed. Laboratory Many patients rely on a caregiver or family member to
values and vital signs such as blood pressure are examples assist them with their medications. These individuals can
of objective data.[*] Objective data are not influenced by be a valuable source for patient drug history data.[51
opinion or perception of the patient. Objective data are
not infallible and can be limited. For example, if a patient
has their blood level checked for drug therapy manage- I VlEWl
ment, a laboratory error can occur. Objective data such as
pharmacy refill records can be used to verify subjective ttin
patient information.
The location of the interview should be in a quiet envi-
ronment free of distractions and allowing patient privacy.
Avoid barriers between you and the patient. Respect
patient privacy, and discuss the patient’s health issues
atients only with those directly involved with the patient’s
care. [2,5]
The patient is the most important source of information
regarding their medication therapy. Although the data
from the patient is subjective, the interview process can
provide clarification on medications taken, knowledge of
Introduce yourself initially, and describe your intentions
therapy, and barriers to education or compliance.
and role in the patient’s care. Always maintain good eye
contact and avoid negative body language. For example,
crossed arms or negative facial expressions will not make
the patient feel at ease. It is important to record the his-
The medical record is another source of medication and tory data; however, do not let your record taking distract
health-related information. Access to this record may be from listening to the patient. Maintaining the continuity
limited in certain practice settings; however, it can be a of the interview and listening are key to developing the
valuable tool to review prior to conducting your patient patient’s trust.[21
drug history interview. Some practitioners use medical The history is often affected simply by the way in
release forms to obtain medical record information such which we ask the patient about their health problems and
as laboratory data from other institutions required for drug medications. Using open-ended questions (i.e., cannot be
therapy monitoring.[21 answered as “yes” or “no”) versus closed-ended ques-
tions will require the patient to explain and inform you
about their therapy. Open-ended questioning helps the
practitioner quickly assess the depth of the patient’s
Pharmacy refill records can be a valuable source for knowledge about their therapy and health.“’
assessing what the patient is prescribed and how often the The basic format of the history interview will apply to
patient refills the prescriptions. Clarification of medica- all settings, including acute care, long-term care, ambu-
tion usage should be verified by refill records in your latory care, and retail, and can be adjusted to the specific
practice setting or by contacting pharmacies that the patient needs of that setting. Utilization of patient data collection
uses. Inpatient pharmacists can provide valuable patient forms may be useful for documentation purposes and for
information to the outpatient or retail pharmacists upon guiding the flow and consistency of the interview. There
hospital discharge. This can prevent duplication and are many sources for the format of data collection forms,
medication errors.[51 which are discussed in a later s e ~ t i o n . [ ~ ’ ~ ]
adaptations in interviewing style.’ ’[@ In general, open beneficial to have when counseling patients that do not
the interview with the focus being on the patient (ask speak the same language.
about school, friends, hobbies, work, family, etc.) to
show interest in them personally. Once interest in
“them” is established, the patient will usually open up
to questioning.r61 NENTS OF A PATIENT
DRUG HISTORY
Infants and children younger than 5 years of age:
Interviewing the parent will be required, but with the Demographic and Patient Financial/
infant or child present. It is always best to refer to the Insurance Information
infant/child by name and to the parent by “Mr.” or
“Mrs.” to show both interest and respect. This section of the history should include the patient’s
The information obtained from the parent is third age, date and place of birth, any nicknames, names of
party, but is fairly accurate. Of note, however, the parent both parents, work contact information, gender, ethnicity,
may have preconceived ideas about the nature of the address, phone, emergency contact information, names of
child’s problem. Practitioners must remember to be the pharmacy the patient uses, and insurance informa-
supportive rather than judgmental when interviewing the ti~n.[~]
parent of the child. Avoid questions such as “why did you Most patients are used to providing this type of
give the child that medicine?” This would imply judg- information for their doctor’s office visits, but may
ment and that the parent did not have the child’s best question the pharmacist’s need to inquire. The phar-
interest in mind.[61 macist should explain that updated information will
assist in providing better care for the patient. For
Children older than 5 years of age: Avoid talking example, when a patient’s insurance does not cover the
“down” to children, but rather speak to them normally. medication the patient was prescribed upon hospital
The child can be interviewed about their health and medi- discharge, the cost may prevent the patient from taking
cations, both with and without the parent present. First, ask the medication. Obtaining insurance information prior to
the basic past medical history questions of the parent, then patient discharge as part of the history can prevent this
ask to speak to the child alone. Often, the child can tell you type of problem.
in more detail the severity of a problem or perception of
medication treatment benefit than the parent.[61
Medication Allergies and Intolerances
Adolescents: This population can be difficult to
question at times. It is best to be straight forward, and A medication allergy is a hypersensitivy reaction to the
“real” with this age group. allergen (drug) that provokes characteristic symptoms
(rash, urticaria, bronchospasm, or dermatitis) upon sub-
Aging patients: These patients can be visually or sequent exposure. A medication allergy may be delayed
hearing impaired, have poor memory, or be slow to or not seen with initial administration, but after repeated
answer questions. Be sure to speak slowly and in a lower exposure and antibody development the reaction occurs.
voice, and give extra time for a response to your questions. A drug intolerance is different in that the reaction is not
Most elderly patients may not be at ease with their medical due to an antibodylhypersensitivity response. Intolerance
problems, so be sensitive to them and really “listen.” is the inability of the patient to tolerate the particular
Interview the patient in a comfortable setting free of noise medication due to a side effect of the medication.[61
and barriers. If the patient is cognitively impaired, you Examples of drug intolerance are nausea from codeine or
may have the caregiver and the patient present together. constipation related to an antihypertensive medication.
Remember to include the patient in the discussion by Ask the patient to describe any drug allergies or in-
acknowledging them and establishing a relationship with tolerances using open-ended questions when possible so
them, even if the care provider has to answer questions that they can describe the reaction rather than simply
regarding medication administration, etc.[@ answering with “yes” or “no” to a question. Patients can
often confuse medication intolerance with an allergy. The
Language barriers: An interpreter may be needed in pharmacist can be valuable in clarifying this for the
special situations. Many pharmaceutical companies pro- patient record. The information should be as specific as
vide medication literature in other languages that may be possible, including the description, treatment, and date of
Drug History 287
the intolerance/allergy. For infants, children, and adoles- information helps understand the need for additional
cent, patients give primary attention to any allergies compliance aids or education on monitoring devices to
prevalent during infancy or childhood.r61 improve therapy outcomes.[51
Immunization status is an important part of the medical Barriers to compliance must be identified during the
history. Recording dates of childhood immunizations is history. Emotions, cognitive function, and physical ability
pertinent so that ongoing boosters can be scheduled can affect patient adherence to therapy. If a patient suffers
throughout childhood and adolescence.[61 from depression (emotional barrier), schizophrenia or
Adult immunizations are important to document as dementia (cognitive barrier), or severe arthritis of the
well and include vaccines such as pneumococcusl (for hands (physical barrier), compliance can diminish. Spe-
elderly and those at risk for pneumonia), influenza, he- cial attention should be given to these three areas, and
patitis B, and tetanus. Although not an immunization, skin barriers should be indicated on the history record. This
testing for tuberculosis might also be included under this process directs the implementation of specific aids to
section in high-risk patients (elderly, health care worker, improve compliance.[51
or immunocompromised patient).
ADDITIONAL INFORMATION FOR
Medications PATIENT HISTORIES
This list should include all prescription and nonprescrip- The following sections are typically part of the broader
tion medications (including nutritional supplements, vi- medical history. These sections may be included to
tamins, and herbal remedies) the patient is taking. In- provide a more thorough assessment of the patient’s the-
formation regarding the dosage strength, frequency, rapy and health needs.“-3,5,61
length of therapy, indication for use, and adherence must
be obtained. Perceived benefit from the medication or any
Social History
adverse experiences due to the medication should also be
noted. Remember to inquire using open-ended question-
The focus of the history is the patient’s occupation,
ing with patients using words such as “how,” “what,”
and “when,7$[132.51 lifestyle, family relationships, and support system. Points
of inquiry include job, marital status, diet, social drug use
Examples of open-ended questioning are “What are
(i.e., alcohol, tobacco, illicit drug use), and religious
you taking this medication for?”, “How do you take your
beliefs related to health care. Asking patients about their
medication?”, and “What do you do when you miss a
use of alcohol and illicit drugs can be difficult for
dose of your medication?” Closed-ended questions will
practitioners. It is not our role to pass judgment on the use
not really tell the interviewer how much the patient
of these agents, rather it is our job to gather the in-
understands about the dosing and purpose of medications
formation to properly assess the patient and their health.
without further questioning. Avoid questions such as “Do
Explaining to the patient that health outcomes are often
you take all of your medicine once a day?”, “Do you
affected by lifestyle choices and the family support for the
miss any doses?”, and “Did your doctor tell you what
individual may help with this part of the interview. For
this is for?”. All of these questions could be answered
example, a visually impaired patient would need assist-
with either “yes” or “no,” and additional questioning
ance with drawing up insulin. The support systems in
would then be required for clarification. The open-ended
place to assist the patient with the insulin preparation and
style is efficient in that one type of question tells the
administration need to be identified.
interviewer all the patient’s strong knowledge points and
also pinpoints weak areas.[21
Acute and Chronic Medical Problems
Additional Home Monitoring Knowledge of the patient’s health status will help the
and Compliance Aids practitioner understand the purpose of the prescribed
therapy, select optimal therapies for the patient, and help
Establish records on patient use of any monitoring devices prevent adverse drug-disease state interactions. For
(i.e., blood glucose monitor) or compliance aids. This example, a pharmacist would want to avoid recommend-
288 Drug History
SH (social history):
- EtOH -Tobacco use (amounts)
illicit drugs (list type if yes)
~ job status (list type of work)
~ marital stahis __children (number)
Akrgies/Immunhations:
Medication Type of Reaction Allergy or Intolerance
I I I
Irnmunimtions:
-Pneumococcal vaccine: (dates)
-Hepatitis B: (dates)
-Influenza: (dates)
-Tetanus: (dates)
-R t M R (dates)
Other:
__Prescription
- Medications
I
DoselFreqaency - Therapy Dates
I I
I I
I I
I I I I
COMIIlENTSl SOTES
REFERENC
Specific forms for patient drug histories are not required,
but may benefit the history-taking process. The advan- 1. Young, L.Y.; Koda-Kimble, M.A. Assessment of Therapy
tages of a patient drug history data collection form are: 1) and Pharmaceutical Care. In Applied Therapeutics: The
it establishes a record (written or computerized) for the Clinical Use of Drugs, 6th Ed.; Young, L.Y., Koda-
pharmacist's future use; 2) it provides a format for Kimble, M.A., Eds.; Applied Therapeutics: Vancouver,
prompting questions during the interview; 3) its consistent Washington, 1995; 1-4.
format fosters organized flow of questioning; and 4) it 2. Rovers, J.P.; Currie, J.D.; Hagel, H.P., McDonough, R.P.;
prevents duplication of questioning in the future. The data Sobotka, J.L. Patient Data Collection. In A Practical Guide
recording process should never detract from the inter- to Pharmaceutical Care; American Pharmaceutical Asso-
action with the patient. ciation: Washington, DC, 1998; 26-55.
The format can vary, but most forms will contain lines, 3. Titcomb, L.C. The pharmacist role in drug history taking.
Br. J. Pharm. Prac. 1989, 11; 186-195. (Jun).
tables, or checklists for the patient history components
4. Claoue, C.; Elkington, A.R. Informing the hospital of
discussed in this entry: demographics, social information, patients' drug regimens. Br. Med. J. 1986, 292, 101.
allergy information, medical problems and procedures, 5. Munroe, W.P.; Briggs, G.C.; Dalmady-Israel, C. Establish-
and patient prescription and nonprescription medications. ing a Relationship with Patients and Identifying Needed
Many sources have good examples of patient data Information. In Ambulatory Clinical Skills Program: Core
collection form^.^^'^] An example of a patient history form Module; American Society of Health-System Pharmacists,
is given in Fig. 1. The format of the form will require Inc.: Gaithersburg, Maryland. 1998; 1-22.
modification for the specific care setting and goals of the 6. Bates, B. Interviewing and Health History. In A Guide to
individual practitioner. Physical Examination and History Taking, 5th Ed.; J.B.
Some drug therapy management clinics use computer Lippincott Company: Philadelphia. 1991; 1-26.
databases that store the patient history information and I. CoumaCare Patient Management System. DuPont Pharma-
ceuticals, Chestnut Run Plaza. PO Box 80723, Wilming-
can print out the profiles when needed.[*-lol A few
ton, Delaware 19880-0723. 1-800-474-2762.
examples of data management software programs include 8. Anticoagulation Information Manager. Wellersoft. 5416
CoumaCareE Patient management system, Anticoagula- Parkgrove, Ann Arbor, Michigan 48103. (734) 213-
tion Management Program (AMP) Anticoagulation, and 5360.
Information Manager (AIM)."-91 Pharmacist-managed 9. Anticoagulation Management Program. Telehealth Sys-
anticoagulation and lipid clinics often use software prog- tems, Inc., 520 N. State Road, 135 Suite M78, Greenwood,
rams to store and update patient history information. Indiana 46142. (317) 535-6161.
PROFESSIONAL DEVELOPMENT
atric e
C'reighton Universily, Oinnha, Nebraska, U.S.A.
been such practices to provide information to patients. Development and/or modification of policies and
These were sometimes established using grant funding, procedures.
but failed financially afterward. There have been some Adverse drug reactionlmedication error tracking and
practices for a fee (e.g., 900 phone numbers), with good reporting.
results. Now, more drug information is being provided via Investigational drug information (e.g., Institutional
the Internet. This includes services such as those run by Review Board activities, central depository of study
Internet pharmacies (e.g., http://www.rx.com), pharmacy protocols, providing patients and practitioners with
organizations (e.g., http://www.pharmacyandyou.org), information about investigational drugs, managing
and even individual pharmacists (e.g., http://www. medication studies).
medconsultant. codindex.shtm1). Poison information-occasionally, drug information
Functions of those services tend to center around services are run in conjunction with poison informa-
providing prepared drug information documents (e.g., tion services.
patient information sheets) and answering specific Management of department information equipment,
medication-related questions. These are seldom money- software, and procedures.
making operations, but are often provided as a service to Provision of educational programs and materials,
attract customers to a pharmacy or as a public service. which may include newsletters and web sites.
Potential contract services with industry, managed
Institutional and cademic Practice care, or insurance companies and other groups to
provide specific information services (see the informa-
These two environments are grouped because they are tion listed under those environments for further
similar in nature and are often combined. Typically, information on necessary
practitioners here are located in a dedicated drug A major function for academic, and occasionally
information center that resides in a hospital pharmacy or institutional, drug information centers is education.
medical library. Typically, such services were begun to This can include pharmacy students, residents
provide literature searches and answers for specific (general or drug information specialty residents),
questions and to perform formulary management.rs1 and fellows.
Given the greater concern for the cost of services, the
former service is now sometimes deemphasized. Instead, Drug information practitioners in institutional and
services that will decrease hospital costs (including academic environments may work within a single ins-
liability), increase income, or provide functions that titution or may be involved in a hospital system that
are required by legal or regulatory bodies are often requires services to multiple institutions, perhaps over a
performed. Overall, it has been shown that having a wide geographic region.
drug information service may save 2.9 to 13.2 times
its cost.r6j Industry
The following functions are performed by drug
information practitioners in the institutional and academic Within the pharmaceutical industry there is a major need
environments:L7j for drug information specialists for a variety of functions:
Answer questions and perform literature searches. Answering information requests from health care pro-
Drug formulary management (e.g., evaluating drugs fessionals, employees, and occasionally patients.
for addition or deletion from the formulary, pre- Preparation and management of information databases
paring use guidelines and policies and procedures, for employees.
pharmacoeconomic analysis), including publication Preparation of materials to be distributed directly to
of a drug formulary book, whether in hard copy or health care professionals, employees, and patients.
electronic format. Setting up and managing clinical drug research and the
Quality assurance activities (e.g., departmental quality information derived from it.
assurance, drug usage evaluation, medication usage Preparing Food and Drug Administration (FDA)-
evaluation). This includes setting up, managing, and required information, such as New Drug Applications.
evaluating the data from such activities. Collecting, collating, and using adverse drug reaction
Development and/or modification of evidence-based information.
clinical guidelines. This includes the concepts of di- Provision of training to pharmacy students and
sease state management and outcomes management. residents.
292 Drug Information Pharmacy Practice
It is important to note that in the industrial envir- ing evidence-based, clinical guidelines), and other offi-
onment, physicians often manage the drug information cial documents.
services or other areas that use drug information
practitioners, while they are staffed by some combination
o~ern~ent
of physicians, pharmacists, nurses, or others.
Government organizations at the national or state levels
are and ~nsurance
have a need for drug information specialists. For example,
FDA (http://www.fda.gov) can use the services of drug
Drug information services in a managed care or insurance
information practitioners in the collection, organization,
company environment often deal with issues concerning
management, and distribution of information on drugs
providing the lowest cost therapy for patients (i.e.,
(both investigational and marketed).
keeping reimbursement cost low). At one time, this might
At a state level, drug information practitioners may be
have amounted to individuals (including nonpharmacists)
involved with drug utilization review, whereby data on
simply reviewing and comparing the costs of drugs within
drug usage patterns is collected and analyzed to determine
a therapeutic class. The assumption was that they were all
ways by which drug therapy may be improved.
interchangeable. Fortunately, it has become more widely
Other activities similar to those listed for managed care
recognized that many factors are involved in providing
organizations can also be performed by government drug
the best and least expensive therapy to patients. This
information practitioners. Also, some state and foreign
includes the efficacy of the drug, adverse effect frequency
governments have drug formularies, which drug informa-
and severity, cost of monitoring, the need for additional
tion practitioners would be involved in managing.
care, the length of therapy, and a variety of other
therapeutic, ethical, legal, and patient issues. A full
pharmacoeconomic analysis is necessary to ensure that all
aspects are evaluated. It is not unusual that a drug product
that initially looks to be the least expensive may actually
be the most expensive due to a variety of reasons, such as
a need for increased monitoring, lower efficacy, more There are a variety of resources that may be of value to
severe adverse effects, etc. Drug information centers may drug information practitioners, both in learning how to
evaluate whether reimbursement is available for drugs or perform the various necessary skills and in carrying out
the disease state, what copays might be required, res- the responsibilities.
trictions or authorizations that are needed before medi- There is currently one general reference to guide drug
cation use, and other information. information practitioners and those who would like to
Also, drug information centers in these environments learn the skills. Other general references are currently out
may spend a lot of time preparing information on the best of print, although some may still be obtainable. They are
way to treat disease states to produce optimal outcomes as follows:
for the lowest cost (i.e., disease state management,
outcomes management). This information may be used * Malone PM, Mosdell KW, Kier KL, Stanovich JE.
either actively or passively to educate health care prac- Drug Information-A Guide f o r Pharmacists, 2nd ed.
titioners, particularly physicians and pharmacists. New York: McGraw-Hill, 2001. This is the most
Drug information practitioners in these areas may also complete and up-to-date reference, covering all as-
perform other drug information activities, such as answer- pects of drug information practice, including formu-
ing questions, quality assurance, and electronic informa- lary management and quality assurance. It includes
tion interchange on a national level. Other activities listed extensive lists of references and Internet sites that are
under institutional practice may also be carried out. of use to individuals who are trying to obtain drug
information. Also, this reference covers the evaluation
ssociation of all types of literature, rather than just clinical
studies, which many other drug information books are
Various professional associations have drug information limited to covering.
needs. This may have to do with association publications;
researching items of interest to the association; providing The June and August 1998 issues of Journal of
information for association members or other interested Pharmacy Practice are also devoted to the practice of
people; and preparation of statements, guidelines (includ- drug information and contain a great deal of useful
Drug Information Pharmacy Practice 293
information, similar to the contents of the previously easier use. Also, references dealing with the electronic
mentioned books. management of information are particularly helpful to
There are also references that cover specific aspects of drug information practitioners.
drug information practice:
RT
Galt KA. Analyzing and Recording a Drug Informa-
tion Request. Bethesda, MD: American Society of
There are a variety of professional networking opportun-
Hospital Pharmacists, Inc., 1994. This first module in a
ities available through professional associations for drug
series of three deals with the skills needed to initially
information practitioners. They are presented here in
take a drug information request, mostly from a general
alphabetical order:
practitioner's point of view.
Smith GH, Norton LL, Ferrill MJ. Evaluating Drug
Literature. Bethesda, MD: American Society of
. American Medical Informatics Association (AMIA)-
This group is concerned with health information
Health-System Pharmacists, Inc., 1995. This second
technology. It consists of members in a wide variety
module deals specifically with the skills necessary to
of professional areas. Some professions, such as
evaluate drug literature.
dentists and nurses, have specific working groups in
Galt KA, Calis KA, Turcasso NM. Preparing a Drug
the association. Some drug information pharmacists
Information Response. Bethesda, MD: American
are members, but there is not yet a working group for
Society of Health-System Pharmacists, Inc., 1995.
those individuals. Further information about this
This third module takes the information obtained and
organization can be found at http://www.amia.org.
evaluated using methods in the first two books and
0 American Society of Health-System Pharmacists
describes methods to effectively distribute it. Again, it
(ASHP)-Clinical Practice Section-Drug Informa-
addresses the subject from the point of view of the
tiodPharmacoeconomics Network-Members of
average pharmacy practitioner.
ASHP can also become members of the Clinical
Ascione FJ. Principles of Scientific Literature Eva-
Practice Section, which has many practitioner net-
luation: Critiquing Clinical Drug Trials. Washington,
works. One of these is for drug information and
DC: American Pharmaceutical Association, 200 1.
pharmacoeconomics. This network sponsors continu-
While previous editions of this book were somewhat
ing education programs at the ASHP annual and
broader in scope, the current edition specifically co-
midyear clinical meetings. Members are also provided
vers the evaluation and interpretation of scientific
a time and place to gather at the midyear clinical
papers describing clinical trials.
meeting, and sometimes the annual meeting, to discuss
Slaughter RL, Edwards DJ. Evaluating Drug Litera-
topics in their area of interest. In addition, an e-mail
ture-A Statistical Approach. New York: McGraw-
listserve is available for communications among mem-
Hill, 2001. This book covers a wider area of drug
bers of this network and information is available for
literature evaluation than the previous reference, in-
members at http://www.ashp.org/clinical/index.html.
cluding some information on other topics, such as
This group would be of most interest to institutional
performing a literature search.
and academic drug information practitioners. A va-
Snow B. Drug Information-A Guide to Current
riety of guidelines, as well as position statements of
Resources. Lanham, MD: Scarecrow Press, Inc., 1999.
interest to drug information practitioners on such
This is an extremely comprehensive book that lists and
subjects as formulary management and medication
describes multiple sources of drug information. The
use evaluation, are available at http://www.ashp.org/
focus is very limited, but no other book covers this
bestpracticeshdex.htm1.
subject as completely.
0 Consortium f o r the Advancement of Information,
Policy and Research (CAMIPR)-This is the newest
There are many resources available to the drug - in- of the drug- information associations, formed in 1994
formation practitioner. They will not be presented here to better serve the needs of institutional and academic
due to their vast number, but they are described in some drug information pharmacists."01 This group generally
of the previous references. It should be noted that many of meets in conjunction with the ASHP midyear clinical
those resources are now available electronically (e.g., meeting. There is no cost involved in joining the
evidence-based clinical practice guidelines are available organization; it is only necessary to join their listserve.
at http://www.guideline.gov), allowing wider access and Information on joining and compilations of previous
294 Drug Information Pharmacy Practice
listserve discussions is available at http://druginfo. 4. Franckc, D.E. The role of the pharmacist as a drug
creighton.edu/camipr. information specialist. Am. J. Hosp. Pharrn. 1966, 23, 49.
Drug Information Association (DIA)-The DIA is a 5. Wittrup, R.D. The responsibility of the hospital for drug
information services. Am. J. Hosp. Pharm. 1965, 22,
group devoted entirely to drug information specialists,
58-61.
including physicians, pharmacists, and others. It is
6. Kinky, D.E,; Erush, S.C.; Laskin, M.S.; Gibson, G.A.
mostly involved with drug information practitioners in Economic impact of a drug information service. Ann.
industry practice. Information o n the organization and Pharmacother. 1999, 33, 11 - 16.
its services can be found at http://www.diahome.org. 7. Rosenberg, J.M.; Fuentes, R.J.; Starr, C.H.; Kirschenbaum,
H.L.; McGuire, H. Pharmacist-operated drug information
Other smaller drug information groups also exist." l' centers in the United States. 1995, 52, 991-996.
8. Forrester, L.P.; Scoggin, J.A.; Vclle, R.D. Pharmacy
management company-negotiated contract for drug in-
formation services. Am. J. Health-Syst. Pharm. 1995, 52,
EFERENCES 1074- 1077.
9. Redman, R.L.; Mays, D.A. Drug information services in
1. Anderson, R.D.; Latiolais, C.J. The Drug Information the managed care setting. Drug Benefit Trends 1997, 0
Ccntcr at the Ohio State University Hospitals. Am. J. Hosp. (ALlg), 28-30, 36-40.
Pharm. 1965, 22, 52-57. 10. Vanscoy, G.J.; Gajewski, L.K.; Tyler, L.S.; Gora-Harper,
2. Parker, P.F. The University of Kentucky Drug Information M.L.; Grant, K.L.; May, J.R. The future of medication
Center. Am. J. Hosp. Pharm. 1965, 22, 42-47. information practice: a consensus. Ann. Pharmacother.
3. Amerson, A.B.; Wallingford, D.M. Twenty years' experi- 1996, 30, 876-881.
ence with drug information centers. Am. J. Hosp. Pharm. 11. O'Brien, E. Network helps pharmacists access drug
1983, 40, 1 172---1178. information. Hosp. Pharm. Rep. 1997, I 1 ( S ) , 55.
PHAKMACY PKACTICE ISSUES
Nanette C. Bultemeier
Dean G. Haxby
Oregon State University, Portland, Oregon, U.S.A.
Table 1 Criteria JCAHO surveyors generally look for in cern about product potency and stability. Expiration dates
evaluating compliance and product recalls may go unnoticed.['53161Products
0 There is a system, defined by policy and procedure, for the might be stored in garages and automobile trunks of
control, accountability, and security of all drug samples pharmaceutical representatives, potentially exposing sam-
throughout the organization. ples to extremes in temperatures or humidity.
c The drug samples are properly stored. Significant deficiencies in the security and control of
c Drug sample storage areas are routinely inspected. samples have been well d ~ c u m e n t e d . [ ~ , ' * -In
* ~ fact,
~ it
0 Drug samples are secure. has been estimated that just over half of samples actually
0 Drug samples are labeled and dispensed according to the reach patients.[jl Samples may be used by prescribers
same standardized method that the hospital uses for and staff, or they may be diverted. Personal use of drug
nonsample prescription medications. samples by physicians and other healthcare providers
0 Documentation requirements for sample drugs should be
raises ethical concerns and is not without risk.['*,'']
the same as other nonsample medications ordered and
Limaye and Paauw described three medical residents
dispensed by the clinic or hospital.
0 There must be an effective recall mechanism for drug who self-prescribed antimicrobials and were subse-
samples. quently diagnosed with Clostridium difficile infection.["]
Tong and Lien reported self-medication with samples
(From Ref. [8].) and distribution of samples to nonphysicians by almost
60% of pharmaceutical representatives surveyed at a
Canadian family practice office.[201A contributing factor
drugs.["] Other factors for dispensing samples include to some of these issues is that institutional or facility
improving patient satisfaction and sample policy and procedures are often absent, or com-
pliance is poor. One institution found only 10% com-
pliance when the inventory of samples was compared
G s with the required written documentation. Even after an
educational program in which the policy was explained
Despite the many apparent benefits of sampling, the to the house staff, a second audit found only 26% com-
practice has been heavily criticized. Concerns surround- pliance.[211Poor compliance with policy and procedure
ing sampling include patient safety, product integrity, may jeopardize patient safety, as well as put the institution
security and control of samples, ethical issues, influence at risk for JCAHO recommendations or Board of Phar-
on prescribing habits, and costs to the healthcare sys- macy penalties.
tem,[3.5,9,10,15 - 241 Another concern is that drug choices may be dictated
Important safety controls are lost when samples are more by what is available in the sample closet than by
used. Sampling bypasses the safeguards of pharmacist evidence-based recommendations or by known cost-
medication regimen review and counseling. Drug in- effectiveness. The influence of sampling has potential
teractions, which are screened when prescriptions are implications for patient care and healthcare costs. While
dispensed at pharmacies, may go undetected when sam- studies have shown that sampling may increase sub-
ples are Labeling samples with patients' names sequent prescription of the sampled drugs, research on the
and instructions for use is often inconsistent, if it is done quality of prescribing related to sampling is
at a11,[3S,10,161 one study found that instructions to the A survey by Chew et al. of physicians' self-reported
patient accompanied less than 50% of patient encounters prescribing patterns for three clinical scenarios found that
involving sample dispensing and were predominantly the availability of drug samples led physicians to dispense
verbal in nature.[31 Patient information sheets are infre- and subsequently prescribe drugs that differ from their
quently provided by the manufacturer in sample pack- preferred drug choice.['] In addition, the study found that
aging, and most providers do not have systems to generate when drug samples were made available, 27% of phy-
the extensive printed information that is provided to sicians indicated that they would dispense a drug sample
patients at p h a m ~ a c i e s . " ~There
~ is also concern about not recommended as a first-line agent by the Joint Na-
increasing prescribing errors, because formulary and non- tional Committee on Hypertension.[']
formulary drugs with which prescribers and staff may not Because sampling is labor intensive and is subject to
be familiar are often delivered by representatives.[l6I industry and institutional regulations, it is a very costly
The potential for inadequate sample inventory man- practice. In addition to the wholesale value of samples,
agement in prescribers' offices and inappropriate storage there are other costs, such as packaging, distribution via
of products by pharmaceutical representatives raises con- representatives, prescriber and staff time interacting with
Drug Samples 297
representatives and handling samples, and institutional Some pharmacists dispense samples in the clinic
administration of sample programs. The bulky cardboard when requested by prescribers. A full range of services,
packaging that is characteristic of drug samples not only including assisting with product selection, labeling the
creates an inordinate amount of waste, it also takes up product, and counseling the patient, may be provided.
valuable office Health systems likely incur Sometimes pharmacists supervise nursing staff that or-
the financial burden of giving out “free” samples when der, stock, label, and discard samples.[251 Educational
less expensive medications are available, although there efforts to promote sample compliance and appropriate
is little evidence supporting this. A sample is only free in prescribing are often done or coordinated by pharma-
the sense that neither the prescriber nor the patient paid cists. Providing reviews and summaries of treatment
cash for it when it was received. guidelines and evidenced-based pharmacotherapy that in-
Despite the many shortcomings of sampling, it is often clude formulary and cost information to small groups, via
continued, because it enables prescribers to provide me- newsletters and in postings in sample closets, are com-
dications to indigent patients. However. sampling is an mon academic detailing activities used to counter sam-
inefficient method for helping patients in need of med- pling practices.
ications.’241 Supplies may be inconsistent, and multiple To further encourage prescribing of cost-effective
packages of samples are usually required on a frequent drugs, some clinics request generic samples or prepack-
basis to maintain patients’ needs. Patients often do not get aged first-line medications. Generic samples are available
as much drug as needed, or they are switched from brand from some manufacturers, and at least one pharmacy
to brand based on the samples that are available, creating benefit management company is planning to provide
confusion for patients and prescribers. samples of generic drugs in its efforts to encourage the
use of generic drugs. Unfortunately, there has been li-
mited success in getting prescribers to use generic sam-
ples or prepackaged first-line medications.[”]
Technology is being used to improve sample control
Efforts to address concerns about sampling range from and patient safety. Some facilities have developed da-
development of policies and guidelines for sample use to tabases to generate labels and to log lot numbers of sam-
restrictions and banning of samples. Pharmacists are ples dispensed. Sophisticated systems that include
involved in, and many times spearheading, sample prac- computer-controlled dispensing cabinets are marketed
tice changes.[14,’621325-273 by companies like www.drugsampling.com. These sys-
In facilities where samples are used, important first tems include fingerprint-recognition technology to open
steps to bringing sample practices into compliance in- the cabinets and touch screen monitors that can be used to
clude consulting state and federal regulations and JCAHQ generate medication labels, patient education, and re-
standards (Table 1). Guidelines and recommendations quired dispensing documentation. The systems are paid
from organizations such as the Society of Teachers of for by renting space in the cabinet to drug companies. The
Family Medicine and the Institute for Safe Medication value for the manufacturer, according to a company that
Practices (ISMP) can be markets this type of system, is to maintain sampling
Other innovative approaches to improve sampling pro- privileges in clinics where sampling is at risk of being
cesses have been developed. Multiple-part carbonless banned because of poor control and to provide sample
adhesive forms with space for patient name, date, me- usage information to the manufacturer.
dication name and strength, quantity, directions for use, Restricting samples to drugs available on or preferred
lot number. expiration date, and physician signature have by the organization’s formulary is an approach used by
been created for signing out samples. One copy goes to some organizations to discourage prescribing of non-
the patient, one goes to the chart, and one is kept for formulary drugs. Some clinics appoint a committee,
record maintenance. This type of system helps ensure which usually includes a pharmacist, to develop a for-
written directions, provides a double check on expiration mulary of requested samples based on safety, efficacy,
date, and becomes a log with lot number in the event and ~ o s t . “ ~General
, ~ ~ ] guidelines that one clinic used in
of a recall. Although it is time-intensive, maintaining a selecting formulary samples included: 1) stocking one or
perpetual inventory or auditing closets and sign-idsign- two of the least expensive drugs in each therapeutic class;
out logs on a regular basis is a way to determine if samples 2 ) delaying the addition of new agents until adverse
are being stolen. Posting information about unaccounted reactions and drug interactions are clinically demon-
for samples may heighten awareness of security and com- strated; 3) refraining from adding “me too” drugs unless
pliance issues. they have clear advantages; and 4) accepting drugs that
298 Drug Samples
have generic equivalents offering long-term savings to ling which samples will b e requested and ensuring ap-
patients.[251Some clinics simply restrict samples to those propriate labeling, documentation screening for drug in-
that address the most common needs of patients treated in teractions, and patient education will help improve the use
the practice.[251 Placing restrictions on the types and of drug samples.
quantities of samples requested promotes efficient use of
storage space by reducing the number of unused and
expired products. [ 6,251
Despite implementing many of the controls mentioned
above, more and more facilities are banning sam-
p l e ~ . [ ' ~ Most
~ ~ ' ] cite concerns about complying with re- 1. Pharmaceutical Research and Manufacturers of America.
gulations and the promotion of poor prescribing habits Backgrounders and Facts: Marketing and Promotion
of Pharmaceuticals; Available at: http://www.phrma.org/
that lead to increased costs. Vigilance in enforcing
publications/documents/backgrounders//2000- 10-23.184.
policies prohibiting samples is necessary, because it is
phtml (accessed January 8, 2001).
likely that samples will find their way into clinics.[l6I 2. Wazana, A. Physicians and the pharmaceutical industry: Is
Interestingly, some institutions provide exemptions from a gift ever just a gift? JAMA, J. Am. Med. Assoc. 2000,
the sample bans when a pharmacist in the clinic is res- 283 (3), 373-380.
ponsible for ensuring c ~ m p l i a n c e . " ~ ~ 3. Backer, E.L.; Lebsack, J.A.; Van Tonder, R.J.: Crabtree,
B.F. The value of pharmaceutical representative visits and
medication samples in community-based family practices.
A LT PLES J. Fam. Pract. 2000, 49 (9), 811-816.
4. Haxby, D.G.; Rodriguez, G.S.; Zechnich, A.D.; Schuff,
Coupons or voucher systems have been proposed as an R.A.; Tanigawa, J.S. Manufacturers' distribution of drug
alternative to sample^."^.'^] Voucher systems rely on samples to a family medicine clinic. Am. J. Health-Syst.
Pharm. 1995, 52, 496-499.
prescribers to issue coupons to patients who then present
5. Morelli, D.; Koenigsberg, M.R. Sample medication
the coupons along with their prescriptions to the phar- dispensing in a residency practice. J. Fam. Pract. 1992,
macy of their choice. With the information provided on 34 (l), 42-48.
the voucher, prescriptions are paid for through on-line 6. Wolf, B.L. Drug samples: Benefit or bait? [letter]. JAMA,
pharmacy claims. Medications are dispensed to patients J. Am. Med. Assoc. 1998: 279 (21), 1698-1699.
fully labeled and with counseling. 7. Prescription Drug Marketing Act of 1987, 102 Stat. 95;
Medications for indigent patients may b e obtained 1987.
through pharmaceutical company medication assistance 8. Joint Committee on Accreditation of Healthcare Organiza-
programs.[291These programs provide brand name medi- tions. Pharmacy FAQs; Available at: http://www.jcaho.org/
cations to patients based on financial need. Each com- standards-frm.htm1 (accessed on January 8, 2001).
pany determines the eligibility criteria for its program. 9. Chew, L.D.; O'Young, T.S.; Hazlet, T.K.; Bradley, K.A.;
Maynard, C.; Lessler, D.S. A physician survey of the effect
The application processes and the amount of medication
of drug sample availability on physicians' behavior. J. Gen.
supplied vary. While medication assistance programs Intern. Med. 2000, 15 (7), 478-483.
help thousands of patients obtain medications, it re- 10. Shaughnessy, A.F.; Bucci. K.K. Drug samples and family
quires cumbersome paperwork and frequent reapplica- practice residents. Ann. Pharmacother. 1997, 31; 1296-
tion, and there can be considerable delays in getting 1300.
medication to patients.[301Like sampling, medication as- 11. U S . Senate Committee on Labor and Human Resources.
sistance programs are limited in their ability to help in- Hearings on Advertising, Marketing, and Promotional
digent patients. Practices of the Pharmaceutical Industry. l O I s t Cong.,
2nd Sess., December I 1 and 12; 1990.
12. Weary, P.E. Free drug samples. Use and abuse. Arch.
Dermatol. 1988, 124, 135-137.
13. Bastiaens, L.; Chowdhury, S.; Gitelman, L. Medication
samples and drug compliance. Psychiatr. Serv. 2000,51(6),
Drug sampling is a controversial marketing technique 819.
used to promote pharmaceuticals. Pharmacists should 14. Page, L. More clinics ban drug samples, citing cost, safety
be encouraged to get involved in efforts to promote safe concerns. Am. Med. News 2000, 43 (39), 1-2.
and appropriate use of samples and ensure control and 15, Institute for Safe Medication Practices. Safety briefs. ISMP
security. Clinics and institutions should have and enforce Medication Safety Alert! 1996, I (5); 1.
policies and procedures for managing samples. Control- 16. Institute for Safe Medication Practices. Sample medica-
Drug Samples 299
tions: Safe management is a difficult but necessary pro- 24. Storrs, F.J. Drug samples. A conflict of interest? Arch.
cess. ISMP Medication Safety Alert! 1999, 4 (14), 1. Dermatol. 1988, 124. 1283- 1285.
17. Dill, J.L.; Generali, J.A. Medication sample labeling prac- 25. Sigmon, J.L.; Anastasio, G.D. Drug sample closet. J. Fam.
tices. Am. J. Health-Syst. Pharm. 2000, 57, 2087 2090. Pract. 1992, 34, 262- 263.
18. Westfall, J.M.; McCahe, J.; Nicholas, R.A. Personal use of 26. MeSherry, T.J.; Tonnies, F.E. Dispcnsing medication
drug samples by physicians and office staff. JAMA, J. Am. samples by the pharmacist in an institutional setting. J.
Med. Assoc. 1997, 278 (2). 141 -143. Am. Coll. Health 1992, 40, 136-235.
19. Timaye, A.P.; Paauw, D.S. Personal use of drug samples 27. Erickson, S.H.; Cullison, S. Closing thc sample closet.
by physicians and office staff [letter]. JAMA, J. Am. Med. Fam. Pract. Manag. 1995. 43 47.
ASKC. 1997, 278 (19), 1568-1569. 28. STFM Group on the Pharmaceutical Industry in Family
20. Tong, K.L.; Lien, C.Y. Do pharmaceutical representatives Medicine. Guidelines ,for Residency Program Relation-
misuse their drug samples? Can. Fam. Physician 1995. 41, ships with Phnrmaceutical and Other Proprirtarj Corn-
1363- 1366. panie.~;Society of Teachers of Family Medicine: Kansas
21. O'Young, T.; HaAet, T.K. Removal of drug samples from City, Missouri, 1994.
two teaching institutions. Am. J. Health-Syst. Pharm. 200 29. Pharmaceutical Research and Manufacturers of America.
57, 117% 1180. Directory of Prescription Drug Patient Assistance Pro-
22. Donohoe, M.T.; Matthews, H. Wasted paper in phar- gi-urns; Available at: http://www,phrina.org/searchcures/
maceutical samples. N. Engl. J. Med. 1999,340 (20). 1600. dpdpap/ (accessed January 8, 2001).
23. Pai, M.P.; Graci, D.M.; Bertino, J.S., Jr. Waste generation 30. Prutting, S.M.; Cerveny, J.D.; MacFarlane, L.L.; Wiley,
of drug product samples verses prescriptions obtained M.K. An interdisciplinary effort to help patients with li-
through pharmacy dispensing. Pharmacotherapy 2000, 20 mited prescription drug benefit afford their medication.
( 9 , 593 59s. South. Med. J. 1998, 91 (9), 815--820.
PHARMACY PRACTICE ISSUES
ink
services, program, economic evaluation, cost justification, Each article was assessed for the type of evaluation
cost, cost effectiveness, cost-benefit, cost analysis, cost- and categorized (Table 1). Two factors were considered in
consequence analysis, and cost-utility analysis. Review determining the type of evaluation: the presence of two or
articles, editorials, and other unoriginal reports were more alternatives, and the consideration of both input
excluded from the search. All citations identified were (costs) and outcomes. Evaluations that included two or
screened for inclusion by review of titles and abstracts. more alternatives (i.e., concurrent control group, histo-
Those articles for which abstracts were not available from rical control, preintervention and postintervention design)
the computerized databases were collected manually and were considered true analyses, whereas those that did not
screened for inclusion. include a comparison were labeled descriptions. A de-
Inclusion criteria were English language, original scription of the type of analysis was assigned to the
evaluation, publication between January 1988 and De- evaluation and included the options of cost or outcome
cember 1995 inclusive, assessment of a clinical pharmacy description, cost or outcome analysis, cost and outcome
service (defined as patient-level interaction, and not description, and true clinical economic evaluation. Those
including policy-type interventions unless accompanied articles considered true clinical economic evaluations
by a patient-level interaction), and some economic as- were subcategorized by type, options including cost-
sessment. Exclusion criteria were reviews, editorials, and minimization analysis, cost-benefit analysis, cost-effec-
letters, and studies published in abstract form only. All tiveness analysis, and cost-utility analysis.[61
papers suspected of meeting the inclusion criteria were Descriptive statistics were used to profile and char-
submitted to full review. In addition, the authors examined acterize the articles within each data field abstracted by
personal files, and a secondary search of the titles of the reviewers, including the type of clinical service per-
articles cited in papers meeting the inclusion criteria was formed, the site of the study or evaluation, and the type of
conducted. Papers identified through this search were analysis performed.
again collected and screened for inclusion, and added to
the set of papers subjected to full review.
In the full review process, a modified block randomi- ESULTS
zation scheme was used to confirm inclusion and to ab-
stract information and assess the quality of each article. The results of the search and screen process used are
Each paper was randomly assigned to two of four re- illustrated in Fig. 1. A total of 575 articles were found
viewers. Reviewers were blinded to original authors’ through the original search. A preliminary review of the
names, affiliations, and journal of publication. Reviews abstracts of these articles identified 444 that did not
were recorded on a standard case report form and entered involve the justification of clinical pharmacy services,
into a database for analysis. Discrepancies between re- and these were deleted from the set. Seven articles were
viewers were arbitrated by group consensus. Reviewers added from the files of the authors, and 46 were identified
first made a final check of inclusion and exclusion criteria through the secondary search of the articles found. Thus,
to exclude further any nonapplicable articles. Reviewers 184 articles were subjected to full review. During full
recorded the study setting, objectives, methods, results, review, an additional 80 articles were found that did not
and any additional comments. meet the inclusion criteria: 44 did not review a clinical
Primary search
(n = 575)
I
- Excluded following review
of title and abstract
(n = 444)
from intravenous to oral administration of histamine*-
receptor antagonists (H2RAs). Because of the number of
articles describing targeted drug programs, those articles
are further subcategorized in Appendix 1 based on the
class of drug involved.
Articles Provided in Appendix 1 are the following data for
pulled for Secondary search of citations each article: 1) reference number; 2) the setting in which
further ______> added to full group
the evaluation was conducted; 3) a summary of the pri-
review (n = 46)
(n = 131) mary intent or objective; 4) a description of the anal-
! ytical method of the evaluation; 5 ) number and type of
alternatives included in the evaluation; 6) input cost
Table 3 Analytic methods of cost-justification studiesa lary andlor benefits associated with providing the pro-
gram or service. Some studies used charges (i.e., hospital
Method Number of studies
room, emergency room) rather than true costs.
Outcome analysis 37 Outcomes or consequences of the services described
Outcome description 33 were considered in all the articles. The most common
Economic analysis 19 (12 = 80, 77%) outcome measured was drug costs avoided
Cost and outcome description 13 (i.e., the impact of the program on reducing use or cost
Cost analysis 1 of a particular drug). Other nonfinancial outcomes were
Cost description 1
also measured. including length of hospital stay (n = 14,
aRefer to Table 1 for classification analysis 13%), use of nonpharmaceutical resources. rates of ad-
verse drug reactions, frequency of pharmacist-driven
latory clinics of various affiliations, health maintenance therapeutic interventions, and qualitative changes in pre-
organizations, and community pharmacies. scribing patterns. True clinical patient outcomes were
Table 3 summarizes the analytic methods used in the considered in few studies.
included articles. Although 19 (18%) articles were con- Ninety-three (89%) of the articles described beneficial
sidered full economic analyses (by definition, consider- financial impact of the clinical pharmacy service des-
ing two or more alternatives and measurement of both cribed. Many provided either gross cost savings or, in
input costs and outcomes), most were less rigorous. The those that did consider input costs, net savings. Of the 33
most common types of studies were outcome analyses studies that considered input costs, 31 (94%) demon-
( n = 3 7 , 3 5 % ) , which considered two or more alterna- strated positive findings. Results of these were presented a
tives but excluded consideration of the costs of pro- number of different ways (Table 4).
viding the service, and outcome descriptions ( n = 33, Commonly these articles expressed net savings on an
32%), which failed to consider two or more alternatives annual basis or for the time period of the study. For
and did not consider the cost of providing the service. example, a study in 1992 described annual net cost sav-
The study design of the included articles was further ings of $221,056 for clinical pharmacy services provided
analyzed by individually considering the use of a com- in an ambulatory care clinic.'251 It did not, however, in-
parison group (alternative) and by the types of input clude a control group. In other cases, savings were ex-
costs and outcomes measured. Sixty-one (59%) studies pressed per patient admission or per patient-day. In 1993,
included a comparison group, whereas 43 (41%) did not a well-conducted and controlled evaluation described an
and were therefore considered to be descriptive. The average net savings of $377 per patient admission as a
study designs used in papers that had a comparison group result of clinical pharmacists assigned to selected in-
were a concurrent control group (n=21), a historical patient medical service^."^]
control group ( n = lo), and preintervention and postinter- In seven articles, results were expressed as benefit: cost
vention groups ( n = 30). Precontrols and postcontrols ratios. They differed in type of clinical pharmacy service,
were differentiated from historical control designs in the site of provision of service, and resources invested in the
temporal relationship to the intervention. If a study com- service (Table 5). Nevertheless, the results were impress-
pared measurements taken immediately prior to an in-
tervention and immediately after, it was coded as a prel
post design. If a longer period of time elapsed between
comparison groups (e.g., comparing data from the study Table 4 Studies that considered input costs of
period to the same month 1 year earlier), it was defined as providing service
a historical control.
Seventy-one studies (68%) did not evaluate the cost of Method of expressing results Referencesa
providing the clinical service as part of the economic Net savings annualized or [8,9,11,18.20,24,25.31,36,
evaluation of that service. Most commonly, costs were for time period of study 45,51,53.55,68,79.82,91,
considered as an outcome or consequence of the service 94,98,104,110]
(i.e., as in drug costs avoided) rather than as an input (i.e., Net savingdpatient-day [13- 15,20,38,52,60,71]
as in the investment required to establish and maintain the or patient admission
program under study). Of the 33 (32%) studies that did Benefit : cost ratio [ 11,14,15,41,51,60,98],
consider some input costs, the most common cost as- Other [10,291
sessed was personnel ( n = 25). In these cases, the costs of aReferences may be listed more than once if results were expressed in
the program under study were quantified in terms of sa- different formats.
Economic Evaluations of Clinical Pharmacy Services (ACCP) 305
ively positive, with calculated benefits to cost ranging factor in the economic evaluation or justification of that
from 1.08 : 1 to 75.84: 1 (mean 16.70: 1). service, thus making it difficult to demonstrate true eco-
nomic justification of the service. For those studies that
did consider some input costs, personnel costs were often
DlSCUSSlON singularly included, with nonlabor costs (i.e., overhead)
being omitted. Furthermore, when charges were used,
Assessment of the Literature they were often misinterpreted as costs.
The outcomes measured tended to focus on financial
The conclusions drawn from our review and evaluation of consequences and not to include clinical or patient con-
literature assessing the economic value of clinical sequences. Without consideration of clinical outcomes, or
pharmacy services published from 1988-1995 are mul- without being able to make an assumption that clinical
tifocal. The total number of articles published on this outcomes are unchanged, the true economic impact of the
topic has grown, as demonstrated by the number in this services studied could not be proved.
review (104, average 13/yr) versus the original prospectus Despite the limitations of many of the articles as true
(58, average 4/yr), which included articles published from economic evaluations, this literature contains a wealth of
1974-1987. Although the number of published articles on information pertinent to the clinical practice of pharmacy
this topic appears sufficient, an opportunity does exist for that serves to document innovative and successful ex-
improvement in the quality of study design. periences and programs. Of importance, we did find that
A large percentage (41%) of the articles we reviewed when studies were well conducted (considered true eco-
did not include a comparison group. They did not in- nomic evaluations), the results were likely to be favo-
corporate a study design that would allow one to control rable; that is, the studies were able to demonstrate net
variance, which therefore makes it difficult for the reader savings or positive benefit : cost ratios. Because of lack
to confirm the validity or extrapolate the results to other of standardization in reporting of results and variability
practice settings. This is not to say that these articles are in study design, it is difficult to make a general statement
without value, however. Many are excellent descriptive as to the degree of benefit derived from clinical
reports that provide insight and experience from which pharmacy services. However, we were able to abstract
others may learn. calculated benefit : cost ratios from the seven applicable
Sixty-eight percent of studies did not consider the costs studies and describe a range of value from 1.08:l to
associated with providing clinical pharmacy services as a 75.84:l (mean 16.70:l). In other words, for every
306 Economic Evaluations of Clinical Pharmacy Services (ACCP)
dollar invested in clinical services, on average $16.70 such as clinical patient outcomes are important
was saved. and should be part of the evaluation of any service
These seven studies were conducted in a variety of that affects patient care. Using a disease state
practice environments-university hospitals (3), univer- management approach rather than the targeted
sity-affiliated community hospital (l), governmental drug approach to cost justification may help to
hospital (l), and health maintenance organization clinics identify important outcome measurements that
(2). They evaluated a spectrum of pharmacist-delivered should be considered.
services including pharmacotherapeutic monitoring (4), 4. The concept of opportunity costs (i.e., money spent
pharmacokinetic monitoring (2), and targeted drug pro- on one resource that cannot be spent for other
grams (1). Both of these considerations speak to what we purposes) should be explored. The value of any
believe to be the broad applicability of the studies’ results. given service should be weighed against the pos-
sible services that might be provided. The concept
Limitations of opportunity costs becomes even more important
as health care downsizing and restructuring occur.
We undertook this review and evaluation with the intent 5. Clinical pharmacy services provided in settings
of providing the reader a resource to access original lite- outside the traditional hospital should be included
rature published assessing the economic value of clinical in future economic evaluations.
pharmacy services, and to evaluate the quality of that
literature. The articles included in this review represent
only those published in standard literature. We did not CONCLUSION
consider unpublished studies and therefore our results
may be subject to inherent publication bias (so-called It is hoped that the data summarized in this article will
‘‘file drawer” effect). We included only articles that assist individual pharmacists, departmental managers, and
contained some consideration of the financial impact of health system administrators to document and recognize
clinical pharmacy services. Certainly, many useful the cost effectiveness of pharmacists’ clinical services.
articles describe and evaluate clinical pharmacy services, Pharmacy practitioners should take pride in both the
but focus on nonfinancial outcomes and impact, and are quantity and strength of this literature, and feel empow-
worthy of review. Finally, our review of the literature, ered to use it to justify further expansion or refinement of
although intended to be systematic and thorough, may not their caregiving responsibilities. Attention to our recom-
have captured all the published literature on this topic. mendations regarding the design and performance of
future economic evaluations of clinical pharmacy services
Recommendations will further add to the strength of this literature and the
conclusions that may be drawn from it.
Having reviewed and evaluated the published literature on
the economic value of clinical pharmacy services, we
make the following recommendations to clinicians, ACKNOWLEDGMENTS
investigators, authors, reviewers, and journal editors:
Members of the 1995 and 1996 Publications Committee
1. Future economic evaluations should incorporate of the American College of Clinical Pharmacy were Brian
sound methodology and study designs. Study de- Alldredge, Guy Amsden, Douglas Anderson, Edward
signs should control for variance by using a Bednarczyk (Chair, 1995), S. Diane Goodwin (Chair,
comparison group such as a historical control, 1996), Linda Jaber, David Knoppert, Bruce Mueller,
concurrent control, or pre- and postintervention Michael Otto, Therese Poirier, Jay Rho, Richard Scheife,
measurement. Glen Schumock, Maureen Smythe, Wilkinson Thomas,
2 . Consideration should be given to the input costs, Dennis Thompson, Donald Uden, and Eva Vasquez.
that is, the costs of providing the service, as part Endorsed by the ACCP Board of Regents on August 2,
of the economic evaluation. These costs should 1996.
include direct and indirect costs if possible. From Schumock GT, Meek PD, Ploetz, PA, Vermeu-
Where charges are used, they should be appro- len LC. Economic evaluations of clinical pharmacy ser-
priately labeled and interpreted as such. vices: 1988-1995. Pharmacotherapy 1996, 16(6): 1188-
3. Outcome measurements should include more than 1208, with permission of the American College of
just drug costs avoided. Nonfinancial outcomes Clinical Pharmacy.
Economic Evaluations of Clinical Pharmacy Services (ACCP) 307
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
(Continued)
308 Economic Evaluations of Clinical Pharmacy Services (ACCP)
(Continued)
Economic Evaluations of Clinical Pharmacy Services (ACCP) 309
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
To describe COD None Personnel DCA, NO1 Cost savings of
interventions costs $69.1 lipatient-day;
made by clinical annual net savings
RPh and evaluate $300,079
cost savings and
cost avoidance
impact
To compare cost OA Pre/post None LOS, total Decreased average
and quality of cost/admission total cost/admission
decentralized vs. by $1293; decreased
centralized average pharmacy
pharmaceutical cosUadmission by
services $155 for
decentralized
To examine value OD None None DCA, NO1 Cost avoided of
of clinical pharmacy $3.47/prescription
intervention processed
program in a
community
pharmacy setting
and determine
economic value
To describe OD None None DCA Average estimated Input costs not
program to cost avoidance considered
develop clinical $9306/mo over 5 yrs
pharmacy staff
and determine
cost avoidance to
hospital resulting
from the service
To evaluate and COD None Personnel DCA Net annualized cost
document impact costs avoidance $897,350
of clinical RPh on
costs avoided at
tertiary care
teaching hospital
To evaluate impact COD None Personnel DCA Net annualized cost Emphasized
of clinical RPh on costs avoidance $221,056 need for
cost and quality of documenting
patient care in interventions
ambulatory care
clinics
To evaluate OD None None Interventions 27% of interventions Input costs not
impact of documented prevented serious considered
clinical RPh on effects
medical team
(Continued)
310 Economic Evaluations of Clinical Pharmacy Services (ACCP)
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included esults measured Comments
To evaluate impact OD None None Cost impact of 2.9% of pharmacy Input costs not
of reactive clinical interventions interventions considered;
pharmacy documented prevented potential physicians
interventions on medical harm; assessed RPh
cost and quality limited cost impact service,
of patient care introducing
potential bias
To evaluate daily OD None None DCA Total savings Input costs not
data collection of $126,504 due to considered;
decentralized 2506 interventions clinical outcomes
clinical pharmacy provided not considered;
services no comparative
group used to
assess cost
and outcome
difference
GAAC[291 To evaluate CBA Control Personnel cost Cost avoidance Clinical outcomes
impact of clinical group costs avoidance $4.63 for not considered; no
RPh‘s interventions due to intervention ratio presented
on physician reduced group vs. $1.10
prescribing and number of in control group;
costs in an prescriptions savings in
ambulatory clinic prescription filling
labor noted; labor
costs associated
with program
offset by DCA
UAAC[”] To evaluate impact OD None None cost $19,000 in cost Discussed cost
of ambulatory avoidance reduction for of personnel
clinical pharmacy in drug and interventions. required for
program and to laboratory 184 patients; program, but did
justify personnel use documented not factor cost
for the program clinical outcomes into analysis; no
after interventions comparison group
for analysis
GAAC[311 To evaluate impact CBA Pre/post Costs DCA Total cost decrease Charts assessed
(VA) of clinical RPh on associated of $22,241 during for quality based
cost and quality with program study period on the rate of
of patient care and dispensing suggestion
prescriptions implementation,
generated in but actual patient
the clinic outcomes not
assessed
UACH[321 To evaluate cost COD None Personnel DCA Cost savings No control group;
impact of clinical costs $10,010 (Canadian) measured only
RPh in intensive documented over what the cost
care unit 3-mo study period; of therapy would
cost:benefit have been without
ratio 4 : 1 intervention
(Continued)
Economic Evaluations of Clinical Pharmacy Services (ACCP) 311
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
To evaluate OD None None DCA and Impact of 278 No control group;
impact of service interventions measured only
pharmacy revenue evaluated. what the cost of
faculty providing generated demonstrating therapy would
clinical pharmacy drug cost have been without
interventions on avoidance intervention
drug costs and $1661, generation
pharmacy of $6000 in
department revenue from
revenue pharmacokinetic
consultations
To evaluate CBA Control Personnel DCA Decreased total No ratio
impact of group costs number of presented;
clinical RPh on prescriptions and mentioned but
drug prescribing associated ADRs; did not quantify
and cost savings total cost of value of
prescriptions filled prevented ADRs
in study period
$3872 less than
during control
period; total cost
to administer
program S2250
CH[35] To evaluate OD None None DCA Cost avoidance Input costs not
impact of ranged $2341 - considered; no
documentation $7762/quarter control group;
system for during study clinical outcomes
clinical pharmacy not considered
services
~ ~ " 6 1
To evaluate cost COD None Personnel DCA During 32 days, No control group;
impact of costs cost avoidance clinical outcomes
implementing $1651, labor cost not considered;
clinical pharmacy associated with small sample size
services in program was (number of pilot
intensive care $2599 days assessed,
unit and short
period of
timeiday)
To evaluate OD None None NOI, DCA, Estimated annual Input costs not
acceptance and laboratory drug savings considered
cost savings cost $3891
resulting from avoidance
2-yr
postbaccalaureate
PharmD student
interventions
(Continued)
312 Economic Evaluations of Clinical Pharmacy Services (ACCP)
Objective
(as stated Analytic Comparison 0utcomes
Setting by authors) method group Input costs included Results measured Comments
(Continued)
314 Economic Evaluations of Clinical Pharmacy Services (ACCP)
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
Target drug programs: Antihypertensives
HMOC[631 To evaluate impact OA Control None Average daily Decreased drug Input costs not
of clinical RPh group drug costs costs of $20.61/ considered
consultation on cost patient-year
of antihypertensive
therapy in HMO
family practice
clinic
(Continued)
316 Economic Evaluations of Clinical Pharmacy Services (ACCP)
Objective
(as stated Analytic Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
GHL711 To evaluate impact CBA Control cost of cost of Cost savings Input costs not
(VA) of clinical RPh group treatment treatment S46.0Ypatient considered; small
monitoring on i.v. outcome achieved, I-day sample
ceftriaxone use decrease in LOS
(conversion to
oral cefpodoxime)
UHL7” To evaluate OA Historical None DCA Gross savings Cost associated
antimicrobial control in antibiotic with service
management acquisition considered, but
program and cost $483,032/yr not quantified
evaluate impact
on cost and
quality of
patient care
~ ~ “ 3 1 To evaluate cost OD Historical None DCA Cefazolin dosing Input costs not
impact of two control modification considered;
DUE activities (q6h to q8h) clinical outcomes
performed by resulted in savings not considered
undergraduate of 518,000;
pharmacy students substitution of
metronidazole for
clindamycin saved
s21,000
UH[741 To evaluate cost OA Prelpost None DCA Savings of Input costs not
impact of $12,640 realized considered;
pharmacy-based after program clinical outcomes
antibiotic implementation not considered
optimization
program
GH[751 To evaluate impact OA Pre/po st None DCA Cost reduction Input costs not
(State) of RPh participating of $29,800 considered
in patient care greater in study
rounds on costs period vs.
associated with prestudy period
antimicrobial
drug use
UACH[761 To evaluate OA Control None Drug and Estimated cost Input costs not
impact of clinical group ancillary cost savings $40,000 considered;
RPh-based antibiotic avoidance associated with clinical outcomes
management drug cost not considered
program avoidance and
appropriate use
of laboratory data
UACHK7’] To evaluate impact OD None None DCA Potential to save Input costs not
of renal function $1 1,500 annually considered; no
monitoring program, by adjusting control group;
focusing on imipenem dosages clinical outcomes
appropriate dosages on basis of renal not considered
of imipenem function
(Coiztiizued)
Economic Evaluations of Clinical Pharmacy Services (ACCP) 317
Appendix 1 Evaluations of economic value of clinical pharmacy services-1 988 - 1995 (Continued)
Objective
(as stated Analytical Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
~
UACH[7X1 To evaluate cost OA Historical None DCA Predicted cost Cost associated
impact of control avoidance with providing
computerized approximately program
antibiotic $80,000 in control mentioned but
monitoring vs. study periods, not quantified
program but actual cost
reduction attributed
to program
>$200,000
UH‘7g1 To evaluate impact CBA Prelpost Costs of drug, LOS. infection Cost savings No ratio
on hospital costs of labor, and frequency $14,250 presented
antibiotic program program annually with
using education monitoring and quality of
and antimicrobial implementation care remaining
restriction constant
MC. To conduct OD None None DCA Ceftazidime Input costs not
UH[*’] retrospective dosing in elderly considered;
DUE to determine found to be in clinical
potential cost excess of labeled outcomes
savings of dosing because not considered
ceftazidime renal function
dosage adjustment not considered
UHL8” TO evaluate impact OA Pre/post None LOS, DCA Audit results 3
of clinical RPh’s mo before and
intervention on after intervention
antibiotic costs revealed $3498.40
reduction in drug
costs
UH[*’] To determine impact CBA Pre/post Cost of DCA Net savings Clinical
of antibiotic printing $17,000 outcomes not
monitoring program intervention annually considered;
form personnel costs
not considered;
no ratio
presented
UAGH[’” TO evaluate impact OA Prelpost None Clinical and Documented Input costs not
of compliance with microbiologic reduction of considered
guidelines for third- indicators; $27,000 over
generation DCA 6 mo in pharmacy
cephalosporins expenditure for
antibiotics
UACH[S41 To evaluate impact OD None None Clinical and Savings $38;920 Input costs not
of antimicrobial microbiologic over 7 mo; considered;
intervention indicators, projected annual assumed quality
program laboratory savings $107,000 and clinical
costs, DCA outcome to
be equal
(Conrinued)
318 Economic Evaluations of Clinical Pharmacy Services (ACCP)
Objective
(as stated Analytical Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
(Conrinued)
320 Economic Evaluations of Clinical Pharmacy Services (ACCP)
bjective
(as stated Analytical Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
CH[99] To elaluate cost OD None None Drug and ancillary Estimated cost Input costs not
impact of cost avoidance avoidance considered; no
therapeutic $37,565lyr control group;
interchange clinical outcomes
program for not considered;
H2RA therapy included sunk
costs (nursing
costs associated
with additional
doses of drug)
as costs avoided
CH""] To evaluate OD None None DCA Total $145,557 in Input costs not
impact of cost avoidance in considered; no
therapeutic first yr of program control group;
interchange clinical outcomes
program for not considered
H2RA therapy
HMOC"~'] TO evaluate OA Prelpost None DCA Study group had Input costs not
cost impact fewer prescriptions, considered:
of educational less expensive clinical outcomes
interventions prescriptions, and not considered;
in improving more appropriate small sample
use of H2RA prescriptions after (number of
therapy educational prescribers
interventions than involved in
control group intervention)
UACH"021 To describe OD None None DCA. ADRs. Estimated annual Retrospective
impact of assessment of cost savings analysis; no
therapeutic treatment failure $16.000: reduced evidence of
interchange parenteral H2RA increased
program for use treatment failure
H2RAs on or adverse
cost and patient outcome
quality of
patient care
UH['O3] To evaluate OD None None DCA Decreased number
impact of of days of i.v.
ranitidine i.v. acid-reducing
to oral agents: annual
conversion savings $23,425
project on
cost savings
to hospital
CH[''~] TO evaluate CBA Control Personnel Number of i.v. Lower mean No ratio
impact of group costs doses and number of presented
clinical RPh days of i.v. drug, inappropriate
monitoring and DCA doses in
intervention study group;
program on i.v. projected net
H2RA therapy annual savings
$15,766.37
(Continued)
Economic Evaluations of Clinical Pharmacy Services (ACCP) 321
Objective
(as stated Analytical Comparison Outcomes
Setting by authors) method group Input costs included Results measured Comments
To conduct OA Prelpost None Physician Savings of Input costs not
prospective cost prescribing pattern, $250,000 considered
analysis of DCA, number of estimated for
educational drug interactions 1st yr
efforts to change of program
inappropriate
prescribing of
H2RAs
To evaluate impact OA Prelpost None DCA, pharmacy Cost avoidance Input costs not
of i.v. to oral preparation costs $4214 considered
switch program
for ranitidine
To evaluate impact OA Prelpost None Patient outcome, Decreased cost Input costs not
of H2RA program ADRs, drug but preserved considered
on cost and quality interactions. DCA quality
of patient care
CA, cost analysis; CBA, cost-benefit analysis; CD, cost description: COD, cost/outcome description; CMA, cost-minimization analysis; OA, outcome
analysis; OD. outcome description; CH, community hospital; CP, community pharmacy: ER, emergency room; GAAC, government-affiliated ambulatory
clinic; GH, government hospital; HMOC, health maintenance organization clinic; MC, multicenter; MHF, mental health facility; SNF, skilled nursing
facility: UAAC, university-affiliated ambulatory clinic; UACH, university-affiliated community hospital; UAGH. university-affiliated government
hospital: UH, university hospital; DCA, drug costs avoided; DUE, drug use evaluation; NOI, number of interventions or recommendations; ADRs,
adverse drug reactions; H2RA, histamine2-receptor antagonist; ICU, intensive care unit; LOS. length of hospital stay; NSAIDs, nonsteroidal anti-
inflammatory drugs; RPh, pharmacist; SDC, serum drug concentration; TDM, therapeutic drug monitoring.
322 Economic Evaluations of Clinical Pharmacy Services (ACCP)
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9s. Keith, M.R.; Cason, D.M.; Helling, D.K. Antiulcer prea- ings. Hosp. Formul. 1991, 26; 30-32.
cribing program in a state correctional system. Ann. 103. Baciewicz, A.M. Conversion of intravenous ranitidine to
Pharmacother. 1994. 28, 792 796. oral therapy. Ann. Pharmacother. 1991, 2.5, 251 252.
96. Kirking, D.M.; Svinte. M.K.; Berardi, R.R.; Cornish, 104. Dannenhoffer, MA.; Slaughter, R.L.; Hunt, S.N. Use or
L A . ; Ryan, M.L. Evaluation of direct pharmacist concurrent monitoring and a preprinted note to modify
intervention on conversion from parenteral to oral prescribing of i.v. cimetidine and ranitidine therapy to
histamine H2-receptor antagonist therapy. Ann. Pharmac- oral therapy. Am. .I.Hosp. Pharm. 1989, 46, 1570- 1575.
other. 1991, 25; 80-84. 10s. Fudge, K.A.; Moore, K.A.; Schneider, D.N.; Sherrin,
97. Malcolm, K.E.; Griffin, C.R.; Bennett, T.A.; Robertson, T.P.; Wellman, G.S. Change in prescribing patterns of
L.M. Pharmacist adjustment of H2-receptor antagonist intravenous histamine2-receptor antagonists results in sig-
dosage to meet medical staff-approved criteria. Am. J. nificant cost savings without adversely affecting patient
Hosp. Pharm. 1994, 51, 2152-2154. care. Ann. Pharmacother. 1993, 27, 232-237.
98. Mead, R.A.; McGhan, W.F. Use of histamine2-receptor 106. Santora, J.; Kitrenos, J.G.; Green, E.R. Pharmacist
blocking agents and sucralfate in a health maintenance intervention program focused in i.v. ranitidine therapy.
organiLation following continued clinical pharmacist in- Am. J. Hosp. Pharm. 1990, 47,1346- 1349.
tervention. Drug Intell. Clin. Pharm. 1988, 22, 466-469. 107. Foulke, G.E.; Siepler, J. Antiulcer therapy: An exercise in
99. Oh, T.; Franko, T.G. Implementing therapeutic inter- formulary management. J. Clin. Gastroenterol. 1990, I 2 ,
change of intravenous famotidine for cimetidine and ra- S64--S68.
nitidinc. Am. J. Hosp. Pharm. 1990. 47, I547 1551. 108. Jones, R.A.; Lopez., L.M.; Beall, D.G. Cost-effective
100. Quercia, R.A.; Chow, M.S.; Jay, G.T.; Quintiliani, R. implementation of clinical pharmacy services in an am-
Strategy for developing a safe and cost-effective HL- bulatory care clinic. Hosp. Pharm. 1991. 26, 778--782.
receptor antagonist program. Hosp. Formul. 1991, 26 109. Chrymko, M.M.; Meyer, J.D.; Kelly, W.N. Target drug
(Suppl. D); 20 24. monitoring: Cost-erfective service provided by staff' phar-
101. Raisch, D.W.; Bootman, J.L.; Larson, L.N.; McGhan, macists. Hosp. Pharm. 1994, 2Y, 347, 350 -352.
W.F. Improving antiulcer agent prescribing in a health 110. Wilt, V.M.; Gums, J.G.; Ahmed. 0.1.;Moore, L.M. Out-
maintenance organization. Am. J. Hosp. Pharm. 1990,47, come analysis of a pharmacist-managed anticoagulation
1766- 1773. service. Pharmacotherapy 1996, 15 (6), 732-739.
PHARMACY PRACTICE ISSUES
apart from which it was intended. The following is a the community or hospital pharmacy. However, the dis-
summary of potential misuses of the new technology: pensing pharmacy may still function as a redundancy
check on these issues, continuing to act as a patient ad-
The potential exists for a patient’s confidentiality to be vocate to manage the appropriateness of patients’ drug
violated. Some of the companies offering electronic therapy. The pharmacist will still operate as an integral
prescription solutions download patient information to check and balance concerning overlooked problems and
a vendor-based server for DUR checks. The security of missed patient information pertinent to a patient’s ef-
this information and what it is used for beyond the fective drug treatment.
prescribing process creates the potential to impinge The functions performed by the electronic prescribing
upon the privacy of the patient’s medical information. technology will most likely lessen the technical burden of
The receipt of a prescription can be subject to several the pharmacist, while augmenting the need for nontech-
market barriers. First, the pharmacy must have the nical clinical judgment. This augmentation of clinical
electronic capability to receive the data. Second, the judgment should manifest primarily in the review of a
pharmacy must accept the patient’s prescription drug patient’s situation and pharmacotherapy plan to identify
plan and be willing to operate under the financial barriers to the desired patient outcomes.[151Although the
constraints imposed by the electronic prescribing more obvious problems will have a higher likelihood of
provider. Finally, the potential exists for pharmacy being addressed at the point of prescribing, the pharmacist
benefit managers (PBMs) to use electronic prescribing will still be needed to identify missed pharmaceutical
technology to route prescriptions to preferred phar- errors related to dosage route, timing, duration, frequency,
macies such as mail order companies. interaction, contraindication, and allergies. The main
Physicians will be prompted to adhere to formulary emphases of the pharmacist will likely shift to identifying
restrictions and PBM-driven disease protocols more and treating mismatched medications and indications,
frequently. As a result, evidence-based prescribing may drug overuse and abuse, drug-induced problems, improper
become more dependent on the use of appropriate drug use, and potential medication errors.
clinical knowledge by PBMs rather than health care With a decreased need for pharmacists to identify ob-
providers. vious problems associated with pharmaceutical therapy,
This technology can provide a false sense of security the pharmacist should be free to concentrate on patient-
concerning the clinical judgment of the software prog- centered therapy issues. Pharmacists can spend more time
ramming. The programming is limited to the data it with patients identifying barriers that might prevent a
receives and the problems it is designed to detect. The patient reaching an optimal outcome. Pharmacists can
innate ability of clinicians to question and rationalize then address these issues with education and proactive
is integral to the process of appropriate prescribing. adjustments in the patient’s therapy. The pharmacist can
However, electronic prescribing technology will make concentrate more time on educating patients to better
it easier to overlook the clinician’s importance to the monitor their therapy to increase the likelihood of max-
process. imal therapeutic benefit without troublesome misadven-
Theoretically, it is possible that electronic prescribing tures. Furthermore, the pharmacist could concentrate on
devices will allow unimpeded access to physicians by therapeutic outreach programs such as ‘‘brown bag”
whoever is willing to pay for that access. Physician clinics, diabetic care clinics, and asthma screening.
detailing may become more prevalent through these In a hospital setting, pharmacists can shift their focus
devices and could possibly be confused with unbiased away from dispensing roles, and take a more proactive
medication information. role at the point of care. Lieder reported that the im-
plementation of physician electronic prescribing at Van-
derbilt University Medical Center (VUMC) allowed phar-
macists to have a greater role in the prescribing process.
IMPACT ON PRACTICE OF PHARMACY Pharmacists reported that clinical evaluations were easier
with electronic records available at the touch of a key.
The advent of electronic prescribing will decrease phar- Pharmacists felt free to pursue other areas of need such as
macists’ roles in many areas. In dispensing roles, phar- cost-saving issues (e.g., intravenous to oral conversions of
macists will have less responsibility for order entry, PBM medications). The technology seemed to promote the pre-
formulary management, and disease protocol adherence. sence of pharmacists on the floors to provide drug infor-
Furthermore, a large number of DUR functions will be mation to other health care professionals. The VUMC
taken care of before the patient’s order is received in pharmacy actually maintained the electronic prescribing
Electronic Prescribing 329
$ystem and providcd educationd enhancements directed physician order entry and a team intervention on prcven-
at physician5 a9 the need for intervention, in therapeutic tion of serious medication errors. JAMA, J. Am. Med.
areas aio\e Furthermore, the pharmacy planned to expand Assoc. 1998, 280 (15), 1311-1316.
5. Evans, R.S.; Pestotnik, S.L.; Classen, D.C.; Clernmer, T.P.;
its service, to include an inpatient anticoagulant manage-
ment program ’ ’‘’’ Weaver, L.K.; Orme, J.F.; Lloyd, J.F.; Burke, J.P. A com-
puter-assisted management program for antibiotics and
other antiinfective agents. N. Eng. J. Med. 2001. 338 (4),
232-238.
6. Rivkin, S. Opportunities and challenges of electronic phy-
sician prescribing technology. Med. Interface 1997, 83,
The future appears very bright for electronic prescribing. 77 -83.
Certainly, the upfront costs for irnplcmenting programs, I. Sardinha, C. Electronic prescribing: The next revolution in
pharmacy? J. Managed Care Pharm. 1998. 4 ( I ) , 35 39.
and thc refinement of hardwarc and software specifics are
8. Pankaskic, M.; Sullivan, J. New players, new services:
important issues to resolve. However, the benefits of im-
E-scripts revisited. J. Am. Pharm. Assoc. 2000, 40 (4),566.
proved care, strcamlined workflow, and more efficient 9. Martin, K.D. Digital prescription pads; bad penmanship‘?
use of clinicians’ timc are important enhancements that Essent. Inf. 2000, 2 (1), 3 4.
have continued to cncourage expansion of these technolo- 10. Ukens, C. Are you ready’?Drug Top. 2001. 39; 34 36.
gies. As wider audiences use these applications, continued 11. Staniec, D.J.; Goodspeed. D.; Stember, LA.; Schlcsinger,
research is needed to assess the use and refinements ne- M.; Schafermeycr, K., ct al. The National Council for
cessary to optimally apply these important systems. Prescription Drug Programs: Setting standards for elec-
tronic transmission of pharmacy data. Drug Benefit Trends
1997, I , 29-35.
12. Venot, A. Electronic prescribing for the elderly; will it
improve medication usage. Drugs Aging 2001, 15 (2), 77
80.
Institute for Safc Medication Practices. A Call fo Eliminate 13. Armstrong, E.P. Electronic prescribing and monitoring are
Handwritten Pt-e,tcrip/ioa Within 3 Years: Institute for Safe needed tu improve drug use. Arch. Int. Med..2000, 160
Medication Practices: 2000; I - 12. (18), 2713--2714.
Institute of Medicine. To Err Is Human; Building a Safer 14. Komshian. S. Electronic prescribing; system helps physi-
H d t h System;National Academy Press: Washington, DC, cians avoid errors and offer better service. Phys. Comput.
2000. 2000, 12-15.
Lesar, T.S.; Briceland, L.; Stein, D.S. Factors related to 15. Canaday, B.R.; Yarborough, P.C. Documenting phar-
errors in medication prescribing. JAMA, J. Am. Med. maceutical care: Creating a standard. Ann. Pharmacothcr.
Assoc. 1997. 277 (4). 312 317. 1994, 28, 1292 1296.
Rates, D.W.; Leape, I,.L.; Cullen, D.J.; Laird, N.; Petersen, 16. Lieder, T.R. Computcrizcd prescriber order entry changes
L.A.; Teich, J.M.: Burdick, E.; Hickey, M.; Kleefield, S.; pharmacists’ roles. Am. J. Health-Syst. Pharm. 2001, 58
Shea, B.; Vliet, M.V.; Seger, D. Effect of computerized (lo), 846--851.
PHARMACY PRACTICE ISSUES
that of actual obligation-that which is a true duty in a within the framework of the relationship between health
concrete circumstance. In other words, the prima facie professional and patient discussed earlier. For teach-
obligations are objectives that can be canceled by other ing purposes and because therapy with medication is
prima facie obligations of greater urgency. According to used on almost all patients, this relationship triangle
D. Gracia, their present application consists of[61 could be modified. It could be given a new dimension
by converting it into a tetrahedron with the relationship
The “a priori” moment: The prima facie principles of physician-pharmacist-patient at the base and the socie-
autonomy, beneficence, nonmaleficence, and justice. ty at the upper vertex (Fig. 1). Neither nursing nor the
The “a posteriori” moment: Real and effective family is being excluded, as they are included with the
principles where the prima facie principles that are physician and patient, respectively.
in conflict are arranged in order of importance, taking Professionals within the clinical relationship should
into account the concrete situation and the foreseen work within a legal framework that defines the domain of
consequences. The hierarchy can vary according to each and respects the following patient rights:
each person’s perception of a concrete situation. For
this reason, it is best to keep in mind the greatest num- Confidentiality is the obligation of all health profes-
ber of possible viewpoints in an attempt to enrich the sionals to not reveal to others, without permission of
analysis as much as possible before making a decision. the patient, information relative to the sick person or
the illness, which goes along with the right to
Such is the primary objective of the so-called “Ins- confidentiality of the patient. But this is a prima facie
titutional Committees of Ethics.” obligation, not an absolute one. Thus, when another
Professor Diego Gracia uses a procedure based on the person is in danger or the law calls for it, an exception
analysis of the principles and consequences, like that should be made.
suggested by David Ross, and applies it to clinical ethics. Privacy, a patient right, dictates that no nonauthorized
persons have access to their room, clinical history, or
Decision procedure in clinical ethicsL6] databases where pertinent information can be found.
Revealing clinical, diagnostic, therapeutic, and prog-
1. Analysis of clinical history by problems (bio- nostic information to the patient, as long as legislation
logical, social). does not say anything to the contrary, is in the domain
2. Analysis of the clinical biological data and dis- of the treating physician. This fact does not mean that
cussion of findings. the pharmacist cannot give the patient information on
3. Identification of possible ethical problems-dif- the prescribed medication. But, for the benefit of the
ferentiate, count, and define all the ethical prob- patient, it is best that this be done within the
lems found in the clinical history. framework agreed upon for the collaboration between
4. Selection of the problem that causes a fundamental physician and pharmacist.
conflict of values.
5. Study of the possible courses of action.
6. Selection of the optimum possibility, that which Third parties -Administration
saves the most values in conflict. -Insurance companies
7 . Decision on the course of action to be taken. /r; -Judges
8. Analysis of the strong arguments against the de-
cision, as well as the reasons for the decision (abi-
lity to defend it publicly).
OBLEMS IN THE
PHARMACIST’S CLINICAL PRACTICE
A conflict can arise between the standard of evidence equity, more should be given to the most needy, always
considered necessary by the administration, the rando- applying explicit and transparent criteria.
mized and controlled clinical study (RCT), and the desire As far as cost is concerned, positive discrimination
of the patient to participate in an open trial, compas- occurs when the administration decides in favor of uublic
sionated use (CU). This would mean a conflict between financing of complete therapies for certain pathologies.[171
the principle of autonomy (patient) and that of benefi-
cence (administration).
In favor of the open trials CU, it is argued that a Rationing
minimum is being required (the RCT), which the patient
does not want, and thus falls into a social paternalism. These ethical problems are brought about by the denial or
Furthermore, it is argued that the investigation of the restriction of medicines due to cost.
clinical practice is possible, carrying out studies of re- Rationing according to cost is the systematic and
sults, without having to do studies with a control-arm deliberate denial of some resources, although they could
be very beneficial, because they are considered very ex-
or placebo.
In favor of RCTs, it is argued that since a vulnerable pensive. Those cases for which there are less expensive
population is being dealt with, there could be a com- alternative therapies, which are equally efficient and safe,
are excluded. This would clearly be the most just (prin-
mercial exploitation upon introducing a medication in a
pathology that does not have therapeutic alternatives, ciples of rationality and distributive justice) and suit-
without having obtained a minimum standard of scientific able therapy.
evidence. If all of the patients with this pathology are
offered this medication, no comparison can be made Rationing of a clearly suitable therapy that does not
between this alternative and a placebo. Thus, there will be have an alternative that is equally efficient and safe.
no certainty of its efficacy, and no other posterior therapy The principles in conflict here would be those of non-
can be compared with a placebo. maleficence and justice. The rationing should be
equitable and not infringe upon the "decent min-
imum." This is ethically acceptable when the ration-
Discrimination
ing criteria are explicit and known to those potentially
affected. This is understood within a framework of
This ethical problem is brought about due to a possible
scarce resources in which all of the measures have
discrimination either in the use of or the cost for the
been adopted for the rationalization of these.
patient of the pharmacotherapy.
Rationing of therapies that are thought to be neither
suitable nor nonsuitable (there is no proof for or
Negative Discrimination in the Use of the Pharma- against) which are restricted or denied due to their
cotherapy. This refers to the nonutilization of suitable elevated cost. The conflict in this situation comes
therapies for elderly patients or women without situations about between the principle of beneficence (if the
of comorbidity which justify it."4,'51 The Committee of physician orders the treatment) or the principle of
Ethical and Judicial Affairs of the American Medical autonomy (the patient wants the therapy) and that of
Association has written reports about age-base rationing, justice. No conflict exists if the patient finances hisher
gender, and black- white disparities in clinical decision own treatment, but it does exist if it is financed by the
making. [l6l public health service. Generally, the principle of jus-
In reality, negative descrimination does not pro- tice prevails over the other two, and all exceptions
duce any ethical conflict. It is not ethical in itself, as should be justifiable. For decisions for rationing to be
it does not respect the principles of nonmaleficence just (distributive justice), they need to be adopted by
and justice. the Health Administration.
4. FIP Code of ethics 1997. www.fip.nl/publication/ 12. Council on Ethical and Judicial Affairs American Medical
publication1 .htm. (accessed Oct. 2000). Association. Medical futility in end-of-life carc. JAMA
5. Gracia, D. Fundamentos d~ Hiolica, 1st Ed.; Eudema: 1999, 281, 937-941.
Madrid, 1989. 13. Lachaux, B.; Placebo, L.P. Un Medicamento que Busca la
6. Beauchamp, T.L.; Childress, J.F. Principles of Biomedical Verdad, I st Ed.; McGraw Hill: Madrid, 1989.
Ethics, 4th Ed.; Oxford University Press: New York, 14. Pettersen, K.I. Age-related discrimination in the use of
1994. fibrinolitic therapy in acute myocardial infarction in
7. Gracia, D. Proredimientos c>n Etica Clinica, 1st Ed.; Norway. Age and Aging 1995, 24, 198-203.
Eudema: Madrid, 1991. 15. Miller, M.; Byington, R.; Hunninghake, D.; Pitt, B.;
8. Bucrki, R.A.; Vottero, L.D. Ethical Respon.sahility in Fuberg, C.D. Sex bias and underutilization of lipid-
Pharnzary Practice; American Institute of the History of lowering therapy in patients with coronary artery disease
Pharmacy: Wisconsin. Madison, 1996. at acadeinical medical centers in the United States and
9. Manolakis, M.L.; Urctsky, S.D.; Veatch, R.M. Scdation of Canada. For the Prospective Randomized Evaluations of
an unruly patient. Am. J. Hosp. Pharm. 1994,51. 205-209. the Vascular Effects of Norvasc Trial (PREVENT)
10. van der Heide, A.; van dcr Maas, P.J.; van der Wal, G.; Investigators. Arch. Intern. Med. 2000, 160 ( 3 ) , 343 347.
Kollee, L.A. Using potencially life-shortening drugs in 16. www.ama-assn.org/ama/pub/catcgory/25 I3.html (accessed
neonates and infants. Crit. Care Med. 2000, 28 (7), 2595 Oct. 2000).
2599. 17. Rothman, D.J. The rising cost of pharmaceuticals: An
I I. Winker, M.A.; Flanagin, A. Caring for patients at the end ethicists perspective. Am. J. Hosp. Pharm. 1993, 50
of life. JAMA 1999, 282 (20), 1965. (Suppl. 4), 10-12.
PHARMACY PKACTICE ISSUES
ica
Kansas City, Missouri, U.S.A.
IST AL
Biocthics is a relatively new field of study concerning the The Nuremberg Code'"'' and the Declaration of Hcl-
investigation of ethical issues in medicine, health care, sinkiL5' arc accepted international documents guiding the
and the life sciences. From the standpoint of bioethics, conduct of human clinical research (Appendices 1 and
clinical pharmacy research presents no novel ethical 2). The Nuremberg Code, established in 1948 after the
questions; however, the type and scope of issues involved war crimes trials of 1946, was the first internationally
differ from those faced by other practitioners. It is recognized code for human research. During the early
important for pharmacists to be aware of the ethical 19SOs, ethics committees lor clinical research appeared
issues, givc thoughtful consideration to then, and be in the United States. Until then, physician investigators
sensitive to how they may affect their involvement in and research institutes autonomously determined when
research. The current Code of Ethics for the practice of investigations became dangerous and to what extent re-
pharmacy virtually neglects issues encountered by phar- search subjects should be informed. Later the Depart-
macists as they conduct clinical research."l ment of Health, Education, and Welfare [the present
Pharmacists arc expanding their responsibilities as Department of Health and Human Services (DHHS)], in
health care practitioners by initiating and participating in response to reported abuses of the rights of individuals
clinical research.121These activities range from custodian participating in certain federally supported research en-
of nonclinical and clinical trial information to principal deavors, mandated that all protocols be screened by ins-
investigator cngagcd in original research. For a discip- titutional committees responsible for the protection of
line to survivc as an entity, it must expand its body of human subjects. The fedcral government committed itself
knowledge continuously, rather than relying on other when Congress established the National Commission for
disciplines to create its knowledge base, including gene- the Protection of Human Subjects of Biomedical and
rating data that propose of confirm theories, principles, Behavioral Research in 1974. The commission issued the
or relationships. Belmont report in 1 978;'",7' with that, institutional review
Beca~iscof the naturc of ethics, this article presents boards (IRBs) were born and principles of protecting the
more questions than it provides answers; it is difficult to rights of human subjects participating in research began
predefine the right answers to ethical questions. Most to evolve.
experienced investigators will recognize the circum- The Belmont report describes the basic ethical prin-
stances described and will have developed their own ciples that underlie research involving human subjects:
solutions. The article however, should prove useful to new respect for persons, beneficence, and justice. The report
investigators or trainees, perhaps as a mechanism to discusses application of informed consent, assessment of
introduce discussion with mentors. It identifies ethical risks and benefits, and selection of subjects. Its regula-
issues and questions in clinical pharmacy research regard- tions require that IRBs have not fewer than five members
ing protection of human subjects, informed consent, con- who have the capability to judge research proposals in
flicts of interest, clinical trial design, investigator inde- terms of community attitudes. Therefore, IRBs must in-
pendence, and scientific integrity. clude people whose primary concerns lie in the areas of
legal, professional, and community acceptance rather than
in the overall scientific design.
During the early 198Os, the DHHS developed and
Copyright <C I993 by the American College of Clinical Pharmacy published rules and regulations for the protection of
human research subjects’ participation in federally funded mere existence of a signed form does not guarantee that
research known as the Code of Federal Regulations. The the informed consent process worked for the benefit of the
Food and Drug Administration published similar regula- subject, but it can facilitate the process. The rights of the
tions governing human research and investigations that subject must be protected, and informed consent must be
are intended to support marketing permits for drugs, food requested and obtained.
additives, medical devices, biologic products, and elec- A risk-benefit assessment must be performed before a
tronic devices. These sets of regulations serve as the proposed investigation is submitted to the IRB. Because
cornerstone for the oversight of safe human experimenta- the true risk-to-benefit ratio generally is unknown, clear
tion and guide all who participate in clinical research, evidence for a favorable outcome must exist. Benefits
(e.g., IRBs, investigators, research sponsors, research may be gained by individual participants or by society as
subjects). Generally, state agencies adopt the federal a consequence of the proposed activity.
standards, and local research institutions interpret and Potential participants must agree in writing to the
apply them to all research activities involving humans. conditions of the study after receiving a complete and
understandable explanation of the conditions of participa-
tion, the purpose of the activity, and the possible hazards
PROTECTION OF HUMAN SUBJECTS involved. They must have the right to ask questions and to
withdraw their consent at any stage of the activity.
The IRB is charged, by federal, state, and local ins-
titutions with ensuring that principal investigators ade- Ethical Questions Concerning
quately protect the health and well-being of individuals Informed Consent
whose participation may cause them to be at increased
risk to hazards, defined broadly as physical, psychologic, Informed consent assumes that accurate information is
sociologic, and legal. Thus, it is impossible to conduct being given, that the subject comprehends the informa-
clinical research in humans that would not affect one or tion, and that the subject volunteers to participate. Do
more of these areas. investigators emphasize each aspect appropriately? For
If local institutions receive any federal research example, how does the investigator ensure that the subject
money, all human research must be approved by the comprehends? Examples of methods used are having the
IRB. This is not the basis for IRB review but provides the subject repeat back in her or his own words the infor-
incentive for local institutions to conduct studies that are mation immediately, and repeat it at some future time
ethical. The committee becomes involved in matters such while involved in the research; and using a witness to sign
as confidentiality, anonymity, and moral issues related to the consent form.
experimental activities. Approval from an IRB, however, While preoccupied with the informed consent form,
does not relieve the principal investigator from the basic investigators may neglect using required and appropriate
responsibility of safeguarding the health and welfare of language. How do pharmacists ensure that eighth-grade
participating individuals. This is a moral and professional language is used on the consent form, and is it ever
responsibility that cannot be delegated. verified? If non-English-speaking people are being re-
quested to participate in research studies, the informed
consent form should also be written and presented in
INFORMED CONSENT a language they understand. Computer programs and
English teachers may be used to facilitate this process.
Informed consent comprises two distinct concepts. Thus, two informed consent forms would be prepared, one
Informed means that the researcher provides something in English and one in the appropriate non-English
(information, assistance with a decision) to the subject. language. Investigators should ensure that these issues
Consent means that there is something (permission) that are not neglected.
the researcher requests from the subject. Consent must be How much information is necessary for potential
given freely. subjects to be informed? Should investigators tell the
The informed consent process answers the moral subjects how much money they are compensated per
question, when is it permissible to include competent subject recruited? It is probably unnecessary for subjects
people as research subjects? The answer is, if, and only if, to understand how clinical research is funded (e.g.,
they have given their free and informed consent. Inherent overhead fees, fees for certain services), unless this
in this statement is the idea that investigators should ask information would influence any reasonable person to
for or request consent, not simply to get or obtain it. The participate (or not to participate). The pharmacy profes-
Ethical Issues Related to Clinical Pharmacy Research (ACCP) 337
sion and society as a whole determine what reasonable research subjects. Several factors should be considered in
people usually do, and this is susceptible to change over justifying payment, such as the intensity of the protocol,
time. Research subjects have a right to know what is whether it is funded and by whom, and the degree of
known, including the views of the investigators specif- benefit to subjects other than monetary.
ically and the pharmacy and medical professions in
general. At minimum, investigators should give subjects
the information that the average reasonable person would Influence of Drug Therapy
want to know.
Finally, how informed could a subject be about a new Little information exists about how a patient’s drug
chemical entity when the aim of the study is to gain therapy influences the informed consent process. For
information for the first time in humans? To balance the example, can a patient who has had several doses of
apparent lack of information, the investigator is respons- intravenous morphine give consent to participate in an
ible for carefully monitoring the subject during all stages acute myocardial infarction protocol? Sedated patients
of the investigation. may not understand adequately what they are being told;
therefore, they cannot make up their minds freely. As
another example, how informed can patients be who are
Payment to Study Volunteers experiencing blurred vision from atropine? Does drug
exposure influence continued participation or future
The informed consent process raises ethical questions. consent? If there are any doubts, a family member,
The informed consent form may state that volunteers will guardian, or patient advocate should be involved in the
be paid for their services, yet when does the payment informed consent process.
become simply an inducement? Payment to volunteers for
participation in drug trials is common and usually can be Adverse Effects
subdivided into two types, reimbursement for expenses
incurred incidentally and wage payments. Reimbursement In the context of a clinical trial, informing the patient of
might cover expenses such as transportation costs, costs possible side effects could influence the outcome of the
incurred by participation (e.g., extra blood sampling, new study. However, subjects have the right to know what
drugs or devices being used), and lost work time. Wage may be expected to occur during participation. They must
payments involve remuneration for services provided in be informed of all possible adverse effects consistent with
serving as a research subject. These payments could be the information in the package insert (if available) and the
based on a number of factors, such as time commitment information known from other studies.
required, nature, and number of procedures performed, or
to facilitate recruitment in a timely fashion. Payment
should not constitute an inducement.
When ill persons are offered money over and above ETHICAL QUESTIONS C ~ N C ~ R N I ~ G
expenses to enter a clinical trial of a new drug therapy, MORAL PRINCIPLES
the possibility of coercion exists. The reasoning is that
if the patient is poor, they might not be able to afford Pharmacists, like physicians, have to be aware of the
the therapy without entering the trial. Contrast this sovereignty of the patient. Although the protection of
experience with renally impaired volunteers recruited human subjects is critical, there is little opposition to the
for a pharmacokinetic study of an antibiotic. Renal protection of human rights. However, opposition to other
failure is not the target of therapy. The subjects receive critical issues does exist to various degrees.
no therapeutic benefit from participating and are paid
as volunteers.
The IRBs should review research funding for appro- Questions of Fairness
priateness and possible coercion, specifically as it applies
to subject recruitment. If the amount of payment is so When should we encourage repeated volunteering? Could
high as to induce any reasonable person to participate, studying the same pool of patients have a negative impact
regardless of the risk, it is obviously too high. It becomes on the care of others? In other words, volunteering over
difficult, however, to determine when coercion is present and over again may; 1) deny the benefit of that research to
because the majority of cases are not this obvious. others; 2) make research subjects bear too great a burden
Investigators should be able to justify any payment to themselves; and 3) result in data that cannot be general-
338 Ethical Issues Related to Clinical Pharmacy Research (ACCP)
ized to the rest of the population. Careful examination of Research involving healthy volunteers rarely benefits
the purposes of each investigation must be made to ensure the subjects directly, yet may be harmful to them. Should
that repeated volunteering is beneficial to subjects or to pharmacists then encourage the development and use of
the experimental purpose. Thus, mere expediency of en- new technologies or methods (e.g., noninvasive) to reduce
rolling subjects does not justify studying the same in- risks while maintaining the scientific integrity of pro-
dividuals routinely. In some instances, such as pharma- jects?‘” A simple venipuncture exposes both the subject
cokinetic studies, repeated use of the same subjects may and the investigator to a degree of risk above that which
be acceptable. occurs in daily life.[6-91If the study drug possesses a sa-
Therapeutic research is intended to benefit those who liva : plasma concentration of approximately 1, are we
are the subjects of that research. What are the proper justified in obtaining plasma samples? If the study intent
criteria for inclusion and exclusion that would ensure that is to screen for substances present, investigators should
everyone has a fair chance of benefiting from particip- use noninvasive methods when possible rather than those
ating within the scope of the hypothesis being tested? The requiring venipuncture.
principle of justice or fairness dictates that subjects be
selected equitably, in other words, giving everyone an
opportunity, and not concentrating on individuals with or Conflicts of Interest
without certain diseases, those located in close proximity
to the service institution, or those of a particular gender. Conflicts of interest issues are morally relevant because
For example, patients with liver dysfunction commonly they represent temptations to do wrong. Million-dollar
are excluded from research protocols, but in fact are budgets have ways of creating ethical dilemmas for
frequently the ones who receive the study drugs. Consider investigators. A prevalent problem is the influence of
also, investigations using predominantly individuals of commercial interests on independent drug research. Me-
one race or ethnic minority simply because of their dicine has emphasized disclosure to minimize this prob-
availability. Should we encourage the investigation of lem, but disclosure does not guarantee elimination of
drug disposition in these patients, especially as they relate ethical dilemmas.
to the problem being studied? The American College of Clinical Pharmacy offers
Thus, selection of subjects has the potential to be an recommendations to minimize conflicts of interest in the
ethical dilemma. The Belmont Commission’s interpreta- accompanying position statement “Pharmacists and the
tion of the requirement of is seen in the pharmaceutical industry: guidelines for ethical interac-
following statement: tions.” The statement addresses questions such as, when
is it permissible to accept an honorarium from a sponsor
The selection of research subjects needs to be scrutinized for providing a research talk, contributing to a sym-
in order to determine whether some classes (e.g., welfare posium, or arranging a research-oriented training session?
patients. particular racial and ethnic minorities, or persons It also discusses the type of research that is appropriate to
confined to institutions) are being systematically selected be funded. For example, it is unethical to perform a phase
simply because of their easy availability, their compro-
IV study for the sole purpose of familiarizing practi-
mised position, or their manipulability. rather than for
reasons directly related to the problem being studied.
tioners with a drug so that they will prescribe or re-
Finally, whenever research supported by public funds commend it frequently in the future. Ultimately, the
leads to the development of therapeutic devices and pharmacist has the responsibility to maintain objectivity
procedures, justice demands both that these not provide through the unprejudiced and unbiased performance of
advantages only to those who can afford them and that research activities regardless of the potential for personal
such research should not unduly involve persons from financial gain.
groups unlikely to be among the beneficiaries of sub- Another example of a potential conflict of interest is
sequent applications of the research. the use of finder’s fees to help to identify research
subjects. A finder’s fee is a fee paid to individuals,
If there are known populations of people in whom usually nurses, physicians, and pharmacists, who assist
drug disposition and effect differ, should we neglect in locating potential research subjects. It may not be
enrolling them in clinical trials? Certainly it is expedient wrong to offer such a fee, but it is probably wrong for
to develop protocols that control for factors that may be a investigators to demand it. It would be unethical to deny
source of variability. However, in doing this, investiga- a patient the opportunity to benefit from a study simply
tors must not systematically neglect important segments because the investigator would not receive the money. In
of the population. lieu of paying finder’s fees directly, some institutions
Ethical Issues Related to Clinical Pharmacy Research (ACCP) 339
provide credit to a bookstore account or payment to a research results (e.g.. Clinical Alert) directly to health
special account whose funds can be used only for care providers and the public before the results are pub-
educational purposes. lished. They deem the results too urgent for the public's
health to be delayed by the publication process." 'I What
are the ethical issues of such early release of research
individual Versus Social interest results, and who is the appropriate authority to decide
what is urgent? How complete should the prepublication
When is it permissible to deny some benefits, or put some release of medical research be? What is the track record
subjects at risk, for the sake of research and the benefits it of prepublication releases? Is it unethical that some
promises? For example, when is it permissible to perform journals take months to print research results because of
cost-containment research, and what type of peer review their peer review process? Policies should be developed
and informed consent is necessary?["] This is particularly that define appropriate mechanisms for early release of
relevant for pharmacists because many are involved in research findings, and their effectiveness and impact
this type of data collection and analysis. It is possible that should be evaluated.
some subjects may receive a lower standard of care than
that to which they are accustomed. Thus, experimental
strategies that reduce services may expose subjects to the
possibility of harm without benefit. CLINICAL TRIAL DESIGN
Political or public policy agendas may exist that do not
necessarily reflect the best interests of research subjects. If The design of randomized clinical trials introduces ethical
so, pharmacists must maintain the highest standards of issues."21 Usually, study designs prevent the treatment
integrity. This may require them to become more involved from being modified because of the need to collect suf-
in establishing research priorities at federal, state, and ficient data to allow valid statistical inference. Ethically,
local levels. We should address under what circumstances clinicians are required to provide their patients with the
it is appropriate to encourage studies that are risky, best available treatment; however, the justification for a
potentially unfundable, or would require extensive time or randomized clinical trial is simply that the best treatment
commitment (which usually means a long delay before is not yet known.
publishable results are generated). The probability of What is the proper role for placebo controls? It has
funding should not determine the direction of research. been suggested that, "apart from needing to be both valid
Under what conditions is it permissible to delay the and valuable,' '[131 they must satisfy two premises: there
publication of promising results until more substantial exists (or there is the likelihood to exist) a controversy
evidence is available? The reverse question is an ethical among expert clinicians concerning the relative thera-
dilemma as well. That is, under what conditions is it peutic merits of each treatment, including the placebo;
permissible to publish promising results even though, and the design of the study must warrant confidence that
according to accepted standards, more evidence is needed the results will show which of the regimens is superior
to validate the results? The increasing newsworthiness of and therefore will influence clinical p r a ~ t i c e . " ~ ]
medical research has given this issue much attention, and Placebo controls can be justified if the trial is
conflicts directly with the established, albeit time-con- conducted in an area that falls within one of four
suming, publication process: manuscript preparation, peer broad categories:
review, and revision.
Some have criticized the Ingelfinger rule.L111Over a 1. Conditions for which no standard therapy exists
decade ago, the editor of the New England Journal of at all.
Medicine, Franz Ingelfinger, ruled that no medical 2. Conditions for which standard therapy has been
research would be published if it had been published shown to be no better than placebo.
previously, whether in the scientific or lay press. (The 3. Conditions for which standard therapy has been
rule permits previous publication of abstracts or presenta- called into question by new evidence, creating
tions at meetings.) Most major scientific journals have doubt concerning its presumed net therapeutic
similar policies. advantage.
Vocal patient groups, the lay press, and the public 4. Conditions for which validated optimum treatment
want medical news as fast as possible; results of new is not made freely available to patients because of
research are seen or heard daily in the news. The Na- cost constraints or other considerations (e.g.,
tional Institutes of Health has begun releasing some physical location of treatment centers).
340 Ethical Issues Related to Clinical Pharmacy Research (ACCP)
These categories should be used as initial guidelines. raw data files, and statistical analysis files. Plagiarism is
The federal Food and Drug Administration desires that another serious offense that compromises scientific in-
studies of a new chemical entity be compared with tegrity and is not acceptable.
placebo in small groups of patients during phase Negative data should be published if they are
I1 testing. scientifically sound, particularly when they fill gaps in
At what point should a clinical trial be stopped current knowledge. They also may decrease redundancy
prematurely because enough evidence has been gathered in future investigations. Investigators should publish
to show that some treatment is efficacious? Investiga- complete information when possible; fragmenting data
tors, with the help of statisticians, should develop guide- sets is discouraged.
lines that answer this question before the protocol is
submitted to the IRB (or at least prior to data collect-
ion). These guidelines should be communicated to all
CONCLUSI
persons involved in the research effort directly (investi-
gators and research subjects). A safety committee should
The research process introduces many ethical questions
be responsible for monitoring data collected during a
particularly relevant to clinical pharmacy investigators.
trial and stopping the trial if a predefined boundary is
Most important, investigators must be aware of their
crossed, whether for early evidence of benefit or unac-
moral responsibility to safeguard the health and welfare of
ceptable toxicity.
individuals who participate in research. The informed
consent process is used to ensure that study subjects
understand the conditions of their participation, the
purpose of the study, and the possible hazards involved;
and to ensure that consent is given freely. Investigators
Investigator independence is another important issue. and IRBs must be certain that payments to study vo-
Almost all industry-funded research is reviewed by the lunteers are not excessive or coercive. Finally, clinical
sponsor prior to publication, and if the results are not pharmacist investigators must avoid or minimize potential
favorable, pressure not to publish may be considerable. conflicts of interest by establishing themselves as
Some protocols forbid the investigator to publish results independent investigators performing studies with utmost
without permission; they cite the availability of confid- scientific integrity.
ential commercial information as the reason. The implied
threat is that if the results are published, the investigator
will not receive funding in the future. Pharmacists should
be independent investigators with the right and authority
to publish research findings. The intellectual property is
The subcommittee appreciates the helpful comments and
owned by the investigators and their institution, not the
critical review of the following people: David Brush-
funding agency.
wood, J.D., Peter Iafrate, Pharm.D., Bruce Russell, Ph.D.,
Craig Svennson, Pharm.D., Ph.D., and Russel Thomas,
Pharm.D.
This document was written by the following subcom-
mittee of the 1991-1992 ACCP Research Affairs Com-
Integrity is a complex concept with associations to con- mittee: David R. Rutledge, Pharm.D., Chair; Clinton
ventional standards of morality and personal beliefs about Stewart, Pharm.D., Vice Chair; and Daniel Wermeling,
truth telling, honesty, and fairness. Unintentional invest- Pharm.D. Other members of the committee were Kath-
igator bias is a scientific error. Intentional investigator ryn Blake, Pharm.D.; Jacquelien Danyluk, Pharm.D.;
bias is a form of fraud. Fraud is the deliberate reporting of Jimmi Hatton, Pharm.D.; Dennis Helling, Pharm.D.,
what one believes to be false with the intention of de- FCCP; K. Dale Hooker, Pharm.D.; David Knoppert,
ceiving others."41 Within a research program or insti- M S c . Pharm.; Patrick McCollam, Pharm.D.; Christopher
tution, mechanisms should exist that check for data Paap, Pharm.D.; Michael J. Rybak, Pharm.D., FCCP;
trimming, selective reporting, quality control, and origin- Kathleen Stringer, Pharm.D.; and Joseph DiPiro,
ality. Sloppy research is unethical; examples are incon- Pharm.D., FCCP, Board Liaison. Staff editor: Toni
sistencies in record keeping involving research subject Sumpter, Pharm.D. Approved by the Board of Regents
files, sample preparation and other analytical procedures, on May 21, 1993.
Ethical Issues Related to Clinical Pharmacy Research (ACCP) 341
1. The voluntary consent of the human subject is 1. Biomedical research involving human subjects
absolutely essential. must conform to generally accepted scientific
2. The experiment should be such as to yield fruitful principles and should be based on adequately
results for the good of society, unprocurable by performed laboratory and animal experimenta-
other methods or means of study, and not random tion and on a thorough knowledge of the scien-
and unnecessary in nature. tific literature.
3. The experiment should be designed and based 2. The design and performance of each experi-
on the results of animal experimentation and a mental procedure involving human subjects
knowledge of the natural history of the disease should be clearly formulated in an experimental
or other problem under study that the antici- protocol which would be transmitted to a spe-
pated results will justify the performance of cially appointed independent committee for con-
the experiment. sideration, comment, and guidance.
4. The experiment should be so conducted as to 3. Biomedical research involving human subjects
avoid all unnecessary physical and mental suf- should be conducted only by scientifically qua-
fering and injury. lified persons and under the supervision of a cli-
5. No experiment should be conducted where there nically competent medical person. The respon-
is a priori reason to believe that death or dis- sibility for the human subject must always rest
abling injury will occur except, perhaps, in those with a medically qualified person and never rest
experiments where the experimental physicians on the subject of the research, even though the
also serve as subjects. subject has given his or her consent.
6 . The degree of risk to be taken should never 4. Biomedical research involving human subjects
exceed that determined by the humanitarian cannot be legitimately carried out unless the im-
importance of the problem to be solved by portance of the objective is in proportion to the
the experiment. inherent risk to the subject.
7 . Proper preparations should be made and adequate 5. Every biomedical research project involving
facilities provided to protect the experimental human subjects should be preceded by careful
subject against even remote possibilities of in- assessment of predictable risks in comparison
jury, disability, or death. with foreseeable benefits to the subject or to
8. The experiment should be conducted only by others. Concern for the interest of the subject
scientifically qualified persons. The highest must always prevail over the interest of science
degree of skill and care should be required and society.
through all stages of the experiment of those who 6. The right of the research subject to safeguard his
conduct or engage in the experiment. or her integrity must always be respected. Every
9. During the course of the experiment the human precaution should be taken to respect the privacy
subject should be at liberty to bring the expe- of the subject and to minimize the impact of the
riment to an end if he has reached the physical study on the subject’s physical and mental integ-
or mental state where continuation of the expe- rity and on the personality of the subject.
riment seems to him to be impossible. 7 . Doctors should abstain from engaging in research
10. During the course of the experiment the scientist projects involving human subjects unless they are
in charge must be prepared to terminate the ex- satisfied that the hazards involved are believed to
periment at any stage, if he has probable cause be predictable. Doctors should cease any invest-
to believe, in the exercise of the good faith, igation if the hazards are found to outweigh the
superior skill, and careful judgment required potential benefits.
of him that a continuation of the experiment is 8. In publication of the results of his or her re-
likely to result in injury, disability, or death to search, the doctor is obliged to preserve the ac-
the experimental subject. curacy of the results. Reports of experimentation
342 Ethical Issues Related to Clinical Pharmacy Research (ACCP)
not in accordance with the principles laid down sured of the best proven diagnostic and therapeu-
in the Declaration should not be accepted for tic method.
publication. 4. The refusal of the patient to participate in a study
9. In any research on human beings, each potential must never interfere with the doctor-patient
subject must be adequately informed of the relationship.
aims, methods, anticipated benefits, and poten- 5. If the doctor considers it essential not to obtain
tial hazards of the study and the discomfort it informed consent, the specific reasons for this
may entail. He or she should be informed that he proposal should be stated in the experimental
or she is at liberty to abstain from participation protocol for transmission to the independent
in the study and that he or she is free to committee.
withdraw his or her consent to participation at 6. The doctor can combine medical research with
any time. The doctor should then obtain the professional care, the objective being the acqui-
subject’s freely given informed consent, prefer- sition of new medical knowledge, only to the
ably in writing. extent that medical research is justified by its
10. When obtaining informed consent for the re- potential diagnostic or therapeutic value for the
search project the doctor should be particularly patient.
cautious if the subject is in a dependent rela-
tionship to him or her or may consent under
duress. In that case the informed consent should Nontherapeutic Biomedical Research
be obtained by a doctor who is not engaged in the Involving Human Subjects (Nonclinical
investigation and who is completely independent iomedical Research)
of this official relationship.
11. In case of legal incompetence, informed consent 1. In the purely scientific application of medical
should be obtained from the legal guardian in research carried out on a human being, it is the
accordance with national legislation. Where phy- duty of the doctor to remain the protector of the
sical or mental incapacity makes it impossible to life and health of that person on whom biomedical
obtain informed consent, or when the subject is a research is being carried out.
minor, permission from the responsible relative 2. The subjects should be volunteers-either healthy
replaces that of the subject in accordance with persons or patients for whom the experimental
national legislation. design is not related to the patient’s illness.
12. The research protocol should always contain 3. The investigator or the investigating team should
a statement of the ethical considerations in- discontinue the research if in his or her or their
volved and should indicate that the principles judgment it may, if continued, be harmful to
enunciated in the present Declaration are com- the individual.
plied with. 4. In research on man, the interest of science and
society should never take precedence over con-
siderations related to the well-being of the subject.
Medical Research Combined with
Professional Care (Clinical Research)
and Regulation (?f Clinical Research, 2nd Ed.; Levine, R.J., Ed.; Urban & Schwarzenberg: Baltimore, 1986;
R.J., Ed.; Urban & Schwar~enberg: Baltimore, 1986; 1-18.
425426. 9. Svensson, C.K. Ethical considerations in the conduct of
Anonymous. World Medical Association Declaration of clinical pharmacokinetic studies. Clin. Pharmacokinet.
Helsinki: Recommendations Guiding Medical Doctors in 1987, 4,217-222.
Biomedical Research Involving Human Subjects, Appen- 10. Brett, A,; Grodin, M. Ethical aspects of human experi-
dix 4. In Ethics and Regulation of Clinical Research, 2nd mentation in health services research. JAMA 1991, 26.5,
Ed.; Levine, R.J., Ed.; Urban & Schwarzenberg: Baltimore, 1854 1857.
~
1986; 427-429. 11. Fletcher, S.W.; Fletcher, R.H. Early release of rescarch
Department of Health and Human Services. Code of results. Ann. Intern. Med. 1991, 114, 698-~700.
FedcJral Regulations, 4.5 C.F.R. 46. Pmtec,tion of Human 12. Hellman, S.; Hellman, D.S. Sounding board: Of mice but
Subjects; Washington, DC, 1978. not men. Problems of the randomized clinical trial. N.
National Commission for the Protection of Human Engl. J. Med. 1991, 324, 1585- 1589.
Subjects of' Biomedical and Behavioral Research. The 13. Freddman, B. Placebo-controlled trials and the logic of
Belinont Report: Ethical Principles and Guidelines f o r the clinical purpose. IRB: A Review of Human Subjects Re-
Protpction of Human Subjects of Research. DHEW search 1985, 7 (2), 1-4.
Publication 05-78-0012; US Government Printing Office: 14. Levine, R.J. Ethical Norms and Procedures. In Ethics
Washington, DC; 1978. and Regulation of Clinical Research, 2nd Ed.; Levine,
Levine, K.J. Basic Concepts and Definitions. In Ethics R.J., Ed.; Urban & Schwarzenberg: Baltimore, 1986;
and Regulation of Clinical Research, 2nd Ed.; Levinc, 19-35.
PROFESSI 0 NAL 0R G A N IZAT I 0 NS
Annemieke Floor-Schreudering
Europrnn Sooety of C’linical Pharmacy,
Leidcv, The Netherlands
Yechiel Hekster
University Medical Centre, Nijmegen, The Netherlands
oal
In the 20th century, a conviction developed within the The goal of ESCP i \ to encourage the development and
pharmacy profession that the professional knowledge of education of clinical pharmacist\ in Europe.
pharmacists was not used to its full potential. Activities to The Society tries to achieve this goal by:
assure the safe and appropriate use of drugs became a new
target, leading to activities in the direction of more pa- 1. Membership activities:
ticnt-rclatcd aspects of drug therapy. This perception was a Providing a forum for the communication of
present at about the same time on both sides of thc new knowledge and developments in clinical
Atlantic. It was logically named “Clinical Pharmacy,” p harmac y .
mcaning a pharmacy activity directed to and in contact 0 Dcvcloping links with national and interna-
with the patient. The leaders of this new approach wanted tional organizations of pharmacists, teachers,
to reinforce their message by founding profcssional or- and students interested in the development of
ganizations preoccupied with the teaching and practical clinical pharmacy.
development of Clinical Pharmacy. In 1979, the birth of
the Amcrican College of Clinical Pharmacy (ACCP) and 2. External relations:
the European Society of Clinical Pharmacy (ESCP) took 0 Promoting the value of clinical pharmacy
place simu~taneous~y.”’ services among other health care profcssion-
als, among scicntific societies that share the
same interest, organizations such as WHO
(World Health Organization) and EMEA (Eu-
ropean Agency for the Evaluation of Medici-
The European Society of Clinical Pharmacy (ESCP) is an nal Products), and generally within the health
international society founded by clinical practitioners, service.
rcscarchers, and educators from various countries in 3. Educational activity:
Europe, which constantly looks for new areas of pro-
Enforcing the formation of activities in the field
fessional practice. Since the formation of the Socicty,
of clinical pharmacy and pharmacotherapy
there has been a gradual and sustained growth of clinical
through conventions and specific courses.
pharmacy in many European countries. 0 Promoting the inclusion of clinical pharmacy
teaching at pre- and postgraduate levels.
verall 4. Training:
* Providing accrediting centers, where clinical
The overall aim of the Society is to develop and promote pharmacy activities are carried out and which
thc rational and appropriate use of nicdicines (medicinal are prepared to host visiting pharmacists or
products and devices) by the individual and by society. pharmacy students in each European country.
an ers
The Research and Education Committee is in charge of ESCP ha, about 850 members from 48 countries.
the coordination of educational activities, stimulates and Member\ practice in hospitals. clinics, universities, com-
initiates research project, and takes care of the scientific munity pharmacies, governmental settings, drug infor-
level of these activities. mation centers, pharmaceutical industry, and any other
places where clinical pharmacists are employed. The So-
ciety has four different classes of members: ordinary
members are individuals who are actively involved in
The Special Interest Groups (SIGs) of ESCP are intended pursuing the objectives of the Society; honorary members
to help ESCP meet the evolving needs of its members and are those who have distinguished themselves in a par-
fulfill a growing need for providing targeted services to ticularly honorable way toward the Society; patrons and
ESCP members with similar interests. sponsors are individuals or corporate bodies, who have
The goal is to provide a focal point to gather ESCP expressed their willingness to support the Society finan-
members with common interests and needs in practice, cially; and .student members are individual students or
research, and education, to create a network for: educational institutions.
During its Annual Symposium, ESCP holds a General
e Professional interaction. Assembly for all members and patrons of the Society.
0 Problem solving and discussion of professional issue\.
Continuing education.
e Research. C
B Publications.
The following SIGs are currently active: Cancer Care, October 2002 Florencc. 3 I st European Symposium
Italy on Clinical Pharmacy
Drug Information, Education and Training, Geriatrics,
May 2003 Portugal 4th Spring Conference o n
Infectious Diseases, Integrated Primary Care, Nutritional C1inic;tl Pharmacy
Support, Pediatrics, Pharmacoeconomicr, Pharmacoepi-
demiology, and Pharmacokinetics.
Table 1 Quality “questions” for assessing RCTs avoidance of bias are discussed elsewhere. It is important
to attempt to minimize the effects of bias when reviewing
0 Were subjects randomly assigned to treatment?
0 Was randomization done blindly?
evidence. It is also useful to contact experts on the subject
0 Were all subjects analyzed? of interest, as they will be able to advise on sources of
* Was analysis according to unit of randomization? relevant data and contact details of researchers conducting
0 Were researchers blind to group allocation? trials in the area. Other useful methods of identifying
0 Apart from the intervention, were the two groups treated potentially relevant information include placing notices
equally? about the literature review in professional journals and on
0 Were the groups similar at baseline? web site noticeboards and searching conference abstracts
and lists of grant awards.
It is important to ensure that all the relevant infor- Once the literature search is complete, the identified
mation is identified and critically appraised. This is easier trials need to be retrieved and reviewed critically to
said than done! Evidence that is unpublished or that is not decide whether they satisfy specific standards for
in the public domain is difficult to identify and retrieve. inclusion in the review. A list of some important quality
Pharmaceutical companies might not publish unfavorable criteria for randomized controls is shown in Table 1. It is
results of drug trials, therefore, the clinician or reviewer is essential that studies that do not meet the necessary
reliant upon the cooperation of the company to provide all quality standards be excluded from the final analysis.
relevant trial data for its specific drug. Trials reported in
the English languager4]and those with positive outcomes
are more likely to be published. Problems can also arise if UNDERSTANDING THE EVIDENCE
trial results have been accepted by a medical journal that
has a long time lag before publication. It may be months The results of trials can be used for different purposes.
or years before the results are published. The sources and They could be combined and reviewed descriptively, or, if
Where,
m
T Drug A
Drug B
Table 2 Relative risk
Outcome
If the outcome was cure then the relative risk of cure would be calculated as follows:
The risk of cure with Drug A = a ia + b;
divided by the risk of cure with Drug B = c ic + d
with Drug
B = c ic + d.
Outcome
Yes No Total
Durg A 10 20 30
Durg B 5 , 50 55
Table 3 Number needed to treat Currently, much clinical practice is based on estab-
Absolute risk iduction(ARR) = (a/(a + b)) - (c/(c + d)) lished practice and personal experience. Producing
For the above example, using the hypothetical values in Table 2, changes in practice will involve the dissemination of in-
ARR=(10/(10+20)) - (5/(5+50))=0.24 formation to individual clinicians and persuading them
Therefore, the NNT = U0.24 = 4 that, sometimes against their better judgment, there is a
This means that for every four people treated with Drug A, one benefit in adopting a new approach. Evans and HainesL7]
additional cure is likely to occur. cite 12 initiatives to introduce evidence-based practice,
and they are refreshingly honest in identifying the bar-
riers that are encountered. These included the time
required to support change; the resources needed from
the trials are similar enough, their data can be combined
existing budgets; a failure to always demonstrate quanti-
in the form of a meta-analysis. This technique allows
fiable gains in the real world; a failure to give ownership
reporting the results to a greater level of statistical con-
to all parties; and, probably the most difficult and com-
fidence because of the increased numbers of subjects in-
plex of all, changing professional behavior. This last area
cluded in the analysis.
is a research topic in its own right and is discussed later
An alternative statistic which is sometimes quoted is
in this article.
the odds ratio (OR).This is the odds of an event occurring
Patient resistance to change, as well as professional
in a patient in one treatment group relative to the odds of
resistance, also needs to be addressed. For example, new
the same event occurring in a patient in an alternative
evidence may require changes to be made to a patient’s
treatment group.
current long-term medication. Patients previously satisfied
The results of randomized controlled trials comparing
with their treatment may be reluctant to try a new drug,
two drugs can be used to generate a statistic called the
despite evidence of greater benefit. A concordant and
relative risk (RR) (Table 2). This is a ratio of the risk of an
patient-centered approach is being promoted.“] The cli-
outcome with one treatment and the risk of the same
nician has a responsibility to involve their patients in
outcome with the other treatment.
treatment decisions and to ensure that they understand and
While the relative risk is a standard statistic that can
agree with any changes that are made, as well as address
be used to compare treatments, it can be difficult to un-
any concerns that they may have. In the interests of maxi-
derstand and to relate to practice. For example, although
mizing patient outcomes and cost-effective use of medi-
the relative risk of 3.7 that was calculated above indi-
cines, it is paramount that patients understand and agree
cates that Drug A is associated with nearly four times
with new or existing treatments. Within this framework,
the risk of cure compared with Drug B, this gives no
management decisions may not be in line with current best
indication of the practical implications. For this reason,
evidence, giving rise to a debate about the legal impli-
effects are often quoted as the “Number Needed to
cations and professional ethical issues of this scenario.
Treat” (NNT). The NNT is calculated as the reciprocal
It is important to remember that EBM applies to a
of the absolute risk reduction (ARR).In the example in
range of providers at a variety of levels. Thus, it should be
Table 3, the NNT refers to the number of patients who
used to support decision making by all healthcare
need to receive Drug A before an additional cure is
providers, not just medical clinicians. It is for this reason
likely to occur.
that the term Evidence-Based Practice (EBP) is increas-
ingly used. Pharmacy, nursing, physiotherapy, and all
other professions allied to medicine should, where
APPLYING THE EVIDENC possible, be providing evidence-based treatment at an
individual and service level. For example, evidence can
Having identified the evidence from the available infor- support decisions about whether to treat stroke patients
mation and interpreted it in the context of the original in a dedicated stroke unit or as part of a general ward.[’]
question, the next step is to apply it to practice. This is a
complex and challenging task. The evidence may sug-
gest benefits from discontinuing existing treatments or CRITICISMS OF EVIDENCE- BASE^ MEDICINE
changing to alternative therapy, e.g., using a beta-blocker
in hypertensive patients following a myocardial infarc- There are two levels of criticism applied to evidence-
tion.”] Alternatively, the evidence may recommend based medicine. The first relates to the widespread
against adopting a new “miracle” drug such as the anti- dependence on the randomized controlled trial, and the
cholinesterase inhibitors for Alzheimer’s disease.[61 second relates to the patient-population dichotomy.
Evidence Based Practice 351
Concern has been expressed that gold standard sclerosis (MS). The evidence tells us that treatment with
evidence, i.e., the RCT, may not be as robust as it first interferon-beta-1b will delay time to wheelchair depend-
appears. Critics of this study design argue that the ence and prevent relapses in some subjects. However, the
patient populations are highly selected. Randomized NNT is 18 and at a population level, the economics mi-
controlled trials often exclude patients above a certain tigate against making this a recommended treatment.“ ’]
age or those who are taking other concomitant medica- Conversely, despite their cost, there has been considerable
tions or who have significant comorbidities. Additional- use of statins as lipid-lowering agents to reduce cho-
ly, participants in RCTs often have intensive support lesterol levels in targeted patients.“” This is because the
from medical, nursing, and research staff, contrary to the evidence shows long-term reduction in further coronary
normal situation. The reasons for these exclusions and events, and the exact health gain can be calculated and is
enhanced care are self-evident, but they may mean that deemed w o r t h ~ h i l e . “ ~This
’ intervention is both clin-
the results are not generalizable to the wider patient ically and cost effective.
population. A comparison of randomized and nonrando- Ultimately, it is the clinician who has to weigh the
mized studies has also identified that subjects excluded costs and benefits for each individual patient, taking into
from RCTs tend to have worse prognosis than those who account the evidence but also considering patient factors.
are included.“’] Furthermore, subjects entered into RCTs This has been summarized as “conscientious, explicit and
for evaluation of treatment for existing conditions may judicious use of current best evidence in making decisions
be less affluent, less educated, and less healthy then about the care of individual patients.”“41
those who are not. The opposite is true for trials of pre-
ventive interventions.[ I‘
Secondly, clinicians have argued that evidence-based
guidelines do not accommodate individual patients and WHAT TO DO WHEN THERE IS NO
their specific circumstances or needs. It may be necessary EVIDENCE OR EVIDENCE IS INCOMPLETE
to remind clinicians that guidelines “are not tramlines”-
they apply to a specific population, and their recommen- The EBM movement is a relatively recent endeavor.
dations should be tailored to the needs of their individual With such a wide range of treatments available and
patients. This is discussed later in this article. numerous conditions, it is inevitable that there will not
always be evidence to inform decision making. This may
be due to a lack of collation of the available research
evidence or a lack of research per se. In these instances,
there are several options depending on the immediacy of
the decision.
PATIENT LEVELS If a decision needs to made quickly, advice should be
sought from the most experienced practitioner on the
With increasing healthcare costs, particularly in the field subject. This advice should be interpreted with caution
of drug treatments, decisions regarding the uptake of new and considered in light of whatever published literature
drugs may be made at organizational rather than indi- exists. This should be judged on the basis of the ranked
vidual clinician or patient level. In the United Kingdom, levels of evidence included earlier in this article. New
this is particularly true in areas where NHS budgets con- drugs may be tried in the context of local clinical trials.
strain both the choice of treatment and patient selection. If this is the case, these trials should be expertly designed
EBM can be used to inform these policy decisions, as it and conducted in collaboration with other colleagues.
can assess both the cost-effectiveness and clinical effec- This means that while a treatment may not ultimately be
tiveness of treatments. The final decision can take into the best, it will have been used in a controlled way such
account the wider ramifications of alternative treatments, that it has contributed to generating future evidence.
such as the possible need for residential or surgical care or
the impact on lay carers. A decision may be made at a
population level that a new drug should not be introduced
because of the adverse overall health economic balance, CLINICAL ~FFECTIVENESSAND
whereas at an individual level, it could be worth trying. CLINICAL GOVERNANCE
An example of this patient versus the population di-
lemma is illustrated by the use of the expensive in- There is a growing emphasis on the accountability of
terferon-beta-lb to treat secondary progressive multiple individual clinicians and organizations that provide
352 Evidence Based Practice
address barriers to change may be more effective than patients receiving the most appropriate treatment. It is
those that do not.[241A comprehensive review of imple- also used to inform policy making about both me-
mentation strategies is presented in the Effective Health dical treatments and new services, including models
Cure Bulletin: Getting Evidence Into Practice.[241 of healthcare.
The use of guidelines as a method of summarizing While there are still some caveats, some of which have
evidence is discussed elsewhere in this encyclopedia. been highlighted in this article, EBP is the goal to which
There has been considerable evaluation of the effective- all healthcare professionals should aspire.
ness of different guideline implementation strategies as
methods of eliciting behavior change among healthcare
professionals. Most implementation research has targe-
REFERENC~
ted physician behavior. However, as greater emphasis is
placed on multidisciplinary healthcare teams, strategies
1. Evidence Based Medicine Working Group 1992. Evid-
need to be identified, tested, and adopted, which are ef-
ence based medicine. A new approach to teaching the
fective in promoting evidence-based practice among all
practice of medicine. J. Am. Med. Assoc. 1992, 268,
health professional groups. 2420-2425.
Mass media is a method commonly used to dissem- 2. Sackett, D.; Straws, S.; Richardson, W.; Rosenberg, W.;
inate information to large audiences. This strategy usually Haynes, R.B. Evidence Based Medicine: How to Practise
involves the dissemination of printed materials (e.g., and Teach EBM, 2nd Ed.; Churchill Livingstone: Edin-
guidelines, therapeutic bulletins) to specific health pro- burgh, 2000.
fessionals (e.g., physicians, pharmacists). There is little 3. US Department of Health and Human Services. Agency f o r
evidence to support the use of this method, as it is largely Health Care Policy and Research. Acute Pain Manage-
ineffective in influencing behavior change.[251 ment: Operative or Medical Procedures and Trauma;
Educational outreach visits (also known as academic AHCPR: Rockville, Maryland, 1993.
4. Egger, M.; Zellweger-Zahner, T.; Schneider, M.: Junker,
detailing) have been used by the pharmaceutical industry
C.; Lengeler, C.: Antes, G. Language bias in randomised
for decades to influence the prescribing behavior of controlled trials published in English and German. Lancet
physicians. Although there is little published empirical 1997, 350, 326-329.
evidence of the effect of the pharmaceutical industry’s 5 . Scottish Intercollegiate Guidelines Network. Secondary
promotional activities on prescribing patterns, the invest- Prevention of Coronary Heart Disease following Myocar-
ment of 57% of their pharmaceutical promotion budget on dial Infarction; 2000, Edinburgh.
pharmaceutical representatives and 11% on promotional 6. Coelho Filho, J.M.; Birks, J. Cochrane Collaboration
literature, gives some indication of its importance.[261 Physostigmine for Alzheimer’s Disease. In The Cochrane
There is considerable research evidence of the effective- LibrarjJ,Issue 3; 2002, Oxford: Update Software.
ness of educational outreach as a behavior change strategy 7. Evans, D.; Haines, A. lmplementirzg Evidence-Based
for healthcare professionals.[271 It is no surprise (con- Changes in Health Care; Radcliffe Medical Press: Oxford,
2000.
sidering their origin) that educational outreach visits have
8. Working Party: Royal Pharmaceutical Society of Great
been shown to be effective in achieving change in pre- Britain. From Compliance to Concordance: Achieving
scribing behavior among physicians.[*’] shared goals in medicine taking. RPSGB and Merck Sharp
The use of opinion leaders as an implementation & Dohme, 1997.
strategy has been evaluated in a number of studies, the 9. Stroke Unit Trialists’ Collaboration. Organised Inpatient
results of which are inconclusive.[281This method relies (Stroke Unit) Care for Stroke (Cochrane Review). In The
on persuasion (i.e., the persuasive ability of the opi- Cochrane Library, Issue 3; 2002, Oxford: Update Soft-
nion leader) to influence the behavior of the target ware.
audience. Further evaluation of this strategy is required, 10. McKee, M.: Britton, A,; Black, N.; McPherson, K.;
including methods of describing characteristics of opi- Sanderson, C.; Bain, C. Interpreting the evidence:
nion leaders and how to identify individuals who satisfy Choosing between randomised and non-randomised stud-
ies. Br. Med. J. 1999, 319, 312-315.
these criteria.
11. Forbes, R.; Lees, A.; Waugh, N.; Swingler, R. Population
based cost utility study of interferon beta-lb in secondary
progressive multiple sclerosis. Br. Med. J. 1999. 319
(7224), 1529 153 3.
~
13. Reckless, J. The 4s study and its pharmacoeconomic assessment of the response to symptoms in community
implications. PharmacoEconomics 1996, 9 (2), 101 105.
- pharmacies. Pharm. J. 1986, 237, 807.
14. Sackett, D.; Rosenberg, W.; Gray, J.; Haynes, R.; 22. Watson, M.C.; Bond, C.; Grimshaw, J.M.; Mollison, J.;
Richardson, W. Evidence based medicine: What it i s and Ludbrook, A. Educational Strategies to Promote Evidcnee-
what it isn't. Br. Med. J. 1996, 3 / 2 , 71 72.
~ Based Practice: A Cluster Randomised Controlled Trial
1s. Bond, C. Evidence-Based Phui-macy, 1st Ed.; Pharma- (RCT). I n Health Services Research and Pharmacy
ceutical Press: London, 2000. Practice Conference Proceedings; 200 I .
16. Krska, J.; Cromarty, J.; Arris, F.; Jamieson, D.; Hansford. 23. Mittman, B.S.; Tonesk, X.; Jacobson, P.D. Making good
D.: Duffus, P.; Downic, G.; Seymour, G. Pharmacist led the promise: Disseminating and implementing practice
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controllcd trial in primary care. Age Ageing 2001. 30, 24. Anonymous. Getting evidence into practice. Eff. Health
215 221. Care Bull. 1999, 5 (1).
17. Beney, J.; Bero, L.A.; Bond, C. Expanding the Roles of 25. Freemantle, N.; Wolf, F.; Grimshaw, J.M.; Grilli, R.; Bero,
Outpatient Pharmacists: Effects on Health Services L. Printed Educational Materials: Effects on Professional
Utilisation, Costs, and Patient Outcomes (Cochrane Practice and Health Care Outcomes (Cochrane Review). In
Review). In The Cochmae Library, Ixsue 3; 2002, Oxford: The Cochrane Library, I . s . T L2;
~ ~2001.
Update Software. 26. Association of the British Pharmaceutical Industry.
18. Goodburn, E.; Mattosinho, S.; Mongi, P.; Waterston, A. PHAKMA Fucts & Figures; ABPI: London. 1997.
Management of childhood diarrhoea by pharmacists and 27. Thompson O'Brien, M.: Oxman, A,; Davis, D.; Haynes,
parents: Is Britain lagging behind the Third World'! Br. R.; Freemantle, N.; Harvcy, E. Educational Outreach
Med. J. 1991, 302, 440-443. Visits: Effects on Professional Practice and Health Care
19. Krska, J.; Greenwood, R.: Howitt, E. Audit of advice Outcomes (Cochrane Review). In The Cochrune Librury,
providcd in response to symptoms. Pharm. J. 1994, 252, Issue 3; 2002, Oxford: Update Software.
93-96. 28. Thompson O'Brien. M.A.; Oxman, AD.; Haynes, R.B.;
20. Anonymous. Counter advice. Consumers arc still not Davis, D.A.; Freemantle, N.; Harvey, E.L. Local Opinion
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21. Mobcy, N.; Wood, A.; Edwards, C.; Jepson, M.H. An I S S U P 3; 2002, Oxford: Update Software.
PROFESS I0 NA L DEVE LO P M E NT
.%7cyck~~~c~dia
of Clirzic.ul Pharmacy 355
DOI: I0.1081/E-ECI’120006357
Copyright 0 2003 by Marccl Dekker, Inc. All rights reserved.
356 Fellowships in Pharmacy
1. A clinical scientist with an established record of In an effort to improve fellowship training, ACCP
research accomplishments, which may be exem- instituted a program for peer review of research fel-
plified by: lowships training programs to assure quality of these prog-
rams. This is a voluntary process conducted by an ACCP
a. Fellowship training or equivalent experience. committee to determine whether a program meets the
b. Principal or primary investigator on research ACCP Guidelines for Research Fellowship Training
grants. Programs as detailed above. In this process, both the
c. Published research papers in peer-reviewed preceptor and the fellowship site are evaluated. A positive
pharmacy/medical literature where the pre- review indicates that the program meets the guidelines. At
ceptor is primary or senior author. present, 15 fellowship programs have been recognized as
meeting the g ~ i d e l i n e s . ~ ~ ]
2 . Active collaborative research relationships with
other scientists.
3. Expertise in pharmacotherapeutics in the area
of specialization. FELLOWSHIP RESOURCES
ba
First DataBank, Inc., San Bruno, California, U.S.A.
a result. our customers save valuable programming and Drug Indications, Pregnancy and Lactation Precautions,
processing time. GeriatridPediatric Warnings, Minimumhlaximum Dose
Checking, and Duplicate Therapy/Ingredient Checking. A
few specific modules are highlighted.
First DataBank creates and maintains some of the largest Patient Education Monographs were written for consu-
and most comprehensive drug and healthcare knowledge mers. They are both comprehensive and customizable,
bases in the world, including NDDF PlusTM,based on the
covering the most common prescription and OTC med-
industry standard National Drug Data FileE. One of the ications. The format of these patient education mono-
industry’s most trusted and widely used sources of up-to- graphs is flexible and is available in English and Spanish.
date drug information, NDDF Plus combines descriptive Other patient education materials are available including
and pricing data with a selection of advanced clinical Prioritized Label Warnings that indicate which ancillary
support modules. NDDF Plus delivers information on “stickers” should be placed on a medication being dis-
every drug approved by the Food and Drug Adminis- pensed and Counseling Messages to be used as reminders
tration (FDA). Clinical modules are available to support for healthcare professionals.
healthcare professionals in making critical decisions
about dosing and orders, interactions, allergy alerts, dis-
Drug interactions
ease contraindications, drug identification, and much
more. Plus, several modules offer drug information spe-
First DataBank’s drug interaction modules are meant to
cifically written for the consumer. NDDF Plus is used in a
be able to detect all clinically significant drug-drug
wide variety of applications, such as:
interactions for a given patient in either a prospective or
retrospective manner. Drug-food interaction information
e Determining drug indications.
is also available. Interactions are classified by severity,
e Identifying potential contraindications.
and documentation levels are also noted in coded fields
b Helping prevent adverse drug events.
for searching and filtering applications. Full text mono-
e Identifying drug-drug and drug-food interactions.
graphs describe the drug-drug interaction in detail and
0 Identifying potential drug interactions with alternative
include reference citations in MEDLINE format. A
therapy agents.
“consumerized’ ’ version of the drug-drug interaction
b Offering printed patient education and counseling
monograph has been created for systems that allow
messages.
patients to monitor their medications.
0 Prioritizing medication warning labels for patients.
e Listing recommended doses for common drugs.
Performing indication-specific dose range checking. Prescriber Order Entry
Identifying undesired effects of drugs on lab tests.
b Supporting electronic medical records. Prescriber Order Entry Module (POEMTM)provides a
e Handling prescriber order entry. database of the most common medication orders. These
b Analyzing drug pricing trends. orders are specific to drug, route of administration, for-
b Facilitating drug formulary management. mulation, age, indicatioduse, and weight or body sur-
b Accelerating claims processing and adjudication. face area, if applicable. This enables more accurate
and efficient point-of-care computerized order entry ap-
First DataBank offers comprehensive international drug plications to prevent errors at the prescribing stage of
knowledge bases for several countries outside the United drug delivery.
States, including Canada, Argentina, and Australia. First
DataBank Europe, located in Exeter, England, develops
drug knowledge base products for the United Kingdom. INTEGRATED CO
Examples of clinical functionality in drug knowledge
bases are described below for Patient Education, Drug Success in today’s drug information marketplace requires
Interactions, and Prescriber Order Entry modules. Many products that can be developed quickly and economically,
other pharmaceutical decision support modules are also lowering the cost of entry into a given market. Toward
available and include Drug/Disease Contraindications, that end, First DataBank offers a number of application
360 First DataBank, Inc.
development toolkits that minimize lead times and make development time. With RxWeb, software developers
more efficient use of scarce resources. can create Web-based applications that provide informa-
tion on over 100.000 marketed drugs, as well as alter-
rug l n f o r m a t ~ oFrameworkTM
~ native therapies.
With the most comprehensive food knowledge base and try have created a demand for the rapid deployment of
set of program features, Nutritionist Pro provides tho- new applications.
rough analysis of diets, recipes, and menus. The in- First DataBank is not only meeting healthcare chal-
tuitive user interface design and powerful functiona- lenges but is also leading the industry into an era of
lity of Nutritionist Pro can help ease the workload and greater patient safety and knowledge.
boost the productivity of nutrition professionals in vir-
tually any healthcare delivery, food service, or educa-
tional setting. FIRST DATABANK AS A HEARST
CORPORATION SUBSIDIARY
Medicare-approved hospitals responding, 3 1 did not have particular, peer-reviewed medical literature, including
a formulary system in place even though Medicare randomized clinical trials, pharmacoeconomic studies,
required one.r51The second, looking at academic medical and outcomes research data. If a drug is a new phar-
centers with 500 beds or more, found that the majority of macologic class, unlike any other available drug, the
formularies analyzed were simple drug lists and were not review will fQCUS on efficacy, safety, and the potential
used to guide prescribing decisions.[61 value to the organization’s patient population. For drug’s
As the value of formulary systems became apparent, that are additions to an existing pharmacologic class, the
their acceptance grew, at first just in the hospital setting evaluation takes on a more comparative nature. Reviewers
but later expanding to ambulatory sites. In 1986, the look for studies that compare the new agent to the agent
Pharmaceutical Manufacturers Association officially ac- currently listed on the formulary. If these are limited or
cepted the concept of therapeutic interchange for hospital unavailable, the comparisons are difficult and more
inpatients, but opposed its use in other settings. The AMA subjective. If two agents appear similar in all clinical
released a policy on drug formularies and therapeutic respects, the decision may be a financial one. This process
interchange in both inpatient and ambulatory care settings often results in class review as described later. Reviewers
in 1994.[’] This brought the AMA’s views on formularies must remember that new agents coming on the market
into close alignment with ASHP. In the most recent have been tested in a limited number of patients. Because
survey of pharmacy practice in acute care settings, more a drug’s full adverse effect profile may not be evident
than 90% of health-systems had P&T committees when first released, many committees choose to stay with
responsible for formulary system development and man- the older drug already listed on the formulary until
agement.@] Pharmacy directors reported using pharma- sufficient information is published.
coeconomic and therapeutic information in their system’s Two key components of formulary drug selection are
formulary development process. Today, drug formulary generic substitution and therapeutic interchange. Generic
systems are considered an essential tool used routinely by substitution is the substitution of one drug product for
health plans, pharmacy benefit management companies, another when the products contain the same active
self-insured employers, and government agencies. ingredients and are chemically identical in strength,
concentration, dosage form, and route of administration.
The formulary will list the drug by its generic name,
strength, and dosage form. The product dispensed will be
the least expensive one. As the price of products change,
the product dispensed may change as well. When this
The development of a formulary system within an orga- occurs, the pharmacist should inform the patient if the
nization rests with a multidisciplinary committee. In the physical appearance (e.g., color, tablet size) of their
hospital and health system setting, this is typically called medication has changed. The patient should be assured
the P&T committee. Virtually all hospitals and health- that the new medication is identical to the previous one.
systems have a P&T committee.[81 P&T committees usu- Therapeutic interchange is more complex that generic
ally meet six to eight times annually. An ASHP Position substitution. The AMA defines therapeutic interchange as
Statement on formulary management declares that deci- the authorized exchange of therapeutic alternates in
sions should be based on clinical, quality of life, and accordance with previously established and approved
pharmacoeconomic factors that result in optimal patient written guidelines or protocols within the formulary
care.[’] It advises against decisions solely based on eco- system.‘71 Therapeutic alternates are drugs with different
nomic factors. The Position Statement also recommends chemical structures but which are of the same pharma-
that decisions must include active and direct involvement cologic and/or therapeutic class. They can be expected to
of physicians, pharmacists, and other appropriate health have similar therapeutic effects and adverse reaction
care providers. This may include dieticians, nurses, profiles when administered to patients in therapeutically
administrators and quality management coordinators. equivalent doses. The AMA does not support therapeutic
Formulary system management falls into three general substitution defined as dispensing a therapeutic alternate
categories: drug selection for formulary inclusion, for- for the product prescribed without prior authorization of
mulary maintenance, and medication use evaluation. the prescriber. Therapeutic interchange in institutional
health systems has been used successfully for years.
Drug Selection Working out an acceptable procedure for therapeutic
interchange by the P&T Committee may be easier in this
Drug evaluation for inclusion on a formulary should setting. Therapeutic interchange in outpatient drug
involve a careful assessment of scientific evidence, in programs in less structured ambulatory and managed
364 Formulary Systems
care settings may be more difficult and has been between decreased costs and a well-controlled formulary,
criticized.[''] therapeutic interchange, or both."31 Hospitals that used
either strategy spent 10.7% less for drugs than those that
used neither. Hospitals using both spent 13.4% less than
those that used neither. An estimated $100 million in
Maintaining a formulary is an ongoing process. Policies pharmacy expenditures was saved by the Department of
and procedures for requests to add and delete drugs from Veterans Affairs (VA) in two years by implementing a
the formulary must be in place. This includes changing national f ~ r m u l a r y . " ~A] committee of the Institute of
recommendations for therapeutic interchanges and com- Medicine found that for inpatient discharges for condi-
ponents of drug use guidelines. As the medical evidence tions likely to be affected by the VA formulary's limited
changes in the published literature, the formulary system drug list, no increases in hospitalizations were found.['51
must be able to quickly respond. The committee did recommend to increase physician
Therapeutic class reviews are an important part of representation on formulary committees and to abandon
formulary maintenance. The pharmacologic class of drugs the requirement that a drug be marketed in the United
selected for review should be prompted by criteria set by States for a year before it could be admitted to the
the P&T Committee."'] These criteria may include the formulary. However, convincing research clearly docu-
number of adverse drug reaction reports, new information menting improved patient outcomes is scarce.
in the medical literature, or drug class expenditures. Some Managed care organizations have used formularies to
groups may choose to review the class whenever a request rein in drug costs but a controversial study concluded that
is received to add a new drug from that class to the formularies produced an opposite effect."61 Researchers
formulary. The goal is to always have the best agents found that restrictions on drug availability were linked
within a class available based on the latest medical to increases in other services shifting costs by increas-
evidence. At the time of the review, new drug use or ing the use of either nonrestricted drugs or other health
treatment guidelines may be considered. care services. This study included the use of the restric-
The formulary system should include a mechanism for tion method called prior authorization, a method used to
patients to receive a drug not listed on the formulary if it discourage the routine use of an expensive drug by
is truly needed. A review of these non-formulary drug requiring an approval process before the agent could be
requests may offer insight into areas where the formulary prescribed. In general, the results showed that the more
is not meeting the needs of the health system's patients. restrictive the formulary. the higher the drug costs and
This is true if the review reveals that requests for a the higher the number of prescriptions, outpatient and
specific agent are justified and frequent. The review may emergency room visits, and hospitalizations per patient
show that education is needed for the prescriber to steer per year. The study design and conclusions have been
them toward a more rational formulary choice. highly ~riticized."~]
A prior authorization technique involving non-ster-
oidal anti-inflammatory drugs (NSAIDs) in Medicaid
patients was shown to be highly effective."81 NSAIDs not
Medication use evaluation (MUE) is a performance im- available generically were place on prior approval status.
provement method that is an important part of the This lead to the increased use of generically available
formulary system. MUE focuses on evaluating and im- NSAIDs as first line therapy. For a two-year period, the
proving medication use processes with the goal of opti- result was a 53 percent decrease in expenditures (S12.8
mal patient outcomes.''21 It involves establishing criteria. million) with no concomitant increase in Medicaid
guidelines, treatment protocols. and standards of care for expenditures for other medical care.
specific drugs and drug classes and the medication use
process (prescribing, preparing and dispensing, adminis-
tering, and monitoring).
lowering the quality of carc. owever; such incentives ASHP national survey of pharmacy practice in acute care
may improve quality. For example rewarding physicians scttings: Prescribing and transcribing--1998. Am. J.
guidelines for treating hypertension Health-Syst. Pharrri. 1999. 56 (2). 142- 157.
-blocker and a generic thiazide).""' 9. http://www.ashp.org/bestpracticcs/forinulary/position/
positioi~pdf(accesscd December 2000).
In presentation at the Joseph A. Oddis Colloquium on
10. Carroll, N.V. Formularies and therapeutic interchange: The
Ethics, it was suggested that the pharmacist play the role
health care setting rnakcs a difference. Am. J. Health-Syst.
of a pharmacoethicist on P&T Pharm. 1999, 56 (5). 467 472.
11. org/bestpracticcs/formulary/gui dc/
esscd December 2000).
12. http://www.ashp.org/bestpractices/formulary/gui~le/
mcdication.pdf (acccssed December 2000).
I.http://www.ashp.org/public/news/breaking/DF-fix.pd~ 13. FIarlct, T.K.: Hu, T.W. Association bctween forrnulary
esscti October 2000). strategies and hospital drug expenditures. Am. J. Mosp.
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tury. Am. 3. Hcalth-Syst. Pharm. 1997. 54 (16), 1805- 14. Anon. National formulary a plus for VA. Am. J. Health-
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Am. J. Flcalth-Syst. Pharni. 1 97. 54 (16). 1815 1825. bcr 2000).
4. 16. Horn, S.D. Unintended consequences of drug formularics.
,pita1 Pharmacists: A history. Am. J . Nosp. Pharm. Am. J. Health-Syst. Pharm. 1996 5 3 (18), 2204-2206.
3. 5 0 (SUPPI. 2). S1-43. 17. Curtiss, F.R. Drug formularies provide path to best care.
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18. Snialley. W.E.; Griffin, M.R.: Fought, R.L.:Sullivan, L.;
6. Kuckcr, D.T.; Visconti, J.A. Hospital formularics: Organ- Ray, W.A. Effect of a prior authorization requirement on
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33 (9). 912-9i7. aid patients. N. Engl. 1 . Me
7. Amcrican Mcdical Association. AMA policy on drug 19. Smartwood, D.E. Ethics and managed care forinularics.
forniularics and therapeutic interchange i n inpaticnt and Am. J. Health-Syst. Pharm.
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PHARMACY PRACTICE ISSUES
olesar
Univer.sity of Wisconsin, Madison, Wisconsin, U.S.A.
of Clinird Phcirinac.j
Encjc~loi~ediii 367
DOI: 10.1081IE-ECP I20006217
Copyright 0 2003 h y Marcel Dekker. Iiic. All rights reserbed
368 Gene Therapy
of the market share and therefore are not reviewed. Each rapeutic gene must enter into the cell intact and travel to
of the three major categories of vectors used in clinical the nucleus where it interacts with the host cell ma-
trials has unique attributes and limitations that include, chinery, ultimately being turned into a therapeutic protein
but are not limited to, DNA-carrying capacity, tropism (Fig. 1). A major limitation of most gene therapy is poor
for target cells, in vivo transfer efficiency. duration of transfer efficiency of the gene to the target cell pop-
gene expression, and potential to induce inflammation ulation. To overcome this obstacle, scientists have turned
(Table 1). to the most efficient, naturally occurring gene vectors
known to human kind-viruses. The primary objective is
to produce virus-based vectors that retain the essential
"gene delivering" features. while also eliminating char-
acteristics associated with infection and host toxicity. Due
to the pathogenic nature of viruses, substantial effort has
The fundamental goal of gene therapy is to correct a also been devoted to the development of synthetic vectors
singular genetic defect in the cells responsible for causing that chemically mimic the natural gene delivery features
disease in the host. To accomplish this, the gene of of viruses. The most common viral and nonviral vectors
interest must be isolated and packaged into a delivery used in clinical trials share certain attributes but are quite
vector and then introduced to the recipient. The the- distinct in many ways. As is discussed, these features
have a substantial impact on therapeutic strategies and, in
certain situations, limit the use of vectors in different
disease states.
etroviral Vectors
-
-
_c_
-
Fig. 2 Overview of retroviral vector administration.
nical trials are the double gene constructs. They possess culture to enhance transfection efficiency. However, many
the therapeutic gene, as well as a second marker gene, cells exist in a differentiated state; that is, they do not
such as the neomycin phosphotransferase gene. A sig- replicate and may not readily be removed from the host,
nificant advantage of the double gene construct is that thereby preventing the use of retroviruses. An additional
cells expressing the gene marker protein can be selected theoretical limitation of retroviral vectors involves inser-
in culture and then readministered to the patient. Retro- tional mutagenesis. Integration of the genetic material is
viruses integrate the gene insert into the host cell so they random and may occur anywhere in the host genome. It is
are particularly suited for chronic diseases that require therefore theoretically possible that random integration
long-term gene expression to correct the disease pheno- could disrupt expression of other key proteins.
type.['] One of the biggest limitations of retroviruses is that
they are relatively unstable following systemic ad- enoviral V e ~ ~ o r ~
ministration.[71 For this reason, most human applications
require removal of the target cells for ex vivo gene The most extensively used adenoviruses are serotypes 2
transduction. Retroviral vectors also require that cells (Ad2) and 5 ( A d 3 because both are not associated with
undergo replication during transfection to stably integrate serious infectious disease in humans.['] Similar to
the gene of interest. Therefore, most clinical protocols retroviral vectors, elements of adenovirus DNA genome
involve induction of cell replication during ex vivo cell are removed to prevent replication once inside the
370 Gene Therapy
I Packaging Plasmid
Dibision of Packaging \ ector
into Separate gag-pol and en\ for
1
@=F5iE! Retroyiral Vector
/Transient Methodl
mammalian cell. Removal of these elements also gene product is transient. This can be an advantage if
provides space for insertion of a therapeutic gene temporary expression will correct the defect; however,
(Fig. 3). An additional reason for tailoring the in most strategies, persistent gene expression is required
adenoviral vector genome is to eliminate the expression to correct the underlying disorder. Therefore. mainte-
of antigenic viral proteins that precipitate a host nance dosing of the vector is required to sustain thera-
inflammatory response. A distinct advantage of adeno- peutic benefit to the patient. In this situation, the other
viral vectors is that they have broad cell tropism and major limitation of the adenoviral vectors, host toxicity,
can transfect nondividing cells. They can also be becomes a c o n s i d e r a t i ~ n . ' ~ ~The
' ~ ' adaptive host re-
administered systemically via the intravenous, in- sponse becomes important because memory is generated
tramuscular, and intranasal routes. From a formulation against the vector, thereby amplifying the immune re-
standpoint, adenoviral vectors are superior because rela- sponse upon repeat administration and reducing the du-
tively high titers can be achieved (10" colony-forming ration of gene expression. For these reasons, substantial
units/milliliter) to ensure convenient dosing in a effort is underway to eliminate adenoviral vector-in-
minimal volume. Despite these attributes, the adenoviral duced inflammation by selectively removing key antige-
vectors possess features that limit their utility. Unlike nic determinants associated with the host response. The
retroviral vectors, the gene cassette resides in the fundamental challenge is to make a safe vector without
nucleus independent of the host cell genome. Because removing the ability of the modified virus to efficiently
stable integration is not achieved, expression of the deliver its genetic payload.
Gene Therapy 371
biological hazard, and provided to the patient usually determine how long a particular gene will be expressed in
within hours of receiving the product. Currently, no guide- a specific tissue once the vector has delivered the the-
lines have been published to address the safe preparation rapeutic gene to the targeted cells. Preliminary investi-
and handling of gene therapy products. Handling usually gations have addressed this concern, but are limited to
requires that therapies are prepared in biological cabinets theoretic calculations from in vitro data."41 Ultimately,
under sterile conditions. Appropriate barriers, including this information is essential to develop a gene dosing re-
gloves, gowns, and masks should be worn by those pre- gimen for a given patient, vector, and disease. Many trials
paring and administering the dose. Gloves and other sup- involve treatment of chronic disorders, including AIDS,
plies used in preparation should be autoclaved or de- malignancy, and cystic fibrosis in which the gene is being
contaminated by ultraviolet light prior to disposal in delivered to differentiated cells with a limited life span.
biohazardous waste containers. Patient secretions includ- Therefore, it is presumed that many patients will require
ing blood, urine, feces, and respiratory secretions may be maintenance dosing of a vector to sustain expression of the
decontaminated with bleach prior to disposal. therapeutic gene product over time.
Monitoring clinical efficacy of gene therapy has re-
ceived little attention. For example, in published trials
involving patients with ADA deficiency, the investiga-
tors routinely measured serum ADA protein concentra-
The pharmacokinetic and pharmacodynamic parameters tions to document sustained expression of the therapeutic
of gene delivery vectors are largely uncharacterized in gene."'] In additional, the patients were extensively mo-
humans. However, essential concepts have been described nitored for evidence of improved immune function and
regarding the many unique aspects inherent to in vivo decreased number of infections. In the case of cystic fi-
distribution of macroparticulate DNA carrier systems. The brosis, the cystic fibrosis transmembrance conductance
distribution of most vectors is predictable and, in most regulator (CFTR) protein is not released by transfected
cases, is limited by physical characteristics of a macro- cells and remains associated with the cell membrane in
molecule. In general, all gene delivery systems are rapidly patients. Knowles et al. had to physically remove nasal
cleared from the systemic circulation, within minutes, epithelial cells and then use advanced molecular tech-
after placement into the bloodstream. This often limits the niques to document protein expression and function.[l6'
capability of the vector to transfect cells in the targeted Gene therapy strategies undoubtedly create unique chal-
tissue. Fortunately, many of the vectors used in clinical lenges for the clinician trying to determine when the
trials can withstand physical manipulation, allowing site- next dose of a gene therapy vector should be adminis-
specific administration in an attempt to enhance expres- tered. Measurement of sustained gene expression, or a
sion in defined tissues. Perhaps a greater challenge is to lack thereof, will likely become common laboratory
Table 2 Monogenic diseases: phase I and I1 ongoing gene therapy clinical trials as of February 1, 2001
Number of
Indication Gene open trials Countries
procedure for gene therapy recipients and require spe- cient gene transfer to the airway epithelium using reporter
cialized molecular assay techniques. genes in rodents, followed by partial correction of the
disordered airway electrophysiology in CF mice. Clinical
trials soon followed and more than 150 volunteers with
TH bT cystic fibrosis participated. The results have been both
encouraging. as gene therapy appears to be possible, and
frustrating. as it just do not work that well. There is good
evidence of low levels of gene transfer and small changes
Monogenic, or single gene disorders, are rare hereditary in ion transport, but progress has been hampered by in-
disorders usually identified in childhood. They represent efficient gene transfer, immunity to viral vectors, and a
the purest approach to gene therapy, where potentially, the systemic inflammatory reaction provoked by plasmid
correction of a single gene defect by gene therapy may DNA, resulting in no clinical benefit to date.“93201
lead to correction of the disease state. The major limitation
of gene therapy for monogenic disorders is that the rarity ancer
of these conditions limits the number of patients able to
participate in clinical trials. The majority of gene therapy In contrast to monogenic disorders, cancer is generally
trials for monogenic disorders has focused on severe com- caused by multiple genetic defects, providing no clear
bined immunodeficiency syndrome (SCIDS)[’7”s1 and single target for gene therapy. However, because cancer is
cystic fibrosis (CF).[193201 In addition, small trials are on- the second leading cause of death in the United States,
going in Fanconi’s anemia, hemophilia, and other diseases gene therapy is under intensive investigation. Rather
(Table 2 ) . than correcting the multiple genetic defects found in
tumors, cancer investigators have generally investigated
approaches to conferring drug sensitivity, either by
s transvecting tumor cells with a gene encoding an enzyme
such as herpesvirus thymidine kinase (HSV-TK)[”’] that
Patients with SCIDS, a rare genetic disorder in which can metabolize a nontoxic drug to its toxic form (suicide
ADA is absent, have a greatly impaired immune system. genes) or with p53 (Table 3).[221
The initial success in gene therapy came in 1989, with the The majority of gene therapy clinical trials are for
report of the successful transfection of the normal ADA cancer, with trials ongoing for almost all types of cancers.
gene into T lymphocytes. In the two patients studied, both In addition, gene therapy for cancer is closest to the clinic,
had normal immune function restored without adverse with both p53 and HSV-TK gene therapy in phase 111
effects. Subsequent studies have demonstrated that both clinical trials (Tables 4 and 5).
stem cells and CD34+ umbilical cord cells can be en-
gineered to produce ADA and restore immune function.
Although this disease is extremely rare, it represents the SV-TK
first successful clinical use of gene therapy.[I7 “I
The HSV-TK gene converts nontoxic nucleoside analogs
such as ganciclovir into phosphorylated compounds that
kill dividing cells. Therefore, cells genetically modified
CF should be the ideal candidate for gene therapy be- to express the HSV-TK gene can be killed by the ad-
cause it is a single gene defect and thus presents a clear ministration of ganciclovir.[211
target. The main clinical problem is in the lungs, and the This cytotoxic effect of transduced cells on nontrans-
likely target is the surface epithelium. Methods of topical duced cells is termed the bystander effect.[231Because only
delivery to the airway surface are already well developed. a small number of cells will be transduced with the
All the required components for gene therapy were in cytotoxic gene, when these cells die, they release toxic
place, and CF gene therapy progressed rapidly from pre- products that in turn kill the surrounding (or bystander)
clinical to clinical studies. The gene, although large, could cells. The TK-ganciclovir approach is currently used in
easily be inserted into a virus or produced as a plasmid; several clinical trials for a variety of malignancies, in-
cellular studies showed that CFTR gene transfer could cluding g l i o m a ~ . ‘ ~ ~ ’
produce functional chloride channels and subsequently Adenoviral (Ad)-mediated intrapleural HSV-TK-gan-
showed that cystic fibrosis cell lines could be corrected. ciclovir gene therapy has been tested primarily in phase I
The next steps were the demonstration of relatively effi- and I1 clinical trials in patients with mesothelioma,
374 Gene Therapy
Table 3 Oncology: phase I and I1 ongoing gene therapy clinical trials as of February 1, 2001
~ ~ ~ ~ c a ~ ~ o ~ Gene Number of trials Country
Breast c-erb-b2 U.K.
Cervical HPV U.K.
CML HSV-TK U.S.A.
Colon cancer CC49 zeta TcR chimera U.S.A.
Head and neck INF U.S.A.
Head and neck IL-12 U.S.A.
Glioblastoma HSV-TK Finland, France, Spain,
Switzerland, U.S.A.
Lymphoma MDR I 1 U.K.
Lymphomas and leukemias Specific idiotype 3 U.S.A., U.K.
Melanoma IL-2 6 Germany, France, Italy,
Netherlands, U.K., U.S.A.
Melanoma IL-7, IL-12, Gm-CSF 3 Germany
Melanoma IL-4 2 Italy
Melanoma GM-CSF 1 Netherlands
Melanoma IL-6 1 Poland
Melanoma HLA-B7/beta 2 micro 2 U.S.A.
Melanoma MART1 +gplOO 2 U.S.A.
Mesothelioma IL-2 1 Australia
Metastatic cancer IL2 2 France, Switzerland
NSCLC P53 1 U.S.A.
NSCLC IL-2 1 U.S.A.
NSCLC GM-CSF 1 U.S.A.
O\ arian HLA-A2 1 Singapore
01aiian P53 2 U.S.A., U.K.
01arian, piostate. and breast BRCAl 2 U.S.A.
Ox m a n Mo\ -gamma 1 U.S.A.
Pancreas Cytochrome p450 1 Germany
Prostate IL-2 1 C.S.A.
Prostate PSA 3 C.S.A.
Prostate P53 I C.S.A.
Prostate GM-CSF 2 C.S.A.
Prostate HSV-TK 1 U.S.A.
Renal cell IL-2 + HLA B7 1 Germany
Renal cell HLA B7/Beta 2 micro 2 C.S.A.
Superficial solid tumors IL-2 1 Switzerland
glioblastomas, or ovarian cancer. The gene was adminis- though this may be related to the patient population stu-
tered intrapleurally in patients with mesothelioma or died, which is generally those with advanced refractory
oharian cancer and by direct injection during surgery in disease. Ongoing approaches are evaluating gene therapy
those with glioblastomas. In most phase I trials, the dose- in combination with chemotherapy.[241
limiting toxicity was not reached. Side effects have been
minimal and included fever. anemia, transient liver en- P53
zyme elevations, and bullous skin eruptions, as well as a
temporary systemic inflammatory respouse. Using RNA P53 is the most frequently mutated gene in human cancer,
polymerase chain reaction (PC ), in situ hybridization. with an up to 50% mutation frequency in solid tumors.
immunohistochemistry, and immunoblotting, HSV-TK Most commonly. these genetic changes are missense
gene transfer has been documented in approximately mutations in one allele, although deletions or chain ter-
50% of patients. Clinical activity has been minimal, al- mination mutations can occur.
Gene Therapy 375
Table 4 Oncology: phase I11 ongoing gene therapy clinical Table 6 Cardiology: phase I and I1 ongoing gene therapy
trials as of February 1, 2001 clinical trials as of February 1, 2001
Number Number
Indication Gene of trials Country Indication Gene of trials Country
~ a r d i o v a s ~ uDisease
l~r
Table 5 Infectious disease: phase I and I1 ongoing gene
therapy clinical trials as of February 1, 2001
Angiogenesis, or growth of new blood vessels, appears
Number essential in revascularization after myocardial infarction
Indication Gene of studies Country as well as in treating coronary artery disease and peri-
pheral artery disease. Therefore, cardiovascular gene the-
EBV and CMV pp65 1 U.S.A.
CMV rapy has concentrated on vascular endothelial growth
HIV HIV envhev 3 U.S.A., factor (VEGF) in these diseases[271(Table 6).
Switzerland
HIV CD-zeta 2 U.S.A.
TcR chimera
HIV Antisense 2 U.S.A. Familial homozygous hypercholesterolemia is a rare he-
to pol 1 reditary monogenic disorder caused by mutations of the
HIV Rev+pol 1 2 U.S.A. LDL receptor gene. Individuals have severe hypercho-
Key: EBV. Epstein-Barr virus; CMV, cytomegalovirus; HIV, human lesterolemia associated with premature atherosclerosis. In
immunodeficiency virus. a single study, patients were treated with gene therapy
376 Gene Therapy
Table 7 Other ongoing gene therapy clinical trials as of In a phase I evaluation, VEGF121.10 was administered
February 1, 2001 to 21 individuals by direct myocardial injection into an
Indication Gene Studies Countries area of reversible ischemia either as an adjunct to con-
ventional coronary artery bypass grafting or as sole the-
Amyotrophic CNTF 1 Switzerland rapy via a minithoracotomy. There were no adverse
lateral sclerosis effects attributed to the gene transfer, and patients had
Alzheimer’s disease Nerve 1 U.S.A. decreased angina.[291
growth factor Other trials of VEGF have been reported. A case report
Anemia of end-stage EPO 1 U.S.A. demonstrated improvement in blood supply to an ische-
renal disease
mic limb after intra-arterial gene transfer of a plasmid
Cubital tunnel HIGF- 1 1 U.S.A.
syndrome encoding for VEGF.[301The use of a plasmid-based gene
Hip fracture Parathyroid 1 U.S.A. delivery system, although inefficient, was reasonable in
hormone this situation because VEGF is a potent secreted product.
Rheumatoid arthritis HSV-TK 1 U.S.A. A phase 1 trial of intramuscular delivery of a plasmid-
Rheumatoid arthritis IRAP 1 U.S.A. encoding VEGF in the setting of severe peripheral vas-
Severe inflammatory IL-4 and IL-10 1 Austria cular disease was reported.[311 Gene transfer was per-
disease of rectum formed in 10 limbs in nine patients with nonhealing
Key: CNTF, ciliary neurotrophic factor; EPO, erythropoetin; HIGF,
ischemic foot ulcers. Increased circulating VEGF levels
human insulin-like growth factor: HSV-TK. herpesvirus thylimidine were demonstrated after intramuscular gene delivery. Va-
kinase; IRAP, insulin responsive aminopeptidase. rious measures, including ankle-brachial index and mag-
netic resonance angiography, showed qualitative evidence
of improved distal flow in 8 limbs.
with the LDL receptor. Expression of the receptor was esistance (MDR)
documented, but LDL cholesterol levels remained sub-
stantially elevated 3 to 6 months after gene transfer, In a therapeutic approach, stem cells may be isolated from
611 t27 vs. 550 t51 mg/dL, before and after gene the- patients and genetically modified to express the MDR
rapy, respectively.[2x1 gene.i321These cells are then retuned to the patient prior
to administration of chemotherapy, making the stem cells
resistant to chemotherapy.
ther Diseases
Formation of new blood vessels by the angiodan VEGF is
an experimental strategy for treating myocardial ische- Gene therapy is under evaluation for many diseases,
mia. The VEGF proteins function by interacting with ranging from rare inherited single gene defects to
specific receptors on endothelial cells, which initiates a common disease such as HIV. deafness, autoimmune
cascade of events culminating in endothelial cell migra- diseases, bone regeneration, and many others[4,33,341
tion, proliferation, aggregation into tubelike structures, (Tables 5 and 7).
and networking of the arterial and venous systems.[271
Gene transfer represents one approach to delivering an
angiogen to the heart in which the carrier DNA (cDNA)
coding for VEGF is delivered to the myocardium, with the
myocardial cells used to secrete the VEGF. Studies in The first death attributable to gene therapy occurred in
experimental animals have shown that replication-defi- September 1999, when an 18-year-old patient with or-
cient, recombinant adenovirus (Ad) gene transfer vectors nithine transcarbamylase deficiency died. apparently as a
are advantageous for delivery of angiogens such as direct result of the experimental gene therapy s t u d i e ~ . [ ~ ’ * ~ ~ ]
VEGF, in that Ad vectors provide a high transfection This prompted two senate hearings and resulted in recom-
efficiency, remain highly localized, and express VEGF mendation for implementation of new policies by the
for a period of 1 to 2 weeks, which is sufficient to induce Recombinant Advisory Council (RAC), Food and Drug
collateral vessels to relieve the ischemia but not long Administration (FDA) and NIH, which require earlier
enough to evoke abnormal angiogene~is.‘~’] review of researcher’s plans for monitoring safety and
Gene Therapj 377
quarterly meeting^.[^^-^^' A few of the safeguards imple- Many new gene delivery vectors and protocols are
mented include thorough public evaluation of protocols currently in developmental stages that aim to improve on
before investigational new drug assignment for FDA and the earlier prototypes. The relatively small number of
institutional review board (IRB) approval; the devel- vectors used in clinical trials underscores the complexity
opment of a single, uniform mechanism for reporting of DNA delivery and our lack of knowledge about how
adverse events to the RAC, FDA, and other relevant these macroparticulates are handled and expressed in the
agencies; establishment of a public database of all adverse human body. It is hoped that the recent reprioritization of
events; and nonparticipation of investigators with financial gene therapy studies will improve the design of vectors,
interests in study outcomes in patient selection, the enhance our understanding of the biological interactions
informed consent process, and direct management of between gene-carrying vectors and the body, eliminate
clinical studies. adverse events, and improve information gained from fu-
Further evaluation of this tragic event has identified ture clinical trials. Assuming these events occur, experts
that vector-associated toxicity was not the sole cause for still predict that gene therapy is still more than 5 to 10
this patient’s death. The FDA determined that human years from routine use in patients.
subjects in this investigation were not adequately
protected and that there was substantial financial conflict
of interest. Subsequently, the NIH has discovered hun-
dreds of unreported adverse events among volunteers en-
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PHARMACY PRACTICE ISSUES
Art e
Wilkes Univcrsity, Willes-Barre, Pennsylvania, U.S.A.
I sure that the two products, if used in thc same way in the
same patient, will yield the same result.‘’ I f a drug product
All drugs that are approvcd for sale generally carry at least is subject to this debate, thc innovator always says “no”
two names. The drugs are given a proprietary or trade and the sccond and subsequent manufiacturers always say
name givcn by the company that first develops them. “yes.” In the United States, the FDA scts the standards
These companies often are referred to as the innovator against which the question is resolved, and scientists take
company. The drug is igned a nonproprietary or generic sides usually on the issuc of “arc the current FDA
name, which is agreed to by the WHO lnternational standards good enough.” If the FDA givcs an “A” rating to
Nonproprictary Nomcnclature (INN) Committee and thc a drug product, it is in cffect telling the prescriber that the
U.S. Adoptcd Names Council (USAN). A new drug is drug product will yicld the same therapeutic and side-
usually first marketed with some patent protection and at a effects profile as the innovator drug product. The Orangc
price that, at a minimum, recoups the cost of development Book specifies the equivalence rating from the FDA.
over the remaining life of the patent or othcr exclusivity Almost all generic drug products currently marketed are
arrangement. Eventually, protection from competition is rated A; the FDA has not approved a generic without an A
lost to other pharmaceutical companies, often companies rating in decades. Finally, the consumer pays the price,
or divisions of companies that specialize in marketing either in the unnecessarily high cost of drugs if
off-patent drugs. These companies or divisions are called unnecessary studies are performed and gcneric competi-
generic companies. They can apply to thc appropriate tion delayed or in risky drug substitution if the FDA is too
regulatory body such as thc Food and Drug Administration relaxed in its standards. The tests required by the FDA
(FDA) for permission to markct the same active ingredient have changed over the years. They have become morc
under its nonproprietary or generic namc. The generic proscriptive and are based on sound statistical grounds.
manufacturer is not required to do a cornpletc clinical trial The FDA has also increased thc level of oversight of the
to prove effectiveness and safety because that has already pharmaceutical companies that manufacture generic
been well established for the drug. However, it is required equivalents of innovator products. Thus, the regulatory
to show that the new drug product is equivalent to the process has become more stringent, and the level of
original drug product. For the purposes of this article, we assurance that the public has that a generic product is both
define the drug as the chemical that has the pharmaco- safe and effective has gone LIP.The FDA has often statcd
logical effect and the drug product as a dosage form that that there are no known therapeutic failures from
contains the drug and othcr ingredients or excipients that switching among products that have been ruled as
allow thc formulation of thc dosage form. There is a large equivalent by the FDA.
economic incentive for the development of generic drug
products, cspecially for highly successful drug products.
The pharmnccutical company that first brought the product
to market maintains the price at the original level or higher
to continue the cash flow into the company. This allows
the other companies to develop a formulation of the drug In the carly 1970s, most states had antisubstitution laws
and to win approval to market with the knowledge that, that required the dispensing of the innovator product when
even at a fraction of the selling price of thc innovator’s the prescriber wrote for a drug by trade name. Most
product, the company can make a good profit. Some physicians had learned only thc tradc name of the drug
innovators defend their market share by arguing quality product, and these laws ensured that gcneric substitution
and reliability. The FDA must act as an impartial arbitrator would be at a minimum (1). The Amcrican Pharmaceutical
of this debate. The debate is clearly about money, but is Association (APhA) along with other groups pushed for
argued in a scientific forum. The key qucstion is, “Are we the repeal of these laws and opened the way for the growth
of the generic industry. The lack of bioequivalence data plays a key role when evaluating the potential therapeutic
available at that time led to the formation of the Generic impact of a particular dosage form. Knowledge of the time
Drug Bureau within the Food and Drug Administration. to onset of drug action, which is directly related to rate of
As a result of the efforts of that group, the FDA produced absorption, is a significant concern, especially in acute
a book, Appi'oved Drug Pi-oducts With Therapeutic clinical situations such as asthma attack, hyperglycemic
Equivalence Evaluations, in the late 1960s. This became shock, and pain.
known as the Orange Book because of the cover color. The The bioavailability of drugs from specific dosage forms
book has been published annually with monthly updates. is affected by the nature of the inactive ingredients or
The contents are now available on the FDA Website (2). pharmaceutical excipients and the process used in its
In 1984, the Drug Price Competition and Patent Term formulation. (For additional information, see Bioavail-
Restoration Act was passed. This act. also known as the ability of Drugs and Bioequivalency in this Encyclopedia.)
Waxman-Hatch Bill of 1984. encouraged the develop- When comparing similar dosage forms from different
ment of new innovative drugs by established procedures, manufacturers or different lots from the same manufac-
extended patent rights, and facilitated the FDA approval turer, it is most useful to determine the relative
process for generic drugs (3). To address the first goal, the bioavailability of the two products or lots. Some scientists
law created a mechanism to extend the period of patent have attempted to establish an in vitro test that could
protection for manufacturers of innovative new drugs successfully predict in vivo bioavailability. However, to
generally ensuring at least 5 years of market exclusivity date, none has been developed.
after approval. To address the second goal, the law Pharmacokinetics means the application of kinetics to
established an Abbreviated New Drug Application drugs. It can be defined as the study of the time course and
(ANDA) for applications after 1962. Drugs chemically fate of drugs in the body. Teorell is often given credit for
equivalent to those previously approved by a full the origin of pharmacokinetics with his publications,
application process need only be proven bioequivalent, Kinetics of Distribution of Substances Administered to the
not clinically equivalent. Depending on the drug, proof of Body (4, 5 ) . This science is the theoretical support for the
bioequivalence can involve in vitro dissolution studies, in use of bioequvalency testing to establish therapeutic
vivo singie-dose bioavailability studies, in vivo multidose equivalence among dosage forms of the same drug. The
bioavailability rtudies. or a combination of these. first approach to a pharmacokinetic understanding of drugs
However, in vitro dissolution studies alone are not in the body, called compartment analysis, considered the
adequate proof of bioequivalence for purposes of an body as a group of compartments through which the drug
ANDA. must pass. The compartment itself does not exist but
represents the average of many processes that give rise to
the observed phenomenon. The size of the imaginary
compartment can be calculated and is useful in under-
standing the process of absorption, distribution, and
elimination or metabolism of the drug. Regardless of the
model used, a plot of the plasma concentration of the drug
versus time yields a curve that can be described by a
The goal of the testing of generic products is not to polyexponential equation. The area under that concen-
establish the clinical usefulness of the drug but only to tration-time curve (AUC) is directly related to the amount
ensure that the generic product or new formulation has the of drug absorbed. The time to reach peak concentration
same relative bioavailability as or is bioequivalent to the and the peak concentration itself are related to both the
inno\ ator product. dose and the rate of absorption.
Bioavailablity has been defined as a measure of the rate An important limitation of compartment analysis is
and extent of absorption of a drug into the systemic that it cannot be applied universally to any drug. A
circulation after administration of a dosage form. An simpler approach that is useful in the case of
intravenous i.v. dose is considered by definition to be bioequavalency testing is the model independent method.
100% bioavailable. All other routes of administration will It is based on statistical-moment theory. This approach
produce a total bioavailability less than or equal to that of uses the mean residence time (MRT) as a measure of a
the i.v. dose. Thus, only a drug that is completely absorbed statistical half-life of the drug in the body. The MRT can
into the systemic circulation can have the extent of be calculated by dividing the area under the first-moment
bioavailability equal to the dose stated on the label. In curve (AUMC) by the area under the plasma curve
addition to the extent of absorption, the rate of absorption (AUC) (6).
Generic Drugs and Generic Equivalency 381
drugs, with proof of bioequivalency. The use of average drug has four or more competitors, it is no longer profitable
bioequivalence data is under attack. This is because of the for additional generic companies to enter the market.
concern that there might be a significant subject-by- Generic drug manufacturers typically will continue to
product interaction. Regulatory agencies now assume that manufacture drugs that produce little or no profit because
this is not the case (8). The advantage of using individual large purchasers that are their prime customers (chain
bioequivalence studies is the reassurance that if sub- drugs stores, buying groups for smaller community
ject/product interactions do occur, the study design would pharmacies, etc.) prefer to buy from companies that can
control for them, and a more statistically valid measure of supply most of the common generic drugs. For example, if
the rate and extent of absorption of the drug from the two a generic drug firm no longer produces amoxicillin
product would be determined. Some of the disadvantages because it can make more money by shifting its antibiotic
associated with shifting from average to individual production facilities to, for example, a cephalosporin drug
bioequivalence testing are cost, numbers of subjects for which it has less competition, a large chain may chose
needed, and diversity of the study population required. to buy its entire generic antibiotic line from another
[See other articles that address the impact of the new company that supplies both.
metrics on the reliability and cost of the performance of The profitable generic drug companies are profitable
bioequivalence testing (9- 12).] because they have found a strategy to maintain some
control over the price of their products. In the early years
(1984-1988), the best way to get “first approval” from
the FDA apparently was to be first to file, to get assays or
OMY
bioquivalence studies done on difficult to duplicate drugs,
or to find some way to get an expedited approval from
inside the agency. Unfortunately, this sometime involved
The modern generic drug industry in the United States payoffs to FDA review chemists (those FDA experts
really only dates from the passage of the Waxman-Hatch assigned the task of evaluating biostudy results, the
Act in 1984. Within 5 years of passage, generic drugs crucial piece of a generic drug application, remained
captured 40% of the market for prescriptions written remarkably free of the scandal). More often, it involved
inthe United States. Since that time, the generic drug submitting false information to the FDA (including, in a
market share has stablized between 40 and 50% of the few cases, false biostudies). Many generic drug firms did
prescriptions written. However, the dollars paid for not survive the scandal, and others survived only after the
generic drugs are only 10% of the total sales of drugs in previous management and ownership were purged from
the United States. That statistic alone tells us that the the firms.
consumer receives enormous benefit from the substitu- For a short period, it was believed that the profitable
tion of therapeutically equivalent generic drugs when segment of the business involved not production but
available. distribution. After all, if commodity prices approach
A horrendous scandal hit the industry in the late 1980s, marginal cost and the marginal cost of manufacturing
wherein firms representing 75% of the production of the drugs is minimal, but the price to the consumer remains
generic industry pled guilty to one or more criminal significantly more than marginal, there must be middle-
charges involving filing false applications with the FDA, men somewhere making the money. Clearly, those
paying illegal gratuities to FDA personnel, and/or related middlemen were not in the retail pharmacy where profits
crimes to gain an unfair competitive advantage in the continued to be squeezed. Distributors were thought to be
emerging marketplace. Surprisingly, this scandal produced the new profit centers. But a funny thing happened on the
only a small delay in the market share march of generic way to that particular bank.. . .
drugs and only a temporary loss of consumer confidence in Consumers became outraged at the rapid increase in the
generic products. price of pharmaceuticals as the innovator companies (and
The scandal was tied to a phenomenon that still some generic firms) rushed to raise prices and as generic
dominates the business strategies of generic drug firms to drug company after generic drug company was pushed out
this day: the need to obtain approval to manufacture and of the industry in the wake of investigations by a
distribute before other firms enter the market. Because of Congressional committee and a federal grand jury.
the “commodity” nature of the business and the relative Second, the Administration, in response to public concern
ease of entry into the industry, firms devote most of their about the cost of pharmaceuticals, pressured the
resources and managerial talent to obtaining first or second pharmaceutical industry and forced lower prices and
approvals from the FDA for their products. Once a generic significant rebates to the federal and state government
rugs and Generic Equivalency 383
programs that paid for drugs. Wholesale distributors of all between FDA “AB”-rated drugs, the FDA offers the
drugs subject to the federal rebates suffered. assurance that they can expect the same therapeutic
Finally, the firms that thought they could profit most and side-effect profile as the brand drug or another
from the scandal entered the market. These were “AB”-rated generic drug. The FDA offers no such
innovator firms, many of which had already played a assurance if the switch occurs among different drugs,
significant role in the distribution of generics. even if they are in the same therapeutic class. For
Ultimately. the profit margins from generic drug sales example, aspirin and Tylenol may be equally effective in
were not sufficient to carry the overhead of the branded the treatment of headache, but the FDA makes no such
companies, and most left the market or returned to their certification. whereas it makes exactly that certification
distributor role. Even in the case of the firms for Bayer aspirin and Safeway aspirin.
manufacturing and marketing generic versions of their The dominance of the HMO (and related organi-
own branded products, giving them significant advan- zations) and their PBMs (and related organization types)
tage over the remaining pure generic firms in served to accelerate the substitution of generic drugs at
developing and filing of the ANDAs with the FDA the turn of the 21st century. However, even that pres-
and the added advantage of relatively less scrutiny from sure could not slow the re-emergence of a high rate of
the scandal-rocked agency, most had exited the price increase, greater than consumer or comparable
marketed by the end of the decade. wholesale prices as a whole, in prescription drugs.
Some innovator firms entered the generic drug market Innovator companies learned that establishing very
so that they could have a product line consistent with their high prices for “breakthorough” drugs could more than
new business strategy: disease state management. This compensate for the loss of patent protection on a highly
strategy, a function of the rise of HMOs and the return of profitable drug.
the concept of scarcity to prescription drug dispensing, Furthermore, the United States is the only developed
was intended to involve the development of a continuum country in the world that has chosen not to explicitly control
of drug therapies for the treatment of a specific illness the price of any drug product and has used its market power
(diabetes, depression, etc.), wherein the patient would be as a huge buyer relatively sparingly. Consequently. U.S.
tried on the older, less-expensive drug first and. if it did not prices for drug products still under patent are usually
work. the next most cost-effective drug would be substantially above those charged anywhere else in the
administered and so on until the least cost-effective drug world. Generic prices approach cost except for those few
would be the treatment of last resort. Unfortunately, the generics that have managed to eliminate or limit for a
branded companies that selected this strategy found specific period competition from other generics.
themselves competing with doctors. hospitals, and Those generic drug firms that prospered in this
insurance companies for control of the treatment regime restrictive price environment all had one or more niche
of individual patients, a losing proposition for the entity drugs that were immune from corrosive price competition.
with the least amount of information about and access to Some companies mastered a manufacturing process that
the individual patient. produced bioequivalent medicine that the innovator itself
Another factor in reducing prices of all drugs that had found difficult to master lot to lot. Others took advantage
some form of competition was the rise of the HMO and its of certain exclusivity provisions in the law for those that
pharmaceutical watchdog. the pharmacy benefit manager challenged a product patent in court, ostensibly to cover
(PBM). These PBiMs create a formulary of approved drugs the cost of litigation. In other cases, the settlement of those
(drugs for which they would reimburse partially or fully) cases provided some form of licensing or distribution
based on bids from competing companies. rights that permitted the sale of a generic product while the
Much of the public’s confusion regarding generic patent was still valid. Finally, a fortunate firm might find
drugs arose from a practice of the PBMs to pressure itself in possession of the exclusive right to purchase the
doctors to substitute different chemical entities in the raw material from the only source available to generic
same therapeutic class for the prescribed medicine. Such drug manufacturers.
a switch IS called a theraputic substitution as opposed to All generic drug firms capable of generating the
the switching among manufacturers of therapeutically necessary cash to develop and market new drugs are
equivalent drugs (generics and the innovator drug or moving toward that lucrative market. For the time being,
other FDA “AB”-rated substitutes). Therapeutic substi- the United States has chosen to use the market mechanism
tution involves a switch to a different drug, whereas as its only important control on drug prices. Generics are
generic substitution involves a switch to the same drug the competition, and competition is our only real form of
from a different manufacturer. If a patient is switched price control.
384 Generic Drugs and Generic Equivalency
According to the Congresslonal Budget Office (CBQ), Administration. Archives Internationales de Pharmaco-
dynamie et dc Therapie. 1937, 57, 205-225.
consumers saved $8- 10 billion in 1994 because of the use
5. Teorell, T. Kinetics of Distribution of Substances
of generic drugs. In that same 1998 report, CBO cited the Administered to the Body. 11. The Intravascular Mode of
Waxman-Hatch Act, generic substitution laws passed by Administration. Archives Internationales de Pharmaco-
the states, and government health programs as seminal dynamie et de Therapie. 1937, 57, 226-240.
events leading to the acceptance of generic drugs and the 6. Yamaoka, K.; Nakagawa, T.; Uno, T. Statistical Moments
in Pharmacokinetics. J. Pharmacokinet. Biopharm. 1978,
resulting savings.
6 ( 6 ) , 547-558.
I. Benet, L.Z.; Goyan, J.E. Bioequivalence and Narrow
Therapeutic Index Drugs. Pharmacotherapy 1995, 15 (4),
433 -440.
8. Patnaik, R.N.; Lesko, L.J.; Chen, M.L. Individual
Bioequivalence. New Concepts in the Statistical Assess-
ment of Bioequivalence Metrics. FDA Individual Bio-
Knoben, J.E.; Scott, G.R.; Tonelli, R.J. Overview of the equivalence Working Group. Clin. Pharmacokine. 1997,
FDA Publication Approved Drug Products with Thera- 33 (1). 1-6.
peutic Equivalence Evaluations. Am. J. Hosp. Pharm. 1990, 9. Midha, K.K.; Rawson, M.J.; Hubbard, J.W. Individual and
47 (12), 2696-2700. Average Bioequivalence of Highly Variable Drugs and
Food and Drug Administration. Approved Drug Products Drug Products. J. Pharm. Sci. 1997, 86 (1 i), 1193-1 197.
with Therapeutic Equivalence Evaluations; http://www. 10. Snikeris,F.; Tingey, H.B. ATwo-StepMethodfor Assessing
fda.gov/cder/ob/ FDA: Rockville; Available from the Bioequivalence. Drug Inf. J. 1994,28 ( 3 ) , 709-722.
Government Printing Office: Washington, DC. 2000. 11. Holder, D.J.; Hsuan, F. A Moment-Based Criterion for
Weaver, L.C. Drug Cost Containment-The Case for Determining Individual Bioequivalence. Drug Inf. J. 1995,
Generics: Situation in the U.S.A. J. Soc. Admi. Pharm. 29 ( 3 ) , 965-979.
1989, 6 (l), 9-13. 12. Mohandoss, E.; Chow, S.C.; Ki, F.Y. Application of
Teorell, T. Kinetics of Distribution of Substances Williams’ Design for Bioequivalence Trials. Drug Inf. J.
Administered to the Body. 1. The Extravascular Modcs of 1995, 29 (3), 1029- 1038.
PROFESSIONAL DEVELOPMENT
mitment to support those individuals who pursue efficacy, packaging, and advertising of prescription and
additional education. There are a number of residency nonprescription drugs. They are also involved in adverse
and fellowship programs available to these pharma- experience reporting and postmarketing surveillance, and
cists. and opportunities exist to attain a nontraditional function in many other positions ranging from field ins-
PharmD degree. pector to project managers, which are the liaison between
the pharmaceutical industry and the FDA. Other pharma-
cists contribute to the FDA with respect to compendia1
standards, scientific investigations, manufacturing facility
inspections, and the FDA’s research laboratories. In addi-
tion, they also work with expert advisory committees and
The PHS is organizationally part of the Department of review panels. Most FDA pharmacists serve at the head-
Health and Human Services.‘41Pharmacists are probably quarters in Rockville, MD, but others are assigned to the
most familiar with such agencies as the Centers for many regional, district, and local offices throughout the
Disease Control and Prevention (CDC). the Food and United States that carry out inspection and enforcement
Drug Administration (FDA), the Indian Health Service activities. A PharmD degree is preferred but not generally
(IHS). and National Institutes of Health (NIH). In ad- required for many FDA positions.
dition, the PHS has memorandums of agreement with
the Federal Bureau of Prisons (BOP), Immigration and
Naturalization Service, and U.S. Coast Guard (USCG), to Indian Health Service
provide primary health services. The Office of Emer-
gency Preparedness and the National Disaster Medical The IHS employs more than 500 pharmacists who are
System are also located within the Department of Health part of a health care team that provides comprehensive
and Human Services. care to 1.4 million Native Americans and Alaska Natives
in hospitals and ambulatory clinics in 34 states. The IHS
pioneered many of the clinical pharmacy services that
rs d r e v ~tnion are now considered standard practice. Pharmacists have
direct access to the patient’s medical record to ensure
There are currently nine pharmacists who serve at the appropriateness of drug therapy, monitor for adverse
CDC coordinating the CDC Drug Service, which dis- effects. and conduct activities in health promotion and
tributes 13 special immunobiological materials and drugs disease prevention. Indian Health Services pharmacists
to physicians in the United States. Special biological and have long been involved in expanded roles such as
antiparasitic drugs that the CDC distributes include bo- primary care, and many have prescriptive authority under
tulism and diptheria antitoxin, bithionol. ivermectin. pen- medical staff protocols. They are actively involved in
tostam, and other medications with restricted usage in drug selection, dosing. treatment, and evaluation of
the United States. These pharmacists also ensure procure- therapy. Patient consultation has been an integral part
ment of drugs, maintenance of treatment investigational of the IHS pharmacy program for more than 30 years, and
new drug applications (INDs), and timely reporting to the private consultation rooms are used to promote effective
FDA. Other pharmacists who also possess a Master’s patient communication. The IHS offers three residency
degree in Public Health perform epidemiology and field programs: American Society of Health-System Pharma-
work in foreign countries. The CDC has been charged to cists (ASHP)-accredited programs in pharmacy practice
maintain a stockpile of pharmaceuticals that can be im- and ambulatory care, and an American Pharmaceutical
mediately deployed in response to chemical or biological Association (APhA)-accredited residency in community
terrorism events within the United States. pharmacy practice. The IHS also provides their pharma-
cists with the opportunity to pursue a PharmD degree
through a relationship with Idaho State University.
The FDA employs more than 250 pharmacists in all phases National institutes of
of the agency’s regulation of drugs, biologics. medical
devices, medical foods, and veterinary products. Pharma- Opportunities for pharmacists exist in both the intra-
cists serve as reviewers for INDs. new drug applications mural and extramural programs. The extramural pro-
(NDAs), and generic drug approvals, evaluating the safety, gram accounts for nearly 90% of NIH funding and is
Government, Clinical Pharmacy Careers in 387
comprised of sites around the world, whereas the also performing research in the area of patient counsel-
intramural program is located on the NIH campus in ing and compliance.
Bethesda, Maryland. The NIH Clinical Center is a 350-
bed hospital devoted exclusively to patients of the
intramural clinical research program. Its pharmacy is ast
supported by 50 pharmacists in various roles, including
nine clinical pharmacy specialists in the areas of Officers commissioned by the PHS deliver primary care
oncology, infectious diseases, critical care, bone marrow services to USCG members and their families at 26
and solid organ transplant, mental health, drug informa- shore-based sites. Sixteen active-duty, PHS- commis-
tion, and ambulatory care. These pharmacists also serve sioned corps pharmacists are detailed to the USCG. In
as principal and associate investigators in various NIH the early 1990s, the USCG adopted the chart prescribing
studies. Clinical pharmacy specialists generally have a and prescription dispensing model developed by the IHS.
PharmD degree and postgraduate training in residency The USCG pharmacy program is linked throughout the
and/or fellowship programs. The staff also includes United States to the DOD Composite Health Care Sys-
pharmacists with expertise in drug formulation, study tem for computerized dispensing functions.
design, analyticallquality control, and pharmacokinetics.
The NIH also offers four ASHP-accredited residencies.
There are also opportunities for radiopharmacists within
the NIH Clinical Center’s Nuclear Medicine and Positive
Electron Tomography (PET) Departments.
The research program at NIH also uses pharmacists
in many of its 14 institutes. Pharmacists in the National
Cancer Institute’s (NCI’s) Pharmaceutical Management The PHS offers students in medicine, nursing, pharmacy,
Branch are involved in anticancer drug development, and other allied health professions the chance to gain
protocol development, collection of clinical data, distri- career experience at sites throughout the United States
bution of NCI investigational drugs and the Treatment through a program called COSTEP. These salaried po-
Referral Center. In addition, the intramural program of sitions, available during vacation or elective time, provide
the NCI has a pharmacokinetics laboratory where phar- students with valuable experience and insight into career
macists perform basic and clinical research. The opportunities within the PHS.
National Institute of Allergy and Infectious Diseases
(NIAID) Division of AIDS pharmacists participate in
protocol development and implementation, and act as
consultants to more than 300 pharmacists involved in C
NIAID-sponsored AIDS clinical trials.
These programs represent the most common career paths
for pharmacists in the U.S. government. However, there
are additional federal agencies, such as the Centers for
Medicare and Medicaid Services, where pharmacists
The BOP employs more than 120 pharmacists who work serve in nontraditional roles. Although generally not
in both hospital and ambulatory settings in 99 prisons in considered by pharmacy practitioners and students, the
38 states. Pharmacists fill medication orders directly federal government provides a number of innovative and
from the inmate’s medical record, thereby having access unique practice areas for clinical pharmacists.
to full information on the patient. Pharmacists at the
BOP are significantly involved in monitoring compli-
ance, managing drug therapy. ordering and interpreting
laboratory studies, and medication counseling for in-
I
mates in tuberculosis prophylaxis, mental health, HIV/
AIDS. and other more traditional chronic disease clinics. * Pharmacy programs within the PHS and related links
Many pharmacists stationed in hospital settings have a
http://www.hhs.gov/pharmacy/
presence on mental health and medical/surgery floors,
round with physicians, and provide drug information * Links to numerous DHHS agencies
services to the medical staff. Pharmacists at the BOP are http:l/www. hhs.gov/agencies
388 Government, Clinical ~ ~ ~ a Careers
r ~ ain c ~
e VA
http://www.va gov
1. @den, J.E.; Muniz. A,; Patterson, A.A.; Ramirez, D.J.;
U.S. Public Health Servicc Commi\sioned corps Kizer, K.W. Pharmaceutical services in the department of
http://www.usphr.gov Veterans Affairs. Am. J. Health-Syst. Pharm.
@ U.S. Army Pharmacy 761 - ~ ~ 7 6 5 .
http://armypharmacy .org 2. Williams. R.F.; Moran. E.L.; Bottaro, S.D., 11; Dydek; G.J.;
Caouette. M.L.; Thomas, J.D.; Echcvarria. R. Pharmaceu-
U.S. Air Force Pharmacy tical services in the United States army. Am. J. Hcalth-
http://www.af-pharmacicts. or&/ Syst. Pharm. 1997. 54 (7); 773-778.
3. Young, J.H. Pharmaceutical services in the United States
e U S. Navy Pharmacy air force. Am. J. Health-Syst. Pharm. 11999, 54 (7), 783-
http://navymedicine med navy. mil/navypharmacy 786.
4. Paavola, F.G.; Dermanoski, K.R.; Pittman. R.E. Phar-
* DOD Pharmacoeconomic Center
maceutical services in the United S
http://www.pec.ha. osd.mil/ Service. Am. J. Health-Syst. Pharm.
e NIH Pharmacy Department 772.
http://www.cc.nih.gov/phar
PHARMACY PRACTICE ISSUES
ea
Templc University, PhiLidelphia, Pennsylvania, U.S.A.
Pharmaceuticals
frica
Canada created the Patented Medicine Prices Review
Organization
Board (PMPRB) in 1987 to guarantee that pharmaceu-
tical products would not have excessive prices in The Republic of South Africa (RSA) has a most diverse
Canada. The board reviews prescribed and over-the- health care environment, with world-class practice and
counter (OTC) prices and publishes annual guidelines facilities in wealthy urban areas and some of the most
for manufacturers. Compliance with PMPRB guidelines primitive care in poor remote villages, with a vast array
is voluntary; however. since 1993, the board has between these extremes. Primary care is now the focus of
the authority to reduce excessive prices and return the the ANC government in an effort to correct years of
excess amount to the government, and to punish the neglect and undemocratic practices under the earlier
manufacturer. apartheid-oriented regimes. Public health services are
The PMPRB compares prices in Canada with those in being brought to the Black townships as rapidly as
seven industrialized nations (France. Germany, Italy, resources permit (1 1).
Sweden, Switzerland, the United Kingdom, and the United However, there are virtually no funds for new drugs
States) to ensure that Canadian prices are in line with those against HIV infection in patients. a problem most prevalent
of comparable countries. There is some controversy that in the RSA. To maximize the value of its drugs budget, the
existing drug products are well-controlled regarding RSA has enacted legislation to create an Essential Drugs
prices, but that such is not the case with newly introduced List for the public sector, along with generic substitution
pharmaceuticals. authority, the removal of some pharmacists’ unique
Health Care Systems: Outside the United States 391
professional privileges, and legislation permitting the legislation, a pricing board composed of members selected
parallel importation of pharmaceutical products already by the Minister of Health would establish prices for each
registered in the RSA. Obviously, this conserves resources, product and a maximum selling price. Public-sector primary
stretching them for more patients, but this angers the RSA care drugs are reimbursed 100% by the government.
and multinational pharma firms. Hospital care outpatient drugs can have copayments. The
South Africa is still the wealthiest country in Africa, Essential Drugs List would be the core of what is to be
with a (1997) GDP at approximately $130 billion. It must available at public facilities, but there appears to be a long
be noted, though, that aggregate numbers hide massive way to go before most of these agents will be regularly
racial differences. It is improving, but the standard of available on a consistent basis at primary care centers or at
living for Blacks is yet only slightly better than it is in public hospitals (13).
neighboring countries, whereas whites enjoy a standard of The parallel importation of RSA-registered drugs
living similar to that found in North America or Western available at lower prices abroad is the basis for PMA
Europe. An unemployment rate of over 30% (mostly among litigation against the Drug Legislation of 1997. In addition
Blacks) exacerbates the fiscal situation (12). to the price-setting committee, DOH efforts to encourage
Routine immunizations for children, conforming to the the use of generic drugs has proven to be a source of
World Health Organization (WHO) recommended sched- conflict. Other features of the new legislation bar
ule is the governmental policy, but it is not yet dispensing samples or making bonus payments to
accomplished in all regions. Infectious diseases including dispensers of medicines; the creation of a Code of Ethics
HIV remain a serious challenge. Planning and budgeting for pharmaceutical marketing; and a series of safety
for resource allocation are difficult because accurate regulations, dealing primarily with limiting practice to
census figures do not exist. Total health expenditures fully qualified and licensed professionals.
appear to be in the area of $300 per person per year. and it There is a fast lane for new drug approvals if the
is estimated that the private sector accounts for greater product is already in at least one of the following
than 50% of total expenditures. jurisdictions: the United Kingdom, Canada, United States,
Public-sector expenditures emphasize primary care, Sweden, or Australia. Approxmately 85% (by value) of
lately, at the expense of tertiary care facilities. Private- pharmaceuticals go through the nearly 3,000 community
sector spending is primarily through private *‘medical pharmacies. Yet, approxmately 80% of the population rely
schemes.” These are nonprofit organizations supported by on the public sector for drugs, received through clinics,
employer associations and employees. There are slightly hospitals, primary care posts. or military facilities.
fewer than 200 of these schemes, providing insurance and Although there is a 20-year patent period of exclusivity1
care payment for nearly 3 million workers and their 5 protection, the parallel imports option effectively defeats
million dependents (of a total estimated RSA population of this protection.
40 million). The largest area of medical scheme It will be interesting to see how the access to drugs,
expenditure is for medicines, which causes the pressures price controls, and quality improvement forces will
on pharmaceutical pricing addressed below. After drugs, interact and what the actual situation will be in South
the next largest expenditures are for private hospitals, Africa in the coming years, especially as the country
medical specialists, general practitioners, and dentists (13). complies with intellectual property and World Trade
The RSA Department of Health (DOH) has totally Organization policies and rules (16).
restructured the previous apartheid system of racial and
provincial health systems into a coordinated national Japan
health program operated through health regions and local
Organization
health districts. Still, there are major differences in
knowledge, education, expectations. and wealth within After North America and before Western Europe, Japan is
different subpopulations (14, 15). the second largest pharmaceutical market in the world. Its
population of 126 million spends $70 billion on
Pharmaceuticals
pharmaceuticals each year. On average, each Japanese
Until recently, manufacturers were free to establish their resident spends $2000 each year on health care with $550
desired price for a drug. Wholesalers and retailers added of that on pharmaceuticals. Perhaps the primary single
what they chose to reach the retail selling price for features of the Japanese market are the above-average
medications. In 1997, a proposed scheme of prices extending proportion of elderly in the population and the higher than
to the retailer was agreed on, but resistance was met from the usual consumption of drugs. It has been estimated that by
Pharmaceutical Manufacturers Association(PMA). In the the year 2050, nearly 30% of the population will be older
392 ealth Care Systems: Outside the United States
than 65 years of age. The high consumption rate is There is a Japanese pharmacopeia that sets official
attributed to drugs being injected and/or sold by the standards and diverse government agencies that perform
physician, a practice used, in part, to increase the total tasks undertaken by an FDA. It is rumored that the Japanese
price of an office visit (17). will establish a Western-style FDA in the near future.
The primary funding source for health services in Japan One of the most disliked regulations in the view of
is the Social Insurance System (SIS), made up of employee foreign and multinational pharmaceutical companies is the
programs that pay for nearly 55% of care. The Medical requirement for duplicative clinical trials with humans in
Service for the Aged program covers another 35% of care. Japan, because those carried out elsewhere are not
Private expenditures and a very small portion for public recognized. Also of interest is the fact that Japan, like
health promotion and disease prevention make up the Korea and Taiwan, has no separation between prescriber
difference. The Ministry of Health and Welfare (MHW) and dispenser of drugs. Called “Bungyo,” it is a major
maintains overall responsibility for health care services source of revenue for doctors and clinics. Fewer than 20%
and functions via a number of bureaus. Numerous sources of prescriptions ever reach a pharmacy for dispensing (19).
comment that regulations are difficult to understand and Good post-marketing surveillance practices (GPiLISP)
interpret. often overlapping, and that this serves as a rules have been in place since 1993. Postmarketing
barrier to foreign firms desiring to enter a market. experience reports are to be sent to a government agency.
Physicians. for example, are authorized to own and operate Both GPMSP and periodic safety reporting requirements
hospitals, effectively excluding corporate owners or are in place that require a review of the product each year
physicians not licensed in Japan (18). while it is in its re-examination period, immediately after
Universal health insurance was established in 1961. marketing approval. Unlike in the United States, where a
Nearly the entire population is covered through the new drug application is approved for an indefinite period,
employer plans or through programs for the unemployed, in Japan, there is a periodic full reassessment. Such
retired, or self-employed. Employees pay 10% of the cost re-evaluations are conducted every 5 years once the
of treatments, up to an annual ceiling, and also pay a initial re-examination period for a drug product has ended.
portion of their premiums. with their employers. Drug products are distributed primarily via the 2000
wholesalers, and in addition, there exists a small second
Pharmaceuticals
channel with drugs going directly to hospitals, GPs, and
The MHW sets prices for reimbursable drugs (those pharmacies. There are approximately 66,000 pharmacies,
approved for the Social Insurance System). Physicians, most of which are family-owned independents. There are
clinics, and private hospitals are reimbursed at a price chains as well. However, a growing market for OTCs is
slightly higher than their actual acquisition cost. The found in convenience stores.
government has scheduled annual reductions in the Physicians administer and sell drugs to patients as a
reimbursement prices to reduce this source of additional highly profitable sideline. The incentive is for the
income to physicians. Patients make copayments of 20%, physician to use as much of the most costly drug products
although for children and low-income elderly the copay- as possible. There is only a small OTC market, because
ment is waived, and recently a plan to eliminate copayments physicians try to prescribe and dispense as much as is
for persons 70 years of age and older was introduced. possible. Other than some concern about a drug lag, the
The MHW reductions of 5 - 1 0 s of the prices of pharmaceutical environment in Japan is robust. Period-
existing drug products appear to have had the opposite of ically, there are calls to separate prescribing and
the intended impact. Doctors are prescribing more of the dispensing; however, this is not likely in the near future
newest, high-priced pharmaceuticals that have not had given the powerful forces backing the status quo (20).
their margins reduced yet, thereby earning a bigger
amount from the wider difference between their actual cost
and the listed reimbursement amount. nite
With regard to generic drugs, astute observers believe
Organization
that the Japanese government wants its R&D-intensive
firms to be successful. A regulation requires generics to be With a population of more than 60 million and GDP per
priced at not less than 40% of the innovator brand price. It capita of more than US $22,000, the United Kingdom is
is reasonable to assume that the margins (Yakkasa) for one of the richest nations in the world. It is one of the G7
physicians are lower with generic drugs, and that these countries, a member of the European Union, and a member
margins will continue into the future, as will the reference of the Organization for Economic Co-operation and
price scheme (19). Development (OECD).
Health Care Systems: Outside the United States 393
In 1996, total health care expenditure in the United effect for all member countries in 1995. The aim of the EU
Kingdom was approximately 7.0% of the GDP. Public system is to harmonize pharmaceutical regulations
expenditure by the National Health Service (NHS) throughout the EU. The centralized registration procedure
accounts for most of the health care costs. The NHS was is handled by the European Medicines Evaluation Agency
set up after World War 11, with the aim of unifying health (EMEA). Authorization through the central registration
care services by voluntary and local hospitals. The NHS procedure is immediately valid in all EU member
offers free health services to all U.K. residents, funded countries. The decentralized procedure relies on the
through general taxation. principle of mutual recognition. After registration has been
Two of the major characteristics of the U.K. health care obtained in a member country under the centralized
system include health authorities responsible for hospital procedure, application may be made for registration in one
services and GP fundholders responsible for primary care. or more other member countries via the decentralized
In 1996, 100 health authorities became operational in procedure (21).
England, responsible for the provision of NHS hospital and The majority of pharmaceuticals are distributed
community health services covering geographic bound- through wholesalers to retail pharmacies, with large
aries with populations ranging from 125 thousand to over pharmacy chains now dominating the market. There are
1 million. There are four levels of hospital services. At the approximately 11,000 community pharmacies in the
community level, community hospitals offer basic medical United Kingdom (21). In recent years, pharmacy services
care for the treatment of acute cases and patients requiring are increasingly available in supermarkets at the expense
convalescent and long-termherminal care. General prac- of local independent pharmacies.
titioners are the key staff here. At the district level, district Total expenditure on pharmaceuticals in the United
general hospitals operate the key acute units, serving an Kingdom amounted to approximately 8650 million pounds
average population of a quarter-million. At the regional in 1999. accounting for approximately 17% of the total
level, major specialty services such as neurosurgery, health expenditure (2 1). The NHS covers prescription
open-heart surgery, and radiotherapy are provided. At the drugs. However, the government does not reimburse for
national level, highly specialized hospitals provide over-the-counter (OTC) products. The Department of
complex services for parts or for the entire country (21). Health indirectly controls pharmaceutical prices. Because
GPs are the gatekeepers and fundholders of the health the price control scheme is related to profit control, rather
care system. The principle of fundholding is that GPs than to the prices of individual products, pharmaceuticals
manage their own budgets. They can obtain a defined are relatively free-priced in the United Kingdom. The
range of services from hospitals and manage patients at the government operates a negative list for products that are
GP level whenever possible to reduce costs. In the late not reimbursable. The cost of most licensed prescription
1990s, GPs fundholders were organized into Primary Care products is fully reimbursed. However, cost constraints and
Groups (PCGs). These networks of GPs cover wide prescribing budgets mean that GPs will often prescribe a
geographic areas with an average population of 100,000. generic when one is available. As a result, new prescription
In 1999, there were 481 PCGs in England and Wales, and drugs usually have a slower penetration rate in the United
all have unified budgets (e.g., drugs, hospital care Kingdom than in the United States. The recently
services). With a population of a small to medium-sized introduced National Institute for Clinical Excellence
HMO in the United States, these PCGs have a very broad (NICE) will add more barriers to the introduction of new
influence on patient health care and the selection of drugs pharmaceutical products in the United Kingdom.
through formularies.
National Institute for Clinical Excellence
Pharmaceuticals
Funded by the government, the National Institute for
The regulatory authority in the United Kingdom is the Clinical Excellence (NICE) was set up as a Special Health
Medicines Control Agency (MCA) under the Department Authority in the United Kingdom in 1999 and, as such, it is
of Health. The agency’s responsibilities include drug a part of the National Health Service (NHS). It was set up
licensing, clinical trials licensing, pharmacovigilance and to “provide the NHS [patients, health professionals, and
drug safety, communication and provision of information the public] with authoritative, robust and reliable guidance
on medicines, inspection of facilities and enforcement of on current best practice.” Its key functions are “to appraise
regulations, and the British Pharmacopoeia. The United the clinical benefits and the costs of those [health care]
Kingdom is a reference member state for the European interventions and to make recommendations.” Guidance is
Union mutual recognition procedure. The European issued from each appraisal based on the clinical benefits,
Union’s pharmaceutical registration system came into cost-effectiveness, and total economic impact on the
394 Health Care Systems: Outside the United States
National Health Service. The government does not have to remaining 50% of the health care expenditures. The largest
adhere to the recommendations by the NICE in its spending sector is hospital expenditure, representing
guidance and financial payment to health care providers. 34.3% of the total GKV health care expenditures (22).
However, many believe that a negative recommendation The federal government has little executive responsi-
from the NICE will have a detrimental impact on the bility for the provision of health care in Germany. Its
pricing, reimbursement, and sales of the appraised product primary responsibility is to provide a regulatory frame-
not only in the United Kingdom but also throughout work within which the individual Lander have to operate.
Europe, Australia, and Canada. The health ministries of the individual Lander are
The guidance covers both individual health technol- responsible for implementing the federal legislation,
ogies (including medicines, medical devices, diagnostic enacting their own legislation, supervising subordinate
techniques, procedures, and health promotion) and the authorities and the medical profession, hospital planning,
clinical management of specific conditions. The Institute and regional administration.
may recommend a technology for general use, for specific Hospitals in Germany can be classified into three major
indications, or for defined subgroups of patients. Based on categories based on ownership: public, nonprofit, and
the appraisal, a therapeutic intervention (e.g., drug) will be private. In 1997, the public sector operated approximately
classified into one of three categories: category A, routine 40% of general hospitals, and nonprofit organizations
use in the NHS: category B, further trials needed; and operated another 40%. However, the number of privately
category C, not recommended for routine use in the NHS. owned facilities has been increasing steadily over the past
The NICE has a board reflecting a range of expertise decade.
including the clinical professions, patients and user The number of practicing doctors has risen steadily for
groups, NHS managers, and research bodies. The Board thepast 1Oyears.More than70% ofthepracticingdoctors are
ensures that the NICE conducts its business on behalf of specialists, with general medicine as the largest specialty.
the NHS in the most effective manner. Details of the Fewer than 30% of doctors practice without any specialty.
appraisal process and membership of the Appraisals
Pharmaceuticals
Committee are available on the NICE Web site
(www.nice.org.uk). Because the NICE was new at the Germany is a reference member of the EU pharmaceutical
time of completion of this article, its impact on the registration system. The European Medicines Evaluation
pharmaceutical industry is still not clear. Agency (EMEA) handles the centralized registration and
the decentralized registration procedures in individual
countries. After marketing authorization of a product with
~ ~ r n ~ n ~ a new active substance has been granted in one country,
the mutual recognition procedure is compulsory in other
Organization
member countries. The mutual recognition procedure is
With a population of approximately 82 million in 1998 and also compulsory for line extensions and generic products.
a GDP per capita of more than $26,000, Germany is one of Marketing authorization approvals in Germany are valid
the world’s largest economies and health care markets. for 5 years and renewable thereafter in 5 year periods.
The population enjoys a generally good standard of health Germany is the home of some major multinational
with a high degree of public awareness about health- pharmaceutical companies such as Aventis, BASF, Bayer,
related issues. Life expectancy in Germany is among the Boehringer Ingelheim, Merck KGaA, and Schering AG.
highest in the world. In 1997, the life expectancy for males VFA is the research-based manufacturers’ association,
was 74 years and for females 80. Approximately 15.8% of whereas the Bundesverband de Pharmazeutischen Industrie
the population were over 65 years in 1997, and it has been (BPI) represents small and medium-sized companies.
projected that by 2020, the number of German inhabitants Because North America is the largest pharmaceutical mar-
aged over 60 years will be 28.2% (22). ket in the world. many of the VFA pharmaceutical compa-
In 1997, health expenditures in Germany totaled $298 nies locate their key operations in the United States. Exports
billion, equal to 14.2% of the GDP. The health care system to Western European countries represent a major source of
in Germany is decentralized, and health care expenditures income for many of the German pharmaceutical companies.
are covered by a variety of sources/payers. The statutory The pharmaceutical market in Germany is one of the
insurance system (GKV) represents the biggest proportion largest in the world. Based on drug use per capita, Germany
of the total care coverage (for almost 50%). Employers, is second only to Japan in the consumption of pharmaceu-
government budget, private households, private insurance, ticals. The principal distribution channels for pharmaceu-
retirement insurance, and accident insurance cover the ticals in Germany are public retail pharmacies and hospital
Health Care Systems: Outside the United States 395
pharmacies. In 1998, there were 47,322 pharmacists in The private (commercial) sector includes private
Germany, equal to 0.6 pharmacists per thousand population hospitals, doctor’s offices, and practitioners of traditional
(22). Public (retail) pharmacies employed 96% of all medicine. Charity organizations such as the Red Cross also
pharmacists in 1998 and they obtained their supplies play a role in the Mexican health care system.
primarily from wholesalers. Prescribed drugs. including
Pharmaceuticals
both branded and generic products, can only be dispensed in
a pharmacy with a doctor’s prescription. The generics The regulatory authority in Mexico is the Direcci6n
market in Germany is one of largest and fastest-growing in General de Control de Insumos para la Salud (DIGECIS).
Western Europe, representing approximately one-third of The Health Secretariat issues pharmaceutical registration.
the European generics markets. OTC products can be Safety and efficacy must be proven by phase I11 clinical
divided into three overlapping categories: prescription trials in Mexico to register drugs that are new to the
OTC medicines, nonprescription OTC medicines, and Mexican market. All major pharmacopeia (International
freely available QTC products that can be sold freely Pharmacopoeia, US Plzarinacopeia, British Pharmaco-
through all retail outlets such as health food stores, poeia, French Pharmacopoeia, Swiss Pharmacopoeia,
supermarkets, and other retail outlets. European Pharmacopoeia, and Japanese Pharmacopoeia)
are acceptable in Mexico.
exic Most domestic producers in Mexico are wholly owned
or licensed subsidiaries of multinational pharmaceutical
Organization
firms. Exports have been growing fast, with other Latin
Mexico is a federal republic of 31 states and a federal American countries as the major destination markets.
district. The population was officially estimated to be 97.7 However, the United States is the major supplier of
million in 1997. GDP per capita was estimated at pharmaceutical imports in Mexico.
approximately US $4400 in 1998. As a developing nation, Pharmaceuticals in Mexico are subject to government
communicable diseases are still one of the major causes of price control. The private sector accounts for approxi-
mortality, although chronic and degenerative diseases have mately 85% of the pharmaceutical market. Prescription
become the leading cause of death during the past decade. dmgs account for the majority of the pharmaceutical
One of the major challenges for the government is to market, with antibiotics as one of the largest classes.
address the inadequacies of the Mexican health care system. Because the use of generics is still a relatively new
Approximately 10 million people have virtually no access phenomenon, most of the prescribed pharmaceuticals are
to regular basic health care services, and another 20 million branded products. OTC products represent approximately
people have less than adequate access. In 1996, the total one-fifth of the total pharmaceuticals market.
health care expenditure in Mexico was equivalent to
approximately 4.6% of GDP. Spending by the public sector
accounted for approximately 60% in 1996 (23).
There are three sectors in the Mexican health care
su
system: public, social security, and private. The public
sector is primarily directed and operated by the Secretariat As presented, these six representative countries use vastly
of Health. The public sector of health services is under the different organizations, financing mechanisms, goals, and
Secretariat of Health and is coordinated by over 200 health provision structures. In fact, few systems around the world
districts. The Federal District Department provides health are identical because the systems represent the values and
care services to some 3.2 million people in Mexico City. priorities and political as well as economic leanings and
The Mexican Social Security Institute (IMSS) Solidarity traditions of that country. If there were one perfect system,
program covers another 10 million people in rural areas. we would be seeing migration toward that model.
The social security system covers health services for However, because this is not the case, it is reasonable to
government employees, managed by the Social Insurance assume that most of the various systems encountered
Institute of State Employees (ISSSTE), and for private- around the world are at least satisfactory in their
sector workers, managed by the Mexican Social Security foundations and macrolevel characteristics, even if some
Institute (IMSS). The two agencies operate their own of the operating details are not always popular (24).
networks of hospitals and clinics and provide similar The world is full of interesting additional approaches
benefits. Some other smaller social security agencies exist, that a serious student of this subject might wish to explore
providing medical services for special groups such as the further. Some of these include the ‘-need clause” used in
army, navy, and state oil company personnel. Norway, where, for example, their FDA had the authority
396 Health Care Systems: Outside the United States
to refuse to accept and review a new drug because Norway 6. Joseph, S.C.; Koch-Weser, D.; Wallace, N. Worldwide
already had six benzodiazepines on the market. The FDA Oveiview of Health and Disease; Springer: New York,
1977; 7-43.
deemed that sufficient unless the sponsoring company 7. Korman, R.A. Academic Reference Manual: Canadian
knew of a new indication or other therapeutic break- Health Care Information; IMS Health: Mississauga,
through from its use. The Swedes bought all of the then- Ontario, 1999; 80-162.
existing community pharmacies in the country in 1970 to 8. World Pharmaceutical Markets: Canada; Espicom
rationalize distribution, and service level and to create a Business Intelligence: Chichester, UK, May, 1999; 9-48.
9. Alleyne, G.A.O. Health Statistics from the Americas; Pan
monopsonistic body for negotiating with manufacturers in American Health Organization: Washington, DC. 1998;
price-setting. The French and others place new drugs into 17-37.
one of several reimbursement categories. Clearly, life- 10. Alleyne, G.A.O. Health in the Americas: Pan American
saving drugs are put in the 100% reimbursement (to the Health Organization: Washington, DC, 1998; 1, 325-337.
patient) category. Most others strive for the 70% 11. Monekosso. G.L. Eighth Report on the World Health
Situation; African Region; WHO: Brazzaville, 1994; 2,
reimbursement category; however, if the manufacturer 2-37.
cannot agree on a price satisfactory to the Social Security 12. Nokagima, H. Eighth Report on the World Health
agency, the product will be placed in a lower reimburse- Situation; 147-165 Global View: Geneva, 1993; I , 37-59.
ment category, effectively hampering its market success. 13. World Pharmaceutical Markets: South Africa: Espicom
This is a powerful bargaining chip for the government to Business Intelligence: Chichester, UK, Feb 1999; 3- 13.
14. World Development Report 1993, World Bank;
contain drug prices. Jamison, D.T., Ed.; 108- 170 Oxford University Press:
It will be interesting to watch the future in this area to Oxford, 1993; 3-65.
see how medications previously requiring a doctor’s 15. World Tables 1995; World Bank: Washington, DC, 1995;
prescription that move to OTC status are handled, and how 22-66.
nutraceuticals, herbals. homeopathic, and naturopathic 16. Basch, P.F. Textbook of International Health; Oxford: New
York, 1990: 144-326.
drugs, without the benefit of rigorous, randomized clinical 17. Bartholomew’s Mini World Factfile; Harper Collins:
trial or outcome data are handled as well. Similarly, we London, 1995; 44. 102, 175.
can be certain that there will be excitement galore when 18. Eighth Report on the World Health Situation: Western
the nations in Central America and the Middle East decide Pacijic Region; World Health Organization: Manila, 1993;
to control pharmaceuticals and to end the practice of lay- I,79-83.
19. World Pharnzaceutical Markets: Japan; Espicom Business
person purchases of virtually any product without the Intelligence: Chichester. UK, Jan 1999; 10-23.
benefit of a physician’s order. Separation of pharmacy and 20. SCRIP: London UK, 1998, 1999, and 2000.
physician functions will occur in the Far East in the not too 21. World Pharmaceutical Markets: United Kingdom; Espicom
distant future, causing even more excitement or grief. Business Intelligence: Chichester, UK; Feb 1999; 17-70.
If logic dictates, we should expect to see in the future a 22. World Pharmaceutical Markets: Germany; Espicom
Business Intelligence: Chichester. UK, Feb 1999.
trend to offer incentives for prescribers who use the most 23. World Pharmaceutical Markets: Mexico; Espicom
cost-beneficial products (bonuses) and disincentives for Business Intelligence: Chichester, UK, Feb 1999.
patients (reimbursement level co-payment differences) 24. Brudon, P. The World Drug Situation; WHO: Geneva,
and physicians when less than optimal choices are made. 1988; 7-108.
Irrespective of whatever does actually occur, it will be
most interesting to observe.
s:
justice, opportunity, rights, and the functional personnel and members of the U.S. armed forces.
responsibilities of government. When this spectrum of Subsequent federal involvement in the provision of and
social values is held over health, health care, and the the payment for health care has incrementally increased to
administration and financing of health care services, it is include care for individuals with special entitlements. The
not surprising that a vastly different array of designs latter include veterans of the armed forces, the elderly,
emerge. Because health and health care are so tightly indigent people, Native Americans, persons with
wound into personal, cultural, and social beliefs, it is not HIV/AIDS, certain disabled individuals, and qualifying
surprising that such a vast array of health care systems and persons with end-stage renal disease. For example,
notions about health have emerged across the world. qualified veterans of the armed forces have access to a
America’s historical foundations have leaned strongly federal system of hospitals, clinics, and long-term care
to the libertarian philosophical viewpoint (3). The facilities under the Department of Veterans Affairs (a
influence of the “Protestant ethic” from Europe, coupled cabinet-level agency of the executive branch of the federal
with the opportunities that a fresh land provided to government). Since 1965, the federal government sponsors
“become one’s own person,” are strongly borne out in Medicare. a health insurance program for the elderly
American society. An unbridled, free-market economy (65 years of age and over and later the disabled). The
and freedom from governmental intervention in the daily federal government also cost-shares with participating
lives of the citizenry are strong values that have been state governments to provide the Medicaid program (also
integrated into the American lifestyle and American enacted in 1965). The latter is an insurance program for
political economic thought. The notion of “pulling health services directed toward qualifying indigent people.
yourself up by your bootstraps” succinctly reflects these In Medicare and Medicaid, institutional and individual
dominant social, political, and economic values. Such providers participate as contractors under a set of specific
antecedents are reliable markers for characterizing conditions for participation.
America’s health care system. Consequently, it is a State and local (city and county) governments have
fascinating mosaic of pluralistic approaches. It is a limited roles in the provision of health care services. State,
strongly market-driven, industrialized system, which, at county, and city health departments are as differently
the same time. may be described as one of the world’s best organized and functioning, as there are states, counties,
and one of the world‘s most troubled systems. and cities in the United States. These agencies reflect and
The United States does not have a universal health represent the special needs of the geographic areas and
insurance program characteristic of many developed demographic compositions of their respective domains.
nations. Nor does it have national health care services Hence, the functioning and expanse of services offered by
like that of the United Kingdom and other nations. Except the New York City Department of Health is vastly
for those persons in the United States who possess special different from a similar agency in rural Montana.
legal entitlements. the American health care system is This unique approach to the application of a health care
largely a private enterprise; in other words, an industri- system must also be examined in light of the diversity of
alized system. The providers, payers, and institutions of the demography and geography of the United States.
care represent a rich mixture of private agents, Approximately 273 million people inhabit the United
corporations, insurance systems, and governmental States across a geographic expanse of 3.5 million square
agencies. There is not a singular rationalizing source for miles of land. Ranging from the deserts of Nevada to the
setting broad-based national policy and direction for the Rocky Mountains of Colorado and Wyoming to the tropics
health care system as a whole. Rather, the vast market of Florida and the oceanic seaboards of the east, west, and
place of ideas has a variety of options in order to southern coasts, American geography and topography is
implement any proposal for which someone will pay. expansive (5). Hence, a substantial challenge to the
Relman has termed this approach “the industrialization of delivery of health care services exists in this array of
health care” (4). geographical areas.
The role of the national and state governments in the The American population is equally diverse and
health care system is limited to those entitlement programs expansive. There are almost 35 million people who are
that have been legislated into federal or state law or where age 65 or older. African Americans constitute 12.8% of the
there is a federal and state partnership. Federal involve- population, Asian and Pacific Islanders 4%, American
ment in the provision of health care services began with Indians 0.9%, and Caucasians make up 82% of the
the U S . Public Health Service (PHS), an agency of the population (5). Because the United States is largely a
U S . government. The PHS was established in 1798 to nation of immigrants, there are literally hundreds of
provide essential health care services to merchant marine additional ethnic groups that are part of the American
Health Care Systems: Within the Cnited States 399
social fabric. As of March 1997. 25.8 million individuals either because the individuals are not eligible or because
in the United States were foreign-born, which represents a uavment rates do not cover the costs incurred. Small.
l i
30% increase from 1990, when there were 19.8 million isolated rural hospitals are facing similar economic and,
foreign-born individuals in the United States. Mexico was hence, survival difficulties. The plight of rural hospitals is
the place of origin for 7 million or 28% of the total foreign of special significance because their survival is often linked
born population in 1997 (5). During 1996 and 1997. 1.3 to the economic and social survival of a rural community.
million people moved to the United States from abroad, While the world’s population grows at an annual rate of
and 92% of those individuals moved to metropolitan areas. 1.796, the population over 65 increases by 2.5% per year.
Additionally, during this time period, 3 million people left There are just fewer than 600 million people over the age
the central cities and 2.8 million moved to the suburbs (6). of 60 in the world. Approximately 360 million of the
The health care system of the United States should then be world’s over 60 population lives in the developing world,
viewed in the following context: in which 7.5% of the population is elderly. In contrast,
18.3% of the population is elderly in the developed world.
A diverse spectrum of social values. which have
The most rapid changes are occurring in some developing
historically pointed more toward libertarianism than
countries where an increase of 200-400% in the elderly
egalitarianism
population is predicted over the next 30 years (9). Because
Limited roles of the federal, state, and local govern-
of the growth of the elderly population, there has been an
ments in the provision of, and payment for, health care
increase in the demand for geriatric and long-term care
services
facilities. Over the next several decades, the elderly’s
A pluralistic, free-market approach to the provision of
health care consumption in the United States will be
health care services
approximately $25,000 per person (in 1995 dollars)
0 A geographically diverse and substantive land mass
compared to $9200 in 1995 (10). In this respect, the United
0 A culturally diverse and numerically large population
States is following the trends exhibited in most developed
whose characteristics are changing toward more elderly
industrialized countries.
and racial and ethnic heterogeneity
The increased utilization of health care services by the
It is critical that the reader be sensitive to these elderly is expected to put additional strains on an already
contextual variables to understand the American health besieged health care system. Increasing the life span, either
care system and how health care policy is shaped and through preventive measures or through other acts of
implemented in the United States. distributive justice, solves some problems while creating
others. This astounding paradox will assuredly complicate
the political and social processes of decision making.
Equally likely will be the burdens these phenomena add to
an already overburdened national economy.
In the last several years, it is the substitutability that
has been emphasized, as more and more procedures are
Health care services in the United States are provided by a performed in outpatient settings. Many services pre-
broad array of facilities, which are financed from a variety viously performed in the hospital now take place in
of payment sources. As of 1998, there were 6021 hospitals physician offices. In 1996. there were 734,493,000 visits
(7), 1,012,582 hospital beds, 33,765,940 admissions, and to the physician, with an average of 3.4 per person (1 l),
241,574,380 inpatient days. In 1998, the average length of and the most frequent principal reason for a visit was a
stay in community hospitals was 6 days, whereas it was 7.7 general medical examination, with a total of 54.7 million
days in 1975 (7). in 1996. Also in 1996, there were 67.2 million visits to
It is also notable that the numbers ofhospitals in urban and outpatient departments, and 40.3 million inpatient
rural settings are shrinking. In 1993, there were 3012 urban surgery procedures were performed (1 1). This analysis
hospitals and 2249 rural. whereas in 1998, there were 2816 points to the increasing importance of the ambulatory
urban and 2199 rural hospitals (13). The numbers of public care setting as a place for rendering care. The relevance
acute care hospitals decreased from 1390 in 1993 to 1260 in of outpatient care will continue to grow as more medical
1997 (8). Closure of hospitals and simultaneous reductions procedures are performed outside hospitals and greater
in hospital beds has occurred in inner city areas where care is emphasis is placed on preventive care. Outpatient visits
provided for large numbers of indigent patients. Such in community hospitals alone have advanced from
closures are related to the high costs of care. which are not 263,631,000 in 1986 to 301,329,000 in 1990 to
concomitantly reimbursed by state and federal sources 474,193,000 in 1998 (7).
400 Health Care Systems: Within the United States
The National Association of Home Care estimates that development of managed care. In managed care
more than 20,000 providers deliver home care services to settings, the covering company is responsible for
approximately 8 million individuals each year (12). providing services, whereas, at the same time, it is
According to the Health Care Financing Administration exposed to the financial risks of unanticipated services.
(HCFA), the average number of home health visits a year Health Maintenance Organizations (HMOs) contract
per Medicaid beneficiary was 80, compared to 21 visits in with hospitals and certain physician providers for
1989. Additionally, the number of home health agencies services within a negotiated schedule of fees. HMOs
participating in Medicare has increased from almost 5000 and other such managed care organizations specify
in 1988 to over 10,000 in 1997 (13). Care of patients in where and by whom care is to be given. The latter is a
home settings is likely to expand as data further suggest radical departure from the historically preeminent
reduced cost for such care without compromising quality. “freedom of choice” that patients and care providers
Technological and scientific developments related to enjoyed under the traditional indemnity and fee-for-
providing sophisticated treatments in the home will also service reimbursement programs. The traditional method
stimulate growth in this sector of health services. of paying for medical services is fee-for-service when
the provider charges a fee for each service provided,
and the insurer pays all or part of that fee.
Managed care is an umbrella term for HMOs and all
LT RAG
health plans that provide health care in return for preset
monthly payments and coordinate care in a defined
According to the President’s Advisory Commission on network of primary care physicians and hospitals. A
Consumer Protection and Quality in the Health Care network includes physicians, clinics, health centers,
Industry, there are five trends that summarize the medical group practices, hospitals, and other providers
characteristics of health insurance plans of the late 1990s: that a health plan selects and contracts with to care for its
members. An HMO is an organization that provides health
Increased complexity and concentration of health plans
care in return for preset monthly payments. Most HMOs
Increased diversity of health insurance products
provide care through a network of physicians, hospitals,
Increased focus on network-based delivery
and other medical professionals that their members must
Shifting financial structures and incentives between
use in order to be covered for that care.
purchasers, health plans, and providers
There are a number of different types of HMOs. A
The development of clinical infrastructure for utiliz-
staff model HMO is an HMO in which the physicians
ation management and quality improvement (14)
and other medical professionals are salaried employees,
In response to rapidly increasing health care costs, and the clinics or health centers in which they practice
private insurance companies and employers (who pay the are owned by the HMO. A group model HMO is made
premiums in whole or in part for their employees) have up of one or more physician group practices that are not
increased their part in implementing cost-containment owned by the HMO but operate as independent
strategies. A dramatic effort has been the application of partnerships or professional corporations. The HMO
business principles to purchasing and vendor selection and pays the groups at a negotiated rate, and each group is
payment for and selection of health care providers and responsible for paying its doctors and other staff as well
institutions of care. as covering the cost of hospital care or care from outside
Private employers, the federal government, and state specialists. An Independent Practice Association (IPA)
and local governments invest significant financial generally includes large numbers of individual private
rescturces in health care purchasing expenditures. In practice physicians who are paid either a fee or a fixed
1995, private employers contributed S183.8 billion to amount per patient to take care of the IPA’s members. A
private health insurance premiums, whereas the federal Preferred Provider Organization is a network of doctors
government spent $1 1.3 billion on private health insurance and hospitals that provides care at a lower cost than
premiums, and state and local government spent S47.1 through traditional insurance. PPO members have more
billion (14). In 1995, more than 83% of the insured health coverage when they use the PPO’ s network and
population was covered by private insurance, whereas pay higher out-of-pocket costs when they receive care
about 31% was enrolled in a public program, such as outside the PPO network (15).
Medicare or Medicaid. An integrated health system is a network that provides a
Probably the most significant change in the coordinated continuum of services and is clinically and
American health care system in recent years is the fiscally accountable for outcomes. There was a significant
Health Care Systems: Within the United States 401
national health expenditures as a percentage of GNP rose afford to pay for private insurance, the costs associated with
from 5.4% to over 14%. In the same period, dramatic health care were larger than most could afford. After
differences occurred in the source of revenues for health lengthy debate, the U.S. Congress passed legislation in
care expenditures. The pattern of spending these resources 1965 that established Medicare and Medicaid. Medicare
also changed significantly (13). covers over 95% of the elderly in the United States as well
In 1960,49% of health care revenues came from out-of- as many individuals who are disabled. Coverage for the
pocket payments from individuals. Out-of-pocket spend- disabled began in 1973 and is divided in two parts:
ing is defined as expenditures for coinsurance and 1) hospital insurance and 2) supplementary medical
deductibles required by insurers, as well as direct insurance. The total disbursement for Medicare in 1997
payments for services, which are covered by a third was $213.575 billion, and there were 36,460,143
party. In 1990, individual consumers spent S144.4 billion enrollees, of which 32,164,416 were elderly.
directly for out-of-pocket payments for personal health The total expenditure for the Medicaid program was
services (23). This accounted for 38% of all personal $160 billion in 1996. Of the total amount spent in 1996,
health spending. In 1998. consumers spent S183.7 billion Medicaid payments for nursing facilities and home health
in out-of-pocket payments, which accounts for 33% of the care totaled $40.5 billion for more than 3.6 million
$558.7 billion in personal health spending (23). recipients. The average cost per recipient in 1996 was
Consumers have spent and continue to spend less of $12,300, and almost 45% of the total cost of care for
their own personal money for health care services. This individuals using nursing homes and Medicaid was paid
decrease in personal spending has been shifted largely to for home health care (1 3).
third parties, such as private health insurance, government Since the enactment of Medicare and Medicaid, there
programs. philanthropic organizations, and other sources. have been various legislative and administrative changes.
It is evident that the shift away from personal, out-of- The Balanced Budget Act of 1997 enacted the most
pocket health spending has resulted in greater consumption significant changes to Medicare and Medicaid since its
of health care services. This transition reflects the general inception, including a capped allocation of monetary
maxim in health care economics that the consumption of resources to states and the addition of the Children’s
health care services is probably insatiable (24). Moreover, Health Insurance Program. The Children’s Health
unlike other sectors of the economy and the laws of Insurance Program set aside $24 billion over 5 years for
economics they obey, prices for health care services do not states to provide health care to over 10 million children
fall with increased consumption or purchasing. who are not eligible for Medicaid.
According to Iglehart. the decline in personal spending In 1960, public programs paid for one quarter (24.5%)
is “attributed in large part to the growth in health of all health care spending; by 1988, this share had
maintenance organizations (HMOs), which traditionally increased to 42.1%. Together Medicare and Medicaid
offer broad benefits with only modest out-of-pocket financed $351 billion in health care services in 1996,
payments. In the past few years, however, most HMO which is more than one-third of the nation’s total health
enrollees have had increased cost-sharing requirements, as care bill. Additionally, it represents three-quarters of all
employers and health plan managers have sought to public spending on health care. There has been a
constrain spending even further. Out-of-pocket payments significant increase in Medicare managed care enroll-
are still considerably less in an HMO than with indemnity ment-from 3.1 million at the end of 1995 to 6.3 million in
insurance (17):’ However, “The overall declines in per 1999, leaving approximately 33 million beneficiaries in a
capita out-of-pocket spending mask the financial difficul- traditional fee-for-service Medicare program.
ties of many poor people and families. A recent study An area of controversy is the limitation on coverage for
estimated that Medicare beneficiaries over 65 years of age prescription drugs. Spending on prescription drugs is the
with incomes below the federal poverty level (in 1997 the fastest-growing piece of personal health expenditures,
level was $7755 for individuals and $9780 for couples) amounting to $78.9 billion in 1997. Additionally, spending
who were also eligible for Medicaid assistance still spent for prescription drugs has increased at double-digit rates:
35% of their incomes on out-of-pocket health care costs. 10.6% in 1995, 13.2% in 1996, and 14.1% in 1997 (17).
Medicare beneficiaries with incomes below the federal The reason for this rapid growth, according to Iglehart,
poverty level who did not receive Medicaid assistance includes: .‘Broader insurance coverage of prescription
spent, on average, half their incomes on out-of-pocket drugs, growth in the number of drugs dispensed, more
health care costs (17).” approvals of expensive new drugs by the Food and Drug
Historically, a lack of public insurance programs created Administration, and direct advertising of pharmaceutical
obstacles to health care services. For those who could not products to consumers. The use of some new drugs reduces
Health Care Systems: Within the United States 403
hospital costs, but not enough to offset the increase in circles. These notions center on careful examination of
expenditures for drugs (17).” In the year 2000, 86% of the costs and their corresponding outputs. Eisenberg (26)
health care plans hill have an annual limit on brand and defines cost-effectiveness analysis as the measure of the
generic drugs, and there will be increased use of net cost of providing service (expenditures minus savings)
copayments for prescription drugs (25). as well as the results obtained (e.g., clinical results
The budget cuts imposed by Congress in 1997 to help measured singly or a series of results measured on some
balance the budget have restricted the fees that caregivers scale). Cost-benefit analysis determines whether the cost
receive for the elderly and disabled. When federal health is worth the benefits by measuring both in the same units
programs cut funding significantly, as occurred in the (26). Such analyses will be critical, as future policy
Balanced Budget Act of 1997, the resulting cutbacks at the decisions are made with regard to the collection,
institutional and health-system level trickled down to allocation, and utilization of finite resources in the health
providers’ abilities to provide an acceptable level of care system for the enhancement of health status of the
service designed to protect patient safety and foster American people.
appropriate medication use. Partial restoration of the Private-sector strategies and governmental plans to
Balanced Budget Act in 1999 addressed the transition to curb health care costs have not escaped criticism.
an outpatient prospective payment system for hospitals, Ginsberg, for example, argues that the notion of “for
payments to skilled nursing facilities and home health profit” hospital chains has severe limitations with respect
agencies, payments for indirect medical education, and a to garnering large proportions of market share and,
number of rural health care provisions. consequently, greater profits (27). He bases this view on
The dramatic shift of third parties (government, private the limited amount of private funding available for
health insurance) toward paying for a greater and greater hospital care. On the other hand, he sees this sector as
proportion of personal health care services has led to a being able to grow in the area of nursing homes and other
paradigm shift in attitudes and actions toward health care businesses related to the care of the elderly.
financing and cost control. Several approaches have been
adopted in the governmental sector to slow the increases in
costs and expenditures. The most dramatic of these has
been the introduction in 1983 of the prospective payment
system (PPS) to curb the growth in hospital costs and
expenditures. By imposing prospective limits on Medicare
payments to hospitals through a system of reimbursing There are three classes of individuals who have open
average costs of specific diagnoses, hospital utilization has access to and can derive some form of services from
decreased dramatically. The average length of stay and America’s health care system:
admission rates in community hospitals of elderly patients 0 Those who receive support from governmental sources
(those covered by Medicare) dropped sharply after the because of specific entitlements (indigents, elderly, and
introduction of PPS (13). veterans)
Because of cost-containment strategies of both the 0 Those who are provided with basic health insurance
private and governmental sectors, hospital utilization has coverage from their employers
declined. This has resulted in a decline in the number of 0 Those who choose to cover their expenses from out-of-
patient beds, the average length of stay, and patient bed pocket payments
census (7). The present predominant view is that
hospitalization of any patient, regardless of revenue source, There are, however, those who have no specific
is to be avoided wherever possible. Only those patients for financial support or capacity to pay for health care services
whom hospitalization can be fully justified are admitted. and who are not eligible for any type of entitlements.
As much as the financing of America’s health care These individuals must rely on some form of charity care
system is a major issue on the policy agenda of the nation, or services. In addition, there are those who, for reasons of
so too is the continuous question about the relationship geographic remoteness or total inability to gain access,
between the costs and the outcomes of care. As costs have no access to health care services. This group
increase, the numbers of policy analysts, organizations, represents a complex, resource-based demand model,
and governmental agencies calling for a better definition of which also has an equally complex pattern of health care
the cost-outcome relationship has sharply risen. system and services-utilization requirements.
Cost-effectiveness and cost-benefit analyses are fre- With increasing health care costs and consequent
quently mentioned in academic and policy-analysis increases in insurance premium costs, gaining access to
404 Wealth Care Systems: Within the United States
health care services without incurring personal costs has 3. Stroke (169,942 deaths)
become more difficult. Not all services are covered for 4. Pulmonary diseases (108,027 deaths)
individuals in the federal Medicare and Medicaid 5. Accidents (94,948 deaths)
programs. Moreover. there are strict limitations on the 6. Pneumonia and flu (63,727 deaths)
extent of services offered in these programs. A similar set 7. Diabetes (61,787 deaths)
of restrictions may be found in private-sector health care 8. AIDS (31,130 deaths)
coverage strategies. Because few insurance programs and 9. Suicide (30,903 deaths)
none of the federal programs provide coverage for 10. Liver disease (25,047 deaths)
unlimited long-term care, all but the very rich are at risk
of financial ruin. Infant mortality, another measure of the health status of
The health care lexicon includes two new terms to a nation, stated as the number of deaths per live births, was
reflect these problems: underinsured and uninsured. The 7.2 per 1000 live births in 1997 compared to 9.9 per 1000
underinsured may include the “working poor,” those live births for 1988. Overall, these figures are comparable
individuals who have jobs and may be covered by a very to those of the major, industrialized nations of the world.
limited, if any, health insurance program by their Major morbidity in the United States is currently
employers. They are likely low wage earners and those centered on diseases of life style. These morbidities
receiving incomes at. or slightly above, the poverty level. contrast sharply with disease patterns prevalent during the
Typically, they do not qualify for Medicaid entitlements, early part of the 20th century. Outside of AIDS and other
do not have employer-paid health insurance benefits, and sexually transmitted diseases, infectious diseases represent
cannot afford (or choose not to purchase) third-party a small proportion of prevalent morbidity. Rather, life-
coverage for payment of health care services. style diseases, associated with smoking, poor nutrition, a
There are no specific policy plans available to finance sedentary life style, alcohol and other chemical consump-
uninsured and underinsured care. Whether planned as tion. homicides, suicides, and accidents, represent the
charity care or unplanned as financial loss. the “price tag” majority of morbidity in the United States. Significant
for uncompensated care in the United States was $18.5 preventive strategies can markedly reduce the incidence,
billion in 1997, which is 6% of the total of hospital prevalence, and mortality associated with these health care
expenses (28). This percentage has remained constant problems.
since 1984. when the percentage of total expenses for Not surprising, in areas with high concentrations of
uncompensated care was also 6% (8). indigent people, there are similarly high concentrations of
Reduced payments and high levels of uncompensated uninsured individuals requiring intense health care
care have led to the closing of hospital facilities in both services. These areas exist in both rural and urban settings.
urban and rural blighted areas, making access to care even Emergency rooms have become a major resource for
more difficult for some. Whiteis and Salmon (29) refer to primary health care services in areas where physician
this phenomenon as “disinvestment in the public goods.” office services or other service providers (clinics) are not
Because privately owned and not-for-profit hospitals and available because of location, cost, or quality. Emergency
private clinics, pharmacies, and physician’s offices must rooms have also become providers of high-intensity care
rely on their own financial soundness. any threat to that for victims of gun shot wounds, drug overdoses,
foundation may lead to closure. communicable diseases, and other trauma associated with
The amount of uncompensated care is magnified in poor social conditions. Much of the care in emergency
areas where serious social problems exist because health rooms is uncompensated because the quality and amount
status is directly related to social status. Health status exceed the allowable reimbursement. Some trauma centers
should be examined in broad terms by reviewing in economically blighted areas have been closed (30).
morbidity and mortality data available for the whole Hospitals in inner cities and blighted rural areas also
population. The life expectancy of people who live in the care for a higher proportion of “at-risk“ patients than
United States has grown by almost 10 years, from 68.5 hospitals in the for-profit sector generally located in more
years in 1936 to 76.1 years in 1996. Women were expected affluent areas (29). In fact, affluent hospitals sometimes
to live to 79.1 years in 1996, whereas the average for men “dump” their uncovered patients on charity care and other
was 73.1 years (11). The leading causes of death in 1996 public hospitals in order to reduce their financial risks.
among people living in the United States were (1 1): This, however, increases the financial risks of public or
charity hospitals. Again, the reimbursement levels under
1. Heart disease (733,361 deaths) present schemes for large numbers of “at-risk’’ patients
2. Cancer (539,533 deaths) simply do not cover costs; thus, the United States has
Health Care Systems: Within the United Stales 405
witnessed hospital closings, particularly in those areas recently at a national round table that there is an
where such loss is most noticeable (30). ”urgent
c need to i m ~ r o v ehealth care aualitv.” The
1 ,
American health policy continues to grapple with these stringency of managed care and a low inflation rate
issues related to the underinsured and the uninsured (3 1). have slowed the growth of medical spending
A multiple-tiered health care system based on social class appreciably, but a new government study projects
and ability to pay is unacceptable in a nation that boasts that health care expenditures will soon begin
incomparable riches and political agendas of democracy escalating again and will double over the next
and rights. Ginsberg (27) notes: decade. In short, the American system is a work in
progress. driven by a disparate array of interests with
Despite all our efforts of recent years, then, health
two goals that are often in conflict: providing health
care costs continue to increase.. . . There is
care to the sick, and generating income for the persons
undoubtedly waste in the health care system, but
and organizations that assume the financial risk.
no solid proposals have been advanced to recapture
the SlOO billion, plus or minus, that some believe The President’s Commission (32) outlines areas in
can be saved. I believe that we will not reshape our which the American health care system could be improved
national health policy agenda unless and until we in light of the reality that many individuals receive
achieve a broad consensus on the key issues. Do the substandard care and 44.3 million individuals are without
American people, for example, desire to ensure health insurance coverage. This commission outlines
access to health care for the entire population? In several types of quality problems including avoidable
that case they must agree to pick up a sizable errors, underutilization of services, overuse of services,
additional tab, which they have thus far avoided. and variation in services. Based on the reality of these
quality problems, the Commission recommended that the
The issue of quality health care has become an
initial set of national aims should include (32):
increasing issue of concern in the face of cost constraints
and limited access to health care. The President’s Advisory
Reducing the underlying causes of illness, injury and
Commission on Consumer Protection and QualiQ in the
disability
Health Care Iiidustq (32) states that “the purpose of the
Expanding research on new treatments and evidence on
health care system must be to continuously reduce the
effectiveness
impact and burden of illness, injury and disability and to
o Ensuring the appropriate use of health care services
improve the health and functioning of the people of the
Reducing health care errors
U.S.” According to the Commission, there are basic
Addressing oversupply and undersupply of health care
characteristics of health care that, as a nation, we should
resources
strive to achieve. The Commission has created “Guiding
Increasing a patient’s participation in his or her care
Principles for the Consumer Bill of Rights and
Responsibilities” for the health care of people in the The President’s Commission engages a broad consumer
United States. These include the following: advocacy movement in public and private sectors calling
for a major reform of the U.S. health care system to improve
All consumers are created equal.
access to care for more individuals living in America.
0 Quality comes first.
Consistent with previous patterns, however. these calls
0 Preserve what works.
have only led to incremental adjustments in policy and
0 Costs matter.
slight quality changes in direction. The major problems, for
the most part, remain unaffected. Although broad based
health care reform efforts have been unsuccessful, market
T LT forces and more targeted legislation and regulatory efforts
have changed the face of health in the 1990s.
The 1993-94 Clinton health care reform plan, in its
Suggestions for broad reform, which address the financial,
ideology, provided an ambitious plan to eliminate the
access. and quality of care issues for America’s health care
enormous problem of lack of access to health care. It
system, have emerged during the past decade. Iglehart
proposed to guarantee comprehensive health benefits for
emphasizes the irony of the American health care system.
all American citizens and legal residents, regardless of
He writes (17):
health or employment status. The proposal was unsuccess-
By many technical standards. U.S. medical care is the ful due to a number of factors, including its vast scope, the
best in the world, but leaders in the field declared complicated nature of the plan, and an underestimation of
406 Health Care Systems: Within the United States
the politics involved with radically reforming health care. otherwise limiting access to high cost services, for
The failure of the Clinton administration health care example, has resulted from political policy rather than
reform agenda and the subsequent events to revise the from deliberated public policy and rational decision
American health care system are important lessons of making. This is most notably evidenced in the Medicaid
health-care-system related politics. component of the U.S. health care system.
Unfortunately, since the failure of the Clinton As cost pressures continue to mount, there will likely be
Administration plan in 1994, the number of uninsured a return to having patients pay more of the health care
individuals in America has grown. According to the expenditure dollar from their own resources. This will take
Census Bureau, 44.3 million people are uninsured, the form of higher deductibles and co-insurance payments.
comprising about 16.3% of the population. Of those Perhaps returning the burden of health care financing to
uninsured, 15.4% are under 18 years of age, and the largest the individual will raise the collective consciousness of
percentage is among individuals between 18 and 24 years American society that “there is no such thing as a free
of age. People of Hispanic origin make up 35.3% of those lunch” insofar as using and paying for health care services
uninsured and 43% of the total uninsured population are is concerned. Certainly, this phenomenon has occurred in
not citizens of the United States (6). social welfare “reform” in which the programs that have
The number of uninsured persons is expected to had mixed success have been restructured to “roll”
continue to grow. Proposals for health care reform to participants off of welfare to work.
combat this problem include President Clinton’s proposal On the other hand, there are perhaps no solutions
for Medicare buy-in proposals for “middle aged” adults forthcoming on some of the problems represented in the
and House Majority Leader Dick Armey’s (R-TX) arena of health care financing. As Hardin suggests, there is
proposal for a refundable tax credit to pay for insurance indeed a class of human problems that have no technical
for the uninsured. The 2000 presidential campaign opened solution (33). In using Hardin’s analogies, Hiatt (34)
the debate for legislation that will improve health care suggests that “nobody would quarrel with the proposition
coverage for the uninsured. This public debate on how to that there is a limit to the resources any society can devote
enhance access to care will stimulate creative ways to to medical care, and few would question the suggestion
improve the U.S. health care system. However, rhetoric is that we are approaching such a limit. The dilemma
not enough; it needs to be translated into programs that confronting us is how we can place additional stress on the
attack the problem. medical commons without bringing ourselves closer to
The essence of the health care financing dilemma is ruin.”
related to how much a nation wishes to spend, on whom
these funds are to be expended, and by what methods a
relationship among cost. quality, and outcomes might be
determined. In a time when advancing science and
technology is flourishing in the health care field, “high
tech” medicine will continue to evolve with an ever- These are the principal contemporary features of the U.S.
increasing price tag. Furthermore, the costs of unantici- health care system. A massive societal structure is at once
pated and complex disease problems (e.g., HIV/AIDS) add saviour, behemoth, juggernaut, and question mark. It
to the unpredictability of health care system costs. This is certainly will be in a constant state of flux and gradual
all to say that most policy makers understand what needs to change. It therefore bears constant vigilance and careful
be done. They are in a quandary, however, in finding the guidance by those who derive their livelihoods from it and
appropriate and acceptable solution. Hence, it is likely that those who are the beneficiaries of its caring. Most
costs and expenditures will continue to rise (and, thereby, importantly, it will require significant pressure from those
increase the percentage of GNP that will be spent for health who are disenfranchised from it.
care) and that solutions may become even more elusive.
Although some might argue that the available resources
for expenditures on health care are ultimately limited, few
are able to say exactly where that limit is or should be. In
the United States. there has been an expansion of
technologies and procedures based on scientific advance- 1. Donabedian, A. Aspects of iMedical Care Adminis-
tration: Specifiing Requirements for Health Care: Harvard
ments without a concomitant development of a moral and University Press: Cambridge. 1973.
ethical policy for determining who might be best served by 2. Dougherty. C.J. American Health Care: Realities, Rights,
such advancements. Rationing of health care services or and Reforms; Oxford University Press: New York, 1998.
Health Care Systemr: ~ V i ~ hthe
~ nUnited Slate\ 409
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Tipton, S.M. Habits oftlir Heart; Harpcr & Row: New Engl. J. Medicine 1988, 319 (I2), 757-76 I .
York. 1985. 28. www.aha.org (accessed Nov 1999).
4. Relman, A. Reforming the Hcalth Care System. New Engl. 29. Whiteis, D.G.: Salmon. J.W. The Cor[iorziie Trzin.$(,r ( f l
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2879-2886.
PROFESSIONAL DEVELOPMENT
ity (OEQ) was funded. The OEO opened several large higher costs for hospitalization. The HIE also suggested
community health centers throughout the United States. that cost-sharing and enrollment in HMOs was most likely
The federal governments new responsibility for funding to have a deleterious effect on the health of the poorest
and providing healthcare focused attention on the need and sickest groups of patients who were enrolled. As the
to evaluate strengths. weaknesses, and consequences of results of the HIE were published, many private medical
these programs. In 1967, Congress enacted a bill that insurance plans were changed to increase the amount of
made it possible for the Secretary of the Department of out-of-pocket expenses incurred by patients.
Health Education and Welfare (DHEW) to establish the Despite the changes in the design of healthcare plans in
National Center for Health Services Research and the 1980s, the costs of medicaid and medicare and the
Development (NCHSR). This new center consolidated a costs to employers for private health insurance plans in-
variety of research activities in the DHEW, and estab- creased steadily. By the 1990s, there was growing interest
lished other centers for health services research through in healthcare reform. Despite considerable effort by the
contractual arrangements with academic institutions and Clinton Administration to propose these types of reforms,
other organizations. At about this same time, other federal opposition in Congress prevented anything except further
organizations began funding HSR projects. These included tweaking of federally funded plans. In both the public and
the Health Care Financing Administration (HCFA) and the private sectors. payers began to emphasize the value ob-
Department of Veterans Affairs. Ultimately, NCHSR was tained for the dollars spent for healthcare. This emphasis
absorbed into the Agency for Health Care Policy and on cost versus value of services is the focus of many
Research (AHCPR). which has been renamed the Agency current HSR efforts.
for Healthcare Research and Quality (AHRQ).
By the 1970s, it was clear that costs for both Medicaid
and Medicare were increasing more rapidly that anyone
expected. Of particular concern was the scope of cover-
age provided by the Medicaid program and the cost-
based reimbursement policies for Medicare. Despite only The pharmacy profession can offer considerable expertise
limited evidence that health maintenance organizations to the field of HSR. Furthermore, recent changes in the
(HMOs) decreased costs of health care, support was healthcare system mandate that, as a profession, phar-
increasing for use of HMOs in both the public and pri- macy must broaden its focus from individual clinical
vate sectors. During the mid-1970s, Congress passed a interventions to include population and system-level in-
variety of legislation that made changes to both Medicaid terventions and evaluations. The techniques used in HSR
and Medicare, but was unable to enact any proposal for a provide vital tools for pharmacy to influence health
national healthcare program. The concern over costs for policy and, ultimately. delivery of care. Furthermore,
these national programs and the increasing healthcare because of their unique skills and perspectives, pharma-
costs in the private sector were the basis of several HSR cists can offer a distinctive knowledge base that can
projects to examine many aspects of health insurance and inform HSR.
the costs incurred in these plans. However, there were When thinking about pharmacy's involvement in HSR,
problems in most of the studies, so no definitive answer it is helpful to use seven areas of HSR outlined in the
was available. Because of the need for better information IOM's 1995 report."' These are 1) organization and fi-
in this area, the OEQ agreed to sponsor an extensive nancing of health services; 2 ) access to health care;
experiment in health insurance. 3) quality of care; 4) clinical evaluation and outcomes
This controlled trial in healthcare financing, known as research; 5) informatics and clinical decision making;
the Health Insurance Experiment (HIE), was one of the 6) practitioner, patient, and consumer behavior; and
largest and longest running HSR projects ever conducted. 7) health professions work force. By thinking about the
Enrollment of a pilot sample began in 1973, and the last type of research questions considered in each of these
families completed participation in the project in 1982. categories, it is possible to better understand both the
The HIE randomly assigned families to four health contribution pharmacists can make to HSR and what
insurance plans that varied the amount of copayment HSR has to offer the profession of pharmacy.
incurred by the family from 0-95% or to a staff-model
HMO. One of the most notable findings of the HIE was
that free care did not decrease total health care costs. as
some proposed. Rather, plans in which patients received HSR has contributed to many proposals for healthcare
essentially free care resulted in higher total costs and reform since the 1960s. These include managed care,
Health Services Research 411
of pharmacists in ambulatory care or community practice, ically based, understandable information that will guide
Tully and Seston found few studies that clearly demon- decisions about many aspects of healthcare.
strated improvement of economic outcomes.[171Only a Clinical pharmacy has a long history of influencing
minority of the literature reviewed included assessment of provider behavior through medication formularies, clin-
quality of life, patient satisfaction, or functional outcomes ical recommendations, drug utilization review, and pro-
and, when assessed, these parameters were rarely sig- vision of drug information. Pharmacists influence con-
nificantly different after the pharmacists intervention. The sumer behavior through patient education and clinical
authors believed these results were due, in part, to small management strategies designed to optimize clinical out-
sample sizes and problems with research design. It is im- comes. This experience provides a knowledge base that
perative that studies evaluating the impact of pharmacists can be used to enhance HSR studies that seek to under-
activity pay particular attention to study design, sample stand and influence patient, provider, and consumer be-
size, and outcomes measurement. haviors. Pharmacists can also use the information gained
by researchers in this area to improve the effectiveness
linical Decision ~ a k i n ~ of pharmacy practice.
Studies of informatics and clinical decision making con- Health Professions Work Force
centrate on the benefits of using computerized decision
support systems in clinical practice and in research to HSR also asks questions about the education and supply
measure outcomes, efficiency, and effectiveness of care. of health care workers. For example, a project evaluating
Decision analysis in clinical research employs probability care for rural patients with cancer identified both a
analysis to express uncertainty and utility theory to ex- shortage of pharmacists to deliver pharmaceutical care
press patient preferences for health outcomes. and raised questions about how well pharmacy curricula
Computers have been used as a routine part of phar- prepare pharmacists to meet the needs of rural patients.[221
macy practice for many years. Pharmacists use this tech- Other studies evaluate the number of professionals needed
nology in many ways. For example, computers can be to optimize costs of care or evaluate the supply and de-
used to interact with physician colleagues, track patient mand of health care w ~ r k e r s . [ Unfortunately,
~~-~~~ these
behaviors, or as tools to evaluate cost and effectiveness of efforts have not proven particularly successful.[1,26-2s1
medication Pharmacists have also inves- Given the increasing concern over shortages of pharma-
tigated concordance between traditional and computer- cists, it is important for the profession to work with health
ized patient records, and are now incorporating computers service researchers to develop models to better address
into patient assessment and educational activities.[20’211 this issue and to study the consequences of personnel
This familiarity with the technology positions pharmacists shortage^.[^^-^^]
to provide leadership in using informatics to examine and
improve health services.
contracts provide funds to conduct a specific research available in Health Services Research Methods written by
proposal. Both may be funded by public or private in- Leiyu Shi.[331
stitutions. The major difference between contracts and
grants has to do with control of the project and the project
funds. In a grant, the principal investigator generally
controls all aspects of the project including study design,
project implementation, disbursement of funds, and
modifications to the original protocol. In a contract, the The specific educational disciplines of health service
funding entity has much more input into all aspects of researchers are reflected in the wide variety of journals
the project. that now publish health research manuscripts. Journals
Among federal programs, the Agency for Healthcare that are devoted entirely to HSR include Medical Care,
Research and Quality (AHRQ), formerly the Agency for published by the American Public Health Association;
Healthcare Policy and Research (AHCPR), is the leader Health Services Research, the official journal of the
in research to improve quality of care. However, others Academy for Health Services Research and Health Policy
such as the Government Accounting Office, Health (formerly known as the Association for Health Services
Resources Service Administration, HCFA, Office of the Research); and the Journal of Health Services Research
Assistant Secretary for Planning and Evaluation, and and Policy, published by the Royal Society of Medicine,
Centers for Disease Control and Prevention also perform Ltd. Many specialized journals are beginning to publish
HSR. Individual institutes within the NIH also support work based on health services research. For example,
services research. For example, there is a Services Re- Journal of Health Ecoiionzics, American Journal of Public
search and Clinical Epidemiology Branch within the Health, American Journal of Medical Qualiiy, and Ante-
National Institute of Mental Health (NIMH) that funds rican Journal of Epidemiology will accept manuscripts
services research. based on HSR projects. Prominent clinical journals such
The VHA has had a department of Health Services as the New England Journal of Medicine and Journal of
Research and Development (HSR&D) since 1976.[341 the American Medical Association are also increasing the
Since the mid- 198Os, this department has emphasized use number of publications of HSR projects. Pharmacy
of health services research as a tool to improve the health journals also contain some HSR articles, including the
of veterans. Funding from HSR&D is primarily for American Journal of Health-System Pharmacy, Annuls of
investigators in the Veterans Administration system, and Pharnzacotherapy, and Pharmacotherapy.
consists of both investigator initiated research proposals
and solicited proposals for specific research.
A number of large centers in the private sector are
now offering grant funding for HSR. These institutions
may also conduct HSR. These include the Center for
Committee on Health Services Research Training and
Studying Health Systems Change, funded by the Robert
Work Force Issues. Health Senices Research: Work Force
Wood Johnson Foundation, and affiliated with Mathe- and Educational Issues; Field. M.J., Tranquada, R.E.,
matica Policy Research Inc., RAND Health, the Health Feasley, J.C., Eds.; National Academy Press: Washington,
and Policy Center of the Urban Institute, and Emergency D.C.. 1995.
Care Research Institute. Key HSR academic centers in- Ginzberg, E. Health Services Research: Key to Health
clude the Cecil G. Sheps Center For Health Services Re- Policy; Harvard University Press: Cambridge, Massachu-
search at the University of North Carolina at Chapel Hill, setts, 1991.
the Center for Health Services Research and Policy in Mamdani, M.M.; Racine, E.; McCreadie, S.; Zimmerman,
the George Washington University Medical Center School C.: O'Sullivan, T.L.; Jensen, G.; Ragatzki, P.; Stevenson,
of Public Health and Health Services. and Michigan J.G. Clinical and economic effectiveness of an inpatient
anticoagulation service. Pharmacotherapy 1999: 19 (9),
Health Services Research at the University of Michigan.
1064-1074.
There are also resources for identifying funding
McMullin, S.T.; Hennenfent, J.A.; Ritchie, D.J.; Huey,
sources. The Federal Information Exchange provides an W.Y.; Lonergan, T.P.; Schaiff, R.A.; Tonn, M.E.; Bailey,
electronic service that uses e-mail to send grant T.C. A prospective, randomized trial to access the cost
information to researchers. The Directory of Research impact of pharmacist-initiated interventions. Arch. Intern.
Grants and The Foundation Directory are also excellent Med. 1999, 159 (19), 2306-2309.
sources for information regarding federal, state, and Galt, K.A. Cost avoidance, acceptance, and outcomes
private funding institutions. A more complete listing is associated with a pharmacotherapy consult clinic in a Vet-
414 Health Services Research
erans Affairs Medical Center. Pharmacotherapy 1998, 18 Eisen, S.A.; Lofgren, R.; Nichol, K.; Wooliscroft, J.;
(5). 1103-1111. Henderson, W.G. Improving residents' compliance with
Harrison, D.L.; Bootman. J.L.; Cox, E.R. Cost-effective- standards of ambulatory care: Results from the VA Co-
ness of consultant pharmacists in managing drug-related operative Study on computerized reminders. J. Am. Med.
morbidity and mortality at nursing facilities. Am. J. Health- ASSOC.2000; 284 (11); 1411-1416.
Syst. Pharm. 1998; 55 (15), 1588-1594. 19. Monane, M.; Matthias, D.M.; Nagle, B.A.; Kelly. M.A.
McCombs, J.S.; Liu, 6 . ; Feng, W.; Cody, M.; Parker, J.P.; Improving prescribing patterns for the elderly through an
Nichol, M.B.; Hay, J.W.; Johnson, K.A.; Groshen, S.L.; online drug utilization review intervention: A system link-
Nye, M.T. The Kaiser Permanenten'SC patient consul- ing the physician, pharmacist, and computer. J. Am. Med.
tation study: Change in use and cost of health care services. ASSOC.1998. 280 (14). 1249-1252.
Am. J. Health-Syst. Pharm. 1998, 55, 2485-2499. 20. Hudson, T.J.; Owen, R.R.: Lancaster, A.E.; Mason, L. The
8. Straub, L.A.; Straub, S.A. Consumer and provider eval- feasibility of using automated data to assess guideline-
uation of rural pharmacy services. J. Rural Health 1999; 15 concordant care for schizophrenia. J. Med. Syst. 1999, 23
(4),403-412. (4), 299-307.
9. Donabedian, A. Explorations in Quality Assessment and 21. Miller, L.G. Use of patient education and monitoring
Monitoring; Health Administration Press: Ann Arbor, 1980. software in community pharmacies. J. Am. Pharm. Assoc.
10. Every, N.R.; Fihn, S.D.; Sales, A.E.; Keane, A,; Ritchie, 1997, NS37 ( 5 ) , 517-521.
J.R. Quality enhancement research initiative in ischemic 22. Gangeness, D.E. Pharmaceutical care for rural patients:
heart disease: A quality initiative from the Department of Ominous trends. J. Am. Pharm. Assoc. 1997, NS37 (l),
Veterans Affairs QUERI IHD Executive Committee. Med. 62-65: 84.
Care 2000, 38 (6 Suppl. 1): 149-159. 23. Bond, C.A.; Raehl, C.L.; Franke, T. Clinical pharmacy
11. Rust, G.S.; Murray, V.; Octaviani, H.; Shcmidt, E.D.; services, pharmacy staffing, and the total cost of care in
Howard. J.P.; Anderson-Grant, V.; Willard-Jelks, K. Asth- United States hospitals. Pharmacotherapy 2000, 20 (6);
ma care in community health centers: a study by the 609 - 62 1.
southeast regional clinicians' network. J. Natl. Med. Assoc. 24. Institute of Medicine. Summary. The Nation 's Physician
1999, 91 (7). 398-403. Workforce; Lohr, K.N., Vanselow, N.A., Detmer, D.E.,
12. Ellwood, P.M. Shattuck lecture-outcomes management: Eds; National Academy Press: 1996; 1 - 14.
A technology of patient experience. N. Engl. J. Med. 1988. 25. Knapp. K.K.; Paavola, F.G.; Maine, L.L.: Sorofman, B.;
318 (23), 1549-1556. Politzer. R.M. Availability of primary care providers and
13. Blumenschein, K.; Johannesson, M. Use of contingent pharmacists in the United States. J. Am. Pharm. Assoc.
valuation to place a monetary value on pharmacy services: 1999; 39 (2), 127-135.
An overview and review of the literature. Clin. Ther. 1999. 26. Feil, E.C.; Welch. H.G.; Fisher, E.S. Why estimates of
21 (8); 1402-1417. physician supply and requirements disagree. J. Am. Med.
14. Dager, W.E.; Branch, J.M.; King, J.H.; White, R.H.; Quan, ASSOC.1993, 269 (20): 2659-2663.
R.S.; Musallam, N.A.; Albertson, T.E. Optimization of 27. Kindig, D.A. Counting generalist physicians. J. Am. Med.
inpatient warfarin therapy: Impact of daily consultation by ASSOC.1994. 271 (9); 1505-1507.
a pharmacist-managed anticoagulation service. Ann. Phar- 28. Capilouto, E.; Capilouto, M.L.; Ohsfeldt, R. A review of
macother. 2000, 34 (5). 567-572. methods used to project future supply of dental personnel
15. Self. T.H.; Brooks, J.B.; Lieberman, P.; Ryan, M.R. The and the future demand and need for dental services. J.
value of demonstration and role of the pharmacist in Dent. Educ. 1995, 59 (l), 237-257.
teaching the correct use of pressurized bronchodilators. 29. Mott, D.A.; Kreling, D.H. An internal rate of return
Can. Med. Assoc. J. 1983, 128. 129-131 (Jan. 15). approach to investigate pharmacist supply in the United
16. Hanlon, J.T.; Weinberger, M.; Samsa, G.P.; Schmader, States. Health Econ. 1994, 3 (6), 373-384.
K.E.; Uttech. K.M.; Lewis, I.K.; Cowper, P.A.; Landsman, 30. Knapp, K.K. Building a pharmacy work force mosaic:
P.B.; Cohen. H.J.; Feussner. J.R. A randomized, controlled New studies help to fill in the gaps. J. Am. Pharm. Assoc.
trial of a clinical pharmacist intervention to improve in- 2000. 40 (1). 13-14.
appropriate prescribing in elderly outpatients with poly- 31. Magill-Lewis, J. Reverse trend. Drug Topics 2000, 144, 44
pharmacy. Am. J. Med. 1996, 100; 428-437 (April). (Feb. 21).
17. Tully, M.P.; Seston, E.M. Impact of pharmacist providing 32. Beavers, N. Feeling the weight. Drug Topics 2000; 144
a prescription review and monitoring service in ambula- (Jan. 3), 38-40, 42. 47-48.
tory care or community practice. Ann. Pharmacother. 2000, 33. Shi, L. Health Services Research Methods; Delmar Pub-
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18. Demakis. J.G.; Beauchamp, C.; Cull, W.L.; Denwood, R.; 34. www.va.gov/resdev.
PHARMACY PRACTICE ISSUES
Kathleen M. Bungay
The Health Institute, Boston, Massachusetts, U.S.A.
rately measure complex behaviors and feelings. Experi- norm. For example, a 10-fold difference in rates of
mental research designs are rarely possible[51 because the tonsillectomy was observed just within the six New
focus of social science is on the way that numerous social England states.
structures and institutions influence individuals. These
models have their foundation in sociology, psychology,
and economics, and use concepts and methods often fo-
reign to clinicians and clinical re~earchers.'~]
The Rand
accepted by the Medical Outcomes Study (MOS) in- such attributes as intelligence, pain, mental well-being, or
vestigators.[261 functioning is usually a doctorate-level research psycho-
logist and can be known as a psychometrician.
sources. A comprehensive set of standards, widely used in Presently, validity is represented as a process whereby
the assessment of psychology and education, is the we determine the degree of confidence we can place on
manual called Standards for Educational and Psycho- inferences we make about people based on their scores
logical Tests, published by the American Psychological from that scale. Some different types of validity, a
Association ( 1974).[341In addition to these standards, discussion of which is beyond the scope of this chapter,
there are a number of compendia of measuring scales.[21 are called content validity, criterion validity, and con-
struct validity.
Content Validity
bFor more in-depth information on this topic, the reader is directed to Because quality of life represents the broadest range of
Refs. [2] and [29]. human experiences, use of this general term in the health
Health Status Assessment 419
field has led to considerable confusion, particularly conditions to an overall sense of well-being. General
because of the overlap with the more specific concept, measures evaluate aspects of health relevant to all ages,
health status. To make the meaning more specific and to races, genders, and socioeconomic backgrounds. The
retain the important aspects of life quality, HRQQL is measures also permit the examination of the benefits of
both a useful and important term. treatments in comparable units.
Using general health measures, Stewart et al.'451
compared the functional status and well-being of patients
with chronic conditions. They reported the usefulness of
generic (non-disease-specific) health measures for mon-
odels itoring progress and for use as outcomes in studies of
patients with chronic conditions. The authors maintained
Researchers have proposed a number of conceptual that there are several advantages of general measures of
models of the relationships among the components of functional status and well-being over disease-specific
HRQOL."5,16s39-441 Wilson and Cleary, who proposed a measures. Among these, they noted, first, they are useful
model linking clinical variables with HRQQL, argued that for monitoring patients with more than one condition, and
.'the ultimate promise of the ability to measure HRQQL second, for comparing patients with different conditions
will not be fulfilled until it has clear applications to clinical by providing a common yardstick. Last, the same meas-
care."[41 Their pursuit of this goal sets their model apart ures can be appropriately applied to both general (well)
from previously published models. Their model includes and patient (sick) populations, with the advantage of
five levels or subdivisions: biological and physiological comparing patient groups (sicker) with the healthy stand-
variables, symptom status, functional status, general health ard of a general population (Fig. 2 ) .
perceptions, and overall quality of life (Fig. 1).
A comparison of different conceptual models is beyond easured Domains of Health:
the scope of this chapter. Because the conceptual model General Health Status ~ s s e s § ~ e n t
informs the measurement, each may be slightly different
although some commonly agreed upon and frequently
measured general health concepts can be identified and Physical function
discussed. These concepts are: 1) physical functioning, 2 )
mental functioning. 3) social and role functioning, and 4) Physical health is commonly measured in terms of li-
general health perceptions. By denoting a measure as a mitations in the performance of or ability to perform self-
general health status measure, it is understood that the care activities (e.g., eating, bathing, dressing), mobility,
questions are not disease or disorder specific, and that they moderate or more strenuous physical activities, and bodily
cover a range of health states from life-threatening pain. Responses to questionnaire items in this category
Fig. 1 Relationships among measures of patient outcome in a HRQOL conceptual model. (From Ref. [4].)
420 Health Status Assessment
network of friends. He may not feel isolated or unloved, health such as pain, difficulty, level of effort required, or
and his relationships with his wife and children continue to worry and concern about health; and 2) questions in this
be positive. However, to the man for whom music is fuel domain inquire about positive feelings or a positive frame
for mental, financial, and spiritual well-being, the loss of of reference, for example, a favorable health outlook in
his professional role may be devastating. That devastation contrast to questions from other domains that focus on
is a role function loss. If he then lost the friendships he measures of limitation, pain, or dysfunction, and are
developed and maintained through his music, then that usually stated in a negative way. Responses in the general
would be loss of social function. health perception domain are subjective and evaluative.
For many people, physical health problems limit role They are typically ratings rather than reports, for example,
performance. Occasionally, mental disruption can im- a rating of health from “excellent” to “poor.”
pinge on role functioning, but measures of this health
dimension seldom detect mental or emotional problems Disease-Specific Health tatus ~ ~ s t r u ~ e ~ t s
because patients seldom consider role limitations unless
they are asked about them explicitly. Some questionnaires Often, it is necessary to focus on the particular impact
ask specifically about limitations of role function due that a certain disease has on patients. In such cases, gen-
specifically to personal or emotional problems, in addition eral health status tools are inadequate for providing the
to those due to physical health problems. information needed. To overcome this limitation, con-
Measurement of the impact of health on role activities dition- or disease-specific measures are often used in-
has grown, owing in part to legislation and information stead of or along with a general health status instrument.
provided by the passage of the Americans with Disabil- The more narrowly focused disease-specific measure
ities Approximately 55 million working-age requests detailed information on the patient’s perspective
individuals (1 8 -65 years of age) have chronic illnesses on the impact of a disease and its treatment. In addition,
and/or impairments. Disabilities are a potential con- using disease-specific measures allows inclusion of do-
sequence of health problems and signify a partial or total mains of specific interest for the disease under study and
inability to perform social roles in a manner consistent the patients it affects. Among the specific areas pre-
with norms or expectations.[531National survey data viously investigated with disease-specific questionnaires
suggest that 32% of employed adults have ongoing health are sexual and emotional functioning, nausea and vo-
problems that interfere with their ability to perform their miting, chronic pain, anxiety and depression, chronic
job demands.[j4] Historically, although limited, studies obstructive pulmonary disease, cardiovascular disorders,
have used outcomes of “work loss” or amount of time hypertension, epilepsy, benign prostatic hypertrophy, end-
missed from work due to illness or treatment. stage renal disease, diabetes, cancers, AIDS, HIV in-
Role functioning scales usually measure global, role- fection, and migraine.[20’55-571The reader is directed to
level disability indicators to capture disability in paid Refs. [20] and [22] for a more comprehensive listing of
work and/or other activities. However, for some applica- disease-specific questionnaires.
tions, these may be relatively course, distinguishing a The argument in favor of disease-specific question-
limited range of disability levels. Recently, researchers naires is twofold. The first consideration is that, if an
introduced a more detailed measure of work productivity instrument has to cover a wide range of disorders, many
assessing on-the-job impact of chronic conditions and of the questions may be inappropriate or irrelevant for any
treatment.[541 one specific problem. The second reason is to keep the
length of the questionnaire manageable. Thus, there will
General health perceptions be fewer, relevant questions to detect real changes within
patients or to detect differences among them.
The beliefs and evaluations of a person’s over health in On the opposite side of the argument, the cost of a
general, rather than a particular mental or physical aspect, greater degree of specificity is a reduction in generaliza-
constitute their general health perceptions. Questions in b i l i ~ y . ‘ ~ ’ ,That
~ ~ ] is, generic scales allow comparisons
this area reflect each person’s own health preferences, across groups of patients with different disorders, se-
values, needs, and attitudes, and thereby discriminate verities of disease, interventions, and perhaps even
between individuals whose objective levels of physical demographic and cultural groups,[601 as well as being
and mental health, as defined by other measures, appear able to measure the burden of illness of populations
identical. Such self-perceptions are important for two suffering from chronic medical and psychiatric condi-
reasons: 1) reports of behavioral performance do not t i o n ~ , [ ~as
* ] compared with a healthy population. This is
capture important subject manifestations of differences in much harder to do when each study uses a different scale.
422 Health Status Assessment
These questions are about how you feel and how things have been with you during the past 4 weeks. For each question,
please give the one answer that comes closest to the way you have been feeling. How much of the time during the past 4
weeks?
VI w [31 I41 [51 [el
All ost A good bit Some A little None
ofthe ofthe of the of the ofthe ofthe
time time time time time time
Have you been a very nervous person?
Have you felt so down in the dumps that
nothing could cheer you up?
Have you felt calm and peaceful?
Have you felt downhearted and blue?
Have you been a happy person?
Fig. 3 Example of a mental health scale from the SF-36. (From Ref. [5].)
response “all of the time” indicates better health. patient tells you she has diarrhea, you may form an im-
However, other items are stated so that “none of the pression of that diarrhea-seems like a mild side effect.
time” indicates a better health. Such items are reversed However, having her answer survey questions about her
before scoring. An example is “how often have you felt functioning can reveal how trivial or nontrivial the impact
so down in the dumps that nothing could cheer you.” of her diarrhea is to her everyday activities. What would
Persons answering “none of the time” need to be happen if her diarrhea limits her ability to function as the
assigned a scoring indicating better health, or the opposite checkout person in the grocery store? She cannot leave
direction of the endorsed items. her post frequently to go to the bathroom and, if she does,
she could be fired and not be able to provide for her two
vanta rnent young children that she is raising alone. The patient sees
srmat sional the limitation imposed by diarrhea as considerable, and
knowing more about her functioning conveys a different
Self-administered surveys allow the patient to have a message to us than just knowing she is having diarrhea. A
voice in their care. It permits the patient to communicate discussion employing information from a patient self-
to the health care professionals who are caring for them administered health status survey could also lead to the
about what matters most. This may be information that patient revealing that she has decided to stop taking her
you need to know but do not have time to elicit. Ana- medication. She did not think it was working and the
logously to providing a common language for patients and diarrhea was not worth the hassle.
health professionals. the general HRQOL information can
also provide a standard or common language for different
disciplines of health care professionals. For example, a
nephrologist and a psychiatrist can use a common metric
to discuss a dialysis patient’s emotional health. A stand- As pharmacists, we can use evidence from patient self-
ardized method of asking patients about their functioning administered health status surveys in caring for pa-
and well-being can be efficiently used in treatment de- tients.‘681A common model used in teaching students to
cisions and as a monitoring parameter for efficacy and monitor therapy is to first create a problem list and, for
toxicity. The information may also be a tool or indicator every problem on the list, develop an assessment and
for compliance assessments. plan. The diagram in Fig. 4 breaks down the assessment
In addition, HRQOL can be used to add important process. It requires one to write a potential inventory of
information to the evaluation of the effectiveness of an all monitoring parameters. It reminds and guides us to
intervention, in terms that matter most to the patient. For monitor both the efficacy and the toxicity using sub-
example, does the 34-year-old otherwise healthy woman jective and objective parameters appropriate for the di-
diagnosed with depression who just started an antide- sease and the treatment.
pressant feel better or worse? One could just simply ask We can easily incorporate the information from health
her that question when you see her 4 weeks after the start status surveys in any of these boxes. Examples are bolded
of her therapy. As pharmacists, we commonly use the in Fig. 4. Now, instead of just monitoring clinical
question, “Are you having any side effects?” If the parameters of efficacy and toxicity, we can extend our
424 Health Status Assessment
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PROFESSIONAL DEVELOPMENT
CY
illiam E. Smit
Virginia Commonwea Ith University, Richmond, Virginia, U.S.A.
Health systems evolved from a hospital into multiple A health system can own and operate its own licensed
facilities and levels of care during the 1980s and 1990s in community pharmacies. Prescription services and clinical
the United States. A health system can include more than services can be provided.
one hospital, ambulatory care clinics, physician office
buildings, long-term care facilities, and home care ser- Geriatrics and/or Lon
vices. The economic forces, both internal and external to
the hospital, led to the development of health systems. A health system can own and operate its own licensed
From a pharmacy perspective, the scope (range) of phar- long-term care facilities or license beds within the hos-
macy services expanded from acute care to ambulatory pital for long-term care.
care, to home care, to long-term care, and to other diver-
sified pharmacy services. Consequently, positions for cli-
nical pharmacists expanded from acute care to the other
care settings within the health system.
A health system can own and operate its own home care
services for nursing care, prescription drug products, and
pharmacist services.
CTIVlTlE
Information Service
A simple description of the range of career activities
within health system pharmacy would be acute care, am- A health system can own and operate its own drug
bulatory care. and home care to administrative pharmacist information service (DIS) to serve the drug information
needs of pharmacists, physicians, nurses, and other
positions. A more detailed description of pharmacist po-
sitions within the health system is as follows. professional staffs within the system. In addition to drug
information, the DIS focuses on drug formulary and
pharmacoeconomic issues of drug products and drug use
within the system.
Acute care relates to hospitalized patients. Patient care
areas within a hospital include internal medicine, general Therapeutic Drug onitoring Service
surgery, pediatrics, obstetrics and gynecology, critical
care, cardiac care, pulmonary critical care, psychiatry, on- A health system can own and operate a centralized the-
cology, and geriatrics. rapeutic drug monitoring service (TDMS) to focus on the
application of clinical pharmacokinetics to the care of
rnbulatory Care patients within the system.
A health system can own and operate its own ambulatory armacy Services
clinics and physician offices. The physician component
can be either by staff physicians employed by the health Depending on the size and complexity of the health sys-
system or by contract for physician services. tem, pharmacy management positions will range from the
director of pharmacy services to supervisor of a segment nonprescription medications, management of dmg the-
of the pharmacy services within the health system. Some rapy via physician-approved guidelines, monitoring of
examples of pharmacy manager positions include super- drug therapy, and screening tests for hypertension, dia-
visor of the drug information service, supervisor of the betes, and hypercholesterolemia.
therapeutic drug monitoring service, supervisor of ambu-
latory care services, supervisor of community pharmacies, ral
supervisor of clinical services, and assistant director of
pharmacy services. The following list of pharmacist practice activities de-
scribes a general clinical practice model:
TlVlTlE
Clarify prescription orders.
5 Question inappropriate prescription orders.
The typical work settings for clinical pharmacists in a 5 Answer drug information requests from patients.
health system include acute care hospital, ambulatory * Answer drug information requests from physicians,
clinic, outpatient pharmacy, home care pharmacy, and nurses, and other health professionals.
community pharmacy. 0 Monitor patient drug therapy for safety and efficacy
Clinical practice in the hospital could be in the central using a comprehensive patient medication record:
hospital pharmacy, a satellite pharmacy, a pharmacist’s
office, or a patient care area. The hospital pharmacy is - Drug-drug interactions.
usually located on a lower floor of the facility, which - Concomitant drug therapies.
places the pharmacist physically remote from the patient, - Appropriate drug, dose, and dosage form.
physician, nurse, and other personnel. Communications - Patient allergies.
are often by telephone, fax, or information technology - Drug-laboratory test interactions.
rather than in person. A satellite pharmacy is a pharmacy - Drug-food interactions.
area located in the patient care area where drug dis- - Abnormal laboratory tests that are drug induced.
tribution and clinical services are provided. A satellite - Clinical pharmacokinetics.
pharmacy places the pharmacist in the patient care area
where drug distribution and clinical services are provided. e Provide patient medication counseling.
A satellite pharmacy facilitates the placement of pharma- 5 Provide screening tests.
cists in close proximity to the patients, physicians, and Participate in collaborative practice agreements for
nurses. A pharmacist’s office space is often provided as a managing drug therapy.
location for the pharmacist to provide clinical services * Participate in clinical research.
that is in close proximity to patients, physicians, and
nurses. Clinical services can be provided in a drug in-
formation center, often located in the hospital pharmacy,
but it may be located in the medical library. Therapeutic XPERl
drug-monitoring services may be provided from a phar-
macist’s office location. The preferred education for a health system pharmacist is
Clinical practice in an ambulatory clinic may be pro- the doctor of pharmacy degree. A general practice resi-
vided from an office area within the clinic. The patient, dency is also preferred. Some clinical pharmacist prac-
patient medical record, physician, nurse, and other prac- tices prefer pharmacists with a specialty residency. The
titioners are in close proximity to the pharmacist’s office American Society of Health System Pharmacists for the
area. Examples of clinics in which pharmacists have pro- past 25 years has adopted policies and provided programs
vided clinical services include family practice, OB-GYN, to support these preferred education and training pro-
anticoagulation, prescription refill, pain therapy, nutrition, grams. When the criteria can be met for board certifi-
and internal medicine. cation, many health systems support clinical pharmacists
in becoming board certified.
Pharmacist clinical expertise requires practice, prac-
tice, and more practice. Years, usually three to five, are
The health system may own one or more community often acceptable to health systems in lieu of some re-
pharmacies. Clinical services can be provided relating to sidency training. The challenge is to get appropriate cli-
patient drug therapy counseling for prescription and nical practice experience without a residency.
430 Health-Systems, Clinical Pharmacy Careers in
For supervisory positions, three to five years of The following sites are examples within health systems
practice experience is often required. During the practice where pharmacist clinical services are provided:
experience, the pharmacist should demonstrate the ability
to achieve results, complete objectives on a timely ba- e Acute care hospital in the patient care area(s).
sis, possess good communication skills, and demonstrate e Critical care unit.
good working relationships with coworkers, physicians, e Pediatrics hospital.
and nurses. e Neonatal intensive care unit.
For director of pharmacy services, five to seven years e Long-term care facility.
of experience are often required in a similar health sys- e Family practice physician office.
tem. Additional education and training, such as an ad- e Ambulatory care clinic.
vanced residency in pharmacy management or a masters e Home care services pharmacy.
degree in business administration, are often preferred or e Community pharmacy.
required. Ability to manage resources, personnel, plan- 0 Outpatient pharmacy.
ning, financial, and interprofessional relationships with e Drug information services.
good communication skills are often required. e Therapeutic drug monitoring service.
e Oncology.
e Hospice.
many varied activitie5 to provide yuality care to patientc What is the job satisfaction and morale of the phar-
at different level\ ot care macist staff?
How arc pharmacy technicians used in the pharmacy
operations'?
What i \ the compensation and benefit package'?
What i j the strategic plan for the health \ystem and for
the pharmacy services?
A broad categorintion or hospitals is government and
nongovernment. Government hospitals are federal, state, The answers to these and similar questions should con-
and local. Nongovernment hospitals can be categoriLcd vey whether the health system being considered will pro-
into nonprofit and proprietary (for-profit). A teaching vide an environment for clinical practice, job satisfaction,
hospital is one that provides a postgraduatc education and opportunities for growth and career advanccmcnt.
program for physicians. All hospitals exist to provide
services and care to the patients being served. Some of the
key differences between hospitals include the manage- PI
ment decision-making process, type of medical staff,
scope of patient services to be provided, size, and fi-
nancial objectives and strength of each hospital. Thcrc is Some key factors for seeking pharmacist employment in
not an existing method to determine which types of a health system relate to the opportunities to provide
hospitals provide more pharmacy and pharmacist clinical clinical services directly to patients, to collaborate with
services as there are too many variables that determine the physicians and nurses, to copc with the personal chal-
existing scope of pharmacist services. In general, every lenge t o maintain and expand clinical pharmacotherapy
hospital needs more clinical services from the pharmacy knowledge and expertise, to change practice settings for
department and staff than currently exist. the different levels of care and job satisfaction, and to
Some questions to consider whcn looking at a health be viewed as an essential health care practitioner by the
system for possible cmploymcnt include the following: institution, physician, and nurse colleagues. The personal
satisfaction from providing clinical services that benefit
What is the existing scope of pharinacist clinical patients is the best reward for working in a health-sys-
services? What types of services? How long havc they tein environment.
been provided?
Is the hospital a teaching hospital'?
Does the pharmacy havc an afliliation with a school
of pharmacy?
Docs the health system provide pharmacy residencies?
ACCP Guideline, Practicc guidelines for pharmacotherapy spe-
What is the pharmacy director's philosophy regarding
cialists. Pharmacotherapy 2000. 20, 487 490.
~
Carl I. Tullio
Pfizer, Inc., Yorktown, Virginia, U.S.A.
Promotion, U.S. Department of Health and Human Ser- previous initiative. As Healthy People 2000 draws to a close,
vices, coordinated and oversaw the entire process. one objective is trending toward the goal, while the other four
are trending away from the goal.
Next, the focus area objectives for 2010 are presented.
ENT Each focus area contains varying numbers of objectives.
Many of the objectives are aimed at “interventions de-
The two overarching goals of Healthy People 2010 are signed to reduce or eliminate illness, disability, and
the elimination of disparities in health status among racial premature death among individuals and communities.
and ethnic groups and the improvement in the years and Others focus on broader issues, such as improving access
the quality of life for people of all ages. Progress in to quality health care, strengthening public health ser-
attaining these goals will be measured using the 467 vices, and improving the availability and dissemination of
objectives in the 28 Focus Areas (Table 1). Each focus health-related information.” In the diabetes example, the
area contains its own overarching goal. For example, the number of objectives was increased from 5 in the 2000
goal of the diabetes section states, “Through prevention program to 17 for the current program. Each objective
programs, reduce the disease and economic burden of (e.g., increase the proportion of persons with diabetes
diabetes, and improve the quality of life for all persons who receive formal diabetes education.) lists a target
who have or are at risk for diabetes.” After listing the (e.g., 60%) for the year 2010, the rationale behind its
goal, an overview of the issues, trends, disparities, and focus, and the national data tables from which the
opportunities for action is presented. If the topic was measurements will be extracted. Each focus area ends
included in the previous program, Healthy People 2000, with a listing of related objectives from other focus
interim progress toward the objectives is detailed. Using areas, an explanation of the terminology used, and the
the diabetes example, there are five objectives in the references employed.
contain only a few of the focus area’s objectives and may the entire patient must he considered, not just the medical
even contain objectives from a related focus area. For management. Healthy Pcople 201 0 provides thc informa-
example, the tobacco use focus area has 21 objectives, tion needed to help pharmacists develop services that are
while the tobacco use leading indicator follows only 2 of aligned with national goals.
the objectives. The indicators will highlight achicvements For detailed information, the full text of Healthy
and challenges throughout the next decade while serving People 2010 Conference Edition (Volumes 1 and 2) is
as a link to the 467 objectives of the Healthy People 201 0 available online at http://www.health.gov.healthypeop1e/.
program. The leading health indicators are intended to A CD-ROM version (B0071) can bc purchased from
help thc populace more easily understand the importance ODPHP Communication Support Center, P.O. Box
of health promotion and disease prevention. They are also 37366, Washington, D.C. 20013-7366, (301) 468-
aimed at encouraging wide participation in improving 5960. Limited numbers of the print version (B0074)
health in the next decade. are also available from the ODPHP Communication
Support Center.
a I
Donald J. Filibeck
Mt. Carmel Home Infusion, Columbus, Ohio, U.S.A.
vides service for only those patients being discharged Table 2 Home care patient database
from the hospital.
4 Patient’s name, address, phone number, date of birth.
For-profit home infusion providers range from single- 4 Alternate contact information in the event of an emergency.
site, private companies to multiple-site, million-dollar * Information on the status of any advance directive.
companies. All home care providers are licensed by the 4 Height, weight, gender.
state and can chose to become accredited by several ac- 0 Diagnoses.
crediting bodies (e.g., Joint Commission on Accreditation * Location and type of intravenous access and date of
of Healthcare Organizations (JCAHO), Accreditation placement.
Commission for Health Care, Inc. (ACHC), Community * Pertinent laboratory test results.
Healthcare Accreditation Program (CHAP)). Accredita- * Pertinent medical history and physical findings.
tion is a requirement for many insurance companies to * Accurate history of allergies.
e A detailed medication profile, including all prescription and
serve as a provider for their members.
nonprescription medications, home remedies, and investiga-
An advantage of working in home care is the flexibility
tional and nontraditional therapies.
in hours and activities that the home care environment Other agencies involved in patient care.
offers. Positions are available that range from PRN or, to Prescriber’s name, address, phone number, etc.
as needed, to part and full time. As needed positions are * A plan of care.
often used to help cover vacations and scheduled time off * Patient education activities.
or on-call activities. Part-time positions can range from * Anj7 functional limitations.
1 or 2 days per week to 4 or 5 . Average hours per day are * Any pertinent social history.
8 or 10 depending on the home care company.
Because home care personnel must be available 24
hours per day, on-call related activity may be required. Tasks include dispensing-related functions; technician
Depending on the organization and workload activities, oversight; obtaining orders from physicians and then as-
afternoon, evening, or weekend shifts may be used. sessing the orders for appropriateness; assessing the pa-
tient and caregiver for the appropriateness of providing
care in the home; patient and/or caregiver education;
CTI~ITI~S
OF THE HOM providing education for nursing agencies, discharge plan-
ners, etc; answering drug information questions; sales
support; and so on. No one day is ever the same. The fol-
Activities vary greatly, depending on the services pro- lowing explains these activities in greater detail.
vided and the size of the operation. In small offices, the One of the primary roles of the pharmacist is the pre-
pharmacist may wear many different hats. In large offices, admission assessment. This role ensures that each patient
the pharmacist may do only one task on a given day. is assessed for appropriateness using predetermined ad-
mission criteria. Common criteria are outlined in Table 1.
In conjunction with other members of the home care
Table I Home care preadmission criteria team and with the patient’s physician, a decision is made
to either accept the patient for home care services or refer
Patientlcaregiver agrees to receive services in the home. them back to the hospital discharge planner or referral
Patientlcaregiver are willing to learn the necessary steps to
source. Once accepted, an assessment is completed and an
administer their drug(s) in the home.
initial patient database established. Table 2 lists some
4 The home environment is acceptable (clean, access to tele-
phone and running water). of the items that are part of this database. Again, the
0 The patient is readily accessible to the home care provider. pharmacist is an integral part of this process. Much of this
* The patient has adequate family support, both physically and information is obtained via the telephone in conversations
psychologically. with the physician, hospital personnel, or patient. Infor-
4 A physician is readily available in the event of an emergency, mation may also be received via fax or from the home
ongoing clinical updates, and/or order changes. care agency nurse. Pharmacists working in a hospital-
* The medication ordered is appropriate to be given in the based home care pharmacy may be able to go up to the
home environment. floor and obtain this information directly from the medi-
* The indication, dosage, and route of administration of the cal record, floor nurse, and/or patient.
medication(s) ordered is appropriate.
e Labs etc., are ordered to access the effectiveness of the the-
One of the documents that is part of this patient data-
base is the care plan or plan or care. The plan of care
rapy ordered.
should indicate the treatment goals and indicators of de-
ome Care, Clinical Pharmacy Careers in 437
sired outcomes. any interventions that need to be done, jective evaluation of the therapy(ies), make appropriate
and the frequency of those interventions. Any drug-rela- recommendations for changes, and effectively commun-
ted problems that occur or have the potential to occur icate those changes to the patient/caregiver and all in-
should be addressed by the pharmacist, along with other volved health care providers.
members of the patient care team. When multiple pro- On an initial and ongoing basis, the pharmacist
viders are involved with the patient, the pharmacist is in should be providing education to the patient and/or care-
an ideal position to coordinate the information flow and giver. Some of this information may be provided ver-
care of the patient. bally, although most is provided in writing. Table 3 lists
The plan of care should be developed initially and some of these education-related issues. The pharmacist
updated as needed. Based on the drug(s) used and the should be involved in the development of all education-
potential for side effects and adverse drug reactions, the al material.
pharmacist should determine what type of monitoring
is needed (e.g., labs, physical findings) and the frequen-
cy at which it is to occur. The pharmacist must commu- s
nicate this plan to others involved and provide updates
as needed. The range of careers is very diverse. Pharmacists may
Another role of the pharmacist is the selection of pro- choose to remain clinically focused, providing hands-on
ducts, infusion devices (i.e., pump), and ancillary sup- care to the patient. Opportunities exist to do research on
plies. Many factors need to be considered when choosing the delivery and use of drugs in the home environment.
the administration method, infusion device to use, and Extended stability studies are one area where the phar-
what ancillary supplies are needed. macist can become involved. If the pharmacist gets in-
The stability, compatibility of the drug, and volume volved in clinical research, they should ensure that all
of the drug are important considerations when determin- appropriate policies and procedures are followed, that the
ing what method (IVPB, IV push, continuous infusion) patient and health care providers have appropriate in-
or infusion device (elastomeric, electronic infusion de- formation concerning the drug(s), and that all required
vice, etc.) will be used. Nursing agency knowledge and record-keeping requirements are met.
ability of the patient to learn the methodology are all Many sites offer clinical clerkships for undergraduate
important considerations. Patient convenience, prescri- pharmacy students and several post-PharmD residencies
ber preference, and cost must also be considered. Again, in home care exist.
the pharmacist is able to weigh the pros and cons of From an operational perspective, pharmacists who
any method and help the patient care team make appro- have a business background can progress from a staff-
priate decisions. level position to branch, regional, or corporate manage-
The ongoing clinical monitoring is the hallmark of the ment positions. It is not unusual for a mid- to high-level
pharmacist’s involvement. By having regular, ongoing manager to have started out as a staff pharmacist.
conversations with the patientharegiver, physician, and The pharmacist should be actively involved in the
home care nurse, the pharmacist is able to make an ob- organization’s performance improvement activities.“] AS-
pects of care that can be monitored include, but are not
limited to, patient satisfaction, unscheduled admissions,
Table 3 Education-related issues medication errors, adverse drug reactions, infection con-
trol-related issues (e.g., line infections), unscheduled deli-
0 Medication related, including dose, route of administration,
dosage interval, duration, side effects, adverse reactions (and veries, and so on.
their management). The pharmacist must also take an active role in the
e Proper aseptic technique. development, implementation, and review of an organi-
0 Precautions and directions for administering the medication. zation’s policies, procedures, and protocols. The pharma-
0 Equipment use, maintenance, and troubleshooting techniques. cist should ensure that all aspects of care are addressed,
0 Proper care of the vascular access device and site (if ap- including patient care, drug preparation and dispensing,
plicable). quality control, infection control, and equipment main-
0 Home inventory management, how to contact help, emer- tenance. Involvement in such activities can have far-
gency issues (what to do if something goes wrong). reaching effects on efficiency and financial outcomes.
0 Special precautions and directions for the preparation,
As a manager, the pharmacist’s responsibilities in-
storage, handling, and disposal of drugs, supplies. and
clude: 1) setting the goals (both short- and long-term) of
biomedical waste.
the pharmacy, based on the needs of the patients and
438 ome Care, Clinical Pharmacy Careers in
mission/goals of the organization; 2) developing plans to to providc sound pharmaceutical care to the patients
achieve those goals; 3) implementing those plans; 4) as- receiving home care services.
sessing whether the goals are being met; and 5) instituting
corrective actions when necessary.
The pharmacy manager will have multiple areas of
responsibility, such as managing the pharmacy (includ-
ing compliance with laws, regulations, and accreditation 1. American Society of Health-System Pharmacists. ASHP
standards), financial resources (drugs, budgets, reim- guidclines on minimum standards for home care phar-
bursement), and pharmaceutical care and human re- macies. Am. J. Health-Syst. Pharm. 1999, 56, 629 638.
sources (scheduling, hiring, education and training, staf- 2. American Society of Health-System Pharmacists. ASHP
fing needs). guidelines on the pharmacist's role i n homc care. Am. J.
Health-Syst. Pharm. 2
Pharmacists that have a sales/marketing nature can
3. National Home Infusion Association. White Paper: Home
pursue this career tract if so desired. As mentioned prc-
ln/usion Servicrs, Payineizt Modes und Operutionnl Costs;
viously, positions range from branch salcdmarketing to www.nhianet.org.
corporatewide strategic sales management. 4. National Home Inruusion Association. Resourcrs ,for
Priyc,r:r, Physiciatzs & Providers: Overview of' Home
h@sion Therapy; www.nhianet.org.
5. National Home Infusion Association. Resources ,firr
.ricians & Providers: Patient Care Process in
on Thcrupy; www.nhianet.org.
The practice of pharmacy in the home care environment 6. www.nhianet.org.
presents many opportunities for professional and personal I. www.ashp.org.
growth. T h c practice continues to evolve and will 8. Winiarski, D. Performance improvement in action: Ke-
continue to offer pharmacists multiple opportunities (both cliveries of iiilusion supplies. Infu-
clinically and management related), as well as continuing
PHARMACY PRACTICE ISSUES
Ana Clopes
Hospital de la Sta. Creu i Sant Pau, Barcelona, Spain
to different ~tudies][’,~-*~
without loss of effectiveness
of treatment. A meta-analysis carried out by Hughes
The introduction of home care is unavoidably bound to et studied the impact of home care hospital days
the changes that have been taking place in most health (22 studies) and demonstrated a significant reduction
systems over the last 30 years. The financial pressure to in hospitalization days across studies due to home
reduce the hospital length of stay has a direct rela- care, with a cumulative effect size of -0.38 (CI,
tionship on the acceptance of home care, and on the -0.42 to -0.34, p=O.OOl).
growth of other activities such as nursing homes and The patient’s maintenance in hidher family environ-
outpatient clinics. ment. This implies an improvement in the quality of
Home care or hospital at home is defined as a service life“’] and patient satisfaction.“ ‘I
that provides active treatment by healthcare professionals The patient’s involvement in hisher own care. This is
in the patient’s home of a condition that otherwise would not typical in conventional health care and should be
require acute hospital in-patient care, always for a limited considered to improve the effectiveness of treatment.
time period.[” At the same time it breaks the bonds of nonpositive
This definition is the same for all models of health dependence that sometimes exist between the patient
systems but the application and focus of care differ. and the hospital.
However, in most systems home care implies the appli- Avoidance of the risk of nosocomial infections. Patient
cation of high technology in the patient’s home for a care in a nonhospital environment avoids contact with
limited period, rather than care for chronic patients. For hospital organisms, which are usually more resistant to
this reason, in most systems, the referral centers are antibiotic treatment.
the hospitals. Development of health models which integrate the
The concept of home care originated in the university different areas (basically hospital and communi9
hospitals in the forties. In 1947 the Montefiori Hospital in cave). The separation between the different areas of
New York planned to extend the hospital to the patient’s patient care is artificial, while integration implies a
home. But home care was in fact first applied in the higher quality and more individualized care.
sixties with “Hospitalisation a Domicile” in France in
1961.[21It has been implemented in a number of other
countries, including the United States,[31Canada, and the
Netherlands.14] Home care coverage within the Medicare
program in the United States was implemented in 1966. The way home care is organized depends more on the
The acceptance of home care has been faster in North type of care within each country than on the kind of
America than in European countries where there is no care provided. Home care can be classified according
direct cost to the patient or an insurer when a patient is to the type of reference center or according to the type
admitted to a hospital.[51 of structure.
Reference Center
0 Reduction in hospital length of stay.[llThis is reflected The hospital is responsible for the patients and is the
in the decrease in costs [from 30 to 85% according decision-making center. A hospital team organizes,
Table 1 Infections most frequently included in home One option to facilitate the coordination among the dif-
care programs ferent steps is periodic meetings to discuss the cases with
Skin and soft-tissue infections
the participation of all the members of the home care team.
Cellulitis
Abscess
Postoperative wound infection F ~NTERVEN~IO~S
Posttrauma wound infection Home Parenteral Antibiotics
Diabetic foot
Decubitus ulcer
In general, all types of infection and all organisms are
Bone and joint infections
Acute and chronic osteomyelitis susceptible to home IV antibiotic therapy. The treatment
Septic arthritishursitis of patients with bone and joint infections has proven
Prosthetic joint infections highly effective and is now well accepted.[211Other bac-
IV line infection terial infections that have been studied extensively are
Infective endocarditis skin and soft tissue infections and lung infections. The
Ear and sinus infections (sinusitis/otitis/mastoiditis) reason is that these infections fulfill two important
Acute exacerbation of pulmonary symptoms in cystic fibrosis criteria: patients are clinically stable and require pro-
Lung infection (hospital- or community-acquired pneumonia) longed IV antibiotic therapy (>7 days).[221But home care
Gastrointestinal infections (abscesdperitonitis) can be extended to great number of infections: bacterial,
Kidney, bladder, and prostate infections (pyelonephritis/
viral, and fungal (Table 1). The patient's admission to
perinephric abscess)
home care should be considered from the beginning of the
Systemic febrile syndromes
Cytomegalovirus infection infection or should be wait until the patient is clinically
Febrile neutropenia stable, depending on the infection.
Brain abscess A large number of cost-effectiveness studies have been
carried out (Table 2), all with positive results.
Table 3 Opportunistic disease in AIDS candidates for givers receiving hospital-at-home care reported greater
home care satisfaction than those in the hospital group.
Infection Antimicrobial therapy One of the fundamental pharmacological treatments in
this group of patients is the opioid continuous infusion
Cytomegalovirus infection Maintenance and with devices adapted to outpatient treatments as patient-
induction therapies: controlled analgesia pump.
Ganciclovir IV
Foscarnet
Cidofovir
Acyclovir-resistant Foscarnet
Herpes simplex The administration of chemotherapy at home has demon-
Acyclovir-resistant Foscarnet strated that it is feasible and that it produces a decrease of
Herpes zoster adverse effects and an improvement of the quality of life
Pneumocystis carinii Pentamidine IV and a monetary savings.i251
pneumonia Pentamidine aerosol However, home care can also give support to the
Cryptococcosis Amphotericin B patient with cancer in other areas: parenteral antibiotics
Histoplasmosis Amphotericin B in febrile neutropenia, nutrition and fluid support, or
Coccidiomycosis Amphotericin B
pain support.
Drug-resistant Amikacin
mycobacterium
Pneumonia 3rd Generation Cephalosporins
Aminoglycosides
In the support of hematology patients, the therapy can-
didates for home care may be chemotherapy, IV anti-
biotics in febrile neutropenia, blood products, IV im-
tibiotic therapy candidates for home care. The reasons are
munoglobulins, fluid/electrolyte replacement, central line
that the patient is clinically stable and requires long-term
maintenance, and specific treatments such as deferoxa-
therapy. In some cases the induction can also be
mine administration.
considered to be treated at home. These infections and
In the support of hematopoietic stem cell transplantation
treatments are described in Table 3.
there are programs developed to permit treatment with
Other support therapies for AIDS patients that can be
chemotherapy at home and treatment of complications.[261
given at home are nutrition support, parenteral and
enteral, IV immunoglobulins, chemotherapy in lymphoma
or Kaposi's sarcoma, and care of terminally ill patients.
the patient’s suitability for home care on the basis 11. Participation in performance improvement activi-
of criteria described in the protocol (home ties. Patient satisfaction and outcome should be
environment, psychosocial factors, and clinical monitored to detect and resolve problems. Quality
condition). of life should also be considered.
3. Coordination of preparation and delivery of drugs
to the patient or caregiver. Together with the me-
dication, the pharmacist should provide the ancil-
lary supplies and drug delivery systems. The phar-
macist should also ensure appropriate disposal of
cytotoxic products.
e Section of Home Care Practitioners of American
4. Planning home treatment and care, also with an Society of Health-System Pharmacists (ASHP)(USA):
interdisciplinary approach, involving the patient www. ashp.orghomecare.
and in collaboration with other team members. This
e Home Care Highlights of American Society of Health-
home treatment and care plan should be reviewed System Pharmacists (USA): www.ashp.org/public/
and updated periodically and outcome should be news/newslettershomecare/index.html.
assessed.
e ASHP Guidelines (USA): www.ashp.org/bestpractices.
5. Therapy monitoring using parameters previously American Society of Parenteral and Enteral Nutrition
defined in the protocol. The pharmacist should carry (with the Standards of Practice for Home Nutrition
out this monitoring from the medical records and Support)(USA) : www. clinnutr .org .
verbal exchange with the patient and/or the care- Joint Comission on Accreditation of Healthcare Orga-
giver, nurse, physician, and other family members. nizations (USA): www.jcaho.org.
6. Patient and caregiver education about the treatment. American Academy of Hospice and Palliative Medi-
The information should be both oral and written and cina (USA): www.aahpm.org.
include: Edmonton Palliative Care Program (Canada): www.
palliative.org.
e Description of the therapy (drug, dose, route National Council for Hospice and Specialist Palliative
of administration). Care Services (United Kingdom): www.hospice-spc-
m Goal of the therapy. council,org.uk.
Administration technique.
e Agence Nationale d’Accreditation d’Evaluation en
o Special precautions regarding storage, hand- Sante, France (with the recommendations for the
ling, and disposal of drugs. medical records of the home care patients for ambu-
m Emergency procedure. latory nursing professionals) (France): www.anaes.fr.
m American College of Chest Physicians (ACCP) (Patient
7. Information for home care team members regard- Education Guides: Mechanical Ventilation at Home)
ing: (USA): www.chestnet.org/health.science.policy.
6. Coast, J.; Richards, S.H.; Peters. T.J.; Gunnell, D.J.; intravenosa domiciliaria. Enferm. Infecc. Microbiol. Clin.
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~
administration of intravenous antibiotics: An efficient, 51. Williams, D.N. Reducing costs and hospital stay for
cost-effective home care program. J. Can. Med. Assoc. pneumonia with home computerized cefotaxime treatment
1982. 127, 207-211. results with a computerized ambulatory drug delivery
44. Rchni, S.J.; Weinstein, A.J. Home intravenous antibiotic system. Am. J. Mcd. 1994, 97 (2A), 50-55.
PHARMACY PRACTICE ISSUES
Arthur C. Lipman
University of Utah, Salt Lake City, Utah, U.S.A.
the report of the Committee on Care at the End of Life of social workers, nursing assistantslhome health aides,
the Institute of Medicine of the National Academy of chaplains, volunteers, and pharmacists. Persons from se-
Sciences concluded that “palliative care should become, veral other disciplines support the hospice team (Fig. 1).
if not a medical specialty, at least a defined area of As shown in Fig. 1, the central focus of care is the
expertise, education and research.’ ’[41 Hospice and patient, family, and primary care person(s), who is usually
palliative care are often used interchangeably. a family member. They continue to work with their
Hospices provide care for patients with advanced, primary physician. The interdisciplinary hospice team
irreversible disease and a life expectancy measurable in listed in the next concentric circle from the center pro-
weeks to months as opposed to years. The defined unit of vides direct support. This team may include both health
care is the patient and their family. The focus of care care professionals and other persons who are equipped to
spans physical, psychological, social, and spiritual do- deal with issues that are complicating the lives of the
mains. This requires an interdisciplinary team. Nurses patientdfamilies (e.g., financial counselors). The third
usually coordinate home visits and serve as team leaders. concentric circle from the center includes persons who
The patient’s primary care physician normally continues support the team. Pharmacists have both direct patient
to provide care, often in consultation with the hospice care and supportive roles in hospice teams as described in
medical director. Other key members of the team are the following paragraphs.
Fig. 1 The hospice interdisciplinary team. The patient, primary caregiver, and family are the focus of the hospice team’s efforts in
collaboration with the patient‘s primary physician. The core team is represented by the next circle away from the center. The support
team is indicated by the outer circle. Community resources that support hospice care are listed outside that circle. Pharmacists serve on
both the core team (second circle from the center) by providing direct pharmaceutical care to patients and families, and on the support
level (next circle out from the center) by providing professional and public education about drug therapy in the care of terminally ill
patients. (From Lipman AG, Berry JI. Pharmaceutical care of terminally ill patients. Journal ofPharmaceuticaZ Care Pain and Symptom
Control, 1996; 3(2):31-56.)
Hospice and Palliative Care 449
There is a need for elimination of artificial barriers often in an excellent position to recommend hospice care
between the time when a cure is sought and the and to refer families to appropriate programs.
inevitability of death is accepted. This barrier exists, at Services provided by pharmacists in American hos-
least in part, due to the requirement for documenting life pices have only been qualitatively and quantitatively
expectancy by the Medicare Hospice Benefit. The U.S. documented twice, in 1979r51and 1991.[61Many more
Congress defined this benefit in the 1980s through which pharmacists provide these services today than when the
Medicare beneficiaries can assign their medicare part B latter survey was completed, but the observed types and
benefits to any Medicare-certified hospice program. That mix of services do not appear to have changed much since
program then receives a daily fee from Medicare in return the 1990s.
for assuming responsibility for the patient’s total care, Although many pharmacists serve as hospice volun-
including drugs and pharmaceutical care. To be eligible teers, about three-fourths are paid for their services. The
for this benefit, the patient’s physician must certify a majority of pharmacists who provide services to hospice
probable life expectancy of 6 months or less. This arbitrary programs are not employed directly by the hospices, but
time limit has created psychological barriers for physi- by a provider of pharmaceutical services such as a home
cians, patients, and their families, resulting in many pa- health pharmacy or hospital. Many are employees of
tients not being referred, seeking, or receiving the hospice pharmacies that have contracts with hospices to provide
care to which they are entitled. Because pharmacists com- drugs and services. In recent years, specialized hospice
monly have long-standing relationships with families they pharmacy service providers have been developed in
serve and enjoy their patients’ trust, pharmacists are often several parts of the United States.
in the best position to advise patients about the importance The 1991 surveyL6’ reported that dispensing fees
of developing relationships with a hospice program as accounted for about one-half of the reimbursement
soon as possible after determination that the disease has received by pharmacists. In the past few years, payment
a probability of being life ending. for cognitive services has become more common. Some
Hospice and palliative care are becoming much more pharmacists provide only consulting or dispensing ser-
widely recognized by healthcare providers. The American vices, but many provide drug products, home health
Academy of Hospice and Palliative Medicine (founded in supplies and equipment, and pharmaceutical care. Phar-
1988 as the Academy of Hospice Physicians) and the maceutical services other than prescription dispensing
Association of Hospice Nurses are respected national services are not usually required by licensing or cer-
organizations of health care professionals who provide tifying agencies. Payment for cognitive services is at
palliative care. The National Hospice and Palliative Care the discretion of the hospice administration. The ex-
Organization (NHPCO, formerly known as the National perience of many hospices has been that integration of
Hospice Organization [NHO]) includes the National pharmacists directly into planning and provision of pa-
Council of Hospice Professionals (NCHP). The 15 mem- tient care both improves the quality of symptom control
bership sections of the NCHP include an active pharma- and lowers costs. In many hospices, pharmacists are now
cist section. active participants in weekly or biweekly interdisciplin-
ary team (IDT) meetings at which patients’ progress is
discussed and care plans are refined.
P UTI
Newsletters
IASP (International Association for the Study of Pain) Newsletter
(206) 547-6409
American Pain Society Bulletin
American Pain Society; (847) 375-4715; e-mail: info@ampainsoc.org
Texts
Berger AM. Portenoy RK, Weissman DE. Principles and Practice of Supportive Oncology. Philadelphia, Lippincott-Raven, 1998.
Doyle D, Hanks GWC, MacDonald N, editors. Oxford Textbook of Palliative Medicine, 2nd edition. New York and Oxford,
Oxford University Press, 1997. Berger AM, Portenoy RK, Weissman DE. Principles and Practice of Supportive Oizcology, 2nd Ed.;
Philadelphia, Lippincott-Raven. in press 2002.
Web sites
National Hospice and Palliative Care Organization
www.nho.org
PDQ (Physician Data Query)
www.cancernet@icii.nci.nih.gov/
Talarian Map Cancer Pain
www stat.washington.edulTALARIAiTALARIA.htm1
Open Society Institute: Project Death in America
www.cyberspy.com/-websterldeath.htm1
The Palliative Medicine Program
www.mcw.edu/pallmed
Hospice Foundation of America
www.hospice foundation.org
Information about hopsice with links
www.hopsiceweb.com
Hospice Hands web site
http://hospice-cares.com
Purdue Pharma Pain and Palliative Care Information
http://www .partnersagainstpain.com
relevant to hospice care and symptom control is often Preparing routine admission orders
provided at meetings of the American Society of Con- Developing drug-use protocols
sultant Pharmacists, American Society of Health-System Making home visits as needed to assess medication
(previously Hospital) Pharmacists, American Pharmaceu- needs and use, and to educate patientdfamilies about
tical Association, the National Hospice and Palliative medication use
Care Organization, and at some state and local profes-
sional associations. Several journals, newsletters, and web Common educational functions include:
sites focus on pain and symptom control. Examples are
listed in Table 1. Because hospice care is interdisciplinary Providing staff education in drug therapy for symptom
by definition, most programs are open to suggestions of control and other indications
additional ways in which any discipline can contribute to Providing education to patients and their families on
the program’s overall objectives. medication use
Hospice programs are always recruiting and training Providing physician education to hospice patient
new volunteers. Therefore, most readily welcome calls primary physicians
from persons in the community interested in learning Providing public education on drug use in terminal
more about the program or becoming involved in patient care
care. Any pharmacist can simply call a local hospice and Educating hospice volunteers about desired and
make an appointment to meet with the staff to discuss achievable outcomes from medication use
unmet pharmaceutical care needs. These include a range Providing clerkships for pharmacy students
of activities, including administrative responsibilities,
provision of medications, and outcome-oriented phar- Common dispensing functions include the following:
maceutical care.
Common administrative functions include the follow- Dispensing prescription and over-the-counter medica-
ing: tions, including therapeutic interchange
Providing for delivery of medications to patients’
Managing program or facility (if applicable) homes
Serving on the hospice board or professional advisory Extemporaneous compounding of dosage forms that
committee are not commercially available
Negotiating contracts with provider pharmacies Providing home infusion service
Reviewing and ensuring compliance with state and Maintaining patient medication profiles
federal laws and regulations that relate to the provision
of hospice pharmaceutical care and services
Developing drug-related policies and procedures
Participating in continuous quality improvement and
quality assurance activities, including drug-use eva-
luations and cost-avoidance and cost-effectiveness The broad range of relevant pharmaceutical services
studies needed by a progressive hospice program nearly always
Procuring medications for indigent patients through requires more than one provider. Simple. informal needs
pharmaceutical industry patient assistance programs assessments of programs with which pharmacists want to
Managing the hospice formulary affiliate is an effective way to market their services.
Hospice Medicare payments and most other insurance
Common clinical functions include the following: reimbursement is capitated (i.e., a flat daily fee is paid to
the program for all aspects of care). Therefore, the full
Developing pharmaceutical care plans, including range of care must be provided within a defined cost
assessment and monitoring for therapeutic and toxic structure. Efficient formulary management, including
outcomes generic and therapeutic interchange and elimination of
Participating in hospice interdisciplinary team meet- unneeded drug therapy, can improve both patient care and
ings (chart sounds) the fiscal health of the program. Patient and family
Performing drug regimen reviews satisfaction are also important considerations for every
Providing pain and symptom management consulta- hospice program. Medication-related education provided
tions to team members and to patients’ primary by a pharmacist can markedly increase satisfaction.
physicians Hospice nurses often work relatively independently from
452 Hospice and Palliative Care
their patients’ physicians. Therefore, by providing nursing will provide services to dying patients and hospice
education and consultation about patient assessment for programs. An increasing number of pharmacists will
responses to therapy and about drug use, pharmacists can work with hospice programs as a substantial part of
increase their perceived need on the hospice team. thcir practices.
Effective management of pain and othcr symptoms
associated with life-threatening disease is usually
attainable with the proper combination of pharmaco-
logical and nonpharmacological interventions.’” Phar-
Most hospice referrals come to the programs from macists can, and should, play an important role in
patients’ primary physicians. Some come directly from ensuring that their patients receive this care when it
families who have heard about hospice from other is needed.
families that used the service or from presentations made
in the community. Most hospice programs send a nurse to
the paticnt’s home (hospital or nursing home) to assess EF
thc patient and to perform an intake evaluation. This
cvaluation requires a detailed history, including a 1. WHO Expert Committee. Cancer Pain and Palliative
medication history. Care; Technical Report Series, World Health Organiza-
Pharmacists need to know patients' prescription and tion: Geneva, 1990; Vol. 804.
nonprescription medication intake; use of nutritional 2. Lipman, A.G. Drug therapy for terminally ill patients. Am.
supplements that may be pharmacologically active, J. Hosp. Pharm. 1975, 32. 270-276.
physical, and psychiatric diagnoses; and relevant labor- 3. Arter, S.G.; Lipman, A.G. Hospice care; a new opportunity
atory test data when they are available. Usually, that for pharmacists. J. Pharm. Pract. 1990, 3, 28-33.
information is available from the primary physician’s 4. Approaching Death: Improving Care at thi, End of Lije;
Field, M.J., Casell, C.K., Eds.; National Academy Press:
referral and the documentation from the intake interview.
Washington, 1 997.
Frequently, laboratory test data arc not available because
5. Berry, J.I.; Pulliam, C.C.; Caiola, S.M.; Eckel, F.M.
of the hospice philosophy of only doing tests that will Pharmaceutical services in hospices. Am. J. Hosp. Pharm.
directly affect paticnt outcomes. Renal function oftcn can 1981. 38, 1010 1014.
~
be estimated from the quantity and quality of thc patient’s 6. Arter, S.G.; Berry, J.1. The provision of pharmaceutical
urinary output balanced against intake. Careful dose care to hospice patient: Results of the national hospice
titration is often needed in the absence of laboratory test pharmacist survey. J. Pharm. Care Pain Symptom Control
data as patients’ metabolic and elimination capabilities 1993, I (I), 25-42.
decline. Sometimes, pharmacists make home visits to get 7. Lipman, A.G. Cumculum on pain for pharmacy students.
morc complete medication histories, and to ascertain the IASP Newsl. 1992 MayIJune, 2 ~ 4 .
family’s understanding of medications and ability to 8. Jacox, A.; Carr, D.B.; Payne, I<., et al. Management of
Cancer Pciin, Clinical Practice Guideline. AHCPR
administer them correctly.
Publication Number 94-0592, Rockville, MD. Agency
for Health Care Policy and Rescarch; U.S. Department of
Health and Human Services, Public Health Service,
1994.
9. Gavrin, J.R.An annotated guide to pain and palliative care
Most pharmacists will interact with terminally ill patients on the World Wide Web. J. Pain Palliat. Care Pharma-
or their family members at soinc time. Many pharmacists cotherap. 2002, I 6 (2), 37 48.
PHAKMACY P KACTICE I SSU ES
ic ai
Joaquin Ciraldez
Ana Ortega
Antonio ldoate
Azucena Aldaz
Carlos Lacasa
Clinica Universitaria de Navarra, Parnplona, Spain
Quality management
1989- ADDlied research
is now four years. The reason for this extension is that
Rational therapeutics activities conducted by hospital pharmacists have in-
Coordination with primary care
Continued training creased considerably and training had to adapt to these
Etc.
changes. Activities outside the pharmacy service and in
1984.89 Clinical pharmacokinetics
00 proximity to the patient and health care team are
necessary. In the fourth year, residents are supposed to
1974-84 take their knowledge to the bedside and be with the
Committees
Team-work patient and health care team. They have to take res-
Training
Drug information ponsibility for the pharmacotherapy given to each patient,
Rational dispensin work as part of a team, and develop a critical ability to
solving all pharmacotherapeutic problems.[41 The res-
1955 -74 Purchase idency program is regulated, practice-based, and can be
Manufacture
Control
Number o f hospital done only in certain accredited hospitals, and students
Dispensing n have to first pass a national exam.[32s361
Currently, appro-
Management
ximately 100 pharmacists per year can be admitted to the
Fig. 1 Activities conducted by hospital pharmacists and the residency program, which includes all activities conduc-
number of hospital pharmacists in Spain since 1955. ted in hospital pharmacy services.
L
s 50
V d
s b
U
In Spain, a hospital pharmacy training (residency) is a
mandatory in order to work as a hospital pharmacist. This
specialization has been regulated by law since 1982.'3,291 Fig. 2 Number of hospitals per region in Spain (From
Until 1999 the residency program lasted for three years; it Ref. [30]).
Hospital Pharmacy Practice in Spain 455
private hospitals have agreements with the public sector hospital pharmacies are computerized and all have the
or with insurance companies. following tasks: to define requested drugs. to establish
In what follows, some activities conducted by Spanish purchasing procedures according to Spanish law, to
hospital pharmacists will be briefly described. Three ac- place orders, to inform hospital directors of acquisitions,
tivities are considered the foundation of hospital phar- and to develop a quality control program. Spanish re-
macy in Spain: adequate drug selection, drug informa- ferences to management techniques are given in the
tion, and drug delivery. Some Spanish references include
most of the activities developed at Spanish hospitals[73s1
as well as statistics on hospital activity."] Recommenda-
tions of the Spanish Society of Hospital Pharmacists
(SEFH) for some of the activities can be found at Drug dispensing/distribution is one of the main clinical
www.sefh.es/normas/normasy.htm. In addition, there are activities of Spanish hospital pharmacists. Many studies
now many possibilities for networking. The SEFH have shown that the unit-dose distribution system has
facilitates interhospital communication and interest reduced drug errors, and it is one of the main contribu-
groups have been created.13'I Some other international tions of the hospital pharmacy['*] to patient care. Phar-
organizations provide the same opportunities for their macist participation in medical rounds and presence at the
specific topics (e.g., www.senpe.com/Gtrabaj/textos2.htm time of prescription can result in even better patient care
for parenteral and enteral nutrition). Statistical data will and a prompter detection of treatment failures.[133141 Such
not be presented here but can be obtained from a survey "clinical pharmacy" activity is being conducted with
conducted by the SEFH in 1995;"01 more up-to-date some groups of patients in some Spanish h ~ s p i t a l s " ~and
'
figures will become available from the year 2000 survey. is becoming more frequent.
Most Spanish hospitals have a unit-dose drug distri-
an t bution system (Fig. 3). The main objectives of such a
system are the following: knowledge of patient pharma-
There are two important areas in management, clinical cotherapeutic profile, which encourages pharmacist inter-
and purchasing management. In every hospital pharmacy vention before drug dispensation and administration;
service it is necessary to establish basic procedures for decrease of drug errors, interactions, and adverse reac-
drug selection, acquisition, reception, storage, and dis- tions; reduction in treatment costs; decrease of drug ma-
tribution with the least cost and risk for patients. nipulation by nurses on the wards; and billing or econo-
Clinical management refers to an efficient and safe use mic assignment according to each patient's real expenses.
of drugs according to pharmaceutical criteria. To achieve In a unit-dose system, the pharmacy service delivers
this goal there are many possible courses of action; how- drugs to be directly administered to the patient without
ever, the most basic one, which is conducted in all Span- need of further intervention by others. In hospitals, the
ish hospital pharmacy services, is the definition of a distribution of some drugs (e.g., narcotics, compassionate-
hospital-specific drug formulary that lists all the drugs use drugs, research drugs, and drugs for emergencies)
approved by the hospital's Pharmacy and Therapeutics requires a special control and distribution procedure.
(P&T) committee. In Spain a hospital pharmacist is one Normally, these drugs are not sent with the rest of the
of the members of P&T committee, frequently the presi- medication; and the procedure for these drugs will be
dent or the secretary. The P&T committee has the fol- presented later on. The following is a description of the
lowing tasks: to select drugs; to recommend a drug use unit-dose system as it is applied in most Spanish hospital
policy; to educate about correct drug use; to set drug use pharmacy services.
protocols and establish the means of ensuring compli- Medical orders are handwritten by doctors and a copy
ance; to introduce a program for the detection, follow- is sent to the hospital pharmacy service, where it is re-
up, and evaluation of adverse drug reactions; and to co- corded in the computer system. However, in some hos-
operate in a quality control program. Criteria used by the pitals, doctors enter the medical order directly into the
P&T committee for drug selection are, in order of im- computer; few proceed in this way at the moment but
portance: efficacy, safety, cost-effectiveness, therapeutic the number is increasing. In a few hospitals, with some
contribution, and incidence. types of patients, pharmacists are present at the time of
Regarding purchasing management, the main respon- prescription. Prescriptions may specify generic or brand
sibility of the purchasing unit of a hospital pharmacy names depending on the hospital's policy, and pharma-
service is to have available the necessary drugs to treat cists can choose bioequivalent drugs depending on what
hospital patients. Almost all purchasing units in Spanish is available.
456 Hospital Pharmacy Practice in Spain
Medical orders are checked by pharmacists. and doc- then delivered with the rest of the medication. Cytotoxic
tors or nurses are consulted if necessary. At this point, drugs require special control and handling and are not
pharmacists have a good opportunity for intervention. To normally sent with the rest of the medication. Sometimes,
prove the appropriateness of the prescription for a specific in intensive care units and other acute care settings, drug
patient, patient data must be checked. The unit-dose delivery is not based on a unit-dose system but on stocks
system is computerized in all hospital pharmacies. Com- kept on the wards.
puter programs may be in-house or standard. Some Some outpatient services are provided by the inpatient
information can be checked on the computer; in some pharmacy, but discharged patients in Spain cannot receive
cases programs even make suggestions.[16’ Subsequently, drugs from the inpatient pharmacy. At discharge, patients
lists are created for auxiliary personnel to prepare the may receive drug information and a copy of their me-
delivery trolleys to take the medications to the wards. In dication administration record for reference. Computer
a few hospitals, for some specific units, automated de- software (InfoWinE) has been developed by a Spanish
livery (e.g., PyxisE, Suremed”, OmnicellT~) is used. In group (with a Spanish drug database) for this purpose.
this case, pharmacists, or someone under their super- Drugs that require a special delivery procedure are:
vision, have to check the accuracy of the delivery con-
tent. Quality and security in delivering medication must 1. Drugs for compassionate use. Hospital pharma-
be fully guaranteed. These systems require a medical or- cists have to control the ordering, dispensing, and
der, and information regarding patient name, doctor, and use of compassionate-use drugs. These are drugs
quantity of drug dispensed must be recorded. for nonauthorized indications andlor research
In most Spanish hospitals, there is just one delivery a drugs not included in a clinical trial. In Spain,
day, in the afternoon, because in many hospitals doctors activities in relation to these drugs are regula-
see patients between 8 A M and 3 P M However, the ted.[’.’71 In order to use a drug for compassionate
number of visiting hours is increasing and pharmacy care, the pharmacy service of the hospital applies
working procedures may have to adapt to the new si- to the Direccih General de Farmacia y Productos
tuation. Parenteral admixtures and nutritional prepara- Sanitarios with the following documents: a clinical
tions. if chemically stable, are generally prepared for each report in which the doctor justifies the application
patient in a centralized unit (described later), labeled, and for the drug, a consent form signed by the patient,
Hospital Pharmacy Practice in Spain 457
and a form signed by the hospital medical director macy service. A sterile area is normally achieved with a
who is responsible for drug use. It is common vertical or horizontal airflow hood.
practice for the pharmacy service to prepare a
technical report with relevant references to support
the application and to inform hospital directors of
the process.
Centralized units of intravenous therapy (or CIVAS, for
2. Research drugs. Regarding drugs for clinical trials '*central intravenous additive service' ') were created in
conducted at the hospital, the pharmacy service is Spanish hospital pharmacy services as both a consequence
responsible for their reception, storage, dispensing, of the growing importance in the hospital of intravenous
distribution, and return of unused drugs. Spanish drugs, and parenteral nutrition and fluids and as a
requirements are that clinical trials be regula- consequence of the clinical and technical progress in this
ted.[17' A copy of the clinical trials committee ap- area of the pharmacy. In recent years. Spanish hos-
proval must be kept at the pharmacy service, and pital pharmacy services are almost obligated to have a
dispensing is done only after a written and signed CIVAS,"91 and it is now considered, along with the unit-
prescription is received. dose distribution system, one of the main units in the
pharmacy service.[l'] The main objectives of the CIVAS
3. Foreign drugs. Drugs marketed in a foreign coun- are preparation of products therapeutically and pharma-
try but not available in Spain may, according to ceutically appropriate for the patient (right dose, ad-
Spanish law, be obtained but only for the speci- ministration route, chemically compatible, stable); prepa-
fic indications for which the drug is approved in ration of admixtures free of particles, microorganisms,
that foreign country."] The hospital pharmacy ser- or toxins; preparation of admixtures with the correct
vice applies to the Direcci6n General de Farmacia drug in the exact amount; labeling, identification, sto-
y Productos Sanitarios with the necessary docu- rage, and distribution of admixtures according to good
mentation for use with an individual patient or drug control principles; cost control of intravenous
according to a protocol. fluids; monitoring and clinical follow-up of patients;
drug use evaluation studies; and participation in the
4. Stocks in wards. There are some drugs (e.g.,
urgent medications, PRN, drugs dispensed as
needed) and medical devices that have to be in
stock on the ward. These are normally sent to the
floor on a regular basis, according to a fixed
schedule. These stocks are periodically checked
by pharmacists (with regard to composition, ex-
piry date, correct identification), and the results of
the control are filed. The nurse supervisor of each
ward is responsible for the safekeeping of the
stock; the pharmacist is responsible for control
and supervision.
Manufacture
intravenous therapy policy of the hospital (indications, established in Spain, and today activities related to drug
selection, preparation, administration, etc.). information are part of every hospital pharmacy service.
Most hospitals have a computerized CIVAS that is Drug information is another area where clinical interven-
integrated into the unit-dose distribution system. Prepa- tion by pharmacists could be increased.
rations handled in these units include cytotoxic drugs, Information provided by pharmacists can be classified
antibiotics. parenteral nutrition, other drugs, and thera- as passive or active. The former includes answering
py with fluids (Fig. 4). References to Spanish articles questions and preparing the requests/controls for foreign,
dealing with recommendations for managing these units compassionate-use, and research drugs. Active informa-
can be found in the b i b l i ~ g r a p h y . ~Pr~otocols
~ ~ , ~ ~must
.~~~ tion includes providing support to the P&T committee
include every procedure carried out in the unit, from (drug formulary preparation, diffusion of main decisions),
preparation to identification, hazard handling, waste treat- establishment of protocols, writing of the drug informa-
ment, and so on. In Spain, admixtures and nutritional tion bulletin, sessions, adverse drug reactions programs,
preparations are normally prepared by pharmacy nurses advising in- and outpatients, health education activities,
supervised by pharmacists. information management, and so on. Some hospitals make
Centralized units have some advantages, such as less their drug formulary and other information available on
investment in equipment, better use of multidose vials, the Internet (e.g., www.hsanmillan.es/farma/index.htm)
recycling of unused preparations, better working condi- and some participate in the dissemination of drug infor-
tions, a good opportunity for clinical intervention by mation, in the Spanish language, to patients.[321 Addi-
pharmacists, and improvement in the quality of patient tional sources of information and recommendations for
care when the CIVAS is well coordinated with the unit- the management of drug information centers that have
dose system. been proposed by the SEFH and others are given in the
bibliography. [7,8,11,21,221
Enteral and Parenteral
harmacok~~etic§ and
In Spain. preparation of enteral and parenteral nutrition is Therapeutic Drug ~ ~ ~ i t o r ~ n g
carried out in the centralized units of the pharmacy ser-
vices. Hardly any hospitals obtain their parenteral Clinical pharmacokinetics is a multidisciplinary field that
nutrition preparations from an external company. In most has been growing in importance over the last 20 years. Its
hospitals there are some standard nutritional preparations main objective is therapy optimization by achieving drug
as well as others designed for specific patients. Nutrition concentrations in the therapeutic range and thereby
design and patient follow-up is done by hospital phar- obtaining maximum efficacy with minimum adverse ef-
macists or by a team of various professionals (doctors, fect. The concentration-effect relationship of many drugs
dieticians, nutritionists, pharmacists), depending on the is better than the dose-effect relationship. This is due to
hospital. Normally. laboratory data, clinical results, and high interindividual variability. In these drugs, therapeutic
patient progression are observed by pharmacists and drug monitoring is justified.
nutrition support is changed accordingly, which gives To assure the best efficacy, the pharmacist designs a
pharmacists another opportunity for clinical intervention. pharmacotherapy that is specific to each individual pa-
References on how to manage such a service are given tient. This is achieved by obtaining blood samples, ga-
in the bibliography.[73x3191 Computer software is used to thering patient data (clinical situation. laboratory results,
make this task easier, permitting data entry (general physiopathology, progression, therapy), applying pharma-
patient data, lab results, prognosis, nutritional status, diet) cokinetic principles, and applying knowledge of drug be-
and preparation of working sheets, reports, and labels for havior in the population in which the patient is included.
nutrition identification. Complications or incidents can Even though drug concentration is an important piece of
also be registered; some software programs include information, it is not enough on its own and patient
Spanish products for nutrition support (e.g., NutriDataE, follow-up is required. Times of sample collections must
Nutri2000E). be carefully established in order to obtain maximum in-
formation from the minimum number of samples.
Drug information The usefulness of therapeutic drug monitoring has
been demonstrated for some drugs (e.g., some antibiotics,
Drug information is one of the main responsibilities of cardiovascular agents and antiepileptics, theophylline, in-
pharmacists in hospitals and one of their most important munosupressants, litium, r n e t h o t r e ~ a t e ) , [ ~and
, ~ ~these
I are
contributions to a rational use of drugs and better patient the drugs that are included in clinical pharmacokinetic
care. In 1973, the first drug information center was programs in Spanish hospital pharmacy units. The be-
Hospital Pharmacy Practice in Spain 459
nefits of therapeutic drug monitoring of other drugs, such Spain, pharmacoeoconomics is becoming more important
as some anticancer drugs, are now being studied in some due to increased pressure to make the best use of limited
centers.[241 resources. Furthermore, advances in the methodology[261
Sample analysis requires specific techniques, such as have increased the scientific rigor of pharmacoeoco-
fluorescence polarization immunoassay (FPIA) and high- nomics. Pharmacoeconomics is used by Spanish hospital
performance liquid chromatography (HPLC). These tech- pharmacists as a tool for decision making regarding
niques are not always available in the pharmacy and so drugs, medical devices, or related activities. Studies are
sample analysis is not always done in Spanish hospital conducted and pharmacists adapt published studies to
pharmacy services but in laboratories. However, it is a each unique hospital setting.
pharmacist who interprets results, makes recommenda-
tions, and follows up on patients, all as part of clinical
activities to pursue better patient care. In all hospitals with
such a pharmaceutical service, doctors and other members Many Spanish hospital pharmacies participate in the
of the health team welcome the contribution of pharma- selection, ordering, storage, distribution, and provision of
cists, with their pharmacokinetic knowledge, to the information relating to medical devices. Such hospital
rational use of drugs. pharmacies are also involved in rational use programs. A
guide to medical devices used in Spanish hospitals has
Drug Surveillance been published, which gives a classification to each
device.[271
Drug surveillance includes drug follow-up with the pur-
pose of observing, evaluating, and communicating any
adverse reactions that a drug can produce when used in
clinical practice. A drug surveillance program must be
established in every hospital in order to detect these The number of activities conducted by hospital pharmacy
reactions, and the drug information center must support services is continually increasing as the needs of doctors,
this activity technically. Observed events are communi- personnel, and patients evolve. This gives the pharmacist
cated to the regional center for drug surveillance, either the opportunity to develop a range of activities (clinical
directly or through the SEFH. The Spanish Drug Agen- roles, management, administrative duties) that are of
cy[331facilitates drug surveillance activities and the dif- interest to and positive for the hospital. Pharmacists must
fusion of information among professionals. Spain has continue to focus on the impact that technological and
an organized drug surveillance system-a national com- professional changes may exert on the efficacy and safety
mittee reporting to the Ministry of Health was consti- of medications as well as on patient care.
tuted for this purpose in 1987. Spontaneous communi- The role to be played by hospital pharmacists should
cation of adverse drug reactions is voluntary in Spain be determined by all health care professionals, not just by
and is conducted through an official form known as the pharmacists themselves. The 1999 meeting of the Spanish
"yellow card.'"'] Society of Hospital Pharmacists took this into account
and a roundtable was held incorporating representatives
Radiopharmacy of all health team members as well as a representative of
patient opinion based on a survey of patients. Better
In Spain, pharmacy practice is also applied to the study, information for patients, more integration of pharmacists
manufacture, control, and distribution of radiopharma- in the health team, and more direct contact with patients
ceuticals. Radiopharmaceuticals must be isolated from seem to be the activities to be developed in the future.[2s1
other drugs and personnel, and devices must follow Spa- Any activity that contributes to patient care must be
nish regulations.[251Radiopharmacy is part of the hospi- nurtured, no matter who suggests it. Pharmacists as well
tal pharmacy service; however, it is recommended that as other professionals know that teamwork is the key to
the unit be located close to the nuclear medicine de- improving results for the patient.
partment and supervised by a pharmacist specialist in
radiopharmacyI'[.
Pharmacoeconomics
1. Ley 25/1990, de 20 de Diciembre, Boletin Oficial del
Pharmacoeconomic evaluations consist of comparing Estado (B.O.E.) del 21. del Medicamento. (Also at
different alternatives in terms of costs and benefits. In www .msc.es/farmacia/legislacion/home.htm).
460 Hospital Pharmacy Practice in Spain
2. Bonal, J . Management en Farmacia Hospitalaria. I n 17. Real Decreto 561/1993, del 16 de ahril. Boletin Oficial del
I.'armnc,iu Hospitalaria, 2nd Ed.; Editorial MCdica Inter- Estado de 13 de Mayo. por el que sc estahlecen 10s
national: Madrid, Spain, 1992; 30-55. requisitos para la realiLacihn de cnsayos clinicos con
3. Suiik, J.M.; Rel. E. Coinpilucirjnde Legislario'n en I*hrm- mcdicamentos.
acin Ho,spilalaria, 2nd Ed.; Sociedad Espaliola de Farm- 18. Normas de correcta faabricacihn de fdrmulas magistrales y
acia Hospitalaria, Ed.; International Marketing and preparados oficinales. SEFH Bol. Tnf. 1994, XVIII (69),
Communications: Madrid, Spain, 1994; 1290. 15 28.
4. Gitici de Formacidiz de l.q~c~ia1i.sta.s. Famiacia Hospita- 19. JimCneL Torres, N.V. Mezclas, 1ntmveno.sa.s y Nutricicin
laria; Ministcrio de Sanidad y Consumo, Ministerio de Artzfi'cial, 4th Ed.: C.E.E. Convaser: Godella, Valencia,
Educacihn, Cultura, Conscjo Nacional de Especialisa- Spain, 1999; 722.
ciones Farmac6uticas: Madrid, Spain, 1999; 3 1. 20. Manejo de Mrdicainentos Citostciticos, 2nd Ed.: Asocia-
5. SuliC, J.M.; Bel, E. Legislacidn. In Fnrmariu Hospitdaria, cidn Espaliola de Farmackuticos de Hospitales: Madrid,
2nd Ed.; Editorial Mkdica Internacional: Madrid. Spain. Spain. 1987; 56.
1992; 172-268. 21. Proyecto de recomendaciones de la SEFH: Informacidn de
6. Simh, R.M. Docencia. In Farmacia Hospi~ularia,2nd Ed.; medicarnentos. S E € H Bol. Tnf. 1996, X X (77), 15 20.
Editorial MCdica Intcrnacional: Madrid, Spain, 1992; 136- 22. Tordera, M.; Magraner, J.; FernBndez, M.I. Informacionde
157. medicarnentos e internet. Estrategias de btisqucda farrn-
7. Guia de Gestio'n d r 10s Suvicios de F a m a t i n Hmpita- acoterap6utica en la World Wide Web. Farm. Hosp. 1999,
laria; Insituto Nacional de la Salud: Madrid, Spain, 1997, 23 (l), 1-13.
(A1so at w w w .se f.es/guiafarmacia/home. h tm) . 23. Applied Pharmacolzinetics. Principles of Therapeutic Drug
8. Farinacia Hospitdaria, 2nd Ed.; J. Bonal, A. Dominguez- Monitoring, 3rd Ed.; Evans, W.E., Schentag, J.J., Jusko,
(31. Dir.; Editorial MCdica Intcrnacional: Madrid, Spain, W.J.: Eds.; Applied Therapeutics, h e . : Vancouver, Wash-
1992, 1717 pp. ington, 1992.
9. Guia para la Evaluucicin y Mejora de 10s Servicios de 24. AldaL, A. FarmacocinCtica de CitostBticos. Conceptos
Farmacia Hospitalaria; Insituto Nacional de la Salud: Generales. In El Paciente Oncohematolrigico y su
Madrid, Spain. 1998, (Also at www.sef.es/guia/index.htm). Tratainirnto. Mddulos d~ Acrualizncicin Multidi.sciplinar;
10. Situacihn de la Farinacia Hospitalaria. Encuesta- 1995. SEFH, Editores Medicos, S.A.: Madrid, Spain, 1997; 32-
SEFH Bol. Inf. 1996, XX (76), 100. 37.
1I. Curso de Adnziiiistrcicidn de Servicios I-lospitalarios de la 25. Real Decreto 479/1903, de 2 de Abril, por el que se re-
Clinicti Univei~itaria.El Sewicio de Farmacia: Universi- gulan 10s medicamentos RadiofBrmacos de uso hurnano
dad de Navarra: Pamplona, Spain. 1992; 509. ( I ) . Boletin Oficial del Estado nuin 109 de 7 de Mayo
12. Ferrandir, J.K. Distribucihn unidosis dc Mcdicarncntos en de 1993.
Hospitales. In X I X Asciniblpa National de Farmare'ulicos 26. Drummond, M.I:.; O'Brien, B.; Stoddart. G.L.; Torrance,
de Ho.spita1e.s; Graficas Orihn: Madrid. Spain, 1975; 7 1 - G.W. Methods ,for IZconomic Evaluation of Health Care
88. Pi-ogmmmes, 2nd Ed.; Oxford University Press, Tnc.: New
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I>cmonaco, H.J.; Erickson, J.I.; Bates. D.W. Pharmacist 27. Giraldez, J.; Idoate, A,; Romero, R.; Urstia, C.; Errea,
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PROFESSIONAL DEVELOPMENT
INTW
ing in combination with education and referral to a prima- The supervising physician, if applicable. This may
ry care physician when appropriate resulted in a significant be especially needed if the pharmacist has pres-
number of patients receiving follow-up for cholesterol criptive authority.
concentrations that were higher than the NCEP goal^."^' The population to be managed. For example, in the
case of limited resources, the service may be re-
stricted to secondary prevention patients, patients
requiring combinations of drugs, or those with
mixed lipid disorders versus those with only ele-
vated LDL, or other parameters as determined by
Hyperlipidemia management can exist wherever phar- the needs of the facility.
macists practice, including community pharmacies, ins- The means of identification of patients. This could
titution-based or free-standing ambulatory clinics, or vary from seeing potentially low-risk patients,
inpatient services. Despite these different settings, some such as any patient followed in a general medicine
universal requirements need to be addressed. clinic or referred by a primary care provider, to
The nature of the practice may be influenced by the identifying high-risk patients, such as anyone dis-
availability of space in which to provide patient care. For charged from the hospital with a diagnosis of
example, the lack of facilities in which to meet privately myocardial infarction or after a revascularization
with the patient may result in a telephone-based practice. procedure or with other evidence of CHD risk.
Offering lipid management in the community pharmacy The goals of the clinic and methods for achieving
may require an investment in infrastructure. Some re- them. Explain how patients will be evaluated and
modeling of the pharmacy may be needed to provide an how the need and type of therapy will be deter-
area where confidential communications can occur. A mined. Describe any protocols for deciding on
lipid analyzer, as well as a dedicated clean area, must be drug therapy or the rationale for allowing clinical
supplied if blood lipid monitoring is to be offered. decision making instead of following an algorithm.
Staffing must be adequate. A redistribution of duties Will patients be seen once for evaluation and re-
among pharmacists and technicians, possibly in addition commendations, as often as necessary to achieve
to hiring additional pharmacists, may be necessary to control, or indefinitely? How frequently will they
allow pharmacists time to provide the service."61 be seen? Will all contacts be by visit, or will tele-
Most pharmacists will need to justify their provision of phone calls be routinely used?
this service, whether it be in the form of a business plan
for an independent pharmacist or a proposal demonstrat-
ing benefit to an institutional employer. If the pharmacist
will be relying on referrals to the service or will be
collaborating with physicians to implement therapy, the
pharmacist must first determine whether physicians will
use the service and be accepting of input. An evaluation The functions of a pharmacist in lipid management in a
of a cholesterol screening program found that a significant community setting may include screening for elevated
number of physicians in the geographic area were re- cholesterol and/or low HDL cholesterol, providing patient
sistant to their patients directly receiving the results of education and counseling to enhance adherence with drug
their cholesterol tests from the pharmacy. These physi- and nondmg therapy, monitoring of lipid profiles for as-
cians were less likely to contact patients with the results sessment of efficacy, and making recommendations to
of elevated cholesterol values obtained at the screen- providers for drug therapy management.
ing."71 Patients may also be surveyed as to acceptance of
pharmacist management, particularly if they are going to Screening programs
be expected to pay part or all the costs of the service.
In all models, a scope of practice agreement or pro- The accessibility of community pharmacists to both pa-
tocol is recommended, if not required. This should outline tients and physicians makes them an ideal resource for
the following: identifying the presence of lipid abnormalities. Screening
may consist of offering to measure cholesterol levels to
1. The hours of operation. the general population, or may involve targeted screening
2. The pharmacists who are responsible for providing of patients at high-risk for CHD, also called case finding.
the service. In either case, screening should involve more than pro-
Hyperlipidemia Pharmacy Practice 463
vision of a laboratory value. The total and HDL cho- Patients were recruited by the investigator and included in
lesterol values should be evaluated and interpreted in the the study if their primary physicians agreed to allow them
light of the patient's risk factors for CHD. Education to do so. The physicians were recruited by letter and by
about cholesterol and cholesterol-lowering strategies meetings with the pharmacists. Pharmacists provided
should be provided, and the pharmacist should be pre- basic education about lipid disorders, the relationship to
pared to refer the patient to their primary care provider if coronary artery disease, and diet and exercise. Lipopro-
warranted. Failure to interpret these values may result in teins were measured at the pharmacy using the Choles-
unnecessary concern on the part of the patient or, po- techE analyzer. If warranted, drug therapy recommen-
tentially more damaging, result in a patient not seeking dations were provided to the physician via telephone or
care when needed. letter; if accepted, the patient was seen at 2 months to
Gardner and colleagues['s1 demonstrated that a com- assess efficacy and adverse effects. All patients were also
munity pharmacy prescription database can be used to seen by a certified dietician. Significant reductions in
identify patients at risk for CHD. This is important LDL cholesterol were observed, although it is not clear
because it targets those individuals most likely to benefit how many patients reached their therapeutic goal. Given
from lipid-lowering interventions. They identified four choices ranging from $15 to $55, patients indicated they
clinical indicators that were believed to be likely to would be willing to pay $23.75 &$11.42 for each en-
identify patients at risk for CHD: prescription for sub- counter with the pharmacist.
lingual nitroglycerin, prescription for beta-adrenergic Project ImPACT: Hyperlipidemia was a multicenter
blocking agents or thiazide diuretics, males with a pre- community pharmacy-based demonstration project that
scription for nicotine gum or patch, or those receiving oral aimed to demonstrate the benefits of a pharmacist on
hypoglycemic agents or insulin therapy and who were patient adherence and compliance with lipid-lowering
greater than 50 yr of age. A search of the pharmacy therapy.[16] The pharmacists used cholesterol analyzers at
database was performed to identify individuals prescribed their sites to enhance their interactions with patients and
at least one of these agents, and the pharmacy profiles their physicians. Emphasis was placed on patient edu-
were screened to ensure the age and sex met the criteria. cation and communication with the physicians to bring
These subjects, who were invited to a free cholesterol patients to their NCEP cholesterol goals. Of interest,
screening, were compared with an unselected population 62.5% of the patients, who were predominantly primary
who self-referred to the screening. Twenty-one percent of prevention, did reach and maintain their goals by the end
those identified as high risk responded to the invitation. A of the study. Persistence with therapy was excellent, with
significantly greater percentage of the screened patients 93.6% remaining on the prescribed cholesterol-lowering
had cholesterol values that were higher than desired. In agent throughout the study. Compliance with therapy,
addition, two-thirds to three-fourths of the patients with a defined as fewer than five missed doses or refills obtained
clinical indicator had cholesterol values over 200 mg/dl, within 5 days of when due, was 90.1%. Physician accept-
indicating that these indicators may be predictive of the ance of pharmacist interventions was high, with 76.65%
need for cholesterol-lowering intervention. of recommendations resulting in a change. These inter-
Einarson et a ~ [ 'reported
~] the financial feasibility of a ventions involved coordination of care, adverse drug re-
pharmacy-based cholesterol screening program. Subjects actions, drug interactions. drug dosing, drug selection, and
were asked how much they would be willing to pay for a side effects.
cholesterol measuring service in a pharmacy. Patients The participating pharmacies were primarily indepen-
who completed a pharmacy service questionnaire indi- dents, with some chains, clinic pharmacies, health main-
cated they would be willing to pay a mean of S11.54. tenance organizations, and home health/home infusion
Patients who received the service were surveyed after- pharmacies. All pharmacies scheduled patients for ap-
ward, and indicated a willingness to pay $14.47 (1987 pointments with the pharmacist. Most used time before
dollars). Of note, it does not appear that these patients the regular pharmacy hours or on weekends, as well as
received pharmacist education as part of their testing but during usual business hours. Seventy-two percent of sites
were reacting to the value of obtaining cholesterol results changed the pharmacist's duties to accommodate this new
at a pharmacy. role, and 59% changed technician duties. Increasing phar-
macist overlap was also a commonly used strategy. Fewer
Lipid management practices than one-third added pharmacist staff to implement the
program. The average amount of time spent on patient
Shibley and Pughi201 described the provision of phar- encounters was about 45 min for a new patient and 22 min
maceutical care in independent community pharmacies. for a follow-up appointment.
464 Hyperlipidemia Pharmacy Practice
2-day training session that includes material on evidence their specific areas: the Expert Panel on Detection,
of cholesterol-lowering and use of antihyperlipidemic Evaluation, and Treatment of High Blood Cholesterol in
agents, training on the CholestechE analyzer, discussions Adults (Adult Treatment Panel or ATP) develops guide-
on preparing the pharmacy practice site to provide the lines for the detection, evaluation, and treatment of high
service, marketing to patients and physicians, commun- blood cholesterol in adults; and the Expert Panel on
ication with physicians, and reimbursement and billing. Blood Cholesterol Levels in Children and Adolescents
The National Pharmacy Cardiovascular Council offers a developed recommendations for healthy diets for children
comprehensive three-tiered educational program. The Li- and adolescents, and for detection and treatment of high
pid Managers Training Program begins with the basics blood cholesterol in children and adolescents from high-
of lipid disorders and progresses to on-site training in a risk families.
lipid clinic.[321Many state organizations offer certificate The guidelines for treatment recommended by the
programs in lipid management. ATP are considered the standard for dietary and drug
The NCEP was initiated by The National Heart, Lung, therapy in adults. The most recent guidelines were re-
and Blood Institute (NHLBI) of the National Institutes of leased in May 2001;r251the panel is currently revising
Health (NIH) in 1985. The goal of this program is to these and updated guidelines are anticipated after Spring
promote cholesterol awareness in the U.S. population as a 2001. The pediatric guidelines were released in 1992.r261
risk factor for CHD and provide guidelines for choles- The American Diabetes Association clinical practice
terol-lowering to physicians, patients, and the commun- guidelines make recommendations for managing hyper-
ity, thus reducing CHD mortality and morbidity. The lipidemia in persons with diabetes that are more aggres-
program consisted of five panels that are responsible for sive than the current NCEP guidelines, as well as more
evaluation of the evidence and establishing guidelines in specific to this population.[271
atie ucation not be product specific but will contain a company logo
and product brand names.
The second set of tools involves imparting some of this
information to the patient. This can be done verbally,
with written educational materials, with videotapes, or a
combination thereof. The level of the material should be The third set of tools involves the pharmacist’s docu-
adjusted for the educational level of the patient pop- mentation of interventions and results. If lipids are to be
ulation. The information should include definitions of measured and followed, the use of a monitoring flow
cholesterol, triglycerides, and lipoproteins; factors that sheet is extremely useful (Fig. 1). Flow sheets may be on
increase or decrease these values; and the goals for the paper files, created on computer spreadsheets, or use spe-
patient. A risk calculator that can be used to illustrate to cial software programs.
patients how their individual factors increase or decrease Initial demographic data including height should be
their risk of a coronary event should also be included.[2s1 collected. The information obtained at each visit should
In patients without physical limitations, handouts and include weight, exercise, lipid values, drug therapy (if
counseling about beginning an exercise program may be any), and compliance. If available. other pertinent labs
provided, although patients with known vascular disease such as glucose or hemoglobin AlC, liver transaminases,
should be referred to their primary care provider for or measures of renal function should be noted. A com-
guidance on appropriate activity. Providing a diary in ments section is useful to document items such as adverse
which patients can document their activity, heart rate, drug effects, noncompliance, o r other issues that can af-
notes on dietary changes, and weights can be helpful, fect lipid control.
especially in the initial stages of making lifestyle
changes. Information sheets about the individual drugs Communication
should also be distributed. The American Heart Asso-
ciation (AHA) web site provides a variety of tools for the The fourth set of tools regards communication with physi-
health care provider to order for a fee or to download at cians or other primary care providers. Interventions made
no charge.[291 by the pharmacist or recommendations to the physician
Pharmacists who practice lipid management should be may be made by telephone, letter, fax, or personal contact,
familiar with dietary factors that influence lipids. If depending on the practice setting. These communications
referrals to a dietician are allowed by law, the pharmacist are important in both obtaining and maintaining provider
should have a referral base from which to guide the pa- buy-in as well as demonstrating the active role the phar-
tient. Handouts that describe the goals of fat content, macist is playing in the care of the patient. In addition,
specific foods to choose and avoid, and how to read and there is less likelihood for misunderstanding than if all
interpret food labels should be available for distribution. information is provided by the patient.
These are available from a variety of sources. Patients
may be referred to the AHA web site, which offers infor- Lipid Measurement Devices
mation about recommended diets as well as recipes. Drug
companies that market cholesterol-lowering medications Lipid analyzers are not necessarily a needed tool for
often provide free patient information materials that may providing lipid management services but can be very
When to start cholesterol-lowering therapy i n patients L.N.; Gardner, M.E.; Donohue, M. Establishment and eval-
with coronary heart disease: A statement for healthcare uation of a serum cholesterol monitoring service in a
professionals from the American Hcarl Association Task community pharmacy. T h g Iiitell. Clin. Pharm. 1988, 22,
Force on Risk Reduction. Circulation 1997, 0.5, I683 45-48.
1685. 20. Shibley, M.C.; Pugh, C.B. linplernenlation of pharmaceu-
9. Avorn, .I.;Monette, J.; Lacour, A,; Bohn, 1C.L.; Monane, tical care services for patients with hyperlipidemias by in-
M.; Mogun, H., et al. Persistence of use of lipid-lowcring dependent community pharmacy practitioners. Ann. Phar-
medications: A cross-national study. JAMA, J. Am. Med. macother. 1997, 31. 713-719.
21 Bogdcn, P.E.; KoontL, L.M.; Williamson, P.; Abbott, R.D.
10. Andrade, S.E.; Walker, A.M.; Gottleib, L.K.; Hollenbcrg, The physician and pharmacist team. An effective approach
N.K.: Testa, M.A.; Saperia, G.M.; Platt, R. Discontinuta- to cholesterol reduction [see comments]. J. Gen. Intcrn.
tion of antihyperlipidemic drugs-do rates reported in cli- Mcd. 1997, 12, 158--l64.
nical trials reflect rates in primary care settings'? N. Engl. J. 22. Furmaga, E.M. Pharmacist management of a hyperlipidc-
Med. 1995, 332, 1125-1 131. mia clinic. Am. J. Hosp. Pharm. 1993, 50. 91 95.
11. Pearson, T.A.; Laurora, 1.; Chu, H.; Kafonek, S. The Lipid 23. Schectman, G.; Wolff, N.; Byrd, J.C.; Hiatt, J.G.; Hartz, A.
Treatment Assessment Program (I,-TAP). Arch. Intern. Physician extenders for cost-effective management of hy-
Med. 2000, 160, 459-467. percholcsterolcniia. I . Gen. Intcrn. Med. 1996, 11; 277
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maceutical care on optimum colestipol treatment in elderly 24. Birtcher, K.K.; Bowden, C.; Ballantyne, C.M.; Huyen, M.
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PROFESSIONAL DEVELOPMENT
Steven C. Ebert
Meriter Hospital, Inc., Madison, Wisconsin, U.S.A
Infectious diseases pharmacists typically practice in a An increasing number of infectious diseases pharmacists
hospital setting that allows them to devote all their time practice in outpatient settings. These individuals usually
to managing antimicrobial therapy. All aspects of in- practice in one of two areas. One area is in outpatient
fectious diseases pharmacotherapy, including interven- clinics, where they are directly involved in patient care.
tions on antimicrobial selection, antimicrobial dosing, This is particularly true for pharmacists who specialize in
and intravenous-to-oral conversion are the responsibility treatment of patients infected with human immunodefi-
of the infectious diseases pharmacist. In addition, the ciency virus (HIV) or other chronic infectious diseases
pharmacist is usually responsible for analyzing new (e.g., leprosy). Pharmacists take medication histories,
antimicrobials for formulary inclusion, medication use counsel patients about their medications, assess response
evaluations. and antimicrobial restriction or therapeutic to antimicrobial therapy, and make adjustments in the-
interchange policies. rapy, as necessary.
Some infectious diseases pharmacists may collab- Infectious diseases pharmacists also make valuable
orate with infection control practitioners to reduce noso- contributions to patient care in the managed care set-
comial infections and control antimicrobial resistance. ting. By evaluating antimicrobial prescribing patterns,
Others may work closely with clinical microbiologists creating drug treatment protocols, directing formulary
to design institution-specific susceptibility testing and re- decisions. and “counterdetailing’ ’ prescribers, infectious
porting methods, and to generate periodic antibiotic sus- diseases pharmacists help to curtail inappropriate anti-
ceptibility reports. biotic prescribing that may lead to increased antibio-
In hospitals with a significant pharmacy influence on tic resistance.
antimicrobial therapy, it may be impossible for the in-
fectious diseases pharmacist to perform all the functions a c e u ~ i c Industry
~l
described here. Instead, the pharmacist may need to
delegate the responsibility for conducting standardized An increasing number of infectious diseases pharmacists
antimicrobial “protocols” (therapeutic interchange. intra- have found a career in the pharmaceutical industry. Some
venous to oral, aminoglycoside pharmacokinetics) to initially take positions in pharmaceutical sales. Others
other pharmacists, while maintaining accountability for may be hired as research associates, where they assist in
the quality of these programs. the collection and analysis of data for clinical studies.
Although the salary for many hospital pharmacists who More often, they are hired as “medical science liaisons.”
practice exclusively in the area of infectious diseases These individuals interact with physician and pharmacist
comes from the hospital in which they practice, a sub- practitioners, where they provide drug information, grant
stantial number are cofunded by hospitals and schools of support for research and educational efforts, assist in
pharmacy or medicine. medication use evaluations, and give in-services to me-
dical and pharmacy staff.
Combined with other responsibilities Promotions within industry have lead many of these
pharmacists into advanced positions such as Director of
In hospital pharmacy departments with limited resources Medical Affairs. Associate Director for Research, or As-
or incomplete antimicrobial management programs, phar- sociate Director for Education.
Infectious Diseases Specialty Pharmacy Practice 471
esearch ~rganization and apprising the service members of any imminent drug
interactions or adverse effects. The pharmacist also
Some infectious diseases pharmacists join contract re- monitors patients followed by the service, to assess
search organizations. These organizations work primarily therapeutic response and/or adverse events. Finally, the
with pharmaceutical companies to test the in vitro activity pharmacist serves as a resource for drug information for
of new antimicrobials, assess their efficacy in intro and service members.
animal infection models, and conduct clinical trials. Phar- The advantages of rounding with an infectious diseases
macists may be hired into positions ranging from re- consult service include a sense of “teamwork” and
searcher to director. camaraderie; the backing of an infectious diseases phy-
sician, which means that most recommendations will be
Government followed; direct interaction with only a limited number of
(infectious diseases) physicians, which will quickly
Some infectious diseases pharmacists have been hired in- establish mutual trust and respect; and the potential for
to government positions. These individuals direct govern- collaboration in research. Disadvantages include limited
ment-initiated studies, care for patients in clinics, and patient exposure (usually only patients involved in “con-
formulate policies regarding medication use. Infectious sults” are followed) and, potentially, limited usefulness if
diseases pharmacists currently hold positions in the Food the infectious diseases attending physician is knowledge-
and Drug Administration, National Institutes of Health, able in antimicrobial pharmacology.
and World Health Organization.
Pharmacist-infectious diseases
Independent Consultant physician collaboration
Many infectious diseases pharmacists devote some time Another common practice model for hospital-based
to work as consultants. In most cases, they serve as ad pharmacists is a one-on-one collaboration between an
hoc consultants for pharmaceutical companies, where infectious diseases pharmacist and an infectious diseases
they assess the likely impact of a newer antimicrobial physician. Under this model, the infectious diseases
andlor providing advice on direction of future studies. physician is generally responsible for standard infectious
They may also educate pharmaceutical sales staff or write diseases “consults.” The pharmacist acts as an extension
review articles. of the infectious diseases physician’s clinical practice
Other infectious diseases pharmacists work full time clinical practice, rather than competition or duplication.
as consultants. Usually, they are employees of larger The pharmacist identifies patients in whom antimicrobial
consulting firms that are hired by hospitals or other health therapy is suboptimal (i.e., wrong drug, wrong dose,
care institutions to detect inefficiencies in process and to questionable indication, potential for IV-to-oral conver-
improve financial success. sion). After conferral with the infectious diseases physi-
cian, an intervention is recommended or implemented.
These interventions usually follow predefined criteria es-
ICAL PRACTICE SETTl tablished by the Pharmacy and Therapeutics Committee.
Some advantages of this model are the establishment
Hospital Setting of a close relationship between infectious diseases
physicians and pharmacists, the backing of the infectious
Rounding with an infectious diseases diseases service and the Pharmacy and Therapeutics
consult service Committee on interventions, and the potential for
pharmacists to bill for clinical pharmacy services through
Most infectious diseases pharmacists who practice in a a physician provider. Potential disadvantages exist if the
hospital setting round with an infectious diseases consult infectious diseases physician and pharmacist do not
service. This service usually consists of an infectious interact well.
diseases physician, an infectious diseases medical fellow,
medical students, an infectious diseases pharmacist, and Independent practice
(possibly) pharmacy students, residents, or fellows. Pa-
tients are usually identified through infectious diseases Under a third practice model in the hospital setting,
“consults.” The pharmacist usually acts to “optimize” infectious diseases physicians and pharmacists conduct
the antimicrobial regimen by adjusting antibiotic doses separate services: the physician handles infectious di-
472 Infectious Diseases Specialty Pharmacy Practice
seases consults, and the infectious diseases pharmacist the spectrum of therapy based on culture and suscept-
identifies patients with inappropriate antimicrobial ther- ibility report^)'^-^] and intravenous-to-oral conversion of
apy and makes interventions. Under this system, the antibiotics[73s1have shown that interventions by pharma-
Pharmacy and Therapeutics Committee will ideally grant cists can reduce costs and lengths of stay without ad-
the pharmacist some authority to automatically order versely effecting quality of patient care. However, more
modifications in therapy. This model is used when research and publications are necessary to fully docu-
infectious diseases physicians are either unwilling or ment the beneficial impact of infectious diseases phar-
unable to become involved in interventions concerning macist interventions.
antimicrobial therapy. A potential disadvantage is the
perceived “competition” between infectious diseases
physicians and pharmacists for consults. Indeed, the In- MATERIALS USED BY INFECTIOUS
fectious Diseases Society of America (IDSA) has issued a
statement condemning the independent practice of a
Journals
pharmacist to advise physicians on selection of anti-
microbial therapy.[21 In hospitals that have limited or no
A number of published journals specifically directed
infectious diseases physician presence, this model may be
toward infectious diseases and antimicrobial therapy are
the only viable option.
available as resources for infectious diseases pharmacists:
utpatient Settin
Clinical Infectious Diseases-This journal, formerly
As mentioned previously, some infectious diseases named Reviews of Infectious Diseases, is an official
pharmacists have established effective clinical practices publication of the IDSA. Articles are primarily directed
in the outpatient setting. The most common example of at the diagnosis and treatment of infectious diseases,
this is the presence of a pharmacist in an HIV clinic. The including clinical trials. Frequently, “State of the Art”
myriad of antimicrobial drug interactions and adverse articles are published that summarize current therapy of
effects associated with antiretroviral therapy, the need to a particular infection. In addition, IDSA guidelines for
periodically assess antiretroviral efficacy, and the con- the treatment of infectious diseases are published in
siderable potential for noncompliance literally necessitate this journal.
the need for a pharmacist in any established HIV clinic.
Infectious diseases pharmacists work with infectious The Journal of Infectious Diseases-This journal is also
diseases andlor immunology physicians. Pharmacists con- published by IDSA. The contents of this journal are
duct medication histories and answer drug information generally directed at the cellular mechanisms of patho-
questions. In some settings, they may act under protocol genesis and immunity of infection. From a pharmacist
to assess patient response to antiretroviral therapy based practitioner standpoint, it is of less usefulness than
on virologic and immunologic measures, and to make Clinical Infectious Diseases.
appropriate modifications in therapy.
Antimicrobial Agents and Chemotherapy-One of the
official journals of the American Society for Microbio-
ECT ISEASES logy, this journal focuses on characterizing and quan-
ON T CARE tifying the activity of antimicrobial agents against va-
rious pathogens. Many papers are directed at mechanisms
The original published reports of the impact of infectious for antimicrobial resistance and activity of newer anti-
diseases pharmacists’ interventions on patient outcomes microbials in vitro. Studies of the efficacy of antimic-
were limited to therapeutic drug monitoring of aminogly- robials, as measured via in vitro pharmacokinetic and
cosides. Therapeutic drug monitoring of aminoglycosides animal infection models, are published frequently. Stu-
by pharmacists resulted in more appropriate utilization of dies of drug treatment in humans are also published, but
serum aminoglycoside concentrations, more serum con- less frequently.
centrations within the therapeutic range, and reduced
nephrotoxicity when compared with monitoring by phy- Journal of Antimicrobial Chemotherapy-This British
sicians (Destache et al.).[31 publication addresses all aspects of infectious diseases
Subsequent reports of the impact of interventions by pharmacotherapy and therapeutics. Both American and
infectious diseases pharmacists have focused more on European authors contribute to this journal. A review
improving the antimicrobial therapy process. Specif- article at the beginning of each issue addresses a pertinent
ically, reports of “antibiotic streamlining’’ (narrowing clinical issue. Supplements are published regularly that
Infectious Diseases Specialty Pharmacy Practice 473
focus on new antimicrobial agents. More so than other the text, it is well written and is a useful resource for those
journals, this journal regularly addresses pharmacoki- looking for information on antimicrobial pharmacoki-
neticlpharmacodynamic issues. Although it is very pop- netics, interactions, and adverse effects.
ular, it occasionally suffers from lack of relevance, in that
position papers are usually European rather than Amer- Kucers, Crowe, Grayson, and Hoy, eds., The Use of
ican organizations. Antibiotics (Butterworth-Heinemann, Oxford, 1997)-
“Kucers” remains the standard as a reference text for
Infectious Diseases Clinics of North America-This antimicrobial pharmacology. Arranged by drug classes,
quarterly, hardbound journal focuses on a single infec- this text describes the clinical pharmacology of all known
tious disease topic in each issue. Experts in the field of antimicrobials, and has the advantage of its long
infectious diseases author state-of-the-art articles that publication history to include “classic” references in
are useful for review or for teaching purposes. Although antimicrobial pharmacokinetics, adverse effects, and
the articles usually do not present breaking informa- interactions. Because of the evolving nature of anti-
tion, they are useful in defining current practice in infect- microbial resistance, the sections on in vitro activity are
ious diseases. often dated and of limited usefulness when comparing
antibiotics.
Infectious Diseases irz Clinical Practice-This is a very
pragmatic journal with topics that clearly state that this Yu, Merigan, and Barriere, eds., Antimicrobial The-
journal is authored “by practitioners, for practitioners.” rapy and Vaccines (Williams and Wilkins, Baltimore,
Although it is not currently referenced in MEDLINE, 1998)-This text, first published in 1998, is a laudable
this journal offers special insights into practice-rela- attempt to create a comprehensive reference of patho-
ted issues that are authored by eminent infectious di- genic organisms and antimicrobials. Unlike Principles
seases practitioners. and Practice of Infectious Diseases, the text does not
specifically address infectious diseases syndromes.
Journal of Infectious Diseases Phaiwzacotherapy-This Approximately half of the chapter authors are infectious
journal, still in its infancy, is the first attempt by clinical diseases pharmacists. Chapters are addressed by patho-
pharmacy practitioners to author a journal devoted en- gen and by corresponding therapeutic agent(s). They are
tirely to infectious diseases pharmacotherapy. It is also relatively short but extremely well referenced and
not referenced in MEDLINE. Although it has suffered clinically relevant. Each chapter devoted to a pathogen
from “identity crisis,” the articles are excellent. well is divided into sections on general description, micro-
referenced, and pertinent to current practice. Hopefully, biology. susceptibility, and treatment of infections
this journal will continue to grow in stature over the next caused by that pathogen. Chapters on antimicrobial
few years. agents are divided into sections on chemistry, antimi-
crobial activity, pharmacodynamics, pharmacokinetics,
In addition to those described here, a number of and adverse effects. Overall, this is a very useful text.
journals devoted to internal medicine andlor pharmaco- Hopefully, it will continue to a second (and subsequent)
logy topics will from time to time publish articles con- edition.
cerning infectious diseases. They are not discussed further
in this article.
Guidelines
Infectious Diseases Society of America (IDSA)-The Society of Infectious Diseases Pharmacists (SIDP)-
IDSA is the single most common source of guidelines for SIDP, formed in 1990, is the only organization entirely
treatment of infectious diseases in the United States. devoted to practice and research by infectious diseases
These guidelines are created largely on an ad hoc basis pharmacists. Currently, more than 400 infectious diseases
and are published in Clinical Infectious Diseases. pharmacists are members of SIDP. An elected Board of
Examples of such guidelines include treatment of com- Directors and active standing committees conduct the
munity-acquired pneumonia, urinary tract infections, and majority of SIDP’s business. SIDP provides grants to
febrile neutropenia. Unfortunately, no systematic process members to conduct research, and also awards funds to
for generating and routinely updating these guidelines support three infectious diseases residencies annually.
appears to be in place. SIDP also cosponsors two to three educational symposia
with other societies each year.
Centers f o r Disease Control and Prevention (CDC)- A 1-day annual meeting is held in conjunction with
The CDC has begun to exert itself in the area of treatment ICAAC (see below). In addition, members receive a
guidelines for infectious diseases.[’] Well known for their quarterly newsletter and may visit SIDP’s web site
reports and recommendations that are published in (www .sidp.org).
Morbidity and Mortality Weekly Report, the CDC has
now also issued guidelines for treatment of community- Interscience Conference f o r Antimicrobial Agents and
acquired pneumonia. Although these guidelines are Chemotherapy (1CAAC)-The annual meeting, sponsored
generally more conservative than those issued by other by the American Society for Microbiology (ASM), is the
groups, they do carry the weight of the CDC and the U.S. largest meeting devoted to infectious diseases in the
government. Hopefully, the issuance of guidelines by the world. Infectious diseases physicians and pharmacists, as
CDC will continue. well as microbiologists and infection control practitioners,
comprise the majority of ICAAC attendees. More than
American Thoracic Society (ATSj-The ATS has 15,000 people gather at ICAAC to review the most recent
issued guidelines for the treatment of community- and research on antimicrobials and attend state-of-the-art
hospital-acquired pneumonia. These guidelines have also symposia. The sheer volume of information presented at
proven valuable as a reference point for clinicians want to this meeting makes time management a priority. Numer-
establish treatment guidelines in their own institution. ous infectious diseases pharmacists attend this meeting
Although ATS guidelines carry considerable political every year and are able to network over the 4-day meeting.
influence, they are typically more consensus driven than
evidence based in nature. Infectious Diseases Society of America (IDSA)-IDSA
is an organization primarily composed of infectious
Other organizations-Other organizations may occa- diseases physicians. However, more than 50 infectious
sionally publish guidelines for the use of antimicrobials in diseases pharmacists are members of IDSA. Topics at
selected clinical settings. For example, the American IDSA’s annual meeting parallel the content of their two
Society of Health-System Pharmacists published guide- journals, Journal of Infectious Diseases and Clinical
lines for surgical and nonsurgical prophylaxis in 1999. Infectious Diseases, and include cellular and biochemical
When such guidelines are published, most infectious mechanisms of infectious diseases, and the epidemiology,
diseases pharmacists will obtain them and use them as a diagnosis, and management of infectious diseases. The
resource. However, the sporadic publication of guidelines limited presence of infectious diseases pharmacists at
from these sources means that practitioners are often left IDSA makes networking more difficult.
without specific guidance in many therapeutic areas.
International Society of Antiinfective Pharmacology
(ISAPj-ISAP is a small but influential organization of
ET infectious diseases physicians and pharmacologists whose
focus is infectious diseases pharmacokineticslpharmaco-
dynamics. The society is truly international in scope, with
members from the United States, Canada, and Europe.
ISAP’s 1-day annual meeting is held immediately after
A number of professional societies exist that are either ICAAC and consists of state-of-the-art lectures on current
entirely devoted to infectious diseases or support subgroups concepts in antimicrobial pharmacodynamics. The timing
directed toward infectious diseases. Infectious diseases of the ISAP meeting and its relatively “low profile” limit
pharmacists are active members of all the organizations. the number of infectious diseases pharmacists that attend
Infectious Diseases Specialty Pharmacy Practice 475
this meeting, but those who do attend remain avid sup- troviral agents and combinations are presented, in
porters of ISAP. addition to presentations outlining the best means for
caring for these patients. Unfortunately, infectious di-
American College of Clinical Pharmacy (ACCP)-The seases pharmacists currently are not fully ‘‘recognized’’
ACCP is an organization devoted to the promotion of at this meeting, and problems with registration have
clinical pharmacy practice and research. ACCP holds two occurred. Many other pharmacist societies are lobbying to
meetings annually. The content of material presented at correct this problem.
these meetings spans the scope of clinical pharmacy
practice. However, ACCP has created specialized practice industry C~nsultantsh~ps
and research networks (PRNs), one of which focuses on
infectious diseases. For an additional $10, an ACCP From time to time, infectious diseases pharmacists are
member can join a PRN. PRN members hold business and invited to serve as consultants at small meetings held by
scientific sessions at ACCP meetings, which allows for pharmaceutical manufacturers. Typically, 6 to 12 con-
networking among members. ACCP also supports PRN sultants are invited to give their opinions about the
listservs on its web site. Finally, ACCP supports a per- likelihood of success of a new antimicrobial, or to suggest
sonnel placement service at its fall meeting, where mem- new marketing or research strategies. These meetings
bers can recruit residents and fellows. serve an additional purpose in that they allow an ad-
ditional opportunity for interaction and networking be-
International Conference of Chemotherapy (ICC)- tween the pharmacists in attendance.
The ICC is a biannual conference that is similar in size
and scope to ICAAC, but is usually held outside the
United States. Although the content is excellent, the
travel, registration, and housing expenses make this
meeting cost prohibitive for most American infectious
1. Board of Pharmaceutical Specialties. Statement #9903, Ad-
diseases pharmacists. Those who do attend enjoy the
ded Qualifications for Infectious Diseases; March 6, 1999.
opportunity to interact with practitioners and researchers 2. Infectious Diseases Society of America Hospital pharma-
from around the globe. cists and infectious diseases specialists. Clin. Infect. Dis.
1997, 25. 802.
International Conference on Macrolides, Azalides, 3. Destache. C.J.: Meyer, S.K.; Bittner, M.J.; Hermann, K.G.
Streptogramins, and Ketolides (ICMASK0)-ICMASKO Impact of a clinical pharmacokinetic service on patients
is a biannual conference that is attended primarily by treated with aminoglycosides: A cost-benefit analysis.
infectious diseases researchers who present their research Ther. Drug Monk 1990, 12, 419-426.
on macrolides, azalides, streptogramins, and ketolides. 4. Gentry, C.A.; Greenfield, R.A.; Slater, L.N.; Wack, W.;
This is a relatively small, intimate meeting that allows for Huycke, M.M. Outcomes of an antimicrobial teaching
networking for those in attendance. program in a teaching hospital. Am. J. Health-Syst. Pharm.
2000, 57. 268-274.
5 . Berman, J.R.; Zaran, F.K.; Rybak. M.J. Pharmacy-based
American Society of Health-System Plzarmacists antimicrobial monitoring service. Am. J. Hosp. Pharm.
(ASHP) Midyear Clinical Meeting-ASHP’ s midyear 1992, 49, 1701-1706.
clinical meeting is one of the largest annual meetings of 6. Briceland, L.L.; Lesar, T.S.; Lomaestro, B.M.; Lombardi,
pharmacists in the world. The scope of topics presented at T.P.; Gailey, R.A.; Kowalski, S.F. Streamlining antimi-
the meeting is very diverse, ranging from clinical topics to crobial therapy through pharmacists’ review of order
reimbursement issues. No specific subgroup of pharma- sheets. Am. J. Hosp. Pharm. 1989, 46. 1376-1380.
cists devoted to infectious diseases exists within the 7. Paladino, J.A.; Sperry, H.E.; Backes, J.M.; Gelber, J.A.;
ASHP. However, numerous infectious diseases satellite Serrianne, D.J.; Cumbo, T.J.; Schentag, J.J. Clinical and
symposia and research papers are presented during the economic evaluation of oral ciprofloxacin after an ab-
meeting. Many infectious diseases pharmacists use this breviared course of intravenous antibiotics. Am. J. Med.
1991, 91, 460-472.
meeting to recruit residents and fellows.
8. Ramirez, J.A.; Vargas, S.; Ritter, 6 . : Brier, M.E.; Wright,
A,; Smith. S.; Newman, D.; Burke, J.: Mushtaq, M.; Huang,
International Conference on Retroviruses-The Inter- A. Early switch from intravenous to oral antibiotics and
national Conference on Retroviruses focuses specifically early hospital discharge: A prospective observational study
on the treatment of patients with HIV infection. This of 200 consecutive patients with comminuty-acquired
conference attracts pharmacists who care for these pneumonia. Arch. Intern. Med. 1999, 159, 2449-2454.
patients. A variety of papers dealing with new antire- 9. www.cdc.gov.
PROFESSIONAL ORGANIZATIONS
I CTI
The Institute for Safe Medication Practices (ISMP) is a ISMP’s work, which focuses primarily on improving the
nonprofit organization devoted entirely to safe medication safety of medication distribution and use, naming, pack-
use and to the prevention of medication errors. A broad- aging, and labeling, falls into five key areas. These areas
based and interdisciplinary organization, ISMP aims to are knowledge, analysis, education, cooperation, and com-
provide impartial, timely, and accurate medication safety munication. All efforts are built on a non-punitive ap-
information at all times. As an independent watchdog proach and systems-based solutions.
organization, ISMP receives no advertising revenues and
depends entirely on volunteer efforts, educational project,
grants, and donations to pursue its work. ISMP’s work has
been acknowledged and honored by a number of orga- itiat ives
nizations worldwide. For example, in 2000 ISMP received
e Independent review of all errors reported to the USP-
the prestigious Award of Honor from the American Hos-
ISMP Medication Errors Reporting Program (MERP)
pital Association (AHA). In addition, in 1998 the Institute
and acting partner in the FDA’s MedWatch Program.
received the highly regarded Pinnacle Award from the
a Comprehensive collectiodanalysis of error information
American Pharmaceutical Association (APhA) and the
through the organization’s global information-sharing
Healthcare Quality Alliance (HQA).
network.
e Original and impartial research and practitioner sur-
veys on medication errors and prevention.
To continually expand knowledge about medication Comprehensive use of failure mode and effects ana-
errors and prevention methods through system analysis lysis (FMEA) to learn where or when errors are most
in an interdisciplinary and cooperative manner. likely to occur and to help prevent them.
To collaboratively develop and implement effective A thorough review process, using an innovative com-
error-prevention strategies to reduce the risk of medi- puter software program, to study and prevent product
cation errors. name- and packaging-related errors.
To educate healthcare policymakers about legisla- Site visits and confidential consultations in various
tive and regulatory steps that can help prevent medica- healthcare delivery settings and throughout the health-
tion errors. care industry.
To communicate broadly and to educate healthcare A wholly owned subsidiary called Medical Error Re-
professionals and the public about the nature of me- cognition and Revision Strategies (Med-E.R.R.S.@)>
dication errors, how to prevent them, and how to man- which works confidentially with pharmaceutical com-
age errors that do occur. panies to predict error potential and thereby avoid
To provide professional support for healthcare practi- problems that might stem from proposed drug names,
tioners in preventing and handling medication errors. labels, and packaging.
ISMP provides the Sollowing products and services that ISMP Medication Safety Alert!-the nation’s only
are targeted to healthcare professionals, pharmaceutical biweekly. .publication that reaches nearly every U.S.
industry, insurance industry, and regulatory agencies: hospital and tens of thousands of healthcare professio-
nal with warnings about medication errors and prac-
Slidc programs, CD-ROMs, posters, books, and vi- tical prevention strategies.
deotapes on mcdicaiion safety including such topics as Special electronic and dircct mail hazard warnings
Failure Mode and Effects Analysis (FMEA); timely targeted to healthcare professionals.
and accurate educational sessions and conferences, Scholarly and practical articles and continuing edu-
slide programs, and presentations. cation columns that reach practitioners in virtually
Knowledgeable and articulatc speakers including nur- every healthcare field.
ses, pharmacists, and physicians. Wcb site with timely and accurate information on er-
Frcc, Web-based access to archived issues of the bi- rors and prevention recommendations for healthcare
weekly ISMI’ Medication Sufety Alert! newsletter. professionals and consumers.
Safe Medication Managemcnt Fellowship that pro- Media relations campaigns that reach millions of
vides postgraduate training to healthcare practitioners hcalthcare professionals and the public evcry month
in safe medication management. by placing crror-prevention information in healthcare
publications and with the nation’s most prestigious
news organizaiions.
Official partnership in the U.S. Food and Drug Contact I ~ ~ Q rMartin ~ ~S. tGoldstein,
~ ~ ~ Director
: of
Administration’s (FDA) MedWatch program. Program Development, Institute for Safe Medication
Collaborative work toward error prevention with the Practices, 1800 Ryberry Road, Huntingdon Valley, PA
American Hospital Association (AHA), the Joint Com- 19006, 2 15.947.7797, mgoldstein @ isrnp.org.
mission on Accrcditation of Healthcare Organizations
(JCAHO), the National Coordinating council on Mcdi-
cation Error Reporting and Prevcntion (NCCMERP),
the National Patient Safety Foundation (NPSF), the
United States Pharmacopeia (USP), and dozens of
othcr consumer and professional organizations. Institute for Safe Medication Practiccs; www.Ismp.org.
Highly effective educational efforts with legislative ISMP, Medicatian Safety Alert! Huntington Valley, Penn-
and regulatory bodies to improve the safety of sylvania.
medication use.
PROFESSIONAL ORGANIZATIONS
st
Maria-JosC Otero
Alfonso Dominguez-Gil
Hospital Universitario de Salamanca, Salamanca, Spain
misintcrpretatioii of handwritten orders, errors in pre- The education and dissemination of information is
scribing and monitoring, or errors in drug administration. another primary ob.jective of TSMP-Spain: If everyone
ISMP-Spain carcfully reviews and analyzes all re- understands the nature and causes of medication errors,
ported errors, and depending on the characteristics, sends there is a much greater possibility of improving patient
a copy of the report to the Spanish Medicines Agency safety. In this sense, TSMP-Spain makes educational
(AEM) and to thc pharmaceutical companies whose prcscntations and holds conferences at healthcare pro-
products are mentioned in the reports. This information fessional meetings to provide information about adverse
is also shared with the IS drug events. ISMP-Spain also publishes opinion articles
ISMP-Spain publishes information about submitted and practical articles in Spanish healthcare journals in
reports on their wcb site www.usal.cs/ismp and includes an effort to broadly disseminate a culture of safety and
safety recommendations designed to help reduce the pro- error prevention.
bability of such errors recurring. The goal is to make this Another important goal of ISMP-Spain is to encou-
information readily availablc to healthcare profcssionals. rage the development of local medication error reporting
and analysis systems in individual healthcare organiza-
tions. TSMP-Spain has coordinated a project with the
Spanish Society of Hospital Pharmacy to creatc a standard
terminology and cl ification system of medication
It is the belief of TSMP-Spain that the first step in the errors so that healthcare organizations can design da-
long road to reducing adversc drug events is getting tabascs and analyze medication error reports using the
everyone to recognize this problem and t o become same system.
committed to combating it. To achieve this goal it will
ry to effectively quantify the extent and cost of
this problem on a national basis. Thc next step would then UT
be to identify solutions appropriatc for the Spanish
healthcare system, solutions that will lead to the re- TSMP-Spain believes in the importance of coordinating
cation errors. For this reason: a key ini- efforts to enhance patient safety in countries all over the
, Spain is to carry out and to promote world. It is open to the creation of a work platform in
rcscarch on the incidcnce, nature, and cause of adverse Europe and also to cooperating with Spanish-speaking
drug cvents in diffcrcnt settings, as well as their impact countries with any initiatives they may undertake to
on patients and healthcare costs. This effort will compile improve their medication systems.
important reference material to help improve safety in
Spanish healthcare.
Institute o f Medicine, Washington, District o f Columbia, U.S.A.
INT
The Institute of Medicine (TOM) was chartered by the The Institute’s portfolio of activities is extensive, ranging
National Academy of Sciences in 1970 “to improve the from issues of scientific integrity to the future of specific
health of the American people and peoples of the world” areas of health sciences research. The Institute has
by advancing the health sciences and by providing undertaken studies on the processes of innovation, in-
analysis of important issues in health and health policy cluding new drug, vaccine, and biologics development.
for government, the professions, and the public and Its Roundtable for the Development of Drugs and
private sectors. The Institute is an independent, non- Vaccines Against AIDS was an important example of
governmental organization. It carries out its work largely IOM’s ability to convene disparate opinions around im-
through committees of pro bono experts who employ an portant issues. In this case, the roundtable included re-
evidence-based deliberative process to produce scientif- presentatives of the National Institutes of Health, the
ically valid nonpartisan reports. Studies originate in se- Food and Drug Administration, the pharmaceutical in-
veral ways: by Congress mandating that an Executive dustry, AIDS activists, and other interested parties. Other
Branch agency contract with the IOM; by direct request of roundtables have considered such issues as the devel-
Executive Branch agencies, foundations, or other private opment of drugs for new and emerging infections, an-
organizations; or as self-initiated projects when the tibiotic resistance, and the development of biologics
Institute determines that an important or highly sensitive and devices.
issue might not be the subject of a request from an outside The Institute’s studies have had a profound effect on
organization. In addition to committee studies, IOM plays public health. The range of topics that have been the
a unique convening role by sponsoring workshops, round- subject of TOM studies is wide and varied. Some exam-
tables, symposiums, forums, and other activities that ples follow:
enable parties on all sides of an issue to come together
and discuss problems and solutions in a neutral, un- In addition to recommending priorities for new vaccine
biased setting. development, IOM committees have also provided
The Institute also has an honorific function. Each year analysis and advice regarding complications associated
it elects 60 regular members, five senior members, and with vaccines, barriers to immunization, immunization
five foreign associates. Elected members include distin- finance, and appropriate uses of vaccines.
guished individuals whose expertise and leadership cover An IOM committee examined the role of women in
the broad range of biomedical sciences, public health, clinical trials-a complicated issue involving scien-
nutrition, environmental sciences, and social and com- tists, industry, and ethicists who evaluated the par-
munity medicine, as well as pharmacy, the development ticipation of women, particularly women of child-
of new drugs and biologics, and vaccine and drug safety. bearing age, in drug trials.
The Institute’s charter stipulates that at least one-quarter The 1999 report entitled To Err is Human: Building a
of IOM members be from professions other than those Safer Health Care System emphasized that medication
primarily concerned with medicine and health. Thus, the errors were an important contributor to morbidity and
membership includes leading ethicists, economists, and mortality. Yet this committee also noted that the
social and behavioral scientists, among others. elimination of such errors will require a comprehen-
sive systematic approach involving physicians, nurses, regard to this issue and also focused on the devel-
hospitals, pharmacists, patients, and others in health opment of antibiotic-resistant organisms. It has been
care working together. Better information technology, followed by a number of efforts in both public and
computerized data entry, and nonpunitive reporting of private sectors to respond to these threats.
near misses were a few of the elements recommended The Institute is also responsible for establishing “diet-
as an approach to accomplish this goal. ary reference intakes”-quantitative estimates of nu-
Substance abuse has been the subject of several IOM trient intakes to be used for planning and assessing
studies, which have covered a whole host of issues diets for healthy people-which update and replace the
related to the topic, including federal regulation of recommended dietary allowances.
methadone treatment, the development of medications The 1986 report Confronting AIDS: Direction f o r
for the treatment of opiate and cocaine additions, and Public Health, Health Care, and Research was an
community-based research to find better ways to treat IOM-initiated project that addressed seriously what
people who abuse drugs. had been to that time a largely ignored epidemic.
Fluid replacement has been examined both in relation Subsequent reports have addressed needle exchange,
to conditions such as heat stress and when used to the behavioral and mental health aspects of HIV in-
resuscitate and treat combat casualties and civilian fection and AIDS, and the prevention of perinatal
injuries. transmission of HIV. The most recent IOM report
The FDA Advisory Committee process and other FDA on the subject, No Time to Lose: Getting More from
roles and functions have been the subject of IOM stu- HIV Prevention, provides a comprehensive review of
dies that have led to significant changes in the agen- current HIV-prevention efforts in the United States,
cy’s function. In one important study, Halcion: A n as well as a framework for future activities.
Independent Assessment of Safety and Efficacy Data, Several studies have focused on environmental issues,
an IOM committee addressed the difficult problem of including the concept of environmental justice, en-
the criteria and procedures for withdrawing a pre- vironmental and occupational education and training
viously approved drug from the market. in medicine and nursing, and the role of environmental
In 1997, the report Pharmacokinetics and Drug In- factors in illness (e.g., asthma).
teractions in the Elderly and Special Issues in Elderly Among the reports issued by the Institute on tobacco
African-American Populations considered the special and tobacco control, the 1994 report, Growing Up
challenges confronted by proper use of agents in these Tobacco Free: Preventing Nicotine Addiction in
groups. Children and Youths, was particularly influential in
A landmark 1988 report, The Future of Public Health establishing national policy.
(soon to be updated), identified many of the critical The Institute also conducts a significant program in
challenges to education, practice, and applications of international health, including efforts to control he-
public health. In 1998, the Institute helped develop the patitis and diarrheal diseases in the Middle East, that
prototype leading indicators for “Healthy People are being conducted through collaborations involving
2010,” the nation’s blueprint for prevention. The im- American, Israeli, Egyptian, and Palestinian scientists.
portance of community organization and partnerships More recently, Jordan has joined the academies from
in furthering the public health has been underscored by these countries in addressing problems of water con-
a number of other Institute reports. servation and micronutrients in the region.
A series of studies on health and behavior and the role
of the social and behavioral sciences in health have The full text of Institute of Medicine publications is
had important implications for public health, as well as available on-line at the National Academy Press’ web site,
for other aspects of medicine. The 1992 report Emerg- www.nap.edu. Additional information about the Institute
ing Infections: Microbial Threats to Health in the and its activities, as well as a list of all publications, can
United States was among the earliest warnings with be found at www.iom.edu.
PHARMACY PRACTICE ISSUES
CAM practitioners spend far more time with their patients disease. Other tools that are available to the integrative
than conventional practitioners, listening attentively and medicine practitioner include hypnosis, guided imagery,
attempting to truly understand what the patient wants and TCM, Ayurvedic medicine, homeopathy, osteopathy,
who they are as an individual.[*l] A patient can thus leave chiropractic treatments, and a host of others. Discussion
a session with a feeling of empowerment and a belief that of such complex systems is beyond the scope of this
they can be well again. article. [251
The actual foundation upon which the integrative mo-
del rests is the creation of a deeply respectful and un-
DEW derstanding relationship between patient and practitio-
ner.[’l 261 The practitioner recognizes that they are merely
The basic tenet of integrative medicine is that it neither the means by which patients can discover, or actually
rejects conventional medicine nor uncritically accepts rediscover, their innate capacity to restore health. This
CAM.“] Just as various alternative practices are as yet process begins with asking open-ended questions and
unproven and some do carry significant risk, practitioners listening patiently to the answers with a nonjudgmental
of integrative medicine recognize that it is also important attitude.1211 Patients are allowed to make choices about
to be just as analytical of conventional medicine. For therapies or lifestyle changes that are consistent with their
example, the fact that adverse reactions to prescription values and philosophical beliefs, which reconfirms one of
medications represent between the fourth to sixth leading the primary reasons they are using CAM.[17.261 Medical
cause of inpatient deaths came as a shock to many in the decision making is shared rather than dictated by inform-
healthcare field.12’] An Institute of Medicine survey found ing the patient of all possible alternatives, whether con-
iatrogenic illnesses to be the eighth leading cause of ventional or CAM. This requires that the practitioner
death, exceeding the deaths attributable to motor vehicle becomes knowledgeable about a wide array of potential
accidents, breast cancer, and acquired immunodeficiency interventions that may be useful to their patient, as well as
syndrome.[233241 Consequently, in weighing the risks in- which interventions should be avoided.[261
herent to any therapy, conventional or CAM, the integ- Essential to a partnership in medical decision making
rative practitioner seeks the least invasive, least toxic, and is the necessity that each patient realigns his or her own
least costly interventions whenever possible. approach toward health and the healthcare system. Cur-
Another cornerstone of the integrative model is the rently, our Western culture advertises and promotes poor
assertion that healing optimally occurs when all factors choices in lifestyle that ultimately result in burgeoning
that influence health, as well as illness, are addressed. healthcare expenditures. Fundamental to this new pa-
Beyond the patient’s physical condition lie the mental, radigm of healthcare is the requirement that individuals
emotional, and spiritual influences on quality and du- take responsibility for their own wellness, making healthy
ration of life.L232o1Sir William Osler is quoted as saying, choices concerning nutrition, physical activity, and res-
“It is more important to know what sort of patient has a ponse to stressful situations.
disease than what sort of disease a patient has.’”21 Whe- Finally, it is recognized that to ensure patient trust
ther searching for relief from illness or for promotion of and compliance, health professionals must develop and
health, patients choosing the integrative model are of- model a healthy lifestyle for themselves. To this end,
fered more tools than just drugs or surgery.“] The most integrative practitioners are encouraged to examine
common recommendations made are modification in diet and remedy the indoctrination of the current system
and increase in level of physical activity. Stress reduction that rewards the overworked, driven, and harried health-
techniques (e.g., biofeedback, yoga, tai chi) are encour- care professional.
aged to be used in place of negative coping activities As part of the analysis and critique of both CAM and
(e.g., tobacco, alcohol, recreational drugs) during difficult conventional modalities, integrative medicine practitio-
times. Positive coping skills can also be based in spiritual ners search for accurate information in texts, primary
practices such as prayer, church attendance, meditation, literature, and the Internet to counsel their patients on the
or even such common activities as nature walks. Com- relative efficacy, safety, and appropriate use of these the-
munity involvement including volunteer work can also rapies. To ensure validity of research findings, it is be-
help to increase an individual’s positive outlook. These coming increasingly evident that other methodologies, in
cornerstones of a healthy life (good nutrition, physical addition to the randomized controlled trial, need to be
activity, and stress reduction) are considered the primary conceived and completed to fully evaluate these uncon-
means by which illness can be both prevented and treated. ventional therapies as well as the integrative medical
Health, therefore, becomes more than just the absence of model itself.
484 Integrative Medicine
Research methodologies must be developed that allow for 2. Maizes, V.; Caspi, 0. The principles and challenges
studying systems as a whole (e.g., using systems theory or of integrative medicine. West J. Med. 1999, 171 (3),
multidimensional outcome measures) to determine whe- 148-149.
ther component parts are truly synergistic.[321A small step 3. Guerrera, M.P.; Ryan, A.H. Integrative medicine: An old
concept with new meaning. Conn. Med. 1999, 63 (1),
in the right direction has been the creation of four bo-
50-51.
tanical centers by ODS”~’ These centers are charged with
4. Weil, A. The significance of integrative medicine for the
studying the effects of marketed dietary supplements cur- future of medical education. Am. J. Med. 2000, 108 ( 5 ) ,
rently purchased and used by the public, rather than the 441 -443.
reductionistic search for a solitary active principle. 5 . Anonymous. Quackery persists. JAMA, J. Am. Med. Assoc.
Another roadblock on the path to credibility is an ap- 1972, 221 (8), 914.
parent bias on the part of mainstream medical journals 6. Eisenberg, D.M.; Kessler, R.C.; Foster, C.; Norlock, F.E.;
when reviewing research or position papers on CAM or Calkins, D.R.; Delbanco, T.L. Unconventional medicine
integrative medicine. Journals may appear to be more in the United States: Prevalence, costs, and patterns of use.
willing to publish negative results for CAM modalities N. Engl. J. Med. 1993, 328 (4), 246-252.
than those that indicate a positive outcome.[331Although 7 . Eisenberg, D.M.; Davis, R.B.; Ettner, S.L.; Appel, S.;
Wilkey, S.; Van Rompay, M.; Kessler, R.C. Trends in
editors insist that the review process is objective, it may
alternative medicine use in the United States, 1990- 1997:
be that the bar is set higher for CAM, and such bias has
Results of a follow-up national survey. JAMA, J. Am.
been recognized by such authorities as the editors of the Med. Assoc. 1998, 280 (18), 1569-1575.
New England Journal of Medicine.[341As research me- 8. Skolnick, A.A. FDA petitioned to “stop the homeopathy
thodology in the CAM field improves and a biased edi- scam.” JAMA, J. Am. Med. Assoc. 1994, 272 ( 5 ) , 1154-
torial policy is corrected, the system of peer review may 1155.
be more fairly applied to all scholarly submissions. 9. Barrett, S.; Tyler, V.E. Why pharmacists should not sell
homeopathic remedies. Am. J. Health-Syst. Pharm. 1995,
52 (9), 1004-1006.
10. Dalen, J.E. Is Integrative medicine the medicine of the
future? A debate between Arnold S . Relman, MD, and
Andrew Weil, MD. Arch. Intern. Med. 1999. 159 (IS),
2 122-2 126.
Given the current state of healthcare in the United States,
11. Relman, A.S. A trip to stonesville: Andrew Weil, the boom
most efforts by the political, academic, and corporate in alternative medicine and the retreat from science. New
entities have been in the direction of repair of the system Repub. 1998. http://www.tnr.com/archive/l298/l21498/
rather than creation of a new model. The results of these relman 121498.html.
labors have been equivocal at best. A growing number of 12. Dietary Supplement Health and Education Act of 1994
people planning the future of healthcare now envision the (DSHEA). In The Complete German Commission E
need for a totally new system, one that retains the be- Monographs: Therapeutic Guide to Herbal Medicine, 1st
neficial technologies of conventional medicine while Ed.; Blumenthal, M., Ed.; Integrative Medicine Commu-
returning the focus of the profession toward health rather nications: Boston, 1998; 12.
than The result would be a system of health- 13. Nahin, R.L.; Straus, S.E. Research into complementary and
alternative medicine: Problems and potential. BMJ 2001,
care in which the public once again trusts and respects the
322 (7279), 161-164.
healthcare practitioner as an ally, rather than as part of
14. Stem, M. NIH Announces Two Additional Centers for
what often appears to be a mechanistic, profit-driven in- Dietary Supplement Research. Office of Dietaq Sup-
dustry. Integrative medicine as a new medical model may plements; National Institutes of Health, 2000, Sep. 20,
fill the need for a totally new system, such that in the http://www.nih.gov/news/prlsep2000lods-20.htm (ac-
future the term “integrative” will no longer be needed, cessed January 2001).
and we will all simply practice good medicine.r301 15. Boisset, M.; Fitzcharles, M.A. Alternative medicine yse by
rheumatology patients in a universal healthcare setting. J.
Rheumatol. 1994, 21 (l), 148-152.
16. Nam, R.K.; Fleshner, N.; Rakovitch, E.: Klotz, L.;
Trachtenberg, J.; Choo, R.; Morton, 6 . ; Danjoux, C. Pre-
valence and patterns of the use of complementary therapies
1. Gaudet, T.W. Integrative medicine: The evolution of a new among prostate cancer patients: An epidemiological analy-
approach to medicine and to medical education. Integrative sis. J. Urol. 1999, 161 ( 5 ) . 1521-1524.
Med. 1998, 1 (2), 67-73. 17. Astin, J.A. Why patients use alternative medicine: Results
486 Integrative Medicine
of a national study. JAMA, J. Am. Med. Assoc. 1998, 279 27. Gaudet, T.W., Unpublished data, The University of
(19), 1548 1553. Arizona Program in Integrative Medicine.
18. Donnelly, W.J.; Spykerboer, J.E.; Thong, Y.H. Are pa- 28. Berman, B.M. Complementary medicine and medical
tients who use alternative medicine dissatisfied with education. BMJ 2001, 322 (7279), 121 122.
orthodox medicine? Med. J. Aust. 1985, 142 ( l o ) , 29. Rowcll, D.M.; Kroll, D.S. Complementary and alternative
539- 541. medicine education in United States pharmacy schools.
19. Anonymous. What are the Major Types of Complementary Am. J. Pharm. Educ. 1998, 62 (4), 412--419.
and Alternative Medicine:); http://nccam.nih.gov/health/ 30. Rees, L.; Weil, A. Integrated medicine. BMJ 2001, 322
whatiscam/index.htm#4 (accessed July 2002). (7279), 119-120.
20. Kaptchuk, T.J.; Eisenberg, D.M. The persuasive appeal of 31. Tracey, E. Deliver3; cf Comp1ementui-y Medicine Needs
alternative medicine. Ann. Intern. Med. 1998, 129 (12). Improvement; Reuters Health Newsservice: Washington
106 1 1065.
- DC, 2000, December 1 1 .
21. Gianakos, D. Alternative healer. Ann. Intern. Med. 2000, 32. Bell, 1. 2000, Personal Communication, October 18.
133 (7), 559. 33. Ezzo, J.; Berman, B.M.; Vickers, A.J.; Linde, K. Com-
22. Lazarou, J.; Pomeranr. B.H.; Corey, P.N. Incidence of plementary medicine and the Cochrane collaboration.
adverse drug reactions in hospitalized patients: A meta- JAMA, J. Am. Med. Assoc. 1998, 280 ( I X ) , 1628-
analysis of prospective studies. JAMA, J. Am. Med. Assoc. 1630.
1998, 279 (15), 1200 1205. 34. Tye, L. Journals breaks with past: New editor cleans slate
23. To Err is Human: Building a SaJer Health System; Kohn, at medical publication. Boston Globe Online. Archivcs
L.T., Corrigan, J.M., Donaldson, M.S., Eds.; National 2000, September 12.
Academy Press: Washington, D.C., 2000. http://www.nap. 35. Carlson: R.J.; Ellwood, P.M.; Etzioni, A,; Goldbeck, W.B.;
edu/openbook/030906837 l/html/index.html (accessed Gradison, B.; Johnson, K.E.; Ktzhaber, J.; Koop, C.E.;
January 2001). Lee, D.R.; Lewin, L.S.; McNerney, W.J; Ray, R.D.; Riley,
24. Leape, L.L. Institute of Medicine medical error figures are T.; Schmoke. K.L.; Thier, S.O.; Tilson, H.H.; Tuckson,
not exaggerated. JAMA, J. Am. Med. Assoc. 2000, 284 R.V.; Warden, G.L. The Helmont Vision ,for Healthcare in
(1); 95--97. American; Institute for Alternative Futures: Alexandria,
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26. Sugarman, J.; Burk, L. Physician’s ethical obligations ative Approaches (CA4.s) in US Healthcure: Executive
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ASSOC.1998, 280 (18), 1623.- 1625. Virginia, 1998.
PROFESSIONAL RESOURCES
nt stracts (A
Carol Wolfe
American Society of Health-System Pharmacists,
Bethesda, Maryland, U.S.A.
INTRODUCTlO HISTORY
International Pharmaceiitical Abstracts (IPA) is the The inaugural issue of IPA was published in January 1964
official abstracting and indexing service of the American under the leadership of IPA’s founding editor, Donald E.
Society of Health-System Pharmacists. IPA is unique Francke. The seminal concept for IPA was created in
in its international coverage of pharmacy and related 1957 when Dr. Francke established a section called
health journals. “Selected Pharmaceutical Abstracts” in the Bulletin, the
forerunner of the American Journal of Health-System
Pharmacy. Dr. Francke’s early objective for IPA was to
“serve as an alerting service to keep the busy pharmacy
practitioner, professor, researcher, and student keenly
An expert panel selects, abstracts, and indexes the most aware of a wide variety of information to permit him to do
pertinent articles from over 600 journals published a better professional job.”
throughout the world. Translators with pharmacy expert- In late 1966, Dwight R. Tousignaut succeeded Donald
ise review the major pharmacy journals published in Francke as editor of IPA. IPA’s production process was
languages other than English and prepare abstracts in computerized in 1970, and ZPA’s first electronic licensing
English. In addition, ZPA publishes abstracts of meetings arrangement was formalized in 1971 in an agreement to
conducted by the American Society of Health-System supply magnetic tape to the National Library of Medicine
Pharmacists and the American Association of Colleges of for use in its ToxLine database.
Pharmacy. Over 15,000 abstracts per year are added to the The International Pharmaceutical Abstracts (Coden:
IPA database covering the clinical and scientific literature IPMAAH; ISSN: 0020-8264) is published by the Amer-
related to pharmacy, as well as legal aspects, professional ican Society of Health-System Pharmacists twice each
practice issues, and trends in education and research. month, on the 1st and 15th. Its circulation is primarily
IPA’s unique structure supports searching by drug class, electronic. The print and electronic subscription rates
disease state, MeSH heading, generic or trade drug name, are available upon request. Internet access to IPA Pharm-
and chemical registry number. Search is available at $90 per 100 searches. The edi-
Examples of topic areas targeted for coverage are drug torial and subscription offices are located at 7272
evaluations, pharmacology, investigational drugs, tox- Wisconsin Avenue, Bethesda, Maryland 208 14, U.S.A.
icity, therapeutic advances, new technology, herbals, and (Telephone: 301-657-3000, extension 1241; Fax: 301-
adverse drug reactions. Although a printed version of IPA 664-8857; E-mail: ipa@ashp. org; Web site: http://www.
is available from ASHP, use is now primarily electronic. ashp.org; Managing Editor: Victoria Ferretti-Aceto).
Online versions are available by subscription through The first edition of the IPA Thesaurus and Fre-
several database vendors, including Silverplatter, Ovid, quency List was published in 1981. Now in its eighth
Dialog, Cambridge Scientific Abstracts, STN Inter- edition, the Thesaurus provides a controlled vocabulary
national, DataStar, DIMDI, and EBSCO Publishing. designed to support robust searching of pharmaceuti-
Individuals may also economically purchase online cal literature.
search blocks by selecting “IPA PharmSearch” at
www.ashp.org.
C S
Victoria F. Koche
Jan ion Creighton University, Omaha, Nebraska
Joi sio
ealt
Kathryn T. Andrusko-Furphy
Atascadero, California, U.S.A.
hospitals deemed status in the 1960s if they were JCAHO drome epidemic of the late 1980s and early 1990s also
accredited. Organizations who were JCAHO accredited fueled the growth in the home infusion industry. How-
were deemed compliant with the Medicare Conditions of ever, this industry's interest in the home care accredita-
Participation for hospitals. Consequently, today the ma- tion program that started in 1998 stemmed more from
jority of hospital systems must participate in the JCAHO competitive marketing reasons and financial reasons more
accreditation process and adhere to its standards. from the pressures of managed care and other third-party
The long-term care (LTC) accreditation process is payers instead of federal funding. About this time,
actually the second oldest JCAHO program and has been JCAHO changed its name from the Joint Commission
accrediting LTCs since 1966."] More than 2800 orga- on Hospital Accreditation to the Joint Commission on
nizations participate in this program. However, unlike Healthcare Organizations, thus acknowledging the chang-
hospitals, it has not received deemed status to date. Con- ing shape of health care delivery.
sequently, many skilled nursing home facilities continue The home health agency or skilled visiting nurse com-
to not opt for JCAHO accreditation to the same level as ponent of home care also has diverse reasons to seek
hospitals. Instead, they adhere to state licensing require- JCAHO accreditation. JCAHO received deemed status in
ments alone. In the late 1990s, a resurged interest in the 1993 for its Medicare-certified organizations. However,
LTC accreditation process occurred precipitated by man- non-Medicare agencies also exist across the United States.
aged care's interest in JCAHO accreditation. Many man- In fact, not all states require agency licensing. However,
aged care organizations were requiring JCAHO accred- the movement in the last decade has been for states to
itation to service their patient population and LTC beds. require agencies to be licensed. More often, similar mar-
However, the advent of the Prospective Payment System keting and financial motives to attract third-party payers
(PPS) in 1999, fueled by the balanced Budget Act of have also fueled the motivation for non-Medicare home
1996, has more recently left a mixed signal as to the value health agencies to seek JCAHO accreditation. However,
and cost of being JCAHO accredited. the Balanced Budget Act of 1996 has had profound
The home care accreditation program"] is one of the effects on home health agencies and forced the closure
more diverse processes. The reasons for the 6400 orga- and consolidation of agencies as PPS took effect on
nizations to participate in accreditation are actually four October 1, 2000.
separate and distinct submarkets: home infusion pharma- The hospice segment of home care usually has a
ceuticals; home medical equipment; home health, per- federal funding component as well. JCAHO just received
sonal care, and support; and hospice. Collectively, these deemed status in 1999."] Originally, JCAHO had a se-
entities are often referred to as alternate site. That is, parate accreditation program for hospice; however, the
alternate to hospitalization. First, the home infusion or hospice standards have been folded into the home care
home intravenous (IV) segment. As an organized form of standards manual.
health care delivery, home infusion has only been in use Of this diverse segment of health care, home medical
since the early 1980s. Early patients requiring home in- equipment (HME) is probably the most diverse group
fusion services were generally those with chronic disease within this segment. Participants range from HME dealers
in which lifetime hospitalization was not an option (e.g., with little to no clinical expertise providing ambulatory
short gut syndrome requiring parenteral or enteral nu- aids such as wheelchairs, walkers, and intense clinical
trition, hemophiliacs requiring factor VIII). The changes services and equipment, such as clinical respiratory the-
in the Medicare reimbursement structure or diagnosis- rapists providing oxygen, ventilators, and apnea monitors.
related groups (DRGs) in the mid-1980s had only an in- Unlike hospitals and home health care that receive federal
direct impact on the growth in patients serviced in the funds through Medicare part A benefits, HME receives
home care setting because Medicare does not pay for federal payment through Medicare part B benefits. As of
prescription medications, including most IV medications yet, deemed status or the requirement to be JCAHO
in the outpatient or ambulatory setting. Mainly, the accredited has not been a motivating factor for seeking
growth in home infusion occurred due to the financial accreditation in this market. However, there are some
pressures of managed care influences to release patients reports that it may be required in the future. Marketing
more quickly from the hospital when therapies were and financial reasons from third-party payers and man-
considered safe, yet required prolonged use of IV medi- aged care predominantly have been the motivating force
cations. For example, the use of IV antibiotics for the to voluntarily seek JCAHO accreditation. In addition,
treatment of such conditions as osteomyelitis and other other healthcare organizations, such as hospitals and LTC
soft-tissue infections, such as cellulitis or status post- facilities that are JCAHO accredited, require their vendors
surgical infections. The human immunodeficiency syn- to be accredited. This exempts these HME organizations
Joint Commission for the Accreditation of Health-Care Organizations 495
from being included in the hospital, home health, or LTC home care requirements for collecting outcomes data
organization's accreditation process. for ORYX.
With the changes in health care delivery, ambulatory The goal of the JCAHO accreditation process is that
care is also a growing segment of accreditation. Current- it will continue to be standards driven with an increased
ly, more than 1000 centers are accredited. These include emphasis on continuous data. In the last few years, the
ambulatory surgery centers, community health centers, JCAHO accreditation process-in particular, for hospi-
group medical practices, Native American health clinics, tals-has been challenged. Payers continue to challenge
and other specialty centers. In addition, they received the value of the accreditation process cost versus qual-
deemed status in 1996.'31 ity. As health care organizations continue to evolve,
change, and consolidate, so must JCAHO evolve, change,
and consolidate.
ACC R EDIT In 1999, the Board of Commissions established an
Oversight Task Force for the Accreditation Process Im-
When not motivated to participate for involuntary reasons provement (API) Initiative. The purpose is to oversee the
such as the withholding of federal funding, most health continuous improvement in the accreditation process."]
care organizations find the JCAHO accreditation process The resulting changes are intended to enhance the eva-
to be an investment into risk management. Organizations luation of critical patient safety and patient care functions
agree to be measured against national standards set by and to achieve an accreditation process that remains con-
health care professionals. No longer is the accreditation sultative and focused on performance improvement. A
process a set of minimum standards. Once the standards white paper was published outlining a future operational
emphasis were structural in nature. Structural standards model that will continue to build and expand on tech-
assumed that care should be good because the opportunity nology, performance data, presurvey self-assessments, a
existed for such, such as the right physical plant or the fully automated interface with JCAHO, increased sur-
right number of staff. In 1987, the Agenda for Change veyor development, and a more continuous accreditation
was launched. Its emphasis is based on actual organiza- process. Instead of a once every 3 years site visit, two
tional performance and processes performed; that is, is the 18-month site visits would occur that evaluate select
care provided actually safe and quality oriented? Orga- standards. In addition, since health care entities are so
nizations during the last 10 years have had to show that diverse, there is a desire to create a model that is more
the care provided is in fact efficacious, efficient, cost data driven, less predictable, and more customized to an
effective, and safe. JCAHQ has almost gone full circle individual organization.
with Dr. Codman's origin idea, except the current JCAHO
process continues to be standards based, not just outcomes
based. Organizations must show that access to care is
timely, staff is oriented and competent, and sentinel
events and complaints are incorporated into the organiza- www.jcaho.org.
tion's assessment processes. 1999-2000 Comprehensive Accreditation Manual for
However, JCAHQ is also striving for a more con- Home Care. Joint Commission on Accreditation of Health-
tinuous and data-driven process. The precursor to their care Organizations. One Renaissance Boulevard Oakbrook
Terrace, Illinois 6018 1.
ORYX Initiative or outcomes performance measurement
2000-2001 Comprehensive Accreditation Manual for
was the IMS system first launched in 19Wt4] In 1998, Ambulatory Care. Joint Commission on Accreditation of
hospitals and LTC facilities began to participate in the Healthcare Organizations. One Renaissance Boulevard
collection of outcomes data via select clinical measures Oakbrook Terrace, Illinois 6018 1.
and began to submit that data to JCAHO for analysis. ORYX: The Next Evolution in Accreditation. Joint Com-
Home care has followed suit in the year 2000. How- mission on Accreditation of Healthcare Organizations. One
ever, as of this writing, JCAHO is looking to modify its Renaissance Boulevard Oakbrook Terrace, Illinois 6018 1.
PROF ESSlON AL ORGAN IZATlONS
VS (
Robert M. Elenbaas
American College of Clinical Pharmacy,
Kansas City, Missouri, U.S.A.
Diane B. Crutchfiel
Pharmacy Consulting Care, Knoxville, Tennessee, U.S.A.
INTRODUCTlON HISTORY
The role of the clinical pharmacist in long-term care, The concept of consultant pharmacy was first born in the
also called a consultant pharmacist, continues to expand early 1970s with the formation of the American Society of
with the recognition of drug-related problems that af- Consultant Pharmacists (ASCP), which has since also
fect the quality of life of seniors. In addition to the become known as America's Senior Care Pharmacists.
potential adverse outcomes associated with medication- About the same time, the centers for Medicare and Med-
related problems, the cost of these problems is stag- icaid Services (formerly the Health Care Financing Ad-
gering. In fact, the total annual direct medical cost of ministration) recognized the importance of medication
medication-related problems in nursing homes exceeds management for the frail elderly in nursing homes, and in
$7 billion."' 1974, required that all medications for Medicare residents
of nursing homes be reviewed on a monthly basis. In
1987, the requirement was amended so that all Medicare
and Medicaid residents are required to have a monthly
medication review by a pharmacist. In addition to the
Consultant pharmacists closely monitor each nursing need for therapeutic drug monitoring, pharmacists recog-
home resident's medication regimen, monitoring for po- nized the need for unit dose packaging and specialized
tential drug or disease interactions, dosing irregularities delivery services for nursing home residents in an effort to
or side effects, and for medication use that may be con- reduce medication errors and increase the efficiency of
sidered inappropriate for the geriatric resident. This re- the systems.[31
view is multifaceted and takes into account the in- A pharmacy career in long-term care is typically as-
formation provided in the written medical record, as well sociated with the provision of consultant pharmacy ser-
as input from the staff, resident, and family. Various vices to nursing home facilities. More recently, however,
services are provided to the facility (Table 1). Inservice the opportunities for pharmacists in this practice setting
education programs are provided to the nursing staff have expanded far beyond the role of providing medica-
and to family or resident meetings, if requested. Con- tions and medication reviews to only nursing homes.
sultant pharmacists frequently participate on interdiscip-
linary care plan teams that focus on individual resident
needs, such as fall risk assessment, weight loss evalua- Table 1 Types of consultant pharmacist services
tions, or pain management programs. Through ongoing e Drug regimen review
monitoring of quality assurance programs, the consul- e Drug information
tant assists the facility in providing quality improve- * Quality assurance programs
ment for better resident care and in meeting state and e Inservice education programs
federal regulations. * Therapeutic drug monitoring
The success of consultant pharmacists' drug regimen 0 Patient counseling
reviews was reported in the Fleetwood study, which e Pain management
demonstrated that the reviews improved therapeutic e Interdisciplinary care planning
outcomes by 43% and save as much as $3.6 billion 0 Pharmaceutical care planning
e Pharmacokinetic dosing services
annually in costs associated with medication-related
e Drug research programs
problems.[21
Table 2 Job settings for consultant pharmacists tively with physicians, nurses. and other healthcare
providers because the interdisciplinary approach is key
e Nursing facilities (skilledlintermediate care)
e Assisted living facilitieshoard and care homes to providing positive patient outcomes by improving the
e Correctional institutions quality of life for residents in the variety of available long-
e Hospitals (subacuteltransitional care) term care settings. Postgraduate training programs, or
4 Home health agencies short-term clinical rotations, are available in a variety of
4 Industry geriatric-related topics, including dementia, Alzheimer’s
e Mental institutions disease, geropsychiatry, and Parkinson’s disease, through
e Alcohol or drug rehabilitation centers the ASCP Research and Education Foundation.
e Mental retardation facilities
e Community health centers
e Retail pharmacies
e Health maintenance organizations PROFESSIONAL OUTLOOK
e Hospice
e Retirement communities As mentioned previously, careers are not limited to those
e Adult day care serving the elderly who reside in a nursing home. Some
e Physician offices states require consultant pharmacist services in assisted
e Ambulatory care centers living facilities. As the senior population continues to
(From Ref. [l].) grow, so does the need for pharmacists trained specif-
ically in the area of geriatrics.
Within the job settings, consultant pharmacists may be
self-employed or work for a provider pharmacy. Provider
Terms such as consultant pharmacist and senior care
services typically include the operation and management
pharmacist are used interchangeably to describe the type
of the medication distribution system and consultant
of pharmacist, rather than focusing on the physical setting.
services typically refer to the clinical services. Some
In addition to providing services for 1.8 million residents
consultants provide only the consulting services and
in more than 16,000 nursing homes in the United States,
others provide consulting services, in addition to dispens-
consultant pharmacists also provide medications and
ing the medications.
medication reviews for jails and prisons, home health
Innovation has been the key word in the evolution of
agencies. and assisted living facilities, among others
the practice of consultant practice in long-term care
(Table 2 ) . settings. Thus. it will continue to be a key to the future
success of pharmacists willing to step out of the tra-
ditional pharmacy practice settings and provide much
TRAINING AND
needed services to the growing senior population.
CE RTIFIGATION REQUIREMENTS
i
arbara Zarowitz
Henry Ford Health System, Bingham Farms, Michigan, U.S.A.
of pharmacy students interested in a managed care career characteristics, realizing that knowledge related specif-
should pursue external rotations in progressive managed ically to managed care practice can be acquired. Large
care settings. Experience with claims and benefit man- organizations, whether managed care organizations,
agement, formulary management, disease management, HMOs, IDSs, or PBM firms, are often willing to provide
quality certification, and large relational databases is very on-the-job training to advance pharmacists’ skills in man-
important. Pharmacists interested in account management aged care. However, prospective employers may pref-
may benefit from formal training in business administra- erentially select candidates with previous managed care
tion and finance. Table 1 summarizes career opportunities experience, thus underscoring the importance of selecting
that may require advanced training as a prerequisite. elective rotations in managed care settings.
Desirable skills and knowledge are summarized in
Table 2. In addition to academic training, managed care
pharmacists are called to respond to a rapidly changing,
GE
often unstable financial and clinical environment. Indi-
vidual behavioral characteristics that are helpful in these
circumstances may include flexibility and ease of response
Many opportunities exist for career growth in managed
to change, open-mindedness, ‘.pioneerism,” and respect
care practice settings, just as they do in other practice
for the sense of urgency surrounding health care business
environments. New graduates can usually qualify for staff
evolution. Many managed care organizations are willing to
pharmacist careers in benefit design, clinical, data analyst,
hire pharmacists with desirable behavioral and clinical
or case management positions. Advancement can follow
experience at entry-level positions, with or without ad-
vanced skills enhancement through external degrees or
Table 2 Desirable skills, knowledge, and behaviors of clinical training programs. Much of the management of phar-
pharmacists in managed care macy benefits, irrespective of the site of practice, is
science and can be learned didactically. However, a sig-
Problem-solving skills
nificant component of success in a managed care phar-
Exemplary oral and written communication skills
Knowledge of population management and
macy career, like other pharmacy career paths, depends on
pharmacoeconomic principles facility with the art of the application of managed care
Facility with large relational databases and skills, knowledge, and strategies-the so-called “craft’ ’ of
information systems the managed care pharmacist. The development of “craft’ ’
Business and financial expertise skills requires experience through application. which can
Comfort with the measurement science only be learned during practice. Entry-level pharmacists
Solid clinical skills, knowledge, and behaviors may move on to clinical manager or team leader posi-
A sense of urgency tions, or transition into higher business or administra-
Comfort in rapidly changing, unstable environments tive positions.
Motivated by challenge A parallel track is available within PBM companies
Teamwork
for pharmacists with retail pharmacy experience. Phar-
Interpersonal skills
macy network management and contracting have be-
504 Managed Care, Clinical Pharmacy Careers in
come important mechanisms for managing costs and All-Inclusive Care for the
enhancing revenue to health plans and PBMs. Retail
pharmacy experience and business skills are desirable
characteristics for pharmacists desiring advancement in There are several PACE programs across the United States
the more traditional roles of pharmacists within managed that serve as day care and/or home care opportunities for
care organizations. elderly patients, referred to as participants.['] PACE pro-
Board certification and other postgraduate credentials grams offer an alternative to nursing home placement,
may be useful to individuals, depending on their practice enabling frail elderly people to remain independent in their
setting. However, in general, these credentials have not homes within the community. When elders enroll in a
attained widespread acceptance as prerequisites for ad- PACE program, their care becomes the responsibility of
vancement within managed care organizations. The pau- the program. PACE programs are funded through me-
city of qualified individuals to deliver exemplary phar- dicare and medicaid. The PACE program is responsible for
macotherapy services, while balancing business and provision of both drug therapy and medical care. Phar-
financial prerequisites has led to a limited candidate pool macists can serve an important role in optimizing and
for managed care pharmacy positions. Over time, as a simplifying drug therapy, at lowest cost. Given that many
greater number of pharmacists enter and advance in man- of the participants are seniors with multiple concurrent
aged care clinical pharmacy careers, board certification, medications, careful individualization of dose is essential
certificate programs, and association affiliations or recog- to minimize adverse events.
nition may become more important delineators of high-
quality pharmacists. In the interim, it is more important
that pharmacists gain experience in the field and determine Utilization Mana~ement
their compatibility with a career in managed care.
Managed care pharmacists are moving up the ranks Clinical pharmacists have been redeployed in ambulatory
within their organizations. In a survey conducted among managed care settings to work with primary care providers
200 managed care pharmacists in 1997, the five most to enhance both the quality and cost effectiveness of care
frequent job titles were director of pharmacy, regional di- delivered.[3361They are highly integrated within the system
rector of pharmacy, pharmacy manager, vice president of of care delivery. Population management strategies are
pharmacy, and director of pharmaceutical divi~ion.'~' used to identify the high-cost or low-quality providers with
Many clinical pharmacists report directly to vice presi- the greatest need for pharmacy care management. Provider
dents or chief executive officers within their organizations. profiles are used to continuously provide feedback to phy-
sicians, identifying cost-reduction and quality improve-
ment opportunities. Clinical pharmacists can work with
individual physicians or groups, such as a PPO or PHO, to
IES OF CLINICAL ~ H A R M A C Y ensure that the highest quality of care is provided within
PRACTICE IN MANAGE the capitation limits of the plan or group. Improvements in
quality are accomplished through the pharmacists'' role in
Hospice the development of clinical guidelines and pathways,
while helping physicians understand the patients' ' phar-
Hospice services are often offered as part of an IDS or macy benefits. Pharmacists may also work with individual
managed care organization. Typically, when patients and high-risk patients to streamline drug therapy, decrease
their families determine that end-of-life measures are cost, and improve patient medication safety.
indicated, they search for options to make the patient
maximally comfortable, with appropriate care, and at an
affordable cost. Hospice care can be offered as a pur- pecialt~Clinics
chased service or a covered benefit. In most cases, hos-
pice care is capitated and must operate within a budget or In managed care, it is often a small percentage of patients
lose money.[41 Pharmacists practicing in hospice settings (approximately 20%) who are responsible for the majority
may be called on to optimize rational pharmacotherapy of the cost (80%)-often referred to as the 80/20 rule. It
and help to discontinue medications deemed no longer has been shown to be cost effective to manage these high-
necessary for patient comfort. In this regard, the phar- risk patients in specialty clinics or programs. Disease
macist and the rest of the patient's care team are man- management programs offer many patients with specific
aging care within a capitated limit. conditions, enhanced management strategies to improve
Managed Care, Clinical Pharmacy Careers in 505
Beverly L. Black
American Society of Health-System Pharmacists,
Bethesda, Maryland, U.S.A.
health systems. However, unique skpus are necessary Ability to work in teams
for effectiveness in managed care; some of these skills
will require additional training and education. Also, a The pharmacist must understand role definitions, develop
different attitude is essential; for example, pharmacists empathy for other team members, and acquire the skills
must be willing to take risks and accept new respons- necessary to surpass expectations.‘‘I Team relationships
ibilities-oaes that may be unlike those of a traditional are essentially balancing acts that can be upset easily if
position.[51 someone does not understand the practice philosophy or
There are certain skills that clinical and dispensing the role definitions within the team.
positions have in the managed care setting. These in-
clude drug information knowledge, communication and Innovative positions
mediation skills, assertiveness, and the abiIity to work
in teams. Managed care systems offer innovative pharmacy practice
positions in such areas as pharmacoeconomics, disease
Drug ~n~ormation
knowledge state management, outcomes research, wellness program
management, and technology assessment. For individuals
The trends that are occumng in managed care are those willing to expand their pharmacy practice aqd develop
of disease state management, outcomes, welhess pro- new skills, these positions can offer unique opportunities
gram emphasis, technology, and pharmacoeconomics. and growth.
The important role of the pharmacist with regard to drug
information is to assimilate and combine information Care coordinators and clinic coordinators
with other components for use in the decision-making
processes. These include not only patient-specific de- Some organizations have created interdisciplinary round-
cisions, but also formulary decisions, for the entire man- ing teams for inpatient care. The responsibility for
aged population. coordinating the transition from hospital to ambulatory
Pharmacists have the specific background to make the care is delegated to these teams. For example, pharmacists
appropriate recommendations for product selection; how- from the Hh.IO’s home N service attend rounds within the
ever, is no longer the product’s pharmacologic advantage contract hospitals, focusing on monitoring drug therapy
over other medications the only factor in selection. Phar- with respect to quality and cost effectiveness and fa-
macoeconomics and population characteristics, as well as cilitating a smooth transition from hospital to home care.
many other factors, must be considered.[6’ Many MCOs are using pharmacists to influence
Other essential skills for pharmacists in managed care physician prescribing and to conduct clinics promoting
include the following. appropriate use of pharmaceuticals. In addition, these
pharmacists participate in direct patient care activities
Communication and mediation skills that relate to drug therapy, such as ordering and moni-
toring laboratory tests and providing effective patient
Understanding what other healthcare team members are follow-up to ensure patient satisfaction and high-quality
looking for and communicating effectively is vital. As care. Many of the pharmacist-coordinated clinics pro-
pharmacists increase their involvement in direct patient viding this patient care have been shown to improve pa-
care, interacting with patients will require the ability to tient outcomes and satisfaction and to support the
present information in terms that the patient will efficient provision of services from other members of
understand. With respect to being a mediator, the goals the healthcare team.@’
of cost containment must be clearly understood and
accepted by all parties in order for success to be achieved; Disease management and the patient
this responsibility often falls to the pharmacist.
Disease management has been defined as quantifying,
Assertiveness tracking, and controlling the unique set of cost drivers in
any disease and the interactions of these drivers over the
Healthcare and pharmacy are not exempt from market course of the disease across all elements of the healthcare
pressures, and pharmacists must accept the fact that, ~ystem.~’lStudying the distribution and effects of me-
unless they assert their role and importance in the services dications in populations (pharmacoepidemiology),as well
that they offer, they may not be needed. as the costs and comparisons of alternative courses of
508 Managed Care Pharmacy Practice
therapy (pharmacoeconomics), helps determine where counseling patients and producing the outcome of better
disease management can change practice the most.[lol overall healthcare at lower costs. Application of principles
These conditions are generally the most common, ex- of disease prevention and management in individual or
pensive, and treatable (e.g., asthma, diabetes, peptic ulcer group counseling sessions can help patients learn how to
disease, depression, cardiovascular disease) and provide care for themselves properly, thus reducing healthcare
the greatest opportunity for economic savings when dis- costs and improving their quality of life."']
ease management programs focus on them."'] In the future, wellness programs will most likely be
Disease management requires that pharmacists add a a joint effort among payers, employers, patients, and
number of skills to their professional role. These skills providers. In these programs, pharmacists could serve
include managing information systems to collect and as coordinators to ensure appropriate utilization of re-
organize data, total quality management to improve pro- sources, effective communication, and optimal patient
cesses, teamwork with patients and other professionals, outcomes."']
budgeting to obtain compensation, teaching clinical care
and appropriate drug use, and the ability to help move Evaluating clinical and economic data
pharmacy from compartmentalized care to integrated
care.[121Most models of disease management use the The focus on disease state management and outcomes will
pharmacist in a clinical role that goes beyond dispens- require that data on a patient's drug therapy be accessible
ing. Pharmacists are ideally qualified to participate in to both hospital and ambulatory care providers. The
disease management because of their knowledge of pharmacist can play an integral role in the coordination
drug therapy, communication, computer applications, and dissemination of these data. For example, institutional
and marketing, as well as sales, finance, and basic pharmacists will need to establish communication links
wellness issues. Pharmacists have a great opportunity in with pharmacy providers in other settings to ensure op-
these situations, given their ability to communicate timal and seamless care."']
complex concepts in easily understood terms to help Pharmacists can provide a valuable service in evalu-
employee groups take advantage of disease manage- ating the data resulting from treatments and helping
ment option^."^] patients make the most of their prescribed therapies.[201A
In the future, as healthcare systems make the transition pharmacist could help select the appropriate formulary
from stage 1 (primarily fee for service) to stage 4 (pri- drug within a drug class and then teach the patient how to
marily capitation), opportunities for disease management take the medication correctly.
will i n ~ r e a s e . " ~For
] many MCOs, shifting from for- Pharmacists also have a role as pharmacoeconomic
mulary management to disease management will be a analysts in comparing medications. Sometimes the in-
means of improving the overall quality of care, reducing vestment in a more expensive medication reduces other
costs, and expanding patient involvement in care.[151De- costs to the HMO, but the data must be collected and
cisions will not be based on individual components of tracked for these assumptions to be proved. To perform
care, such as the cost of drugs or other treatments; rather, these analyses successfully, the pharmacist must be able
a disease will be viewed in its entirety. As customized to evaluate and interpret statistics and research articles.
cost-management techniques are applied to each disease A sound understanding of pharmacoeconomic principles
and patient, the pharmacist will assume a greater role in, is also essential.
and responsibility for, patient outcomes."61 As more information about a given treatment is re-
ceived, the pharmacist must always be prepared to per-
Managing health form the analysis again and incorporate the new in-
formation. Depending on new research or changes in the
Wellness programs have been described as the commun- HMO-covered population and its needs, the pharma-
ity outreach component of disease management. These coeconomic evaluation may lead to different results at a
programs can link with disease management programs to later date.
provide follow-up support. Because of the financial pressures to reduce health-
Pharmacists are ideally positioned to play a major care costs without compromising quality, the pharmacist
role in wellness programs. Combining their outstanding must have the ability to apply basic quantitative skills to
clinical skills acquired during formal education, intern- evaluate options and then to blend those results with
ships, externships, and work experiences with significant qualitative information to make decisions and recom-
transferable skills, especially communication and inter- mendations.[211 Pharmacists will have to work directly
personal skills, makes pharmacists ideal candidates for with prescribers, helping them interpret and use phar-
Managed Care Pharmacy Practice 509
macy claims data to achieve the best patient outcomes. dards. The Managed Care Pharmacy Practice Standard
Having a basic understanding of business and knowing can be found on the ASHP web site.[251
when to seek additional information are increasingly In addition to the Accreditation Standard and Learning
necessary to operate successfully within the managed Objectivesfor Residency Training in Managed Care Phar-
care environment. macy Practice, ASHP has published the following stand-
ards and guidelines, which provide guidance on model
Measuring outcomes clinical practices to managed care pharmacies. (Note: The
citations provided are from the American Journal of
Measuring outcomes shifts the emphasis from products to Health-System Pharmacy, but each of these standards or
patient results, which could eliminate the need for for- guidelines can also be located on ASHP’s web site.[361)
mularies.[221simply put, outcomes measurements evaluate
systems and decide what works and what does not. ASHP Guidelines on Pharmaceutical Services for Am-
Healthcare providers are increasingly relying on phar- bulatory Patients. [261
macists to perform outcomes research and quality-of-life ASHP Guidelines: Minimum Standard for Pharmacies
~271
studies. Pharmacists can apply basic quantitative skills in Institutions.
in evaluating options and combine the results with qual- ASHP Guidelines on a Standardized Method for Phar-
[2Sl
itative information to make decisions and recommenda- maceutical Care.
tions. For disease state management programs, meas- ASHP Guidelines for Obtaining Authorization for Do-
uring outcomes can be the key to success.[231 cumenting Pharmaceutical Care in Patient Medical
As health delivery systems move toward total managed Records.[291
care, the need for outcomes studies will increase.i241 ASHP Statement on the Pharmacist’s Responsibility
Issues to be addressed by outcomes research will include for Distribution and Control of Drug Products.[301
clinical efficacy of interventions, health-related quality of ASHP Statement on the Pharmacist’s Role with Re-
life, patient satisfaction. employee productivity, and re- spect to Drug Delivery Systems and Administration
~311
source utilization. Pharmacists can either participate in or Devices.
direct outcomes research. Outcomes studies may also be ASHP Technical Assistance Bulletin on Drug For-
~321
used to support a pharmacy position for interventions. mularies.
Outcomes research must always be patient focused and ASHP Technical Assistance Bulletin on the Evaluation
1331
useful for improving patient care. Many pharmacists of Drugs f o r Formularies.
already have the data to do their own outcomes research. ASHP Guidelines on Medication-Use Evaluation.[341
Questions about appropriate prescribing and compliance ASHP Guidelines on Adverse Drug Reaction Monitor-
[351
can be answered by using pharmacy claims data. That ing and Reporting.
information could be a tool in providing positive feedback
to the patient, as well as to the prescriber. Other organizations that provide guidance on model
clinical practices are those that measure pharmacy quality
and utilization in the managed care area. The primary
organizations are as follows:
L PRACTICES IN
M A N A G ~ DCARE The Joint Commission on Accreditation of Healthcare
Organizations (JCAH0)-JCAHO began providing ac-
The American Society of Health-System Pharmacists creditation services by focusing on hospitals; more
(ASHP) and the Academy of Managed Care Pharmacists recently, its services have been expanded to provide
developed the Accreditation Standard and Learning accreditation services for a wide continuum of healthcare
Objectives for Residency Training in Managed Care providers. In fact, JCAHO shifted its accreditation focus
Pharmacy Practice in 1997. This standard outlines spe- toward a continuous quality improvement (CQI) process
cific requirements and principles that managed care and incorporated outcomes measures into the standards.
pharmacies should have in place for training residents. Information on JCAHO and its standards can be found at
The relevant practice areas include direct patient care, www.jcaho.org.
drug information, population-based pharmaceutical care,
business administration and management activities, and The National Committee for Quality Assurance
practice management. Regular accreditation surveys and (NCQA)-NCQA was founded in 1979, in an effort to
visits ensure that each site maintains the practice stan- establish a comprehensive quality measurement process
510 Managed Care Pharmacy Practice
for MCOs. The focus of the NCQA accreditation process setting. Some of the more prominent organizations
is the effective implementation of a CQI process into the include the following:
medical services provided by the managed care organ-
ization. Information on NCQA and its standards can be The American Society of Health-System Pharmacists
found at www.ncqa.org. Center on Managed Care Pharmacy (www.ashp.org).
The American Association of Health Plans (www.aahp.
The Health Plan Employer Data and Information Set or&.
(HEDIS)-The HEDIS reporting system is a series of The American Medical Informatics Association
specific performance measures designed to provide (www.amia.org).
healthcare consumers with the information they need to The American Telemedicine Association (www.
reliably compare MCOs. HEDIS measures are self-re- atmeda.org).
ported by participating MCOs on a quarterly basis. Infor- The Academy of Managed Care Pharmacy (www.
mation on HEDIS, which is a joint project with NCQA, amcp.org).
can be found at www.ncqa.or~pages/progr~s~edis. The National Business Coalition on Hedth (www.
nbchorg).
Publishe~
~ e f @ r e n ~toe § SCRIPT (http://scriptproject.org).
Mistry SK. Helping primary care providers with 1. Knapp, K.K.; Blalock, S.J.; O’Malley, C.H. Survey of
appropriate, cost-effective prescribing. Am J Health- Managed Care and Ambulatory Care Pharmacy Practice
Syst P ham . 2000; 57:1575. in Integrated Health Systems, 1999; ASHP: Bethesda, MD,
Knapp KK, Blalock SJ, O’MalIey CH. ASHP survey 1999; 5.
2. Knapp, K.K.; Blalock, S.J.; O’Malley, C.H. Survey of
of ambulatory responsibilities of pharmacists in man-
Managed Care and Ambulatory Care Pharmacy Practice
aged care and integrated health systems-1999. Am J in Integrated Health Systems, 1999; ASHP. Bethesda, MD.
Health-Syst Phaniz. 1999; 56243 1-43. 1999; 5.
Carroll NV. Formularies and therapeutic interchange: 3. Survey of Managed Care and Ambulatory Care Pharmacy
healthcare setting makes a difference. Am J Health- Practice in Integrated Health Systems, 1999; ASHP:
Syst P ham . 1999; 56467-72. Bethesda, MD, 1999; 5.
Knowlton CH. Pharmaceutical care in 2000: engaging 4. ASHP Center for Managed Care. Innovative Roles for Man-
in a moral covenant in turbulent times. Am S Health- aged Care Pharmacists; ASHP: Bethesda, MD, 1998; 13.
Syst P ham . 1998; 55:1477-82. 5. Knapp, K.K.; Blalock, S.J.; Q’Malley, C.H. Survey of
Kay B, Crowling GH, Kershaw VI et al. Perspectives Managed Care and Ambulatory Care Pharmacy Practice
on pharmacy’s role in managed care. Am J Health-Syst in Integrated Health Systems, 1999; ASHP: Bethesda. MD,
1999; 3.
P ham . 1998; 55:1482-8.
6. Knapp, K.K.; BIalock, S.J.; O’Malley, C.H. Survey of
Reeder CE, Kozma CM, O’Malley CH. ASHP survey Managed Care and Ambulatory Care Pharmacy Practice
of ambulatory care responsibilities of pharmacists in in Integrated Health Systems, 1999; ASHP Bethesda, MD,
integrated healthcare systems-1997. Am J Health- 1999; 4.
Syst P ham . 1998; 55:35-43. 7. Knapp, K.K.; Blalock, S.J.; Q‘Malley, C.H. Survey ofMan-
Hawkins PR. Pharmacist as health education coor- aged Care and Ambulatory Care Phanmacy Practice in
dinator. Am J Health-Syst Pharm. 1997; 54:1497-9. Integrated Health Systems, 1999; ASHP: Bethesda, MD,
Hepler CD. Where is the evidence for formulary ef- 1999; 4.
fectiveness? [Letter] Am J Health-Syst P ham . 1997; 8. Knapp, K.K.; Blalock, S.J.; 0’Malley, C.H. Survey of
54:95. Managed Care and Ambulatory Care Pharmacy Practice in
Additional citations validating the benefits of clinical Integrated Health Systems, 1999; ASHP: Bethesda, MD,
1999; 6.
pharmacists’ participation in managed care are listed
9. Toscani, M.R. Introduction to Disease Management. In
in the Bibliography. Paper Presented at ASHP Midyear Clinical Meeting. h’ew
Orleans, LA,1996, Dec. 10.
Professional ~etworking~ ~ p o ~ u n i t i e s 10. Larson, L.N.; Bjornson, D.C. Interface between pharma-
coepidemiology and pharmacoeconomics in managed care
There are many professional networking opportunities for pharmacy. J. Manage. Care Pharm. 1996,Z (3), 282-289,
clinical pharmacists who practice in the managed care May/Jun.
Managed Care Pharmacy Practice 511
1 1 . Marcille, J. Is there a place for pharmacists in the new 32. American Society of Hospital Pharmacists. ASHP tech-
world of disease management? J. Manage. Care Pharm. nical assistance bulletin on drug formularies. Am. J. Hosp.
1996, 3 (I), 16-21. Jan./Feb. P h m . 1991,48, 791-793.
12. Campbell, W.H.; Newsome, LA.; Ito, S.M. The 33. American Society of Hospitd Pharmacists. ASHP tech-
Evolution of Managed Care and Practice Settings. In A nical assistance bulletin on evaluation of drugs for
Phannacist ’s Guide to Principles and Practices of Man- formularies. Am. J. Hosp. Pharm. 1988, 45. 386-387.
aged Care Pharmacy; Ito, S.M., Blackbum, S. Eds.; 34. American Society of Health-System Pharmacists. ASHP
Foundation for Managed Care Pharmacy: Alexandria, guidelines on medication-use evaluation. Am. J. Heath-
Virginia, 1995; Vol. 5. 13. Syst. Pharm. 1996, 53. 1953-1955.
13. Innovative Roles for Managed Care Pharmacists; 7-8. 35. American Society of Hospital Pharmacists. ASHP guide-
14. Toscani; 7. lines on adverse drug reaction monitoring and reporting.
15. Rosenburg, G.B. Opportunities for alliances between Am. J. HOSP.P h m . 1995, 52, 417-419.
industry and pharmacy. Am. J. Hosp. Pharm. 1994, 51, 36. www.ashp.org.
3061-3065.
16. Marcille, J. Is there a place for pharmacists in the new
world of disease management? J. Manage. Care Pharm.
1996, 3 (I), 20, Jan./Feb.
17. Boysen, H. 1996, Personal communication, Oct.
Following are some selected references to published
18. ASHP Center for Managed Care. Innovative Roles for Man- materials validating the benefits of pharmacists’ participa-
aged Care Pharmacists; ASHP: Bethesda, MD, 1998; 8. tion in managed care:
19. Bond, W.E. Direct contracting: The next purchaser strategy.
J. Manage. Care Pharm. 1996, 2 (I), 11 16; Jan./Feb.
~ Butler, C.D. Practical approaches to meaningful outcomes
20. Kostoff, L. 1996, Personal communication, Nov. analysis. ASHP Home Care Meet. 1995, 2, HC-24, Aug.
21. Boysen, L. 1996, Personal communication, Oct. Goss, T.F. Overview of outcomes studies conducted in managed
22. Marcille, J. Is there a place for pharmacists in the new care organizations. ASHP Midyear Clin. Meet. 1996, 31, PI-
world of disease management? J. Manage. Care Phann. 58, Dec.
1996, 3 (I), 18. Jan./Feb. Grasela, T.H. Pharmacoepidemiology: Scientific basis for out-
23. Buchner, D. Role and Importance of Outcomes Measure- comes research. Ann. Pharmacother. 1996,30,188- 190, Feb.
ment in Maximizing the Success of Disease Management Hedbfom, E. Process of identifying medication-relatedoutcomes.
Initiatives. In Abstract Presented at ASHP Midyear Cli- ASHP Annu. Meet. 1996, 53, PI-85, Jun.
nical Meeting, New Orleans, LA, 1996; Dec. 11. Horn. S.D. Clinical practice improvement model and how it is
24. Gross, T. Considerations in Developing and Selecting used to examine the availability of pharmaceuticals and the
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Meeting, New Orleans, LA, 1996; Dec. 10. Horn, S.D.; Sharkey, P.D.; Phillips, H.C. Formulary limita-
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Pharm. 1989,46, 338-339. 1995, NS35, 51-58, Aug.
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1989,46, 2342-2343. Trends 1996, 8 (Suppl. C), 29-35, Mar.
PHARMACY PRACTICE ISSUES
*
[ear rams
Albert I . Wertheimer
Stephen H. Paul
Temple University, Philadelphia, Pennsylvania, U.S.A.
dent always came along to derail comprehensive reform. Social Security A C ~ . [ ~his
] section of the legislation
In 1965, the “Great Society” under President Lyndon B. covers inpatient hospitalization, critical access hospitals,
Johnson moved forward with legislation providing a level skilled nursing facilities, hospice care, and limited home
of care for the elderly (Medicare). Medicaid was also en- hea1th~are.I~’ Critical access hospitals are small facilities
acted at the same time to cover low-income aged, blind, that provide limited outpatient care and inpatient services
and disabled individuals, and parents and their dependent to individuals in rural areas.
children on welfare. Piecemeal health coverage for select Most people pay for “Part A” during their working
populations was continuing, and comprehensive reform years. They therefore receive this insurance benefit
was thwarted. These two federally initiated health pro- automatically when the appropriate time comes. Em-
posals did not include mandatory ambulatory drug cover- ployees and employers each pay 1.45% tax on all wages
age. In 1988, the Medicare Catastrophic Act was signed and salaries.
into law by President Ronald W. Reagan and promptly The medical portion is “Part B.” and it is included
vetoed by President George H. W. Bush before it could be in the legislation as “Part B” of Title XVJU. It covers
implemented. This legislation would have provided a pre- medical services including physician care, outpatient hos-
scription drug benefit and a cap on patient liability. The pitalization senlices. and selected medical activities not
law was rescinded, because high-income elderly felt they covered in “Part A,” such as occupational and physical
would pay more in premiums than they would receive in therapists. This section will pay for diabetic supplies when
benefits.Dl medically necessary.
The passage of the Omnibus Budget Reconciliation The cost to the Medicare patient changes each year.
Act (OBRA) of 1990 provided poor seniors who qualified During the year 2001, it was $50.00 per month. This
for Medicare and Medicaid a level of mandatory patient charge is deducted from the recipients’ monthly So-
care provided by pharmacists in addition to cial Security check before it is received. The premiums
prescription coverage. paid by participants represent 25% of the program’s cost.
The 1990s witnessed the creation of optional non- The remaining 75% is paid directly by a federal bud-
federal prescription benefits for Medicare beneficiaries get appropriation.
enrolled in Health Maintenance Organizations (
and in 1997, Medicare+Choice was established by Re- Healthcare C o w e ~ a ~Optio
e
sident William J. Clinton which created numerous choices
for recipients. The start of this millennium has witnessed Eligibility for Medicare enables individuals to select one
the commitment of President George W. Bush to create a of a myriad of choices for receiving care.
prescription benefit program for the elderly. This program
could take several different paths. There could be com-
prehensive Medicare reform with prescription coverage
and pharmaceutical care becoming a mandatory or op- The first Medicare health insurance is now called the
tional benefit. There could also be just a prescription be- “Original Medicare Plan.”[61 This is a fee-for-service
nefit passed for categorically defined individuals. Another plan. The provider charges a fee to the patient and or the
option could be a block grant program enabling states to government each time the service is provided. This
receive federal funds. States could have the flexibility in arrangement is offered nationwide.
choosing to establish a drug benefit or enhance pharma- The federal government has authorized supplemental
ceutical coverage with existing voluntary plans. Failure insurance polices to aid in paying for services not covered
of a political consensus among the President, Congress, in the Original Medicare Plan. Up to ten supplemental
the pharmaceutical industry, pharmacies, and patients plans can be marketed by private insurance carriers. These
could result in no additional prescription and pharma- plans must be labeled “Medicare Supplement Insurance.”
ceutical care coverage for consumers, at least until the There are high-cost and lower-cost policies. They differ in
next presidential election in 2004. the scope of coverage, deductibles, and copayments. Se-
veral of these optional programs have limited outpatient
prescription coverage. In addition to these supplements
that are also called Medigap policies, the standardized
The basic Medicare insurance program, which provides benefits may also be sold as “Medicare Select” policies.
benefits to consumers who are 65 or older, consists of The Medicare Select benefits should be less expensive,
two components. because the freedom-of-choice to choose providers is
The hospital portion is “Part A.” It receives its name limited to selected physicians and hospitals. Insurance
from the fact that it is “Part A” of Title XVIlT of the carriers may not add or subtract benefits to the “
514 Medicaid and Medicare Pharmaceutical Programs
Supplement Insurance" policies. The only variable Extending Drug Coverage to All
allowed is the premium charged. Medicare Beneficiaries
There are various ways to contain the drug benefit. The Step therapy for the drug treatment of patients creates a
drug benefit could be restricted by placing a cap on the ‘‘road map” to be used with various medications in order
value of the benefits provided for a benefit period. to control the disease or medical condition. The initial step
Another restraint would be to provide drug coverage after is usually the most common one used in this situation.
a drug benefit deductible was exceeded or only provide More complex steps are not attempted to correct the pa-
the benefit for catastrophic situations. This type of action tient’s situation until the earlier steps have failed.
would save drug money; however, the overall costs for
healthcare would probably increase. Drug evaluation. Drug evaluation is an ongoing, syste-
The pharmacy profession has recognized that the matic process designed to maintain the appropriate and
benefits to society greatly exceed the cost of the drugs. effective use of medications. It involves the review of the
The benefits of the drugs and pharmacy care center physicians’ prescribing relationships, review of the phar-
around an improved quality of life, a decrease in overall macists’ dispensing patterns, and patients’ use of medica-
healthcare expenditures, and an increased life span.[”] tions. This evaluation goes by several names in different
healthcare setting^."^' The names include DUR (drug uti-
Administration of the drug benefit. Proposals being lization review), DUE (drug use review), and MUE (medi-
discussed utilize the private-sector model of the Phar- cal use evaluation).
macy Benefit Manager (PBM). Some proposals utilize
multiple PBMs for a geographic area, while others rely Resource-Based Relative Value System
on a single PBM to manage the program. The issue of
whether they will be merely a claims processor or have Reimbursement for health services is extremely compli-
additional responsibilities is varied. The remaining pro- cated. Providers want higher reimbursement, and payers
posals require government management of the drug be- desire to reduce, maintain, or limit increases paid each
nefit. The managerial control would occur at the federal year. HCFA developed a methodology to deal with phys-
or state level. ician reimbursement and allow for an increase in payments
for physician services. It is a system based on approxi-
Additional tools to manage the pharmacy benefit. mately 7500 relative value service codes. These codes are
Coordination of the Medicare benefit by implementing a more complex than the approximate 450 Diagnosis Rela-
multidisciplinary approach to patient care should produce ted Groups (DRG) used by hospitals in their Medicare
a quality outcome for the beneficiary. From the pharmacy reimbursement. In addition to the service codes, the for-
perspective, numerous issues should be addressed.[13] mula has a relative value unit (RVU) for practice expen-
Some of the concerns include: ses and a separate one for malpractice insurance. Added to
these components is a geographic practice cost index
Formulary coverage. A drug formulary is an instru- (GPCI) for each defined work service area. The GPCI is
ment that contains safe, effective, and affordable designed to take into account high- as well as low-cost
medications designed to improve or maintain patient practice expenses and physician services as compared to
health. The breadth and depth of coverage and the the national average for each constituent of the model. A
ability to add drugs are imperative to maintaining a conversion factor (CF) is also part of the model. This var-
workable drug formulary. iable is designed to maintain fiscal budget neutrality in the
event total payments exceed a certain monetary sum, de-
Pharmaceutical care and disease management. The
termined by Congress, each year. The complexities in-
collaborative efforts of the interdisciplinary team of
volved can be understood more completely by checking
pharmacists and other health professionals help to
out the designated HCFA web site.[’61
ensure patients are utilizing medications appropriately.
The model used to compute physician payment can be
Critical (clinical) pathways and drug step therapy. expressed as:
These concepts can be effectively used to create a sy-
nergistic impact on improving the health of the elderly. Physician Payment
Critical pathways are designed to provide continuity of = [((RVU service activity x GPCI service activity)
care and decrease the fragmentation of services. Their + (RVU practice expense
use helps guide the patient and family through the ex-
x GPCI practice expense)
pected treatments and progress. It also increases the
satisfaction of patients, families, health professionals, + (RVU malpractice expense
t141
and the various payers for healthcare services. x GPCI malpractice expense)) x CF]
516 Medicaid and Medicare PharmaceuticalPrograms
The physician payment model is not perfect; however, The program covers children under six years whose
it represents a quantum leap forward compared to how family income is no more than 133% of the federal
pharmacy practitioners are reimbursed. The reimburse- poverty level definition, pregnant women up to 133% of
ment in many Medicare+Choice plans, in most state the poverty level, some Medicare beneficiaries, and re-
Medicaid programs, and private PBM (third party) cipients of adoption assistance and foster care programs.
arrangements fails to recognize that the costs for pro- Medicaid covers virtually all outpatient and inpatient
viding the pharmacy benefit changes at the practitioner health and rehabilitative services, home health, long-term
level. PBMs only recognize that the pharmaceutical care, dental, prosthetic, pharmacy, and optical services
cost changes. and goods. Pharmacy benefit rules state:
Pharmaceuticals 19,337,543
Physicians 18,554,746
EDlCAl Hospital outpatient 12,157,729
LabK-ra y 9,380,689
The 50 states, District of Columbia, Puerto Rico, Guam, EPSDT 6,174,628
and the Virgin Islands and other territories all have Clinic 5,285,415
medical assistance (Medicaid) programs that vary some- Dental 4,965,202
what but are within federal guidelines. States qualify Hospital inpatient 4,408,162
for federal reimbursement by agreeing to provide be- Other practitioners 4,341,915
nefits to certain categories of needy persons who meet Personal support services 3,108,432
the requirements of the block grant for (TANF), tempo- Family planning 2,011,124
Nursing facility 1,645,728
rary assistance to needy families, and the subsequent aid
Home healthcare 1,224,714
to families with dependent children (AFDC) programs,
ICF-mentally retarded 126,490
and for blind and disabled persons receiving social secu-
rity income. (From Ref. [ZO].)
Medicaid and Medicare Pharmaceutical Programs 517
acquisition costs (EAC) were established. For drugs cer- requires that states provide prospective DUR and re-
tified by the FDA as being interchangeable, if the pre- trospective DUR programs. The prospective DUR activity
scriber writes on the face of the prescription: “brand is performed at the time of dispensing.[221
necessary” or “medically necessary,” the patient can As is the case of an HMO patient presenting a card at
receive the branded product instead of the generic equi- the pharmacy, the Medicaid patient does the same thing.
valent product. For 1998, HCFA spent $13.52 trillion for Each state decides whether it will have a patient co-
19.3 million recipients which is about $700 per recipient payment, and if so, its amount. About 15 States have no
that year. copayment requirement, and the others charge between 50
The top ten states in prescription expenditures for 1998 cents and $3.00 per prescription.
(in descending order) were California, New York, Florida, The pharmacy is paid a dispensing fee that ranges
Texas, Ohio, Illinois, Pennsylvania, Massachusetts, North between $3.00 and $5.50 per prescription, depending
Carolina, and New Jersey. The ten lowest expense states upon the state. The pharmacy is reimbursed the wholesale
were Oklahoma, Arizona. Tennessee, Wyoming, North price of the drugs minus a discount, which is a percentage
Dakota, South Dakota, Alaska, Nevada, Hawaii, and reduction from the “sticker” price (called AWP or
District of Columbia. For all states, drugs and related average wholesale price) which is higher than the actual
services consumed 9.5% of the total Medicaid budget. price paid by most pharmacies due to quantity discounts,
Because of this more than $13 trillion expenditure, in direct purchases from manufacturers, and the taking ad-
1990, Congress considered alternative means to reduce vantage of “deals.” The discount averages about 11 or
this expense. The result was a compromise where in 12% of the average wholesale price. This brings the in-
exchange for Medicaid formularies to be open to all gredient reimbursement more in line with the actual price
drugs, manufacturers agreed to agree to a rebate pro- paid by the pharmacy.
gram with HCFA in the OBRA 1990 legislation. Re- For an example, let us consider a drug where the AWP
bates were to be a minimum of 10% of that state’s pur- is $60.00. The patient paid $3.00, and the pharmacy will
chases from a company. OBRA was amended in 1992, be reimbursed $60.00 less 12%, which equals $52.80 less
and today, manufacturers pay 15.1% of the average ma- the $3.00 patient copayment or $49.80 by that state
nufacturer’s price back to the state for innovator (single- Medicaid agency. In addition, the pharmacy will receive
source) products, and 11% is returned for generic, multi- $4.00 as a dispensing fee.
source products. [ 2*I Because of budget problems in some states from time-
To give one a feeling for the quantities involved, the to-time, limitations have been implemented on occasion.
total rebate for 1998 was $2.5 billion. While all drugs Some states have limited the number of prescriptions per
should be available, state Medicaid agencies may restrict month for limited periods or established caps on the value
availability of certain drugs of limited value, regarding of the benefits. Usually, these have been lifted when the
safety, effectiveness, or clinical outcome if the drug may budget situation improved, especially because there is no
be obtained through the prior approval procedure. Other evidence that such restrictions are cost-effective overall,
drugs may be excluded completely if they are: and, in fact, there is considerable suspicion that patients
might not get needed drugs, resulting in potentially mas-
0 For anorexia, weight gain, fertility, hair growth, cos- sive hospital or other costs.
metic effect, smoking cessation, or symptomatic relief With such a huge price tag, HCFA administrators and
of cough or cold. legislators are always searching for means to reduce costs.
0 Vitamins or minerals or OTC drugs (fluorides and Some relief has come from the prior authorization pro-
prenatal vitamins excluded). gram as well as from a mandatory generic dispensing
0 Drugs requiring monitoring to be obtained from the policy in many states, but additional savings are still
manufacturer. desired. There has been discussion about placing reci-
* Barbiturates or benzodiazepines. pients in managed care plans that are capitated and hav-
ing the practitioners control utilization with actual incen-
A significant component of the Medicaid drug program tives. Some states have asked for supplemental rebates
is a Drug Utilization Review (DUR) activity, which is that provide a discount well beyond the OBRA 1990
defined as a structured and continuing program that re- dictated amount.[231
views, analyzes, and interprets patterns of drug usage in Health economists continue to advocate greater em-
a given healthcare environment against predetermined phasis on prevention, screening, patient education, well-
standards. This is conducted for two purposes: to improve ness education with emphasis on nutrition, smoking, and
the quality of care and to assist in containing costs. OBRA alcohol use reduction, avoidance of substance abuse, and
51s Medicaid and Medicare Pharmaceutical Programs
prenatal care as examples of strategies to reduce illness and Means, Subcommittee on Health, U.S. House of Rep-
trauma and cost throughout life. Perhaps enrollmcnt in rcsentatives, March 27, 2001.
capitatcd managed care organizations can provide the 12. R x price controls likely unless manufacturers help curb
costs, Vt. Gov says; McCaughan, M., Ed.; The Pink Sheet
environment and suitable incentives for greater cost
2001. 63 (14); 6.
savings in the future.
13. Where W e Stand: Medicare Pre.ccription Drug Coverage;
Stables, C., Ed.; Academy of Managed Care Pharmacy:
Virginia, 1999; 1 - 12.
14. Sapienza, A.; Broescker. A. Health Care Professionals and
Interprofessional Care. In Introducfion to Health Care
1. Wright. J.W. 2001 New York Times Almanac; Penquin: D e l i v e p A Primer for Pharmacists; McCarthy, R., Ed.;
New York, 2000: Vol. 153. Aspen Publishers, Inc.: Maryland, 1998; 48-59.
2. Phavnzacj and the US Health Care Sjstem, 2nd Ed.; 15. Drug Use Evaluation; The Academy of Managed Care Phar-
Fincham, J., Wertheimcr, A,, Eds.: Pharm. Products macy. http://amcp.org/public/pubs/concepts/drugusc.html
Press: Hinghamton, New York, 1998; Vol. 34. (accessed March 2001).
3. h t t p :// w w w . M E D I C A R E . G O V/3 5 / m i l e s tones .a s p 16. http: // www .hcfa.gov/ stats/pufiles. htm#rvu; http: //www.
(accessed April 2001). MEDICARE.GOV/publicati~~ns/pubs/pdf/204Yfina.pdf
4. Social Security Act. http://www.ssa,gov/OP_Horne/ssact/ File: /publications/pubs/pdf/2049fina.pdf.
comp-toc.htm, accessed April 2001. 17. Medicare PBMs could offer “loose” and ‘.tight” Rx op-
5 . Medicare and You 2001, HCFA-10050; Health Care tions-Rep. Johnson; McCaughan, M., Ed.; The Pink
Financing Administration: Maryland, 2000; Vol. 5; I -73. Sheet 2001, 63 (14); 9 10.
6. Medicare and You 2001, HCFA-10050; Health Care Fi- 18. http://www.healthnewsdaily.com/rs/channels/fdc/HND/
nancing Administration: Maryland: 2000;Vol. 14; 1-73, Current + Articleshnd + pink/stories/0425p2.asp.
7. http://www.MEDICARE.GOV/publications/pubs/pdf/19. Pharmaceutical Benefits Under Stat<. Medical Assistance
2049fina.pdf File: /publications/pubs/pdf/2049fina.pdf. Programs, 1999; National Pharm. Council: Reston, Vir-
8. Medicare 2000:35 Years of Improving Americas’ Health ginia, 2000; Vol. 4.8.
and Security, pp. 2, July 2000,Medicarc factl0.pdf http:// 20. Pharmaceutical Benefits Under State Medical Assistance
www.medicare.gov/FAQs/Top20.asp, April 15, 2001. Programs, 1999: National Pharm. Council: Reston, Vir-
9. Medicare 2000:35 Years of Improving Americas Health ginia, 2000;Vol. 4.12.
and Security, pp. 2,July 2000,Medicare factl0.pdf http:// 21. Pharmaceutical Benefits Under State Medical Assistance
www.medicare.gov/FAQs/Top20.asp, April 15, 200I . Programs, I Y Y Y ; National Pharm. Council: Reston, Vir-
10. Laying the Groundwork for a Medicare Prescription Drug ginia. 2000:4.32.
Benefit, Statement of Dan L. Crippen, Committee on Ways 22. Wertheimer, A,; Navarro, R. M m a g e d Cure Pharmacy:
and Means, Subcommittec on Health, U.S. House of Rep- Principles and Practice; Pharm Products Press: Bingham-
resentatives, March 27, 200I . ton, New York, 1999; Vol. 232.
11. Laying the Groundwork for a Medicare Prescription Drug 23. Sultz. H.:Young, K. Healthcare USA; Aspen: Gaithers-
Benefit, Statement of Dan L. Crippen, Committee on Ways burg, Maryland, 2001 ; 272.
PROFESSIONAL DEVELOPMENT
0
e IC
Lara E. Storms
Virginia Commonwealth University School of Pharmacy,
Richmond, Virginia, U.S.A.
Cindy W. Hamilton
Hamilton House, Virginia Beach, Virginia, U.S.A.
University
Lili F. VClez, PhD Director, Biomedical Writing Program, University of the Sciences in Philadelphia
Other
Beth Rhoads, BS Recruiter, Pharmaceutical Search Professionals, Inc.
"Some titles and affiliations have changed since the interviews were conducted
providing continuing education o r promoting a new drug. search the literature, collaborate with other team members
Regulatory documents are required for drug development; to analyze and interpret data, write an outline and then the
examples include clinical investigator brochures, clinical first draft, edit it: and coordinate revisions. In the case of a
trial reports, new drug applications, and package inserts. monograph, the medical communicator can work with a
With these projects, the medical communicator can re- graphic artist to design and produce a printed product.
Activities
Critically evaluating the literature Moderating focus groups Writing
Editing Researching
Interviewing Reporting
Media
Audio Journals Radio
Books and book chapters Monographs Slides
Compact discs Newsletters Television
Internet Newspaper articles Video
Table 3 Estimated annual income for pharmacists employed as medical communicators in different settings in June 2000
Annual income ($)
Pharmaceutical
Freelance
Education
Not Stated
Fig. 1 Primary section in American Medical Writers Association (AMWA) chosen by all members ( n = 4637) and pharmacists
(n = 137) in July 2000. PRAM =public relations, advertising, and marketing.
522 Medical Communications, Clinical Pharmacy Careers in
pharmaceutical company because it is intellectually tions, but this can be misleading because self-employed
challenging and, with the finished product, “there is people must pay for their own equipment, benefits, and
something tangible.’ ’ Pharmaceutical companies offer the part of social security that is otherwise paid by
opportunities for advancement and comprehensive be- employers. In addition, freelancing can be very solitary
nefits such as a retirement package; paid vacation, because of minimal interaction with professional collea-
holidays, and sick leave; and medical and dental in- gues and patients.
surance. Entry-level salaries can be higher than in Pharmacists who work at professional associations and
some settings because pharmaceutical companies typ- publishing companies solicit manuscripts for journals, or-
ically require some experience. ganize the peer review process, and edit manuscripts.
Medical communication companies prepare edu- Pharmacists also write news, editorials, and monographs
cational, promotional, and regulatory materials, usually for their journals, newsletters, web sites, and other publi-
for pharmaceutical companies. Contract research organi- cations. Thompson likes being an editor at a professional
zations, which oversee clinical trials for pharmaceutical organization because her job encourages creativity, but
companies, may also prepare regulatory materials. she admitted that “being an editor is not a 40-hour a week
Phillips said that her job at a medical communications job and sometimes I feel overwhelmed.” Salary informa-
company “allows me to work with some of the leading tion is not available for pharmacists who work in these
physicians and pharmacists in the world.” Overstreet settings, but Thompson said, “Medical communicators
added that her position allows her “the flexibility to do a should expect lower wages from non-profit organizations
variety of different things every day, and the opportunity like ASHP.” The benefits, however, are comparable to
to learn about new techniques and new therapies to those offered by pharmaceutical companies, and there are
supplement my pharmacy background.” Benefits vary opportunities for advancement. Sorkin said, “There is a
depending on the size of the organization. There are trade-off and people just have to determine what works
opportunities for advancement to positions such as best for them.’ ’
editorial director or even president, but Phillips lamented
that she has less time to write now that she is president of
her own company.
Freelance was the second most popular AMWA WHAT TRAINING AND SKILLS
section chosen by pharmacists. Advantages include ARENEEDED?
working in a home office and being self-employed, in-
dependent, and flexible. Russo explained, “As a free- The minimum training and skill requirements for a
lancer, I’m able to choose the projects that I’m interested medical communicator are knowledge of medicine and
in doing.” Curtis, Hamilton, and Russo agreed that free- ability to communicate. Hamilton explained, ‘‘By their
lance writing has some disadvantages, especially regu- training, pharmacists know and understand medicine and
lating the workflow. Curtis explained, “Often you are the drug development process.” Curtis added, “Having
juggling projects with very tight deadlines for multiple the clinical knowledge about drugs and therapeutic areas
clients, and every client is important, so things can get really helps to bring some expertise to the writing.”
really stressful.” The earnings potential for freelancers Another relevant aspect of pharmacy training is drug
appears to be one of the highest in medical communica- literature evaluation, because medical communicators
Table 4 Resources for pharmacists interested in learning about career options in medical communications
Type of resource Examplea (Internet address) Comments on example
Professional organization American Medical Writers Association Annual conference, regional meetings,
(www.amwa.org) workshops, networking
Colleges and universities University of the Sciences in Philadelphia Degree in biomedical writing, article on career
(www,usip.edu/graduate/biomedical-writing.htm) opportunities (www.home.earthlink.net/-rhetrx/
bmw/)
Practical experience Hamilton House Clerkship for pharmacy students, list of
(www.hamiltonhouseva,com) recommended books
”The examples were selected because they provide information available on the Internet, including links to other useful web sites.
Medical Communications, Clinical Pharmacy Careers in 523
are expected to research new therapeutic categories. macists take classes as nonmatriculating students or via
It is also helpful to have good computer skills, inclu- the Internet.
ding familiarity with word processing and presenta- A degree in biomedical writing is not likely to become
tion software. a prerequisite for a career in medical communications,
All but two of the interviewees agreed that good according to the interviewees. VClez explained, ‘‘There is
writers are trained, not born. Vtlez said, “A writer is a lot of lost creativity and innovation when you force
simply someone who is willing to keep at it.” Pakes people to have a particular credential before they can
disagreed and said, “I don’t think that you can take just participate in a certain field.” However, Vtlez continued,
any old pharmacist and turn them into a writer. A person
is either a writer or they’re not. What you do is you hone Traditional pharmacy education does not stress written
your skills and become a better writer.” communication abilities. This means pharmacists inter-
Regardless of whether good writers are trained or born, ested in biomedical writing could probably benefit from
good medical communicators must be organized, accu- additional coursework. Knowing why a text needs to be
rate, flexible, curious, self-motivated, disciplined, and written in a particular way gives you more confidence and
flexibility than only knowing what needs to be written.
able to meet deadlines. Good pharmacists also have many
of these qualities. Hamilton explained, “Pharmacists are
Practical experience is also available. Pharmaceutical
typically very well organized because we are trained to
companies, professional associations, and publishers
put the right medication into the right bottle and
offer residencies and fellowships in medical communica-
administer it at the right time. These skills are transferable
tions or related areas, such as drug information. Schools
to medical writing.”
of pharmacy offer clerkships for students under the
Another skill that is transferable from some pharmacy
direction of medical communicators. Finally, there is on-
settings to medical communications is the ability to
the-job training. Overstreet said, “PharmDs are a hot
manage a business. This is especially important for the
commodity right now, even without experience. Some
individual freelance writer who must balance the time
employers are willing to accept a new PharmD graduate
required to manage the business with the time required to
and train them themselves.’ ’
write and generate income. Russo said, “You need to
Interviewees offered advice for making the transi-
have an appreciation and an understanding of marketing”
tion from traditional pharmacy practice to medical com-
to thrive in the freelance business.
munications. To learn how to differentiate between good
and bad writing, pharmacists should read and critically
evaluate the published literature. To gain insight about
E
career opportunities, pharmacists can interview a medi-
cal communicator[51 or search the Internet; some web
~ i t e s ’ ~ offer
’ ~ ] links to other useful sites. To develop a
There are many ways for pharmacists to obtain training
writing portfolio, pharmacists should write for publica-
and improve their communication skills (Table 4). Pro-
tion; an example of a popular target for new writers is a
fessional organizations offer workshops on writing and
newsletter published by an institution or local profes-
other relevant topics. For example, AMWA, an educa-
sional association. In fact, pharmacists can try medical
tional organization that promotes advances in biomedical
writing on a part-time basis while maintaining a tradi-
writing, offers a certificate for completing their core and
tional pharmacy career.12] Sorkin concluded, “If you’re
advanced c~rricula.‘~] Workshops are available at the PO-
interested in medical writing, you just have to get into it
pular annual meeting in late autumn, at regional meetings
and do it. You won’t know how good you are and if you
throughout the year, and through an onsite option.
like it until you do it.”
AMWA membership also provides credibility and a
venue for networking, which can lead to writing assign-
ments or even full-time employment.
Colleges and universities offer courses and degrees CONCLUSIONS
in technical writing, journalism, and communications.
The University of the Sciences in Philadelphia offers Medical communications is an attractive career option for
a master’s degree in biomedical writing, the only de- pharmacists because jobs are available and pharmacists
gree program of its kind in the United States. Ac- are well suited for the work. Employment is attainable in
cording to VClez, about one-fourth of the students in the many settings, some of which offer competitive salaries.
master’s program are pharmacists, and many other phar- Sorlun attributed the abundance of career opportunities to
524 Medical Communications, Clinical Pharmacy Careers in
ic
Deena Bernholtz-Goldman
Fujisawa Healthcare, Inc., Deerfield, Illinois, U.S.A.
to answer questions with regards to company recom- with healthcare professionals, the data must be easily
mendations. The PI, as it is known in the United States, is retrieved, if required.
a summary of the new drug application (NDA) provided
to the FDA from the manufacturer for the approval of a Summary
new product. This summary reflects in-depth discussions
between the FDA and the manufacturer, and generally In summary, the development of a well-balanced reply
represents certain compromises on the part of both parties. to an inquiry involves the use of published materials in
The information within the PI becomes the foundation for the same manner as that conducted in an academic or
approved promotional materials and is used by healthcare clinical setting. In an industry setting, PI information and
professionals as general guidelines for the use of the unpublished data on file with the company are used. In
product, although the entire wealth of information known addition, the information communicated must be sci-
about any given product is not included in the PI. The PI entifically accurate, balanced, supported by appropriate
should be the first resource used to answer an inquiry. literature, and should not include the author’s edito-
Even if additional off-label information on a specific topic rial perspectives.
is provided, the PI datdrecommendations should be
described first.
in the life cycle may generate less interest in the medical frequently asked questions. Commercially available elec-
community and therefore fewer calls. Along similar lines, tronic databases are available specifically for this setting.
the type of inquiry depends on the type of product. These types of databases enable the medical information
Intravenous products used in an acute setting may representative to document all calls; store, generate, and
generate questions of a clinical nature that require more maintain standard replies; and generate reports as needed.
in-depth research than that of a consumer call regarding Systems of this nature can be customized to a degree for
an OTC product and its proper storage. the particular needs of the company. Alternatively, similar
systems can be developed by a company’s own informa-
tion systems department.
the accuracy of the data and the fair balance with which committees include representation from many different
the data are used. groups in the organization, each contributing their ex-
pertise in a given area. The following is meant to exem-
plify several types of committees that may have medi-
cal information representation, but is not meant to be
Safety reporting all inclusive.
tailored for the specific location because government- These communications can be made available to all
approved indications and labeling for the same products employees to educate them on the products they support.
may vary by country.
c r
ts
Marie A. Chisholm
University of Georgia College of Pharmacy, Athens, Georgia, U.S.A.
1. Medicare benefits due to age, disability, or end- Therefore, BIPA 2000 expanded Medicare benefits
stage renal disease (ESRD). to lifetime coverage, or for as long as the patient needs
2. Medicare part B. immunosuppressive therapy, for patients who have Me-
3. Received a solid organ transplant that was medi- dicare due to age or disability. The lifetime coverage
care “covered” at the time of transplant. benefits of BIPA 2000 do not include patients who have
4. Surgery performed at a medicare-approved trans- Medicare based solely on ESRD. Currently, those
plant facility. patients who have Medicare due to ESRD only and
5. A viable transplanted organ. meet criteria in items 2-4 will receive immunosuppres-
sive coverage for 36 months posttransplant.
Prior to January 2000, medicare provided outpatient
immunosuppressive therapy for 36 months posttransplant
to patients who were Medicare eligible due to age or dis- REFERENCE
ability and met criteria in items 2-5 listed previously. As
of January 2000, eligible beneficiaries whose Medicare 1. Department of Health and Human Services (DHHS) Health
coverage for immunosuppressants expired during the year Care Financing Administration. JunuuT 24, 2001, HCFA-
2000 received an additional 8 months of Medicare cov- Pub. 60AB.
Marie A. Chisholm
University of Georgia College of Pharmacy, Athens, Georgia, U.S.A.
Table 2 Information frequently requested by medication information may lead pharmaceutical manufacturers to
assistance programs consider ending the assistance program or creating more
Patient and physician's names and contact information stringent eligibility criteria. Therefore, it is important to
Physician's state license number and drug enforcement ensure that patients report accurate information during the
number enrollment process and that the intended party receives
Name, strength, and amount of medication requested the medication. By adequately screening and monitoring
(prescription) information, healthcare professionals will be able to
Patient's income and other financial disclosures ensure that patients in need receive the intended benefits
Patient's insurance coverage of thesc programs.
Patient and physician signatures
Vicki S . Crane
Parkland Health and Hospital System, Dallas, Texas, U.S.A.
%9E
PCS
Medication Errors and Adverse Drug Events Prevention 535
CIC VIEW
Standing apart from the acaderic
researchers, the CLinical Initiatives
Center sees four discrete activities in
the medication use process that need
reform-physician prescribing, order
processing, drug delivery and
reporting and event capture
(shown below)-mutually-exclusive
intellectual divides each describing a
specific problem in need of attention.
Our recommended best practices
address these problems, their
components and their root causes.
1 Sent to
Fig. 1 Incidence of ADEs lends insight to reform strategy. (01999 The Advisory Board Company.) (Continued).
with elaborate systems for scoring the severity of tegrates individual accountability with systems’ enhance-
medication errors and threats of severe punishment. ments on a continuum that provides reliable, safe care
The individual accountability approach focuses on the to each patient. The recommended best practices with-
individual who generated the error or ADE as being in this article address these problems, their compo-
fully responsible. The systems’ approach focuses on the nents, and their root causes, as well as point out stra-
system failures that set up individuals to generate errors. tegies for identifying and preventing medication errors
What is needed is an approach that appropriately in- and ADEs.
536 Medication Errors and Adverse Drug Events Prevention
II 111
Encouraging Increasing Supporting Leveraging
Reporting ~aent~ication Physician Pharmacy
Ordering Expertise
Fig. 2 Identifying and preventing ADEs. (01999 The Advisory Board Company.)
Medication Errors and Adverse Drug Events Prevention 537
bining at some point to cause a harmful patient outcome. use process and are directly exposed to its hazards (e.g.,
The harmful outcome was long in coming and was a heavy workload, drug supply shortages, paperwork asso-
natural result of the way the system was designed and ciated with new Medicare compliance regulations). The
operated. According to the process-improvement ap- blunt end of the system is where regulations, new drug
proach, medication-use is a complex system with many technologies, and reimbursement policies are structured,
potential points of failure. Each latent point of failure and where many of the competing demands within the
within the system is in itself insufficient to cause an system are created. For example, there is a constant com-
accident (e.g., the sterile-products pharmacist catches an peting demand not only to produce care very quickly but
error made by a technician in preparing an intravenous also to have it be error free. Despite this competing de-
admixture). The pattern of these potential failures is dy- mand, safe operations are the rule and harmful outcomes
namic and depends on the individual elements of the are infrequent.
medication-use process. When a visible failure occurs, people focus on eva-
There is a “sharp end” and a “blunt end” to the med- luating the performance of health care providers. Because
ication-use process; both may harbor latent points of fail- the negative outcome is known, this results in a bias to-
ure. The sharp end of the system is where the health care ward hindsight in which the events leading to the negative
providers are. They interact directly with the medication- outcome are seen as obvious, even though they may not
V VI VII VIII
Writing Dispensing Reinforcing Supplementing
Orders Drugs Nursing Nursing
Accurately Precisely staff Staff
Fig. 2 Identifying and preventing ADEs. ( C 1999 The Advisory Board Company.) (Continued).
538 Medication Errors and Adverse Drug Events Prevention
have seemed obvious to the provider at the time of the database, JCAHO's Sentinel Event Alerts (high-alert
adverse drug event. Hindsight bias is the greatest obstacle medications), and the media. Regardless of whether there
to making personnel performance more robust and resi- is medication error or ADE specific to a health care
lient in providing patient safety. Retelling of these "ce- practice environment or not, if the medication error or
lebrated accident" or "first stories'' reinforces the view ADE is happening elsewhere, it could likely happen at the
that the provider acted alone in creating the error. individual practice site. Examples of preemptive strikes to
The immediate reaction to celebrated accidents in protect patients from harm include instituting protocols for
many health care organizations is to blame the provider use, restrictions on the duration or route of therapy, goal
and institute new training, rules, technology, and discip- setting, education, and feedback procedures, and some-
linary actions so that this type of error will never reoccur. times even turning down requests for a drug to be added to
Investigation of the harmful outcome then stops. Many of the formulary.
these new changes are not tested thoroughly, add com- Because prescribing errors have been identified as a
plexity to the already fragile system, and introduce new leading cause of preventable medication errors and ADEs,
types of failures; thus, the cycle of harmful outcomes reforming physician prescribing should also be given a
merely repeats itself at different points in the medication- high priority. Although computerized physician order
use process. In the case of medication use, the classic entry with clinical decision support would appear ideal,
celebrated accident occurs when a potentially lethal drug many organizations may not have the information systems
is misused (e.g., a patient receive a dose 10 times too infrastructure or funds to accomplish such a goal in the
high) and the patient dies as a result. What typically hap- near future. It is generally recognized that leveraging
pens next is that restrictions are placed on the use of the pharmacy expertise is in many cases the most cost-ef-
offending drug and on the provider's related functions. fective way to support physicians in reforming prescribing
Unfortunately, these restrictions can keep patients who through a variety of initiatives. Examples of leveraging
may benefit from the drug from receiving it in a timely pharmacy expertise include dedicated unit pharmacists,
and accurate manner, and can prompt the provider to fo- pharmacy admissions interviews, pharmacy-managed pro-
cus on getting through cumbersome mechanics rather than tocols, and pharmacist-led ambulatory care c l i n i ~ s . [ ~ , ' ' , ' ~ ~
paying attention to the drug's safe use. Restrictions should Thus, the process-improvement approach to the safety
be thought of in the context of the entire medication-use of the medication-use cycle goes beyond the celebrated
process, not just one drug. The thought process should be cases and first stories to scientifically investigate the sys-
expanded to include safe handling of other potentially tem as a whole. Data on near-misses and uncelebrated er-
lethal drugs, not just the one that harmed a patient. rors should be analyzed to find hidden flaws and strengths,
Because each step in the medication-use cycle can be and to better understand the dynamics of our medication-
associated with preventable medication errors and ADEs, use system. Scientific investigation of the whole cycle-
systems must be assessed and enhanced, in their entire peeling away the layers of the onion-will reveal latent
scope and each component. Fig. 2 lists 22 examples of points of failure and facilitate a redesign that substan-
strategies for identifying and preventing medication er- tially reduces the occurrence of harmful outcomes."
rors and adverse drug events by reforming various com-
ponents of the medication-use cycle. In addition, in their roach
standards for medication use, the Joint Commission of
Accreditation of Healthcare Organizations (JCAHO) re- The second scientific approach to prevention focuses on
cognizes that the multidisciplinary teams must be respon- negative patient outcomes (ADEs) rather than on process
sible for all components of the medication-use cycle. (medication errors). The outcomes-measurement approach
Keys to improving reporting and event capture usually pioneered by C l a ~ s e n " ~views
] the process-improvement
result when reporting is nonpunitive or easy to do, or angle as flawed because it does not distinguish between
when dedicated resources such as an ADE specialist or medication errors and ADEs. Although dissecting med-
observers are in place or incentives are used."'] Although ication errors may improve patient outcomes, only 1% of
reporting and event capture can be improved, they will all medication errors result in ADEs and 50% of ADEs
never be perfect. A related and important strategy is to can be p r e ~ e n t e d . " ~The
] extensive studies of the drug-
proactively learn from the experience of other organiza- use process and of error prevention have often been done
tions. Comparisons can be made with other organizations at the expense of demonstrating ways of identifying and
through such reporting mechanisms as the Institute for preventing ADEs that produce actual patient harm.
Safe Medication Practices (ISMP) Newsletter, FDA Improving the system (preventing medication errors)
Alerts, USP' s MedMARx national medications errors does not necessarily improve patient outcomes or reduce
Medication Errors and Adverse Drug Events Prevention 539
costs. The outcomes-measurement approach advocates plan through a multidisciplinary team approach with the
the rigorous study of the epidemiology of actual ADEs, support from executive management, 3) set priorities
combined with continuous quality improvement techni- and timelines for corrective actions in accordance with
ques and nonpunitive communication to achieve a true the organization's strategic planning and budgeting pro-
impact on patient safety through improved outcomes. cesses taking into account the cost effectiveness and
Specifically, the outcomes-measurement approach feasibility of the strategy for the organization, and 4)
asserts that rigorous tracking of actual ADEs, coupled work through local constraints or risks to provide a safer
with an epidemiologic investigation of their sources, is the medication-use system for patients. The process-improve-
foundation for improving patient outcomes through ment approach may be more appropriate in a health care
prevention, research, and education. Computerized sur- practice environment where systems are clearly not
veillance systems have already shown great potential to providing the safety net they should be. In other or-
prevent ADEs through such mechanisms as alerts about ganizations, a focus on preventing negative outcomes
drug allergies, drug interactions, and inappropriate do- may provide the best investment in patient safety. Both
sages. Many ADEs result from a lack of integrated in- strategies have validity because processes and out-
formation at the point of clinical decision making rather comes overlap.
than from carelessness or lack of knowledge.
Measurement of the outcomes of ADEs cannot wait
until the health care organization has an electronic medi-
cation record or a comprehensive, computerized disease- TY
management surveillance system. An ADE outcomes-
The objective of this section is to introduce readers to the
prevention project should be selected and implemented.
concepts of human reliability in the complex medication-
Good tools certainly make measurement faster and easier,
but in their absence there are still many outcomes-mea- use cycle. It is not intended to replace comprehensive
treatments of the discipline of human factors research
surement strategies that can be successfully used to pre-
already available but rather to provide a starting point for
vent ADEs. Various researchers have studied the causes
readers to view human reliability and specifically human
of ADEs by tracking them to their root causes, even
errors in the medication-use cycle from a different and
though this was done through an entirely manual system
of chart reviews and drug usage evaluation^."^^ Common more dynamic The study of human
reliability gives insights into how health care providers
findings of major causes of preventable ADEs were re-
operate under competing demands and time limits in
lated to dosage errors (e.g., with renally excreted drugs),
caring for patients. There are many factors affecting
drug allergies, and initial use of new drugs. Pharmacists
human reliability. Some factors move human reliability
can use many drugs with potentially severe adverse ef-
fects safely with appropriate monitoring, intervention, and toward loo%, while others drive it away"' (Fig. 3).
Human reliability never reaches 100% all the time but
education. Typical examples from the literature or an
knowing what influences human behavior to become
organization's own ADE-tracking or medical records sys-
more reliable can be used to develop added strategies to
tem might include analyzing the use of antimicrobials in
association with ADEs, admissions due to ADEs or visits
to ambulatory clinics due to ADEs."~-'~]
100%
Systematic and timely feedback are keys to generating
cooperation so that ADEs in progress do not become more
severe and can be prevented in the future. Feedback
should be communicated in a nonpunitive way to en-
courage cooperation with and enthusiasm for a program
of research, education, and prevention.[*']
reduce medication errors and ADEs. Three types of such as task design, technology and information man-
human behavior influence human reliability and thus can agement. work measurement and methods improvement,
be used to expand the approaches to reducing medication and policies and procedures. Resource system analysis
errors and associated ADEs‘~’(Fig. 4). includes such factors as tools, equipment, support from
others, and time. In exhibiting imperfect behavior, health
care providers are trying to do their best, are not engag-
ing in risk-taking behavior, and are in a situation where
The first aspect of human reliability focuses on situa- their human reliability or performance is shaped by the
tions where humans can not produce 100% reliability all system in which they operate. Thus, solutions to imper-
the time. Although we cannot change our nature as fect behavior decreasing human reliability are not dis-
humans, we can change the medication-use system in ciplinary or punitive but are systems analysis and re-
which we work. Imperfect behavior is the product of design oriented.
systems design. The classic example is physician hand-
written medication orders that are often illegible or in-
complete. This is a system designed to produce errors. It
is natural or normal for errors to occur with this “as- The second aspect of human reliability focuses on situa-
designed” system. For the average physician, pharma- tions where humans unintentionally engage in risk taking.
cist, nurse, or patient, quality and safety fail when the At-risk behavior means that intentional conduct uninten-
medication-use system fails. The approach to decreasing tionally results in creating a significant and unjustifiable
imperfect behavior and increasing human reliability is risk that may cause an undesirable outcome. The classic
to identify and change those system factors that ne- example of this is the need for the health care provider to
gatively affect human reliability. These system factors provide patient care simultaneously, both quickly and ac-
fall into four categories: people, environment, actions, curately under conditions of competing demands and time
resources. Human system analysis includes such factors limits. There are three at-risk cognitive factors affecting
as knowledge, skills, physical capability, adaptability, human reliability (both expertise and error) within the
and fallibility. Environmental system analysis includes medication-use cycle: knowledge factors, attentional dy-
such factors as temperature, noise, light, peer commu- namics, and strategic factors.‘211
nication, facility layout and location, and management/ Knowledge factors are the types of knowledge that are
labor relations. Action systems analysis include factors available to solve problems as they arise in the medi-
Medication Errors and Adverse Drug Events Prevention 541
cation-use process. It is normal for health care providers Thus, attributes of at-risk behavior are judged against a
to adopt a limited number of strategies to deal with pro- specific outcome, judged risky by an external observer,
cesses or routine variations within the medication-use involve a choice between different behaviors, are not
process. However, when an unusual or surprising situation understood to be of significant or unjustifiable risk by the
presents itself, the relevant knowledge may be inadequate, health care provider taking the risk, and are generally
imprecise, or too simplified. For example, risks of new considered more blameworthy than system-induced or
drug therapy are not always perfectly predictable, because imperfect behavior errors.
drugs are tested in a small subset of the general po- The approach to decreasing at-risk behavior and in-
pulation. Known adverse effects do not occur in all reasing human reliability is to change incentives so those
patients given the new drug. In many cases, it is easier to safe behaviors are chosen over at-risk behaviors. In health
see the benefits the patient could receive from the drug care systems where mediation-use systems already have
than to determine the risks associated with the drug. appropriate checks and balances, changing at-risk beha-
Attentional dynamics are how humans control and viors represents the largest opportunity for safety and
manage the mental workload as circumstances develop quality gains since medication errors and ADEs are often
and change over time. The mind can pay attention to only side effects of weak cognitive functions. The analysis and
so many situations at a time, so attention shifts as events corrective actions should include 1) creating a tally sheet
occur. If a situation comes to light that does not agree of incentives for comparison of safe behaviors with at-risk
with what is expected, attention usually shifts to in- behaviors for a specific function or area in the med-
vestigate. An ICU patient often receives numerous intra- ication-use cycle so that safe behavior can be compared
venous medications. If the wrong one is infused (e.g., a with at-risk behavior, 2) rate each incentive as strong or
vasopressor), the patient would receive an incorrect drug weak, and 3) modify incentives to change behavior. It is
and suffer the consequences. The responding health care essential to recognize that the strength of safe or at-risk
providers might not immediately discern that the wrong behaviors is influenced by the following factors: 1) cer-
drug was infusing. The providers would probably focus tain consequences are stronger than uncertain conse-
their attention on whatever seemed necessary to address quences, 2 ) consequences are stronger than policies and
the patient’s adverse reaction (e.g., lowering the blood procedures or other environmental factors, and 3) imme-
pressure) even though the source of the event was not diate consequences are stronger than delayed conse-
known. Humans are great at recovery after an event, even quences. In exhibiting at-risk behavior, the health care
when their lack of attention might have been the source of provider’s conduct is intentional but they do not under-
the problem. stand that the conduct itself significantly increases the risk
Strategic factors are how humans deal with situations of a negative consequence, and is a situation where their
when conflicting goals are present and the best course of human reliability or performance is shaped by expediency
action is not readily apparent (because, for example, of and at-risk incentives rather than safe practices and po-
limited resources and the need to act immediately). The tential consequences. The health care provider may be
health care provider must decide whether to act im- negligent in that they should have been aware of a
mediately with inadequate information, to wait for more substantial and unjustifiable risk and under the law may
information to be become available, or to consider other be required to provide compensation. However. for the
alternatives. This may result in the misapplication of health care organization, the solutions to at-risk behavior
usually good guidelines. In hindsight (after all the stra- decreasing human reliability are not disciplinary or pu-
tegic factors are known), the decision made as the si- nitive but are incentive oriented. Punitive sanctions are an
tuation evolves often appear to be reckless. If a phar- obstacle to other initiatives such as event r e p ~ r t i n g . ‘ ~ ]
macist receives five critical orders simultaneously, then Correct solutions to at-risk behaviors include such things
he/she must decide which one to fill first or to call for as enhanced management -front line worker communica-
help. The pharmacist must decide whether to dispense tion and direction, increased health care team training
the drugs immediately or first check a suspiciously high versus just technical or professional training, and consis-
dose in relationship to other variables when the values tent errors management awareness.
are not immediately available. If the pharmacist dis-
penses the suspiciously high doses and the patient’s Mi
outcome is positive, the dispensing will be reviewed as
uneventful even though the safety margin was reduced. The third aspect of human reliability focuses on si-
However, if the outcome is negative, the pharmacist may tuations where humans intentionally engage in risk
be seen as reckless and having made an error. taking. High-culpability behavior means that the person
542 Medication Errors and Adverse Drug Events Prevention
consciously disregarded the fact that their conduct time to be in the pharmacy profession and pharmacists
would significantly and unjustifiably increase the risk should act the part. The following practice management
that negative consequences would occur. The risk must guidelines are presented as a practical approach by which
be of such a nature and degree that, considering the pharmacists can shape their own practice environments
circumstances known to the healthcare provider, its dis- to decrease medication errors and ADEs and increase
regard involves a gross deviation from the standard of patient safety. Medication quality only begins when pa-
care that a reasonable employee would observe in his tient safety begins. Therefore, medication safety strate-
situation. The approach to decreasing high-culpability gies should be an essential part of evidence-based me-
behavior is disciplinary or punitive because high-culp- dicine practices.
ability behavior must be changed or the person cannot
continue to function as a healthcare provider. High-cul- Practice management guideline #I : Make medication
pability behavior is the single behavior where punitive safety improvement a pharmacy leadership priority. Every
sanctions should be considered as a s~lution."~ Punitive recent treatise on error management recognizes lever-
strategies may include such things as progressive discip- aging pharmacy expertise as an essential key in prevent-
linary actions, time off, punitive training or duties, and ing medication errors and ADEs. A multidisciplinary
even termination. medication safety team and a 5-year medication safety
In summary, human nature can not be changed, but plan should be part of every pharmacy department or
the changing the circumstances under which it operates health care team's strategic plan. As the drug therapy
in the medication-use process can enhance human re- experts, pharmacists should be in leadership positions to
liability. Traditional responses to a medication error and create medication cultures of safety.
resultant patient harm include discipline, new rules, re-
training, technology, or environmental changes. These Practice management guideline #2: Stop using the
responses have a place but they address symptoms rather medication error reporting system primarily for punish-
than trying to understand human reliability. Unfortunate- ment and shift the emphasis to using reporting for
ly, most of the time traditional responses have assumed improvement. Instead, help to create an environment in
that human recklessness or high-culpability behavior was which fear may be alleviated in large part by creating an
the root cause of the error when it was not. Traditional open and safe environment for detecting, reporting, and
approaches have sought to regiment, rather than en- investigating how errors and ADEs occur so they can be
hance human reliability. Preventable medication errors reduced in the future. Extend the collegial peer review
and ADEs happen because of reliance on weak human process of morbidity and mortality conferences to the
cognition and reliability. Strategies that seek to mini- context of improving medication safety. There has been a
mize human error (e.g., adding additional procedures and great deal of erosion of trust, and it is exceedingly dif-
steps) can often make the system more prone to medi- ficult to have a high-performance organization without
cation errors and ADEs at other points, even though the having a high-trust organization.
intention was exactly the opposite. Strategies designed to
enhance human reliability have a higher probability of Practice management guideline #3: Initiate and main-
making the medication-use cycle safer for patients. Much tain ongoing self-assessments of the safety of individual
effort has been put into improving processes and out- clinical practices as well as with the health care team, the
comes in the medication-use system, but human relia- pharmacy department, and the organization. Use the learn-
bility has been largely ignored. Successful preventive ing experiences of others and self to proactively imple-
strategies must take into account human abilities and ment known "best practices" locally to prevent medica-
limitations, and will use these strategies to correct for the tion errors and to develop your own safety audit tools. Be
limitations, and to enhance the abilities. dissatisfied with the status quo and seek to develop an
error management vision and then take the practical first
steps to implement it.
THE ROLE OF THE PHARMACIST
Practice management guideline #4: Be accountable
The IOM Report has given health care a clear mandate to for medication safety by designing, implementing, and
make the medication-use cycle safer and has given phar- maintaining safe practices in the medication-use cycle.
macists a clear opportunity to shine. Pharmacists must This might include such things as educating patients and
have an unwavering commitment to the priority of pre- their families regarding appropriate use of their medica-
venting medication errors and ADEs. Now is a significant tions, using protocols for the use of potentially lethal or
Medication Errors and Adverse Drug Events Prevention 543
narrow therapeutic index drugs, insisting that pharmacy The urgent need to enhance the safety of drug therapy
(not nursing) prepare all intravenous admixtures, and im- shows that the medication-use cycle must change. Phar-
plementing technology, automation, and information sup- macists as the drug therapy experts are positioned to
port systems that enhance the frontline pharmacist’s abi- shape their practice environments to focus attention on a
lity to care for patients. critical set of priorities to enhance the medication-use
cycle to better serve patient welfare and safety.
Practice management guideline #5: Integrate medica-
tion safety understanding into all pharmacist, technician,
resident, student training continuing education, and CONCLUSION
evaluations. Ensure that everyone understands that
medication safety is everyone’s business and everyone Much of the knowledge developed about medication
has a role in keeping patients safe. If the messenger aide errors and ADEs has depended on the ability of individual
does not understand the importance of delivering the pharmacists to detect problems and take an active part in
needed intravenous admixture to the right patient care resolving them. The increasing use of complex medica-
area on time, everything that the clinical specialist did in tion regimens has drawn attention to the number of
customizing the drug therapy and the staff pharmacist in iatrogenic medication errors and ADEs, as well as their
reviewing the medication profile and preparing the order associated costs. Pharmacists must work to reduce pre-
can become academic. disposing factors so that safety can be enhanced and costs
reduced. A new practice model as an adjunct to evidence-
Practice management guideline #6: Realize that com- based medicine practices must be created to prevent
peting priorities and severe financial constraints are the medication errors and ADEs, and to let others outside the
environment in which health care organizations operate pharmacy know that we are ready to lend our expertise
today. If the organization needs to improve revenues and energy to this critical endeavor.
or margins by a certain percentage, can the pharmacist
quantify how medication error and ADE prevention con-
tribute to the financial goal? Further, can the pharmacist REFERENCES
demonstrate why the health care organization should shift
limited resources to medication error management over 1. Voelker, R. ‘Treat systems, not errors,’ experts say. JAMA,
some other worthy and cost-effective goal? Demonstration J. Am. Med. Assoc. 1996, 276. 1537-1538.
of a positive impact on patient outcomes and health care 2. To Err is Human: Building a Safer Health System; Kohn,
costs is a prerequisite to getting needed resources for L.T., Corrigan, J.M., Donaldson, M.S., Eds.; National
medication safety, but it is not a guarantee. Financial con- Academy Press: Washington. DC, 1999.
straints and competing priorities are perhaps the most 3. Medication errors rank as a top patient worry in hospitals,
daunting challenge, but they are also simultaneously the health systems. ASHP Press Release. September 7, 1999.
4. Medication Errors; Cohen, M.R., Ed.; American Phar-
greatest opportunity.
maceutical Association: Washington, DC, 1999.
5 . Error Reduction in Health Care: A Systems Approach to
Practice management guideline # 7 Make medication Improving Patient Safety; Spath, P.L., Ed.; Jossey-Bass
safety research a priority. How can technology and in- Publishers: San Francisco, 2000.
formation management be deployed to make the medica- 6. Human Error in Medicine; Bogner, M.S., Ed.; Lawrence
tion-use cycle safer and position pharmacists to better Erlbaum: Hillsdale, New Jersey, 1994.
care for patients? How will gene therapy affect the de- 7. Marx, D. Managing Human Error in High-Risk Industries
mand for traditional drug therapies, and will pharmacists Seminar. Houston, Texas; December 1999.
be in the forefront of safely managing gene therapy? In- 8. The Advisory Board Company. The Year 2000 Engage-
tuitively, medication error and ADE prevention should ments; The Advisory Board Company: Washington, DC,
result in better financial, clinical, and humanistic out- 2000.
9. Runkle, D.C. The Scientific Investigation of Avoidable
comes, but added meaningful outcomes measurement and
Patient Injury: Two Approaches. In Proceedings of
research are needed to validate that business costs rise
Enhancing Patient Safety and Reducing Errors in Health
significantly with poor quality and safety. If pharmacists Care; Schettler, A.L., Zipperer, L.A., Eds.; National
do not make medication safety research a priority, it is Patient Safety Foundation: Chicago, 1998; 51 -52.
likely that this role will be filled by other health care 10. Cook, R.I.; Woods, D.D.; Miller, C. A Tale of Two Sto-
providers, regulatory agencies, or even sophisticated in- ries: Contrasting Views of Patient Safety; National Pa-
formation systems. tient Safety Foundation: Chicago, 1998.
544 Medication Errors and Adverse rug Events Prevention
I I. Reason, J. Human Error; Cambridge Univ. Press: New 17. Princc, B.S.; Goetz, C.M.; Rhin, T.L.; Olsky, M. Drug-
Uork, 1990. related emergency department visits and hospital admis-
12. The Advisory Board Company. Prescription f o r Change sions. Am. J. Hosp. Pharm. 1992, 49. 1696-1700.
Seminar; The Advisory Board Company: Washington, DC, 18. Aparasu, R.R.; Helgeland, D.L. Visits to hospital
September 30-October 1, 1999; Dallas, Texas. outpatient departments in the United States due to
13. Crane, V.S. New perspectives on prcventing medication adverse effects of medications. Hosp. Pharm. 2800, 35,
errors and adverse drug events. Am. J. Health-Syst. Pharm. 825 831.
2000; 57, 690-697. 19. Leape, L.L.; Cullen, D.V.; Clapp, M.D.; Burdick, E.;
14. Classen, D.C. Adverse Drug Events and Medication Errors: Demonaco, H.J.; Erickson, J.1.; Bates, D.W. Pharmacist
The Scientific Perspective. In Proceedings of Enhancing participation on physician rounds and adverse drug events
Putient S c f e y and Reducing Errors in Heulth Caw; Na- in the intensive care unit. JAMA, J. Am. Med. Assoc.
tional Patient Safety Foundation: Chicago, 1998; 56-60. 1999, 282, 267-210.
en, D.C.; Evans, R.S.; Pestonik, S.L.; Horn, S.D.; 20. Clemmer, T.P.; Spuhler, V.J.; Berwick, D.M.; Nolan, T.W.
Menlove, R.L.; Burkc, J.P. The timing of prophylactic Cooperation: The foundation of improvement. Ann. Intern.
administration of antibiotics and the risk of surgical wound Med. 1998, 128 (12, part I); 1004-1009.
infection. N. Engl. J. Med. 1992, 326, 281 286. 21. Cook, R.I.; Woods, D.D. Operating at the sharp end: The
16. Dennehy, C.E.; Kishi, D.T.; Louis, C. Drug-related illness complexity of human crror. In Human Error in Medicine;
in emergency department patients. Am. J. Health-Syst. Bogner, M.S., Ed.; Erlbaum: Hillsdalc, New Jersey, 1994;
Pharm. 1996, 53, 1422-1426. 258-287
PHARMACY PRACTICE ISSUES
It is helpful to get organization-wide consensus on the corrective actions had the desired impact (docu-
priorities for medication use improvement. Issues that fall ment improvement) and to guide subsequent in-
into more than one category, for example, frequent and cremental steps if further improvement is needed.
high risk or problem-prone, should be addressed or
evaluated first. To be most effective, a majority of MUE program
resources need to be devoted to education and process
improvement, rather than measurement and simple data
CESS collection. An additional important component is regular
(at least annual) evaluation of the overall MUE program
In its simplest form, the MUE process is an ongoing to assess its value and improve the MUE process.
improvement cycle with no set beginning or end. For each
identified high-priority issue, there are four major action
steps:
1. IdentiJL or determine the standard of care or Assessments of medication use can be performed through
optimal use: Therapeutic guidelines and consensus a concurrent, retrospective, or prospective study design
documents and standards established by national (or a combination of these approaches). Each type has
professional organizations or governmental groups advantages and disadvantages.
often define ideal processes and outcome goals. Retrospective review is conducted after the patient has
Healthcare organizations may adopt national guide- received a medication, and the treatment is complete.
lines, or adapt them for local use. An evidence- Medical charts or computerized records are screened to
based medicine approach can also be used to de- identify patterns and trends. This may be the simplest type
velop guidelines or clinical pathways to meet local to perform, because large amounts of data can be reviewed
needs. It is important to gain consensus from prac- quickly, and the outcomes are known. Information gained
titioners who will utilize guidelines as part of the from large retrospective reviews is helpful for problem
implementation process. Ideally, guidelines and identification and initiating actions that will benefit future
protocols should be shared across an organization patients. However, inaccurate or incomplete documenta-
to encourage implementation before current prac- tion could limit the usefulness of information collected.
tices are evaluated. Concurrent review is performed during the course of
2. Data collection (compare actual to optimal): This treatment and often involves ongoing monitoring of drug
step is the “evaluation,” where performance is therapy. Concurrent evaluation gives pharmacists the
measured against objective criteria for the pro- opportunity to intervene if potential problems are de-
cesses or outcomes of care. Criteria may relate to tected, and thus, current patients can benefit. This type
indications (for selection of a particular medication of review also allows additional information to be col-
or procedure), processes (drug dosing and ad- lected if documentation is incomplete (such as querying
ministration, patient assessment and monitoring) prescribers, observing behavior, or interviewing patients).
or outcome measures (cure, relief of symptoms, The concurrent approach can be integrated with case
treatment failure, adverse drug event, patient sa- management or ongoing pharmacist monitoring activities.
tisfaction). It may be more time-consuming if data is collected on
3. Intervene: If indicated, corrective actions should be individual patients over time. Furthermore, if outcome
taken to improve processes, practices, or medica- data is required, it may be months or years before out-
tion use. Possible actions include the development comes are known and data collection can be completed.
of consensus statements or guidelines when they do Prospective review takes place before medication use,
not already exist, providing feedback on perform- and thus, its usual focus is on patient assessment and
ance, education of health professionals (seminars, prescribing. This approach to evaluation can detect and
newsletters, feedback letters, one-on-one commun- resolve potential problems in individual patients before
ication), creation of tools to support use of guide- they occur. Pharmacists routinely perform prospective
lines and treatment protocols (such as standard reviews when assessing new medication orders for pos-
order sets. computerized pathways, pocket cards), sible drug interactions, accurate dosing, or duplicate the-
redesigned processes, or patient education. rapy. Data collection occurs at only one point in time and
4. Evaluate the impact of the intervention: Additional can easily be integrated with daily pharmacist care ac-
data collection or ongoing monitoring to ensure tivities. However, while data collection for a single pa-
548 Medication Use Evaluation
tient may not be very time-consuming, it can take a long Expensively” or “Don’t Use Ever,’”171because the focus
time for data to be collected on enough patients to draw became punitive actions against individual practitioners
conclusions and guide improvement efforts. with a focus on cost control rather than quality im-
provement. To have legitimacy within the organization,
the emphasis must be on actions that truly improve
outcomes for patients. The program must have both
the administrative authority to promote positive change
The professional literature, national treatment guidelines, and support (“buy-in”) from practitioners at every level.
and locally developed protocols provide key resources for One important consideration is to avoid using words that
the development of MUE criteria. Various professional imply control or a loss of professional autonomy, because
groups as well as private businesses also produce medi- these can be threatening to practicing physicians. Rather
cation-specific, disease-specific, or process-oriented cri- than labeling an action “appropriate” (with the connota-
teria that can be adapted for local tion of condescending approval or disapproval), state that
Performance measurement systems, such as the it is “consistent with the published literature” or “meets
HEDISE (Health Plan Employer Data and Information Medical Staff-approved criteria”; use “evaluation” rather
Set) managed by the National Committee for Quality than “enforcement” and “consult” or “inform” instead
Assurance (NCQA)[I4’ and the ORYX Initiative of the of planning an ~~intervention.~9“8’
Joint Commission on Accreditation of Healthcare Organ- Because evidence-based medicine is an evolving dis-
izations (JCAHO)“~] provide indicators for identifying cipline, and the state of knowledge is constantly changing,
concerns and monitoring the impact of improvement guidelines must be frequently updated. Indicators, cri-
initiatives. In Australia, the government is developing a teria, and even process improvements need to be reas-
searchable database of major quality use of medications sessed to ensure they remain valid.
(QUh4) initiatives as a means of sharing resources and Often, an MUE program commits to too many ini-
ideas.[I6] tiatives, resulting in insufficient time and energy to
Computerized databases (such as insurance billing files complete any of the projects. Follow-through is essential
or electronic medical records) greatly improve the ability when corrective actions are implemented-the impact
to gather and evaluate information compared to manual must be assessed and adjustments made if needed. If an
data collection (e.g., chart reviews). Computer software MUE program becomes authoritarian, bureaucratic,
programs, including proprietary software designed spe- emphasizes analysis of data rather than action, or loses
cifically for MUE functions, may be helpful in managing sight of its mission to improve care, it will be ineffective.
data and reporting. MeTE must be seen as a tool or means to foster improved
medication use processes and safer, more effective me-
dication use, rather than an end in itself. Achieving and
VALUE OF MUE maintaining improvement requires not only streadin-
ing systems and processes, but also changing the be-
The key to MUE is not the “drug use review” or havior of healthcare practitioners and patients-a diffi-
“evaluation” but the improvement process that is guided cult proposition.
by the information learned about medication use. The
MUE program can be an important tool for gaining pro-
fessional consensus and focusing organizational energy
on activities that will improve medication-related out-
comes. An MUE program can be used to integrate a Stolar, M.H. Drug-use review: Operational definitions.
number of important medication improvement initiatives, Am. J. HOSP.P h m . 1978, 35 (1). 76-78.
such as the formulary system, adverse drug reaction re- Todd, M.W. Drug Use Evaluation. In Handbook of
porting, medication error prevention, pharmacist inter- Institutional Pharmacy Practice, 3rd Ed.; Brown, T.R.,
Ed.; American Society of Hospitai Pharmacists: Beth-
ventions, and other clinical pharmacy services.
esda, Maryland, 1992: 261-271.
Medicaid progam: Drug use review program and elec-
tronic claims management system for outpatient drug
LIMITATIONS AND PITFALLS OF claims. Fed. Regist. 1992, 57.49397-49412 (Nov. 2).
Principles of Drug Utilization Review @UR) adopted by
According to critics, the way DUE was practiced in many American Medical Association, American Pharmaceutical
institutions might better be described as “Don’t Use Association, and Pharmaceutical Manufacturers Asso-
Medication Use Evaluation 549
ciation, 199 I , (based on a quotation from Ruckcr TD. Drug- 10. Phillips, M.S. Collaborating with physicians in the drug-
utilimtion review: Moving toward an effective and safe usage evaluation process. Top Hosp. Pharm. Manage.
model. In Society and Medication: ConfZicting Signals ,ji)r 1991, I / (I), 38 45.
Prrscribers and Patients; Morgan, J.P., Kagan, D.C., Eds.; 1 1 Criteria ,for Drug Use Evaluation; American Society
Lexington Books: Lexington, MA, 1983; 25-5 I ) . of Hospital Pharmacists: Rethcsda, Maryland, 1993;
5. American Society of Health-System Pharmacists. ASHP Vol. 4.
guidelines on medication-use evaluation. Am. J. Health- 12. APhA Guide to Drug Treatment Protocols: A Resource for
Syst. Pharin. 1996, 53 (X), 1953 -1955, May also be ac- Creating and Using Disease-Specqic Patlzways; Mano-
ccssed at http://www.ashp.org/bestpractices/formuIary/ lakis, P.G.. Ed.: American Pharmaceutical Association:
guide/medication.pdf (accessed October 2000). Washington, DC, 1996.
6. The Academy of Managed Care Pharmacy. Drug Use 13. Drug Regimen Review: A Process G ~ i i dJor
e Pharmacists,
Evaluation. In Concepts in Managpd Care Phurmacy Ap- 3rd Ed.; American Society of Consultant Pharmacists:
prcivpd by the AMCP Board of Directors; June 12, 1999 Alexandria, Virginia, 1998.
(accessed at http://www.amcp.org/professional_res/ 14. http://www.ncqa.org and http://www.ncqa.org/Pages/
concepts/index_conccpts.asp, July, 2002). Communications/News/somcr~l00.htm (assessed Oct
7. Nadzam, D.M. Development of medication-use indicators 2000).
by the Joint Commission on Accreditation of Healthcare IS. http://www.jcaho.org/oryx-frm.html (assessed Oct. 2000).
Organizations. Am. J. Hosp. Pharm. 1991. 48 (9), 1925 16. http://www.quminap.health.gov.au (assessed Oct. 2000).
1930. 17. Enright, S.M.; Flagstad, M.S. Quality and outcome:
8. Angaran, D.M. Quality urance to quality improvement: Pharmacy’s professional imperative. Am. J. Hosp. Pharm.
Measuring and monitoring pharmaceutical care. Am. J. 1991, 48 (9), 1908 1911.
Hosp. Pharm. 1991, 48 (9), 1901- 1907. 18. Teagarden, J.R. A-E-I and you. Thrcc words you can’t use
9. Dzierba, S. Limited resource approach to drug-use review. in drug usage evaluation programs. Hosp. Pharm. 1991,26
Top Hosp. Pharm. Manage. 1991, I 1 (l), 87-91. (7), 590, 615.
PHARMACY PRACTICE ISSUES
“Drugs used to treat human immunodeficiency virus and its clinical manifestations.
NR = not reported, WIG = intravenous immunoglobulin.
New England Journal of Medicine has pointed out, surance Association of America: 1) The American Hos-
“publication of an article on the unapproved use of a pital Formulary Service Drug Infomation ( A H F S DI);
drug in a peer-reviewed journal is no guarantee of safety 2 ) The American Medical Association Drug Evaluations
or efficacy.”[81 However, in some clinical situations, (AMA DE); and 3 ) The United States Phamzacopeial
such as pediatrics, unlabeled uses may be rational and Drug Information (USP DI). The infomation in
represent the most appropriate treatment for optimal pa- is derived from published medical literature, as we11 as
tient care. scientific meetings, educational programs, professional
When the unlabeled use of an approved drug endangers interactions, and comments provided by editorial review-
the public health, the FDA is obligated to investigate ers. Not all unlabeled uses included in A N F S DI are well
thoroughly and to take whatever action is warranted to established. Some unlabeled uses may be acceptable but
protect the public. The FDA can require a change in the are considered investigational because of limited experi-
labeling to warn against the unlabeled use, seek evidence ence. Unlabeled uses listed in the USP DI are selected by
to substantiate the use, restrict the channel of distribution, USP Advisory Panels based on current literature, current
and even withdraw approval of the drug and remove it prescribing, and utilization practices. The AMA DE is no
from the market. In such instances, the official labeling longer published, but its contents have been incorporated
may include a prominently displayed “box warning” to into USP DI. None of these authoritative textbooks in-
alert practitioners that certain uses are hazardous and, in clude references.
effect Additional resources that pharmacists can use for in-
formation about unlabeled indications include medical
and pharmacy textbooks, handbooks, journals, electronic
databases, and the Internet. Although the Internet can be
The American Society of Health-System Pharmacists a useful resource for finding information, many sites of-
states that pharmacist should serve as patient advocates fer unreferenced information, often with unsubstantiated
and drug information specialists concerning unlabeled claims. Drug information services staffed by pharmacists
uses of medications.“’] Pharmacists must evaluate the trained in the retrieval, interpretation, and dissemination
available information to assess product efficacy and of medical literature are excellent resources for deter-
patient safety. Therefore, pharmacists must have access mining if an unlabeled use of a drug is appropriate.
to accurate and unbiased information about unlabeled Another concern for pharmacists is manufacturers’
uses of prescription drugs. The following textbooks are distribution of information on unlabeled drug uses. The
recognized as authoritative sources on unlabeled uses by FDA Modernization Act passed by Congress in 1997 al-
the FDA, Blue CrossBlue Shield, and the Health In- lows pharmaceutical companies to distribute reprints of
552 Medication Use for Unapproved Indications
peer-reviewed journal articles or reference textbooks that carriers and managed care providers have elected to cover
include information about unlabeled uses of their products only those indications included in FDA-approved product
to health care practitioners." 1,121 The FDA does not in- labeling. Coverage has frequently been denied for un-
clude pharmacists as .'health care practitioners" thus li- labeled or non-FDA-approved indications, citing these as
miting access to informatior, about unlabeled indications "investigational' ' ~ s e s . 1 ~ ~ 1
disseminated by the pharmaceutical companies to physi- The Health Insurance Association of America has
cians. Pharmacists can and should gain access to this and created guidelines to assist insurers in assessing coverage
other information using the drug information resources for unlabeled drug uses. A growing number of insurance
discussed previously. It is important to perform a com- carriers are following these guidelines, which encourage
prehensive review of all information available on the un- the use of references such as the three authoritative drug
labeled uses of a medication and to not determine product sources, peer reviewed literature, and consultation with
efficacy or patient safety on the basis of a single source. experts in research and clinical practice to make specific
drug coverage decisions.[101
Dispensing a medication for an unlabeled use, dose, or At this time, there is minimal financial impact on phar-
dosage form does not violate federal law. In fact, to date, macists when insurance coverage is denied for an un-
no pharmacist is known to have been prosecuted for dis- labeled use of a medication. However, lack of FDA
pensing a product for an unlabeled use. However, a de- approval for drug reimbursement can affect patient safety.
viation from the safe and effective guidelines provided in Results of a 1991 General Accounting Office survey of
the product labeling does expose the pharmacist to some medical oncologists showed denials for unlabeled drug
liability. A pharmacist may be subject to malpractice ac- use by insurance companies were having adverse effects
tion if patient injury results froni the administration of a on the treatment decisions of one of every eight cancer
medication for an unlabeled use.[13314' patients.[161When an oncologist learns that a service,
Lack of criminal prosecution is not a predictor of future procedure, or drug is not covered by insurance, they often
actions or exposure to civil litigation. Therefore, it is choose another less effective therapy that will not jeo-
important for a pharmacist to be familiar with labeled pardize the patient's financial situation."'] Consequently,
indications and unlabeled uses of a drug and to be prepared pharmacists must consider if the chosen therapy is fi-
to defend the appropriateness of a drug's use in the event of nancially appropriate for the patient. If the patient can not
litigati~n.'~]Liability will be minimized if the pharmacist. afford the unlabeled medication, the pharmacist should
in the exercise of sound professional judgment, concludes assist in selecting the best alternative therapy.
that the use is rational, safe, and rea~onable."~]
In addition, a patient is entitled to know when a drug is
used for an unlabeled use. It is reasonable for the phy-
sician or pharmacist to inform the patient that the drug's
use is not FDA approved, it is safe and effective for other FDA-approved product labeling is not intended to set the
uses, and some data exist to support its unlabeled use. standard of medical practice, but to ensure consumer safe-
Such discussions should be documented in the patient's ty. However, product labeling often reflects the manufac-
medical record.[12]A consent form signed by the patient is turer's regulatory or financial concerns rather than current
highly recommended but is not currently necessary if the literature-supported information. Pharmacists must pos-
drug is used in the normal practice of sess good drug information skills, and have access to ac-
curate and unbiased information to assess therapeutic
appropriateness when dispensing medications for unla-
beled indications.
Pharmacists are faced with product efficacy, patient
Reimbursement for unlabeled uses of drugs has become safety, liability, and reimbursement issues when medica-
an important medical and financial issue. Decisions on tions are used for unlabeled indications. Lack of FDA
coverage for drug therapy are complicated because it is approval for a specific use should not prevent a phar-
often difficult to differentiate between an accepted stan- macist from dispensing an available drug. Rather, drugs
dard of practice, an evolving standard of practice, and should be used in a manner consistent with good medical
investigational therapies. Consequently, many insurance practice and in the patient's best interest. It is good pro-
Medication Use for Unapproved ~ n ~ j ~ ~ ~ ~ o n $ 553
fcssional practice for a pharmacist to bc familiar with a ing approved drugs for unlabeled indications. Am. J. Hosp.
drug's unlabeled uses, to evaluate the literaturc supporting Pharm. 1983, 40 (l), 792-794.
its use, and to kccp the patient informed. 14. McKenzie, C.A.; Barnes, C.L.; Boyd, J.A.; Poinsett-
Holmes. K. Unlabcled uscs lor approved drugs. U S .
Pharm. 1993. 18 ( 2 ) , 63- 76.
15. Lactz, T.; Silberman, 6. Rcimburserncnt policies constrain
the practicc of oncology. JAMA 1991. 266 (21); 2996-
2999.
1. Gorman, C. Double-duty drugs. Time 1995, 146 (12), 16. Ojf-Lube1 Driigs: Reimbucr.cmc~nt Po1ic.ic.c Corz.s/rain
96 97. Physicians in Their Choicc of Canrer Thc,mpie,s, GAO/
2. Cranston, J.W.; Williams, M.A.; Niclscn, N.H.; Bczman, PEMD-9 1-14; U.S. General Accounting Office: Washing-
R.J. For the council on scicntific affairs. Unlabeled indi- ton. DC 1991; 1-59.
cations of Food and Drug Adininistration-approved drugs. 17. Mortenson, L.E. Health care policies affecting the treat-
Drug Inl. J. 1998, 32, 1049 1061. ment of patients with cancer and cancer research. Cancer
3. Department of Health and Human Services. Use of ap- 1994. 74 (S7): 2204&2207.
proved drugs for unlabeled indications. FDA Drug Bull. 18. Erickson, S.H.; Bergman, J.J.; Schiieeweiss. R.; Cherkin,
1982, 12 (1). 4-5. D.C. Thc use of drugs for unlabclctl indications. JAMA
4. Serradell. J.; Galle, B. Prescribing lor unlabeled indica- 1980, 24.1 (1 5 ) . I543 1546.
~
tions. HMO Pract. 1993; 7 (1). 44-47. 19. Schwinghammer. T.L. Prescribing of oral metoclopramide
5 . Li, V.W.; Jaffe, M.P.: Li, W.W.; Haynes, H.A. Off-label for nonapproved indications. Drug Jntell. Clin. Pharm.
derinatologic therapies: Usage, risks, and mechanisms. 1984, 18 (4), 317 319.
Arch. Dermatol. 1998. 134 ( I I), 1449-1454. 20. Rrosgart. C.L.: Mitchell. Charlebois. E.; Coleman, K.;
6. Ratko, T.A.; Burnett, D.A.: l'oulke, G.E.; Matuszewski, Mehalko, S . ; Young: J.: Ahrams, D.Tl.1. Off-label drug use
K.A.; Sacher, R.A.; University Hospital Consortium Expert in human immunodeficiency virus disease. J. Acquired
Panel for Ofl-Label Use of Polyvalent Intravenously Ad- Immune Defic. Syndr. Hum. Rctrovirol. 1996, 12 (1). 56-
ministered lrnmunoglobuliri Preparations. Recommen- 62.
dations for off-labcl use of intravcnously adininistcred 21. Kayburn, W.F.; Farmer, K.C. Off-label prescribing during
immunoglobulin preparations. JAMA 1995, 273 (23). pregnancy. Obstet. Gynccol. Clin. North Am. 199'7. 24 ( 3 ) ,
1865 1870.
~ 47 1-478.
7. Chen, C.; Danekas. L.H.; Ratko, T.A.: Vlasscs, P.H.; 22. McQueen, K.D.; Milton, J.D. Multiccnter postmarketing
Matuszewski, K.A. A multicenter drug use surveillance of surveillance of ondansctron therapy in pediatric paticnts.
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13 Podell, L.B. Legal implications of preparing and dispens-
PHARMACY PRACTICE ISSUES
Y
William A. Miller
University of lowa, lowa City, lowa, U.S.A.
pharmaceutical representatives. Today's Doctor of Phar- Clinical Pharmacy (ACCP) was successful in getting the
macy curriculum prepares pharmacy graduates to retrieve, Board of Pharmaceutical Specialties to recognize phar-
analyze, and provide drug information to other health macotherapy as a specialty practice. The terms pharma-
professionals, patients, and committees concerned with cotherapy and pharmacotherapist were used in the final
health policy. In the last decade, there has been an ex- specialty petition, because these terms more clearly con-
plosion of information available to providers and patients noted a different type of pharmacist than the terms cli-
using information technology and the Internet. It is clear nical pharmacy and clinical pharmacist.1s391ACCP or-
that the provision of drug information, as suggested by the ganizational leaders and individuals involved with the
Commission, remains central to the future of pharmacy petition to recognize clinical pharmacy and eventually
practice. It is also clear that our educational programs pharmacotherapy did so with a belief that patient care
must prepare pharmacists to have more advanced drug quality would be enhanced by board certification of phar-
information skills to enable them to continue to be a pri- macists and thus meet the criterion set by the Commis-
mary source of drug information. sion. Since the report of the Commission, other know-
ledge-based specialties have also been approved as a part
Defining Pharmacy and Phar of the clinical pharmacy movement. Today, the profession
continues to debate the concept of differentiation and
The study commission indicated that a pharmacist must specialization as evidenced by the current debate con-
be defined as an individual who is engaged in one of the cerning the credentialing of pharmacists to provide di-
steps of a system called pharmacy. The Commission as- sease management services to patients and the need to
serted that they could not define a pharmacist simply as recognize advanced practice pharmacists in community
one who practices pharmacy. Rather, a pharmacist must settings who have greater knowledge and clinical skills
be defined as a one who practices a part of pharmacy, than many community pharmacists. Thus, the observa-
which is determined by the activities carried on in the tions of the Commission on differentiation and speciali-
subsystems of pharmacy. Further, the Commission stated zation live on.
that a pharmacist is characterized by the common deno-
minator of drug knowledge and the differentiated addi-
tional knowledge and skill required by his particular role.
The Commission predicted that the future role of phar- The Commission opined that curricula of colleges of
macists would emphasize dispensing of drug information pharmacy should be based upon the competencies desired
and not drugs.[51The Commission noted that although the for their graduates rather than upon the basis of know-
concept of clinical pharmacy was still evolving, it should ledge available in the several relevant sciences. The Com-
be regarded as a powerful force internal to pharmacy that mission suggested that one of the first steps to review a
would produce change in the system of pharmacy and the curriculum for a college of pharmacy would be to weigh
practice of pharmacists.[61 The Commission opined that the relative emphasis given to the physical and biological
differentiation did not equate to specialization. The Com- sciences against the behavioral and social sciences. The
mission defined differentiation based upon differences in Commission said we should start with the outcomes of the
place of practice, function, compensation arrangements, curriculum and work backwards to determine the course-
and patients served. The Commission stated that special- work needed to achieve the desired outcomes."01 Major
ization should be based upon uniqueness of knowledge changes in curricula for producing pharmacists have
and not place or function of patient service. Further, the occurred since the report of the Commission. The work
Commission offered cautionary comments about potential of the American Association of Colleges of Pharmacy
negatives in specialization and stated that specialization (AACP) Commission to Implement Change in Pharma-
could only be justified by improved quality and effec- ceutical Education" 1,121 and the revision of standards by
tiveness of patient care.[71Although the Commission re- the American Council on Pharmaceutical Education
port influenced the thinking of clinical pharmacy leaders (ACPE) led to adoption of the Doctor of Pharmacy deg-
about differentiation and specialization, clinical pharmacy ree as the sole entry-level degree for the profession. The
leaders rejected the notion that all pharmacists have the clinical component of most pharmacy curricula is now the
same knowledge and ability to improve the quality and single most significant component of the curriculum. The
effectiveness of patient care, and thus, pursued recog- Commission report was criticized for being too general
nition of clinical pharmacy as a specialty rather than as a and not specific about changes that should be made to
differentiated area of pharmacy practice as defined by the improve the curricula of colleges of pharmacy.[21 The re-
Commission. After many years, the American College of port of the Commission to Implement Change in Phar-
556 Millis Commission-Study Commission on Pharmacy
maceutical Education and revised ACPE standards pro- sider offering advanced professional degree programs
vided the specific detail needed to guide colleges to re- beyond the baccalaureate degree.[’41The Commission did
vise their curricula. Regretfully, some college curricular not define the terms graduate and advanced professional
reviews have ignored the recommendation of the Com- level. However, the report stimulated discussion of the
mission by approaching curriculum revision by starting role of Master of Science, Ph.D., and fellowship programs
with the existing curriculum and working forward to im- as methods to develop clinical scientists, further devel-
prove the outcomes of the curriculum. This approach opment of Doctor of Pharmacy degree programs as ad-
as noted by the Commission leads to less innovative vanced professional degree programs, and further devel-
and satisfactory approaches to achieving desired curri- opment of postgraduate residency programs to produce
cular outcomes. differentiated pharmacists for advanced professional
roles. The Commission considered the Doctor of Phar-
The Concept of Clinical Scientists macy as an advanced professional degree and warned
against colleges offering this degree without adequate re-
The Commission opined that the greatest weakness of s o u r c e ~ . [ ~The
~ ’ debate on the preparation of clinical
colleges of pharmacy is a lack of an adequate number of scientists or tenured track faculty continues today. A ma-
clinical scientists who can relate their specialized scien- jor issue likely to be confronted by academic pharmacy
tific knowledge to the development of the practice skills and the practice community is the future role of residency
required to provide effective, efficient, and needed programs in the preparation of pharmacy graduates for
patient service^."^] The concept of a “clinical scientist” general practice.
was discussed and debated in many forums after the
Commission offered this opinion. Since the report,
colleges of pharmacy with a research mission have hired Environment for the Preparation
faculty into tenured track faculty positions that require of Pharmacists
significant clinical research for promotion in addition to
teaching and service through clinical practice. These The Commission opined that the optimal environment for
faculty are now considered clinical scientists who con- pharmacy education is the university health science center
tribute to the advancement of scientific knowledge to but felt that adequate arrangements of colleges not located
enhance patient care. As tenure track clinical pharmacy in health science centers could be made to provide an
faculty developed as scientists, the amount of time they acceptable environment for the education of students at
spend in practice has declined due to the time demands the baccalaureate level.“41 This recommendation was
required to be a successful researcher and teacher. In debated within academic pharmacy. It caused colleges of
addition to tenured clinical faculty, full-time clinical pharmacy to examine whether they had adequate re-
track faculty positions have been developed at most sources and the environment to offer a postbaccalaureate
colleges to teach therapeutics and other clinical courses Doctor of Pharmacy degree program. It helped spur col-
and to serve as practitioner role models for students. leges to develop relationships with hospitals and other
Clinical pharmacy practitioners in various settings also healthcare organizations to provide clinical education and
frequently hold adjunct faculty appointments at colleges to add sufficient clinical faculty to deliver a quality post-
of pharmacy and serve as role models and teachers for baccalaureate Doctor of Pharmacy degree program. Over
clinical clerkships. Clinical faculty now significantly time, colleges with sufficient clinical faculty offered post-
contribute to the scholarship and research conducted by baccalaureate Doctor of Pharmacy degree programs.
colleges of pharmacy. Soon, all colleges will offer the Doctor of Pharmacy de-
gree as their sole professional degree program. Clinical
The Role of Graduate and Advanced pharmacy practice has evolved beyond the walls of the
Professional Educational Programs university hospital and other tertiary care hospitals to
community hospital, community pharmacy, ambulatory
The Commission stated that colleges of pharmacy with care settings, and other innovative practice sites. Today’s
adequate resources should offer programs at the graduate curricula are designed to prepare pharmacists to provide
and advanced professional level for more differentiated clinical pharmacy services to patients in all practice set-
roles of pharmacy practice. The Commission recognized tings. All colleges now seek and have arrangements with
the need for advanced professional education and stated multiple organizations to provide an acceptable envir-
that colleges without adequate resources and outside the onment for the preparation of pharmacists to provide
environment of a health science center should not con- clinical services.
Commission OIZ Pharmacy; Health Administration Press:
Ann Arbor. Michigan, 1975.
3. Pharmacists .for the Future: 7’he Report of the Study
The Commission opined that all aspects of credentialing Commission on Pharmacy; Health Administration Press:
of pharmacists and pharmacy education should be brought Ann Arbor, Michigan, 1975; 139.
4. Physicians’ I k s k Reference; Medical Economics Com-
together under an umbrella organization such as a Na-
pany: Montvale. New Jerscy, 2000.
tional Hoard o l Pharmacy Over the years,
5. Pharmacists ,for the Future: The Report o[ the Study
this recommendation has been debated through many Commission on Pharmacy; Health Administration Press:
forums. Today, many leaders in pharmacy believe the Ann Arbor, Michigan, 1975; 11-14, 139-140.
creation of a new organization to provide oversight for all 6. P1zarzaci.st.s ,for the Future: The Report of thc Study
crcdentialing and accreditation programs in pharmacy Commission on Pharr71acy; Health Administration Press:
would benefit the profession and society. A new cre- Ann Arbor, Michigan, 1975; 92-94.
dentialing and accreditation organization could better co- 7. Plzurmacists ,for the Future: The. Report of the Study
ordinate all programs and minimize intcrorganiaational Commis.sion on Pharmacy; Health Administration Press:
competition to allow a more unified vision and direction. Ann Arbor, Michigan, 1975; 104- 106.
Perhaps with time, the right political and organizational 8. Definition of clinical pharmacy as a specialty in clinical
practice. Committee on Clinical Pharmacy as a Specialty.
circumstances will occur to bring this recommendation of
American Pharmacy Association. Drug Intel. Clin. Pharm.
the Commission to fruition.
1985, 1Y (2); 149-150.
9. A petition to the Board of Pharmaceutical Specialties re-
questing recognition of pharmacotherapy as a specialty.
The American College of Clinical Pharmacy. Am. Pharm.
1988. NS28 ( 9 , 44-50.
The work of the Study Commission o n Pharmacy has had 10. Pharmacists fbr the Future: The Report or the Study
an important impact on the development of clinical phar- Commission on Phar/nacy; Health Administration Press:
macy and pharmaceutical education. It, coupled with Ann Arbor, Michigan, 1975; 109, 121- 128.
other signilicant reports and individual and organizatio- 11. Miller. W.A. Planning for pharmacy education in the 21st
nal leadership. have advanced the profession. As a result, century: AACP‘s leadership role. Am. J. Pharm. Educ.
pharmacists are now better educated and trained and play 1989, 53; 336-339.
a more significant role in concert with other health pro- 12. Papers from the Commission to implement change in
viders to help ensure drugs are used safely and effec- pharmaceutical education. Am. J. Pharm. Educ. 1993, 57,
tively in patient care. 166-399.
13. Pharmacists for the Future: The Report of’ the Study
Commission on Pharmacy; Health Administration Press:
Ann Arbor, Michigan, 1975; 123-126, 142.
14. Pharmacists [or the Future: The Report oj” the Study
Commission on Pharmacy; Health Administration Press:
1. Buerki, R.A. In search of excellence: The first century of Ann Arbor, Michigan, 1975; 129-132, 143.
the American Association of Colleges of Pharmacy. Am. J. IS. Pharmacists for the Future: The Report of the Study
Pharm. Educ. 1999, 63 (Suppl.). 167 172. Commi.ssion on Phnr-macy; Health Administration Press:
2. Pharrmcist.s ,for tlie Future: The Report qf the Study Ann Arbor, Michigan, 1975; 135-138, 143.
PROFESSIONAL RESOURCES
Rachel Crafts
Idaho Drug Information Service, Pocatello, Idaho, U.S.A.
turers are not held liable for inherent or unavoidable clude continuation of vaccine research and development,
adverse events under the theory of strict liability. Second, licensing, distribution, and monitoring.[261
a manufacturer is responsible for providing adequate The NCVIA is a no-fault, nontort compensation pro-
warning of possible side effects. Prior to 1986, a ma- gram for persons injured by certain covered vaccines. The
nufacturer had to prove that despite adequate warning, purpose of a no-fault compensation program is to resolve
the plaintiff would still have received the necessary the controversy surrounding government-mandated ad-
innoculation."' ministration of vaccines for ~chool-aged-children.[~~~The
NCVIA applies to any vaccine containing diphtheria, te-
tanus, pertussis, measles, mumps, rubella, poliovirus, he-
patitis B, H. infuenzae type b, and varicella or conjugate
pneumococcal antigens.[28' With the probability that rare
instances of injury will ensue during mass innoculation
Escalating numbers of lawsuits. primarily aimed at DTP practices, the act provides insurance coverage against ad-
vaccine manufacturers during the 1970s and 1980s, forced verse vaccine events.c4]
many manufacturers from the market. The remaining
manufacturers increased DTP vaccine prices, making the
limited products available very expensive.[251 Widespread The National Vaccine Injury
vaccine shortages combined with exorbitant increases in Compensation Program
vaccine costs placed mandatory vaccination protocols for
school-aged children in serious threat of discontinuation. To effectively address the vaccine litigation crisis, the
A battle fought largely by the American Academy of Vaccine Injury Compensation Program (VICP) was
Pediatrics called for government reform to ensure the fu- established by the NCVIA and became effective on
ture of the U S . vaccine supply and continuation of mass October 1, 1988."91 The directive of the VICP is to bring
immunization programs.[81 In 1986, Congress passed the together information about vaccinations (VAERS was
National Childhood Vaccine Injury Act (NCVIA), ad- officially adopted in 1990), collaborate with the CDC for
ministered by the Department of Health and Human Ser- developing vaccine administration information forms,
vices. This legislation was aimed at the "prevention of promote the development of safer vaccines, and establish
human infectious disease through immunization and to a federal compensation program for those injured by
achieve optimal protection against adverse reactions to covered vaccines. The compensation program is funded
vaccines."[251 The NCVIA program responsibilities in- via an excise tax on vaccines compensable under the
VICP.[4,301The VICP largely replaces traditional tort law information defining possible untoward events. Failure
for deciding vaccine-related injuries and was designed to to warn represents the bulk of litigation suits. Thus, phar-
stabilize the vaccine market by decreasing liability costs macists should be aware of vaccine contraindications
of manufacturers and health care providers and to ease and keep abreast of information regarding possible ad-
reward recovery by eligible claimant^.'^'^^] verse outcomes."'
The VICP established the Vaccine Injury Table (VIT) Clinicians administering vaccines covered by the NCVIA
(Table 1) to facilitate the process of justifying compensa- are protected against litigation surrounding possible
tion to injured vaccinees. The VIT lists specific vaccines vaccine-related adverse events.[331Pharmacists are com-
with corresponding injuries to be compensated if injury monly involved with the administration of pneumococcal
manifests within the predetermined time frame. There- 23-valent and influenza virus vaccines-vaccines not
fore, the table eliminates the need for determining a currently covered by the NCVIA.[281Despite this, phar-
causal relationship between vaccine and injury.[4,532x,311 macists should be familiar with this far-reaching legis-
lation and understand both the ramifications and limita-
tions on vaccine coverage.
Since 1971, the National Center for Health Services Health care practitioners administering vaccines covered
Research has recognized the clinical role of pharmacy to by the NCVIA are required to record pertinent information
include immunization.[2x1Pharmacists administered more in either a permanent patient record or a vaccine log. The
than 100,000 immunizations in 1997 alone, and as of July patient's name, date of administration, vaccine name, ma-
1999, 30 U.S. states officially recognized pharmacists as nufacturer, lot number, provider name, address, and title
having the authority to As defined by the are all r e q ~ i r e d . [ ~ ~
Administration
-~~] of a NCVIA-co-
Model Pharmacy Practice Act of the National Association vered vaccine also requires practitioners to give vaccine
of Boards of Pharmacy, the practice of pharmacy includes information statements (provided by state health depart-
services not limited to compounding, dispensing, labeling, ments and the CDC at www.cdc.gov/nip/publications/VIS/
interpreting, and evaluating prescriptions, but also the default.htm) to patients or guardians outlining product use,
administration and distribution of drugs and devices.[331 benefits, risks, and wa,ings.[33,34.36,371 Ph armacists in-
volved with the administration of pneumococcal, influ-
enza, and other vaccines should also adopt this practice.
Liability
eases are controlled and even eliminated in some regions tion receipt. Am. J. Public Health 1999, Feb., 89 (2), 164-
of the world, complete eradication (with the exception 170.
of polio) is unlikely in the near future.‘’’ Although the 13. Rota, J.S.; Salmon, D.A.; Rodewald, L.E.; Chen. R.T.;
conrred benefit received from mass immunization is Hibbs, B.F.; Gangarosa, E.J. Processes for obtaining
nonmedical exemptions to state immunization laws. Am.
among the greatest of public health achievements, the
J. Public Health 2001, Apr., 91 (4), 645-648.
fact remains that vaccine products are not completely
14. Meszaros, J.R.; Asch, D.A.; Baron, J.; Hershey, J.C.;
safe. Under the NCVIA, research and development of Kunreuther, H.: Schwartz-Buzaglo, J. Cognitive processes
new vaccine products will also foster the production of and the decisions of some parents to forego pertussis
safer and more efficacious vaccines. Further attributes vaccination for their children. J. Clin. Epidemiol. 1996,
of the NCVIA include the VICP along with VAERS Jun., 49 (6): 697-703.
and their capability for accumulating data regarding the 15. Weibel, R.E.; Benor; D.E. Reporting vaccine-associated
safety of vaccines. paralytic poliomyelitis: Concordance between the CDC
and the National Vaccine Injury Compensation Program.
Am. J. Public Health 1996, May, 86 ( 5 ) , 734-737.
16. Weibel, R.E.; Caserta, V.; Benor, D.E.; Evans, G. Acute
REFERENCES encephalopathy followed by permanent brain injury or
death associated with further attenuated measles vaccines:
1. Prins-Stairs, J.C. The National Childhood Vaccine Injury A review of claims submitted to the National Vaccine
Act of 1986. Can congressional intent survive judicial Injury Compensation Program. Pediatrics 1998, Mar., 101
sympathy for the injured? J. Leg. Med. 1989, Dec., 10 (4), (3 Pt. 1); 383-387.
703-737. 17. Griffin, M.R.; Ray, W .A,; Mortimer, E.A. ; Fenichel, G.M. ;
2. P. Chen. R.T.; Rastogi, S.C.; Mullen, J.R.; Hayes, S.W.; Schaffner, W. Risk of seizures after measles-mumps-rubella
Cochi, S.L.; Donlon. J.A.; Wassilak, S.G. The Vaccine immunization. Pediatrics 1991, Nov., 88 (5), 881 -885.
Adverse Event Reporting System (VAERS). Vaccine 1994, 18. Cody; C.L.; Baraff, L.J.; Cherry, J.D.; Marcy, S.M.;
May, 12 (6). 542-550. Manclark, C.R. Nature and rates of adverse reactions
3. Bedford, H.; Elliman, D. Concerns about immunisation. associated with DTP and DT immunizations in infants and
BMJ 2000, Jan. 22, 320 (7229), 240-243. children. Pediatrics 1981, Nov.; 68 (9,650-660.
4. Ridgway, D. No-fault vaccine insurance: Lessons from the 19. Howson, C.P.; Fineberg, H.V. The ricochet of magic
National Vaccine Injury Compensation Program. J. Health bullets: Summary of the Institute of Medicine Report,
Polit. Policy Law 1999, Feb., 24 (l), 59-90. Adverse Effects of Pertussis and Rubella Vaccines. Pe-
5. Mariner, W.K. The National Vaccine Injury Compensation diatrics 1992, Feb., 89 (2), 318-324.
program. Health Aff. (Millwood) 1992, Spring. I 1 (l), 20. Duclos, P.; Ward, B.J. Measles vaccines: A review of
255-265. adverse events. Drug Saf. 1998, Dec., 19 (6), 435-454.
6. Evans, 6. National Childhood Vaccine Injury Act: Revi- 21. Gale, J.L.; Thapa, P.B.; Wassilak, S.G.; Bobo, J.K.; Men-
sion of the vaccine injury table. Pediatrics 1996, Dec., 98 delman. P.M.; Foy, H.M. Risk of serious acute neurological
(6 Pt. 1). 1179-1181. illness after immunization with diphtheria-tetanus-pertussis
7. General recommendations on immunization. Guidelines vaccine. A population-based case-control study. JAMA, J.
from the immunization practices advisory committee. Cen- Am. Med. Assoc. 1994, Jan. 5, 271 (l), 37-41.
ters for Disease Control. Ann. Intern. Med. 1989, Jul. 15, 22. Miller, D.: Madge, N.; Diamond, J.; Wadsworth, J.; Ross, E.
I l l (2). 133-142. Pertussis immunisation and serious acute neurological
8. Smith, M.H. National Childhood Vaccine Injury Com- illnesses in children. BMJ 1993, Nov. 6, 307 (6913),
pensation Act. Pediatrics 1988, Aug., 82 (2), 264-269. 1171-1 176.
9. Evans, G. Vaccine liability and safety revisited. Arch. 23. Hoffman, H.J.; Hunter, J.C.; Damus, K.; Pakter, J.;
Pediatr. Adolesc. Med. 1998, Jan., 152 (l), 7-10. Peterson, D.R.; van Belle, G.; Hasselmeyer, E.G. Diph-
10. Ten great public health achievements-United States, theria-tetanus-pertussis immunization and sudden infant
1900-1999. MMWR, Morb. Mortal. Wkly. Rep. 1999 death: Results of the National Institute of Child Health and
Apr. 2, 48 (12), 241-243. Human Development Cooperative Epidemiological Study
11. National, state, and urban area vaccination coverage levels of Sudden Infant Death Syndrome risk factors. Pediatrics
among children aged 19-35 months-United States. 1998. 1987, Apr., 79 (4), 598-611.
Morb. Mortal. Wkly. Rep. CDC Surveill. Summ. 2000 24. Braun, M.M.; Ellenberg, S.S. Descriptive epidemiology of
Sep. 22, 49 (9), 1-26. adverse events after immunization: Reports to the Vaccine
12. Mayer. M.L.; Clark, S.J.; Konrad, T.R.; Freeman. V.A.; Adverse Event Reporting System (VAERS), 1991- 1994.
Slifkin, R.T. The role of state policies and programs in J. Pediatr. 1997, Oct., 131 (4), 529-535.
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563
26. 42 U.S.C.A. $300, aa-2. relatcd to immunizations. Hosp. Pharm. 1998, Jan., 33 (11,
27. Stratton, W.T. Physicians’ obligations undcr the National 97 115.
Childhood Vaccine Injury Act. Kans. Med. 1989, Feb., YO 34. 42 U.S.C.A. $300, ad-25.
( 2 ) , 32 33. 35. Current trends national childhood vaccine injury act: Re-
28. Grabenstcin, J.D.; Bonasso. J. Hcalth-system pharmacists’ quircmcnts for permanent vaccination records and for re-
role i n immunizing adults against pneumococcal disease porting of selected events after vaccination. MMWR, Morb.
and influenza. Am. J. Health-Syst. Pharm. 1999, Sep. I, 56 Mortal. Wkly. Rep. 1988, April 0
(17 Suppl. 2), S3-S22. 36. Publication of vaccine information pamphlets. MMWR,
29. Clayton, E.W.; Hickson, G.B. Compciisation under the Morb. Mortal. Wkly. Kcp. 1991, Oct. 25. 40 (42), 881-
National Childhood Vaccine Injury Act. J. Pecliatr. 1990, 882.
r.. I l h (4). 153 ~ 5 0 8 . 37. 42 U.S.C.A. $300, aa-26.
30. http://frwcbgate3.access.Epo.gov(accessed January 200 1 ). 38. Current trends vaccine adverse event reporting systcm-
31. 42 [J.S.C.A. $300, aa-14. Unitcd States. MMWR, Morb. Mortal. Wkly. Rep. 1990,
32. http://bhpr.hrsa.gov/vicp/table.htm (accessed January Oct. 19, 39 (41), 730-733.
2001). 39. Evans, 6. Vaccine injury compensation programs world-
33. Grabenstein, J.D.; Baker, K.R. Legal and liability issues wide. Vaccine 1999, Oct. 29, 17 (Suppl. 3), S25-S35.
PROFESSIONAL ORGANIZATIONS
Kevin M. Jarvis
Biocentric, Inc., Berkley, Michigan, U.S.A.
Table 1 Classification of accreditation survey standards and not the quality of systems or processes in the health
plan. The primary objective of HEDIS reporting is to pro-
Category Example
vide purchasers of health plan services (i.e., employers)
Access and service Do health plan members have with objective information about the relative value and
access to the care and service accountability of health plans by focusing on basic areas
they need? of performance (Table 2).[61Essential services evaluated
* Are providers in the health with HEDIS include preventive medicine (e.g., immun-
plan free to discuss all ization and screening programs), prenatal care, acute and
available treatment options?
chronic disease management, and mental health pro-
* Do patients report problems
getting the necessary care?
grams. Other areas of performance that are included in
0 How well does the health HEDIS measures include member access and satisfact-
plan follow up on grievances? ion, health plan utilization, and financial stability of the
Qualified providers Does the health plan assess each health plan.@’ The Committee on Performance Measure-
provider’s qualifications and what ment identifies areas of priority for which measures
health plan members say about should be developed.[21 The responsibility of developing
their providers? the actual measure is left up to the Measurement Advi-
Does the health plan regularly sory Panels, which identify the best measures and meth-
check the licenses and training odologies for assessing healthcare performance. Via the
of providers? Measurement Advisory Panels, measures are updated on
* How do health plan members rate
a regular basis to reflect advancements in performance
their personal doctor or nurse?
Staying healthy Does the health plan help people
measurement and information systems technology, as
maintain good health and avoid well as changes in the managed care industry.
illness?
0 Does it give its doctors guide-
lines about how to provide
appropriate preventive health s
services?
@ Are members receiving tests Beginning in 2002, the NCQA will implement a flexible
and screenings as appropriate? health plan evaluation program that applies to various
Getting better How well does the health plan care
for people when they become sick?
* How does the health plan
evaluate new medical procedures, Table 2 Examples of effectiveness of care measures in
drugs, and devices to ensure that HEDIS 2000
patients have access to safe and
effective health care? Childhoodladolescent Breast cancer screening
Living with illness How well does the health plan care immunization status
for people with chronic conditions? Chlamydia screening Cervical cancer screening
0 Does the plan have programs in in women
place to assist patients in manag- Prenatal care in first Controlling high
ing chronic conditions such as trimesterkheck-ups blood pressure
asthma? after delivery
* Do diabetics, who are at risk for Cholesterol management Comprehensive diabetes care
blindness, receive eye exams as after heart attack
needed? Use of appropriate Beta blocker treatment
medications for people after a heart attack
(From Ref. [2].) with asthma
Follow-up after Antidepressant medication
hospitalization for management
mental illness
Advising smokers to quit Flu shots for older adults
Medicare health
Another means by which the NCQA evaluates health plans
outcomes survey
is via HEDIS reporting, which differs from the accredi-
tation process in that HEDIS measures the performance (From Ref. [6].)
566 National Committee for Quality Assurance
CTI
2. National Committee for Quality Assurance (NCQA) Web Web site. Available at: http://www.hedis.org. Accessed
site. Available at http://www.ncqa.org. Accessed July 12, September 10, 2000.
2000; Septembcr 10, 2000. 7. National Committee for Quality Assurance (NCQA). Dis-
3. Bell, D.; Brandt, E.N., Jr. Accreditation by the National ease Management Fact Sheet. Available at: http://www.
Committee for Quality Assurance (NCQA): A dcscriplion. ncqa.org/Programs/Accreditation/Certification/DM%20
J. Okla. State Med. Assoc. 1999, 92 ( 5 ) , 234- 237. FactY~20Sheet.pdP.Accessed March 30, 2002.
4. O'Kane, M.E. A new approach lo accreditation of' HMOs. 8. American Society of Health-Systems Pharmacists. Ac-
J. Health Care Benefits I, 48-53, Sept./Oct. tion guide for pharmacists in the managed care world. Prac-
5. Sennett, C. An introduct tice-level stratcgics. Available at: http://www.ashp.org/
Quality Assurance. Pediatr. mana,oedcare/ashpactionguide.pdf. Accessed March 30,
6. Hcalth Plan Employer Data and Information Set (HEDIS) 2002.
PROFESSIONAL ORGANIZATIONS
Calvin 1. Anthony
Robert A. Malone
National Community Pharmacy Association,
Arlington, Virginia, U.S.A.
pharmaceutical delivery services to ensure fair compen- pond to the emerging needs and challenges of the phar-
sation, enhancing professional knowledge through cre- macy marketplace.
dentialing to deliver the highest levels of personalized The House of Delegates and standing committees
pharmacist care, and continuing to refine the mission of structure ensures that the NCPA membership at large has
the profession. the opportunity to provide maximum input into asso-
ciation policies and programs.
The leadership of the NCPA can be found at
ncpanet.org.
UCTUR
Executive Vice Pvesident:
Calvin J. Anthony, P.D.
The current organizational and governance structure of
NCPA is essentially unchanged from that created by the
organization’s founding fathers in 1898, and has served as
its enduring strength in the intervening 102 years. The
MISSION
structure consists of a full-time salaried Executive Vice-
President, who serves as the Chief Executive Officer of
The mission of the association is quoted as follows:
the Association, as well as eight officers and six members
of the Executive Committee, elected to staggered terms of We are dedicated to the continuing growth and pros-
office once a year. The officers and members of the perity of independent community pharmacy in the
Executive Committee (OEC), which also includes the United States.
Executive Vice-president as an ex-officio member, are 0 We are the national pharmacy association represent-
responsible for the management of association priorities ing the professional and proprietary interests of
and activities. independent community pharmacists and will vig-
The OEC are named at the annual meeting of the as- orously promote and defend those interests.
sociation’s House of Delegates, which meets once a year 0 We are committed to high-quality pharmacist care and
at NCPA’s Annual Convention. Officers and Executive to restoring, maintaining, and promoting the health
Committee members typically serve a period of 12 to 14 and well-being of the public we serve.
years in association leadership as each moves up the 0 We believe in the inherent virtues of the American
ladder of responsibility (for example, from fifth Vice- free enterprise system and will do all we can to
President to fourth Vice-president, service on the Exe- ensure the ability of independent community phar-
cutive Committee, President-Elect to President). macists to compete in a free and fair marketplace.
The House of Delegates is comprised of representa- 0 We value the right to petition the appropriate legis-
tives, who are appointed by their respective state or local lative and regulatory bodies to serve the needs of
pharmacy associations, to serve in this policy-making those we represent.
body. The House of Delegates provides policy guidance 0 We will utilize our resources to achieve these ends in
to the association’s OEC through deliberations and pass- an ethical and socially responsible manner.
age of resolutions and policy positions, which are gen-
erated by eight standing committees that meet each year
to formulate policy directives.
The eight committees are consumer affairs and public
relations, home healthcare pharmacy services, long-term CURRENT MAJOR lNlTl
care pharmacy services, independent pharmacy chains, OR DIRECTIONS
management, national legislation and government affairs,
third-party payment programs, and professional relations. The year 1999-2000 ushered in the second century of
One NCPA member from each state is nominated by his independent pharmacy service to the nation’s communities
or her state or local pharmacy association and appointed and NCPA’s existence as the only national association
by the NCPA president to serve on a committee. The representing independent pharmacy. The new millennium
committees review and evaluate current NCPA policies finds the association’s membership robust and thriving,
and activities, develop recommendations for existing and thus stemming a decade-long decline in independent store
new projects, and offer suggestions on how best to res- count brought about by a difficult managed care envi-
570 National Community Pharmacists Association
ronment and aggressive chain drugstore and mail order Another bill that garnered widespread bipartisan sup-
incursions in the marketplace. port was the patient bill of rights, which riveted national
There are nearly 25,000 single-store independent attention on remedies proposed to improve the quality of
pharmacies, independent chains, independent franchises, health care and eliminate managed care abuses. Chief
and independent pharmacist-owned supermarket phar- among the bill’s provisions is the restoration of patient
macies in the United States or nearly half of the rights to have better access to the provider of their choice
52,600 total stores in the pharmacy sector. Independent and prescriptions selected by their physicians.
pharmacy today represents a $49 billion marketplace, Another legislative victory for independents was re-
where independents’ prescription sales are $4 1 billion sounding support in both the House and Senate for land-
or nearly one-half of the retail Prescription market. mark legislation that enables pharmacists, wholesalers,
Independent pharmacies dispense 1.1 billion prescrip- pharmacy buying groups, independent chains, and other
tions annually. licensed distributors to purchase Food and Drug Admi-
The average independent’s pharmacy sales are $1.97 nistration (FDA)-approved medicines from other coun-
million, up 37% in the last 3 years; average pres- tries, including Canada, the United Kingdom, and the
cription sales are $1.64 million, up 43% in the last European Union. Current law restricts imports to drug
3 years. manufacturers. The Senate’s 74 to 21 vote in July 2000
Independents are rated the best pharmacies in Ame- placed the import legislation before a House-Senate
rica by consumers because of their personal attention, conference committee, where a vote was imminent in
the speed and efficiency of dispensing, and the medi- late-September.
cation information provided. According to the 1999 On the regulatory front, a 20-year campaign waged by
Ortho Biotech Retail Pharmacy Digest, consumers using NCPA for federal recognition of community pharmacists
independent pharmacies reported the highest level of as vital sources of medication information for consumers
satisfaction, and customers of independent pharmacies earned Food and Drug Administration (FDA) sanction in
were the most likely to recommend their pharmacy to a spring 1999. Pharmacists will now be included on the
friend or relative. labeling for over-the-counter (OTC) medications-as in
Independents are leaders in providing pharmacist care “Ask your doctor or pharmacist.” NCPA was promi-
services: Nearly 42% of independents are certified to nently featured at the White House ceremony announcing
provide disease management services, and more than the FDA OTC label recognition.
12,000 community pharmacists have completed disease On the professional development front, the NCPA-
management programs offered by NCPA’s National created NIPCO continued to lead the way in developing
Institute for Pharmacist Care Outcomes (NIPCO). programs that help establish pharmacist care services in
Highlights of NCPA’s 1999-2000 year were forged on community pharmacies. To date, more than 12,000 com-
both the legislative and technology fronts as the asso- munity pharmacists have completed NIPCO-accredited
ciation grappled with the age-old challenges of third-party disease management programs in pharmacist care skills,
issues and saw many of its initiatives in the great health- cardiovascular care, respiratory care, diabetes care, im-
care reform debate of the early 1990s become standard munization skills, osteoporosis, and mental health.
fare for public embrace. At the same time, NCPA defined On the business development front, NCPA and the
a brand new frontier for independents in the realm of the Chain Drug Marketing Association (CDMA) announced
Internet and the World Wide Web. an alliance, which bore fruit as a combined Expo 2000
It was no small achievement that NCPA marshaled midyear meeting sponsorship and the promise of other
widespread support in the House of Representatives for joint marketing programs. CDMA represents more than
the Campbell/Conyers Bill (the Quality Health Care 100 small and regional drugstore chains.
Coalition Act), calling for collective negotiations by NCPA was instrumental in the formation and funding
pharmacists and other healthcare providers, free of the of two major foundations that will benefit community
shadow of antitrust. By the time of a key vote on the pharmacy in 1999. The first is the Institute for the Ad-
measure, more than one-half of the House of Representa- vancement of Community Pharmacy, which received a
tives (220 members), showing broad bipartisan support, $27.5 million grant from Knoll Pharmaceutical Company
signed on as cosponsors of the bill-a clear signal that to benefit community pharmacy. The board of directors is
this was an issue whose time had come. The bill passed composed of the CEOs of NCPA and the National Asso-
the House in late June 2000 by a resounding vote of 276 ciation of Chain Drug Stores (NACDS). The second is the
to 136-a 2 to 1 margin. result of the distribution of funds from a $723 million
57 B
settlement approved by a U.S. district court judge of a Lastly, NCPA and TheraCom, Inc., a leading provider
price-fixing case involving 20 major brand name phar- of specialty drugs, formed the Specialty Drugs Network in
maceutical manufacturers. Approximately $18.5 million early 2000. The Specialty Drugs Network represcnts the
of settlement proceeds has bccn set aside for a new largest and most comprchensive network in the United
foundation, “the Foundation for the Advancement of States for the distribution, administration, and care of pa-
Retail Pharmacy.” tients in need of specialty drugs. The network will enablc
The Intcrnet and World Wide Web became a reality for independent pharmacists to dispense a growing array of
many of NCPA’s members. In August 1999, Corner- specialty pharmaceuticals for those drugs they choose to
Drugstore.com was launched as the first national Internet dispense and with “just-in-time” inventory control that
solution for independents. Community pharmacists signed offers cost-cffective management of these medications.
up in droves to become part of the largest virtual network The network also offers professional education to build
of independents anywhere in the nation. Independents clinical competency through a specialty pharmaceuticals
could build their own web sites by using CornerDrug- certificate training program.
store.com templates, or join their web site in the national In all, 1999-2000 was a good start to the second cen-
network hosted by CornerDrugstore.com. To date, more tury-the new millennium-for the independent. As the
than 4000 independent pharmacies have enrolled in the figures indicate, independent community pharmacy has
program, which has earned the endorsement of more than becomc a formidable market force, one to be reckoned
50 pharmacy organizations. with in the years ahead.
PROFESSIONAL ORGANIZATIONS
professional and industry representation, including boards pharmacists with 2 or more years of experience; however,
of pharmacy, colleges of pharmacy, interdisciplinary there is no traditional practice experience requirement.
health professionals, national health care associations, Demonstrated competence, rather than years of experi-
payers, pharmaceutical manufacturers, practitioners, pub- ence, is the factor being evaluated. Also, unless the exams
lickonsumer advocates, quality assessment organizations, are being used as personal assessment tools, continu-
and state pharmacy associations. These advisory groups ing professional education programs designed to prepare
are scheduled to meet annually. pharmacists for NISPC examinations are strongly recom-
mended. During the first 2 years, the exams were of-
fered, 1649 pharmacists took 1973 examinations with a
success rate of 56%.
egistration Process
Under an agreement with NISPC, the NABP has de-
veloped examinations that are psychometrically valid and
The cost of a single NISPC DSM examination is $135. If
legally defensible. NISPC currently offers four disease-
a person registers for two or more exams on the same
specific examinations that assess a pharmacist’s compet-
registration form, there is a charge of $135 for the first
ency in the management of diabetes, dyslipidemia, asth-
and $110 for each additional exam. To register for an
ma, and anticoagulation therapy. Pharmacists can pursue
examination, contact the NISPC Testing Center to request
credentialing in one, two, three, or all four areas of prac-
a DSM Registration Bulletin. Also available is the
tice. NISPC DSM examinations are administered daily
electronic testing DSM Examinations Candidate’s Review
in a computer-based format through LaserGrade, Inc.’s,
Guide (CRG), which contains information about the
nationwide system of testing centers. Each exam consists
examinations and sample questions. The CRG may be
of multiple-choice questions and takes approximately 3
purchased for $10 through the NISPC Testing Center or
hours to complete. Results are made available in 7 to 10
downloaded for free from the NISPC web site (www.
business days.
nispcnet.org). A CRG order form is also included in the
Pharmacists who earn a passing score on the NISPC
DSM Registration Bulletin. The NISPC Testing Center
DSM examinations are credentialed and issued a cer-
address is 700 Busse Highway, Park Ridge, IL 60068.
tificate by NISPC. The certificate documents to employ-
The Center phone number is (847) 698-6227, the fax
ers, peers, and the public that they possess the knowledge
number is (847) 698-0124, and the e-mail address is
and skills to provide disease-specific services to patients.
dsm@nabp.net.
NISPC-credentialed pharmacists are recognized on the
NISPC and NABP web sites.
Information about the NISPC DSM examinations
is available in the Disease State Management (DSM)
Examination Registration Bulletin. In addition to a
registration form and information about the testing NISPC will continue to support efforts to revise state and
procedures, the Bulletin contains the competency state- federal laws and regulations that limit a pharmacist’s
ments, or blueprint, upon which the DSM examinations ability to provide DSM services. State boards of phar-
are developed. Also included in the Bulletin are the macy will be encouraged to adopt the NISPC compe-
standards and objectives for each DSM examination. tencies, standards, and objectives, and to provide for
Cross-referenced to the competency statements, the inspectors that are credentialed and competent to eval-
standards and objectives delineate the knowledge base uate the quality of care that is being provided. The pre-
expected of pharmacists providing disease-specific prim- ceding will position boards to address any complaints
ary care services. brought to their attention regarding the quality of care
provided by the pharmacists they have licensed. Colleges
of pharmacy will be encouraged to make available the
Examination Eligibility ~ @ ~ u i ~ @ m e n t s knowledge and skills that will adequately prepare their
graduates to pass the NISPC exams immediately after
Pharmacists seeking the NISPC credential must be li- licensure. Colleges and pharmacy associations will be
censed in good standing with their state board of phar- encouraged to provide continuing professional education
macy to sit for the examinations. The NISPC DSM exams with the depth and breadth of content required for suc-
are designed to assess the competencies of practicing cess on the NISPC exams. They will also be encouraged
574 National Institute for Standards in Pharmacist Credentialing
ginning of the century. With effective medications and treatment of major diseases. Through clinical research,
psychotherapy, the 19 million Americans who suffer from promising discoveries in the laboratories are translated
depression can now look forward to a better, more pro- into new therapies and treatments for patients. The NIH
ductive future. Vaccines protect against infectious dis- also has facilities in the Rockville, Maryland, area and the
eases that once killed and disabled millions of children NCI Frederick Cancer Research and Development Center
and adults. Dental sealants have proved 100% effective in (FCRDC) at Fort Detrick in Frederick, Maryland. The
protecting the chewing surfaces of children’s molars and National Institute of Environmental Health Sciences,
premolars, where most cavities occur. In 1990, NIH re- which studies the adverse effects of environmental factors
searchers performed the first trial of gene therapy in hu- on human health, operates from its main facility in Re-
mans. Scientists are increasingly able to locate, identify, search Triangle Park (RTP), North Carolina. Other labo-
and describe the functions of many of the genes in the ratory facilities include the NIH Animal Center in
human genome with the ultimate goal of developing Poolesville, Maryland; the National Institute on Aging’s
screening tools and gene therapies for cancer and many Gerontology Research Center in Baltimore, Maryland; the
other diseases. Division of Intramural Research of the National Institute
on Drug Abuse, also in Baltimore; the National Institute
of Allergy and Infectious Diseases’ Rocky Mountain
Laboratories in Hamilton, Montana, and several smaller
TITUT NTE FFlCES field stations.
The 14-story Warren Grant Magnuson Clinical Center
The NIH is an amalgam of many diverse research and (http://www.cc.nih.gov) is the NIH’s hospital and center
support organizations (Fig. 1). A list of NIH’s 27 Insti- for clinical research. Patients come from all over the
tutes and Offices (along with links to their web sites) is world to participate in clinical studies here. Each year, the
available at http://www.nih.gov/icd/. The missions and Clinical Center admits about 7000 inpatients. The am-
activities of the Institutes and Centers are described at bulatory clinical research unit accounts for nearly 68,000
http://www.nih.gov/icd/programs.htm. The Institutes in- outpatient visits per year. Patients at the NIH participate
clude the National Cancer Institute, the National Heart, in clinical trials that span a wide range of diseases and
Lung, and Blood Institute, the National Institute of Mental conditions. The Clinical Center also houses the Visitor
Health, the National Institute of Allergy and Infectious Information Center, which is NIH’s information liaison
Diseases, and the Human Genome Research Institute. and host to thousands of visitors each year. Construction
Centers include the Vaccine Research Center, the Fogarty began in 1997 for the new Mark 0. Hatfield Clinical Re-
International Center, the Center for Scientific Review, search Center. The Hatfield Center will house the research
and the National Center for Complementary and Alter- hospital’s 250 beds for inpatient and outpatient care, out-
native Medicine. Other notable components of the NIH patient facilities, and research laboratories. It will connect
are the Warren Grant Magnuson Clinical Center, Office of to the current building, which opened its doors in 1953.
Social and Behavioral Research, and the National Library The hallmark of the original building is the proximity of
of Medicine. the patient care to scientific labs. The new facility will
amplify the bench-to-bedside tradition, providing a cru-
cial link from the rapidly moving biomedical findings of
the laboratory into the mainstream of medical practices.
NIH intramural scientists conduct their research in labo- The Clinical Center Pharmacy Department (http://www.
ratories located on a 300-acre campus in Bethesda, and in cc.nih.gov/phar) provides extensive clinical and research
several field units across the country and abroad. Maps of services and conducts several highly regarded training
the campus and of the local area are located at http:// programs. Pharmacists also contribute directly to the NIH
www.nih.gov/about/maps.html. The Intramural Research intramural and extramural research programs.
Programs, although representing only a small part of the
total NIH budget, are central to the NIH scientific effort. Fundin
First-rate scientists are key to NIH intramural research.
They collaborate with one another regardless of institute From a total of about $300 in 1887, the NIH budget has
affiliation or scientific discipline, and have the intellectual grown to more than $20.3 billion in 2001. The NIH is
freedom to pursue their research leads in NIH’s own funded through direct appropriations from the U S . Con-
laboratories. These explorations range from basic biology, gress. Approximately 82% of the investment is made
to behavioral research, to studies on the diagnosis and through grants and contracts supporting research and
National Institutes of Health 577
National Institute of National institute of Child Nationai ImtItUte on Natlonal lmtilute of National Instituteof National lntfilute National In~fttuteof National Institute of
Biomedical Imaging and Health and Human Deafness and Other Denial and Craniofacial Diabetes and Digestfve on Drug Abuse Environmental Heaith General Medical
Bloengineerlng IHNB) Development IHNq Communication Research IHW and Kidney Disease% (HNG) Sciences (HW sc,encei IHNSI
Disorders IHNB! WKI
Fig. 1 The Mission of the National Institutes of Health is science in pursuit of knowledge to improve human health. This means
pursuing science to expand fundamental knowledge about the nature and behavior of living systems; to apply that knowledge to extend
the health of human lives; and to reduce the burdens resulting from disease and disability. The National Institutes of Health seeks to
accomplish its mission by: 0 Fostering fundamental discoveries, innovative research, and their applications in order to advance the
Nation's capacity to protect and improve health; 0Developing, maintaining, and renewing the human and physical resources that are
vital to ensure the Nation's capability to prevent disease, improve health, and enhance quality of life; 0Expanding the knowledge base
in biomedical, behavioral, and associated sciences order to enhance America's economic well-being and ensure a continued high return
on the public investment in research; and @ Exemplifying and promoting the highest level of scientific integrity, public accountability,
and social responsibility in the conduct of science
training in more than 2000 research institutions through- nationwide. Information regarding the types and conduct
out the United States and abroad. In fact, NIH grantees are of clinical trials is also provided.
located in every state in the country. These grants and
contracts comprise the NIH Extramural Research Pro-
Training
gram. Approximately 10% of the budget goes to NIH's
Intramural Research Programs, the more than 2000 pro-
Clinical research training is an integral part of the NIH
jects conducted mainly in its own laboratories. About 8%
mission. Training opportunities are available for students,
of the budget is for both intramural and extramural re-
physicians, other health care professionals, and postdoc-
search support costs.
toral researchers. These training programs vary in scope
and can range from several weeks to several years in du-
Clinical Studies ration. Information regarding NIH research training op-
portunities is available at http://www.training.nih.gov.
Information regarding clinical trials conducted at the NIH Several remote-access resources have been developed
Clinical Center in Bethesda, Maryland, can be found at for training researchers and clinicians. For example, the
http://clinicalstudies.info.nih.gov/.ClinicalTrials.gov course on Clinical Research Training (http://www.cc.nih.
(http://clinicaltrials.gov) provides information on federal gov/ccc/cr/index.html) was developed to assist those with
and private medical studies at thousands of locations an interest in conducting clinical research. Other train-
578 National Institutes of Health
ing programs are described at http://www.cc.nih.gov/ scientists as well as public members who are interested in
profscientists.cgi. health issues or the biomedical sciences, determines the
project’s overall merit and priority in advancing the re-
search agenda of the particular NIH funding institute.
CTS Altogether, about 38,500 research and training applica-
tions are reviewed annually through the NIH peer review
Information regarding NIH grants and funding opportun- system. At any given time, the NIH supports 35,000 grants
ities may be found at http://www.grants.nih.gov/grants/ in universities, medical schools, and other research train-
index.cfm. The grants page provides information about ing institutions both nationally and internationally.
NIH grant and fellowship programs, policy changes. ad-
ministrative responsibilities of awardees, the Computer
Retrieval of Information on Scientific Projects (CRISP)
database, and the numbers and characteristics of awards
made by the NIH. CRISP is a searchable database of Scientific resources available from the NIH are described
federally funded biomedical research projects conducted at http://www.nih.gov/science/. These include research
at universities, hospitals, and other research institutions. sourcebooks, documents relating to molecular biology
The database, maintained by the Office of Extramural and molecular modeling, research labs on the Web, lib-
Research at the National Institutes of Health, includes rary and literature resources, model organisms for bio-
projects funded by the National Institutes of Health medical research, reagent programs, data banks, animal
(NIH), Substance Abuse and Mental Health Services care and use guidelines, NIH-supported human specimen
(SAMHSA), Health Resources and Services Administra- resources, bioethics resources, and lab safety and waste
tion (HRSA), Food and Drug Administration (FDA), management resources. to name a few. Protomechanics, a
Centers for Disease Control and Prevention (CDCP), guide for intramural scientists on preparing and conduct-
Agency for Health Care Policy Research (AHCPR), and ing a research study, is available at http://www.cc.nih.
Office of Assistant Secretary of Health (OASH). Users, govlccclprotomechanics/.
including the public, can access the CRISP interface to The National Library of Medicine is another principal
search for scientific concepts and emerging trends and unit of the NIH. The 10-story Lister Hill Center houses
techniques or to identify specific projects and/or inves- the Lister Hill National Center for Biomedical Commu-
tigators. This grants page also contains information re- nications and the National Center for Biotechnology In-
garding research contracts and research training oppor- formation. Both are components of the National Library
tunities and provides access to the NIH Guide for Grants of Medicine. The Library produces and publishes Index
and Contracts. The Guide is the official document for Medicus. a comprehensive monthly listing of articles ap-
announcing availability of NIH funds for biomedical and pearing in the world’s leading medical journals. The Lib-
behavioral research and research training. rary also operates a computerized Index Medicus, known
as MEDLINE (PubMed), and has pioneered the introduc-
tion of large medical bibliographic databases.
NIH Image is a public domain image processing and
Final decisions about funding extramural research are analysis program for the Macintosh. It was developed at
made by senior scientific staff at the NIH headquarters. the Research Services Branch (RSB) of the National
But long before this happens, the process begins with an Institute of Mental Health INIMH), part of the National
idea that an individual scientist describes in a written ap- Institutes of Health (NIH). The software is located at
plication for a research grant. The project might be small, http://rsb.info.nih.gov/nih-imagelDefault.htm1.
or it might involve millions of dollars. The project might
become useful immediately as a diagnostic test or new
treatment. or it might involve studies of basic biological
processes with practical value that may not be apparent for
many years. Each research grant application undergoes a A wide array of health information is provided by the
peer review process. A panel of scientific experts, pri- NIH to consumers and healthcare professionals. The
marily from outside the government, who are active and NIH Health Information Index, available at http://www.
productive researchers in the biomedical sciences. first nih.gov/ health / InformationIndex 1HealthIndexIPubincov.
evaluates the scientific merit of the application. Then, a htm, provides information on diseases currently under
national advisory council or board, comprised of eminent investigation by NIH or NIH-supported scientists and
National Institutes of Health 579
major NIH research areas with links to the appropriate Complementary Medicine (http://nccam.nih.gov/). These
institute(s), center(s), or other component(s) to call for include fact sheets, consensus reports, and the Comple-
information, along with the appropriate phone numbers. mentary and Alternative Medicine Databases (CAM).
The NIH web site does not offer personalized medi-
cal advice to individuals about their condition or treat-
ment. The resources on this site should not be used as NE VENTS
a substitute for professional medical care, and patients
are urged to work with their medical care providers for The News and Events page (http://www.nih.gov/news/)
answers to personal health questions. For general med- is the source for NIH news, calendars of events, press
ical questions, patients are encouraged to visit the releases, special reports, and information about NIH-
Health Information (http://www.nih.gov/health/) section sponsored events-including events of interest to the
of the NIH web site. MEDLINEplus at http://www.nlm. media and those available through NIH Videocasting.
nih.gov/medlineplus/ is another useful source for ob- Information regarding NIH Consensus Development
taining information on various conditions, diseases, and Conferences and NIH State-of-the-Science Conferences
wellness programs. The site also has a medical encyc- can be obtained via http://odp.od.nih.gov/consensus/
lopedia, a medication guide for consumers (USP DI defaukhtml. NIH clinical alerts and advisories (http:I/
Advice for the Patient), a glossary, medical dictionaries, www .nlm.nih.gov/databases/alerts/clinical_alerts.html)
health-related directories, special NIH programs, and are provided to expedite the dissemination of findings
other resources. For questions relating to specific foods, from NIH-funded clinical trials where such release could
or prescription, or over-the-counter drugs, the Food and significantly affect morbidity and mortality. The NIH
Drug Administration’s (FDA) web site http://www.fda. Calendar of Events, or “Yellow Sheet,” is located at
gov/ is recommended. Healthfinder at http://www. http://www.nih.gov/news/calendar/nihcalendar.htm. It
healthfinder.gov/ contains valuable information on lists NIH-sponsored meetings and other meetings of in-
choosing quality medical care. Also, toll-free medical In- terest to scientists, healthcare professionals, and the
formation Hotlines may be found at http://www .nih.gov/ general public. It is updated daily, and the listed meetings
health/infoline.htm. are free and open to the public.
Extensive information resources are available directly
from the Institutes and Centers that comprise the NIH.
For example. the National Cancer Institute provides
extensive cancer-related information through its Can-
cerNet program (http://cancernet.nci.nih.gov/) and the The e-mail and phone directory for NIH employees may
Cancer Information Service (1-800-4-CANCER). This be found at http://directory.nih.gov/.
includes cancer statistics. cancer information for Information about employment opportunities and sum-
patients, and access to a bibliographic cancer database mer internships at NIH may be found at http://www.nih.
(Cancerlit) and the cancer information database PDQE govlaboutlindex.html#employ .
(Physician Data Query). Health information and clinical The emergence of several abuses of the research pro-
guidelines are also available from other Institutes and cess has generated some confusion about which office
Centers. The National Heart, Lung, and Blood Institute, handles what type of abuse within the Department of
for example, provides information for patients, health- Health and Human Services (HHS). The attached docu-
care professionals, and the general public about various ment (http://ori.dhhs.gov/) was prepared to help clarify
vascular, heart, lung, blood, and sleep disorders (http:l/ the matter.
www.nhlbi.nih.gov/health/ index.htm). Authoritative Information regarding Freedom of Information Act
national clinical guidelines pertaining to asthma, choles- (FOIA) requests may be found at http://www.nih.gov/icd/
terol, chronic obstructive pulmonary disease, hyperten- od/foia/index.htm.
sion, obesity, and others are also available (http://www.
nhlbi.nih.gov/guidelines/ index.htm). Most of these NIH
guidelines and those from other reputable organizations
may also be accessible from the National Guideline REFERENCE
Clearinghouse (http://www.guideline.gov/). Information
regarding dietary supplements and herbal products is 1. National Institutes of Health Home Page (http://www.nih.
available from the National Center for Alternative and gov).
PROFESSIONAL RESOURCES
e
IC
Joan K. K o ~ t ~ - 5 r a d ~ e y
JB Ashtin Group Inc., Canton, Michigan, U.S.A.
Y
The NLM dates back to 1836 as a collection of medical MEDLINE is a bibliographic database that contains more
texts in the office of the United States Army Surgeon than 11 million references to journal articles from 4300
General.['] Publishing of the Index Medicus (a printed, national and international biomedical journals, covering
monthly subject/author guide to medical journals) com- the period from 1966 to the present.[" Types of journals
menced in 1879 under the direction of John Shaw indexed in MEDLINE include pharmacy, allied health,
Billings. By 1910, this once-modest library of the Surgeon nursing, medicine, veterinary medicine, dentistry, pre-
General's office had grown to be the largest medical clinical science, and life science journals. Each week,
library in the world. The National Library of Medicine nearly 8000 reference citations, created by the NLM and
became the official name of this collection in 1956 when its partners, are added to the MEDLINE database.
the United States Army transferred the oversight of the As Yahoo! and Excite are to the World Wide Web,
library to the U.S. Public Health Service. PubMed and Internet Grateful Med are to MEDLINE (see
The goal of the NLM has remained constant-to Tables 2 and 3). Although both of these latter search
increase the availability of medical literature worldwide. services access MEDLINE, the two differ in the way
In the past 50 years the NLM, working to achieve this searches are c~nducted.'~] (Search strategies and instruc-
goal, has contributed tremendously to the biomedical field tions for PubMed and Internet Grateful Med will not be
(Table 1). In 1971, the NLM launched MEDLINE, an included within this article because this information can
index to biomedical articles, to support the information be found in detail on their respective Web sites). Each
needs of healthcare professionals.[4351
Originally used only service offers access to different databases. Accessing
by trained librarians, MEDLINE became directly acces- each database is simple and there is a direct link on the
sible to healthcare professionals in the 1 9 8 0 ~ . [During
~] PubMed home page to Internet Grateful Med and vice
the past two decades, the NLM expanded the topics of its versa. Results from searches in both services offers direct
databases and now includes a variety of databases on links to full-text articles from more than 800 participating
Table 1 Highlights of the National Library of Medicine Grateful Med. Since 1998, Internet Grateful Med searches
since 1956 MEDLINE using the PubMed retrieval engine.[31
Computerization of the Index Medicus and the development Once a MEDLINE search has been done via either
of MEDLINE PubMed or Internet Grateful Med, the user has the option
Provision of free access to the MEDLINE database of ordering listed articles from Loansome DocE, an
Development of international, online, article-ordering service from the
The NLM Web site (www.nlm.nih.gov), which is a portal to National Network of Libraries of Medicine.“] Before
information on its healthcare databases, news, research users can place an order, however, they must identify an
programs, and library programs “Ordering Library,” then register using the Loansome
PubMed, a free NLM database search service Doc registration page. Although there is no fee for using
MEDLINEplus, a Web site for consumer health information Loansome Doc, there is a charge for copies of articles.
the National Network of Libraries of Medicine
Development and implementation of an integrated library
catalog (LOCATORplus) that can be searched through
the Internet
Creation of
A grant program, to support research in medical informatics
and in biotechnology and health information The NLM has brought about important changes to
The Toxicology and Environmental Health Information pharmacy practice and research. By searching MEDLINE
Program, to facilitate governmental and nongovernmental and its other databases, pharmacists, pharmacy research-
literature (this program operates TOXNET, ers, and pharmacy students can find answers to clinical
http://toxnet.nlm.nih.gov/) questions, seek help in decision making, obtain informa-
The Lister Hill National Center for Biomedical Communica- tion to support research, expand their knowledge on a
tions (http://lhncbc.nlm.nih.gov),which oversees NLM
certain drug topic, and explore and obtain available data
research and development
to prepare educational tools for colleagues, students,
The National Center for Biotechnology Information (NCBI,
www.ncbi.nlm.nih.gov), which is responsible for the data- patients, and consumers.
bases that contain DNA and protein sequences, genome When a pharmacist or pharmacy student has a clinical
mapping data, and 3-D protein structures. question, a good place to begin seeking an answer is the
The National Information Center on Health Services Research medical literature. MEDLINE is used often to solve
and Health Care Technology clinical questions;“’,’ rare clinical conditions have been
PubMed Central diagnosed from the results of a MEDLINE search.[41Some
hospitals or medical libraries offer search systems that will
(Adapted from Ref. [l].)
search medical literature from MEDLINE and other
sources, such as Best Evidence and the Cochrane Lib-
journals. The services offered by PubMed and Internet rary.“’] Other sources for clinical decision making by
Grateful Med are updated continually, and the reader is pharmacists include clinical practice guidelines. The NLM
encouraged to visit their Web sites often to check out offers the Health ServicesB’echnology Assessment Text
new features. (HSTAT),[12] a free resource that allows users to access
The NLM developed PubMed as a user-friendly search full-text evidence reports, clinical practice guidelines and
tool to explore MEDLINE. For each citation listed in a consensus statements (such as those from the NIH and the
search result, the user has the option to click on “Related AHCPR), technology assessments, and other documents
Articles,” which takes the user to a listing of additional useful in healthcare decision making. One other inte-
citations that are related to the search topic. Additionally, resting resource made available online by the NLM is
PubMed offers access to publisher Web sites for full-text the Online Mendelian Inheritance in Man@ Web site.[l3]
articles, a citation matcher (service that assists a user in This site, primarily for healthcare professionals, is a
finding a complete citation), and access to the molecular searchable database of human genes and genetic disorders.
biology databases of the NCBI. One of the newest Aiming to bring the benefits of advanced technology to
features of PubMed is called “Cubby,” a page on the site the healthcare profession, other NLM programs, like the
that allows the user to store a search and update it in the Visible Human Project, offer new opportunities to study
future (users need to register for this free service). human anatomy and options to further medical research.
AIDSLINE soon will be added to PubMed.”’ A user can The Visible Human is essentially a database
search MEDLINE and 14 other NLM databases (e.g., of electronic transverse CT, MRI, and cross section
AIDSLINE, AIDSDRUGS, TOXLINE) via Internet images from an entire female and male human cadaver.
582 National Library of Medicine
"See Table 3.
(Adapted from Refs. [1, 3, 7-91,)
Susan C. Fagan
University of Georgia College of Pharmacy, Athens, Georgia, U.S.A.
Melody Ryan
University of Kentucky, Lexington, Kentucky, U.S.A.
neurological patient, depending on the patient’s dia- 5. Renal: Is it necessary to adjust doses for poor
gnosis, some systems should receive special attention. renal function?
Some examples of potential neurology-associated pro- 6. Hepatic: Is there evidence of hepatic dysfunction
blems that can be detected by a review of systems are that may require dosing adjustment of antiepi-
as follows: leptic agents or statins?
7. Endocrine: Diabetes increases risk of stroke, may
1. Vital signs: Are there any abnormalities that worsen stroke outcomes, and causes peripheral
could be drug related? For example, sympatho- neuropathy. Thyroid disorders may contribute to
mimetics or stimulants may cause hypertension mental status changes. Is the patient postmeno-
that could increase stroke risk. Temperature, pausal, increasing stroke risk?
heart rate, and blood pressure are important the- 8. Hematology: Does the patient have a blood
rapeutic monitoring parameters for niedications dyscrasia attributable to antiepileptic drugs or
such as antihypertensives, corticosteroids, and other medications? Is the patient hypercoagul-
stimulants. Weight gains or losses can be at- able, causing an increased risk of stroke? Does
tributed to some medications, such as valproic the patient have any particular bleeding risk that
acid and tricyclic antidepressants for weight gain limits antiplatelet drug use?
or topiramate for weight loss. 9. Gastrointestinal: Does the patient have nausea,
2. Cardiovascular: Does the patient have atrial fib- vomiting, diarrhea, or constipation caused by a
rillation, a coronary artery disease history, or hy- medication or neurological disease state?
perlipidemia increasing stroke risk? Could or- 10. GU/reproductive: Because of neurological dis-
thostatic hypotension be due to medications for ease, some patients must use a urinary catheter,
Parkinson’s disease treatment? Is a medication predisposing them to urinary tract infections and
such as amantadine causing peripheral edema? requiring frequent antibiotic use. What form of
3. Pulmonaq: Does the patient require medica- contraceptive does the patient use, if any? Oral
tions for pulmonary disease that may affect contraceptives may be less effective with anti-
neurological functioning such as beta agonist- epileptic drugs or may contribute to headaches or
induced tremor? Could a medication such as stroke risk in a smoker. Is the patient pregnant or
beta-blockers prescribed for essential tremor breastfeeding, thus prompting close examination
cause deterioration of pulmonary function? of medication use? Stroke risk is also increased
Could an acute pulmonary illness such as pneu- in the postpartum period.
monia be contributing to delirium? Does the 11. Musculoskeletal: Does the patient have muscular
patient have a history of pulmonary embolism pain that could be caused by statins? Does the
that may indicate a predisposition to throm- patient have muscular spasms or central spas-
boembolic disorders? Is the patient a current or ticity requiring an antispasmodic? Does the pa-
past smoker, contributing to stroke risk or tient complain of arthritic joint pain? Are tension
migraines? headaches a problem? Does the patient have a
4. Fluid/electrol~te/nutritonal status: Does the tremor that could be attributed to medication use
patient require nutritional supplementation as is such as lithium, valproic acid, or beta agonists?
the case for folic acid during pregnancy to prevent Does the patient have weakness that could be due
neural tube defects, a vitamin BI2 deficiency- to medication use, underuse, or overuse (e.g., py-
associated peripheral neuropathy, or a disease- ridostigmine underuse, antispasmodic overuse)?
associated inability to ingest adequate nutrition 12. Neurological: Discussed later.
(amyotrophic lateral sclerosis or debilitating 13. Psychological: Does the patient have under-
stroke)? Does the patient have adequate hydration treated depression, schizophrenia, or bipolar dis-
(dehydration affects cerebral blood flow)? Are order that may complicate neurological dis-
feeding tubes present, requiring special dosing ease treatments? Could psychotic symptoms be
form considerations? Is the patient hypoalbu- caused by neurological illnesses such as diffuse
minemic, which may impact dosing adjustments Lewy body disease or Huntington’s chorea?
for highly protein-bound medications? Is the Could hallucinations be caused by medication
patient on the ketogenic diet for seizure control use such as dopaminergic agents? Does the
that requires careful examination of all carb- patient require medication for attention-deficit
ohydrate sources, including medications? disorder?
586 Neurology Specialty Pharmacy Practice
Mental status Greeting the patient daily: Does the patient remember Dementias, delerium, stroke, encephalopathies,
you? Does the patient know where helshe is? agents that cause sedation and/or confusion
Assess alertness, speech, memory, and ability to
communicate and compare with baseline. Mini
Mental Status Examination may be required for insurance
approval of some therapies for Alzheimer’s disease.
Cranial nerves Note facial tone and symmetry, gaze preference, Myasthenia gravis (ptosis), Parkinson’s disease
and ptosis; check for nystagmus by having patient (masked facies), stroke (palsy), antiepileptic
follow object across visual field; engage in conversation drug therapy (nystagmus, slurred speech)
to assess for slurred speech.
Motor function Assess handshake for ability to lift arm against gravity Stroke (arm and leg weakness), Parkinson’s
and motor control; move toward target (your hand); disease (tremor, bradykinesia, rigidity,
assess tremor (resting, action, and postural) of hand; dyskinesias), essential tremor
assess grip strength. Ask patient to lift leg off bed.
Observe for dyskinesias.
Sensory function Touch patient on both armdlegs and assess symmetry; Stroke, neuropathy (diabetes, HIV, drug-induced)
inquire about paresthesias.
Gait Do not test in hospitalized patient (ask the patient if Stroke. vertigo, Parkinson’s disease, antiepileptic
he/she has been walking); observe patient walking drug toxicity
normally, heel-to-toe, and turning.
Neurology Specialty Pharmacy Practice 587
Ischemic stroke TPA, heparin, ASA, clopidogrel, ticlopidine, Neurological worsening, bleeding, PT/APTT,
dipyridamole and aspirin, warfarin, surgery INR, CBC
Back pain Analgesics, surgery, antibiotics if infectious Pain, sedation, cultureskensitivites
Bell’s palsy Steroids, acyclovir, artificial tears and lubricants Weakness. paresthesias
Guillain barre Plasmapheresis, IVIG Hemodynamics, respiratory status, renal
function
Headache Surgery if SAH, IV DHE, analgesics, triptans Pain, sedation, neurological status
Multiple sclerosis Methylprednisolone, beta interferons, glatiramer Weakness, paresthesias. vision, injection
acetate, antispasmodics, anticholinergics technique
Seizures Antiepileptic agents Seizure activity, CNS side effects, respiration,
EEG
Subarachnoid Surgery, BP control, nimodipine, volume expansion, Neuro status, BP, hydration status, EKG, ICP
hemorrhage sedation, seizure prophylaxis, stool softeners,
ventricular drainage
TINvertebrobasilar Surgery, antiplatelets, heparidwarfarin Neuro status, bleeding, platelets, BPkydration,
insufficiency aPTT, INR
Weakness, acute Depends on final diagnosis Dmg induced? Infectious?
generalized
Key: TPA, tissue plasminogen activator; ASA, aspirin; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international
normalized ratio: CBC, complete blood count; IVIG, intravenous immune globulin; SAH, subarachnoid hemorrhage; IV DHE, intravenous
dihydroergotamine; CNS, central nervous system; EEG, electroencephalogram; BP, blood pressure; EKG, electrocardiogram; ICP, intracranial pressure;
TIA, transient ischemic attack.
guideline development (e.g., treatment of hypertension in lary medications, or requesting patient assistance from
stroke patients), critical pathway/protocol d e ~ e l o p m e n t , ~ ~ ] pharmaceutical companies for medically indigent pa-
adverse drug reaction reporting, and Pharmacy and tients. Patients determined to be nonadherent to their
Therapeutics Committee new drug evaluations. medication regimen should also be investigated for the
cause. This etiology may be as diverse as lack of un-
derstanding of the disease state to difficulty tolerating the
medication to inability to afford the medication. In most
cases, the pharmacist can assist the patient with these
barriers to adherence.
The clinical pharmacist positioned in the outpatient In the neurology population, patient medication edu-
setting can also significantly affect patient care. In con- cation is very important as regimens can be very complex
trast to the inpatient neurological specialist, the outpatient and the patient may have communication or comprehen-
specialist usually cares for more chronic neurological sion difficulties. The pharmacist may develop educational
problems and may develop a long-standing relationship materials and clear, concise directions for medication
with their patients. The elements of the pharmacotherapy adjustments to help patients. Specialized calendars or
history, review of systems, and neurological exam are the dosing charts can provide a visual reminder to patients in
same as previously described for the inpatient setting. addition to verbal counseling.
Table 3 lists common outpatient neurological diagnoses From these basic clinical pharmacy functions, the
with the medications used and monitoring parameters ambulatory neurological pharmacist may choose to sub-
used by clinical pharmacists. specialize in any of the common disease states seen in
Formulating the pharmaceutical care plan is a very neurology clinics. In disease states where medication
important part of the outpatient neurological pharmacists’ plays an important role in patient care and close moni-
duties. Special care must be taken to remove barriers to toring is necessary, the pharmacist can be an essential part
the patient obtaining the required medications. This may of patient management. As previously mentioned, the
involve facilitating refill requests, obtaining insurance or majority of clinical pharmacist involvement in neurology
health maintenance organization approvals for nonformu- has been in epilepsy clinics. There are several good re-
588 Neurology Specialty Pharmacy Practice
Key: CNS, central nervous system: NSAIDs, nonsteroidal anti-inflammatory drugs: COMT, catechol-0-methyltransferase; CBC. complete blood count;
TIA, transient ischemic attack; INR. international normalized ratio.
ports of these clinics in the literature.’4-81 The reported Pharmacists may be involved in a multidisciplinary
responsibilities of the clinical pharmacists included taking stroke program with an outpatient component. Here the
medication histories, performing directed neurological pharmacist may monitor and adjust anticoagulation
examinations, ordering laboratory evaluations for mon- treatment and provide safety monitoring for ticlopidine
itoring medications, assessing adverse drug reactions, through collaborative care agreements with the prescriber
providing medication counseling, and providing pharma- and the patient.“” Vigilant monitoring of disease states
cokinetic consultations. that may contribute to stroke risk such as diabetes,
The role of the clinical pharmacist in a specialty hyperlipidemia, or hypertension with appropriate medica-
headache clinic has been described by Adelman and Von tion adjustments can also be the realm of the pharmacist.
Seggem.”’ This individual obtains medication histories Extensive patient education materials may be necessary,
and extensively counsels patients on their medication and the clinical pharmacist may want to participate in
regimens. In addition, the clinical pharmacist determines community education efforts such as stroke screenings.“
changes to the patient’s therapeutic regimen to enhance Other medication-intensive neurological disorders in-
effectiveness and minimize toxicity. clude Parkinson’s disease and multiple sclerosis. Al-
Neurology Specialty Pharmacy Practice 589
though specific pharmacist interventions have not been nurses, etc.). Many hold faculty appointments at Colleges
reported in the literature for these disease states, some of Pharmacy and/or Medicine. In addition, pharmacy
opportunities for involvement can be envisioned. For specialists participate in and conduct clinical and/or basic
Parkinson's disease, the pharmacist may develop a col- research in the neurosciences.
laborative relationship with the neurologist and make ne-
cessary adjustments to medication regimens in response
to patient needs. In this case, the pharmacist would likely
develop a specialized set of physical assessment skills,
including detailed motor examination. Parkinson's dis-
ease-specific diaries and medication regimen handouts The following guidelines may be helpful in providing care
could be provided to this population and be used for to neurology patients:"21
dosage adjustments. The multiple sclerosis population can
also benefit from pharmacist involvement. When disease- 1. Practice advisory: Thrombolytic therapy for acute
modifying therapies such as beta interferons, glatiramer ischemic stroke. American Academy of Neuro-
acetate. or immunosuppressants are prescribed, a great logy, 1996 ( 5 pages).
deal of patient education must be performed. Patients 2. Intravenous immunoglobulin preparations. Univer-
must understand that these medications are not curative, sity Health System Consortium, 1999 Mar (216
but slow progression and/or decrease multiple sclerosis pages).
exacerbations. In addition, the patient must be instructed 3. Second report of the Expert Panel on the De-
in self-injection technique for the parenteral products and tection, Evaluation, and Treatment of High Blood
monitoring regimens must be established for the immu- Cholesterol in Adults (Adult Treatment Panel 11).
nosuppressants to ensure patient safety. Other issues that National Heart, Lung, and Blood Institute (U.S.),
the pharmacist may address include therapy for muscle 1993 Sept (Reviewed 1998) (169 pages).
and bladder spasticity, fatigue, sexual dysfunction, pain, 4. Sixth ACCP consensus conference on antithrom-
and urinary tract infections. botic therapy. American College of Chest Physi-
cians, 2001 (20 pages).
5. Practice advisory on selection of patients with
multiple sclerosis for treatment with Betaseron.
American Academy of Neurology, 1994 (reviewed
1998) (4 pages).
Very few examples of outcomes research in neurological 6. Sixth report of the Joint National Committee on
pharmacy exist. However, one historical control study the Prevention, Detection. Evaluation and Treat-
determined that the implementation of a pharmacokinetics ment of High Blood Pressure. National Heart,
consultation service in an epilepsy clinic decreased sei- Lung. and Blood Institute (U.S.), 1997 Nov (33
zure frequency and number of adverse effects compared pages).
with the baseline frequency in the 4 months prior to of- 7. Practice guideline for the treatment of patients
fering the service."] A second study conducted in the with Alzheimer's disease and other dementia of
pediatric epilepsy population described the effect of es- late life. American Psychiatric Association, 1996
tablishment of a specialty pediatric epilepsy clinic with Dec (93 pages).
clinical pharmacy services. Compared with patients seen 8. An Algorithm (Decision Tree) for the Management
before the beginning of the clinic. patients seen in the of Parkinson's Disease: Treatment Guidelines.
specialty clinic had decreased numbers of antiepileptic Neurology 1998; 50 (suppl 3) S1-§57.
drugs and decreased doses of these medications. Fre- 9. PRN Opinion Paper: The Ketogenic Diet. Phav-
quency of seizures was not examined in this report.[81 macothevnpy 1999; 19:782-786.
OT ITI
nizations (American Society of Health-System Pharma- nical outcomes in an ambulatory-care epilepsy clinic. Am.
cists, American College of Clinical Pharmacy) and within 88, 45, 1549-1551.
the confines of neurology subspecialty groups (American 8. Summers, B.; Summers, R.S.; Rorn, S. The effect of a
specialist clinic with pharmacist involvement on the man-
Epilepsy Society). In addition, stand-alone groups of
agement of epilepsy in paediatric patients. J. Clin. Hosp.
clinical specialists, usually in collaboration with psy-
Pharm. 1986, 11, 207 214.
~
chiatry specialists (College of Psychiatric and Neurologic 9. Adelman, J.U.; Von Seggem, R.L. Office Rx: A renewed
Pharmacists), develop and offer high-quality, intensive professional relationship. N. Carolina Med. J. 1995,56 (6),
continuing education several times per year in the United 262-264.
States. The introduction of electronic communication has 10. Ryan, M. In Collaborative Cure Agreements to Facilitate
facilitated the exchange of clinical experiences and in- Pharmaceutical Care. International Pharmaceutical Abs-
formation via list servs and e-mail directories available on tructs, 32nd American Society of Health-System Pharma-
the Internet. cists Midyear Clinical Meeting, Atlanta, Georgia, Dec. 7-
11, 1997; American Society of Health-System Pharma-
cists: Washington, DC, 1997, 3412273, 2164.
1I . Ryan, M.; Kammer, R. In Report on a Multidisciplinary
Stroke Screening. International Pharmaceutical Ahstructs,
33rd American Society of Health-System Pharmacists
I. Cippole, R.J.; Strand, L.M.; Morley, P.C. The Patient Care
Midyear Clinical Meeting, Las Vegas, Nevada, Dec. 6- 10,
Process. In Pharmaceutical Cure Practice; Cippole, R.J., 1998; American Society of Health-System Pharmacists:
Strand, L.M., Morley, P.C., Eds.; McGraw-Hill: New
Washington, DC, 1998, 3513328, 2359.
York, New York, 1998; 121-176.
12. see www.guidelines.gov.
2. Nelson, W.J.; Edwards, S.A.; Roberts, A.W.; Keller, R.J.
Comprehensive self-medication program for epileptic
patients. Am. J. Hosp. Pharm. 1978, 35, 798 801.
3. Gonzaga-Camfield, R. Developing an emergency depart- Y
ment team for treatment of stroke with recombinant tissue
plasminogen activator. Crit. Care Nurs. Clin. North Am. Graves, N.M. The role of the pharmacist in investigational AED
1999; 11, 261 268.
~
trials. Epilepsy Res., Suppl. 1993, 10, 201-209.
4. Kootsikas, M.E.; Hayes, G.; Thompson, J.F.; Perlman, S.; McCauley, J.W.; Mott, D.A.; Schommer, J.C.; Moore, J.L.;
Brinkman, J.H. Role of a pharmacist in a seizure clinic. Reeves, A.L. Assessing the needs of pharmacists and phy-
Am. J. Hosp. 1990, 47, 2478- 2482. sicians in caring for patients with epilepsy. J. Am. Pharm.
5. Hixon-Wallace, J.A.; Barham, B.; Miyahara, R.K.; Ep- ASSOC.1999, 39, 499-504.
stein, C.M. Pharmacist involvement in a seizure clinic. J. Mort, J.T.; Tasler, M.K. Managing dementia-related behavior in
Pharrn. Pract. 1993; 6 (6). 278-282. the community. J. Am. Pharm. Assoc. 1996, NS36 (4), 249-
6. Allen, J.P.; Ludden, T.M.; Walton, C.A. The role of cli- 256.
nical pharmacists in a epilepsy clinic. Drug Intel. Clin. Pitterle, M.E.; Sorkness, C.A.; Wiederholt, J.B. Use of serum
Pharm. 1978, 12, 242-244. drug concentrations in outpatient clinics. Am. J. Hosp. Pharm.
7. Ioannides-Demos, L.L.; Home, M.K.; Tong, N.; Wodak, J.; 198542, 1547 1552.
Harrison, P.M.; McNeil, J.J.; Gilligan, B.S.; McLean, A.J. Turner, C.J.; Pryse-Phillips, W.Can. J. Clin. Pharmacol. 1999, 6
Impact of a pharmacokinetics consultation service on cli- (2), 113-117.
PROFESSIONAL DEVELOPMENT
Catherine A. Heyneman
Idaho State University, Pocatello, Idaho, U.S.A.
~aximum
time to
completeb
Schoolkollege Enro11ment (yr) Web site URL CostC
North Carolina Open 3 http://www .pharmacy.unc.edu/ (R) $$
xpharmdindex.htm1
North Dakota State Restricted 6 http:l/www.ndsu.nodak.edu/ $$$
instruct/hanel/pharmacy/ntp-let. htm
Ohio Northern Open 5 http:/lwww.onu.edu/ $$$$$
pharmacy/ntpdldefault.asp
Ohio State Open 6 http://www.pharmacy . $$$
Ohio-state.edulntpd1
Oklahoma (Southwestern Not admitting” No web site found
Oklahoma State University
and Oklahoma University)
Duquesne (Pennsylvania) Open 5 http:l/www .duq.edulpharmacyl
Programslnon-traditional.htm1
Philadelphia (Pennsylvania) Open 5 http :l/www.usip.edulgraduate/f ex
Wilkes (Pennsylvania) Start Fall 2001 No web site found
Temple (Pennsylvania) Discontinued
Rhode Island Discontinued
South Carolina Not admitting” No web site found
South Dakota see Univ. Minnesota
Tennessee see Univ. Kentucky
Texas Schools Restricted 5 http:l/www.txpharm.orgl $$$
Utah see Idaho State
Virginia Commonwealth Open 2 http://www.pharmacy.vcu.edu/ (R) $$$
nontradlindex. html
Shenandoah (Virginia) Open 4 http:l/pharmacy .su.edu/ $$$$
Ntdplindex. html
Washington (University of In-state preferred 5 http://depts.washington.edul (R) $
Washington and Washington expharmd
State University)
West Virginia Restricted 6 http://www.hsc,wvu.edu/ $%$$
soplacademicl
Wisconsin Open 6 www.pharmacy.wisc.edu1ntpd (R) $$$
(R) =Resident; (NR) = Nonresident.
Relative cost scale: $ = $6- 10,000; $$ = $1 1- 15,000: $$$ = $16-20,000; and $$$$ = 521 -25,000; $$$$$ > $26,000.
‘Indicates programs that did not continue after 2000-2001.
bUsual time frame for completion-where applicable, maximum time requirement (max.) is presented.
‘Costs are subject to change and may vary depending on credit load taken or length of time to complete degree requirements.
Only those schools providing nontraditional approaches accurate information, verification was attempted using the
(i.e., alternative curricular pathway to an on-campus AACP’s Pharmacy School Admission Requirements for
program) are included here, although it is worth noting 2001-2002[91 and a telephone call to the program, if
that several schools still offer traditional on-campus needed. Nonetheless, many programs are still under devel-
postbaccalaureate Pharm.D. programs. opment and others are continuing to experiment with new
A general comparison of the admission requirements, techniques and methodologies to enhance nontraditional
didactic coursework, and clerkship curricula is provided learning. Therefore, program requirements and curricula
for current NTPD programs in Tables 1-3. This infor- may change quickly and frequently. A web site address
mation was collected from a review of each program’s (URL) is provided where available, and readers are encou-
web site andlor written information. To ensure current and raged to contact the schools for more specific information.
594 Nontraditional PharmB. Programs
Vi s
those individuals with irregular schedules or other computer capabilities can result in student dissatisfaction
conflicts. In addition, it allows students to ‘.fast forward” and frustration. As with other educational mediums,
quickly through information that may have been acquired students should carefully investigate the quality of web-
previously while allowing “replay” to review new in- based materials and attempt to validate program claims
formation when needed. via inquiries to active students whenever possible. In a
The major disadvantage of videotaped coursework is speech, Dr. Victoria Roche cautioned against becoming
the inability to interact directly with the instructor or other enamored with technology for its own sake.‘131Studies
classmates. However. most programs currently employ comparing cybercourses and traditional didactic formats
the use of supplemental or web-based interactions with are essential to apply the most effective learning strategies
instructors or online small group discussions to overcome, in the future.
or at least minimize, these deficiencies. Occasionally, NTPD program didactic requirements are remarkably
poor technical quality may substantially impact course similar; the marked differences reported in Table 2 can be
delivery and practitioners considering these programs accounted for primarily by differences in prerequisite
may want to review sample videotapes or discuss this coursework or delivery methods used. Few programs
issue with current students. provide a self-paced format and, despite the widespread
potential for self-paced curricula, most NTPD programs
Distance Learnin follow a traditional semester sequence. Thus, flexibility
may be an important distinguishing characteristic depend-
Using a variety of available technologies, transmission of ing on the self-directed nature, motivation, or family and
live didactic lectures to remote classrooms remains a com- work demands of individual students. Conversely, self-
mon vehicle for course delivery. For many practitioners, paced programs tend to be less interactive because
this format is probably easiest to assimilate because it students are generally at different points in the curriculum
closely resembles more traditional teaching methods and at any given time. They are less conducive to small-group
affords at least some direct student and instructor in- learning activities (e.g., case discussions and interactive
teraction. A regular class schedule and close geographic projects) and are best suited for practitioner-students that
proximity to one of the regional transmission sites are the are highly self-directed.
major limitations to distance learning programs.
Dramatic improvements in computer technology have One of the more difficult issues facing nontraditional
fostered the development of unique web-based ap- programs has been the development of methodologies for
proaches to curriculum delivery. Several programs offer assessing learning acquired through previous experience.
virtually all didactic coursework via the Internet, and Obviously. daily practice affords a rich environment for
nearly all NTPD programs are gravitating toward this new continuing education, yet the extent to which individual
educational tool. Some programs have found it necessary practitioners use this varies considerably. To address this
to contract with private corporations to assist with the issue and provide a mechanism for assessing prior learn-
rather daunting task of redesigning their entire curricula ing. many schools and colleges have developed innov-
to an online, interactive format. ative evaluation processes. Portfolio review has become
Web-based didactic coursework generally allows stu- an increasingly popular mechanism in this regard. Under
dents greater flexibility in determining their own study this process, student-practitioners are given academic
schedule and may allow easier incorporation of sup- credit if they can document their ability to perform spe-
plemental educational materials (e.g.. Internet links to cific learning objectives. Frequently, this involves des-
additional information and/or demonstrations). The posi- cribing in significant detail work situations or patient
tive quality of web-based flexibility must be tempered by cases that demonstrate the student-practitioner‘s ability to
recognition of technological limitations, however. Many understand and perform the objective appropriately. Com-
students find themselves feeling isolated and have dif- mon examples include the following types of information
ficulty coordinating group projects over the Internet. and documentation:
Even with recent technological improvements, not all
web-based coursework measures up to advertised bene- * A statement of career goals.
fits, and significant problems may occur. Slow transmis- * A detailed description of current practice activities,
sion rates, server malfunctions, and poor utilization of including services provided and patient population
596 Nontraditional Pharm.D. Programs
Didactic
coursework
(semester Challenge Portfolio Self-
Schookollege credits)a examsb reviewb Qtherb%d paced Delivery methods'
Samford (Alabama) 56 (includes Distance learning by
clerkships) videoconferencing
Auburn (Alabama) 44 Internet, CDs, traditional
lectures
Arkansas 21 Internet, videotapes
Arizona 24 AACP Consortium,
videotapes
Colorado 35 All Internet-based
course delivery
Nova Southeastern 31 Distance learning to
(Florida) regional sites, Internet
Florida 27 Videotapes, Internet,
3 days on-campus/
semester
Georgia Schools 29 Distance learning,
(Mercer and videotapes, tele-
University of Georgia) conferencing, Internet
Idaho State 28 BCPS (10) Videotapes, Internet
Midwestern (Illinois 35 quarter Eveninglweekend classes
and Arizona) hours
Illinois -Chicago 24 BCPS, DI, Internet, web con-
and Statistics ferencing
Purdue 28 Yes Videotapes, Internet,
regional workshop sites
Iowa 29 Recent grads Videotapes, Internet,
only weekend
Kansas 24 All Internet-based
course delivery
Kentucky 26 Yes (4) Videotaped case studies,
Internet, interactive
patient activities
Louisiana at Monroe Distance learning,
videotapes, Internet
Xavier (Louisiana) 24 Videotapes, Internet
Maryland 24 On-campus and distance
learning, Internet
Massachusetts Discontinued
Minnesota 26 ( 1 5 ) total curri- Internet with 1 week-
culum endyear on campus
Mississippi 33 BCPS (32) Problem-based learning
format via chat
room groups
Missouri-Kansas City 22 Videotapes
Montana 25 BCPS (14) Internet, one course
videotaped
Creighton (Nebraska) 34 BCPS Converting to Internet-
based courses
New Mexico Two courses BCPS (all ASHP Clinical Skills
(see delivery didactics) Program and the ACCP
methods) Pharmacotherapy Self-
Assessment Program
(PSAP)
(Continued)
Nontraditional Pharm.D. Programs 597
Samford (Alabama) None, but patient monitoring Yes None Yes, but not all
required for disease modules
Auburn (Alabama) 8 (typically) Yes Clerkship requirements All
are individualized
Arkansas 16 (4 weeks on-campus) Yes None 12 Weeks self-
directed study
Arizona 26 Yes None Under certain
circumstances
Colorado 30 Yes Portfolio waiver (12) (15)
Nova Southeastern 16 Yes
(Florida)
Florida No, patient Yes Yes
monitoring required
for disease modules
Georgia Schools 18 Yes Precepted clerkships (6)
(Mercer and
University of Georgia)
Idaho State 28 Yes Substitution only (16)
Midwestern (Illinois) 20 (32 quarter hours) Yes Yes Under certain
Circumstances
Illinois-Chicago 30 (20 semester credits) No ASHP residency (12) Clerkships must be
completed in Chicago
Purdue 28 Yes Under certain
circumstances
Iowa 35 (28 semester credits) Yes Under certain
circumstances
Kansas 20 Yes Yes
Kentucky 32 Yes Yes. but not all
Louisiana at Monroe TBA
Xavier (Louisiana) 15 (9 semester credits) No Yes
Maryland 4.5 (total approx. 180 hours) Yes All
Massachusetts Discontinued
Minnesota 25 Yes Yes, maximum 15 One practice enhancement
credit hr total for clerkship
didactic and clerkships
Mississippi 24 Yes 30% of clerkship Optional case management
requirement
Missouri-Kansas City 28 Yes (8) (4)
Montana 28 Yes No All
Creighton (NE) 24 Yes (8) (12)
New Mexico 36 Yes (16) No
Albany (New York) 25 Yes (5) One self-directed rotation
A & R Schwartz (New York) 16
Buffalo (New York) 36 Yes Yes
North Carolina 28 Yes Under certain
circumstances
North Dakota State 36
Ohio Northern 24 (30 quarter Yes (8) 10 quarter (8) 10 quarter
hours) hours hours
Ohio State TBA
(Continued)
Nontraditional Pharm.D. Programs 599
served; generally, this includes examples of written and should be investigated thoroughly to ensure that
patient work-ups or care plans that relate to specific career goals and objectives are satisfied.
educational objectives. The types of clerkship experiences and time commit-
Documentation (i.e., dates, location, and copies of ment vary considerably among NTPD programs (Table 3).
handouts, etc.) of presentations at pharmacy or other Internal medicine and ambulatory care constitute the core
professional meetings. clerkship requirements of many programs, with electives
Previous educational activities including disease state in mental health, pediatrics, geriatrics, and drug informa-
management programs, certifications, etc. tion commonly offered. Some programs, such as Idaho
Other community or preventative health care State University’s NTPD program, offer a capstone rota-
activities. tion during which the student implements and documents
the resultant benefits of some aspect of pharmaceutical
care at their original place of employment. This serves not
only to further the goals of the profession, but also rewards
employers for their flexibility and patience by upgrading
The experiential component presents special challenges the level of care at the employment site.
for both NTPD programs and students, particularly in Most programs allow for part-time completion of
rural areas.[14’ Although credit for work-related experi- clerkships. This can be arranged on a half-time basis (e.g.,
ence and some flexibility in designing the clerkship 4 hours per day) or, more frequently, students may com-
schedule are offered. the majority of programs require a plete one 4- or 6-week rotation, followed by returning to
significant clerkship component, typically 24 to 28 weeks. full-time work for a period of time. This allows students
Because many programs require full-time clerkship train- significant financial flexibility.
ing, a temporary leave of absence, use of vacation time or Restrictions vary with respect to fulfillment of clerk-
other work arrangements are necessary. Although this ship requirements at the student’s place of employment.
frequently imposes financial and personal difficulties, it is Some programs require students to complete as many
perhaps the most important aspect of Pharm.D. education clerkships as possible outside their normal workplace,
600 Nontraditional Pharm.
reasoning that exposure to different practice environments sire to enhance personal job satisfaction. Examples of
and styles will ultimately benefit the student-practitioner. internal motivations include a desire to improve clinical
Other programs have taken the opposite approach, and skills to optimize patient care, as well as the desire for
encourage students to complete all experiential rotations greater responsibility in making decisions regarding drug
in their normal workplace under the construct that this therapy. It has been our experience that students who are
provides an opportunity to enhance the practice setting internally motivated tend to progress faster through the
by practicing pharmaceutical care skills on their own nontraditional Pharm.D. curriculum and have a lower at-
patient population. trition rate compared with those students who are exter-
Many NTPD programs have simply funneled their nally motivated.
nontraditional students through available traditional clerk- The motivations of pharmacists interested in pur-
ship sites, whereas other programs have combined tra- suing a nontraditional Pharm.D. degree have been sur-
ditional sites with the identification and approval of new veyed.[20-221The most important reasons given for seeking
clerkship venues. The older NTPD programs have the a postbaccalaureate degree were improvement of clinical
advantage of expanding clerkship opportunities by using skills, enhanced work quality, and increased personal
nontraditional graduates as preceptors. satisfaction. Kelly et al. surveyed Pennsylvania pharma-
Evaluation of clerkship outcomes and competencies cists and discovered that the degree of satisfaction with
are, by nature, much more subjective than their didac- current employment was inversely correlated with like-
tic counterparts. This element, combined with the fact lihood of enrolling in an NTPD program; more than 73% of
that clerkship requirements of traditional, entry-level pharmacists who found their jobs to be “very unfulfilling”
Pharm.D. candidates often take priority over nontradi- stated they would probably apply.‘231
tional clerkship need^,"^"^] results in the potential for Two surveys of nontraditional Pharm.D. program
inclusion of clerkship sites with less than minimal qual- graduates have assessed the effect of the degree on prac-
ifications. Some programs have attempted to sidestep the tice Respondents from both surveys re-
costly and time-consuming process of evaluating and ported spending a significantly greater percentage of their
approving off-site clerkships by creating regional sites time performing pharmaceutical care (e.g., making the-
(satellites) where students congregate at predetermined rapeutic recommendations, developing treatment plans)
intervals (usually monthly or at certain times during the and less time dispensing or processing prescriptions
semester) for clinical practice assessments via paper case compared with their last position as a BS-trained phar-
presentations and group interaction. Students are then macist. The respondents also reported significantly
expected to accumulate direct patient contact experience greater levels of job satisfaction after graduation from
independently by following patients identified from their their respective NTPD programs.
workplace. Students from hospital pharmacy environ- Dunn et al. surveyed nontraditional Pharm.D. students
ments may encounter no difficulty finding interesting currently enrolled at the University of Arkansas.[251The
cases to follow; those with pharmaceutical industry or majority of respondents from this survey reported en-
community pharmacy backgrounds will have more hancements in self-esteem, pride in their profession, and
difficulty, and run the risk of sacrificing their capstone an elevation in the overall level of pharmaceutical care at
clerkship experience for the sake of convenience. their practice site. More than 85% of the Arkansas non-
traditional Pharm.D. students stated that they had gained
confidence in their ability to provide pharmaceutical care
as a result of the program.
wane. Given the high costs of starting a NTPD program and rigor expected of other doctoral-level programs.
(both in terms of faculty time and distance learning Thus, the goal of nontraditional education is not to make
infrastr~cture)[~] and the limited time frame to recoup any it easy to obtain the degree. but rather to make it easier to
investment, some universities have developed unique return to school. Substantial time, effort, and self-sacrifice
partnerships. For example, the University of Florida has can be expected of nearly all programs, and these gen-
partnered with a private corporation to facilitate delivery erally will directly correspond to enhancement of clini-
of course materials. However, Idaho State University cal skills and abilities. At this juncture, the evolution of
(ISU) has taken a different approach. ISU has entered into NTPD programs has virtually assured that practitioners
a collaborative clinical training agreement with the will be required to earn their doctorate and that grand-
University of Utah. As a result, ISU benefits from this fathering of the Pharm.D. degree will not occur.
agreement by bringing additional out-of-state students Considerable effort has gone into designing NTPD
into its established NTPD program, whereas the Univer- programs that achieve the same educational endpoints as
sity of Utah benefits by avoiding the high startup and their on-campus entry-level counterparts. The use of
maintenance costs of repackaging their curriculum into standardized patients as an assessment method has been
a distance learning format. Utah pharmacists also proposed as a mechanism to document parity between
benefit from the agreement by having access to ISU's nontraditional and traditional tracks.[261 Evidence sup-
NTPD program at a reduced tuition rate. As the pool ports the equivalency of nontraditional education;"" yet,
of prospective NTPD program applicants dries up, the issue is still somewhat controversial.["] Hopefully,
many more universities may consider such col- this will quickly disappear since NTPD programs are now
laborations to minimize costs, while still providing this required to demonstrate equivalent educational outcomes
essential educational service to practitioners. as part of their ACPE accreditation process.[271
Considerable resources have been allocated toward the Perhaps more controversial is the relative quality and
development and implementation of NTPD programs, equivalency between various NTPD programs. especially
generally without any corresponding increase in appro- with respect to major differences in clerkship require-
priated budgets or overall institutional support. Hence, ments for some programs. The ability to take time off
programs have been largely developed and are solely from work to complete full-time or even half-time
dependent on practitioner-derived tuition fees to maintain clerkship experiences is certainly a major impediment to
and support their existence. Total tuition costs for in-state pursuing a NTPD, and flexibility in designing the
residents of NTPD programs range from approximately clerkship program is imperative. This has resulted in
$5000 to $15,000, excluding the costs of textbooks, development of truly unique experiential components in
computer use, etc. Nonresident tuition rates are usually an attempt to overcome this critical element. The major
2-3 times higher. issue is whether NTPD programs requiring primarily self-
Financial cost, unfortunately, is a major impediment to directed clerkships (i.e., no or very limited onsite pre-
participation. Because these programs are designed for ceptor supervision) are able to provide the breadth and
full-time working practitioners, demonstration of fin- depth of clinical educational experiences compared to
ancial need is usually difficult and most practitioner- with more traditional clerkship programs (i.e.. student-
students will not qualify for federal financial aid pro- practitioner progress directly monitored by onsite pre-
grams. Thus, for those individuals who do not work for ceptor). Given the significant differences, debate will
institutions or corporations that offer employee educa- likely continue until more extensive experience accumu-
tional benefits, financing their return to school will lates or an objective comparison of NTPD programs and/
require careful consideration. Even with financial assist- or graduates can be made.
ance, a substantial burden of the cost will accrue to the
individual. Although a few programs may offer schol-
arship assistance specifically for nontraditional students,
these are extremely rare.
Clearly established goals, strong self-discipline, and an Final resolution and adoption of the Pharm.D. as the sole
extremely supportive family and employer are essential entry degree have provided the impetus for development
attributes of successful nontraditional students. Although of innovative nontraditional programs. Practitioners are
schools/colleges have expended significant efforts to de- now afforded a variety of equivalency-based academic
sign and implement user-friendly programs to allow full- degree programs from which to select. Consideration of
time practitioners to return to school, prospective can- career goals must be carefully weighed against the
didates must approach this process with the same intensity potential financial and personal costs.
602 Nontraditional Pharm.D. Programs
(accessed 101
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The authors acknowledge Ms. Kathleen Moe for her 14. Scott, D.M.; Miller, L.G.; Letcher, L.A. Assessment of
assistance in collecting the individual NTPD program desirable pharmaceutical care practice skills by urban and
rural Nebraska pharmacists. Am. J. Pharm. Educ. 1998,62,
information.
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15. Carter, R.A. In nontraditional education-assuring quality
is job one. Am. J. Pharm. Educ. 1994, 58, 411-413.
16. Vanderbush, R.E.; Dunn, E.B.; Morrison, W.J. Nontradi-
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Morrison, W.J. Nontraditional clerkships at the University suing a Pharm.D. degree through a nontraditional program.
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6. Fjortoft, N.F.; Engle, J.P. Effect of the nontraditional 22. Joyner, P.U.; Pittman, W.; Campbell, W.H.; Dennis, B.H.
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external Pharm.D. degree program. Am. J. Pharm. Educ. resources for nontraditional Pharm.D. programs in Penn-
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Distance learning via Lotus Notes Learning Space in a traditional Pharm.D. on practice patterns based on a survey
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Meeting in Tucson, Arizona, September 22, 2000; http:// (accessed 11/2/00).
PHARMACY PRACTICE ISSUES
Dietary supplements * Products (other than tobacco) intended to supplement the diet.
Products containing one of more of the following: * May be marketed in a food form if not “represented” as a
* Vitamin. mineral, herb or other botanical conventional food and labeled as a dietary supplement.
An amino acid or metabolite 0 Specific health or structureifunction claimsa can be made if
* An extract the FDA deems adequate scientific substantiation exists.
* Any combination of the above
Fortified foods 0 Foods enriched with vitamins and minerals, usually up to
0 Breakfast cereal 100% of the DRI.
* Vitamin B added to baked goods 0 Often mandated by law to replace nutrients lost during
processing.
Functional foods 0 A food or ingredient that may provide a health benefit
soy beyond the “traditional nutrients” it containsb
* Salad dressing with omega-3 polyunsaturated fatty acids 0 Specific health or structure/function claims can be made
0 Carrots with 170% of daily requirement of vitamin A if the FDA deems adequate scientific substantiation exists.
* Super fortified foods have more than 100% of the DRI
and/or foods with added botanicals or other supplements.
Medicinal foods 0 Food formulated to be consumed or administered internally
* Food to treat diabetes, obesity, or heart disease, sold while under the supervision of a physician.
through physicians, not by conventional retailers * Intended for specific dietary management of a disease or
condition for which distinctive nutritional requirements
are established.
Nutraceuticals 0 Dietary supplements and fortified foods enriched with
Orange juice with calcium nutrients not natural to the food.
0 Dietary/herbal substances in pharmaceutical dosage forms
that go in to making these determinations are costly. As a control standard to ensure that the label reflects what is in
result, companies that are successful can be expected to the bottle.
market products that will be branded and extensively The problem is illustrated by reports that labeled
promoted (Table 3). concentrations of active ingredients often significantly
overestimate the content in the dosage form. In one report,
nearly one-third of the brands tested did not contain what
their manufacturers ~ 1 a i m e d . lIt~ ’is a serous problem that
C TRACEUTICALS undermines the nutraceutical market, encourages skeptics
who criticize the value and role of nutraceuticals, and
Some of the most popular nutraceutical products marketed (most importantly) is potentially harmful to the public.
today are botanicals such as St. John’s wort, echinacea,
ginkgo biloba, saw palmetto, and ginseng. Unfortunately,
manufacturers are not required to prove their safety or
efficacy before marketing them. Dosages are not standar-
dized. The quality of the raw source and the plant parts
used are not regulated. And. unlike prescription drugs or The issues surrounding nutraceuticals and functional
over-the-counter medicines, there is no federal quality foods are important to pharmacists for two reasons. It is
~ ~ ~ r a c e ~and
t ~ Functional
ca~§ Foods 605
I
matters. Almost two-thirds of respondents in one sample
stated that they regularly talk with their pharmacist when
I I I I choosing an OTC product. and 58% have come to think
of their local pharmacist in the same terms as their fa-
mily doctor.[61
In the future, according to Dr. Benadette Marriott, who
is vice president of programs and communications at the
Burroughs Wellcome Fund, the need to guide consumers
through the maze of functional foods and nutraceuticals
may lead to significant changes in pharmacy practice.
Food stores will continue to evolve into "one-stop
weilness centers," where consumers go for basic wellness
screening activities, nutritional counseling, and medica-
tion advice. At the center will be the pharmacy, where
pharmacists will work with nutritionists and others to help
consumers recognize their options and select among
Fig. 1 Options for categorizing functional foods and nutra- several sources of an ingredient in order to safely treat or
ceuticals. lower their risk for disease."]
Table 2 Examples of functional foods. their key components, and potential health benefits
~ ~ n c ~ i food
on~l ey component Potential health benefits
Table 3 Examples of products marketed or planned to be marketed as functional foods by pharmaceutical companies
Novartis: Aviva product line Breakfast bars, cereals, and beverages.
Claims: Benefits the heart, bones, and digestion.
Marketed in United Kingdom and Switzerland.
U.S. launch planned.
McNeil Consumer Health, Division of Benecol brand margarine, salad dressing, and health bars in U.S.
Johnson &Johnson Claim: Reduce LDL cholesterol up to 14% within two
weeks of product use.
% In first few months, Benecol margarine captured
-2% of U.S. margarine sales.
Mead Johnson, Division of Bristol-Myers Squibb 0 EnfaGrow nutrient-enriched oatmeal and snack line for toddlers,
marketed primarily to physicians.
Allergy alert: EnfaCrow Nutritional Oatmeal for Toddlers in maple
brown sugar and cinnamon and strawberry flavors may contain
trace amounts of milk protein, not listed in the ingredients.”
e Viactiv Soft Calcium Chews sold in U.S. grocery and drug stores.
m Claim: To meet women’s special nutritional needs.
“From Ref. [9].
economical. In the year 2010, there are no fewer than Regard advertising and articles about supplements with
five sources of lycopene, listed here in order of in- caution:
creasing cost: Be cautious of any product that claims to “boost” the
immune system or “rejuvenate” health. Advise
Nutritional lycopene: vine-ripened tomatoes (and consumers to look for specific findings, not vague
other foods). claims.
Organically grown sources of lycopene: organically Nutraceuticals can have side effects under certain
grown tomatoes. circumstances and should be thoroughly tested before
Lycopene-enhanced functional foods: genetically being used by the public.
enhanced tomatoes with guaranteed high levels of Remember, if it doesn’t have side effects, it probably
lycopene.a hasn’t been thoroughly tested.
Nutraceuticals: dietary supplements that isolate and
contain high levels of lycopene. Natural first, supplement second:
Prescription drugs: pharmaceutical-grade lycopene When there is a choice between a vegetable and a pill,
containing the highest concentrations of lycopene recommend to eat the vegetable.
and clinically tested to meet FDA standards for safety Nutraceuticals are products that isolate recognized
and efficacy.‘: active ingredients. It is often not clear whether the
active ingredient is as effective when taken in the
absence of other nutrients found in food.
When taking supplements, consumers should take
them with food to aid absorption and minimize the risk
of GI upset.
The challenge facing the pharmacist is to guide this
patient through the maze of study results and conflicting Read the label; then, get a second opinion:
claims. There are few absolute answers, but there are Before buying anything, read the label.
guidelines that can help consumers make intelligent Confirm the value of the supplement with a health
decisions.[71And it is likely that the guidelines for today care advisor.
will be valid a decade from now.
Moderation is best:
More is not always better; vitamin C, selenium, and
vitamin D are examples where too little has no effect,
‘%Currently, not marketed. but too much has adverse effects.
Start with low doscs and work up. A commitment to prevention and health promotion Food TeLhnol
taking nutraceuticals is a long-term strategy. Starting 52 (2), 51 62
4 Hemphill, C Putting Dietary Supplenzmt\ to thc Tect, The
doses that are too high increase the risk of side ef-
New York Times, June 20, 2000 [Accessed 20 Tune 2000 ]
fects, which will dampen the consumer’s resolve to
Available at 1JRL: http://www.nytimes.com/library/
continue treatment. national/science/heaIth/062O~~~~hthlab-tests.ht~ni.
5. Augsburger, L.L. In Introduction and Welcoming Re-
K w p evevythiizg in perspective: mnrks, AAPS Dietary Suppleinenls Forum: Exploring the
Supplements arc only part of the picture. They are not Science oP Nutraceuticals, Washington, DC. June 28-30,
substitutes for a hcalthy diet, strcss reduction, exercise, 2000.
weight control, and (when needed) prescription drug 6. AICR. Seniors Prefer Taking Supplements to CYztrizging
therapy. Diet; American Institute for Cancer Research (AICR), 3 1
Nutraccuticals do not offsct thc negative effects of August 2000 IAccesscd 12 November 2000.1 Available at
http://www.newswise.com/articles/2000/X/S~J~SU~V.
smoking.
CRI .html.
Finally, remind consumers not to become obsessed by
I. Moyad, M.A. 7 ’ h ABC’s
~ g r Nutrition and Supplemr~nt.s,for
Prostate Cuncer; Sleeping Rcar Press: Chelsca, Michigan,
one disease. For cxample, men concerned about prostate
2000.
cancer and women concerned about breast canccr should . Functional foods and nutraceuticals. Nutr. Sci.
not ignore their risk factors for heart disease. y 2000, 5 ( 7 ) , 292 296.
9. SafetyAlert.com. Mead Johnson Issues Allergy Alert /or
Two Flavors or EnfaGrow Nulritional Oatmeal J I I - Tod-
dlers; 10 January 2000 [Accessed 13 November 20001.
Availablc at LJRL: http://www.safetyalerts.com/recall/f/00/
en fgrw .htm.
http://www.n ytimes.com/library/national/ 10. Wlarriott, R.M. Ti] Dietar.); Supplements: Clinicnl Studies
/062000hth-lab-tests.html. and Trials to Evaluate thr I?[fic.ucj and Stlj?t~ of’ Nut-
2. Block, 6.;Patterson, B.; Subar, A. Fruit, vegetables, and raceuticals m r l Dietary Suppletnpnts: A p p r o t ~ l
cancer prevention: A epidemiological evi- hliizg Bloc-k.r and the Coizsuiner Quntidar-).,AAPS Dietary
dence. Nutr. Cancer B Supplements Ikrum: Exploring the Science of Nutraceu-
3. Hasler, C.M. Functional foods: Their role in disease ticals, Washington, DC, June 28-30, 2000.
DlSTl NGU ISHED PERSONALITIES
created and published more than 100 practice standards, was a key lacilitator and motivator in the 1960 creation of
as well as numerous guidelines, technical assistance bul- the ASHP/AHA joint statement of the legal basis of the
letins: and position papers, many of which dealt with hospital formulary system, widely regarded as a crucial
clinical pharmacy issues. In 1962, ASHP produced the catalyst for the development of clinical pharmacy services
first Statement on Accreditation of Hospital Pharmacy in hospitals. The quality and quantity of publications
Internship Training Programs; in the Oddis era more than created by ASHP during the Oddis years stimulated
10,000 residcnts graduated from 375 programs accredited pharmacy’s development as a clinical profession. As the
P. In 1968, ASHP created the ASHP Executive sole accrediting body for residency and tcchnician-train-
Residency Program, which produced 26 graduates under ing programs, ASHP during the Oddis administration
Qddis’s stewardship. In 1969. the ASHP Research and contributed substantially to the skill levels of clinical
Education Foundation was created. In addition to the nu- pharmacy practitioners. Oddis was one of the profession’s
merous honorary doctor of science degrees bestowed on strongest advocates for making the doctor of pharmacy
him, Oddis received the Harvey A.K. Whitney Lecture degrcc the entry-level standard. As much as anything else,
Award, pharmacy’s highest award, presented by ASHP in it was Oddis’s persistence-behind the scenes, in a gen-
1970; the Hugo H. Schacfcr Award, presented by APhA tlemanly and nonconfrontational manner-that crystal-
in 1983; the Donald E. Francke Medal, presented by lized these achievements for pharmacy.
ASHP in 1986; the Remington Honor Medal, presented
by APhA in 1990; and the Andre Bedat Award, prcsentcd
by FIP in 1994.
Table 1 Oncology specialty practice roles dardized prescribing vocabulary, patient education,
interdisciplinary team review of medication errors and
Oversee cancer drug preparation and dispensing in patient
care settings communication issues, and medication error reporting
Direct patient care with cooperation from drug manufacturer^.[^] The use of
Investigational drug services standardized chemotherapy order forms improves com-
Research pleteness of physician ordering, prevents potential me-
Drug information dication errors, and reduces the time spent by pharmacists
Educational instruction clarifying orders.141 The oncology pharmacist is instru-
Outcomes assessment mental in the development of such forms. Chemotherapy
Pharmaceutical industry checklists can also be used in the drug order verification
Medical communications process. Some institutions include these on the product
patient label, as well.
In an effort to identify opportunities to reduce chemo-
pharmacists. Preventing medication errors is a vital goal of therapy medication errors, a multidisciplinary committee
this process. reviewed practices of more than 100 hospitals' processes
to prevent chemotherapy errors.[51 A summary of the
authors' recommendations is presented in Table 2. The
nurse and pharmacist should both be independently res-
Oncology pharmacists are responsible for ensuring that ponsible for checking each item.
medication orders for antineoplastic agents that are re-
leased for patient care administration are complete, ac-
curate, and appropriate for each patient. The increased
use of cytotoxic agents for patients with nonmalignant Pharmacists assume overall responsibility for the acqui-
diseases, such as rheumatologic and dermatologic dis- sition, preparation, handling, and distribution of antineo-
orders, has led to more complex therapies in patient care plastic agents within their healthcare system. Pharmacists
settings where healthcare professionals are less familiar are necessary to ensure optimal safety and minimal expo-
with these agents and their potential toxicities. While
nonspecialists assume this role in many settings, institu-
tions that provide care to large numbers of patients with Table 2 Recommendations for chemotherapy
cancer most often involve pharmacists with specialty order verification
training in oncology to minimize medication errors and Check entire set of chemotherapy orders against an
optimize pharmacotherapy. acceptable reference.
Strategies for preventing medication errors in onco- Verify current body surface area, height, and weight.
logy include using of standardized chemotherapy order Verify the final dose of each drug.
forms, conducting computer-assisted chemotherapy order Check the rate of administration, amount, and type of
screening, allowing only pharmacists to prepare cytotoxic admixture solution.
agents, and double-checking drug orders."] Several or- Check the antiemetic regimen and prehydration and
ganizations have developed processes for uniform med- posthydration orders for omissions and additions of
ication order reviews; in addition, institution-specific ancillary medications.
Compare current chemotherapy orders with previous orders
processes may be developed through the pharmacy and
and discuss significant discrepancies with prescriber.
therapeutics and other interdisciplinary committees. Check that an x-ray has been performed and read to
Although a number of computerized medication order- confirm central venous access for newly placed lines
screening software programs are increasingly utilized, for vesicant chemotherapy infusions.
the flagging of excessive drug doses is not the only basis Confirm parameters with standard references or the research
for order review. Also, if the patient has received prior protocol to determine that any dose modifications that have
courses of chemotherapy, a comparison between the new been made are appropriate; discuss significant discrepancies
and past orders should be made; significant discre- with prescriber.
pancies are addressed with the prescriber. Determine that pertinent (hematologic, organ-specific tests
Key recommendations for preventing chemotherapy based on the chemotherapeutic agents used) laboratory
values are within normal parameters; discuss significant
medication errors are well recognized and include: edu-
abnormalities with prescriber.
cation of healthcare providers, an established dose-ve-
rification process, established dose limits, use of stan- (Adapted from Ref. 151.)
Oncology Specialty Pharmacy Practice 613
sure risks for themselves, other pharmacy staff, indivi- cancer therapies. Pharmacists frequently collaborate with
duals who administer cytotoxic drugs, and patients who other healthcare practitioners to develop patient education
receive those agents. Although clinically focused practice materials to address general complications of their cancer
positions typically do not require pharmacists themselves treatment as well as drug-specific information sheets.
to prepare antineoplastic agents, in many settings, those Cancer.gov, a National Cancer Institute Web site for cur-
activities often comprise part of their responsibilities. rent and accurate cancer information, makes some of
Regardless of whether those pharmacists actually prepare these materials accessible online.[431Chemotherapy and
the agents themselves, the overall responsibility for drug You: A Guide to Self-Help During Treatment, a patient-
handling, preparation, and appropriate dispensing falls to focused booklet that addresses common treatment-related
the pharmacist. He or she is typically involved in de- side effects and coping strategies, is also available on-
veloping training, recertification, and employee-monitor- line.i441 Many commercially available print and online
ing policies. Determining technician competencies for drug information resources provide patient cancer med-
drug preparation and handling and documenting tech- ication education sheets; however, practitioners often de-
nician training are also important components of this velop their own patient education information materials
process.[61 Anyone who is involved with any aspect of for use in their specific patient care settings.
this process needs to understand the risks and protective
measures that are available to them. The Occupational
Safety and Health Administration (OSHA) Technical
Manual on Hazardous Drug Exposure[411and the ASHP Patient monitoring functions comprise a key component
Technical Assistance Bulletin on Handling Cytotoxic and of clinical pharmacists’ activities in oncology practice.
Hazardous Drugs[421are easily accessible resources. The Examples of common patient care problems addressed by
ASHP Technical Assistance Bulletin,[71 last reviewed in clinical oncology pharmacists are listed in Table 3. Based
1996, is currently under review and updated guidelines on their understanding of the nature and time course of
will likely be released in the near future. Criteria for specific drug-related toxicities and an individual patient’s
facilities and personnel for administration of parenteral characteristics, pharmacists may anticipate certain treat-
antineoplastic agents have been developed by the ment toxicities and provide input in the design of the
American Society of Clinical Oncology.[*] regimen to minimize adverse outcomes. Drug dose reduc-
tions and use of hematopoietic growth factors, chemo-
protective agents, certain antiemetic agents, or other an-
cillary medications may be recommended. For patients
Oncology pharmacy specialists provide guidance and who develop significant toxic effects, pharmacists assess
assistance to address drug administration issues and pro- their current and previous drug therapy history to assist in
vide input toward the development of guidelines for managing these problems.
administration of certain medications within their health-
care system. The rationale for such guidelines may in-
volve the potential to reduce medication errors, infusion- Table 3 Common patient care problems in oncology
related reactions, or treatment-related toxicities or to pharmacy practice
optimize drug delivery of time-consuming treatment re-
e Medication education and compliance
gimens in busy outpatient treatment settings. Oncology e Dose verification
pharmacists, through their efforts in reviewing primary a Adverse drug effects
literature and participating as investigators in clinical e Nausea
studies, facilitated the recognition that certain agents that e Mucositis
were initially approved by the FDA for administration e Cytopenias
over 24 hours (i.e., pamidronate, paclitaxel) could be 0 Infection
safely administered over shorter time periods. e Fatigue
0 Pain
0 Nutrition
0 Therapeutic drug monitoring
Patient education is standard practice and crucial for
0 Practice guideline development and adherence
e Medication error prevention and tracking
patient well-being and compliance. As such, patients are e Quality improvement
typically required to provide written informed consent 0 Pharmacoeconomic assessment
prior to receiving antineoplastic agents and other anti-
614 Oncology Specialty Pharmacy Practice
Therapeutic drug monitoring is another important as- newsletters, e-mail notices, chemotherapy administration
pect of pharmacists’ patient-monitoring responsibilities. guideline updates, andfor interactive in-services. Pharma-
Target blood concentrations of cyclosporin have been cists who spend a significant portion of their day in
established for minimizing graft versus host disease and patient care areas may find that their presence stimulates
renal dysfunction whereas optimal busulfan blood con- even more requests for drug information from other
centrations are associated with minimizing graft versus healthcare providers.
host disease and venous occlusive disease. Serum me- At the National Institutes of Health Clinical Center,
thotrexate level determinations are important for estab- oncology clinical pharmacists participate as members on
lishing appropriate leucovorin rescue treatment regimens. the NCI Physician’s Data Query online cancer informa-
The pharmacist ensures that the levels are obtained at the tion service supportive care and drug information panels
appropriate time intervals and are processed in a timely and serve on the Board of Pharmaceutical Specialties
manner. When patients are discharged prior to having Council on Oncology Pharmacy Practice.“’] These phar-
completed methotrexate serum level monitoring, pharma- macists. in conjunction with the NIH Division of Safety,
cists may continue to estimate methotrexate levels to developed the first recommendations for safe handling
determine an appropriate dosing schedule and duration of and disposal of antineoplastic drug products and waste.
leucovorin therapy. Research investigations of therapeutic
drug monitoring offer further opportunities to improve
patient care. At St. Jude Children’s Research Hospital,
investigations by oncology pharmacy specialists demons- Providing education to healthcare providers and trainees,
trate that. by individualizing doses of certain chemother- in addition to patients, is an important responsibility of
apeutic agents based on drug elimination, survival rates clinical practitioners. The interdisciplinary nature of on-
can be increased for children with acute lymphocytic cology patient care practice settings makes them desirable
leukemia (ALL).[91 experiential training rotations for medical, nursing, phar-
Therapeutic drug monitoring and pharmacokinetic macy, physician’s assistant, social work, physical therapy,
dosing adjustments are also important for nononcologic occupational therapy, and psychology students. Oncology
agents as well. Aminoglycosides, vancomycin. and an- clinical pharmacists likely interact with most of these
ticonvulsant agents are frequently administered to on- disciplines in their practice setting and serve as primary
cology patients; the patients may be followed by an ins- preceptors for pharmacy students. residents, and/or fel-
titutional pharmacokinetics service or by the oncology lows during their training program. Salary support for
pharmacy specialist. In selected situations, requests for many practitioners is, in part, based on their responsibil-
drug levels may be initiated for agents that are not rou- ities for pharmacy student education.
tinely monitored in general clinical practice. Cancer centers typically require nursing staff who
administer cytotoxic agents to participate in chemothe-
rapy certification programs. The oncology pharmacy spe-
cialist, in conjunction with oncology nurse specialists,
Clinical pharmacists in all practice settings routinely generally participates in the administration of thzse pro-
provide drug information to other healthcare providers; grams. Pharmacists also participate in ongoing education
drug queries are particularly common in oncology programs for house staff and medical hematology-on-
practice due to the specialized nature of these agents cology fellows.
and complex treatment regimens. The use of oncologic
agents for non-FDA-approved indications is not uncom-
mon and many patients receive drugs for an off-label in-
dication. Pharmacists are responsible for ensuring that the
literature supports such uses and that therapy is delivered It is not unusual that an individual patient, during the
safely in conjunction with other agents that the patient course of treatment for his or her malignancy, will receive
may be receibing. care in both an outpatient and inpatient environment.
When new agents become available for use within a Although most chemotherapy is administered to patients
healthcare system, the oncology pharmacy specialist is in ambulatory treatment clinics, some patients will be
usually the individual responsible for providing drug in- hospitalized to receive certain complex treatment regi-
formation to the general pharmacy staff, nursing staff, mens or for complications due to the treatments or under-
house staff, and prescribers. The provision of this infor- lying disease process. Those patients who are undergoing
mation can be disseminated through memorandums, induction treatment regimens for an acute leukemia, re-
Oncology Specialty Pharmacy Practice 615
ceiving high-dose chemotherapy in preparation for stem the chemotherapy process (ordering, dispensing, and ad-
cell transplantation, or receiving salvage treatment regi- ministration), treating patients with febrile neutropenia,
mens for refractory tumors are most likely to be hos- and managing peripheral blood stem cell patients. A
pitalized sometime during the course of their disease. Due clinical pathway for treating febrile neutropenia, which
to the nature of patient problems and heavy practice includes the use of hematopoietic growth factors, was
workloads, busy cancer treatment programs require mul- implemented and reevaluated. In patients undergoing
tiple clinical practitioners to cover ambulatory and in- peripheral blood stem cell transplantation, pharmacists
patient care settings. Regardless of whether the patient screen medication orders and participate in patient care
care setting is inpatient or outpatient, the basic functions of rounds to ensure that inappropriate medications are
the medication review and patient monitoring processes, avoided, antiemetic therapy is safe and cost-effective,
as well as provision of drug information and patient and electrolyte supplementation therapy is appropriate
education by oncology pharmacy specialists, are similar. and well-tolerated." Professional activities that are
common in the inpatient treatment setting include phar-
macotherapeutics monitoring, pharmacokinetic dosing,
managing clinical protocols and critical pathways, main-
Typically, pharmacists attend and participate in patient taining patient profiles, conducting patient monitoring,
care rounds and discussions with the medical staff. Even a and providing adverse drug reaction (ADR) reporting
small portion of time devoted to this activity can yield and documentation.
tremendous information that can provide the pharmacist Depending on the institution, the nurses also attend
with an opportunity to discuss intended therapeutic in- patient care rounds with the medical staff or discuss
terventions or suggest modification or discontinuation of patients' status with other healthcare professionals.
current therapies. This can improve the efficiency of the Through these discussions, additional patient care issues
therapeutic decision-making process through facilitating are frequently identified. Discharge planning rounds
immediate interventions and decrease unnecessary drug typically involve social workers, patient representatives,
wastage by previewing medication orders before they are and nurse case managers. The pharmacists may assist in
delivered to and prepared by the pharmacy. Examples this process by helping to initiate therapy that is ap-
may include initiating appropriate patient-specific anti- propriate for the discharge setting and that will be covered
biotic dosage regimens, ensuring appropriate first-line adequately financially. The knowledge that imminent
antiemetic prophylaxis, or recommending changes in discharge is pending may help the pharmacist to suggest
analgesic therapy. In addition, the presence of the phar- converting parenteral drug therapy (e.g., antibiotics, anal-
macist in this setting generally stimulates questions by the gesics, antiemetics) sooner during the hospitalization to
medical staff, thereby providing opportunity to improve get the patient stabilized on the new therapy prior to
drug knowledge. Moreover, pharmacists may be alerted to discharge. Pharmacists also assist in arranging for qua-
certain patient-specific issues that may not be obvious lifying patients to enroll in indigent drug assistance pro-
through a review only of hospital orders or the patient's grams. The Pharmaceutical Research and
medical chart. of America provides a directory of patient medication
At the University of California, San Francisco, ap- assistance program^.'^']
proximately seven clinical pharmacists provide oncology Inpatient cancer patient care settings differ among
services to adult inpatients."] These practitioners perform institutions. In some settings, patients are managed di-
admission medical histories, attend rounds with medical rectly by internal medicine house staff; the oncologist
house staff, attend bone marrow transplant rounds, make may be an attending physician for that service or a he-
therapeutic interventions, provide drug information to matology-oncology specialty service may interact with
staff and patients, perform medication order reviews, the medical house staff in a consultative arrangement.
perform ongoing drug utilization reviews and evaluation, Patients may be admitted for direct care by a hematology-
follow practitioner adherence to institutional drug therapy oncology specialty service or an oncology nurse prac-
guidelines, and coordinate medication discharge planning titioner service. Although patients' needs are the same,
and counseling. regardless of their primary care team, the pharmacists'
At Cedars-Sinai Medical Center, oncology pharmacists interactions may vary, depending on those individuals.
provide services to hospitalized patients on a specialized Furthermore, the pharmacists' position may be entirely
inpatient unit and in an ambulatory infusion center." In based within the pharmacy department or supported by
these settings, targeted areas to improve patient outcomes, the hematology-oncology department. If the institution
prevent adverse drug reactions, and reduce costs include has a pharmacokinetics service, pharmacokinetics issues
616 Oncology Specialty Pharmacy Practice
Table 4 Specialty oncology patient care services require readmission to the inpatient unit during this pe-
riod of care. Antibiotic use guidelines for prevention and
Stem cell transplantation
management of infection were developed and a clinical
Pediatric oncology
Gynecologic oncology pharmacist is responsible for following pharmacokinetic
Solid tumor services parameters, toxicities, and microbiologic results for all
Surgical oncology patients. A system was developed in which drugs could be
Radiation oncology supplied to patients in the clinics and drug usage could be
Palliative care tracked for patient profile records and reimbursement
Hematology purposes. A bone marrow transplant clinical pharmacist is
Hospice available on-call to answer questions and to meet with
Home infusion patients at the clinic site if necessary. Delivery of phar-
Outpatient clinics macy services through the entire treatment program is
achieved through coordination efforts between the bone
marrow transplant clinical pharmacists, the outpatient
may be addressed by that service or by the oncology pharmacy, and the inpatient pharmacy satellite and faci-
pharmacist, or may be shared. The oncology pharmacist litates a cost-effective and safe approach to administering
also interacts with other clinical pharmacists that are in- high-dose chemotherapy to patients with solid tumors.
volved in a patient's care (e.g., infectious diseases, nut- In an evaluation of system distress in this treatment
ritional support, pain, etc.). setting, the most frequent symptoms involved loss of
Institutions that care for large numbers of cancer appetite, fatigue, insomnia, and intermittent nausea."31
patients also have subspecialty oncology services to Medication compliance was determined to be greater than
which specific pharmacists may be assigned. Examples 90% and is believed attributable in part to patient and
of these services are listed in Table 4. At M.D. Anderson caregiver education by pharmacy and nursing personnel.
Cancer Center, for example, clinical pharmacists provide
direct patient care in concert with the leukemia, lympho-
ma, bone marrow transplantation, medical breast cancer,
gastrointestinal, critical care, and pediatrics services. The Clinical practice opportunities for oncology pharmacy
clinical pharmacists participate in drug regimen design specialists in outpatient treatment settings are significant
and monitoring; provide pharmacokinetic dosing recom- as patients continue to receive increasingly complex anti-
mendations, drug information, and comprehensive patient cancer therapies outside of the inpatient unit. Pharmacists
education; and precept experiential training rotations for conduct medication and patient profile reviews, perform
residency candidates and pharmacy students. medication histories, provide patient counseling and drug
information, and participate in therapeutic decision-
making. Within Veterans Affairs Medical Centers and
some other practice settings, pharmacists see patients as
In the transitional patient care setting, patients may be primary care providers and initiate prescriptions for anal-
receiving follow-up from pharmacists for chemotherapy gesics, growth factors, antiemetics, and other ancillary
that has extended from the inpatient to the outpatient medications by protocol. The scope of clinical pharmacy
environment. Pharmacists may also expedite chemothe- practitioners' activities in oncology clinics is not well do-
rapy orders for patients who are being admitted."] An cumented in the literature, however.
example of such a treatment setting where continuous Raehl et al. reviewed results of questionnaires that
pharmaceutical care is delivered is the autologous bone were sent to directors of pharmacy in one-half of acute-
marrow transplant (ABMT) outpatient program at Duke care general medical-surgical hospitals in the United
University Medical Center.[12] This program required States that had at least 50 licensed beds to determine the
months of planning with input from nurses, physicians, extent that pharmacists provide ambulatory clinical phar-
and pharmacists to deliver pharmaceutical services to macy service^."^] Overall, pharmacists performed non-
meet individual patients' needs. Patients undergo 5 days dispensing activities in ambulatory clinics in 19% of
of hospitalization to receive high-dose chemotherapy, responding hospitals. Pharmacist involvement in onco-
continuous hydration, and antiemetic therapy after which logy clinics occurred in 9% of institutions, second only to
time they are discharged with hematopoietic growth fac- diabetes clinics (lo%), and was more common than in
tors, prophylactic oral antibiotics, antiemetics, and elec- cardiology (6%) or geriatrics, infectious disease, or pain
trolyte supplements. Approximately half of patients clinics (4%).
Oncology Specialty Pharmacy Practice 617
In a prospective study to evaluate the impact of a cli- available from typical drug information resources. At
nical pharmacist in outpatient hematology-oncology many institutions, these activities comprise the sole re-
clinics, patient charts and profiles were reviewed and pa- sponsibilities of one or more pharmacists dedicated to
tient interviews were conducted to obtain medication research protocols and investigational drugs. Cancer
hi~tories."~] Within a 36-day time period, 21 1 interven- centers also often have a clinical trials review committee
tions were documented; the majority of these interven- that is separate from the Human Subjects Review Board.
tions were not related to chemotherapy. The most frequent Pharmacist participation in any initial trial review process
activities consisted of patient counseling and therapeutic is crucial to ensure that the project is feasible, coordination
recommendations. Of the problems identified, most were and dispensing practices are worked out. and any clinical
of high and moderate significance and pharmacy interven- trial involving chemotherapeutic agents does not have a
tions yielded positive clinical outcomes. The physician significant negative financial impact on the institution.
acceptance rate to pharmacists' interventions was 94.5%. Situations may arise when a patient is in need of a drug
In a unique practice role at the University of Califor- that is not available commercially or in an ongoing cli-
nia, San Francisco (UCSF), a clinical pharmacist has been nical trial at the institution. The oncology pharmacy spe-
responsible for setting up chemotherapy and heparin ad- cialist may arrange to obtain the drug which may only be
ministration via external or implanted infusion pumps."' available from the pharmaceutical company or the
The pharmacist also monitors the patient for treatment National Cancer Institute for nonresearch (compassionate)
toxicities and efficacy, and provides pump maintenance. use.[161 The NCI Cancer Therapy Evaluation Program
Thus, this practice setting enables the pharmacist to man- (CTEP) Treatment Referral Center provides guidelines
age patients' outpatient chemotherapy first-hand, identify and contact information for this process.[461
potential treatment-related problems. and initiate any ne-
cessary changes to optimize the treatment regimen. In
addition, UCSF has recently implemented a distribution
and clinical pharmacy service 40 hours a week using 5 While provision of drug information comprises a portion
pharmacists (4 with specialized training in oncology). of an oncology pharmacy specialist's daily activities,
These pharmacists work out of the Cancer Infusion Center some practitioners devote their entire career to the prac-
and service 60 to 70 patients weekly. tice setting in drug information. Large comprehensive
Oncology pharmacists who care for patients in out- cancer centers such as Memorial Sloan-Kettering and
patient practice settings typically review patients' med- M.D. Anderson are examples of institutions where care is
ication and medical profiles in advance of seeing the devoted to patients with cancer and workload justifies
patients. This enables them to identify those individuals having an oncology clinical pharmacy specialist in drug
who are most likely to have medication-related issues or information. Pharmacists resolve general oncology drug-
poor symptom management, and who will benefit from related queries and provide key information to solve a
the pharmacist's interventions. specific patient problem. However, their responsibilities
extend beyond these activities.
Pharmacists serve as members of the healthcare sys-
tem's Pharmacy and Therapeutics Committee which di-
Investigational drug use is an important aspect of phar- rects the review process for considering medication ad-
macotherapy for patients with malignancies. Oncology ditions to and deletions from the drug formulary. The
pharmacy specialists have an important role throughout committee may review and manage data from the ADR
the investigational drug use process; their responsibilities reporting program and from medication usage evaluations
may involve directly maintaining drug-dispensing records and reviews, and may monitor policies for medication
and investigational protocols, participating in protocol use guidelines.
development, having membership on institutional review Other institutional programs that typically involve
committees, developing and disseminating information pharmacists include pharmacoeconomics, outcomes re-
about the protocols and drugs to the pharmacy and nurs- search and management, quality improvement, and reim-
ing staff, and coordinating protocol management between bursement assistance programs.
study investigators, institutional staff, and study sponsors.
Protocols for the use of investigational agents are devel-
oped and made readily available to all involved personnel.
Included in these protocols are drug-specific character- Patient participation in clinical research trials is a
istics and information that would not otherwise be readily significant component of cancer care therapy, particularly
618 Oncology Specialty Pharmacy Practice
at comprehensive cancer centers and their affiliated me- Table 5 Outcomes related to anticancer therapy
dical practices and institutions. Whereas all oncology esirable outcomes ~ ~ ~ e § i outcomes
~ a b ~ e
pharmacy specialists facilitate these activities, some
practitioners focus their entire clinical practice in clinical Cure Mortality
research. Examples of their responsibilities include de- Improved survival Progression of disease
veloping and reviewing research and funding proposals, Decreased mortality rate Worsening of symptoms
screening and recruiting patient participants, overseeing Slowing of disease Side effects
medication disbursement, evaluating patient response and progression
Decreased symptoms Severe organ toxicity
treatment outcomes, managing adverse effects, providing
Prevention of disease Increased cost of
patient education, overseeing study records and report symptoms ancillary therapies
forms, reviewing and interpreting study data, and sum- Decreased cost
marizing and reporting study results. of treatment
Clinical pharmacists participate as principal and co- Low incidence of Drug resistance
investigators on studies that are purely clinical in nature, adverse effects
basic and translational research, pharmacoeconomic stu-
(From Ref. [18].)
dies, and outcomes-based research. Oncology pharmacy
specialists have had a significant impact on oncology
therapeutics through their participation in trials in drug
cancer patient care are a particularly active area of in-
development (pharmacokinetics, pharmacodynamics, and
vestigation. Both disease and symptom-specific assess-
pharmacogenetics), supportive care, pharmacoeconomics,
ment tools are available and can be used to document
and outcomes research. Several oncology pharmacy spe-
quality-of-life outcomes for individual patients and with-
cialists receive NIH support for their research activities.
in a treatment population.
Although the impact of this has not been formally
ascertained, a method for designing and implementing
toxicity outcome indicators for specific chemotherapy
protocols has been described.[”] For each clinical pro-
tocol, clinical monitoring criteria were established; phar-
The benefits of oncology specialty pharmacist practi-
macists are able to use predetermined agent-specific mo-
tioners are evidenced by the high demand for skilled
nitoring and toxicity ratings to document and improve
clinical practitioners in oncology patient care settings.
pharmaceutical care services for oncology patients.
Furthermore, the Board of Pharmaceutical Specialties
(BPS) recognized oncology as a pharmaceutical specialty
in 1996. Information regarding the specialty certification nt
process can be accessed at the BPS Web site.[471Phar-
macists are examined on their ability to collect and in-
terpret clinical data to recommend, design, implement, Oncology pharmacists develop drug and use practice
monitor, and modify pharmacotherapeutics plans and guidelines; the impact of these guidelines has been re-
optimize drug use for patients with cancer; basic knowl- ported extensively at professional meetings and to some
edge of malignant disease processes and their manage- degree in the professional literature. Hirsh et al. report
ment; ability to provide education and medication-related that pharmacist involvement in the development and im-
counseling, and ability to address public health issues plementation of guidelines for managing extravasations
related to oncology pharmacy practice; and knowledge of from antineoplastic agents resulted in prompt and uniform
the drug development process. The petition requesting management of these drug effects.[201However, the mag-
specialty recognition of oncology pharmacy practice to nitude of this impact was not quantified.
the BPS in 1992 delineated the societal need and demand Pharmacists who have been responsible for the design
for highly skilled oncology pharmacy practitioner^."^] and implementation of antiemetic dosing guidelines
Ignoffo and King have identified potentially import- have resulted in significant cost savings at many institu-
ant patient outcomes related to anticancer therapyrlg3 tions.[21,221
In addition, patients who are treated according
(Table 5 ) . By documenting the incidence of specific to established practice guidelines have satisfactory or
outcomes associated with patient care services, pharma- improved antiemetic ~ o n t r o l . [ ~Moreover,
~ . ~ ~ ] institutio-
cists can establish a threshold at which corrective meas- nal drug use guidelines serve as educational tools and
ures can be instituted. Quality-of-life issues related to help to improve the drug-ordering and -administration
Oncology Specialty Pharmacy Practice 619
process. Significant cost savings and improved health following a discussion by the Oncology Care Committee.
outcomes have resulted from practice guidelines for he- The pharmacist provided education in the form of in-ser-
matopoietic growth factors and intravenous-oral drug vices or written material to the appropriate staff, resulting
interchange programs. in a reduction in the average length of stay for chemo-
Publications by NIH Clinical Center clinical oncology therapy administration, the number of variances in timing
pharmacists have received national attention and improve of chemotherapy, and the number of problem cases.
pharmacy practice processes; examples include ways to An analysis of self-reported interventions by hematol-
standardize expression and nomenclature of cancer treat- ogy-oncology pharmacists and staff was also performed to
ment regimens[241 and pharmacy procedures for dealing document pharmaceutical care interventions over a period
with gene therapy products.[251 of approximately 8 months at the Walter Reed Army
Through a pharmacist’s development of a clinical Medical Center.[321The interventions were analyzed to
pathway for a methotrexate infusion protocol in pediatric determine the types of interventions that are most fre-
patients, prechemotherapy hydration parameters were quently performed, prescribing errors encountered, med-
reached sooner and length of stay decreased from an ication cost avoidance that resulted from the interventions
average of 3.27 days to 2.4 days.[261This was associated and types of interventions that are associated with medi-
with a savings of approximately $600 per patient. At the cation cost interventions, and intervention acceptance rate
same institution, a change in empiric antibiotic therapy in by physicians. Interventions were entered into a personal
penicillin-allergic patients and other changes resulted in a computer and analyzed using CliniTrend Web Support
decrease in length of stay by approximately one day System software (ASHP). Medication cost avoidance was
(average 5.48 days versus 4.66 days) that was associated determined if less medication was used, an equally ef-
with a savings of approximately $1500 in direct costs per fective but less costly medication was used, or a medi-
patient. Criteria for developing, implementing, and eva- cation that could not be reused was not prepared.
luating critical pathways in oncology practice have been A total of 503 interventions were reported; clinical
published.[27p291 consultations, correction of prescribing errors, and patient
treatment procedures accounted for approximately two-
thirds of the interventions (Table 6). In this study, all
clinical interventions were related to chemotherapy-re-
McClennan et al. conducted a prospective 2-month inter- lated toxicities or drug-dosing and -administration issues.
vention study to determine clinical outcomes associated The 167 documented clinical consultations were related
with pharmacist interventions at a tertiary referral cancer to nausea or vomiting (29.3%), chemotherapy dosing or
institute in Australia.[301Clinical pharmacists documen-
ted clinical interventions and relevant patient informa-
tion which were assessed by an independent pharmacist. Table 6 Summary of interventions reported by
Members of the healthcare team reviewed and discussed hematology-oncology pharmacists at Walter Reed Army
Medical Center (October 1, 1995-May 31, 1996)
medical progress notes to determine outcomes. Of 674
total interventions that were documented during the study, Intervention umber %
outcomes were assessed for 10% of the interventions re-
ported; 90% of the interventions led to documented cli- Clinical consultation 167 33.2
Correction of prescribing error 85 16.9
nical benefit. Pharmacist interventions most frequently
Patient treatment procedure 65 12.9
consisted of initiating changes in drug therapy associated Clarifyingherifying prescription 38 7.5
with antiemetic, antimicrobial, and analgesic agents. with physician
Pfeiffer documented the impact of an oncology phar- Other 33 6.6
macist’s review of chemotherapy administrations.[311 Enrolling/monitoring patient in 28 5.6
The pharmacist reviewed chemotherapy admissions on a clinical trial
monthly basis for 20 months. Pertinent patient demo- Formulary or therapeutic interchange 26 5.1
graphic data, chemotherapy administrations information, Compatibility consultation 23 4.6
and admissions stay data were collected and were com- Verifying patient’s chemotherapy schedule 20 4.0
pared to an ideal that was predetermined based on the Drug information counseling for patient 10 2.0
institution’s admissions standards and chemotherapy care Alerting physician of need for a test dose 5 1.o
Patient counseling (other than 3 0.6
maps. The pharmacist identified opportunities for edu-
drug information)
cation for cases where length of stay exceeded the insti-
tution’s standards or where problems were identified (From Ref. [32].)
620 Oncology Specialty Pharmacy Practice
One
and
Through pharmacist involvement with other healthcare
providers, identifying opportunities for medication reim- Oncology pharmacy specialists frequently participate in
bursement from drug manufacturers with indigent drug developing and monitoring adherence to health system
access programs can result in significant cost savings. In a guidelines for patient care. Several professional organiza-
program for procuring medications at no cost for indigent tions have developed guidelines which serve as valuable
patients, a full-time pharmacist was responsible for resources for practitioners (Table 7). Information and
identifying qualifying patients, assisting in the application treatment guidelines for cancer pain management have
process, and coordinating receipt and distribution of the been developed by the American Pain Society and the
medication^.'^^] In 1992, during the first year of the Agency for Healthcare Policy and Research (AHCPR).
program, 200 patients were served and the potential cost Furthermore, the Joint Commission on Accreditation of
avoidance resulting from obtaining these free medications Healthcare Organizations (JCAH0)[481 has developed
was estimated at S150,OOO. The medications obtained standards for assessing and managing pain in accredited
included immune globulin, antiemetics, growth factors, healthcare organizations. Standards are available for am-
cancer chemotherapy, antimicrobials, and interferons. bulatory care, behavioral healthcare, home care, health-
Pharmacy-managed investigational drug services rep- care network, hospital, long-term care, and long-term care
resent an additional opportunity to reduce costs, particu- pharmacy practice settings. Internet Web sites for phar-
larly in oncology patient care settings where there is high- maceutical manufacturers of analgesics such as Roxane
volume use of investigational drugs. In a study of cost Laboratories[491and Purdue Pharma L.P.1501are also sour-
avoidance associated with investigational drug services at ces for professional and patient-oriented information and
two institutions in Washington State, drug costs asso- resources. Talaria is a cancer pain management resource
ciated with acquired immunodeficiency syndrome and for healthcare professionals that provides multimedia
oncology accounted for the largest figures.[341 instructive and interactive tools regarding pain manage-
ment, in addition to general technical i n f ~ r m a t i o n']. ~The
~
Patie National Comprehensive Center Network (NCCN), Amer-
ican Society of Clinical Oncology (ASCO), and the
Oncology pharmacist participation in home delivery of American Society of Health-System Pharmacists (ASHP)
chemotherapy for selected patients with good home care are among several groups that have produced practice
support can result in cost savings with antiemetic con- guidelines for cancer or supportive care treatments.
Oncology Specialty Pharmacy Practice 621
Table 8 Resources for drug handling, drug development, and investigational drug management
American Society of http:l/www.ashp.org/ ASHP technical assistance bulletin on handling
Health-System Pharmacists cytotoxic and hazardous drugs.
Cancer Therapy Evaluation http:/lwww .cancer.gov/ Information for investigators, healthcare
Program (CTEP) clinical-trials/ professionals, and patients related to
cancer drug development and clinical
trials; guideline and policy information
for clinical trials and investigation drug
use and accountability.
Cancer Trials Support Unit http://cancertrials.nci.nih.gov Investigator’s Handbook for participants
(CTSU) of the National in clinical studies of investigational agents;
Cancer Institute directory of research tools and services
for cancer researchers; clinical trials
information; links to cooperative study
group Web sites.
Blood
The American Society of Hematology (ASH),'541 an
Cancer Practice (Chemotherapy update column, organization of clinicians and scientists who are involved
edited by R. Ignoffo and R. King) in care and research related to hematologic disorders, pro-
Current Opinion in Oncology vides online access to meeting abstracts and its meeting
European Journal of Cancer educational booklet, among other educational materials.
Gynecologic Oncology Practitioners will find that the focus of these materials is
Hospital Pharmacy (Cancer chemotherapy update. primarily in hematologic malignancies and stem cell
by Solimando and Waddell) transplantation, immunology, and hemostasis. The Amer-
Journal of Clinical Oncology ican Society of Clinical Oncology (ASC0),[551an orga-
Journal of Oncology Pharmacy Practice nization of oncology professionals, also posts searchable
New England Journal of Medicine
meeting abstracts. The ASCO Online Journal Club
Oncology
Seminars in Oncology
provides online reviews of key oncology-related articles
The Lancet in the medical literature and can be accessed at the or-
ganization Web site. The American Association of Cancer
Research[561allows searchable access to proceedings ab-
stracts and other association-related symposia. Medscape
journals. A library that contains access to these journals is
Hernatology-On~ology[~~~ is an outstanding online re-
recommended (Table 10). Since many publishers provide
source for hematology-oncology practice guidelines, news,
e-mail notification of the current table of contents for
conference summaries, and treatment updates. Many full-
selected journals at no cost, a subscription to these services
text reviews and clinical updates are available as well.
can help the practitioner keep up with new developments.
Registration is required but access to all materials is free.
These online sites are a source of new research and drug
Online publications
research findings in hematology-oncology.
Highlights in Oncology Practice, CA-A Cancer Journal
for Clinicians, and Cancer Control Journal are available
online free of charge. These high-quality publications
provide timely reviews of oncology-related topics that
many oncology and general practice practitioners find
useful (Table 11). Practitioners will also find that online S
publications from several academic and government
centers can be valuable resources for timely and accurate Specialized oncology pharmacy practice residencies are
information regarding alternative and complementary minimum 12-month postgraduate programs that are de-
medicines (Table 11). signed to develop competencies for practitioners to par-
CA-A Cancer Journal for Clinicians http://www.ca-joumal.org/ Peer-reviewed journal from the
American Cancer Society
Cancer Control Journal http://www.moffitt.usf.edu/ Published by the H. Lee Moffitt
pubslccji Cancer Center and Research Institute
Highlights in Oncology Practice http://www.meniscus.com/web/ Serial publication for healthcare
publications/hl/index.htm professionals from Meniscus Limited
Other Online Resources http://nccam.nih.gov/ National Center for Complementary
and Alternative Medicine, National
Institutes of Health
http://www.cancer.gov/ Office of cancer complementary
occam/index.html and alternative medicine, National
Cancer Institute
http://dietary-supplements. Office of Dietary Supplements,
info.nih.gov/ Kational Institutes of Health
624 Oncology Specialty Pharmacy Practice
ticipate in care of oncology patients and oncology drug provide national and international networking opportu-
distribution within oncology healthcare systems. The nities for oncology pharmacists.
American Society of Health-System Pharmacists has de- Several professional oncology-focused organizations
veloped accreditation standards for oncology specialty are available for pharmacists to join. In particular, on-
residency programs;1581individuals who are considering cology pharmacist membership and attendance at annual
such programs, accredited or nonASHP accredited, should meetings of the American Society of Clinical Oncology
refer to these educational objectives. Specialized phar- (ASCO) and the American Society of Hematology
macy residency training in oncology will provide the (ASH)'541 are common. There are numerous other orga-
practitioner with the skills and knowledge to work ef- nizations related to pain and palliative care, as well as
fectively as a multidisciplinary team member to improve specialty oncology areas. Pharmacists are active members
patient care.[381 Residency programs provide excellent in their institutions' cooperative oncology groups and par-
opportunities for the resident to develop professional ticipate in and attend those meetings as well.
relationships with other oncology practitioners.
Oncology specialty review courses are offered by
the American Society of Health-System Pharmacists[591
and the American College of Clinical Pharmacy.'601
Some organizations offer mini-traineeships (ASHP, Trends and issues regarding the safety and efficiency of
ACCP) to enable practitioners to develop clinical ex- delivery of patient care services in oncology are similar
pertise in specialized practice settings; Roxane Labora- worldwide, although the structures of these services vary
tories has sponsored a Scholar Program for healthcare among different healthcare systems and in their maturity.
practitioners in pain and palliative care for several The need for standards for pharmacist training and
years. Participation in these review courses and training knowledge in oncology in these treatment settings is
programs allows practitioners to network with other si- widely recognized. Since European hospitals typically
milarly interested individuals outside their practice set- have fewer pharmacists than do American hospitals, the
ting or institution. provision of comprehensive clinical services in some
countries has yet to be accomplished.1391Some chemo-
aniz therapy use guidelines have been developed by oncology
pharmacy groups. Guidelines for pharmaceutical care of
The Section of Clinical Specialists of the American cancer patients, developed by the London oncology
Society of Health-System Pharmacists'611 provides net- pharmacy group, specify that chemotherapy given on
working opportunities for ASHP members who practice nononcology wards should be dispensed by pharmacists
or conduct clinical research in oncology pharmacy prac- who possess some basic clinical training and pharmacists
tice. Members also have input for specialty practice edu- with overall oncology responsibility should oversee such
cational programming and receive a networking directory therapy in London.[401
to assist in identifying other practitioners with similar Policy guidelines for pharmacy services have also been
practice andor research interests. established and adopted by the Society of Hospital Phar-
The Hematology/Oncology Practice and Research macists in A~stralia.'~'] These guidelines suggest specific
Network (PRN) of the American College of Clinical areas for which pharmacists should place special empha-
Pharmacy[621is organized to facilitate dissemination of sis: potential chemotherapy drug-drug interactions, eme-
clinical practice, research, and teaching-related infor- tic control, analgesia, and gastrointestinal preparations.
mation in hematology and oncology and is also a re-
source for hematology and oncology expertise among its
membership. Members direct and participate in edu-
cational programming and network to establish collab-
orative relationships. Oncology clinical pharmacy specialists are well-recog-
The International Society of Oncology Pharmacy Prac- nized for their expertise and valued contributions toward
t i t i o n e r ~ ' ~was
~ ] formed at the IV International Sym- improving the efficiency, safety, and outcomes of care
posium on Oncology Pharmacy Practice held in 1995. The provided to patients with malignancies. Formal programs
mission of this organization is to promote and enhance such as oncology specialty residencies offer exceptional
oncology pharmacy practice worldwide for the purpose of opportunities for practitioners to gain the specialized
improving cancer patient care. Annual meetings of ISOPP knowledge and skills needed to meet challenging practice
Oncology Specialty Pharmacy Practice 625
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Despite the wide recognition and appreciation of on-
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PHARMACY PRACTICE ISSUES
in infants born to women in Europe and Canada who had methotrexate for uterine choriocarcinoma). Beginning as a
taken the drug while pregnant. At the time the news small grant-oriented program to develop antileukemia
broke, Congress was working on amendments to the 1938 agents, the program was based on the use of transplantable
law that required sponsors to provide proof of drug tumors in syngeneic rodents as a system for testing new
efficacy before receiving market approval. The thalido- drugs. After the NCI drafted an agreement allowing for the
mide catastrophe propelled Congress to require sponsors trade secret status of data, industry submitted compounds
also to show proof of safety. To implement these two for screening of bioactivity. Within three years, the Cancer
requirements, the FDA created the IND process requiring Chemotherapy Program had grown into a $35 million
sponsors to test for and establish relative safety before industrial contract effort. After a few missteps, when the
embarking on clinical trials to determine drug efficacy. FDA would not accept the cancer-funded research results
The FDA set up the NDA approval process for ruling on as provided, the FDA and NCI developed a clear
safety and efficacy before the drug could be marketed understanding of how data needed to be provided. From
interstate (4). that point until at least the early 1980s, the NCI was
An essential interplay developed between patent involved in the development and/or clinical testing of
protection and regulatory requirements. Patent protection every antineoplastic drug available in the United States
became essential for emerging products developed by ( 11- 13).
research-intensive, vertically integrated firms that looked In 1966, the National Institute of Neurological and
to a few major market winners to survive in this era of Communicative Disorders and Stroke, as it was then
increased development costs (5). Patent time used in the named, established the Antiepileptic Drug Development
IND and NDA premarket stages reduced the time Program to develop clinical trial methodologies and then
remaining for manufacturers to protect their products, to conduct clinical trials of antiepileptic agents already
once marketed, against less costly generic drug compe- available in other countries. The program later developed a
tition. Drug development also became more expensive. screening program similar to that of the NCI. The Institute
Development costs in the late 1960s and early 1970s, filed INDs for drugs that entered clinical testing, and by
before the FDA amendments became operationally 1981, four drags had commercial sponsorship by the NDA
implemented, were estimated to range from a low of stage (14, 15).
$2.7 million to a high of $16.9 million per new chemical Although most of the federal funding for drug programs
entity (NCE) (6, 7). y the late 1970s, the estimate had by the National Institutes of Health (NIH) was for the
risen to $54 million (8). Since then, estimates have development of drugs for rare diseases-cancers and
continued to leap upward: $124 million in the late 1980s, epilepsy-the NIH also devoted funding to development
$231 million in 1991, and $500 million today (9, 10). of other categories of orphan drugs. These included drugs
By the late 1960s and early 1970s, market winners to prevent and treat substance addiction and relapse,
generated most of a company’s profits and also helped contraceptives for women of childbearing age, and some
encourage brand loyalties by prescribing physicians. Other vaccines being developed by NIH and by the Centers for
drugs needed to at least break even. Although not Disease Control (now the Centers for Disease Control and
blockbusters, these drugs generally were for large markets. Prevention). Before 1983, when the Orphan Drug Act was
Drugs for rare diseases usually did not break even and signed into law, NIH drug development programs and
became therapeutic orphans. They became wards of grant-supported research had resulted in 13 drugs for
government and university-sponsored development efforts. the treatment of rare diseases being approved and on the
Cancer treatment drugs were among the first wards of market. In the 17 years before the Orphan Drug Law, the
government. Even before the 1962 amendments to the pharmaceutical industry had developed and marketed
Food, Drug and Cosmetics Act, the federal government 34 drugs or biologicals for use in rare diseases or condi-
had developed and maintained a role in stimulating the tions (16). Ten of these marketed orphan drugs and
development of cancer drug treatment that was not being biologicals had been developed solely by industry without
addressed by industry. The National Cancer Institute (NCI) government or university support (17).
created the Cancer Chemotherapy Program in 1955 with a
$5 million Congressional authorization. Congress decided
that the NCI should take on the challenge. Impressed with
he
industry’s spectacular antibiotics development, Congress
recognized that a low ROI was precluding industry’s Nonetheless, several articles published in medical
interest in exploiting the early successes in antitumor drugs journals by academic researchers chronicled their plight
(antifol aminopterin for acute childhood leukemia and in formulating new dosages for available drugs or
Orphan Drugs 629
that industry sponsors had marketed or had made were profoundly affected by rare diseases and conditions,
available on a compassionate basis to specialists; and on survey data revealing market and reguiatory
2. Drugs and biologicals listed by the FDA as under disincentives to therapeutic progress, Congress passed the
development, but needing a commercial sponsor for Orphan Drug Act during a lame duck session in December
A approval and marketing; and 1992. Called ”the golden egg of the lame duck Congress”
gs under development by NI by the head of the Generic Pharmaceutical Industry
grantees. Association (GPIA), the bill was signed into law the first
week of January 1983 (30). The act (Public Law 97-414)
From this survey, the Subcommittee learned that
was supported initially by the GPIA, which had begun
industry had marketed 34 drugs for the treatment of rare
seeking sponsors for developed orphan products, and
diseases extending back to 1945 and had made an
eventually by the PMA after certain provisions were
additional 24 drugs (under development) available to
deleted or modified. Provisions in the law, and in
physicians on a compassionate basis for treating patients
subsequent amendments in 1984, 1985, and 1988,
with rare diseases. Most (82%) of the marketed drugs were
addressed market and regulatory issues and provided
for conditions affecting fewer than 100,000 people in the
incentives for pharmaceutical industry development of
United States; 10% were for 100,000 to 500,000 people,
drugs for the treatment of rare diseases.
and the remaining 8% were for up to 1 million people.
The law, as amended, defines a rare disease or condition
Industry respondents indicated that substantial federal
as one that affects fewer than 200,000 persons in the
funding had been provided for research andlor develop-
United States. Alternatively, the disease or condition can
ment (R&D) for all but 10 of these marketed drugs.
affect more than 200,000 persons in the United States, if
The picture of disincentives confirmed claims by
there is no reasonable expectation that the cost of
industry spokespeople sponsors indicated that the RUI for
developing and making a drug available for such disease
83% of the drugs was lower than the sponsors’ average
or condition in the United States will be recovered from
return for marketed drugs, whereas development costs
U.S. sales of the drug. Therefore, a drug can be designated
were higher than average for 12% of these drugs. Other
by the FDA as an orphan by demonstrating applicability of
issues cited by industry were the lack of clarity of FDA
the law’s financial criteria, regardless of the total number
clinical testing guidelines when small numbers of patients
of people affected in the United States.
were available and involved. This further eroded the
are the availability of two market incentives and the
sponsors’ ability to estimate the length of clinical testing,
reduction of regulatory barriers. The FDA Office of
and therefore the length of remaining patent protection
Orphan Products Development administers nearly all the
time, once the drug was approved. Survey data indicated
law‘s provisions.
that industry-sponsored marketed orphan drugs took an
One incentive is seven years of market exclusivity
average of 5.75 years for clinical testing (from filing the
granted by the FDA for a specific indication of a product.
IND to filing the NDA). Unpatented orphan products were
Exclusivity begins on the date the FDA approves the
increasingly unlikely to be submitted for NDA approval,
marketing application for the designated orphan drug and
suggesting the importance of having at least some period
applies only to the indication for which the drug has been
of market protection. Whereas nearly two-fifths (39%) of
designated and approved. An application for designation
industry-sponsored drugs for the treatment of rare diseases
as an orphan drug for a specific indication must be made
had been marketed in the 1 9 4 0 ~even
~ though they were
before submission of the NDA (or biologic product license
not protected by patent, this fell to 29% by the 1970s.
application, PLA) for market approval (31). Other
Liability claims had been filed against the nanufacturers
sponsors can receive approval for a different drug to
of one-fifth of the marketed orphan drugs. The promising
treat the same rare disease or can receive approval to
finding was that one in four industry-sponsored marketed
market an identical drug for some other orphan or common
orphan drugs also had a common indication. This
indication. Market exclusivity, therefore, only precludes a
suggested that orphan drugs were a relatively good market
second sponsor from obtaining approval to provide an
gamble (29).
identical drug for the identical orphan indication for which
the first sponsor received exclusive market approval.
Initially, market exclusivity pertained only to unpatented
products. A 1985 amendment allowed exclusive approval
for all orphan drugs, whether patented or not. This change
Rased primarily on Congressional testimony marshaled by was designed to provide incentives for sponsors of
NORD revealing that millions of people and their families products for the treatment of rare diseases whose patents
Orphan Drugs 31
would expire before or soon after approval, or in cases in Finally, the FDA is required to encourage sponsors to
which prior publication (usually by an academic or design open protocols for drug availability to patients not
government scientist) had precluded issuance of a patent. included in clinical trials.
A second incentive provides tax credits equal to 50% of
the costs of human clinical testing undertaken in any given
year by a sponsor to generate data required for obtaining
f
FDA market approval through successful completion of
the NDA process. The Internal Revenue Service admin- The FDA approved 201 orphan products between 1983
isters the tax credit provisions. and March 2000 (33). In the 17 years since passage of the
The act provides for the FDA to award grants to support act, therefore, the number of approved orphan drugs has
clinical studies of designated orphan products under- increased sixfold from the number approved in the 17 years
development. FDA grant funding as of March 2000 from before the act (Table 1). The drugs are classified within
the FDA totaled $126.3 million. From initial funding in 16 therapeutic categories, primarily for the treatment of
1983 of $500,000 in grants, the grant program peaked in cancer, infectious disease. AIDS and related conditions,
1994 at $12.3 million and has declined slightly but steadily and central nervous system conditions (Table 2). Included
thereafter, totaling $1 1.1 million in 1999 (32). Appli- in the 201 approved drugs are 24 (12%) that received
cations are reviewed by outside experts and are funded FDA grant support for clinical trials (34). A list of these
according to a priority score. The FDA Office of Orphan grant-supported products is available at the FDA Office
Product Development provides information at its website of Orphan Products Development website (www.fda.gov/
(www.fda.gov/orphan/GRANTS/patients) on investi- orphan/GRANTS).
gators seeking research subjects. Listed by the name of The number of sponsors of approved orphan drugs
the disease or condition, information includes a descrip- (nearly all of them produced at pharmaceutical or
tion of the study, criteria for inclusion in clinical trials biotechnology companies) has increased fr
(such as age, stage of disease, etc.), and contact 34 drugs marketed before the act) to I 10 as
information on the clinical investigator seeking partici- The number of approved drugs per sponsor ranges from
pants for clinical trials. Patients, their families, or their one to eight, with a preponderance of one-drug sponsors
physicians are able to follow up with the clinical (Table 3). A total of 813 products have received orphan
investigator. designations as of March 2000. Sponsors of approximately
To address regulatory barriers the FDA also provides 25% of these designated products have filed INDs for the
formal protocol assistance when requested by the sponsor products, indicating that they are under active deyelop-
of an orphan drug. Although formal review of a request for ment (35).
protocol assistance is the direct responsibility of the FDA Many of the designated and approved orphan
Centers for Evaluation and Research (one for drugs, the products are developed at biotechnology companies.
other for biologicals), the Office of Orphan Products Beginning in the 1970s. molecular biology had be,oun to
Development is responsible for ensuring that the request spur the creation of biotechnology research companies.
qualifies for consideration. A sponsor need not have These companies reportedly recognized early on that
obtained orphan drug designation to receive protocol market exclusivity, and lack of competition to develop
assistance. products for the treatment of rare diseases. provided
protection essential to raising venture capital. As a
result. orphan drugs are now among biotechnology ' s
most prevalent, and, according to some. most lucrative
Table 1 Designated and approved orphan drug products
products. Between 1988 and 1992, biotechnology
Pre-1983 1989 1991 3/2000 product designations increased by 3156, from 8 to 39%
of total orphan designations (36). In addition to industry,
Cumulative total 34" 36 54 235 however, sponsors have included a university. an
approved orphan individual researcher, and a state public health unit,
products which in aggregate sponsored six orphan drugs at the
Total sponsors 17 110 time of approval. Lists of approved
of approved orphan drugs can be obtained from the
orphan drugsb
Orphan Products Development. These data suggest that
"At the time, these were called drugs for rare diseases, not orphan drugs. orphan drug development has consistently risen over the
bSponsors identified only for the two endpoints. years since the law was enacted. Aggregate sales of
632 Orphan Drugs
Table 2 Approved orphan drugs: Number per therapeutic drugs between $26 and $100 million, and two products
categorya more than $100 million. Biotechnology firms produced
four of the 11 drugs with relatively high sales.
~ u ~ ofbapproved
e ~ Those orphan drugs that command high prices have
generated intense controversy over whether the market
W = 201
exclusivity provision is creating an unnecessary mono-
Cancer 49 poly, keeping prices artificially high. One example is
Infectious disease 23 recombinant human erythropoietin (r-EPO), intended for
Central nervous system 22 patients with chronic renal failure-related anemia. EPO
Hematopoetic 21 eliminates the need for frequent blood transfusions by
AIDS, AIDS-related 21 patients with end-stage renal disease who are undergoing
Endocrine 18 kidney dialysis. These patients are covered under the
Inborn errors of metabolism 12 federally financed Medicare program. Both Amgen Inc.
Renal 8 and Genetics Institute applied to the FDA for market
Cardiovascular disease I exclusivity for their r-EPO products. Amgen was the first
Respiratory 5
Gastrointestinal 5 to receive FDA approval and market exclusivity. Genetics
Bone 3 Institute was the first to receive a patent. On appeal, the
Immunological 2 court ruled that Amgen had exclusive marketing rights.
Dermatological 2 Sales of r-EPO exceeded $100 million in the first six
Antidote 2 months of marketing, paid for by Medicare. By 1991, sales
Urinary tract 1 totaled $400 million (38).
Human growth hormone (r-hGH), another example,
"Does not include drugs for rare diseases marketed before the 1983
generated sales of $150 million in 1991. Intended to treat
Orphan Drug Law.
approximately 12,000 children in the United States with
retarded growth caused by a lack of endogenous pituitary
hormone, two companies provide r-hGH. Genentech
orphan drugs have been reported to be more than $1
/97\ received FDA market exclusivity in 1985. Eli Lilly
billion a year ( = ' I .
received market approval two years later, based on the
determination that the two products differed by one amino
rici acid (39,40). But the shared market did not lead to price
competition: each company was earning approximately
$20,000 per child annually, depending on the dosage
By the early 1990s, U.S. sales data collected for 41 of the needed.
approved orphan drugs that had been on the market for a A third example, aerosol pentamidine, generated sales of
year or more indicated that 75% of the products had $130 million in 1991. Helping to prevent Pneurnocystis
generated earnings of less than $10 million per drug. Three carinii pneumonia associated with the human immunode-
products had earnings between $10 and $25 million, six ficiency virus (HIV), the increasing number of users
resulting from a rapidly escalating HIV prevalence rate was
expected to soon exceed the 200,000 population figure
Table 3 Approved orphan drugs per sponsor, March 2000" specified in the law. This example, along with the other two,
prompted efforts to seek a legislative remedy. A series of
rugs per sponsor Sponsors
amendments were introduced and passed by Congress in
69 1990 that sought to eliminate orphan status for products
19 intended for use in epidemics and to allow shared market
6 access for identical products developed simultaneously for
2 the same indication, in the hope that this would lead to price
5 competition. The amendments were vetoed (41). As Arno,
2 Bonuck, and Davis present in Milbank Quarterly, AIDS
1 treatment drugs exemplify the policy dilemma of how to
2
use the Act to meet the legislative intent of stimulating
"Does not include sponsors of drugs for rare diseases approved before the development of drugs for small patient populations without
Orphan Drug Act of 1983. resulting in prices that make such drugs inaccessible (42).
Orphan Drugs 633
Another, more recent, example is enzyme therapy for 11. Devita, V.: Oliverio, V.T.: Muggia, F.M.; Wiernick. P.W.;
Gaucher’s disease, an inborn error of metabolism, treated Ziegler, J.; Goldin, A,; Rubin, D.;
Henney, J.; Schepartz, S.
The Drug Development and Clinical Trials Programs of the
with Ceredase. The therapy, which requires more than a Division of Cancer Treatment, National Cancer Institute.
ton of placenta annually to extract and make the drug, can Cancer Clin. Trials 1979, 2, 195-216.
cost as much as S500,OOO per year per person, depending 12. Zubrod, C.G.; Schepartz, S . ; Leiten, J.: Endicott, K.M.;
on the dosage needed. A 1996 National Institutes of Health Carrese, L.M.; Baker, C.E. Cancer Chemotherapy Reports
technology assessment panel addressed issues in diagnosis October 1996, 50 (7); DHEW: Washington, DC, 1968.
and treatment of the disease and concluded that despite 13. Rate of Development of Anticancer Drugs by the National
Cancer Institute and the US.Pharmaceutical Industry and
the success of enzyme therapy, treatment is limited by the the Impact of Regulation. Final Report f o r the A7ationaZ
cost. The panel reported that it was imperative to define the Cancer Institute; University of Rochester Medical Center:
appropriate clinical indications for treatment and to New York. 1981; 40.
determine the lowest effective initial and maintenance 14. Krall, R.A. Anti-Epileptic Drug Development.
doses (43). and a Program for Progress. Epilepsia 297
Although the survey undertaken prior to the Act found 398 -408.
15. Program Performance Summary. National Institute of
that retail costs of drugs for the treatment of rare diseases A7eurological and Communicative Disorders and Stroke
were reportedly higher than the manufacturer’s average Antiepileptic Drug Development Program; NINCDS:
for 60% of the products marketed before the act, the Washington, DC, 1982.
pricing for some orphan drugs after the act, as exemplified 16. Orphan Drugs in Development, 1992 Annual Survey.
by these examples, is a critically important consequence of Pharmaceutical Manufacturers Association: Washington,
DC, 1992.
the law. This consequence merits continued public
17. Orphan Drug Act Report, 97th Congress, 2nd Session.
scrutiny. It is a sign of progress that for some orphan Washington, DC; Sept 17: 1982.
drugs, accessibility rather than availability is now the 18. Van Woert. M. Profitable and Non-Profitable Drugs. N.
challenge requiring creative solutions. Engl. J. Med. 1978; 298 (16), 903-906.
19. Rawlins, M. No Utopia Yet. Br. Med. J. 1977. 2, 1076.
20. Rawlins, M. Editorial. Lancet 1976, 2(7970), 835-836.
21. Walshe, J.M. Treatment of Wilson’s Disease with Trientine
(Triethylene Tetramine) Dihhydrochloride. Lancet 1982, I ,
643 -647.
22. Asbury, C.H. Medical Drugs of Limited Commercial
1. Asbury. C.H. Medical Drugs of Limited Commercial Interest: The Development qf Federal Policy; Johns
Interest: Profit Alone is a Bitter Pill. Intern. J. Health Serv. Hopkins School of Hygiene and Public Health Thesis,
1981, 11 (3), 45 1-462. Baltimore, 1981; 157-175.
2. Provost, G.P. Homeless or Orphan Drugs. Am. J. Hosp. 23. Lasagna, L. Who Will Adopt the Orphan Drugs?
Pharm. 1968, 25, 609. Regulation 1979, 3 (6). 27-32.
3. Silverman, M.: Lee, P.R. Pills, ProJits and Politics: 24. U S . Food and Drug Administration Report. Interagency
University of California Press: Berkeley, 1974; 2. Task Force Report to the Secreta? of DHEW; FDA:
4. Harris. R. The Real Voice; Macmillan: New York, 1964;
Washington, DC. 1979;. 1-82,
21-25.
25. Asbury, C.H.; Stolley, P Orphan Drugs: Creating Federal
5. Temin, P. Technology, Regulation and Market Structure in
Policy. Ann. Intern. Med. 1981, 95 (2). 221-224.
the Modern Pharmaceutical Industry. Bell J. Econ. 1979; 10
(2), 427-446. 26. Holtrman, E. Rep. H.R. 7089, 96th Congress. 2nd Session.
Washington, DC, April 17, 1980.
6. Report of the Panel on Chemicals and Health of the
President’s Science Advisory Committee, 73-500, NSF, 27. Klugman. J.; Seligman. A. Testimony, Serial No. 97-17,
U.S. Government Printing Office: Washington, DC; 1973. U.S. Government Printing Office: Washington, DC, 1981;
7. Schwartzman, D. Innovation in the Pharmaceutical 10-16.
IndustT; Johns Hopkins University Press: Baltimore. 28. Leave of Reality (Editorial). The Wall Street Journal
1976; 106-107. March 12, 1981.
8. Hansen. R.W. The Pharmaceutical Development Process: 29. Asbury, C.H. Orphan Drugs: Medical vs. Market Value;
Estimates of Development Costs and Times and Effects of D.C. Heath: Lexington, MA, 1985; 136-155.
Proposed Regulatory Changes. Issues in Pharmaceutical 30. Waxman, H.R. Rep. H.R. 5328,97th Congress, 1st Session.
Economics; Chien, R.. Ed.: Lexington Books: Lexington. Washington, DC, 1981.
MA. 1980; 151-181. 31. FDA Office of Orphan Products Development,
9. DiMasi, J.: Hanson, R.; Grabowski, H.; Lasagna, L. The www.fed.govlorphan1aboutlprogovw.htm (accessed Feb
Cost of Innovation in the Pharmaceutical Industry and 2000).
Health Economics. J. Health Econ. 1991, 10, 107-142. 32. Personal Communication. FDA OOPD, March 2000.
10. Rosenbaum, D.E. The Gathering Storm Over Prescription 33. FDA List of Approved Orphan Products through
Drugs. The New York Times NQV.14, 1999, 1, Section 4 02/24/2000, FDA: Washington, DC, 2000; Provided on
(Week in Review). Request from the FDA OOPD.
63 rpban Drugs
34. Grant-Supported Products with Marketing Approval, FDA 42. Arno, P.S.; Bonuck, K.; Davis, M. Rare Disease Drug
OOPD, Washington, DC, www.fda.gov/orphan/grants/ Development and AIDS: The Impact of the Orphan Drug
magrants (accessed Ikb 2000). Act. Milbank Q. 1995, 73 (2), 23 1-252.
35. Pcrsonal Communication, FDA OOPLI, March 2000. 43. NIH 'Technology Panel on Gaucher Disease. Gaucher
36. Schuman, S.K. Tmplcinentation of the Orphan Drug Act. Disease. Current Issues in Diagnosis and Treatment. J. Am.
Food Drug Law J. 199%,47(4), 363-403. Mcd. Assoc. 1996, 27.5 (7), 548-553.
37. Grady, D. In Quest to Cure Rare Diseases. Some Get Left 44. Asbury, C. Orphan Driigs: Medical v s Murket Value; D.C
New York Times; Nov. 16, 1999.
(2 Heath and Company: Lexington, MA, 1985.
38. J.M. Recombinant Erythropoietin: Orphan Product 45. Scheinberg, I.H., Walshc, J.M. Eds. Orphan Diseases and
with a Silver Spoon. Intern. J. Technol. Assess. Health Care O r ~ ~ h aDuugs;
n Manchester University Press: Manchester,
UK, 1986.
39. Hilts, P.J. Seeking 1,imits to a Drug Monopoly. The New 46. Wagner, J. Orphan Technologies. Int. J. Technol. Assess-
York time.^; May 14, 1992, D I ; I. , 8 (4), www.fda.gov/orphan.
40. Asbury, C.H. Evolution and Current Status of the Orphan ; Bonuck, K.; Davis, M. Rare Diseases, Drug
Drug Act. Intern. J. Technol. Assess. Health Care 1992, 8
(4), 573-582.
41 Asbury, C.H. The Orphan Drug Act: The first 7 years. J.
PROFESSIONAL DEVELOPMENT
Internet resources, is also included to facilitate your fear regulatory scrutiny when opioid medications are
understanding of clinical pharmacy in pain management. prescribed for pain control.
Several studies have been published regarding phar-
macists’ attitudes and knowledge about opioid medi-
cation.E 11,121 These studies have revealed pharmacists
as barriers due to insufficient inventories of opioid anal-
gesics, and inadequate counseling of both patients and
Numerous barriers exist that lead to suboptimal man- their families about the importance of using these med-
agement of pain, and these barriers affect patients, health ications. In the study by ressler and colleagues. 79% of
care professionals, and the health care system. The Agen- pharmacists surveyed falsely believed that a patient
cy for Healthcare Policy and Research (AHCPR) pub- using sustained release morphine 150 mg every 12 hours
lished a guideline for the management of cancer pain in would become “addicts” if this dosing level was
March 1994.[61 This publication discusses the major continued.“
barriers that currently exist to appropriate pain manag- Numerous barriers still exist to pain management.
ment. Patients can be reluctant to report their pain, and These barriers may come from the patient themselves,
they may be concerned that pain means worsening disease their physician. or other health care professionals, in-
or that it may distract their physician from treating the cluding pharmacists. One of the most important roles a
underlying cause. Patients may not take their pain pharmacist working in pain management can fill is the
medication due to concerns of addiction, worries of provision of education. not only to the patient and their
opioid side effects, or concerns about becoming resistant family, but also to pharmacists, physicians, nurses, and
to pain medications. Patients and their families can be other health care professionals.
misinformed regarding pain management. We live in a
“just say no” society where opioids are confused with
illicit drug use. Patients and their families need to
understand the difference between using a medication
for a medical reason and using one to maintain a high. A
useful analogy is comparing insulin use in diabetics with The exact mechanisms of pain transmission are unknown.
the use of opioid medications for a painful condition. Pain is a complex interaction involving receptor stimu-
Both are recognized disease slates requiring appropriate lation, pzin transmission, and response. Pain is generally
management of their disease process. divided into two categories: acute and chronic. These
The health care system has given low priority to pain categories have different characteristics, which affect the
management due to inadequate reimbursement for pro- approach to treatment. Patients may suffer from both
vision of services, the legal regulation of controlled sub- acute and chronic pain at the same time.
stances. and problems of treatment availability or lack of Acute pain may manifest itself as a warning when we
those trained to provide these services. The most sig- do something harmful to ourselves. Postoperative pain is
nificant barrier to pain management is lack of know- also classified as acute pain. Acute pain is considered to
ledge of the basic principles for appropriate pain man- be meaningful, linear, and reversible. The therapeutic
agement. Several surveys have been conducted in health goal is pain relief, and sedation is often a desirable effect.
care professionals, including physicians. nurses, and phar- Medications chosen for treatment of acute pain should
macists. These studies have revealed a lack of know- have a rapid onset of action and a short duration of act-
ledge and education in pain management leading to fear ion. These opioids are administered on a prn, or as
in both prescribing, dispensing, and administering of needed basis, usually through an IV with the doses being
opioid standardized.“61
A survey of 59 questions sent lo physicians practicing Chronic pain is usually defined as pain that persists for
in the state of Texas revealed many areas of concern when months to years. This may be due to a specific disease
prescribing opioids.[14’ Ten percent of those surveyed state, such as arthritis, diabetes, AIDS, or cancer. Chronic
would withhold opioid medications until a patient in pain is considered to be meaningless. cyclical, and
severe pain had either a prognosis of less than I year or irreversible. The therapeutic goal is pain prevention and
was terminal. Forty percent were extremely concerned sedation is an undesirable adverse effect. Two forms
regarding potential addiction. ore than one-half falsely of medication are needed, a long-acting formulation to
believed that opioid addiction is a common occurrence prevent the pain and a rapid-acting formulation to
with legitimate prescribing. The physicians surveyed also cover episodes that “breakthrough” the long-acting
Pain Management, Pharmacy Practice in 635
opioid. Therefore, the patient takes an opioid on a Behavioral interventions help patients gain a sense
scheduled basis around the clock and uses supple- of control over their pain management and should be
mental quick-acting opioids to manage additional pain. introduced early in the course of their illness. When
Dosages are titrated for the individual patient and can deciding on the appropriate behavioral intervention,
vary significantly.[l61 consideration must be given to the intensity of the
In general, chronic pain is more difficult to manage pain, the expected duration of pain. and the patient’s
than acute pain due to the psychological problems caused mental clarity, past experience with technique, physical
by unrelenting pain. Chronic pain is usually divided into ability. and desire to employ active or passive tech-
two categories: malignant and nonmalignant pain. Malig- niques. Relaxation techniques are easily taught to pa-
nant pain is associated with a diagnosis of cancer and, tients and include focused breathing, progressive muscle
more recently, HIV/AIDS. The nonmalignant category relaxation, music-assisted relaxation, and meditation.
includes back pain, neuropathic pain, migraines, and These techniques are more useful when combined with
many other diagnoses of chronic pain. pleasant images.
The use of physical modalities to manage pain may
lead to a decreased requirement for pain-relieving drugs
and, just as with behavioral interventions, should begin
The first step in managing a patient’s pain, whether it is early in the disease process. Cutaneous stimulation tech-
acute or chronic in nature, is assessment. There are niques include the application of heat or cold, massage,
numerous methods available to assess pain, including pressure, and vibration. Exercise techniques should be
verbal, visual analog, categorical. and faces scales. These aimed at preventing immobilization and may include
methods are discussed in detail in several publica- range of motion and stretching. Counterstimulation
- ~ ’ ]choice of pain assessment scale will
t i o n ~ . [ ~ , ’ ~The techniques include the use of transcutaneous electrical
depend on the environment in which pain will be as- nerve stimulation (TENS) devices or acupuncture. These
sessed, the patient’s ability to comprehend the scale, and last two techniques have not been formally studied in
how detailed the assessment needs to be. Most pharma- cancer-related pain.
cists will find a simple verbal scale of 0 to 10, with 0 = n o
pain and 10 = worst pain imaginable useful.
A component of the new JCAHQ standard is doc-
umentation of pain assessment and intensity in all pa- Nonopioid agents available for pain management include
tients. In addition, the interventions that are performed acetaminophen, nonsteroidal antiinflammatory agents,
based on the pain assessment, such as administration of a muscle relaxants. antidepressants. anticonvulsants. corti-
pain medication, need to be documented along with the costeroids, bisphosphonates, and topical preparations,
reassessment of the effect of these interventions. Pharma- such as lidocaine patches. Depending on a patient’s
cists can play a key role in developing standardized presenting complaints of pain, one of these agents may
assessment forms that include recommendations for pain be an acceptable medication to start. All these medica-
medications based on the results. tions can also be used in combination tbith opioid
agents. Nonsteroidal agents are useful for pain due to
muscle injury or bone metastases. Corticosteroids may
be useful in patients suffering from pain due to inflam-
mation or edema, such as spinal cord compression.
Patients suffering from either acute or chronic pain Bisphosphonates are useful in the management of pain
problems may benefit from nonpharmacobgic measures. due to bone metastases. The other agents are discussed
These measures may also be combined with pain more in-depth under the section entitled, “Neuropathic
medication. The AHCPR guidelines for the management Pain Management.”
of cancer pain contains a chapter outlining these op-
tions.[61Nonpharmacologic interventions are divided into
behavioral (psychosocial) interventions and mechanical
(physical) interventions. Examples of behavioral in-
terventions include biofeedback, self-hypnosis, and re- The American Pain Society (APS) published quality
laxation or imagery training. Examples of mechanical assurance standards for relief of acute pain and cancer
interventions include exercise, cutaneous stimulation, pain in 1991.[221These standards were updated and re-
and acupuncture. published in 1995.[’71 In February 1992, the AHC
638 Pain Management, Pharmacy Practice in
published a guideline on Acute Pain Management: Opeu- surgery at an increased cost, but with minimal increases in
ative or Medical Procedures and Trauma.[231In 1995, pharmacy and nursing time.
the American Society of Anesthesiologists published An article report by Triller and colleagues’271 details
guidelines for acute pain management in the perioper- their development of a clinical pharmacy program at an
ative existing home health care agency. The pharmacy resident
The AHCPR guideline has information about manage- undertook a pain management initiative in this patient
ment strategies for various surgeries, including dental, population. Patients who had reported pain were iden-
radical head and neck, neurosurgery, chest and chest wall, tified and, at admission, 53% reported pain interfering
abdominal, perianal, and musculoskeletal. Other sections with activities of daily living. Twenty-nine percent of
of the guideline address pediatric and geriatric acute pain these patients were still experiencing pain at discharge
management. A discussion of handling patients with po- from the home health care service. Charts of the next 20
tential addiction problems and those with concomitant patients admitted to the service who had complaints of
disease states is also included. Another important section pain were reviewed. This review revealed that pain
is recommendations for handling patients with shock, assessments were routinely occurring; however, docu-
trauma, or burns. mentation of interventions was lacking. A committee was
The AHCPR guideline is well referenced and an formed to develop documentation methods and staff
excellent beginning point for developing acute pain education programs. This article identifies several critical
services. The guideline ends with several useful ap- areas for pharmacy involvement in the home care setting,
pendices, including a summary of the existing scien- including the management of pain.
tific evidence for pain interventions, potential nonphar- A publication by Blau and colleagues focuses on the
macologic interventions, relaxation techniques, and adult organization of a multidisciplinary hospital-based acute
and pediatric dosing for nonsteroidal antiinflammatory pain management program.[281 This article stresses that
agents and opioids. Several tools are also included, appropriate management of postoperative pain may im-
such as an initial pain assessment form and a monitor- prove the outcome of surgery, decrease time in the sur-
ing form. gical intensive care unit, and therefore allow for earlier
The APS, the American Society of Anesthesiologists, discharge of the patient. The first step to initiate a pain
and the AHCPR guidelines outline the basic patient right management program is to compile an interdisciplinary
of being pain free. Improving the quality of pain man- team. The critical members of this team include phy-
agement includes several key areas. These areas are sicians, nurses, pharmacists, social workers, and psy-
1) defining levels of pain that trigger a review of the chologists. The involved physicians in acute pain man-
patient’s care plan, 2) providing reference information agement are usually anesthesiologists. The role of the
on the basic analgesic principals that is readily available pharmacist is as an educational resource, consultant, and
and near the area where orders are written, 3) educating technical support. This article does a superb job of de-
patients to report pain and provide assurance that pa- scribing the basic steps to developing an acute pain man-
tients will receive attentive analgesic care, 4) developing agement service, and the authors include a copy of the
and implementing policies for the use of analgesic tech- preprinted physician’s order form they developed.
nologies, 5 ) coordinating and assessing these measures, Another article describing the implementation of a
6) charting pain assessments with a display of the as- pain management service at a U.S. Army medical center
sessment used and relief provided by the intervention, was published.[291 Even though this project was de-
7) surveying patient satisfaction with pain management, veloped and implemented by clinical nurses, it pro-
8) providing specialized analgesic technologies and vides useful information for pharmacists for develop-
nonpharmacologic interventions, and 9) periodic mon- ing recommendations for an epidural and PCA service.
itoring of the efficacy of pain treatments. Unfortunately, The author also includes copies of their institution’s pain
even with the publication of these guidelines, data still assessment flow sheet and pain assessment form. An
show that postoperative patients continue to suffer from article describing the application of the American Pain
significant pain.[251 Society’s guideline in the management of pain in sur-
In 1994, Smythe and colleagues[261published a study gical, oncology, and hospice inpatients in Taiwan was
evaluating pharmacy and nursing time requirements, also published.[301 This article contains useful infor-
quality of pain control, and cost of patient-controlled mation on performing patient satisfaction surveys on
analgesia (PCA) versus intramuscular (IM) analgesic patients undergoing pain management in an inpatient
therapy. This study showed the PCA therapy provided setting, which is another requirement of the new
better pain control than IM therapy after gynecological JCAHQ standards.
Pain Management, Pharmacy Practice in 639
The JCAHO has identified pain management as an management counseling and a plan developed for home
import focus for accreditation visits starting in 2000 and management when necessary.
2001. Standards have been developed for ambulatory
care, behavioral health care. home care. health care
networks, hospitals, long-term care, and long-term care
pharmaciesL3 These new standards should help improve
acute pain management in these settings.
There are numerous additional helpful references for
acute pain management. These include the 1999 AHSP
Therapeutic Position Statement on the Safe Use of Oral In March 1994, the AHCPR released a clinical practice
Nonprescription and a review of cyclo- guideline for the management of cancer pain.[61 This
oxygenase-2 enzyme inhibitors and their role in pain guideline builds on the previous WHO report published in
management.r331For patients with renal or gastrointestinal 1990.’41This guideline is an excellent reference contain-
problems, a helpful discussion of the nonopioid con- ing complete information on patient work-up and as-
siderations can be found in Pain.[341A useful reference sessment. Numerous tools for assessment are provided,
to support the development of acute pain management including the Brief Pain Inventory (Short Form), visual
services is the 1994 article by Lewis and colleagues.[351 analog scales, and the faces of pain scale. Discussions of
This article discusses the physiological consequences of nonopioid and opioid doses are included, in addition to
acute pain and the importance of appropriate anal- conversion tables for switching a patient from one opioid
gesic therapy. agent to another. Other chapters focus on pediatric and
There are many roles for pharmacists in the manage- geriatric therapy, and the use of these principles in HIV/
ment of acute pain. The changes in the JCAHO standards AIDS patients.
provide an excellent opportunity for pharmacists to be- The AHCPR guidelines recommend using the WHO
come active in the pain management movement. Policies, three-step method for managing cancer pain. Patients
procedures, and institution-specific guidelines need to be should be started on a nonopioid pain medication, such
developed and implemented. Pharmacists have essential as acetaminophen or a nonsteroidal antiinflammatory
knowledge of opioid medications. their half-lives, po- agent. If this does not relieve their pain, proceed to
tency, and management of adverse effects. Unfortunately, the next level of a weak opioid agent, such as codeine
there have not been many publications by pharmacists or hydrocodone, with or without a nonopioid. If this
discussing their pain management practices. Therefore. does not relieve their pain. proceed to the final level
pharmacists who successfully implement acute pain of a strong opioid, such as morphine, with or without
services should make every effort to publish their efforts a nonopioid.
and results. The WHO published an update to their 1990 report on
Pharmacists should be involved in all steps of pain cancer pain relief in 1996.[51This update presents the
management. This includes the initial development of advances in pain management since the mid-1980s. This
pain management policies and procedures; development includes new drug entities and dosing recommendations.
of standardized pain assessment and documentation In addition, it includes a guide to opioid availability from
forms; development of standardized treatment orders, around the world. The American Society of Anesthesiol-
including recommendations to manage adverse effects; ogists published their guidelines for cancer pain manage-
education of staff on the implementation of the new pain ment in 1996.1361
management standards; and quality assurance efforts to Numerous other publications are available in the area
evaluate the policies and procedures. of cancer pain ~ m n a g e m e n t . [ ~The
. ~ ~AHCPR
~~’ guide-
Some institutions use pharmacists to round on all lines are an excellent starting place for pharmacists in-
patients receiving PCA therapy. The patient’s total usage terested in chronic pain management, regardless of it
over 24 hours is reviewed and changes are recommended being due to malignant or nonmalignant conditions. These
when necessary. Other institutions have pharmacists on guidelines built on the original recommendations by
their pain management teams. These pharmacists see a WHO published in 1990.
mixture of both acute and chronic pain patients. Their Recently, the National Comprehensive Cancer Net-
roles are varied. but include recommendations of adjuvant work (NCCN) published their practice guidelines for
medications to facilitate in pain relief, patient counsel- cancer pain.[’81 This publication has numerous useful
ing, health care professionals. and patient education. figures and tables outlining the process for cancer pain
Patient’s who are being discharged should have pain management and serves as an update to the 1994 AHCPR
640 Pain ~ ~ n a g e m e nPharmacy
t, Practice in
guidelines. The NCCN guidelines provide the best il- pain, equianalgesic dosage conversions, use of adjunct
lustration of today’s management of cancer pain. medication, and barriers to pain management.
The biggest impact of these guidelines is changing the During the first 3 years that this service was in place,
basic approach to pain management. Instead of starting all 1029 patients with pain were seen by the ADS and 941
patients out on the first level of pain management (91%) had some kind of interaction with the service’s
(nonopioid), the NCCN guidelines recommend matching pharmacist, with an average of 3.5 recommendations per
the pain medication to the patient’s pain level. The patient patient. These recommendations ranged from correcting
should undergo a comprehensive pain assessment, in- medical omissions or incorrect dosing, to changing the
cluding rating their pain using the verbal 0 to 10 scale route of administration or dosing schedule, to providing
discussed previously. If their rating is between 1 and 3, agents to manage constipation.
the NCCN recommends starting them on a nonopioid; Bonomi and colleagues[451 published an excellent
for a rating between a 4 and 6, then begin a short-acting pharmacist guide to quality-of-life assessment in acute,
opioid and titrate as needed; and for a rating between chronic, and cancer pain. The various quality-of-life
7 and 10, rapidly titrate opioid. At any point, an ad- assessment tools are presented and discussed to help
junct analgesic may be added to the regimen.[1s1 guide the pharmacists in documenting appropriate pain
In addition, the NCCN guideline stresses the import- management of these patients. This information can
ance of beginning a bowel regimen in all patients started also be used to document the importance of pharmacy
on opioids, the use of antinausea medications as re- involvement in pain management services. Additional
quired, and psychosocial support and educational activi- helpful tools include two recently published scales, one
ties. In addition, the effectiveness of a pain regimen can of which assess symptoms related to malignancyr461and
be reassessed at 24 to 72 hours, depending on the se- the scale rating the amount of symptom distress[471 in
verity of their initial complaint. This guideline also pro- cancer patients.
vides a discussion of surgical or interventional pain man- Several reviews have also been published regarding
agement strategies. the management of pain caused by bone metastases.
A 1999 article discussing a pharmacist-based analgesic The most recent advances include the utilization of the
dosing service for cancer pain management provides bisphosphonates and new radioactive compounds.[481
useful information for pharmacists interested in starting The American Society of Clinical Oncology (ASCO)
an inpatient pain management service in oncology.[441 published clinical guidelines for the use of bisphos-
Northwestern Memorial Hospital has a 33-bed dedicated phonates in breast cancer in 2000.[491
oncology unit that admits 15 to 20 patients per week from
both attending and private physicians. On average, 44%
of admitted patients have pain as a continuing problem. A
bedside analgesic dosing service (ADS) was developed to The American Society of Anesthesiologists published
educate rotating interns, residents, and fellows on their guidelines for chronic pain management in 1997.[501
appropriate pain management techniques. This service The purpose of these guidelines is to optimize pain
uses 40% (16 hours) of a full-time clinical pharmacist’s control, while minimizing adverse effects and costs, and
hours with rounds being performed each weekday after- enhancing functional abilities, physical and psycho-
noon. The pharmacist is available throughout the day if a logical well-being, and quality of life. The guidelines also
patient’s pain requires immediate intervention. After- review adjuvant analgesics that are available for pain
hours and weekend coverage is provided by the pharma- management, in addition to opioid therapy.
cist staffing the oncology satellite pharmacy. A key component for management of chronic pain,
Upon admission, the cancer patient is asked to com- whether malignant or nonmalignant, is the development
plete a survey to assess their current pain situation. A of a multimodality and integrated treatment approach in-
copy of the form is provided in the article. Every 8 hours, volving medical, physical, and behavioral therapies. This
a nurse records three pain-intensity values on the bedside approach should include physicians (anesthesiologists,
flow sheet. After a patient is seen and evaluated, re- neurologists, rehabilitation), pharmacists, social workers,
commendations are conveyed orally to the prescribing phycologists, and physical therapist^.'^'] When conven-
physician or documented in the progress notes. Verbal tional therapies fail to provide adequate pain control, the
orders are obtained when rapid changes are needed to patient may require interventional pain management.[521
analgesic orders. An education series is provided every More recently, there has been a treatment shift in the
month by the ADS attending physician or pharmacist to management of chronic nonmalignant pain. Increasingly,
cover basic approaches to management of cancer-related physicians are including opioids in their management
Pain ~ a n a ~ ~ Pharmacy
m e ~ ~ Practice
, in 641
plans for patient^.[^^-^'] Studies have shown that noci- for prescribing opioid analgesics is essential in preventing
ceptive pain responds favorably to opioids, neuropathic discrimination against this patient population. In addition,
pain responds reasonably well, and idiopathic pain counseling patients on appropriate regimens to prevent
syndromes do not seem to respond.[581This change has opioid-induced constipation should occur in all patients
led to increased concerns regarding opioid addiction. receiving a opioid prescription.
However, once publication showed that increased med-
ical use of opioid analgesics to manage pain does not
appear to contribute to increases in the health consequen-
ces of opioid analgesic abuse.[591
Patients who have a past addiction history need to be
closely followed when opioid medications are prescribed. There are special considerations in the management of
In addition, the health care team may decide to employ an elderly patients with malignant and nonmalignant pain. A
opioid contract in these patients. Whenever possible, major concern is the undertreatment of elderly patients
these patients should be managed by a pain management in pain, based on a fear of increased toxicity. In 1998,
clinic and only one physician should be allowed to Bernabei and colleagues[671reported a retrospective study
prescribe opioids.[601 evaluating the adequacy of pain management in the
Model guidelines for the use of controlled substances elderly and minority cancer patients being admitted to
for the treatment of pain are available.[611These guide- nursing homes. Thirty eight percent of patients reported
lines recommend the following steps when evaluating daily pain; however, only 26% of these patients were
the use of controlled substances for pain control: 1) eval- receiving morphine. Patients older than the age of 85 were
uate the patient, 2) develop a treatment plan, 3) sign an even less likely to receive weak or strong opioids. In
informed consedagreement for treatment, 4) review pa- addition, 26% of the patients experiencing daily pain were
tient periodically, 5) seek consultation when appropriate, receiving no medication for this complaint.
6) maintain medical records, and 7) comply with con- This is another area primed for active pharmacy
trolled substance laws and regulations. involvement as many of these patients are in nursing
There are numerous publications of recommendations homes. These patients are usually undergoing monthly
to treat various chronic pain problems. The purpose of this medication reviews by pharmacists who can suggest
chapter is not to review the various treatments in pain appropriate dosages and combinations for the manage-
management, but to provide an overview and references. ment of pain. An article by Shimp[6s1 estimated that
Therefore, included in the following paragraphs is a brief 45-80% of nursing home residents and 20-50% of
listing of chronic pain conditions and treatments. These elderly in the community suffer from pain. This article
articles provide basic reference information for pharma- discusses appropriate selection of therapy and the risks
cists interested in pain management. for adverse effects.
Treatment recommendations for post herpetic neur- The elderly patient usually has multiple medical prob-
algia were published in 1996 by Kost and colleagues.[621 lems, in addition to pain. A helpful article was published
Several reviews on the treatment of back pain have been in 1998 by Ruoff for practicing physicians.1691This article
recently Treatment guidelines for discusses issue with the use of nonsteroidal antiinflam-
migraine were published in 1999.[651In 1998, a review matory and opioid medications in the elderly and patients
of the treatment of burn pain was published by Ulmer and with comorbid conditions.
Pharmacists (ASHP) both have pharmacy-specific groups Medical College of Wisconsin Palliative Care Medi-
devoted to pain management. Descriptions of these cine Program: http:/lwww.mcw.edu/pallmed/ (accessed
groups and enrollment procedures can be found at the October 2001).
organization web sites: OncoLink: http:llcancer.med.upenn.edu/(accessed
October 2001).
a ACCP: http://www.accp.com/index.html(accessed Pain Net: http://www.painnet.com/ (accessed &to-
October 2001). ber 2001).
0 ASHP: http://www.ashp.org/ (accessed October 2001). Project on Death in America: http://www.soros.org/
death/index.htm (accessed October 2001).
In addition to pharmacy organizations for pain man- Robert Wood Johnson Foundation: http://www.rwjf.
agement, there are several national societies devoted to org/main.html (accessed October 2001).
this cause. These organizations are multidisciplinary and University of Texas Caner Pain Page: http://palliative.
provide an excellent resource for pharmacists who want mdanderson.org/ (accessed October 2001).
to specialize in pain management. The area of pain Wisconsin Cancer Pain Initiative: http:l/www.wisc.
management in which you want to specialize will once edulwcpil (accessed October 2001).
again affect the organization you choose to join: World Health Organization’s Cancer Pain Release:
http://www.medsch.wisc.edu/ HOcancerpainI (accessed
0 American Academy of Pain Management: http:// October 2001).
www.aapainmanage.org/ (accessed October 2001). The web sites of pharmaceutical companies who
0 American Academy of Pain Medicine: http://www. manufacture medications to relieve pain should be
painmed.org (accessed October 2001). searched regularly for continuing education programs
0 American Chronic Pain Association: http://www. for pharmacists and physicians in both acute and chronic
theacpa.org/ (accessed October 2001). pain management.
0 American Pain Foundation: http://www.painfounda-
tion. org/ (accessed October 2001).
0 American Pain Society: http://www.ampainsoc.org/
(accessed October 2001).
a American Society of Addiction Medicine: http:// Even in the twenty-first century the adequate treatment of
www.asam.org/ (accessed October 2001). pain is lacking. There are several reasons for this. includ-
a American Society of Anesthesiologists: http://www. ing lack of education of health care professionals on the
asahq.org/homepageie.html(accessed October 2001). basic principles and knowledge of pain management.
m International Association for the Study of Pain: http:// Pharmacists can play a vital role in o~ercomingthe under-
www.halcyon.codiasp/ (accessed October 2001). treatment of pain. Roles include education of health care
a National Chronic Pain Outreach Association: http:/l professionals, patients. and their families; development of
neurosurgery.mgh.harvard.edu/NCPAINOA.HTM (ac- clinical treatment pathways for acute and chronic pain: and
cessed October 2001). monitoring and documenting outcomes of pain manage-
0 National Foundation for the Treatment of Pain: http:// ment, and providing guidance for improvement.
www .paincare.org/ (accessed October 200 1). Pain management is a significant expectation of the
JCAHO in their year 2000 surveys. Expectations not only
include established treatment pathways, but also docu-
mentation of outcomes and patient satisfaction.
cists. whether in acute or home health care. community,
or ambulatory settings should strive to become leaders in
the area of pain management.
Purdue Fredrick: http://www.partnersagainstpain.com/
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Abbott Total Quality Pain Management: http://www.
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PHARMACY PRACTICE ISSUES
medications correctly. Pharmacists and other health @ Assesses the patient's understanding of the reason(s)
practitioners can use patient medication counseling for therapy
strategies to ensure that patients: 1) take the medication B Assesses any actual andlor potential concerns of
correctly; 2) deal effectively with problems or adverse problems of importance to the patient
effects that might arise from taking the prescription: 3) 0 Discusses the name and indication of the medication
remain compliant with recommended therapies; and 4) Explains the dosage regimen, including scheduling
know how to assess if the medication is working. and duration of therapy when appropriate
B Assists the patient in developing a plan to incorporate
the medication regimen into their daily routine
0 Explains how long it will take for the drug to show and
The value and importance of patient medication counsel- effect
ing has been recognized in the literature"' and by federal B Discusses storage recommendations and ancillary
A 90),'*' which has mandated the instructions (e.g., shake well, refrigerate)
in information to patients. When this 0 Tells patient when they are due back for a refill
medication information is combined with the specific e Emphasizes the benefits of completing the medication
needs and perspectives of the patient (e.g., the patient's as prescribed
health beliefs; education level; emotional: physical. psy- e Discusses potential (significant) side effects
chological. social, and cultural needs), effective medi- 0 Discusses how to prevent or manage the side effects of
cation counseling should result. The responsibility of the the drug if they occur
health practitioner (pharmacist) is to ensure that the in- b) Discusses precautions (activities to avoid, etc.)
formation is appropriate to the patient and is effective in e Discusses significant drug-drug, drug-food, and
helping the patient to modify or maintain appropriate drug -disease interactions
medication-taking behaviors. Communication Skills in e Explains in precise terms what to do if the patient
Pharmacy Practice provides a complete overview of misses a dose
counseling skills, issues, and methods.'61 a Explores with the patient potential problems in taking
In 1994, the United States Pharmacopiea (USP) the medication as prescribed (e.g.? cost, access)
established an Ad HOGPanel. on edication Counseling '3 Helps patient to generate solutions to potential
Behavior Guidelines. This panel was a subgroup of the problems
USP Consumer InterestIHealth Education Advisory '3 Provides accurate information
Panel. The work of the panel resulted in the development 0 Uses language that the patient is likely to understand
of patient medication counseling inventory delineating 35 0 Uses appropriate counseling aids to support counseling
behaviors that could be part of a patient counseling B Responds with understandinglempathic responses
session.'3' The behaviors are divided into four groups that c Presents facts and concepts in a logical order
structure the counseling session into: I) the introduction e Maintains control and direction of the counseling
of the session; 2) the content of the session; 3) the process session
followed; and 4) the conclusion of the session. The be- 0 Probes for additional information
haviors (detailed descriptions are available ar the USP e Uses open-ended questions
web siteL3])include the following: m Displays effective nonverbal behaviors
e Verifies patient understanding via feedback
Conducts appropriate counseling by identifying self m Summarizes by acknowledging andlor emphasizing
and the patient or the patient's agent key points of information
Explains the purpose of the counseling session e Provides an opportunity for final concerns and
Reviews patient records prior to counseling questions
Obtains pertinent initial drug-related information (e.g., 0 elps patient to plan follow-up and next steps
allergies. other medication, age)
Warns patient about taking other medication, includ- This inventory of behaviors was designed to be re-
ing over-the-corner drugs, herbalslbotanicals, and levant to a wide variety of counseling situations and can
alcohol, which could inhibit or interact with the provide a framework for pharmacists and other health
prescribed medication professionals in providing patient medication education
Determines whether the patient has any other medical and counseling.
conditions that could influence the effects of this drug It should be noted that. for any given patient
or enhance the likelihood of an adverse reaction counseling encounter, any combination of these items
Patient EducatiodCounseling 9
may be included to focus attention on the specific needs medication was for?”, the pharmacist can discern if the
of the patient and may also include verbal instruction, patient knows what condition is being treated. Other
written information. or demonstration. The practitioner questions can be employed to assess
should keep in mind that the patient’s ability to use knowledge of the medication directions, ‘’
written information effectively may be limited, depending doctor tell you to use this medication?” and expected
on the nature of the written information. The USP Drug outcomes, “What did your doctor tell you to expect.”
Information Advice for the Patient”’ provides an ex- Once the existing knowledge of the patient is determined,
cellent resource for patient-oriented material, including the pharmacist can fill in any information gaps that are
pictograms for use with hearing- or language-impaired identified. Verifying the patient‘s understanding of the
patients. Also, demonstration, such as with the use of information communicated will then complete the coun-
inhalation aerosols or insulin injections, may be used to seling. Counseling in this manner can improve the
either educate or verify how a patient is using one of efficiency of medication counseling because only in-
these products. formation that the patient does not already know is pro-
In addition to pharmacist-patient education, there are vided. It also ensures and reinforces patient knowledge
a variety of other resources available for use in patient through the verification process.
teaching. These include company-prepared materials such
as videotapes and audiotapes for patients, booklets, leaf- The PAR technique
lets, and even periodic newsletters. For some disease
states, pharmaceutical companies have formed virtual In medication counseling there are often times when
support groups where questions can be discussed online patients can present with challenging or difficult to handle
with various health professionals. In addition, there are situations. These situations can arise from behavior on the
texts prepared to assist the pharmacist in determining part of the patient or the pharmacist. Some patient
the most appropriate information for a patient encounter examples might include when a patient is in a hurry to get
such as the Patient Coitnselirzg Handbook.[” back to work, has a sick child, has a hearing impairment,
or does not speak English well. On the pharmacists side of
the process, challenging situations could arise as a result
of a busy pharmacy, interruptions, or lack of confidence
about the ability to counsel. These challenging situations
may be the result of either functional (e.g., disability such
There are many different techniques that pharmacists and as loss of hearing, a patient who is a wheelchair user) or
other health professionals may use to provide patient emotional (e.g., a patient who is angry, in a hurry. or who
medication counseling. In addition to the information re- is confused by their problem) barriers. Any barriers to
quirements of patient medication counseling. the com- communication that are present must be resolved before
munication skills employed by pharmacists are important effective counseling can occw.
to good patient education. In particular, skills that build When confronted with a potential or apparent com-
rapport (proper introductions. learning and using pa- munication barrier, the goal of the pharmacist should be
tient names, talking in lay terms, etc.), good listening to react and respond to the patient in ways that defuse
skills (summarizing, paraphrasing, and the use of tension to effectively remove barriers. The PAR (Prepare,
empathic responses). appropriate body language (tone of Assess. and Respond) technique,‘” originally developed
voice, eye contact, posture, etc.), and interactive techni- in the field of psychology. involves preparing for each
ques (use of open-ended questions) are key to good phar- patient encounter, assessing situations before and after
macist-patient communication. Structured counseling they arise, and responding to patients in a manner that
strategies that have been developed for pharmacists to removes any barrier to communication.
enable them to provide better care are presented in the To effectively prepare for a patient encounter; a phar-
following paragraphs. macist examines the environment in the pharmacy set-
ting, the prescription, the patient profile. as well as any
interactive patient counseling personal knowledge of the patient to identify potential
barriers to communication before they arise. Once a prob-
Interactive patient counseling method^'^'^] use open- lem has emerged or been identified during a counseling
ended questions to determine what the patient knows session, the pharmacist must assess it accurately. To
about the medical condition and its treatment. For assess, pharmacists must identify possible emotional or
example, by asking “‘What did your doctor tell you this functional barriers. This may require careful observation
650 Patient E ~ u c a t i o ~ ~ o ~ n s e ~ ~ ~ g
and attention to the patient to determine the exact nature of manage their medication regimen better. For example,
the problem. providing information to alleviate patient fears about
Once the pharmacist has identified and assessed a side effects, affirming the need for a medication,
problem that has been identified, it is necessary to assurance about benefits, or even helping the patient
respond to the patient in an appropriate manner. The PAR to plan a typical day to include taking their medication
technique suggests that the use of empathic responses, on schedule.
reflecting patient feelings, and the use of probing
questions to encourage patients to talk will help in
resolving communication barriers. Pharmacists should
keep in mind that the ultimate goal is to ensure that the
patient takes the medication correctly. This can be
accomplished through medication counseling only after Patient education and medication counseling are an
any communication barriers have been removed. Acting integral part of the healthcare process. The two-way flow
in this manner, rather than reacting defensively to the of information in these processes is important to improve
patient, can open the lines of communication and the quality of care and patient outcomes, and to build
facilitate patient education. patient-practitioner relationships. Through medication
counseling, pharmacists can ensure that patients take their
Counseling for compliance medications correctly. Knowledge of a wide variety of
communication and counseling skills is important to
A process referred to as the RIM (Recognize, Identify, successful patient education. Specific methods are avai-
and Manage) te~hnique‘~’ structures a process for phar- lable to assist pharmacists in providing effective counsel-
macists to use to help patients solve compliance problems ing and patient education.
through patient education. To maximize patient compli-
ance with recommended therapies, pharmacists can learn
to recognize objective and subjective forms of evidence to
determine if the patient has a potential problem with me-
dication compliance. Some examples of objective evi-
dence might include reviewing the patient profile to 1. Hatoum, H.T.; Akhras, K. 1993 bibliography: A 32 year
identify problems with the refill record, the presence of literature review on the value and acceptance of ambula-
tory care provided by pharmacists. Ann. Pharm. 1993, 27,
complex regimens, or patients with high-risk disease
1106-1 118.
states. Subjective evidence, for example, might involve
2. Public Law 101-5008. S4401, 1927(g) November 5 , 1990
comments from patients expressing uncertainty about the and Fed. Regist., November 2, 1992; 57FR(212): 49397-
effectiveness of their therapy, questions about the dose 4940 1.
prescribed, or hesitation when asked how the medication 3. www.usp.org.
may be working. 4. Pfizer Corporation, New York, New York, USA and the
Using various forms of empathic or reflecting US Indian Health Service.
responses, universal statements. and probing questions, 5. Ekedahl, A. Open-ended questions and ‘show and tell’ a
pharmacists can learn to identify the specific causes of way to improve pharmacist counseling and patient’s
noncompliance. For example, questions such as “It understanding of their medications. J. Clin. Pharm. Ther.
sounds like you are unsure about how to take this 1996, 21, 95-99.
medication” (reflecting response), “Tell me more about 6. Tindal, W.N.; Beardsley, R.S.; Kimberlin, C.L. Commu-
nication Skills in Pharnzacy Practice, 2nd Ed.; Lea and
how this medication makes you feel dizzy” (probing
Febiger: USA, 1994.
question), and “Many patients will feel sleepy after 7. USP DI Advice for the Patient, 16th Ed.: United States
taking this medication” (universal statement) can be Pharmacopeial Convention: Rand McNally, Rockville,
useful in determining the nature of the patient’s problem. Maryland, 1996.
Once a compliance problem has been identified, 8. Patient Counseling Handbook, 3rd Ed.; American Phar-
pharmacists can use patient education to help patients to maceutical Association: Washington, DC, 1998.
PHARMACY PRACTICE ISSUES
Suzan E. ~ u ~ ~ k a r s ~ a ~
Henry Ford Hospital, Detroit, Michigan, U.S.A.
dividuals can identify and understand. However, indivi- lization takes into consideration that individuals with
duals might not have the expertise to assess unfamiliar or moderate expectations of a healthcare service will likely
ambiguous services. In these instances, individuals might be indifferent if those expectations are met. However,
base their evaluations on their expectations of whether or individuals with high expectations of a healthcare service
not such a service should be offered to them or on how the might be delighted if a healthcare provider met their high
service experience makes them feel. expectations. Thus, the focus in this conceptual frame-
work is the degree of affective response and not only how
well expectations were or were not met. Also, Kucukar-
TISFACTION AS DlSCONFl slan, Pathak, and Segal showed that this conceptual view
EXP EC~ATIONS of satisfaction can be very useful in cases when indi-
viduals have no prior expectations of a healthcare ser-
In his conceptual article, Oliver described satisfaction as a vice.[161In the healthcare domain, individuals often do not
result of one comparing an expectation to the actual service know what to expect when experiencing a healthcare
experience. This gap between the expectation and service service. In these cases, how a person feels would be an
experience then can impact how one feels about the service appropriate way to gauge patient satisfaction because
experience or the individual’s satisfaction with the knowledge about the service and prior expectations about
service.[’] The disconfirmation of expectations model that the service are absent.
Oliver describes in his paper has been tested and validated
by various researcher^.['^-'^^ This model states that
individuals compare their experiences with the service to
expectations. These expectations serve as a reference SATISFACTION A -
EQUITY BASED
point.[’] Although many researchers have accepted this ASSESSMENT
view of satisfaction, they have held different opinions about
which expectations, or comparison standards, are most A fourth conceptualization of patient satisfaction is an
pertinent and about which interrelationships among vari- equity-based assessment. This is a comparison of one’s
ables are most important in the satisfaction p r o c e s ~ . [ ’ ” ~ ~ outcomes versus inputs with respect to someone else’s
outcomes versus i n p ~ t s . ~ ~The
’ ’ ~resulting
’ perception of
fairness has a direct relationship to satisfaction. Indivi-
AS A F F E C ~ - ~ A S E D duals who perceive that a service provider has gained
more than they have are likely to be less satisfied. Studies
show that perceptions of fairness increased as the dif-
Satisfaction also has been viewed as a pleasurable ferences between inputs and outputs increased in favor of
response to a service encounter. This type of conceptua- the individual. 91 ’,
Patient Satisfaction 653
Such an approach to understanding patient satisfaction widely used and accepted measure of patient satisfaction
assumes that fairness is the key determinant of patient with medical care.
satisfaction. An understanding of the key inputs and out- A widely accepted example of patient satisfaction
puts of a healthcare service are required as well. There measurement that is specific to pharmacy services is
are only a few examples of this approach in the MacKeigan and Larson's Patient Satisfaction with Phar-
healthcare l i t e r a t ~ r e , " ~ . ' but
~ ] it could be quite useful macy Services Questionnaire (PSPSQ).[22.231Introduced
in situations where equity is a primary consideration in 1989,[221MacKeigan and Larson patterned their mea-
(e.g.. satisfaction with insurance coverage for health- sure after Ware et al.'s Patient Satisfaction Questionnaire
care services). (PSQ).[71 Eight dimensions of pharmacy services were
used for the questionnaire: 1) explanation; 2) considera-
tion; 3) technical competence; 4) financial aspects; 5 )
accessibility; 6) drug efficacy; 7) nonprescription pro-
ducts; and 8) quality of the drug product dispensed. Over
time, this measure has been tested and revised. In 1994,
Larson and M a ~ K e i g a n ' ~further
~] refined their ques-
No single, standard conceptualization of patient satis- tionnaire into a 33-item measure reflective of seven di-
faction is applicable to all situations. When selecting a mensions: 1) explanation; 2) consideration; 3) technical
conceptualization of satisfaction, the investigator must competence; 4) finance; 5 ) accessibility; 6) product avail-
identify the research question. For example, if the primary ability; and 7) general. Reliability and validity of this
research objective is to compare service providers in measure are s ~ p p o r t e d , ' ~and
~ . ~it~has
] been used in the
terms of how well individuals rate specific aspects of ser- pharmacy services
vice performance. an experience-based evaluation of per-
formance would be appropriate. If the research is fo-
cused instead on the relationship between individuals' su
evaluation of a service and their future commitment
to the service provider, a satisfaction measure that ref-
lects evaluative and affective reactions by the individual Because a number of conceptualizations of patient sa-
would be appropriate. tisfaction can be used, the measurement of patient sa-
Also, one should remember that patient satisfaction tisfaction must fit the context of the overall research
might not be the most relevant outcome for study. Per- process. A research process proposed by C h u r ~ h i l l in-
[~~~
formance, quality, loyalty, complaining behavior, trust, or volves six stages: 1) formulate the problem; 2) determine
some other outcome might be more useful for decision the research design; 3) design data collection method and
making, planning, implementation, and evaluation related forms; 4) select a sample and collect the data; 5) analyze
to healthcare products and services. It is important to link and interpret the data; and 6) prepare the research report.
the construct being measured to the problem or decision Each stage is linked, and decisions made at one stage will
that the study results will help address. affect decisions made at other stages.
Two popular patient satisfaction measures for which When investigating patient satisfaction, one must also
psychometric properties have been investigated and re- consider the requirements and limitations imposed by the
ported include 1) Ware et al.'s Patient Satisfaction Ques- research process itself. For example, the purpose of the
tionnaire (PSQ)[7,20,211 and 2) MacKeigan and Larson's research, potential users of the data, time and money
Patient Satisfaction with Pharmacy Services Question- available for the study, the population of interest, and the
naire (PSPSQ).[22231 data collection methods will all influence the type of
Ware et al.'s Patient Satisfaction Questionnaire satisfaction measure determined to be the most approp-
(PSQ),[7320211 and related versions. has become one of riate. Limitations in these factors must be recognized,
the most widely used measures of satisfaction with me- whether a new measure of patient satisfaction is being
dical care.'241 The most recent version, called the Short- developed or an existing measure is being used.
Form Patient Satisfaction Questionnaire (PSQ- 18). can be Because the meaning attributed to a satisfaction mea-
obtained from RAND Corporation, Santa Monica, Cali- sure by the investigator may not be the same as the
f ~ r n i a . " ~This
] version contains 18 items that focus on meaning imputed to it by the respondents, a systematic
seven distinct areas: 1) general satisfaction; 2) technical process for developing measures should be followed that
quality; 3) interpersonal manner; 4) communication; 5 ) includes: 1) specifying the domain of the construct; 2)
financial aspects: 6) time spent with doctor; and 7) acces- generating a pool of items and determining the format of
sibility/convenience. Acceptable reliability and validity the measure; 3) having the initial pool of items reviewed
have been reported for this It constitutes a by experts; 4) considering inclusion of validation items;
654 Patient Satisfaction
5) administering items to a development sample; 6) pu- MacKeigan and Larson's Patient Satisfaction with Phar-
rifying the measure; and 7) optimizing the practicality macy Services Questionnaire (PSPSQ).['2*231However,
of the measure (see Ref. [28] for a useful summary of no single standard measure of patient satisfaction is ap-
this process). plicable to all situations. We suggest that an existing
When using existing measures of satisfaction or when measure of patient satisfaction, with demonstrated re-
developing new measures for a specific research purpose, liability and validity, should be used if it fits the con-
acquiescent responding can be a problem. Acquiescent struct domain of the study. Whenever a new satisfaction
responding is the tendency to agree with statements of an measure is needed, its conceptualization should be de-
attitudinal nature regardless of the statement's content.[241 fined carefully and a systematic process for developing a
To overcome this problem, the use of a balanced multiple- measure should be followed.
item measure, asking several positively worded questions
and several negatively worded questions, is crucial to
the measurement of patient satisfaction. This method
tends to cancel out any systematic tendency to simply
agree with items contained in the questionnaire.[241 1. Donebedian, A. The Definition of Quality and Approaches
Finally, when comparing satisfaction among groups of to its Assessment, Vol. 1. In Explorations in Quality
individuals who belong to different health plans or access Assessment and Monitoring; Health Administration Press:
different care providers within a health plan, it is im- Ann Arbor, 1980.
portant to control for case-mix. Case-mix refers to the 2. 1997 Novartis Report on Member Satisfaction within
different patient attributes that might be apparent in Managed Care; Novartis Pharmaceuticals Corporation:
different settings.1241To the extent that patients self-select 59 Route 10, East Hanover, NJ 07936-1080, 1997.
or are assigned to different comparison groups in non- 3. Carey, R.6.; Seibert, J.H. A patient survey system to
random ways, comparisons of satisfaction ratings may be measure quality improvement: Questionnaire reliability and
validity. Med. Care 1993, 31 (9), 834-845.
biased by factors other than the provision of the health-
4. Dearmin, J.; Brenner, J.; Migliori, R. Reporting on QI
care services in the compared groups. For example, re-
efforts for internal and external customers. J. Qual. Improv.
lationships between health status and patient satisfaction 1995, 21 (6). 277-288.
have been reported.[241Thus, it is often prudent to control 5. Oliver, R.L. Satisfaction: A Behavioral Perspective on the
for the effects of health status when comparing patient Consumer; Mc6raw-Hill: New York, 1997.
satisfaction among or between groups. Other factors 6. Schommer, J.C.; Kucukarslan, S.N. Measuring patient
might account for differences in satisfaction scores de- satisfaction with pharmaceutical services. Am. J. Health-
pending on the question being addressed in the study. Syst. Pharm. 1997, 54, 2721 -2732.
Case-mix control variables such as age, gender, socio- 7. Ware, J.E.; Snyder, M.K.; Wright, W.R.; Davies, A.R.
economic status, disease severity, physical functioning, Defining and measuring patient satisfaction with medical
service expertise, or service provider familiarity also care. Eval. Program Plan. 1983, 6, 291-297.
8. Hall, J.A.; Dornan, M.C. What patients like about their
should be considered for inclusion in the study. Methods
medical care and how often they are asked: A meta-analysis
used to control or adjust for case-mix variables can then
of the satisfaction literature. Soc. Sci. Med. 1988, 27, 935-
be used (e.g., restriction, stratification, matching, statis- 939.
tical adjustment). Johnson[241has written a useful sum- 9. Oliver, R.L. A cognitive model of the antecedents and
mary of these methods. consequences of satisfaction decisions. J. Mark. Res. 1980,
17, 460-469.
10. Woodruff, R.B.; Cadotte, E.R.; Jenkins, R.L. Modeling
consumer satisfaction processes using experienced-based
norms. J. Mark. Res. 1983, 20, 296-304.
Patient satisfaction is an individual's judgment about the 11. Cadotte, E.R.; Woodruff, R.B.; Jenkins, R.L. Expectations
extent to which a healthcare product or service provides a and norms in models of consumer satisfaction. J. Mark.
Res. 1987, 24, 305-314.
pleasurable level of consumption-related fulfillment. In
12. Tse, D.K.; Wilton, P.C. Models of consumer satisfaction
the recent literature, patient satisfaction has been
formation: An extension. J. Mark. Res. 1988,25, 204-212.
conceptualized in four ways: 1) performance evaluation; 13. Yi, Y. The determinants of customer satisfaction: The
2) disconfirnation of expectations; 3) affect-based as- moderating of role ambiguity. Adv. Cons. Res. 1993, 20,
sessment; and 4) equity-based assessment.[61 Commonly 502- 506.
used patient satisfaction measures include Ware et al.'s 14. Schommer, J.C. Roles of normative and predictive
Patient Satisfaction Questionnaire (PSQ)",20,211 and expectations in evaluation of pharmacist consultation
Patient Satisfaction 655
services. J. Consum. Satisfac., Dissatisfac., Complain. medical care. JAMA, J. Am. Med. Assoc. 1989, 262 (7),
Behav. 1996, 9, 86- 94. 925-930.
IS. Spreng, R.A.; MacKenzie, S.R.; Olshavsky, R.W. A 21. Marshall, G.N.; Hays, R.D.; Sherbourne, C.D.; Wells, K.B.
reexamination of the determinants of consumer satisfac- The structure of patient satisfaction with outpatient me-
tion. J. Mark. 1996, 60, IS 32. dical care. Psychol. Assess. 1993, 4. 477-483.
16. Kueukarslan, S.N.; Pathak, D.S.; Segal, R. The Relation- 22. MaeKeigan, I J . : Larson, L.N. Development and valida-
ship of Expectations and Pcrccived Equity with Consu- tion of an instrument to measure patient satisfaction with
mers’ Evaluation of Pharmaceutical Information Services. pharmacy services. Med. Care 198
In Presented at American Marketing Association 1996 23. Larson, L.N.; MaeKeigan, L.D. Further validation of an
Winter Edurators’ Conference. Nilton Head, South Ca- instrument to measure patient satisfaction with pharmacy
rolina; 1996; Feb. 5 . services. J. Pharm. Mark. Manage. 1994. 8, 125 139.
17. Oliver, R.L.; Swan, J.E. Equity and discoiirirmation 24. Johnson, J.A. Patient Satisfaction. In Pharmac.orconomics
perceptions as influences on merchant and product satis- and Outcomes: Applications ,fiir Patient Cure; American
faction. J. Consum. Res. 1989, 16, 372-383. College of Clinical Pharmacy, 1997; 111- 154.
18. Oliver, R.L.: Swan, J.R. Consumer perceptions of in- 2s. Malone, D.C.; Rascati, K.L.; Gagnon, J.P. Consumers’
terpersonal equity and satisfaction i n transactions: A field evaluation of value-added pharmacy services. Am. Pharm.
survey approach. J. Mark. 1989, 53, 21-35. 1993, NS33 ( 3 ) , 48-56.
10, Pathak, D.S.; Kucukarslan, S.N.; Segal, R. Explaining 26. Johnson, J.A. A Comparison ol Satisfaction with Pharmacy
patient satisfaetion/dissatisfaction i n the high blood pres- Services between Mail and Traditional Pharmacy Patrons
sure prescription drug market: An application of equity and an Evaluation of the Relationship of Health Status.
theory and disconfirmation paradigm. J. Consum. Satisfac., PhD Dissertation; University of Arizona, 1996.
Dissatisfae., Complain. Behav. 1994, 7, 53-73. 27. Churchill, G.A. Marketing Rewarch: Methodological
20. Tarlov, A.R.; Ware, J.E., Jr.; Greenfield, S.; Nelson, E.C.; Foundations; Dryden Press: Orlando, Florida, 1995.
Pemn, E.; Zubkoff, M. The medical outcomes study: An 28. DeVellis, R.F. Scale Development Then? and Applica-
application of methods for monitoring the results of tions; Sage: Newbury Park, California, I99 1.
PHARMACY PRACTICE ISSUES
s
osalie Sagraves
University of illinois, Chicago, Illinois, U.S.A.
about educating children about medications may be found dynamic changes that occur secondarily to physiologic
on their website (www.usp.org). The following informa- changes in maturing neonates, infants, children, and
tion pieces have been developed by the USP:[51 adolescents that can affect drug absorption from various
routes of administration as well as drug distribution,
Guide to Developing and Evaluating Medicine Edu- metabolism, and elimination. To be more knowledgeable
cation Programs and Materials f o r Children and about pharmacokinetic changes, therapeutic drug mon-
Adolescents (joint publication of the American Wealth itoring (TDM) must be undertaken for drugs with narrow
Association and USP). therapeutic indexes and for those for which pharmaco-
A Kid's Guide to Asking Questions about Medicines. dynamic data (i.e., pharmacologic response that correlates
Teaching Kinds about Medicines. to the drug concentration at the receptor site) correlates
Talking to Children about Their Medicines (pamphlet with pharmacokinetic information. Also addressed will be
developed jointly by Pfizer and USP to be dissemi- drug administration by various routes including intraven-
nated to pediatricians and children's families). ous (i.v.), oral (P.o.), intramuscular (i.m.), subcutaneous
An Annotated Bibliography of Research and Programs (s.c.), percutaneous, rectal, otic, nasal, ophthalmic, and
Relating to Children and Medications. inhalation. Another issue discussed is product selection
for pediatric patients.
The USP worked with the National Center for Health To better understand changes in drug disposition, the
Education in New York to develop educational materials pediatric population needs to be categorized into various
that can help school systems nationwide to know more groups (Table 1) because children vary markedly in
about medications that students may need to take. The USP their absorption, distribution, metabolism, and elimina-
also adopted the following resolution to address the work tion of medications. This occurs because neonates, in-
that needs to be done in the area of health e d ~ c a t i o n : ' ~ ] fants, children, adolescents, and adults have different
body compositions ( i t . , as to their percentages of body
Facilitate and contribute to the development of a rational water and fat) and have their body organs in different
school medicines policy, including guidelines for student,
stages of development.
faculty, and staff medicine education, for acquisition,
transport, storage, administration, use, and disposal of
medicines; for protection of privacy; and for record-
keeping in primary and secondary schools. Initiative should TIC
be undertaken in collaboration with appropriate partners.
Gestational age Time from the mother's last menstrual period to the time the baby is born;
at birth, a Dubowitz score in weeks gestational age is assigned, based on
the physical examination of the newborn
Postnatal age Age since birth
Postconceptional age Age since conception, i.e., gestational plus postnatal age
Neonate First 4 weeks or first month of life
Premature neonates Born at less than 37-weeks gestation
Fullterm neonates Born between 37- and 42-weeks gestation
Postterm neonates Born after 42-weeks gestation
Infant 1 month to 1 year of age
Child 1-12 years of age
Adolescent 12- 18 years of age
658 Pediatric Dosing and Dosage Forms
modified by physiologic maturation of the child from adult levels until 6-8 months of age and may be
birth through adolescence. Physiologic changes that occur associated with Gastrointestinal transit time
can affect drug absorption, distribution, metabolism, and may be prolonged and peristaltic activity unpredictable in
elimination. The most dramatic changes occur during the young infants;"" both appear affected by the feed-
neonatal period. ing."31 Lebenthal and colleagues noted that breast-fed
infants, older than 45 days of age, had gastric transit times
longer than 10 h while formula-fed infants had transit
times less than 10 h.'I4' It should also be noted that young
Drug absorption from the gastrointestinal (GI) tract is infants have a propensity to reflux their gastric contents
dependent on patient factors, physicochemical properties because of GI immaturity. All these factors affect the
of the orally administered drug, and the drug formulation. extent to which a drug may be absorbed.
Patient factors that affect GI absorption include absorptive
surface area, maturation of the mucosal membrane, gastric Enzyme activity and microflora in the
and duodenal pH, gastric emptying time, GI motility, gastrointestinal tract
enzyme activity, bacterial colonization of the GI tract, and
dietary intake, including the specific gastric content status Pancreatic enzyme activity may be low at birth, but
at the time when a medication is Patient enzymes such as amylase, lipase, and trypsin develop to
factors are influenced by rapid maturational changes that adult levels within the first year of life."51 Premature
occur throughout early childhood, but which occur infants appear to have lower amylase levels than do full-
primarily during the first few months of life. term infants. Low concentrations of pancreatic enzymes
Most drugs are absorbed across the GI tract by passive may be the reason why newborns have a decreased ability
diffusion, but a variety of drug physicochemical factors to cleave prodrug esters such as chloramphenicol
influence the extent of absorption. These factors include ~ a l m i t a t e . ~Lipid-soluble
~] drugs may not be well ab-
molecular weight, lipid solubility, ionization as well as sorbed by neonates because of low lipase concentrations
disintegration and dissolution In addition, drug and bile acid pool.[*]
absorption may be dependent on the dosage form selected More information is needed about the microflora of the
(e.g.. a liquid, a tablet that may need to be crushed, or a GI tract and its effect on drug absorption. In addition, the
sustained-release product), and the particular brand effects of various diets and antibiotic use can alter the
selected. For time-release preparations. the release microflora of the GI tract.[71
characteristics must also be taken into consideration.
Absorptive surface area
Gastric pH
The surface area of the small intestine in young infants is
When examining patient-specific factors such as gastric proportionately greater than in adults. This physiologic
pH, which affect oral absorption, it should be noted that difference may allow for increased drug absorption from
infants born vaginally who are at least 32-weeks the GI tract.
gestation, usually have gastric pHs between 6 and 8 at
birth.[73X1Gastric pH then falls rapidly within a few hours
after delivery to a pH of less than 3.[7,81
The initial gastric l n t r a ~ u s ~ u l Absorption
ar
pH is alkaline compared to that of adults and results from
the presence of amniotic fluid in the infant's When a child is unable to take a medication orally or the
Thereafter, gastric pH remains acidic until approximately drug is unavailable for oral use, there may be a need to
day 10, then a nadir in acid production occurs between administer a drug parenterally by either the i.v. or i.m.
days 10 and 30 of life. Then gastric acid production route. Of these, the latter may be less desirable because
begins to increase, but gastric pH and maximal gastric of pain, irritation, and decreased drug delivery as
output may not mirror that of adults on a per kilogram compared to i.v. administration. Drug absorption after
basis until after the neonatal period.[71 i.m. administration depends on various physicochemical
and patient factors. Physicochemical factors to be
Gastric emptying and gastrointestinal motility considered include lipid or water solubility, drug con-
centration, and surface area. When addressing drug sol-
Gastric emptying time in neonates, especially those less ubility, it should be noted that lipophilic drugs readily
than 24 h of age, may be variable.[71 It may not reach diffuse through the capillary walls of endothelial cells
Pediatric Dosing and Dosage Forms 659
whereas water-soluble drugs diffuse at fairly rapid rates for solubility, and they are insoluble in the muscle after
from interstitial fluid to plasma via pores in capillary i.m. administration."']
membranes."61 A lipid-soluble drug may be more rapidly Complications associated with i.m. administration
absorbed i.m., but a water-soluble drug may be more include nerve iniurv, muscle contracture, and abscess
. , <
desirable because the drug must be stable in an aqueous formation."91 Less common problems include intramus-
solution until administered. After administration, the drug cular hemorrhage, cellulitis. skin pigmentation, tissue
must then be water soluble at physiologic pH until ab- necrosis, muscle atrophy, gangrene. and cyst or scar
sorption formation. In addition. injury may occur from broken
Drug absorption may be dependent on concentration, needles and inadvertent injection into a joint or vein.""
but available data do not allow us to determine whether an
increased or decreased drug concentration results in better
absorption. An increase in the osmolality of a pharmaceut-
ical preparation secondary to the addition of another The S.C. route is used for the administration of drugs such
substance such as an excipient may decrease or slow down as insulin that require slow absorption. Injection tech-
i.m. adsorption.[I6]Absorption occurs more rapidly when nique and patient factors, such as fluid status and physical
diffusion involves a large area of muscle or the drug build, are important."'] Exercise. elevation or warming of
spreads over a large muscle mass. The massaging of an the injection site, or inadvertently administrating a drug
injection site after i.m. administration increases the rate of i.m. rather than S.C. can increase absorption and be
absorption."61 dangerous in some situations, such as hypoglycemia oc-
A physiologic determination of i.m. drug absorption is curring in a diabetic patient from excessive insulin ab-
dependent on the adequacy of blood flow to muscle sorption."'] Adverse effects that can occur secondarily to
groups used for drug administration. Absorption rates S.C. administration include tissue ischemia, sterile and
differ at injection sites because blood flow varies among nonsterile abscesses, lipodystrophy. cysts, and granulo-
different muscle groups. For example, the absorption matous formation.
of a drug-administered i n in the deltoid muscle is
faster than from the vastus lateralis that, in turn, is more
rapid than from the g l ~ t e u s . " ~ ~This
" ~ occurs because
blood flow to the deltoid muscle is 7% higher than to
vastus lateralis and 17% higher than to gluteal muscle If an i.v. line cannot be placed, the intraosseous drug
groups."'] Physiologic conditions that reduce blood flow administration route can be used for pediatric patients
to a muscle group may adversely alter the rate and/or during, for example, cardiopulmonary resuscitation (CPR)
extent of a drug-administered i.m. Decreased perfusion because drug delivery by this route is similar to that for
or hemostatic decompensation, frequently observed in ill i.v. administration.[201 If drug or fluid delivery by this
neonates and young infants, may reduce i.m. drug ab- route is sluggish, a saline flush can be used to clear the
sorption. Drug absorption may be adversely affected in needle. Intraosseous administration is used to deliver
neonates who receive a skeletal muscle-paralyzing agent medications such as epinephrine, atropine, sodium bicar-
such as pancuronium"61 because of decreased muscle bonate, dopamine, diazepam, isoproterenol, phenytoin,
contraction. A small muscle mass in neonates and young phenobarbital, dexamethasone, and various antibiotics.[201
infants may also reduce the ability of a drug to be ade-
quately absorbed. P ~ r c u t a n ~ oor~Trans
s ermal ~ ~ s o r ~ t ~ o n
The injection technique used may alter i.m. absorption.
This was noted when needles of different lengths were The percutaneous (transdermal or topical) route for
used. The use of a longer needle (38 vs. 31 mm, 1 1/2 vs. systemic drug delivery is used infrequently for pediatric
1 1/4 in.) for i.m. administration in adult patients resulted patients. Medications are typically applied to the skin for
in higher diazepam serum concentrations."*] This their local effect. In the future, this route may be used
probably occurred because the drug administered with more frequently for systemic effects as more transdermal
the shorter needle was actually administered S.C. rather systems are developed for drug delivery.
than i.m. The percutaneous absorption or the transdermal
Some drugs are absorbed more slowly after i.m. than delivery of a drug occurs in the following manner.
oral administration; examples include diazepam, digoxin, Initially a topically applied drug is absorbed into the
and phenytoin. This probably occurs because these drugs stratum corneum and diffuses through that layer of skin
require a mixture of alcohol, propylene glycol, and water into the epidermis and then into the dermis where drug
660 Pediatric Dosing and Dosage Forms
molecules reach capillaries and enter the circulatory phenol absorption.[”] Toxicity has also been noted with
system. Diffusion through the stratum corneum is the rate- the topical application of iodine and alcohol-containing
determining step unless skin perfusion is decreased. If the products.[231
latter case, diffusion is controlled by the transfer of drug
molecules into capillaries rather than by the diffusion Application site
process previously explained. Percutaneous or transder-
ma1 absorption[21.221is affected by The ability of a drug to be absorbed transdermally depends
on the thickness of the stratum corneum. For example,
Patient age. absorption occurs more readily through abdominal skin
Application site. than through skin on the plantar surface of the foot. To-
State of hydration of the stratum corneum. pical absorption may be enhanced from a particular site
Thickness and intactness of the stratum corneum. by the application of an occlusive dressing.
Physical characteristics of the solute, and
Physical characteristics of the vehicle or solvent.
Status of the stratum corneum
Drug diffusion may be explained by Eq. 1:
Percutaneous absorption of a drug is enhanced by the
hydration of the stratum corneum. Such hydration affects
the absorption of hydrophilic drugs more than lipophilic
drugs. Drugs will penetrate damaged skin more than intact
where J is flux, K,,, is the partition coefficient, D , is the skin. Skin damaged because of dryness will allow for
diffusion constant under specific conditions such as increased drug penetration through areas where the skin is
temperature and hydration, C, is the concentration cracked or broken.
gradient, and 1 is the length or thickness of stratum
corneum.[211
Solute
Lipid-soluble drugs are better absorbed into the
stratum corneum than are water-soluble drugs, but the The penetration of the solute (or drug) depends on its
latter do not easily traverse the stratum corneum. Thus, polarity and on the polarity of the delivery vehicle.
lipid-soluble drugs are more likely to be stored in the
stratum corneum, whereas water-soluble drugs are more
likely to diffuse across the stratum corneum to the epi- Vehicle or solvent
dermis and dermis.[211
Drug-delivery vehicles typically used for topical applica-
tion include lotions, ointments, creams, emulsions, and
Patient age
gels. Substances such as emulsifiers may be added to the
drug and vehicle to improve the texture of an emulsion, a
Drug absorption transdermally is not appreciably differ-
stabilizer to preserve drug stability, the vehicle, or both, a
ent in various age groups of patients except for neonates
thickening agent to increase viscosity, or a humectant to
less than 32-week gestation at birth.[231Drug absorption
draw moisture into the skin.[211It is particularly important
is increased in premature neonates, because the stratum
to consider the vehicle and other additives when select-
corneum is not completely formed at birth. An example
ing a topical drug preparation for a neonate, especially
of increased drug absorption occurred in two premature
when premature, because of the greater possibility of
neonates who were repeatedly washed with 3% hexa-
absorption of not only the drug but also other product
chlorophene and developed encephalopathy secondary to
ingredients. Toxic reactions have occurred in neonates
drug absorption.[211The absorption of the corticosteroid
from ingredients considered “inactive.’ ’
betamethasone valerate after topical application in
children resulted in hypothalamus-pituitary-adrenal axis
suppression. Children may have increased drug absorp- Trans
tion from the percutaneous application of drugs not be-
cause of higher absorption rate but because of a greater Drugs chosen for delivery via a transdermal drug-delivery
topical application or a larger dose per kilogram. Exam- system must adequately penetrate the skin in such a way
ples of deaths in children from percutaneous drug that the system determines the delivery rate that should be
absorption include those caused by salicylic acid and fairly constant.[”] In addition, the drug must not irritate or
Pediatric Dosing and Dosage Forms 661
sensitize the skin. It is hoped that in the future more drugs usually low compared to that in other areas of the GI tract,
will be developed for transdermal delivery. This could a drug may not be completely soluble. In addition, a
become an alternative route for drug delivery to children variety of organisms colonize the rectum, and it is debated
who have difficulty with oral administration. whether these organisms are involved in drug metabol-
ism.[251Absorption is also influenced by the dosage form
E ~ d o t ~ a c Absor
~@a~ used. For example, drugs are rapidly absorbed rectally
from aqueous or alcoholic solutions, whereas absorption
The endotracheal (ET) route has been used to administer from a suppository depends on its base, the presence of a
medications during CPR when other routes, such as the surfactant, particle size of the active ingredient(s), and
i.v. route, are unavailable. It provides rapid access as well drug concentration.[251 The following problems may be
as rapid drug absorption and distrib~tion.'~~] Some studies associated with the rectal route for drug administration:[251
have shown that the time to reach peak absorption is
similar to that for the i.v. route, but serum concentrations 0 Decreased absorption secondary to defecation of the
achieved were 10-33% of that achieved with i.v. rectally administered pharmaceutical product.
administration, resulting in a weaker response. A depot Less adsorption rectally than orally because the ab-
effect has also been demonstrated for drugs such as sorbing surface area of the rectum is smaller.
epinephrine. Work needs to be done to determine the 0 Dissolution problems for rectally administered medi-
optimal dose by this route, drug-delivery vehicle, and the cations because of lower fluid volume in the rectum
most effective delivery technique. than in the stomach, duodenum, etc.
0 Microorganisms in rectum may cause degradation of
Rectal Absorpti~n some medications.
0 Patient or parent acceptance.
The rectal route is used for local and systemic therapy for
the following reasons:[251 Distribution
than men do because they have a higher concentration of to the increased number of binding sties on neonatal
body fat. Thus. neonates, because of their high TBW. erythrocytes.[301
have a higher V , for water-soluble drugs such as amino-
glycosides than older children or adults. For example, the Drug penetration into the central nervous system
V, for an aminoglycoside such as gentamicin approx-
imates that of extracellular cellular fluid volume, 0.5 - 1.2 A drug is more likely to cross into the central nervous
Llkg for a neonate, but only 0.2-0.3 Llkg for an older system (CNS) of a neonate rather than an older child or an
child or an adult.@] adult. This most likely occurs because its CNS is less
Adipose tissue increases from as little as 0.5% in a mature and the blood-brain barrier is less formed. This is
premature infant to approximately 16% of body weight an important consideration when antimicrobial therapy is
for a full-term infant.'26'271 BOYS experience a spurt in needed for the treatment of bacterial meningitis or
body fat between the ages of 5 and 10 years. and then a anticonvulsant for seizures.
gradual decrease in fat content until about 17 years of age;
girls usually have a rapid increase in adipose tissue at etabolism
puberty.['] Thus, one would expect neonates and young
infants to have a decreased V , for lipid-soluble drugs. Although drug metabolism can occur in various body
This has been noted for diazepam in neonates who have organs including the lungs, GI tract, liver, and kidneys as
exhibited an apparent V , of 1.4- 1.8 L k g compared to well as in the blood, the liver is the primary organ for
2.2-2.6 Llkg in adults.[281 metabolism. Most drugs are metabolized from lipid-
soluble parent compounds to more polar, less lipophilic
Protein binding metabolites that are more readily eliminated renally.['I
young children readily sulfate acetaminophen; in adults achieve the same serum concentrations. This may be due
the major metabolic route is gl~curonidation.[~Little is to decreased digoxin absorption or increased renal
known about acetylation in neonates or infants. It is elimination.[*]
believed that neonates have an extremely low capacity for
acetylation at birth, but this pathway matures at ap-
proximately 20 days of age.[291 T G
Theophylline is an example of a drug that is readily
metabolized in neonates by N-methylation to caffeine Therapeutic drug monitoring should encompass the en-
(process not relevant clinically in older infants, children, tire drug-use process including drug selection, product
and adults). It is also a compound that has pharmaco- selection, administration route, patient age, appropriate
logic activity versus apnea (like theophylline), but which dosing on a m g k g or mg/m2 basis, and monitoring se-
may have toxicity when it is not readily metabolized rum concentrations when appropriate and observing the
by the liver, and its elimination is slowed by immature patient for optimal drug effect(s) and possible adverse
kidneys.[@ drug events.
Neonates require close monitoring if their mothers
received enzyme inducers such as phenytoin, phenobar-
bital, carbamazepine, or rifampin during pregnancy or if
they need one of these drugs themselves.['61Examples of
drugs that inhibit the metabolism of other medications For many drugs, especially for those with narrow
include cimetidine, erythromycin, and ketoconazole.[16] therapeutic indexes, serum concentration ranges have
been determined that correlate to minimum and maximum
therapeutic effects as well as to the development of
toxicity. Therapeutic serum concentration ranges for
The kidneys are the major route for drug elimination, various drugs have been developed for adults, and these
especially for water-soluble compounds or the metabo- data have been applied to pediatric patients including
lites of lipid-soluble drugs. Renal drug elimination is neonates. Such data may be appropriate to monitor drug
dependent on renal blood flow, glomerular filtration, and therapy in children, but possibly not in children of all ages
tubular secretion and reabsorption. These functions or possibly not in children at all. For example, Painter et
appear to mature at different rates in the neonate and al.[341noted that neonates need higher serum phenobar-
infant. Full-term infants achieve renal blood flow similar bital concentrations than do older children and adults to
to that of adults by the age of 5-12 months; glomerular terminate seizures. Gilman et al.[351observed that higher
filtration approaches adult values by the age of 3-5 phenobarbital loading doses were needed to achieve
months.[61 Premature neonates exhibit lower rates for serum concentrations in neonates that would reduce the
glomerular filtration at birth than do full-tern neonates, occurrence of seizures. Thus, there may be a need for
and more time is required of them postnatally to develop different serum concentration ranges for various drugs
filtration ability.[321This is probably due to their lack of needed by different age groups of patients for a similar
as many functional nephrons at birth. Tubular function is pharmacodynamic or therapeutic outcome.
less mature in the neonate at birth than is glomerular Free serum concentrations, rather than total concentra-
filtration, and it matures at a slower rate. Tubular tions, of some drugs such as phenytoin may need to be
function begins to approach adult values by 7 months monitored in some patients, including neonates, who have
of age. Renal function is equal to that of adults by 1 year low serum albumin. Gilman has advocated the possibility
of age. of using individualized dosing and serum concentration
Aminoglycosides (e.g., gentamicin, tobramycin, ami- range for pediatric patients because children, especially
kacin) and digoxin are drugs whose eliminations are neonates, have rapidly maturing functions of various
affected by renal maturation. The renal elimination of organs and changes in albumin for drug binding.[361
aminoglycosides in neonates and young infants parallels Serum concentration monitoring of various drugs
the maturation of glomerular function and correlates with administered to pediatric patients may appropriately give
creatinine clearance.[331The renal elimination of digoxin information about the drug but not its metabolites. This
parallels kidney maturation. Dosage adjustment for this may be a problem when children metabolize specific
drug is necessary as renal function matures in neonates drugs differently than adults with resulting differences in
and young infants. In addition, older infants and children metabolite concentrations or the presence of different
require higher mg/kg doses of digoxin than do adults to metabolites. This has been noted when premature infants
664 Pediatric Dosing and Dosage Forms
have been administered theophylline for central apnea. A aminoglycosides it may be important to obtain both
major metabolite of theophylline in neonates is caffeine, peaks and troughs.
although only small concentrations of this metabolite are
noted in older children and a d ~ l t s . ' ~ Caffeine
~ , ~ ~ ] is
effective in treating apnea, and thus may add to the
effectiveness of theophylline. This may help explain
why lower theophylline serum concentrations may be Drugs for pediatric patients should be dosed on a mg/kg
needed for apnea rather than asthma. In addition, the or a mg/m2 basis using information available for the
presence of the 4-en metabolite of valproic acid noted in patient's age group. In addition, the patient's renal and
the serum of infants and young children, but not adults, hepatic functions must be considered. The route for
receiving this medication for seizures may be respons- administration must be determined based on the severity
ible for the hepatoxicity of this drug in young pediatric of the illness, the availability of the medication for a
patient~.[~~'~~] particular route of administration, and whether the patient
is able to take a medication orally.
Serum Drug C ~ n c e ~ t r a t i o ~ § The Bibliography succeeding the References at the
end of this chapter contains a list of handbooks and
Because of the cost associated with therapeutic drug other references that are useful sources of dosing infor-
monitoring, serum drug concentrations must be drawn mation for neonatal and/or pediatric pediatrics. In addi-
appropriately to provide useful information. Drugs tion, drug information centers in pediatric hospitals or
typically followed pharmacokinetically are those with university settings are another excellent resource for
narrow therapeutic indexes for which there is an as- pediatric drug information.
sociation between pharmacokinetic and pharmacodyna-
mic data or toxicity. For many drugs, especially for those
administered orally, the determination of trough concen-
trations (serum concentrations obtained prior to adminis- IN MEDICATIONS
tration) may be most appropriate. This eliminates dif-
ferences in absorption rates that could influence peak Pharmaceutical products may contain, in addition to the
concentrations (e.g., orally administered phenobarbital, active or therapeutic agent(s), a variety of other ingre-
phenytoin, carbamazepine, or valproic acid). Trough con- dients that are termed inactive or inert that are categorized
centrations may be important for drugs such as digoxin as excipients or additives (flavorings, sweeteners, pre-
that take time to distribute to tissue receptors in such a servatives, stabilizers, diluents, lubricants, etc.). The
way that serum concentrations reflect pharmacodynamic words inert or inactive are misnomers for some excipients
effects. Peak concentrations are best used for determin- because some have been shown to cause adverse effects.
ing toxicity and therapeutic effects of drugs with short Neonates and young children are at risk for such adverse
half-lives. effects, because they may not be able to metabolize or
Table 2 gives therapeutic serum concentrations and eliminate an ingredient in a pharmaceutical product in the
pharmacokinetic information for some drugs administered same manner as an adult. In addition, patients of various
to pediatric patients. ages have experienced allergic reactions to excipients
such as tartrazine dyes.
Technical Factors Benzyl alcohol is a preservative that may be present in
multidose vials of bacteriostatic sodium chloride and
Sample size and timing of blood drawing bacteriostatic water for injection and pharmaceuticals
for serum concentration determination available in multidose vials for parenteral use. An
association between the presence of benzyl alcohol in
Because of the small blood volume and the small size of solutions used for flushing intravascular catheters and to
veins, it is technically difficult to draw blood from reconstitute medications and a gasping syndrome and
neonates, infants, and young children for therapeutic deaths in neonates was first reported in the early
drug monitoring, and it is therefore important to 1980s.[40,411 The neonates also displayed clinical findings
determine the best drawing schedule. For example, when such as an elevated anion gap, metabolic acidosis, CNS
are peak and trough data needed compared to trough depression, seizures, respiratory failure, renal and hepatic
data only? For anticonvulsants administered orally or failures, cardiovascular collapse, and death. Those at
i.v., trough concentrations are needed, whereas for highest risk were premature infants who weighted less
Pediatric Dosing and 665
than 1250 g at birth.[40423 In a study by Benda et al., Initially, it was believed that benzyl alcohol was only
premature neonates who survived benzyl alcohol admin- toxic in neonates who received doses greater than 99 mgl
istration were compared to neonates born after the use of kg,[421but it has been suggested that lower doses may be
benzyl alcohol-containing flush solutions was discontin- toxic, resulting in kernicterus and intraventricular hemor-
ued.rd31They noted that survivors had a higher incidence r h a g e ~ . [ ~Therefore,
~ ' ~ ~ ] pharmaceutical preparations and
of cerebral palsy (50%) compared to infants who did not fluids containing benzyl alcohol should be avoided in
receive benzyl alcohol flushes (2.4%) (P < 0.001). In ad- premature neonates.
dition, the incidence of cerebral palsy and developmental Benzoic acid and sodium benzoate are added in low
delay was 53.9% versus 11.9% in the two populations concentrations to various pharmaceutical preparations as
(P < 0.001). The cause is probably associated with benzyl bacteriostatic and fungistatic agents. Hypersensitivity
alcohol use and the inability of neonates, especially those reactions to benzoates have occurred when administered
who are premature, to adequately metabolize benzyl al- to allergic patients, such as those with asthma, those who
~ o h o l . [ The
~ ~ ] American Academy of Pediatrics,[451the do not tolerate aspirin, and those with a history of urti-
Centers for Disease Control,[461and the FDA[471recom- aria.[^^] Hyperbilirubinemia and systemic effects attrib-
mend that the administration of products containing ben- uted to benzyl alcohol may occur in premature neonates
zyl alcohol be avoided in infants. Preservative-free i.v. because benzyl alcohol is metabolized to benzoic
flush solutions are acid.[441
666 Pediatric Dosing and Dosage Forms
Propylene glycol is found as a solvent in some i.v. when an ethanol-containing product is used in conjunc-
multiple vitamin preparations and a variety of pharma- tion with medications such as metronidazole, sulfo-
ceutical preparations for parenteral administration in- namides, or chl~ramphenicol.[~~] The CNS effects (mus-
cluding phenytoin, digoxin, and diazepam. MacDonald et cle incoordination, a longer reaction time, behavioral
al.[501noted that neonates who received MVI-12 (pro- changes) are the most commonly reported acute adverse
pylene glycol dose of approximately 3 g/day) versus those reactions associated with ethanol ingestion. Such reac-
who received MVI concentrate (propylene glycol dose of tions have occurred with blood ethanol concentrations in
approximately 300 mg/day) had a significant increase in the range of 1- 100 mg/100 ml.[571Lethal ethanol doses
seizures. In addition, infants in the first group suffered in children occur at approximately 3 g m k g although
from hyperbilirubinemia and renal failure. (Although deaths due to ethanol-induced hypoglycemia have oc-
MVI concentrate is no longer on the market in the United curred at lower doses or because of interactions with
States, it was used in the early 1980s.) other medications.[573581 Chronic ethanol exposure may
Serum hyperosmolality has been reported in infants induce hepatic enzymes, and may thus alter the clearance
who received vitamin preparati~ns,[~'j and in burn pa- of drugs such as phenytoin, phenobarbital, and war-
tients due to the topical absorption of propylene glycol- f a r i r ~ . [ ~Examples
~] of other additives that have been
containing In addition, bum patients have problematic in pediatric patients include lactose,[551tar-
experienced metabolic acidosis with a high anion gap, trazine dyes[443551 and s ~ l f i t e s . [ ~ ~ ]
decreased ionized calcium concentrations, acute renal It is therefore important for health care professionals,
failure, and death from topical propylene glycol absorp- and especially those who are responsible for selecting
Problems associated with the oral ingestion of and administering medications to premature neonates, to
propylene glycol-containing products by children include examine pharmaceutical preparations for the presence of
CNS depression, seizures, and cardiac dy~rhythmias.[~~] inactive ingredients as well as for the active drug. The
Mypotension, cardiac dysrythmias, respiratory depres- provision of medications should be based on choosing
sion, and seizures have occurred after the rapid adminis- the safest preparations possible. Various brands of me-
tration of phenytoin that may be associated with the propy- dications should be compared to ensure that products
lene without hazardous excipients. In the hospital setting,
The American Academy of Pediatrics Committee on pharmacy and therapeutics committees and the phar-
Drugs recommends that medications intended for pediatric macy department play important roles in this process
use be ethanol free.[571If, because of stability or solubility because they compare pharmaceutical preparations for
problems with the active ingredients(s), liquid medications formulary selection. In the outpatient setting, physicians
need ethanol as an ingredient, but they should not contain and pharmacists must responsibly select the most
more than 5 % v/v ethanol.[571The Academy also recom- appropriate brand of a particular medication. Kumar
mends that the ingestion of a single dose of an ethanol- et a1.[601 recommend that labeling for pharmaceutical
containing product by a pediatric patient should not result products should include the names and the amounts of
in blood ethanol concentrations greater than 25 mg/100 excipients as well as active ingredients to help health
mL, the volume of a packaged liquid medication should be care professionals select appropriate drug products
of a minimal amount so that its entire ingestion would not for neonates.
result in a lethal dose and safety closures should be on all
medicinals containing greater than 5% v/v ethanol. In
addition, the Academy suggests that children under 6 years
of age who need an ethanol-containing OTC preparation
be under medical supervision and that doses of any etha- Without being properly instructed about methods used for
nol-containing product be spaced at intervals to avoid administering i.v. medications to pediatric patients, health
ethanol accumulation.[571 care personnel may give a medication incorrectly, re-
The Academy of Pediatrics made their recommen- sulting in an inappropriate or unexpected therapeutic res-
dations concerning ethanol exposure from medications ponse. Therefore, it is important that health care personnel
based on potential acute and chronic ethanol-related (nurses, physicians, pharmacists) understand how medi-
problems. Acutely, the coadministration of ethanol may cations are administered by this route.
alter drug adsorption or metabolism, and may result in The i.v. route is most frequently chosen for medication
drug interactions (e.g., increased sedation when taken delivery when a patient's clinical condition requires that a
with sedatives). Disulfiram-like reactions have occurred medication be administered by the most expeditious and
after the ingestion of an alcohol-containing medication or complete method possible. In addition, some drugs are
Pediatric Dosing and Dosage Forms 667
only available for i.v. administration. Although this route their study using an in vitro system for drug adminis-
is the most reliable for drug delivery to the systemic tration (Fig. 1) that infusion rates as well as the location
circulation, problems can occur that reduce and/or delay of the injection sites in the i.v. infusion system influence
medication delivery because of the product selected, the infusion profile of i.v. administered medications.
dosage volume needed, or frequency of administration, Fig. 1 shows the effects of different i.v. fluid rates on
but problems can also be associated with the i.v. delivery the length of time to infuse 95% of a gentamicin dose
system used. The latter occur most frequently when a administered at various sites in the infusion system.[631
small medication volume is administered at a slow rate as It was reported that at a slow infusion rate of 3 ml/h, a
is often needed for a neonate or young infant. A brief drug takes longer to be infused and that the time for
discussion of problems associated with i.v. drug delivery infusion time depends on the site of administration (i.e.,
to pediatric patients is given here. A thorough overview of the further the drug injection from a patient, the longer
i.v. drug administration to pediatric patients is provided in to administer 95% of the medication, see Fig. 2 ) . Thus,
Refs. [61] and [62]. it took approximately 400 min to infuse gentamicin at
an infusion rate of 3 m l h via a Y-site in the admi-
Disposable IV Equi nistration system. However, the same drug administered
on Drug Delivery at a butterfly injection site at the same fluid flow rate
reduced the length of time to administer 95% of the
Infusion rates and location of injection sites drug to less than 20 min. Gould and Roberts also stated
that the time needed for drug administration in their i.v.
The first article to explore problems that can occur with system was longer than what had been expected.[631
i.v. drug delivery to pediatric patients was published in
1979 by Gould and Roberts.[631 They demonstrated in Type of injection site
qv = Pr4
4nL
2
.- 40
:'
f - i
i
s
', ',
x ET
x
20
0 '.. --___\\ , ,\
0 , k.. 1 T----.-- ,
0 40 80 120 160 200 240 280 320 360 400
Flashball Injection Site
100 - .____
-. ',
~
,
..-.
. Metriset Injection Site
,s'
-
Infusion Rates:
3mVhr
- - - - - IOmlihr
-
Infusion Rates:
- - - - +
3mlihr
lOmVhr
- - - - - -,25mVhr
,_. _. - , 100mVhr
x
0 40 80 120 160 200 240 280 320 360 400 0 40 80 I20 160 200 240 280 320 360 400
Time (Minutes) Time (Minutes)
Fig. 2 Influence of i.v. flow rate on the infusion profile of gentamicin. (From Ref. [61].)
es of Intravenous
Manual administration is not as accurate as using a Fig. 3 Examples of retrograde system setups. (From Leff,
syringe pump for drug administration. It has been used for R.D.; Roberts, R.J. Methods for intravenous drug administration
small volumes of medication (<3 ml), a low flow rate in the pediatric patient. J. Pediatr. 1981, 98, 631-635.)
(<20 mlh), or if the antegrade (forward toward the
patient) injection of a drug bolus is safe.[611If a med-
ication is to be administered antegrade, it should be and ability to detect occlusions. Other important factors
administered slowly into a microinjection site toward the include an alarm system, ease of operation, ability to be
patient; microbore tubing should be placed between the cleaned easily, and safety from children inadvertently
injection site and the patient to reduce the time to get the trying to change pump settings. A syringe pump is best
drug to the patient. Leff and Roberts[611recommended for delivering small dosage volumes and when intermit-
that the volume of the drug to be injected by the antegrade tent intervals are needed for medications. It is the
technique should be a smaller volume than the tubing mechanical device most often selected for medication
fluid volume between the injection site and the patient. If administration because it can be used for intermittent
the medication volume is too large to be safely given by administration of small and large doses, or for the
antegrade administration, but the i.v. fluid flow rate is low continuous infusion of medications at low rates. A drug
(< 20 ml/h), the drug may be administered by a retrograde can be administered separately from the primary i.v. fluid
technique (Fig. 3). flow rate, with the drug and the fluid mixing for a short
distance therefore in microbore tubing (see Fig. 4) before
Mechanical system for drug administration reaching the patient. In addition to being able to more
accurately deliver medications than by manual methods,
If a mechanical system is chosen for drug administration, syringe pump systems have the advantage of being able
the appropriate infusion device must be selected based on to separate the administration of incompatible drugs,
its operating mechanism, flow accuracy, flow continuity, reduce difficulties associated with the administration of
670 Pediatric Dosing and Dosage Forms
A ~ I O NOF ORAL ~ E ~ I ~ A T I
- Syringe infusion
Pump
The oral route is typically the preferred route for medi-
cation administration to pediatric patients. Other routes
may be used, if the patient cannot take a medication orally
because of vomiting, being unable to swallow, or the
medication is unavailable for oral use. In addition, for
stopcock
specific problems it may be better to deliver the medica-
Fig. 4 Syringe pump setup with drug administered separately tion directly to the area being treated, for example, inha-
of the primary i.v. fluid flow rate. Mixing of the drug and i.v. lation, ophthalmic administration, or otic administration.
fluid occurs at a stopcock and for a short distance in microbore
tubing. (From Leff, R.D.; Roberts, R.J. Methods for intravenous osage Forms
drug administration in the pediatric patient. J. Pediatr. 1981, 98,
63 1-635.)
Oral liquids
multiple doses, and shorten the time required to ad- Liquid medications are the most commonly administered
minister medications. oral medications to pediatric patients because of the ease
of swallowing by infants and young children who cannot
dditional Comments About swallow solid dosage forms. However, availability of
some medications as liquid formulations may be limited.
If not available in liquid form, a solid dosage form may
Reed and Galt6] recommended the following steps to need to be modified by the pharmacist, other health care
decrease problems associated with i.v. drug administra- provider, or by the parent. If a solid dosage form is mo-
tion to pediatric patients: dified, for example a suspension is prepared, will the drug
be stable and for how long, and will it be absorbed
1. Standardize and document total time for drug differently than the original dosage form? These are just
administration. a few questions that must be answered about the ex-
2. Document the volume of any solution used to flush temporaneous preparation of a drug product for a pediat-
an i.v. dose. ric patient.
3. Standardize infusion techniques for drug adminis- Alcohol-free products should be selected for pediatric
tration, especially for those with a narrow thera- patients whenever possible. Furthermore, the inactive
peutic index. ingredients or excipients contained in an oral preparation
4. Use the largest gauge cannula that can be used. should be identified. This is especially important if the
5 . Standardize dilution and infusion volumes for patient is known to have had an adverse reaction to a
drugs given by intermittent i.v. injection, and particular excipient or there is another reason to avoid a
avoid attaching lines for drug infusion to a central particular additive in a medication. The Committee on
hub with solutions infused at widely disparate Drugs of the American Academy of Pediatrics recom-
rates, and mended that pharmaceutical products contain a qualitative
6. Use low-volume i.v. tubing and use the most distal listing of inactive ingredients in order that products
sites for drug administration. containing these substance could be avoided in patients
who had problems with specific adjuvants.1551 Kumar
In addition, one must remember that for infants the et a1.[601contains lists of inactive ingredients (sweeteners,
amount of fluid required for drug administration may take flavorings, dyes, and preservatives) found in many liquid
away from the amount of fluid available for nutrition. medications such as analgesics, antipyretics, antihistamine
Thus, with medication administration, the fluid volume decongestants, cough and cold remedies, antidiarrheal
must be as restrictive as possible so that the bulk of the agents, and theophylline preparations. The authors of the
Pediatric Dosing and 671
Table 3 Osmolalities of liquid pharmaceuticals for suspensions must be prepared. An excellent information
oral administration source about the preparation of liquid dosage forms for
smolality (mean §EM) pediatric patients has been published by Nahata and
Hipple (Nahata, M.C., Hipple, T.F. Pediatric Drug
Propylene glycol 8326 f 1467 Formulations, 4th Ed. Harvey Whitney Books: Cincin-
Saccharin-containingdrugs nati, 2000).
Albuterol 65
Haloperidol 47
Suspensions 2500 * 246
Product selection
Sugar-containing”drugs 5574 f 594
“Sucrose, mannitol. glucose. and others. Products for oral administration should be in a dosage
(From Ref. [66].) form most readily taken by the child. If the child is old
enough to participate in the decision-making process, he
or she may state a preference for a liquid, chewable tablet,
previous article and Golightly et al. have reviewed adverse tablet, or capsule, if the needed drug is available in a
effects associated with many inactive ingredient^.'^^'^^] variety of dosage forms and appropriate dosage. If a liquid
Liquid medications, taken orally, can cause diarrhea medication is needed, a product should be chosen based
and other GI symptoms, or they may aggravate GI distress on texture, taste, and ease of administration. Other factors
that a patient is already experiencing. These GI effects that must be considered are the absence of alcohol and
can be associated with the high osmolality of some oral dyes, and an osmoIality that is close to physiologic (280-
liquids. Qsmolalities have been determined for various 290 mOsm/kg). Are there excipients or adjuvants in the
oral liquids.i661 For preparations containing propylene product, and if so, what are they and what is their
glycol. or various sugars (e.g., sucrose, mannitol, glu- concentration? Is there bioavailability information or
cose), osmolalities were noted to be high (see Table 3). It pharmacokinetic information for the oral medication in
is important to compare various brands of liquid me- pediatric patients, and if so, in what age groups? Is there
dications because they may contain different excipients information about the extemporaneous product that is to
and may have different osmolalities. be prepared?
Rebecca Chater, a North Carolina pharmacist, recom-
ust s mends that pediatric patients be involved in medication
counseling in order to improve their understanding of why
Most medications have shorter half-lives in children than a medication is needed. In the counseling process, the
in adults, and therefore children may need sustained- word medication should be used and not drug because of
release products to maintain serum concentrations in the the connotation associated with the latter in today’s
therapeutic range. For example, a sustained-release Chater recommends that, when possible, a
theophylline product may be needed for a child with product be selected that requires the fewest number of
asthma. It may need to be administered every 8 h to the doses administered per day, for example, every 12 h
child as compared to every 12 h for a healthy, non- dosing rather than every 8 h, so the medication does not
smoking adult to maintain therapeutic serum concentra- need to be taken to school or day care for administration.
tions. When choosing a sustained-release theophylline If a medication must be given outside of the home, she
preparation for a child, it must be remembered that recommends that two small labeled bottles be dispensed
because of differences in release properties, theophylline or one large bottle with a small empty bottle labeled to be
sustained-release products are not interchangeable. A used for medication administration at day care or school.
product selected for the pediatric asthma patient should be Health care providers including nurses, pharmacists,
reliably absorbed with a minimal serum concentration and physicians should demonstrate to parents and older
variation and not a preparation that has exhibited a children how medications should be administered and
difference in bioavailability when administered with or offer appropriate dosing devices (oral syringe, dropper,
without food.[67-691 cylindrical medication spoon, or a small-volume doser
with attachable nipple) to enable parents to accurately
Extemporaneous liquid preparations measure liquid products. A household teaspoon or
tablespoon should not be used for medication adminis-
Because many medications are not available as liquid tration because they are inaccurate. Kraus and Stohl-
preparations, there are times when powder papers or meyerL7’] explain the use of a new oral liquid medication
672 Pediatric Dosing and Dosage Forms
delivery system that can be used for infants and young the mouth may result in gagging or choking. The oral
children who still use a bottle for feeding. syringe should be of an appropriate size to allow for
administration into the inner cheek.
The following information is presented to help health care Oral solid dosage forms
providers counsel parents and older children on how
medication should be administered by various routes. A medication available only as a solid dosage form, may
be prepared as an extemporaneous liquid (e.g., suspen-
Oral liquids sion) or it may be modified for oral use, for example, by
crushing. As mentioned previously, a sustained-release
An oral liquid medication needed for an infant or young product should not be crushed or chewed. For a solid,
child should be shaken well, if required, and then ad- nonsustained-release medication, the product can be
ministered accurately using an appropriate device. If a crushed and mixed with a small amount of food just
dropper or an oral syringe is used, the liquid should be prior to administration. Examples of foods that may be
administered toward the inner cheek. Administration in used for mixing include applesauce, yogurt, or instant
the front of the mouth may allow the child to spit out the pudding, but the medication should not be added to an
medication, whereas administration toward the back of entire dish of food or to infant formula, because the infant
Fig. 5 A technique for anterior lateral-thigh intramuscular injection. (From Ref. [ 191.)
Pediatric Dosing and Dosage Forms 673
or child may not eat/drink the entire portion and thus not this injection site, and it occurs more commonly in infants
receive the total amount of medication. because of their lack of gluteal muscle mass.[731Injury to
the gluteal nerve, resulting in muscle atrophy, has
occurred even when the injection technique was appro-
OT TES priately perf~rmed."~'Other nerves including the pu-
dendal, posterior femoral cutaneous, and the inferior
cluneal nerves have been damaged because of poor
injection technique. [ 91 Additional adverse effects asso-
Absorption of i.m. administered medications depends on ciated with this drug administration route are discussed by
the injection site because perfusion of individual muscle Bergeson et al.[191
groups differs. For example, drug absorption from the A technique for gluteal administration is shown in
deltoid muscle is faster than that from the vastus lateralis Fig. 6 although other techniques are also used."g1 All
that is more rapid than from the g l ~ t e u s . " ~In
" ~addition,
~ techniques involve the determination of the upper outer
lower perfusion or hemostatic decompensation, frequently quadrant (see Fig. 6 for anatomical landmarks). After the
observed in ill neonates and young infants, may reduce location of the upper outer quadrant is determined, the
i.m. absorption. It may also be decreased in neonates who needle should be inserted at a 90" angle to the surface on
receive a skeletal muscle-paralyzing agent such as which the patient is lying."" This site can be used for
pancuronium because of decreased muscle contraction. older children. A 1-in. (2.5-cm) needle has been recom-
In addition, the smaller muscle mass of neonates and mended."'] The volume of drug that can be administered
young infants provide a small absorptive area. in this manner is 0.1-5 ml for older children and adults."']
The injection technique and the length of the needle The ventrogluteal (gluteus medius and minimus) site
used may affect drug absorption, and thus serum con- may be less hazardous for i.m. administration than the
centrations. For example, using a longer needle (1 1/2 vs. 1 dorsogluteal (gluteus maximus) site."g1 The technique is
1/4 in. or 3.8 vs. 3.1 cm.) for i.m. administration resulted shown in Fig. 7.[19]The person administering a drug i.m.
in higher diazepam serum concentrations in adults."'] ventrogluteally should first note the anatomical landmarks
Therefore, it is important to select the appropriate site (anterior superior iliac spine, tubercle of the iliac crest,
for drug administration as well as the appropriate length and upper border of the greater trochanter). The needle is
and needle bore. Sites that can be used for i.m. ad-
ministration include anterior thigh and vastus lateralis,
gluteal area and deltoid.
The midanterior thigh (rectus femoris) and the middle
third of the vastus lateralis are used for i.m. administration
to young infants as well as to older ~hildren."~]These
sites are better developed and larger than other muscle
groups that are used for drug administration to older
children or adults. The technique is shown in Fig. 5.[19]
With the patient lying supine, the "needle should be
inserted in the upper lateral quadrant of the thigh, directed
inferiorly at an angle of 45" with the long axis of the leg
and posteriorly at a 45" angle""" to the surface on which
the patient is lying. The person administering the injec-
tion should compress the tissues of the injection site to
help stabilize the extremity. A 1-in. (2.5-cm) needle has
been recommended for pediatric patients by Bergeson
et al.1191while Newton et a1.[18] recommend a 23-26
gauge 11/2-in. (3.8-cm) needle. The volume of drug that
can be administered in this manner is 0.1-1 ml in in-
fants and 0.1-5 ml in older children and adults."s1
The gluteal musculature develops as the infant or child
increases his or her mobility; it becomes a more suitable
injection site in children who are ~ a l k i n g . " ~Damage
"~~ Fig. 6 A technique for gluteal-area intramuscular injection.
to the sciatic nerve is the major problem associated with (From Ref. [19].)
674 Pediatric Dosing and Dosage Forms
Ot ic Adrn inistration in order to spread the medication across the eyeball and be
absorbed if the effect is to be systemic.[761In addition,
Otic preparations should be at room temperature prior to it has been recommended to gently put pressure on the
administration. If the otic product is a suspension, it inside corner of the eye for 3-5 minutes to retard
should be gently shaken for approximately 10 sec. before drainage of the m e d i ~ a t i o n . ' ~Do
~ ]not use the eyedrops if
a d m i n i ~ t r a t i o n . ' ~Prior
~ ] to otic administration, the in- they have changed color or if there is any particulate
dividual administering the medication should wash their matter in the ophthalmic solution. The dropper should not
hands thoroughly. The child should be lying on his or her be rinsed after use because this could lead to contamina-
side, and the earlobe should be gently pulled down and tion of the dropper and the medication. The package insert
back to straighten the outer ear canal (for adults the should be reviewed for specific information.[761
earlobe is pulled up and back). Then the prescribed Another method for administering eyedrops to
number of drops should be instilled into the ear without children recommends that the drops be applied to the
placing the dropper in the ear canal. The patient should be inner canthus of the eye while the patient keeps hisher
kept in a position with the ear tilted for approximately 2 eyes closed until told to open them after medication
min to help keep the drops in the ear.'75' This procedure administered.[771 Approximately 66% of the medication
may be repeated for the treatment of the other ear, if administered in this fashion was absorbed. In addition,
needed. The tip of the dropper should wiped with a clean this method may increase compliance and make children
tissue after use. more cooperative.
For the administration of an ophthalmic ointment to a
child who can cooperate, the child should tilt his or her
head backwards and look up. After the hands have been
washed, the person to administer the medication should
For adults, the first step in administering nose drops or squeeze out and discard the first 0.25 inches of ointment
a nasal spray is blowing the nose to clear the nasal and discard it. Thereafter, the eyelid(s) should be gently
passages of mucus and other secretions, but infants and pulled down for drug administration. A thin layer of
young children are unable to do this. Therefore, the nasal ointment (0.25-0.5 inches) should then be placed in the
passages may need be cleared with a bulb syringe prior lower eyelid(s). Afterwards, the eyelid(s) should be
to medication administration. A child should lie down on closed for 1 to 2 min to allow for the spreading of the
his or her back, or a young infant or child should be medication and absorption. During this process, the tip
placed in a lying position, and the head should be tilted of the ophthalmic applicator should not touch the eye.
slightly backwards. An appropriate amount of medication After administration is completed, the tip of the appli-
should then be placed in each nostril. Thereafter, the cator tube should be cleaned with a clean tissue and be
infant or child should remain quiet for a few minutes to tightly capped.[761The package insert should also be re-
allow the medication to be absorbed. The dropper should viewed for specific information.
be rinsed with hot water before it is returned to the
medication container. Inhalers
2. Food and Drug Administration. Regulations Requiring 18. Newton, M.; Newton, D.; Fudin, J. Reviewing the big three
Manufacturers to Assess the Safety and Effectiveness of injection routes. Nursing Feb. 1992, 92, 34-42.
New Drugs and Biological Products in Pediatric Patients, 19. Bergeson, P.S.; Singer, S.A.; Kaplan, A.M. Intramuscular
21 CFR Parts 201, 312, 314, and 601, Docket No. 97N- injections in children. Pediatrics 1982, 70, 944-948.
0165; U.S. Department of Health and Human Services; 20. Sagraves, R.; Kamper, C. Controversies in cardiopulmon-
Washington, DC, August 17, 1997. ary resuscitation: Pediatric considerations. DICP, Ann.
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105th Congress. Washington, DC, 1997. 21. Ghadially, R.; Shear, N.H. Topical Therapy and Percutan-
4. Food and Drug Administration. List of Approved Drugs f o r eous Absorption. In Pediatric Pharmacology: Therapeutic
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49. Jadine, D.S.; Rogers, K. Relationship of benzyl alcohol to June 1991, 48, p-35, Abstract.
kernicterus, intraventricular hemorrhage, and mortality in 67. Maish, W.; Sagraves, R. Childhood asthma. U.S. Phar-
preterm infants. Pediatrics 1989, 83, 153- 160. macist 1993, Jan., 36-58, 105.
50. MacDonald, M.G.; Getson, P.R.; Glasgow, A.M.; Miller, 68. Hendeles, L.; Weinberger, M.; Szefler, S. Safety and
M.K.; Boeckx, R.L.; Johnson, E.L. Propylene glycol: efficacy of theophylline in children with asthma. J. Pediatr.
Increased incidence of seizures in low birth weight infants. 1992, 120, 177-183.
Pediatrics 1987, 79, 622-625. 69. Hendeles, L.; Weinberger, M. Selection of a slow-release
thcophylline product. J. Allcrgy Clin. Immunol. 19
743-751.
70. Martin, S. Catering to pediatric patients. Am. Phar Hurriett Lane Handbook, 15th Ed.; Sibenry, G.K., Iannone, Eds.;
32, 47-50. Mosby: St. Louis, 2000.
71. Chater, R.W. Pediatric dosing: Tips lor tots. Am. Pharm. I,eff, R.D.: Roberts, R.J. Pmctical Aspects o f Intravenous Drug
1993. 33, 5 5 56. Administration; American Society of Health-System Pharma-
72. Kraus, D.M.: Stohlmeyer, L.A.; Hannon, P.R. Infant ' Bethesda, 1992.
acceptance and effectiveness of a new oral liquid Nahata, M.C.: Hipple, T.F. Pediatric Drug Formulations, 4th
cation delivery system. Am. J. Health-Syst. Pharm. Ed.; Harvey Whitncy Books: Cincinnati, 2000.
56, 1094 1101. Nelson, J.; Bradley, J. Nelson's 2000-2001 Pocket Rook of
73. Gilles, F.H.; Matson, D.D. Sciatic nerve injury following Pediatric Antinzicrobial Zherapy, 14th Ed.; Lippincott Wil-
misplaced gluteal injection. J. Pediatr. 197'90,76, 247-254. liams &L Wilkins: Philadelphia: 2000.
74. Administration guides. Drug Store News 8993, Dec.. / 3 . Phelps, S.; Hak: E. Guidelines,for Administmtioiz qflntravenous
7-14. Medications to Pediatric Patients, 6th Ed.: American Society
7s. Proper Use of Ear Drops. In Facts and Comparisons: of Health-System Pharmacists: Bethcsda, 1999.
Burnham, T.H., Ed.; Walters Kluwer Co.: St. Louis, Taketomo, C.K.: Hodding, J.H.; Kraus, D.M. Pediatric Dosage
January 2000; 1802. Handhook, 8th Ed.; Lexi-Comp., Tnc.: Hudson, OH, 2002.
76. Recommended Procedures for Administration of Solu- The Pedicitric Drug Handbook, 3rd Ed.; Benitz, W.E., Tatro,
tions or Suspensions (Ophthalmics). In Fact.r and C o n - D.S., Davis, S., Eds.: Harcourt Hcalth Sciences Group: St.
pari.mns; Burnham, T.H., Ed.: Walters Kluwcr Co.: St. Louis, 1995.
Louis, January 2000; 1725. Young, T.; Mangum. B. Neqfiix 2000, 13th Ed.; Blackwell
71. Smith, S.E. Eyedrop instillation for reluctant children. Br. Science: Oxford, 2000.
J . Ophthalmol. 1991, 75, 480 481.
PROFESSIONAL DEVELOPMENT
ia ctice
Marcia L. Buck
University of Virginia Medical Center,
Charlottesville, Virginia, U.S.A.
formulations has been targeted by the FDA.["] In October their study of the impact of pharmacy intervention on
1992, the FDA took the first steps toward improving the medication errors in two children's hospital^."^] The
amount of pediatric information available on drug labeling pharmacists in this study detected, and prevented, mis-
as part of their ruling entitled, ''Specific Requirements on takes at a rate of 5 errors per 1000 medication orders. The
Content and Format of Labeling for Human Prescription majority of the errors (64%) occurred in children younger
Drugs: Revision of 'Pediatric use' Subsection in the La- than 2 years of age. This study received considerable
beling." These new regulations were designed to promote attention in both the medical and lay press. It continues to
the inclusion of information gained from new clinical trials serve as a landmark citation for the support of pharmacist
as well as information gained from previously published participation in pediatric acute care. In addition to error
studies and case reports in children. In an effort to support prevention and cost savings, pediatric pharmacists have
this research, a network of pediatric pharmacology units also documented their value in their contributions to our
(PPRUs) were created at medical centers throughout the knowledge of medication use in children. It is now com-
United States. Many of the PPRUs include pharmacists as mon for studies of new drugs in children to have at least
investigators. Further progress was made in December one pharmacist a ~ t h o r . [ ' ~ -Pharmacists
*~] have also added
1994, when the FDA announced plans to mandate labeling to our knowledge of pediatric medicine by publishing
information on pediatric use for all pertinent new drug case reports describing drug interactions and toxicities."']
applications. Manufacturers also were required to examine In addition, pharmacists have conducted studies of ex-
their existing products to determine if there was adequate temporaneous oral liquid formulations and intravenous
cause to modify their pediatric sections to include more drug compatibility, which have alleviated many of the
specific pediatric dosing and safety information. problems with pediatric drug a d m i n i s t r a t i ~ n . [ ' ~ , ~ ~ ]
As anticipated, this ruling generated considerable con-
cern on the part of manufacturers who saw this as a po-
tential roadblock to drug approval for adults patients and PE Y RE ES
an additional expense. The FDA took a stronger stance on
November 21, 1997, with the enactment of the Modern- Pediatrics, unlike most other areas of pharmacy practice,
ization Act. This ruling was the first major amendment of encompasses a wide variety of disease states. Clinical
the Food, Drug, and Cosmetic Act and was designed to pharmacists must not only have an understanding of the
incorporate changes for the twenty-first century, including effects of growth and development on drug disposition,
advances in technology and trade practices, as well as but also a general appreciation for therapies related to
changing public health concerns. The Modernization Act disease in any organ system. Despite the complexity of
covers many different aspects of the drug approval pro- this patient age group, relatively little emphasis is given to
cess, such as fast track policies, industry guidance, and pediatrics in most pharmacy school curricula. In a survey
postmarketing studies, but one of the most significant of pharmacy schools, an average of 16.7 hours was de-
changes has been the tightening and enforcement of voted to pediatric didactic content.[211Most pediatric
regulations relating to pediatrics. The complete Modern- pharmacists develop their knowledge base in the clinical
ization Act became effective on April 1, 1999, and an setting, beginning with experiential training during
increase in industry-sponsored research has already been postgraduate programs and continuing throughout their
observed. It is anticipated that the implementation of the careers. There are a number of resources available to
Modernization Act will usher in a new era in pediatric provide information on pediatric medications for those
drug research and provide opportunities for many pe- beginning their study of pediatric pharmacy. Table 1
diatric pharmacists to contribute to the expansion of our provides a list of topics that may serve as a guide for
knowledge of pediatric therapeutics. developing a basic knowledge of pediatric therapeutics.
Refere~c ~
Texts
DOC FIT
Fortunately for students and new practitioners, the phar-
The benefits of having a clinical pharmacist within a macotherapy texts most frequently required for didactic
pediatric practice setting have been documented in several therapeutics courses contain introductory chapters on
different ways. Reducing medication errors and patient pediatric^.[*^-^^] These general chapters can be very help-
costs have been the primary methods by which new or ful as brief overviews to pediatric specialty practice.
additional pediatric pharmacy positions have been General pediatric texts, such as the Nelson Textbook of
j ~ s t i f i e d . " ~ "In~ ~1987, Folli and colleagues published Pediatrics, are also useful to provide a basic understand-
Pediatric Pharmacy Specialty Practice 681
Table 1 Pediatric topics for clinical pharmacists the Pediatric Dosage Handbook and the Handbook of
Pediatric Drug T h e r ~ p y . [ * ~ Both
* * ~ ] of these references
~~
reign countries, such as Canada’s MotherRisk program. veillance studies such as a retrospective review of methyl-
Like many of the handbooks and references described phenidate These policy statements, guide-
earlier, this text lists drugs by generic name in alpha- lines, and reviews will make useful additions to the files
betical order, making it easy to use for quick consulta- of most pediatric clinical pharmacists.
tions. A separate quarterly update subscription is also
available from the publisher.
Source URL
Agency for Healthcare Research and Quality www.ahrq.gov
American Academy of Pediatrics www.aap.org
American College of Clinical Pharmacy www.accp.com
Centers for Disease Control and Prevention www.cdc.gov
Food and Drug Administration (FDA) www.fda.gov
FDA Pediatric Medicine Page www.fda.gov/cder/pediatric/index.htm
Harriet Lane Links www.med.jhu.edu/peds/hll
Institute for Safe Medication Practices www.ismp.org
Kids Meds www.kidsmeds.org
MedWatch (Adverse Event Reporting) www.fda.gov/medwatch
Neonatal and Paediatric Pharmacists Group www.nppg,demon.co.uk
Pediatric Critical Care Medicine www.pedsccm.org
Pediatric Pharmacy Advocacy Group www .ppag.org
PEDINFO www.pedin fo.org
U.S. Pharmacopeia: Children and Medicine www .usp.org/informationlprograms/children
Vaccine Adverse Event Reporting System www.vaers.org
aAccessed June 2002
Health-System Pharmacists’ Clinical Midyear Meeting. pediatric practitioners to expand our knowledge of drug
PPAG also organizes the Pediatric Adverse Drug Re- disposition in children and improve the quality of their
action Program (PADR), a central database of adverse health care.
effects in children. For more information about this group,
visit their web site at www.ppag.org. Both the ACCP
Pediatrics PRN and PPAG offer a wide array of member
services, including mailing lists for communication
among their members. An international group, the Neo-
natal and Paediatric Pharmacists Group (NPPG), may 1. Buck, M.L. Pediatric Pharmacotherapy. In Pharmacothe-
also be of interest. This organization was formed in rapy SelfAssessment Program, 3rd Ed.; Carter, B.L., Ed.;
1994 to advance the quality of pharmacy services for American College of Clinical Pharmacy: Kansas City,
children in the United Kingdom. Their web site (www. Missouri, 2000; 179-202, Module 9.
nppg.demon.co.uk), offers links to a variety of resources 2. Zenk, K.E. Challenges in providing pharmaceutical care to
pediatric patients. Am. J. Hosp. Pharm. 1994, 51, 688-
and bulletin boards for subgroups in oncology, as well as
694.
pediatric and neonatal intensive care.
3. Nahata, M.C. Lack of pediatric drug formulations. Pe-
diatrics 1999, 104 (3 Supplement Part 2), 607-609.
4. Buck, M.L.; Connor, J.J.; Snipes, C.J.; Hopper, J.E.H.
Comprehensive pharmaceutical services for pediatric
patients. Am. J. Hosp. Pharm. 1993, 50, 78-84.
Pediatric pharmacy practice has come a long way since 5 . American Society of Hospital Pharmacists ASHP guide-
Shirkey first coined the term “therapeutic orphans” to lines for providing pediatric pharmaceutical services in
describe the lack of information and research support for organized health care systems. Am. J. Hosp. Phann. 1994,
children requiring medications.[421As we begin the twen- 51, 1690-1692.
ty-first century, there are a growing number of pediatrics 6. Martin, S. Catering to pediatric patients. Am. Pharm. 1992,
1 (NS32), 47-50.
drug resources available to the health care provider. We
7. Klotz, R. Is the pediatric pharmacist needed? Hosp. Pharm.
have seen the benefits of increased information in the
1971, 6 (7), 18-20.
medical literature, the publication of several pediatric- 8. Cupit, G.C. An approach to pediatric pharmacy practice.
specific dosage handbooks, and the advent of the Internet Hosp. Pharm. 1974, 9 (lo), 399-400, 402.
as a means of sharing information with colleagues. These 9. Oakley, R.S. Pharmacy practice in a small pediatric
changes, along with a renewed interest from the FDA in hospital. Am. J. Hosp. Pharm. 1984, 41, 694-697.
pediatric drug research, are coming together to allow 10. Scott, S.A.; Smith, R.S.; Mason, H.L. Pharmaceutical
684 Pediatric Pharmacy Specialty Practice
services in hospitals treating pediatric patients. Am. J. 25. Behrman, R.E.; Kliegman, R.M.; Jenson, H.B. Nelson
Hosp. Pharm. 1985; 42; 2190-2196. Textbook of Pediatrics, 16th Ed.; W.B. Saunders: Phila-
11. Buck. M.L. Impact of new regulations for pediatric la- delphia, 1999; 2414 pp.
beling by the Food and Drug Administration. Pediatr. Nurs. 26. Pediatric Pharmacology: Therapeutic Principles in Prac-
2000, 26 (1). 95-96. tice, 2nd Ed; Yaffe, S.J.. Aranda, J.V., Eds.; W.B.
12. Tisdale, J.E. Justifying a pediatric critical-care satellite Saunders: Philadelphia, 1992; 663 pp.
pharmacy by medication-error reporting. Am. J. Hosp. 27. Module 9, Pediatrics. In Pharmacotherapy Self-Assessment
Pharm. 1986. 43, 368-371. Program, 3rd Ed; Carter, B.L., Ed.; American College of
13. Folli, H.L.; Poole, R.L.; Benitz, W.E.; Russo, J.C. Med- Clinical Pharmacy: Kansas City, Missouri, 2000; 277 pp.
ication error prevention by clinical pharmacists in two 28. Taketomo, C.K.; Hodding, J.H.; Kraus, D.M. Pediatric
children’s hospitals. Pediatrics 1987, 79 ( 5 ) , 718-722. Dosage Handbook, 8th Ed.; Lexi-Comp, Inc.: Hudson,
14. Findling, R.L.; Preskorn, S.H.; Marcus, R.N.; Magnus. Ohio, 2001; 1302 pp.
R.D.; D’Amico, F.; Marathe, P.; Reed, M.D. Nefazodone 29. Handbook of Pediatric Drug Therapy, 2nd Ed.; Spring-
pharmacokinetics in depressed children and adolescents. J. house Corporation: Springhouse, Pennsylvania, 2000;
Am. Acad. Child. Adolesc. Psych. 2000; 39 (8), 1008- 807 pp.
1016. 30. 2000 Red Book: Report of the Committee on Infectious Di-
15. Erenberg, A,; Leff, R.D.; Haack, D.G.; Mosdell, K.W.; seases, 25th Ed.; Pickering, L.K., Ed.; American Academy
Hicks, G.M.; Wynne, B.A. Caffeine citrate study group. of Pediatrics: Elk Grove Village, Illinois, 2000; 855 pp.
Caffeine citrate for the treatment of apnea of prematurity: 31. Yaster, M.; Krane, E.J.; Kaplan, R.F.; Cote, C.J.; Lappe,
A double-blind, placebo-controlled study. Pharmacothe- D.G. Pediatric Pain Management and Sedation Handbook;
rapy 2000, 20 (6); 644-652. Mosby: St. Louis, 1997; 674 pp.
16. Avent, M.L.; Gal, P.; Ransom, J.L.; Brown, Y.L.; Hansen, 32. Phelps, S.J. Teddy Bear Book. Pediatric Injectable Drugs.
C.J. Comparing the delivery of albuterol metered-dose 6th Ed.; American Society of Health-System Pharmacists,
inhaler via an adapter and spacer device in an in vitro Inc.: Bethesda, Maryland, 2002; 423 pp.
infant ventilator lung model. Ann. Pharmacother. 1999, 33 33. Buck, M.L.; Hendrick, A.E. Pediatric Medication Edu-
(2); 141-143. cation Text, 3rd Ed.; American College of Clinical Phar-
17. Hovinga, C.A.; Chicella, M.F.; Rose. D.F.; Eades, S.K.: macy: Kansas City, Missouri, 2001; 276 pp.
Dalton, J.T.; Phelps, S.J. Use of intravenous valproate in 34. Briggs, 6.6.;Freeman, R.K.; Yaffe, S.J. Drugs in Preg-
three pediatric patients with nonconvulsive or convulsive nancy and Lacration, 6th Ed.; Williams & Wilkins: Balti-
status epilepticus. Ann. Pharmacother. 1999; 33 ( 5 ) : 579- more, 2002; 1595 pp.
584. 35. Committee on Infectious Diseases, American Academy of
18. Zell-Kanter. M.; Toeme, T.S.; Spiegel. K.; Negrusz. A. Pediatrics Recommended childhood immunization sched-
Doxepin toxicity in a child following topical administra- ule-United States, January-December 2001. Pediatrics
tion. Ann. Pharmacother. 2000, 34 (3). 328-329. 2001, 109, 162.
19. Nahata, M.C.; Morosco, R.S.; Hipple, T.F. Stability of 36. Committee on Drugs, American Academy of Pediatrics
mexiletine in two extemporaneous liquid formulations The transfer of drugs and other chemicals into human milk.
stored under refrigeration and at room temperature. J. Am. Pediatrics 2001: 108. 776-789.
Pharm. Assoc. 2000. 40 (2), 257-259. 37. Committee on Drugs, American Academy of Pediatrics
20. Nahata, M.C.; Morosco, R.S.; Hipple, T.F. Stability of la- Guidelines for the ethical conduct of studies to evaluate
motrigine in two extemporaneously prepared oral suspen- drugs in pediatric populations. Pediatrics 1995, 95: 286-
sions at 4 and 25°C. Am. J. Health-Syst. Pharm. 1999, 56, 294.
240- 242. 38. Committee on Drugs and Committee on Hospital Care,
21. Low, J.K.; Baldwin, J.N.; Greiner, G.E. Pediatric phar- American Academy of Pediatrics Prevention of medication
macy education for U.S. entry-level doctor of pharmacy errors in the pediatric inpatient setting. Pediatrics 1998,
programs. Am. J. Pharm. Educ. 1999, 63; 323-327. 102, 428-430.
22. Nahata, M.C.; Taketomo, C. Pediatrics. In Pharmacothe- 39. Andrew, M.; Michelson, A.D.; Bovill, E.; Leaker, M.;
rapy: A Pathophysiologic Approach, 5th Ed.; DiPiro, J.T., Massicotte, M.P. Guidelines for antithrombotic therapy in
Talbert, R.L.. Yee, G.C., Matzke. G.R., Wells, B.G., pediatric patients. J. Pediatr. 1998, 132, 575-588.
Posey, L.M., Eds.; McGraw-Hill: New York, 2002; 69-77. 40. White, S.R.: Yadao, C.M. Characterization of methylphe-
23. Bolinger, A.M.; Chan. C.Y.J.; Zanwill, A.B. Pediatrics. In nidate exposures reported to a regional poison control cen-
Applied Therapeutics: The Clinical Use of Drugs, 7th Ed.; ter. Arch. Pediatr. Adolesc. Med. 2000, 154, 1199-1203.
Koda-Kimble, M.A., Young, L.Y., Eds.; Lippincott 41. University of Virginia Children’s Medical Center webpage
Williams & Wilkins: Baltimore, 2000; 91-1 -91-27. at www.med.virginia.edu/medicine/clinical/pediatrics/
24. Levin, R.H. Pediatric and Neonatal Therapy. In Textbook of CMC/cmchome.html (accessed June 2002).
Therapeutics: Drug and Disease Management, 6th Ed.; 42. Shirkey, H. Editorial comment: Therapeutic orphans. J.
Herfindal, E.T., Gourley, D.R., Eds.; Williams & Wilkins: Pediatr. 1968, 72, 119- 120.
Baltimore, 1996; 1687- 1696.
PHARMACY PRACTICE ISSUES
ss s
Carl E. Trinca
Edward H. Q’Neil
Western University, Pomona, California, U.S.A.
The Pew Commission Reports are a series of forward- The first Commission Report, Healthy America: Practi-
looking documents that critically examine the education tionersfor 2005,[51set the stage for the Commission’s ten-
and training of health professionals in the context of the year agenda by establishing the premise that reform of the
most dynamic decade ever faced by the nation’s system that prepares health professionals is central to
healthcare providers. Anchored by four “Commission” crafting good healthcare policy for the nation. It described
reports, the series is complemented by public policy pa- a framework for change within its view of evolving
pers, task force recommendations, and research reports on healthcare trends, laid out specific challenges to health
such topics as accreditation of educational programs,[’] profession educators and administrators, and proposed an
regulation of the healthcare workforce,[21and federal gra- agenda for action. The Commission made it quite clear that
duate medical ed~cation.‘~’ the success of its work was dependent on broad-based input
and participation from all stakeholders, and it established
advisory panels and health and public policy task forces,
and launched research activities supporting its work.
The following three reports built on this initial
framework. Each provided an updated snapshot of the
Established in 1989 by the Pew Charitable Trusts[41 and
evolving healthcare system in the United States including
administered initially at Duke University and later at the
sections on access, quality, financing. and satisfaction.
University of California-San Francisco’s Center for the
These sections were generally followed by observations
Health Professions, the Commission was “inspired by the
and general recommendations to the healthcare and health
belief that the education and training of health profes-
profession education systems, followed by specific
sionals is out of step with the evolving health needs of the
recommendations to individual professions.
American people.” Since its inception, five values have
Perhaps the most thoughtful and valuable contribution
guided the Commission’s work:
of the Commission was its 1993 presentation Health
Professions Education f o r the Future: Schools in Service
Universal access to basic healthcare services coordi- to the Nation[61and subsequent revisions of competencies
nated by the states, but implemented and supported by (Table 1 ) for successful practice in the 21st century. This
combined federal, state, and private resources. effort has been used uniformly across the health pro-
More efficient use of resources to better manage fessions by schools, professional associations, accrediting
capacity and the outcomes of care while using best agencies, and regulatory bodies.
practices and reducing duplication. Critical Challenges: Revitalizing the Health Profes-
Socially desired outcomes based on empirical evidence. sions f o r the Twenty-first C e n t u ~ , ‘ ~the
] Commission’s
Creativity and innovation through experimentation third report published in 1995, noted that while the federal
with new providers, technologies, administrative struc- government was unable or unwilling to reform the health-
tures, and ways to involve the patient within a modern care system, a number of market-driven forces were at
regulatory framework. work directly challenging the high costs of the system.
Informed choice and greater public responsibility The most controversial recommendations in this Report
through better use of information, decision making, centered on the belief that an oversupply of health
and incentives for behavioral change. professionals was imminent: The numbers of health pro-
Table 1 Twenty-one competencies for the twenty-first century quantifying pharmacists’ perceptions of their education.
Rather, a continuing case was being built for the inclusion
Embrace a personal ethic of social responsibility and service.
Exhibit ethical behavior in all professional activities. of medication use within the context of responsible
Provide evidence-based, clinically competent care. healthcare. Clearly the trends affecting healthcare in
Incorporate the multiple determinants of health in clinical care. general (i.e., coordinated care, diversity and aging,
Apply knowledge of the new sciences. expansion of science and technology, consumer empow-
Demonstrate critical thinking, reflection, and problem-solving erment) would have a profound impact on pharmacy.
skills. The second Report dedicated a chapter to pharmacy and
Understand the role of primary care. introduced the term “pharmaceutical care” as a “res-
Rigorously practice preventive healthcare. ponsible and participatory” process to a broader audience
Integrate population-based care and services into practice. outside of the profession. It was no easy task to suggest
Improve access to healthcare for those with unmet health needs. that pharmacists “contribute to the drug therapy decision-
Practice relationship-centered care with individuals and
making process, including the determination of dose,
families.
schedule, form, and delivery method; provide the
Provide culturally sensitive care to a diverse society.
Partner with communities in healthcare decisions. medication; and monitor patient compliance, progress,
Use communication and information technology effectively and outcomes.”
and appropriately. Specific strategies recommended in the second
Work in interdisciplinary teams. Report included curricular reform, documentation of
Ensure care that balances individual, professional, system, and pharmacist-patient-physician interactions, medication-
societal needs. use information systems, clinical training in non-ins-
Practice leadership. titutional sites, and faculty development. These strat-
Take responsibility for quality of care and health outcomes at egies provided guidance and supported the work of the
all levels. American Association of Colleges of Pharmacy’s Com-
Contribute to continuous improvement of the healthcare system.
mission to Implement Change in Pharmaceutical Edu-
Advocate for public policy that promotes and protects the health
cation“’] and its Center for Advancement of Pharma-
of the public.
Continue to learn and to help others to learn. ceutical Education.
As previously described, the third Report offered a
radical recommendation for pharmacy: “Reduce the
number of pharmacy schools by 20-25% by the year
fessionals entering practice should be reduced by closing
2005.’ ’ The rationale for this recommendation, supported
schools in medicine, nursing, and pharmacy.
with preliminary data, was several-fold:
The Commission’s final recommendations were pre-
sented in its fourth report. Recreating Health Professional 0 Managed care would require a knowledge base and
Practice f o r a New Century[*]built on previous work and, skill set different from contemporary phannacy prac-
as with earlier reports, suggested a strategic guide for tice, more aligned with clinical pharmacy and phar-
changing schools, regulations, and professional practice. maceutical care.
0 Technology, robotics, and technicians could do
the manipulation-intensive work of pharmacists
ACV more efficaciously.
0 Schools were perceived to be moving too slowly to
From the outset, pharmacy practice and pharmaceutical get in step with the evolving healthcare needs of
education figured in the Commission’s agenda. In 1990, the American people. A less controversial recom-
preceding its first report, Perspectives on the Health mendation suggested that pharmaceutical education
Professions[’] was commissioned and the chapter on focus even more on issues of clinical pharmacy,
pharmacy authored by Jack R. Cole and Jere E. Goyan. It system management, and working with other health-
described pharmacy’s evolution as a profession, and care providers.
presented the contemporary challenges facing pharmacy
education and practice. Like other chapters, it served to As one of its five case studies, the third Report
identify common themes and initiate a dialog between the highlighted pharmaceutical care in education and prac-
Trusts, professional leadership, and Commission staff. tice. The Commission specifically chose to offer phar-
Dr. Goyan also participated in the deliberations maceutical education’s experience in the decade:
resulting in the first and second Commission Reports. In
the first Report, little about pharmacy was specifically The process of educational evaluation and reform that has
published except for the results of survey research accompanied this professional evolution can serve as an
Pew Health Professions ~ ~ ~ ~ Reports
~ i s ~ i i ) ~ 687
example as other hcalth professions re-examine their Health Professions Commission: San Francisco, California,
missions in light of ongoing changes in the health care June 1999.
delivery system. 2. Finocchio, L.J.; Dower, C.iM.; Blick, N.T.; Gragnola,
C.M.; Taskforce on Health Care WorkPorce Regulation.
The fourth Rcport set forth three recommendations Strength(,ning Consumer Protection: Priorities f o r Health
for pharmacy, each \upporting the view& of previous Care Workforce Regulation; The Pew Health Professions
Commission: San Francisco, California, October 1998.
Commi\\ion’s work:
3. Pew Health Professions Commission Federal Policy
Taskforce. Beyond the Bulanced Budget Act of 1997:
Continue to orient pharrnaceutical education to reflect
Streiigthrning Feclci-ul G M E Poliry; The Pew Health
pharmacists’ changing practice rolcs and settings un-
Professions Commission: San Francisco, California, Octo-
der managed care and in clinical drug therapy. Re- ber 1998.
fcrenced within this recommendation are various elc- 4. The Pew Charitable Trusts support nonprofit activities in
ments of the 21 competencies and more cinphasis on the areas of culture. education, the environment, health and
residency training. human services. public policy and religion. Based in
Embrace an interdisciplinary approach to healthcare. Philadelphia, Thc Trusts make strategic investments that
Again the competencies are referenced as well as encourage and support citizen participation in addressing
collaboration with pharmacy technicians and other critical issucs effecting social change. In 1999, with more
allied health workers. than $4.9 billion in assets, The Trusts awarded $250
Provide opportunities for re-training and continuing million to 206 nonprofit organizations.
5. Healthy America: Practitioners f o r 2005, an Agenda ,fiir
education for practitioners to develop skill sets for
Action ,Fir U.S. Health ProJessional Schoo1.r; Shugars,
expanded clinical roles beyond dispensing pharma-
D.A., O’Neil. E.H., Bader, J.D., Eds.; The Pew Health
ceuticals. lncluded in this rccommendation is greater Professions Commission: San Francisco. CaliPornia, 1991.
emphasis on distance education and collaboration with 6. O’Neil. E.H. Health Pr(fe.ssioi7.s Eduration ,for the
managed care and chain pharmacy settings in devcl- Future: Schools in Servicx to the Nation; The Pew
oping and delivering re-training programs. Health Professions Commission: San Francisco, Califor-
nia, 1993.
The Pew Charitable Trusts also supported other I. Pew Hcalth Professions Commission. Critical Clzullcnges:
pharmacy-based initiatives during thc 1990s, which wcre Kevitalizing the Health Professions ,for the Twenly-First
stimulated by the work of the Commission. The Pharmacy Cmtuvy; UCSF Center Por the Health Professions: San
Manpowcr Project‘”’ worked with state boards of I:rancisco, California, 1995.
8. O’Neil. E.H.; Pew Health Professions Commission. Rec-
pharmacy to establish B method for monitoring supply
reating Hralth Prt~kssionulPractice ,fiir u New Cmtiiry;
and determining base-line numbers of and demographics
The Pcw Health Professions Commission: San Francisco,
for practicing pharmacists. The Scope of Pharmacy California, December 1998.
Practice Project’I2’ provided a contcmporary update to 9. Pery7ectivc.s on lhe H e d t h Pi-ufe.s.rioa.7; O’Neil, E.H.,
an earlier study that described what pharmacists do in Hare, D.M.. Eds.; The Pew Health Professions Commis-
varioils practice settings. The results of these efforts, and sion: Duke University, Durham, North Carolina, 1990.
thcir respective databases, are available to researchers for 10. 1’uper.r f r o m the Commi.ssion to Implement Chungr in
continuing analysis. Phurmaceulical I?lucutiori; The American Association of‘
Colleges of Pharmacy: Alexandria, Virginia, 1992.
11. The Scopc‘ oj” Pharmacy Pructic(> Project: Final lirport;
Greenberg, S., Smith, I.A., Eds.: The American As-
sociation of Colleges of Pharmacy: Alexandria, Virginia,
1994.
1. Taskforce on Accreditation of Health Professions Edu- 12. National Census of Pharmacists. The Pharmacy Manpower
cation. Strutegies jbr Chaizge and Improvement; The Pew Project, Inc.: Alexandria, Virginia, 1992.
PHARMACY PRACTICE ISSUES
specified depending on the type of medicine. In general tient contribution ($20.30) represented 40% of the ave-
terms, medicines for chronic diseases can be prescribed rage PBS dispensed price of general prescriptions. Each
in quantities adequate for one month of treatment at Australian has on average six prescriptions for PBS
standard doses with five repeat supplies providing a to- medicines each year; however concessional patients have
tal of six months of therapy per prescription. The maxi- an average of 20 prescriptions per year, resulting in 79%
mum PBS quantities for medicines for acute conditions of government expenditure on the PBS being directed to
reflect standard treatment periods. Manufacturers supply concessional
most medicines in packs corresponding to the PBS max- In the mid- 1990s, expenditure on pharmaceuticals-
imum quantities. [41 largely expenditure on PBS listed medicines-accounted
Medicines listed in the PBS Schedule fall into three for 15% of total healthcare expenditure in Australia,
categories of restriction: 1) Unrestricted medicines can which was 8.5% of gross domestic product. Of the total
be prescribed at the discretion of the medical prac- outlays on the PBS, manufacturers receive 67%, pharma-
titioner; 2 ) restricted medicines should only be prescribed cists 26%, and wholesalers 7%.[71
for specific therapeutic uses; and 3) authority medicines Although the government’s dominant position has
are also restricted to specific therapeutic uses but can enabled it to maintain relatively low costs for individual
only be prescribed following approval from a govern- medicines, the PBS is an uncapped government program
ment agency .[41 in which the level of overall government subsidy is
largely driven by doctors’ prescribing habits. With the
introduction of new drugs that have benefits over older,
R16 s cheaper medicines and with a population that is aging, the
government outlay has increased rapidly. In the seven
The federal government has used its position of dominant years from 1992 to 1998, the cost to the government of
funder in the prescription market to negotiate prices for PBS prescriptions increased by 107%. An increase in
medication that historically have been 30-40% lower prescription volumes of 6.5% in calendar 1999 over the
than in the United States and Western Europe. Wholesale previous year resulted in a further increase in government
distributors and pharmacists are allowed to add specified expenditure of 14.5% .
mark-ups, and pharmacists also receive a professional
dispensing fee resulting in the “PBS dispensed price.” In
1999, the average PBS dispensed price was $26.35, which
equated to 3.65% of average weekly
Most patients pay a co-payment toward the PBS dis-
pensed price. Neither the price nor the therapeutic use of Different brands of the same drug may be listed in the
the medicine is a factor in determining the level of the co- PBS Schedule at different prices and the federal go-
payment. There is one level of co-payment for general vernment subsidizes up to the price of the lowest priced
patients and a lesser one for patients with concessional brand. As a result of this policy, patients are required to
status. General patients pay the cost of the dispensed pay a surcharge on their patient co-payment if they choose
medicine up to a maximum of $21.00. All people of re- the higher priced brand of a drug when a lower priced
tirement age, on pension, receiving unemployment or generic exists.
welfare benefits, and all Veterans pay the concessional This policy promotes generic substitution and pharma-
co-payment of $3.50 per medication (year 2001 rates). cists are allowed to substitute a bioequivalent medicine
After dispensing a prescription, the pharmacist submits it without reference to the prescriber if the patient agrees
to the Federal Government’s Health Insurance Commis- and the prescriber has not vetoed such substit~tion.[~]
sion, which pays to the pharmacist the PBS dispensed
price less the applicable patient co-payment. If a family
unit requires chronic medication and reach expenditure
thresholds on PBS prescriptions approximating either 30 This policy extends the principle of brand price premiums
or 50 prescriptions per calendar year, a stepped safety net to four therapeutic groups of medicines that are clinically
scheme provides a higher level of subsidy. At maximum similar. The groups are angiotensin converting enzyme
safety net benefit, the patient co-payment is eliminated.[71 inhibitors, calcium channel blockers, HMG CoA reduc-
In 1999, the concessional patient contribution (then tase inhibitors, and H2 receptor antagonists. There is at
$3.20) represented 14% of the average PBS dispensed least one drug in each group available at the basic patient
price of concessional prescriptions, and the general pa- co-payment without supplementary charge.14]
690 Pharmaceutical Benefits Scheme (Australia)
Both the Brand Price Premium and Therapeutic Group reviews for domiciliary patients. While reviews in the
Premium policies are aimed at establishing benchmark aged care facility setting are at the initiation of phar-
prices within equivalent groups of medicines and pro- macists, reviews in the domiciliary setting are on referral
moting use of the cheapest of the options available. from a medical practitioner.
Under this program pharmacists are being remune-
rated for their clinical expertise rather than for the supply
REV1 of medicines. The federal government has determined
that the cost of this program will largely be met out
The PBS gives priority to listing of medicines for the of savings in expenditure on PBS medicines as a re-
treatment of conditions not amenable to self diagnosis sult of rationalization of prescribing following the medi-
and treatment. Consequently if a particular medicine or cation reviews.[']
a group of medicines no longer requires prescriptions, it Other clinically focused services that are to be funded
may be delisted from the PBS schedule. Similarly if via the MMP include case discussions between pharma-
medicines are deemed to be no longer an acceptable or cists and medical practitioners and support for pharma-
cost-effective therapeutic choice, they may be delisted. cists to work within divisions of general practice as part
Examples of delisting include all antihistamines, all of an integrated, geographically based primary health-
preparations containing dextropropoxyphene, and all na- care service.
sal sprays.
€Dl MAN EN RA
The Medication Management Program (MMP) provides The Pharmacy Development Program (PDP) provides
federal government funding for accredited pharmacists to federal government support for programs of quality ac-
undertake medication reviews. The aims of the reviews creditation of pharmacies, for the provision of medicine
are to: information for consumers, and for research programs to
identify cost effective professional pharmacy initiatives
e Contribute to optimizing the therapeutic effectiveness that can demonstrate net benefits for the Australian
and manageability of the medication regimen. health system.
0
Facilitate a cooperative working relationship between With this federal government support, professional
pharmacists and other members of the healthcare pharmacy bodies have established practice standards,
team in order to benefit the health and well being of measurable performance indicators, and pharmacy accre-
the patient. ditation programs. The standards address health pro-
e Provide an information resource for colleagues in motion, drug dispensing, dose administration aids, patient
relation to patients' medications and the medication counseling, compounding, medication reviews, compre-
review process.['] hensive pharmaceutical care, drug information services,
liaison pharmacy, and pharmacy services in residential
A medication review involves the systematic evalua- care facilities."01
tion of the patient's complete medication regimen in- Funding arrangements for the accreditation and me-
cluding clarification of the indications for use and dicine information services are currently under nego-
administration details of both prescription and. non- tiation but will take the form of block grants to accredi-
prescription medicines plus the outcome of therapy. The ted pharmacies.
process results in the generation of a report by the The MMP and PDP are funded partly from the general
pharmacist documenting interventions and recommen- revenue of the federal government and partly by the
dations to other healthcare providers to optimize thera- transfer of funds from projected growth in remuneration to
peutic outcomes. pharmacists for dispensing of PBS prescriptions. As such,
The MMP replaced the Medication Review Program. pharmacists are being remunerated for services aimed at
Under the initial program pharmacists were funded to improving the use of medication at the expense of growth
undertake systematic medication reviews for residents of in their remuneration from dispensing medication.
aged care facilities (nursing homes and supported care The total of the funds available for pharmacists'
hostels). The MMP increases the level of funding per clinical practice via the MMP and PDP is small in com-
review episode and introduces funding for medication parison with the total PBS expenditure; however, both
Pharmaceutical Benefits Scheme (Australia) 69 1
government and professional organizations support con- livery; Medical Technology Assessment (iroup: Chats-
tinucd expansion in these areas."" wood, Australia, 1999; Vol. 1: 12-14.
6. PHS Statistics (2002); Health Access and Financing,
Australian Department of' Health and Ageing:- - Canberra,
Australia. www.health.gov.au/pbs/s~ats. htm (accessed July
2002).
7. Who Payr.? Where does the money go.? (2002); Health
1. Pharnmceutical Benc<fi'tsScheme (2002); Health Access Access and Financing, Australian Department of Health
and Financing, Australian Department of Health and and Ageing: Canberra, Australia. www.health.gov.au/phsl
Ageing: Canberra: Australia. www.health.gov.au/phs/ pbs/whopays.htm (accessed July 2002).
aboutushtm (accessed July 2002). 8. National Policy Committee Comprehensive Medication
2. Hall. R. Medication in Australia-An Overview of the Key Reviews in Residential Aged Care Facilities. In Phannncy
Decision Makers; MediScene Newsletter, Commonwealth Practice Handbook 2000; Pharmaceutical Society of Aus-
Department of Health and Aged Care: Canberra. Australia, tralia: Canberra, Australia, 2000; 80-82.
2000; 16, Issue 14. 9. Elliot, R.; Thomson, W. Assessment of a nursing home me-
3. Hall, R. Phurmaceutical Betzeji'ts Scheme; MediScene dication review scrvice provided by hospital based clinical
Newsletter, Commonwealth Department of Health and pharmacists. Aust. J. Hosp. Pharm. 1999, 29 ( 5 ) . 255-260.
Aged Care: Canberra; Australia, 2000; 15, Issue 14. 10. Cameron, N. Pharmacy standards ensure professional
4. Schdule of Pharniaccutical Benejks for Approved Phar- consistency. Pharm. Rev. 1999, 23 (2). 58 59.
rnucists and Medical Practitioner; Commonwealth Depart- 11. Wooldridge, M. Federal health minister: Pharmacy's key
ment of Health and Aged Carc: Canberra, Australia, role in nation's health care structure. Pharm. Rev. 2000, 24
August 2000; 25-48. (I), 8-9.
5 . Davey, P.; Lees, M.; Aristides, M.; Ziss, S. Rcport on the 12. Contact for the Pharmaceutical Bendits Branch: telephone
Austrulian System of Phunnaceutical Financing and De- +61 2 62 89 70 99; URL www.health.gov.au/haf/branch.
PROFESSIONAL DEVELOPMENT
Terry L. Schwing
Establish a Therapeutic
f
ASSESSMENT CARE PLAN E V A ~ ~ A ~ I O ~
1. Ensure all therapy is 1. Resolve drug 1. Record actual patient
indicated, effective, therapy problems. outcomes.
safe, and convenient. 2. Achieve therapeutic 2. Evaluate progress in
2. Identify drug therapy goals. meeting therapeutic
problems to resolve 3. Prevent drug goals.
and prevent. therapy problems. 3. Reassess for new
problems.
Fig. 1 The patient care process within a pharmaceutical care practice. Adapted from Cipolle, R.J.: Strand, L.M.; Morley, P.C.
Pharmaceutical Care Practice; McGraw-Hill: New York, 1998, p. 129.
tify drug thelzlpy problems that may be interfering These functions require ongoing collaboration with
with the goals of therapy or placing the patient at fu- the patient and other clinicians to develop and implement
ture risk. a plan that is agreed upon and understood by everyone
A drug therapy problem is an undesirable event involved. The individual providing pharmaceutical care
involving drug therapy that actually or potentially in- is then responsible for ensuring that optimal therapeutic
terferes with a desired patient outcome. Seven major outcomes are achieved.
types of drug-related problems have been identified that
relate to the appropriateness, effectiveness, safety, and Follow-up evaluation
convenience of drug therapy (Table 1). There are mul-
tiple possible causes of each type of problem. The purposes of follow-up evaluations are as follows: 1) to
Drug therapy problems drive subsequent steps in the determine the actual outcomes that were achieved by the
patient care process; therefore, they are stated clearly and plan; 2) to assess the extent to which the plan has achieved
with a high level of specificity. Moreover, they are prior- the desired outcomes; 3) to determine if there are new or
itized according to their degree of urgency as determined changing drug therapy problems that must be addressed;
by the severity of potential harm to the patient. and 4) to determine if anything has occurred that increases
the patient’s risk for developing new drug therapy
Pharmaceutical care plan problems. The patient’s progress is documented accurately
in the pharmacy record and communicated effectively to
The purposes of a care plan are as follows: 1) to solve the patient and other health care providers.
the existing drug therapy problems that were identified The status of each medical condition can be described
during the assessment; 2) to achieve the desired outcomes according the following categories:
for each medical condition; and 3) to prevent the devel-
opment of future drug therapy problems. 0 Resolved-the goals have been achieved and therapy
In creating a care plan, the practitioner: is completed.
0 Stable-the goals have been achieved, but continue
0 Specifies the desired therapeutic goal for each prob- the same therapy.
lem identified. 0
Improved-progress is being made toward achieve-
0 Considers all feasible actions or choices that may be ment of the goals, so continue the same therapy.
made to achieve the stated goals. 0 Partial improvement-progress is being made, but
Outlines interventions designed to resolve drug the- minor adjustments in the therapy are required.
rapy problems. 0 Unimproved-there is no measurable progress yet, but
0
Designs a monitoring plan to assess effectiveness continue the same therapy.
and minimize undesirable adverse effects of drug * Worsened-there is a decline in health, so revise the
therapy. therapy accordingly.
Pharmaceutical Care 695
D r u g ~ r ~ ~ a tneeds
ed Drug therapy problems
Appropriate indication for drug therapy 1. Need f o r additional drug therapy: Patient has a medical
condition that requires initiation of new or additional drug therapy.
2. Unnecessary drug therapy: Patient is taking drug therapy that is
not needed given their present medical condition.
Effective drug therapy 3. Wrong drug: Patient has medical problem treated with therapy that is
less effective, more costly, or more hazardous than alternative therapies.
4. Dose too low: Patient is taking correct drug for medical condition,
but too little of drug is being taken.
Safe drug therapy 5 . Adverse drug reaction: Patient has medical problem caused by an
adverse drug effect, which may include a side effect as well as an
allergic reaction; idiosyncratic reaction; and a drug-drug, drug-food,
or drug-laboratory test interaction.”
6. Dose too high: Patient is taking correct drug for medical condition,
but too much of drug is being taken.
Convenient drug therapy I. Nonadherence: Patient has medical problem resulting from not taking
or receiving drug prescribed.
aIn early descriptions of drug therapy problems, drug-drug, drug-food, and drug-laboratory test interactions were included as a separate eighth type
of problem.
0 Failure-the goals are not achievable with the present maceutical Care at the University of Minnesota. Between
therapy, so initiate new therapy. 1993 and 1999, 14,357 patients received pharmaceutical
0 Expired-the patient died while receiving drug care in 30 different ambulatory practice settings. The
therapy. pharmacists assessed 97,5 11 drug therapy regimens and
identified, resolved, and prevented 19,140 drug therapy
If changes in the plan are required to maintain or im- problems. In a clinical and financial analysis of 1500 pa-
prove its efficacy, safety, or economy, the clinician co- tients conducted between January 1998 and August 1999,
ordinates these changes and communicates them to the pharmacist interventions avoided 193 unnecessary clinic
patient and other health care providers. visits, 72 multiple office visits, 36 emergency department
visits, 28 urgent care visits, and 14 hospital admissions.
Drug costs were reduced on 177 occasions. An estimated
cost savings of $144,626 was realized, which reflects a
A practice management system provides the support ne- savings of approximately $60 per patient. This represents
cessary for effective and efficient practice. The system a savings-to-cost ratio of 2:1 for the pharmaceutical care
must allow for the addition of new patients and ensure the provided. When clinical outcomes of patients were eva-
long-term financial viability of the practice. The system luated, problems were resolved in lo%, stable in 38%,
generally includes the following elements: 1) a statement improved in 17%, and partially improved in 17%.
of the mission of the practice; 2) the physical, financial, Fourteen percent of patients were unimproved, 3% were
and human resources needed to support the practice; worse, and 1% failed therapy. The authors concluded
3 ) a documentation system to evaluate the practice; and that the quality of care provided had a substantial po-
4) reimbursement mechanisms to compensate the cli- sitive impact on the clinical well-being of patients as
nician and support the continuation of the practice. well as on economic outcomes.
AIN
TIC SE
Cipolle and colleagues reported the outcomes achieved by For a patient care practice to be recognized by the fede-
50 pharmacists who had completed the pharmaceutical ral government and other third-party payers, four ele-
care training program of the Peters Institute of Phar- ments must be present: 1) a defined patient care practice;
696 Pharmaceutical Care
2) a documentation system; 3) a formal evaluation sys- absence of a tangible reward system. Pharmacy systems
tem; and 4) reimbursement systems based on the level of may pose impediments related to insufficient support
patient needs. personnel, lack of automated dispensing systems, limited
Pharmacists participating in collaborative patient care physical facilities or poor organization of the available
environments (including disease state management and space, lack of adequate pharmacist compensation for
clinical pharmacy service programs) have experienced cognitive functions, limited communication due to phy-
varying degrees of success in obtaining payment for the sical isolation from the patient and other health profes-
care provided. Although direct payment from patients is sionals, and inability to access necessary patient medical
infrequently sought, a mail survey of 2500 American information. Other real or perceived barriers may include
adults indicated that 56% of respondents were willing the resistance of physicians, administrators, and others;
to pay for comprehensive pharmaceutical care services outdated and overly restrictive state board of pharmacy
after they were provided with a description of what such regulations; and lack of a market-driven demand for
care entailed. pharmaceutical care by the public.
Several different types of billing mechanisms have
been used to gain compensation from third parties for
services that are not tied directly to dispensing a drug
product. Examples include fee-for-service, capitation
payment, and the Health Care Financing Administration Pharmaceutical care is a practice in which the clinician,
(HCFA) 1500 claim form. Each method has inherent ad- working in concert with the patient and other health care
vantages and disadvantages and may not be a suitable providers, takes shared responsibility for the outcomes
method for compensation for a comprehensive pharma- of all aspects of a patient’s drug therapy. The goal of
ceutical care practice. the practice is to ensure that every patient seen by the
Payment for the majority of the patient care services practitioner receives the most appropriate, effective, safe,
provided by physician and nonphysician practitioners economical, and convenient drug therapy possible. This
is based on the resource-based relative value scale is accomplished through the identification and resolution
(RBRVS). The RBRVS ranks services according to the of actual and potential drug therapy problems. The
relative costs of the resources needed to provide them. essential components of a pharmaceutical care practice
The resulting relative value scale is then multiplied by a include a philosophy of practice, a patient care process,
dollar figure to convert the service into a payment sche- a documentation and evaluation system, and a method for
dule. This payment model was successfully applied to obtaining financial compensation. All these elements
pharmaceutical care practice in the Minnesota Phar- must be in place for the practitioner to become recognized
maceutical Care Project. Five levels of patient need were and compensated as a health care provider within the
created based on the following: 1) the number of the U.S. health care system. The future widespread adoption
patient’s medical conditions; 2) the number of medica- of pharmaceutical care practice by the pharmacy profes-
tions the patient is taking; and 3) the number of drug sion has great potential to reduce morbidity and mortality
therapy problems identified. At 10 different community due to preventable drug therapy problems.
pharmacy practices in 1994, the average payment for a
patient encounter was $12.14.
American Society of Hospital Pharmacists. ASHP statement on Larson, R.A. Patients’ willingness to pay lor pharmaceutical
pharmaceutical care. Am. J. Hosp. Pharm. 1993, 50, 1720- care. J. Am. Pharm. Assoc. 2000, 40, 618 624.
www.ashp.org (acccssed Oct. 2000). Manasse, H.R., Jr. Medication use in an imperfect world: Drug
rand, L.M.; Morley, P.C. A New Professional misadventuring as an issue of public policy, part 1. Am. J.
Practice. Phurmaceuficul Cure Practice; McGraw-Hill: New Hosp. Pharm. 1989, 46,929-944.
York, 1998; 1-35, Manasse. H.R., Jr. Medication use in an imperfect world: Drug
Cipollc, R.J.; Strand, L.M.: Morley, P.C.; Frakes. M. The misadventuring as an issue of public policy, part 2. Am. .I.
Outcomes of Phurrnaceutical Care Pructic,i>,Presented in Hosp. Pharm. 1989, 46.1141-1 152.
part at the 1st National Congress of Pharmaceutical Care, McCallian, D.J.; Carlstedt, B.D.; Rupp, M.T. Elements o l a
Donostia-San Sebastian, Spain, Oct. 28-30, 1999. pharmaceutical care plan. J. Am. Pharm. Assoc. 199
Commission to Implement Change in Pharmaceutical Education. 82- 83.
Background Pciper 1. What is the Mission of Phurrnuceuticul Strand, L.M.; Cipolle, R.J.; Morley, P.C. Documenting clinical
Educalion? The American Association of Colleges of pharmacy services: Back to basics. Drug Intell. Clin. Pharm.
Pharmacy: Alexandria, Virginia, 1994; 3 -9. http://www.adcp. 1988, 22, 63-61.
org (accessed Oct. 2000). Strand, L.M.; Cipolle, R.; Morley, P.C.; Ramsay, R.; Lamaam,
FIP StnterniJnt of Proje.rsional Standards: Pharmaceuticul Cure G.D. Drug-related problems: Their structure and function.
(Adopted Septembpr 4, 1YY8); http://www.€ip.nl (accessed DICP 1990, 24 ( I 1); 1093 -1097.
Nov. 2000). The American Pharmaceutical Association. A P/zA Mi.T,sim?, Vi-
Hepler. C.D.; Strand, L.M.Opportunities and responsibilities in sion, Vulues, and Straregic Goals; http://www.aphanct.org
pharmaceutical care. Am. J. Hosp. Pharm. 1990, 47, 533- (accessed Oct. 2000).
543. The American Society of’ Hospital Pharmacists. Implementing
Institute of Medicine Division of Health Care Services Com- pharmaceutical care. Proceedings of a n invitational confer-
mittee on Quality of Health Care in America. 7 b Err is ence conducted by the American Society of Hospital Phar-
Hunzaiz: Building a Sqfer Health System; National Academy macists and the ASHP Research and Education Foundation.
Press: Washington, DC. 1999. http://www.books.nap.edu Am. J. Hosp. Pharm. 1993, 50. 1585- 1656.
(accessed Oct. 2000). Vaneslow, N.A.; Donaldson, M.S.; Yordy, K.D. From the Ins-
Johnson, J.A.; Bootman, L.J. Drug-related morbidity and titute of Medicine: A new definition of primary carc. JAMA
mortality. Arch. Intcrn. Med. 1995, 155, 1949- 1956. 1995, 273, 192.
PROFESSIONAL ORGANIZATIONS
value to the drug itself, making the prescription and use of working group had been coordinated by the General
[51
drugs more rational and consequently more cost effective. Director of Pharmacy of the Ministry of health.
Also, in relation to Spanish universities, the Foundation 0 Competencies document: A competencies document
has to influence the reorientation of its educational pro- of the pharmacy profession is planned with strong
grams and teaching methods in order to create the culture, participation by the Pharmaceutical Care Spain
attitudes, knowledge, and skills required among pharmacy Foundation. The document is intended to define the
students to provide pharmaceutical care to society. Phar- areas in which pharmacists are competent within the
[61
maceutical care should be the main educational objective healthcare practice.
for all schools of pharmacy. Finally, another reason for the
Foundation is the need to inform and to show the benefits
that people can obtain from the pharmaceutical care prac-
tice in terms of ensuring the safety and effectiveness of
their pharmacotherapy. No service will be demanded by During 200 1, the Foundation offered different courses
society if people ignore its existence and the benefits that through the Internet. Topics include:
can be obtained from it.
e Methodology to implement pharmaceutical care into
practice.
0 Concepts on pharmacoepidemiology.
e Pharmacoeconomics.
* Evaluation of the scientific biomedical literature.
In two years of existence, the Foundation has deve-
loped some activities in order to achieve the above- Other courses will be more oriented to pharmaco-
mentioned objectives: therapy:
Journal Pharmaceutical Care Spain: This publication 0 Treatment of blood coagulation disorders.
was initiated in January 1999,‘31with six issues per year. 0 Arterial hypertension.
The contents of the journal are original papers, reviews, Peripheral vascular pathologies.
international news, drug information, etc. Also, a con- 0 Congestive heart failure.
tinuing education program is offered through the jour-
nal to all subscribers. The Foundation held the Second National Congress on
Vade mecum of the official technical information Pharmaceutical Care November 2001 in Barcelona. The
about drugs commercialized in Spain: this is offered main subject of this congress was “communication with
via the Internet to all physicians and pharmacists of patients and with the other healthcare practitioners.” The
the country through the Web at www.saludaliafarma. Foundation believes that communication skills are the
com or www.saludaliamedica.com. main deficiencies of community pharmacists, and these
Procedures manual on pharmaceutical care: Because are essential for pharmaceutical care implementation and
many colleagues plan to initiate provision of phar- practice.[71
maceutical care but do not know how to start, the Some research projects promoted or initiated by the
[41
Foundation published this manual to guide them. Foundation are currently ongoing. A European research
First National Congress of Pharmaceutical Care: Held consortium, with the participation of different countries,
in San SebastiBn with more than 1000 participants, this is proposed to study the influence of pharmaceutical care
congress included several distinguished speakers, in the control and treatment of minor diseases from com-
including Charles Hepler, Linda Strand, J.W. Foppe munity pharmacists, and it has submitted to the European
van Mil, and Robert Cipolle. The Ministry of Health Community in Brussels asking for economic support.
also attended the meeting and 77 communications on Such research will be coordinated by the School of Phar-
Pharmaceutical Care experiences were presented. macy of the University of Manchester, United Kingdom.
Consensus on pharmaceutical care: Due to the differing A project promoted by the European Society of Clinical
conceptions that Spanish professional groups have on Pharmacy is currently studying the number of drug related
pharmaceutical care, and the difficulties in translating problems (DRP) identified by community pharmacists on
English terminology into Spanish, a working party patients discharged from the hospital. A research study on
with all the interested groups was established in order the number of DRP identified by pharmacists in patients
to achieve a consensus document on the subject. This admitted to emergency services of hospitals was initiated
700 Pharmaceutical Care Spain Foundation
to rind out how many patients arc admitted in emergency 2. Bonal, J. Porque se ha creado una Fundacihn de
rooms because they are suffering some DRP, and how Pharmaceutical Carc? Editorial Pharm. Care Esp. 1999,
many of these DRPs could be prevented through phar- 1 ; 1-2.
maceutical care practice. 3. FernandeL-Llimos, F.; Herrera: J. Por quC creamos una
revista? Editorial Pharm. Care Esp. 1999. I , 3 .
The Pharmaceutical Care Spain Foundation is also
4. Alvarez de Toledo, F.; Barbcro, J.A.; Bonal, J.; Dago, A,,
cooperating in an organization called Pharmaceutical Care et al. Manual de Procedimientn.5 en Atc.nci6n Farm-
Network Europe (PCNE) that is promoting pharinaccutical ac&tica, I st Ed.; Fundacicin Pharmaceutical Care Espafia:
care practice and research. One of thc difriculties we havc Barcelona, Septiembre 1999.
in Europe is the diversity of pharmacy organization system 5. Consenso sobre Atencihn FarmacCutica. Grupo de Con-
and practice, as well as languages and healthcare structure. senso de AF (2000). Direccicin General de Farmacia y
Such differences, between European countries, are well Productos Sanitarios. Ministcrio dc Sanidad y Consumo.
discussed by Foppe van Mil.'x' Madrid.
6. Competencias de la prolesicin de Farmacia. CCECS
borrador 2000. Barcelona.
7. Bonal, J. El segundo Congreso Nacional de Atencicin
Farmackutica. Editorial Pharm. Carc Esp. 2000, 2: 387-
3x9.
1, Heplcr, C.D.; Strand, L.M. Opportunities and responsibil- 8. Van Mil, J.W.F. Pharrnaccutical care in community
ities in the Pharmaceutical Care. Am. J. Hosp. Pharm. pharmacy in Europe, challenges and barriers. Pharm. Care
1990, 47, 5 3 3 543. Esp. 2000, 2, 42 56.
PHARMACY PRACTICE ISSUES
morbidity and readmission are the results of multiple reliable, valid, and feasible. To ensure this, they must
factors, and it is difficult to attribute those outcomes to a be carefully selected, thoroughly tested, evaluated, and
specific encounter or element of care without additional used within the context of a comprehensive performance
information about key factors.[16.20-221 Alth ough outcome measurement In isolation, no single measure
studies are increasingly being undertaken, there is much serves as a direct measure of quality but as an indicator of
to be learned about the relationships between processes the need to direct attention to a potential problem.
and outcomes.
eas ent
to the physician or other health care practitioner so the developed primarily process indicators to assess the im-
individual can review their own data. Indeed, when pact of health services. The National Prescribing Service
interventions have shown positive changes in medical (NPS) was launched by the Australian Government in
practice, one consistent finding is that providers were 1998 and is undertaking work in Quality Use of Medi-
given information on how their practices and outcomes cines (QUM). It has also done work in the area of mea-
compared with others in the c ~ m m u n i t y . [ ~Feedback
~,~~] surement of pharmaceutical outcomes.
is successful when used alone or in combination with
education, rewards, or the support of opinion leaders. ns
Pharmaceutical outcome data are also used to improve eut
the quality of care, identify potential problems, and
improve patient outcomes. These data are often used David Eddy at Duke University has written extensively on
within a continuous quality improvement (CQI) cycle, the problems and potential solutions related to phar-
where rate-based performance measures are tracked over maceutical performance measurement systems.[221 Ac-
time and used in conjunction with control charts to show cording to a U S . survey, the most commonly perceived
changes in quality and assess the impact of programs or problems with pharmaceutical performance measurement
changes in process. Information can be fed back to front systems are limitations with billing and administrative
line health care practitioners, areas for possible improve- databases, lack of time to review summary data by
ment identified, appropriate changes made, and reassess- physicians, and incomplete data."'] Other limitations in-
ments initiated. clude risk adjustment (what if my practice has "sicker"
patients), overreliance on administrative (claims) data
ance rather than clinical data (therefore lacking key patient
e ~ ~ u ~ e m Systems
ent outcomes), patient individuality and variation in medical
practice, and lack of capacity for taking into account a
The United States has several major performance mea- discipline-specific rather than a whole programs-oriented
surement systems in place. Two of the most important CQI approach. There has also been some debate on the
systems are those directed by the National Committee reliability of performance measurement systems to assess
for Quality Assurance (NCQA) for managed care orga- the true impact of physician care on the quality of health
nization (MCO) accreditation and The Joint Commission care.[35.36]
on Accreditation in Healthcare Organizations (JCAHO)
for health care organization accreditation. Both NCQA' s
performance measurement system, HEDIS, and JCA-
HO's IMSystem include several pharmaceutical out-
comes indicators.
Several other projects in the United States are deve- Difficulty in obtaining the data necessary for measure-
loping further pharmaceutical outcome measures. SCRIPT ment hinders pharmaceutical outcomes assessment. Both
(Study of Clinically Relevant Indicators for Pharmacolo- clinical and administrative data sources have limitations.
gic Therapy), initiated by the Health Care Financing Medical chart review is time consuming and expensive,
Administration (HCFA), is a multidisciplinary coalition and not all findings and services rendered by providers are
representing 52 public and private sector organizations documented Administrative records, often
that is currently beta-testing several pharmaceutical per- in the form of paid claims for reimbursement, are more
formance measures.[321 The Performance Indicators for readily retrievable, but are collected for administrative
Continuous Quality Improvement in Pharmacy (PICQIP) purposes and need validation to be used for assessing
study, a partnership between the University of Florida and pharmaceutical outcomes.
the American Pharmaceutical Association Foundation Available sources from the public system include
Quality Center, is an example of new pharmacy indicators census data, health expenditure data, physician clinical
being used in a CQI cycle.[33.341 record billing data, prescription drug claims data, popu-
The Canadian Institute for Health Information (CIHI) lation health surveys, hospital and nursing home medical
is actively working on developing drug performance records, and disease- or organ-specific registries. Private
indicators for uptake and application by the Canadian sector data include data from the pharmaceutical indus-
Council on Health Services Accreditation (CCHSA). In try, private insurance industry, drug benefit management
Great Britain, the National Health Service (NHS) has companies, and individual private firms.1381Develop-
established a National Performance Framework that has ments in health care information technology (IT) should
704 Pharmaceutical Outcomes
facilitate the collection of pharmaceutical outcomes data Care advocates the measurement of pharmaceutical care
in the future. outcomes: “High-quality, coordinated, and continuous
medication management for patients should be measura-
ble as a result of the provision of pharmaceutical care
within a primary care delivery model,” and “Pharma-
cists should evaluate all components of the medication-
use process to optimize the potential for positive patient
It is generally accepted that persons have a right to control outcomes.’’14’] Health administrators need to implement
their health information so they are not harmed. Many systematic ways of measuring the processes, outcomes,
jurisdictions are developing guidelines or legislation and costs of medication use. Health policy makers
related to privacy, confidentiality. and security of per- should take note of policy synthesis documents, evidence
sonal health information. For example, in the United of the effectiveness of drug policies implemented in other
States, the Health Insurance Portability and Accountabil- jurisdictions and. when possible. evaluate policies and
ity Act (HIPAA) of 1996 and the associated final Privacy programs to determine their effect on patient outcomes,
Rule of December 28, 2000 (which took effect on April health care resource utilization and costs. Pharmaceutical
14, 2001) gave patients more control over how their companies need to help health practitioners proactively
personal health information is used, and addressed the identify patients at risk for PDRM from their products and
duties of health care plans and providers to protect health help to implement systems to improve drug use. They
information.[391Research ethics committees need to need to continue to participate in methodologically
determine when patients need to give explicit consent sound pharmaceutical outcomes research. Finally, each
for the use of their personal health information for new time they receive a prescription, patients should question
research questions when it has been collected for other what is the intended outcome of this drug and who will be
research questions or administrative purposes. The sound- working with me to ensure that I achieve this outcome?
ness of scientific methodology needs to be assured. The
potential public health benefit of the research needs to be
weighed against any risk to the individual. Guidelines for
data confidentiality and anonymity have been developed
in many jurisdictions and methods for masking or de-
linking personal identifiers or reporting only aggregate
data have been developed and implemented. Conflict of International Society for Pharmacoeconomics and Out-
interest and financial relationships in the research need to comes Research, ISPOR Lexicon Pashos, Klein,
be disclosed. There should also be vigilance on the tech- Wanke, L.A., Eds.; ISPOR: New Jersey, 1998.
nical side of ensuring security of data including controlled Spilker. B. In Quality of Life and Pharmacoeconomics in
access to and storage. maintenance and transmission of. Clinical Trials; 2nd Ed.; Spilker, B., Eds.; Lippincott-
personal health Raven: Philadelphia, PA, 1996.
s IN
Academy of Managed Care Pharmacy (www.amcp.orgj.
American College of Clinical Pharmacy (Outcomes and
Economics PRN) (www.accp.comj.
Improving drug use outcomes requires the participation Academy for Health Services Research and Health Policy
and cooperation of everyone involved in the case process. (www.academyhealth.orgj.
Physicians and other prescribers should specify the thera- Canadian Coordinating Office for Health Technology
peutic objective in writing for each prescription they write, Assessment (www.ccohta.caj.
and this should be communicated to the patient and other International Health Economics Association (www.
members of the health care team. Pharmacists, nurses, and hea1theconomics.orgj.
other health care professionals should monitor patients, International Society for Pharmacoeconomics and Out-
documenting their interactions with patients, and com- comes Research (www.ispor.orgj.
municate this information back to the health care team. International Society for Pharmacoepidemiology (www.
ASHP‘s Statement on the Pharmacist’s Role in Primary pharmacoepi.org).
Pharmaceutical Outcomes 705
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1995, 52 (2), 223-251.
PROF ESSl ONAL ORGAN IZATl ONS
The number of missions has continued to grow since Albania, Bosnia, Cambodia, Equator, Honduras, Kenya,
1992. The association conducts programs in all facets of ali, Mauritania, Moldovia, Montenegro, Niger,
the pharmaceutical profession, namely goods distribution, Serbia, and Soudan.
management, training, technical assistance, and facility
renovation. Consequently, PSF’s organizational structure
has expanded markedly. An International Committee has
been formed that currently includes Belgium, Canada,
France, Italy, Luxembourg, the Netherlands, Poland, and Like all nongovernmental organizations, PSF relies on
Switzerland. Through its sustained efforts, PSF has now two sources of funding: institutional sponsors and
gained worldwide recognition. private contributions. These funds ensure the self-
reliance of the association.
ancia are
Pharmaciens Sans Frontikres is currently operating an The Board is formed of approximately 20 volunteer
emergency mission in Tadjikistan and development or directors, elected by the members of the association.
technical assistance missions in the following countries: Claudi M. Cuchillo currently serves as President.
PSF Luxembourg: Mr. Camille Groos, 13 6. Diderich,
1420 Luxembourg.
Some 30 employees work at the international headquar- * PSF Poland: Mr. Zygmund Ryznerski, Farmaccuci
ters in Clcrmont-Ferrand and at the marketing office in BeL Granic, 2 PL W. Slkorslkiego. 311 15 Mrakow,
Paris, France. The key managers are as follow\: Poland.
PSF SwitLerland: r. Pierre Alain Jotterand,
@ Executive Director: GCrard Plantin de Crochy 2, Case Postale 229, 1024 Ecublens,
Director of Finance: Raphael Chaize S witLcrland.
Director of Human Resourccc: GCrard Pourrcaux
Chief of Marketing: lsabclle Lcroi
a Chief of Accounting: FranCoise Chargueraud
Communication Officer: Samuel Falgoux Over 1000 volunteers arc presently members or
around the world. At any point in time, between 90 to 100
expatriated of diverse nationalities and trades (such as
pharmacists, technicians, nurses, logisticians, and admin-
* PSF Belgium: Mrs. Solange Gos,ieaux, ForEt istrators) and some 400 local staff‘ combine forces to
d’FTouthulst 27, 1000 Brussel\, Belgium. improve health care in the field.
0 PSF Canada: Mr. Hubert Brault, a/s A.Q.P.P, 4378
Pierre de Coubertrn, Montreal, Qc, Canada kI 1 V 1 A6.
PSF Netherlandc: Mr. Tamme,, Apotheker\ Zonder
Grenzen, PO Box 10493, 7301 GL Apeldoorn,
Netherlands.
a PSF Italia: Mrs. Elena Candini, Farm- P i a n a Vittorio The annual general meeting of the members is held in
Emanucle 111 no. 4, Mon7ambano, ltalia. May.
PROFESSIONAL DEVELOPMENT
avid S. Ziska
broad population and these vaccines target the most un- program depends on numerous factors, including, but not
dervaccinated population and can affect the two most limited to, location of the pharmacy (both the state in
vaccine preventable diseases in the United States. which the pharmacy exists, as well as the physical
Combined, these two diseases kill between 50,000 and location in the community), staff size, physical layout of
80,000 people per year. Other vaccine-preventable di- the pharmacy, and other community health professionals
seases that are common in adult populations include currently involved in vaccinations (i.e., physicians, nurse
hepatitis B, hepatitis A, and varicella." Unlike the practitioners, nurses, state health departments). Based on
vaccines for influenza and pneumococcal pneumonia, guidelines approved by the APhA Board of Trustees in
these other diseases require multiple doses and the vac- 1997, there are three levels of involvement for pharma-
cines cost $25 to $60 or more per dose."21 Yet another cists in vaccine advocacy:
vaccine that many are not given because providers simply
forget to offer it to their clients is the tetanuddiphtheria 1. Pharmacist as educator (motivating people to be
vaccine or Td. This vaccine requires a booster every 10 immunized).
years after the age of 11 or 12."31 2. Pharmacist as facilitator (hosting others who
immunize).
3. Pharmacist as immunizer (providing and adminis-
tering immunizations)."61
The elderly suffer most in terms of increased morbidity
and mortality when recommended vaccines are not A logical role for all pharmacists is in the area of
administered. Pneumococcal diseases are the vaccine educating the public about the benefits and importance
preventable diseases that cause, by far, the most mortality of immunizations. Pharmacists regularly speak at local
in the elderly."41 Unfortunately, the vaccine for pneumo- civic, service, and school organization meetings to dis-
coccal-induced pneumonia has one of the lowest admin- cuss health-related issues, and these serve as ideal set-
istration rates. Other vaccines that most elderly and long- tings to speak about the importance of immunizations. By
term care residents should receive include the influenza keeping individual patient profiles, pharmacists also have
and tetanuddiphtheria vaccines. Consultant pharmacists a unique opportunity to identify and directly inform pa-
or pharmacists providing services to long-term care tients with special needs, such as those with a high risk of
facilities are in excellent positions to identify those who infection and the elderly, about the importance of re-
need vaccines."51 ceiving their pneumococcal and annual influenza immu-
nizations. Vast amounts of educational material are avail-
able from local, state, and national organizations to aid in
CTlCES educating children and adults (see Table 2 for specific
contact information). All pharmacists should meet this
There are a number of opportunities for pharmacists to level of advocacy.
develop an immunization service in their current practice. In daily dealings with physicians, nurses, insurance
However, the degree of development for a vaccination companies, and patients, the role of facilitator is com-
Pharmacist Managed Vaccination Programs 713
monplace for a pharmacist. As a facilitator, pharmacists who can provide the vaccine, there are opportunities for
continue to educate and motivate the public about im- pharmacists to expand their level of advocacy by be-
munizations; however, they assume a more active role by coming an immunizer.
ensuring that individuals actually receive their immuniza- For pharmacists to achieve the highest level of im-
tions. This has been accomplished by the development of munization advocacy, a number of responsibilities and
immunization programs that are offered in community decisions must be finalized. These responsibilities have
pharmacies. As early as 1982, ambulatory care pharma- been broken into the following categories: legalke-
cists in Georgia instituted a program to identify and gulatory, training, practice requirements, compensation,
immunize patients at risk for pneumonia and i n f l u e n ~ a . " ~ ] and documentation.
In 1985, community pharmacies in Denver, Colorado,
began to invite nurses to administer vaccines to the pub-
lic. The early 1990s witnessed the development of similar
programs in numerous chain pharmacies."s' As facil- If a pharmacist is interested in developing an immuni-
itators. pharmacists have also played an active role in zation program, the principle legal issue that must be
referring individuals in need of immunization to the addressed is how that state views the administration of
county health clinic, a local physician, or nurse practitio- drugs by a pharmacist. As mentioned previously, more
ner. Even though all pharmacies do not offer immuniza- than 30 states currently authorize pharmacists to vaccin-
tions, the referral of patients continues to be an active area ate. If you are not sure, check with your state board of
of immunization advocacy. pharmacy to determine your options. If your state
In 1994, the University of Washington School of currently does not allow pharmacists to administer drugs,
Pharmacy and the Washington State Pharmacists Asso- this would be an opportune time to get involved with your
ciation developed the first coordinated program to train state pharmacy association and state board to attempt to
pharmacists to administer immunization^."^^ With this change your state pharmacy regulations. If your state
development, the need to host others, (e.g., nurses) in the allows pharmacists to administer medications, additional
pharmacy to provide immunizations began to decrease in legal and regulatory issues should be addressed. Depend-
states that allowed pharmacists to administer drugs. As of ing on a state's practice regulations, initiating a patient
June 2001, 32 states explicitly authorize pharmacists to care service, such as an immunization program, requires
vaccinate.[201Although the role of facilitator is important a pharmacist to establish a collaborative practice agree-
in connecting those in need of immunizations to those ment or protocol with a prescriber. As an immunizer, a
Pharmacist Managed Vaccination Programs
pharmacist is at risk of needle sticks and exposure to in between filling all the prescriptions to a large pharmacy
blood-borne pathogens. Employers and employees must practice (independent or chain store) where the immuni-
become familiar with the regulations of the Occupational zations are provided to patients in a separate, private room
Safety and Health Administration to minimize potential with pharmacists and support personnel dedicated entirely
harm to all employees.[211 to this service.
In the 2000 NCPA-Pharmacia Digest, responding
independent pharmacists reported that on average, 2 1%
of all respondents offered immunizations. Based on the
pharmacy’s sales volume, the range of offerings was 9%
As mentioned previously, certificate programs represent for $500,000 to $750,000 per year in sales to 42% in
the primary method used to educate and train interested pharmacies with more than $4,000,000 per year in
pharmacists in how to develop a pharmacy-based im- sales.[231Generally, vaccine program offerings increased
munization program. The training programs available as sales volume increased. Similarly, the percentage of
provide individuals with the knowledge, tools, and en- pharmacies offering an immunization service tended to
couragement to achieve the highest level of advocacy. A increase as square footage increased. Based on the
list of the organizations offering such programs is pro- pharmacy’s total square footage, the range of offerings
vided in Table 3. The training programs are offered at was 119% for pharmacies with less than 1000 square feet
various times of the year and in various locations. Contact to 32% in pharmacies larger than 4000 square feet.[241
the listed organizations or your state pharmacy associa- There are numerous examples of immunization pro-
tion to identify a program near you. grams being offered in independent pharmacies, as well as
Although many of the training programs focus on in chain pharmacies. Although there are a number of
practicing pharmacists, pharmacy students have also differences among these practice sites-including, but
become active in advocating immunizations. Students in not limited to, staff size, physical space, and facility
all 81 APhA Academy of Students of Pharmacy chapters location-in all cases, the development of an immuniza-
and 40 Student National Pharmaceutical Association tion program is possible. Staff size is a critical issue for a
chapters have been involved with Operation Immuniza- pharmacy developing an immunization service. Some
tion: The Nation’s Pharmacy Students and Practitioners questions that should be asked are “Who will be the
Protecting the Public Health. Since its inception in 1997, immunizers?”, “How will this service effect work
Operation Immunization has helped provide more than flow?”, and “Will staff be dedicated to the immuniza-
125,000 vaccinations.[221 tion program, or will immunizations be administered
by staff in between regular scheduled duties?” In regards
to physical space needs, the minimum requirements for
CtiC nts providing immunizations should include space with pri-
vacy for administering injections (with room to sit and
Although there are levels of advocacy, there are also possibly to lay down in case of an emergency), a dose-
levels of program development. The range of possible preparation area, and a place for patients to wait after the
levels could start in an apothecary-style pharmacy with a immunization.[253261 The physical space used for immun-
single pharmacist providing immunizations to individuals ization programs has varied from a chair at the end of the
counter separated from the waiting area by a partition or
curtain, to stock rooms converted into administration
Table 3 Organizations providing standardized training in areas, to using the owner’slmanager’s office on scheduled
pharmacy-based immunizations days, to having separate counseling facilities already
available. When asked, most immunizers shared that the
r~~nizat~on Internet address
service was easier to set up than expected and most fa-
American Pharmaceutical www.aphanet.org cilities host such a service. Also, future immunizers will
Association obtain a large amount of information regarding staff and
Centers for Disease Control www.cdc.gov physical needs through the respective training programs
and Prevention offered. Another requirement for this service is a ref-
National Community Pharmacists www.ncpanet.org rigerator with freezer for storage of the vaccine supplies.
Association
Vaccine products have specific storage requirements, with
Washington State Pharmacists www.PharmCare.org
standard temperature ranges, so the presence of a quality
Association
refrigeratodfreezer is critical to the service. A back-up
Pharmacist Managed Vaccination Programs 715
plan, such as a cooler or alternative power source for the dicare, the pharmacist, pharmacy, or both must apply for a
refrigerator, is also important in case of power interrup- medicare provider identification number as an immunizer
tions of greater than 24 hours.[271 from the local medicare part B carrier.
Both pharmacists and pharmacies use Health Care
Finance Administration (HCFA) Form 855, Provider/
Supplier Enrollment Application, to request a provider
number. This form may be obtained from medicare part B
The critical aspect of any service is the covering of costs carriers or provided by the previously mentioned training
incurred to provide the service and profit to sustain not programs. This is a cursory review of medicare policies.
only the service, but also the business as a whole. For Training programs will provide additional details, or
immunization programs, as with any patient care service contact your local medicare part B carrier, HCFA regional
developed in a pharmacy, there will be direct and indirect office, or other pharmacy reimbursement publication^.^"^
costs associated with the service. Direct costs are those A fourth method of compensation is direct contracts
that would not be incurred by the business if the service with local area employers. By contracting with an area
were not performed, and indirect costs are those incurred employer, pharmacists have administered influenza and
even if the service in question was not developed.[2s1 pneumococcal vaccines to all employees. This type of
Although each pharmacy is unique, with its own needs on-site program can be offered to various businesses, such
and requirements, the following examples are areas to as plants, office-based facilities, and health care-related
consider in determining potential costs of such a program. facilities, such as assisted living facilities and adult family
As for direct costs, areas such as service personnel costs, homes.[311One popular place for a traveling immuniza-
specialty training, additional liability protection, supplies tion program has been schools. This type of service
and equipment. service workspace, service-specific ad- primarily focuses on the adults (teachers, staff members);
vertising and promotion, and additional information re- however, some pharmacies have also established child
sources must be analyzed to help determine the overall immunization programs. The final method involves
costs of this service. To calculate overall costs, indirect special programs that provide funding to specific popu-
costs must also be added to the formula, such as personnel lations. One such program is VFC. Begun in 1994, child-
costs of nonservice personnel, rent, utilities, taxes, insu- ren eligible for medicaid, uninsured, Native American,
rance, general advertising and promotion, and general re- or Alaska Natives may receive vaccinations. Vaccine
pair and maintenance. Pricing of each immunization will providers are supplied the vaccines for free. Although
depend on a number of variables. By having the expected some immunization programs charge a small administra-
costs of the service, coupled with the cost of the product tion fee, all eligible children will receive an immuniza-
and the other factors such as competition, demand, stan- tion, regardless of whether a fee can be paid. Additional
dard rates, and image, a price for each immunization may details for the VFC program are available by contacting
be determined. your state immunization coordinator or state department
For an immunization service, there are a number of of health.
methods for compensation. The first method is patients
paying cash for the immunization. Patients are familiar
with this payment method based on the model of county/
state health clinics that have long charged a fee for Documentation of vaccination is critical to an immun-
immunization administration. The second method relates ization service. In many cases, reimbursement is not
to billing a patient’s third-party payer. In some cases, obtained without proper documentation. However, with a
vaccines are paid for as a prescription would be, sent large portion of immunizations paid for in cash and
electronically, and the pharmacy is reimbursed for the the need to know which patient received which vaccina-
vaccine as well as an administration fee. The inclusion of tion in case of a recall, there are some documentation
an administration fee varies with groups, so an adminis- issues that must be addressed. The use of software, either
tration fee may also be collected from the patient.[291In specifically designed for vaccines or general patient
other cases, patients pay cash for the immunization and management, is available from several sources. Free
receive a detailed receipt, listing the type of vaccine, software is available from the Center for Disease Control
appropriate billing code, and amount paid. The patients and Prevention’s (CDC’s) National Immunization Pro-
are then responsible for submitting the claim to their own gram ( w w w . c d ~ . g o v ) . [ If
~ ~ patient
] profile software is
insurance company for reimbursement. The third method used to track immunizations, it is critical for an easily
is billing medicare. To claim reimbursement under me- accessible, permanent record to be established for im-
716 Pharmacist Managed Vaccination Programs
munizations because prescription records can be purged to your e-mail in portable document format (pdf) for
and even deleted over time, based on state board viewing on freeware-Adobe Acrobat Reader.
regulations. Depending on the requirements of individual
states. immunizers must determine if there is a require-
ment for the use and filing of consent forms. protocol s
agreements. and other related documentation. The va-
rious training programs provide necessary information There are a number of immunization and vaccine net-
regarding documentation requirements, or your respective works designed to help inform professionals and the
state board of pharmacy can be contacted directly with public about immunization efforts regionally and nation-
specific questions. ally. Listservs can also be helpful to those having specific
questions in need of expert commentary. One should be
cautious, as there is as much helpful information about
immunizations and vaccines as there is unsubstantiated
IF0 N and erroneous information. Look carefully at who spon-
sors and writes the information that you are reading. If the
A variety of resources are available for pharmacists in- information seems inflammatory or extremist, it is pro-
terested in beginning a pharmacy-based immunization bably not scientifically valid or presents a skewed inter-
practice. Some of the best resource people include state pretation of the facts. Also, whenever reading tertiary li-
health officers; county health clinic physicians; state terature, pull the references and interpret the information
department of health vaccine coordinators, especially yourself if you are in doubt of its validity. This is the best
those that administer the CHIP or KidCare-like immun- method of ensuring that you are making decisions based
ization programs; and local, board-certified primary care on first-hand information. Of course, the referenced ma-
and infectious disease physicians. There are also a num- terial must come from a refereed, reputable source or else
ber of excellent web sites (see Table 2). The primary it too is suspect. Table 4 lists some reliable networks,
and most reliable source for vaccine and immuniza- organizations, and listservs that pharmacists can access to
tion information is the CDC web site. Most reliable infor augment their knowledge base.
mation about vaccines and immunization on other web
pages is based on information first published in the public
domain by the CDC in their journal, Morbiditj and
Mortalitj Weekly Report (MMWR). For those interested in
keeping tabs on up-to-the-minute vaccine and immuniza-
1. Grabenstein, J.D. Pharmacy-based Immunization Delivery:
tion changes and recommendations. one should access the Self-study Learning Program, 5th Ed.; American Phar-
CDC listserv. This service forwards all issues of MMWR maceutical Association: Washington, DC, 2000; 5.
2. Grabenstein, J.D.; Bonasso, J. Health-system pharmacist’s
role in immunizing adults against pneumococcal disease
and influenza. Am. J. Health Syst.-Pharm. 1999, 56 (17
Table 4 Immunization netu orks, organizations and listservs
Suppl. 2): s1.
esource eb address 3. Grabenstein, J.D. Pharmacy-based Immunization Delivery:
Self-Study Learning Program, 5th Ed.; American Phar-
Allied Vaccine Group http://vaccine.org maceutical Association: Washington, DC, 2000; 6-7.
APhA http:/lwww.aphanet.org 4. Grabenstein; J.D.; Hartzema, A.G.; Guess, H.A.; Johnston,
(Pharmaceutical Care) W.P.; Rittenhouse, B.E. Community pharmacists as im-
APhA-Pharmacist apha-immpharm-subscribe @ munization advocates: cost-effectiveness of a cue to in-
Immunizer Listseri egroups.com fluenza vaccination. Med. Care 1992, 30 ( 6 ) , 503.
Immunization action http://www ,immunize.org 5. Sisk, J.E.; Moskowitz, A.J.; Whang, W.; Lin, J.D.; Fedson,
coalition D.S.; McBean, A.M.; Plouffe. J.F.; Cetron. M.S.; Butler,
MMWR subscription listserv@listserv.cdc.gov J.C. Cost effectiveness of vaccination against pneumococ-
National immunization http://www.cdc.gov/nip cal bacteremia among elderly people. JAMA, J. Am. Med.
program Assoc. 1997, 278, 1333.
NNII http://wwu .immunizationinfo.org 6 . Grabenstein, J.D. Pharmacy-based Irnrnunization Delivery:
VISI http://www.cdc.gov/niplvisi Self-Study Learning Program, 5th Ed.; American Phar-
APhA, American Pharmaceutical Association: MMWR. Morbidity and maceutical Association: Washington. DC; 2000; 6-7.
Mortality Weekly Report; VISI. The Vaccine Identification Standards I NCPA. 2001 NCPA-Pharmacia Digest; National Commun-
Initiative; KNII, National Network for Immunization Information. ity Pharmacists Association: Alexandria, Virginia, in press.
8. Hoeben, 13.9.: Dennis, M.S.; Bachman, 1C.L.; Bhargava, M.; 21. Gardncr. J.S. Establi\hinev a vaccine administration nro-
Pickard, M E ; Sokol, K.M.; Vu, I,.; Rovers, J.P. Role of ram in the community pharmacy. 1. Am. Pharm. Assoc.
the pharmacist in childhood immunizations. J. Am. Pharm. ,40( l ) , 111.
Assoc. 8997. NS37, 551 562. 22. ish, T. Immunimtion project lauded at APhA2000.
9. www.cdc.gov/nip/vfc/ (acccssed September 2000).
10. http://www.insurekidsnow.gov/childhealth/states/states.asp 23. Huffman, D.C., Jr. 2000 NCPA-Pharmucia Digest; Natio
(accessed September 2000). nal Cornrnunity Pharmacists Association: Alexandria, Vir-
11. Grabenstcin, J.D. Phurmacy-Rased Immunization Delivery: ginia, 2000.
Self-Study Learning Program, 5th Ed.; American Phar- 24. Hullinan, D.C., Jr. 2000 NCPA-Pharnzuciu Digest; Natio-
maccutical Association: Washington, DC, 2000; 3. nal Community Pharmacists Association: Alexandria, Vir--
12. http://www.cdc.gov/nip/vfc/cdc~vaccinc~price~list. htm ginia, 2000.
(accessed September 2000). 25. Grabcnstein, 5 .D. Pharmacy-Based Immunization Delivery:
13. Grabcnstei n, J.D. Phczrmncy-Rased Inzmunizutinn Delivery: SelJ1Study Learning Program, 5th Ed.; American Phar-
Self-Study Learning Program, 5th Ed.; Amcrican Phar- maceutical Association: Washington, DC, 2000; 61 -74.
maceutical Association: Washington. DC, 2000; 3-4. 26. Gardncr, J.S. A practical guide to cstablishing vaccine
14. Spruill, W.J.; Cooper, J.W.; Taylor, W.J.R. Phamacist- y pharmacies. J. Am.
coordinatcd pneumonia and influenza vaccination pro- Pharm. Assoc.
gram. Am. J. Hosp. Pharm. 1 27. lrnmunization Lkliv-
15. Weitzcl, K.W.; Coodc, J.R. Implementation of a phar- ery: Self-study Lenrning Program, 5th Ed.; American
macy-based immunization Pharmaceutical Association: Washington, DC, 2000;
chain. J . Am. Pharm. Assoc 89- 104.
16 h ttp ://w w w .aphanc t . org/ 28. Rupp, M.T. Pricing Pharmucisl Cure Services; National
(accessed Sept 2000). Cornniunity Pharmacists Association: Alexandria. Virgi-
17. Spruill, W.J.; Cooper, 1.W.; Taylor, W.J.R. Pharmacist- nia, 1999.
coordinated pneumonia and influenza vaccination pro- 29. Grabenstein, J.D. Pharmrxy-Bused Immunization Delivery:
gram. Am. J. Hosp. Pharm. 1982, 39, 1904-1906. Selr-Sludy Learning I'ro~rana, 5th Ed.; American Phar-
18. Grabenstein, J.D. Pharmacy-Bused Immunization Delivery: maccutical Association: Washington; DC, 2000; 61 -74.
Selj-Study Learning Progrczrn, 5th Ed.; American Phar- 30. Grabenstcin, J.D. Pharmar yBa.ced inzrnunizatioiz Delivc,ry:
maceutical Association: Washington, DC, 2000; 5 -6. SeIflStudy Learning Program, 5th Ed.; American Phar-
19. Grabenstein, J.D.; Bonasso, J. Health-system pharmacist's maceutical Association: Washington, I X , 2000; 6 I -74.
role in immunizing adults against pneuniococcal disease 31. Beavers, N. Vaccinations, pharmacy style. Drug Top.
and intlucnm Am. J. Health Syst.-Pharm. I99
Suppl. 2), SI. 32. Grabenstein, J. D. Phnrmacy-Bared Immunization Delivriy:
20. http://www.immunir.e.org/laws/pharm.htm (accessed Junc SeLf~S'tudj~Learning Program, 5th Ed.; American Phar-
2001). mltccutical Association: Washington, DC, 2000; 6 1 -74
PHARMACY PRACTICE ISSUES
e
in
individual and shared responsibilities of the physician and Federal Controlled Substances Act (CSA).r231The FDCA
pharmacist. CDTM protocols authorizing pharmacists to involves the establishment of rules and regulations by
initiate or modify drug therapy in effect give the phar- which drugs are imported, manufactured, distributed, and
macist dependent prescribing a ~ t h o r i t y . " ~ ] sold in the United States, and the CSA involves the pre-
vention and control of the abuse of controlled substances.
Federal law does not dictate "who" may prescribe and
does not state provisions for l i c e n ~ u r e . ' * ~The
, * ~ CSA
~ also
States have the '-police power" to take regulatory actions fails to establish specific criteria regarding who may pre-
to protect the public health, welfare, and safety of their scribe, merely stating that the prescriber must be licensed
citizens."81 Thus, states have the authority to license to prescribe under state law and be registered with the
health care professionals and to dictate which health care Drug Enforcement Administration (DEA) to prescribe
professionals can prescribe medications. State statutes controlled substances.r261The supremacy clause (US.
called Pharmacy Practice Acts dictate what duties phar- Constitution, Article VI, Paragraph 2) establishes suprem-
macists may perform. acy of federal law over state law; federal agencies enjoy
any states have enacted legislation that expands the freedom from state or local regulation where Congress
practice of pharmacy to include CDTM. As of June 2000, has not affirmatively made federal agencies subject to
there were at least 27 states granting the statutory autho- state law.
rity for the practice of CDTM.[I9]The nature of CDTM Within federal services and agencies, such as the
prescriptive authority for pharmacists varies from jur- Armed Services, Indian Health Service (IHS), and the
isdiction to jurisdiction and its definition is in flux. In Veterans Administration (VA), there may exist directives
some jurisdictions, the pharmacist will be required to or regulations that confer the authority to prescribe on
acquire advanced training and experience in order to certain classes of practitioners. Federal facilities require
participate in such a role. In other jurisdictions, delegated that their health care professionals be licensed by at least
prescriptive authority may be restricted to certain settings, one state, but the scope of practice of these professionals
such as health care institutions or nursing homes. may be broadened or limited by written policies.[*']
At least one author has defined pharmacist prescriptive The federal government has experimented with va-
authority as "the practice of pharmacy whereby a phar- rious models of pharmacist p r e ~ c r i b i n g . [ * ~ The - ~ ~ ] VA
macist has jointly agreed, on a voluntary basis, to work in and the IHS appear to have the most liberal policies
conjunction with one or more practitioners under protocol toward pharmacist p r e ~ c r i b i n g .341
' ~ ~In the VA, clinical
whereby the pharmacist may perform certain functions pharmacy specialists are required to have an advanced
authorized by the practitioner or practitioners under cer- degree or have completed an accredited residency (e.g.,
tain specified conditions or limitations.' '[*01 This ap- an American Society of Health Systems Pharmacy,
proach does not contemplate prescriptive authority as ASHP, accredited residency) or specialty board certifica-
currently practiced by physicians. Another article in this tion (e.g., a Board of Pharmaceutical Specialties, BPS,
volume will expand on CDTM. certification) before they may prescribe medications
Regarding independent prescriptive authority, no phar- within their scope of practice. The scope of practice is
macists in any state have plenary independent prescriptive established within the local VA facility. Once this cri-
authority. Florida is the only state where pharmacists terion is satisfied, the clinical pharmacy specialist may
enjoy true independent prescriptive authority; however, function as an independent health care provider. In the
this authority extends only to a limited formulary of IHS, pharmacists can be credentialed to provide primary
drugs. listed in 21 categories. There are other restrictions care and use their prescriptive authority to evaluate and
as well. For example, a pharmacist cannot prescribe any manage the care of certain patients.'351
injectable drugs nor any oral drugs for a pregnant woman
or nursing mother. The pharmacist cannot exceed the
manufacturer's recommended dosage or in any case give
more than a 34-day supply.[211
Traditionally, the learned intermediary doctrine, shielded
F tiv drug manufacturers and pharmacists from liability by
imposing on the physician the duty to explain and to warn
The sale and distribution of drugs in the United States is the patient about the effects of specific medications.
primarily controlled by two legislative acts. They are the Courts have remained reluctant to impose a "duty to
Federal Food, Drug and Cosmetic Act (FDCA)'221and the warn" on pharmacists dispensing prescriptions, unless
720 Pharmacist Prescribing
pharmacists voluntarily undertake such a duty, e.g., by and corporate or institutional negligence, where protocols
advertising that they will undertake this duty.[36%371
How- and procedures were inadequate to prevent errors.[431
ever, mandated requirements for patient counseling will Pharmacists assuming additional clinical duties are at
likely soon impact court decisions. As the scope of prac- increased risk for malpractice lawsuits because patient
tice expands and judgmental functions increase, so does assessment, treatment, and prescribing are more complex
the potential for liability. functions than making sure a prescription is filled cor-
As pharmacists gain prescriptive authority, as well as rectly or counseling patients about adverse reactions.
responsibility for primary management of certain medi- There is potential for negligence in any aspect of patient
cal conditions, they must acquire new skills and a new care, including taking a history, performing a physical
awareness of the associated legal and ethical pitfalls. examination, interpreting a laboratory test, or prescribing
Pharmacists will be held accountable for negligence in or renewing a drug.
performing new tasks or for practicing outside the scope
of their practice. Pharmacists must also be aware of
potential conflicts of interest, particularly in the man-
aged care setting. Areas that have historically been prob- The voluntary assumption of different or more sophist-
lems for physicians may also become problem areas icated clinical duties by pharmacists can involve admin-
for pharmacist^.[^^^^^ istrative Administrative actions are brought
by the state board and involve the statutorily authorized
revocation or suspension of a license upon administrative
finding of unprofessional conduct. Examples of unpro-
A patient alleging harm by a prescribing pharmacist can fessional conduct for physicians are prescribing a drug
allege that the pharmacist, acting within the scope of without medical justification, prescribing a drug in exces-
practice of the profession of pharmacy, has performed in a sive amounts, and unlawfully dispensing a controlled
fashion that is substandard and that, as a direct result of that drug to a known addict. Unprofessional conduct might
substandard performance, the patient has suffered harm. also include ethical violations like supplying a patient
This patient would allege that the pharmacist was neg- with drugs in return for sex and performing inappropri-
ligent. A plaintiff can establish negligence by establishing ate physical examinations for sexual purposes.
that a duty to conform to a certain standard of conduct State boards of pharmacy will have to develop guide-
existed, that the duty was breached, that damages occurred, lines and procedures to address the expanded clinical
and that there was a reasonably close causal connection functions of pharmacists so that adequate oversight can be
between the conduct and the resulting injury or damage.[411 maintained. While tightly drawn CDTM agreements and
Traditionally, malpractice actions against pharmacists protocols can eliminate some problems, they cannot
have stemmed from dispensing errors.[421 Dispensing eliminate all the problems.
errors can be distinguished from prescribing errors. Under
a dispensing error standard, if a pharmacists fills a
prescription in the manner in which it was ordered by the
prescriber and there are no other obvious contrain- Criminal sanctions may be imposed on health care pro-
dications to the prescription, the pharmacist is not liable fessionals in certain situation^.[^^'^^] These situations in-
for any harm that comes to the patient. In short, courts clude improper prescribing of controlled substances,
have viewed dispensing as a nonjudgmental technical task Medicaid and Medicare fraud, sexual abuse of patients,
that should be undertaken with great care and accuracy. and even negligent care of patients.
Even alleged errors associated with faulty therapeutic Prescribers must be careful in prescribing controlled
interchanges (e.g., incorrect dosage adjustments made substances; it has been held that a licensed physician who
when one drug is dispensed in place of another) are prescribes controlled substances outside the bounds of
dispensing errors, because pharmacists follow a protocol, professional medical practice is no different from a drug
decided on institutionally, when substituting one drug for “pusher” subject to prosecution under the Controlled
another. Hence, the liability applies to the institution, Substances Act. (21 U.S.C.S.fj841[a][ I]). Criminal liability
which exercised the judgment, rather than to the phar- may extend to the prescribing of controlled substances.[4x1
macist, who executed the decision. There is substantial The position of the Drug Enforcement Administration
case law on systems errors, based on the theory of res- (DEA) is that if a state recognizes the authority of a phar-
pondeat superior, a doctrine in which the employer ac- macist to prescribe controlled substances, then the DEA
cepts responsibility for the tort liability of the employee, will register pharmacists as midlevel practitioners. Spe-
Pharmacist Prescribing 721
registration granting controlled substance privileges con- their scope of practice and not exceed it. Phillips”11 stated
sistent with authority granted them under state law. Other that an adequate legal definition of the scope of practice
DEA regulations, 21 CFR §1301.24(b) and 1301.24(c), of a health care professional, as well as realistic standards
exempt agents and employees of a registered individual for that profession, is necessary in order for the courts to
practitioner, hospital, or institution from the requirement correctly apportion liability for wrongful conduct and
of individual registration when they administer, dispense, correctly apply malpractice theory.
or prescribe controlled substances in the course of their CDTM or prescribing protocols must be written care-
official duties or business. Thus, individual registration fully, and they should be reexamined and updated re-
may not be necessary in order for pharmacists to prescribe gularly to ensure that they are not based on a standard too
controlled substances in an organizational setting. high to be reasonably met at all times and in all settings.
It has long been clear that pharmacists would be liable In the pharmacist’s judgment, a patient’s condition or
for exchanging controlled drugs for sexual favors from treatment requirements may seem only slightly inconsist-
either patients or nonpatients. A pharmacist may now also ent with the written protocol; however, pharmacists must
be liable for writing a prescription in exchange for sexual be aware that protocols may leave little room for dis-
favors. Furthermore, pharmacists doing physical exam- cretion. Pharmacists must be careful not to overstep the
inations must avoid behaviors that could be construed as boundaries of their scope of practice, for this could result
inappropriate touching or sexual assault, both of which in a charge of practicing medicine without a license.
could result in criminal or administrative sanctions. Another issue to be considered is the inadvertent mis-
Smith[491stated that there is currently an “enthusiasm representation of one’s profession to patients. If a phar-
for professional accountability, especially when human macist performs a medical procedure or writes a pre-
life is lost.’ ’ Criminal prosecution of negligence involving scription for a patient while the patient is mistaken about
deliberate disregard of patient safety effectively serves the professional status of the pharmacist, the pharmacist
the dual purpose of deterrence and punishment.[501Like could potentially be charged with breach of the duty to
physicians, pharmacists will have to be sensitive to this obtain informed consent.[521
added potential liability as they undertake the clinical The pharmacist who obtains patient histories, conducts
care of patients, including prescribing medications. physical examinations, orders laboratory tests, and pre-
scribes medications must adopt new attitudes and develop
Sta new judgment skills. Communication is paramount, both
with patients and with other health care professionals,
In analyzing whether a duty has been breached in a particularly physicians. It has been said that poor com-
medical malpractice civil action, an administrative action, munication and emotional issues are at the heart of nearly
or a criminal case, the court considers whether the health all medical malpractice actions.[531Interdisciplinary com-
care professional met the standard of care. If a lawsuit munication is vital to ease the passage of pharmacists into
were brought because of damages caused by an incor- expanded prescribing roles; good communication will
rectly filled prescription, the court would look at the care enhance collaboration in patient care and diminish per-
that a reasonably prudent pharmacist in the community ceived threats to physicians’ autonomy and authority.
would have provided in the same or similar circum- Obviously, expanded clinical roles for pharmacists will
stances. Because prescribing drugs has traditionally been require increased patient contact and strong communi-
a physician function, a pharmacist undertaking this func- cation skills. If the patient and the pharmacist fail to
tion may be held to the standard of care of a physician understand each other, the pharmacist’s risk of liability
rather than the traditional standard of care of a phar- is increased.
macist. This may be a more stringent standard because
most physicians have more clinical training and experi-
ence than most pharmacists. If pharmacists hold them-
selves out as competent to physically assess patients and
prescribe medications, citing additional degrees and board The expansion of pharmacist prescribing may be affected
certification, the court may decide to hold them to the by marketplace factors such as the abundant availability
higher standard. of other nonphysician prescribers,[541the current focus of
722 Pharmacist Prescribing
the health policy arena on medication error^,"^] and the Power-Pak C.E. Program No. 424-000-98-008-HO3 at
nationwide shortage of pharmacists.[561 C D T M is a po- http://www.powerpak.com/CE/PharmLaw (accessed April
litically acceptable stepping stone to independent pre- 22, 2001), at 11.
scriptive authority and is supported by many leading 6. Omnibus Budget Reconciliation Act of 1990, 42 U.S.C.
51396 et seq.
national pharmacy organization^.[^'] O n the other hand,
7. Penna, R.P. Pharmacy: A profession in transition or a
the American Medical Association has taken a strong transitory profession? Am. J. Hosp. Pharm. 1987; 44 (9),
stand against nonphysician prescribing, and it will take 2053-2059.
time for pharmacists to establish themselves as prescri- 8a. Hepler, C.D. Pharmaceutical care. Pharm. World Sci.
b e r ~ . [ ~ Traditionally,
’] pharmacists have been gatekeepers 1996, 18 (6). 233-235.
and patient advocates. However, if suddenly the phar- 8b. Hepler, C.D.; Strand, L.M. Opportunities and responsibil-
macist becomes a physician surrogate, the pharmacist’s ities in pharmaceutical care. Am. J. Hosp. Pharm. 1990, 47
role will be seen differently by the patient. The phar- (3): 533-543.
macist will be acting in a more cognitive discretionary 9. Rosenthal, W.M. Establishing a pharmacy based laboratory
manner and asking for more compensation; from the service. J. Am. Pharm. Assoc. 2000: 40 (2)> 146-148,
patient’s perspective, the pharmacist will also become less 150- 152. 154- 156.
10. National Association of Boards of Pharmacy. 1999-2000
available or approachable. Given the complexity of me-
National Association of Boards of Pharmacy Survey of
dications and the volume of medication errors, there will Pharmacy Law; National Association of Boards of
be an interest by the public in retaining pharmacists in Pharmacy: Park Ridge, Illinois, 1999; 94.
their traditional roles as gatekeepers unless these matters 11. Ukens, C. Iowa pharmacists win Medicaid payments. Drug
can be addressed effectively. Topics 1999, 143 (22), 37.
12. Magill-Lewis, J. More states seek prescriptive authority for
pharmacists. Drug Topics 2000, 144 (6), 57.
13. Conway, A,; Beister, D. Independent plenary prescriptive
authority. J. Pediatr. Nurs. 1995, 10 (3). 192-193.
14. Galt, K.A. The key to pharmacist prescribing: Collabora-
This article has summarized critical legal and ethical tion. Am. J. Health-Syst. Pharm. 1995, 52, 1696-1698.
issues associated with the evolving function of the 15. National Association of Boards of Pharmacy. 1999-2000
pharmacist prescriber. The purpose of this chapter is not National Association of Boards of Pharmacy Survey of
to discourage pharmacists interested in prescribing, but to Pharmacy Law: National Association of Boards of
Pharmacy: Park Ridge, Illinois, 1999: 67.
review critical issues associated with a new role. With
16. Boatwright, D.E. Legal aspects of expanded prescribing
proper training. communication with the patient and the authority for pharmacists. Am. J. Health-Syst. Pharm.
patient’s physician. adherence to the appropriate standard 1998; 55, 585-594.
of care, avoidance of ethical and criminal breaches, the 17. Fink, J.L., 111; Vivian. J.C.; Reid; K.K. Regulation of
modern pharmacist will be able to contribute even more to Pharmaceuticals. In Pharmacy Law Digest, 35th Ed.; Facts
the health care team. and Comparisons, Wolters Kluwer, Co.: St. Louis, Mis-
souri, 2000; 27- 122.
18a. Dent v. West Virginia 129 U.S. 114 (1889).
18b. Gianutsos. G. Pharmacy Law: Prescriptive Authority;
Power-Pak C.E. Program No. 424-000-98-008-H03 at
http://www.powerpak.com/CE/PharmLaw (accessed April
1. Fleischer, L. From pill counting to patient care: Pharma- 22, 2001).
cists’ standard of care in negligence law. Fordham Law 19. States authorize collaborative practice. ASHP News Views
Rev. 1999. LXVIII (1); 165-187. 2000: 33 (6). 3.
2. Green. T.C. Licking. sticking. counting. and pouring-is that 20. Riley. K. Collaboi-ative Prescribing Authority for Plzar-
all pharmacists do? McKee Y. American Home Products macists Gains Momentum; At www.ascp.com/public/pubs/
Corp. Creighton Law Rev. 1991, 24. 1449-1477. tcp/l996/sep/collab.html (accessed April 27, 2001).
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Power-Pak C.E. Program No. 424-000-98-008-HO3 at 27.210, 64B16-27.220, 64B16-27.230, 64B16-27.300.
http://.vvww.powerpak.com/CE/PharmLaw (accessed April 22. 21 U.S.C. § 301, et seq.
22; 2001). 23. 21 U.S.C. 5 801, et seq.
4. Fink, J.L.. 111: Vivian. J.C.: Reid. K.K. Civil Liability. In 24. Gianutsos. 6. Pharmacy Law: Prescriptive Authority;
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5 . Gianutsos, 6. Phai-macy Law: Prescriptive Authoriw; 22, 2001), at 1A.
723
25. Nielsen. J.K. Handbook of I+‘ederalDrug L a t v , 2nd Ed.; 41. Kceton, W.P. Prosser and Keetoii on The Law of Torts, 5th
Mundorff, G.. Ed.; Lea and Febiger: Philadelphia, 1992; Ed.; Wcst Publishing: St. Paul, 1984; $30.
206. 42. Abood, R.R.; Brushwood, D.B. Pharmacy Practice and the
26. Niclscn, J.R. Iiegulations o r Pharmaceuticals. In Pharmucy Law; Aspen: Gaithersburg, Maryland. 1994; 355.
Law Digcst; Fink, 111, J.I+ Vivian, J.C., Rcid, K.K., Eds.: 43. S(,iI e.g. Bookrizan v. Ciolirzo, 684 So.2d 982 (La.App. 5th
Lca and Febiger: Philadelphia, 1992; 54. Cir. 1994). Harco Drugs v. Hollowuy, 669 So.2d 878
27. Nielsen. J.K. Handbook of Federal I h t g Law, 2nd Ed.; (1999, Dunn v. Diyt. o/’ Veterans Afrain, 98 F.3d 1308
Mundort’f. G., Ed.; Lea and Febiger: Philadclphia, 1992; ( I 996).
206, Boatwright at 587. 44. Altman, L.K. Overdoses of canccr drug revealed by
28. Ogdcn, J.E.; Muniz. A,; Patterson, A.A. Pharmaceutical paticnt’s dcath. N.Y. Times 1995, A9, Mar. 24.
services in the Department of Veterans Affairs. Am. J. 45. Canccr center hcgins disciplinary process in overdose
Health-Syst. Pharm. 1997, -54. 761 -765. cases. N.Y. Times 1995, A7, Apr. 3.
29. Paavola, F.G.; Dcrinanoski, K.R.; Pittinan, R.E. Phar- 46. Barrctt, D.C. Homicidc predicated on improper treatment
maceutical services i n the United States Public Health of discasc or injury, 45 ALR3d 114.
Service. Am. J. Health-Syst. Pharm. 1997. 54, 7 6 6 ~772. 47. Annas, G.J. Medicine, death and thc criminal law. N. Engl.
30. Williams, R.F.; Moran, E.L.; Bottaro, S.D., 11. Pharma- J. Med. 1995, 333, 527-530.
ceutical scrviccs in the United Statcs Army. Am. J. Health- 48. California Health and Safety Codc $1 1 ]%(a), 21 U.S.C.
Syst. Pharm. 1997. 54, 773-778. 5841.21, 21 C.F.R. 51306.04.
31. Bayles, U.D.: Hall. G.E.; Hostettler, C. Pharmaceutical 49. Smith, A.M. Criminal or merely human‘? The prosecution
services i n the United States Navy. Am. J. Health-Syst. of negligent doctors. J. Contemp. Health Law Policy 1995,
Pharm. 1997, 54. 778 782. 12 (l), 131-146.
32. Young. J.H. Pharmaceutical services in the United Statcs 50. See e.g. People v. Einaugler, 618 NYS2d 414 (App. Div.2d
Air Force. Am. J. Health-Syst. Pharm. 1997, 54, 783 Dcpt 1994).
786. 51. Phillips, K.S. Nurse practitioners: Their scope of practice
33. VHA Dircctive 10-95-0 19. In General Guidelines for Es- and theories of liability. J. Leg. Med. 1985, 6 , 391-414.
tahlishing Medicutioii Prescribing Authority ,for Clinical 52. Cook, J.H. The legal status of physician cxtcnders i n Iowa.
Nurr-iJ.Specialist.r-,Nur.si>Pructitioners, Clinical P h u r m u y Review, speculations and recommendations. Iowa Law
Specialists and Phy.siciu~zAssistantx: 1995 (Mar. 3). Rev. 1986, 72, 21.5 239.
34. VHA Directive 96-034. In Scope of Practice f o r Clinical 53. Fitzgcrald. M A . ; Joncs, P.E. The inidlcvel provider:
Plzarmucy Specialists; I996 (May 7). Colleague or competitor‘! Patient Carc 1995; 24, (I), 20
35. www.ihs.gov (accesscd April 30, 2001), specifically at (13).
www2.ihs .goviPharmac y/index.asp. 54. NABP Appendix on Prcscribing Authority. In Pharmac,y
36. See Baker v. Arhor Drugs, Inc. 544 N.W. 2d 727 (Mich. Law D i g ~ s t ,35th Ed.; Facts and Comparisons, Fink, 111,
Ct. App. 1996). J.L., Vivian, J.C., Rcid, K.K., Eds.; Woltcrs Kluwer, Co.:
37. Termini, R.B. The pharmacist duty to warn revisited: The St. Louis. Missouri, 2000: 794-796.
changing rolc of pharmacy i n health care and the resultant 55. Continuing efforts to prevent medication errors. lpsa
impact on the obligation of a pharmacist to warn. Ohio Loquitur 2000, 27 (9). 1.
N.U. Law Rev. 1998. 4. 551 566. 56. Thc Pharmacist Shortagc. In Culifoniia Mrdicine; Decem-
38. Krohn. I,. Cause of Action Against Physician for Neg- ber/January 1999-2000 at www.heaIthcarebusiness.com/
ligence in Prescribing Drugs or Medicine. In 9 Causes or archivc.. .rniametlicinc/current/pulsepharmacist.html
Action I . (acccsscd April 27, 2001).
39. Federal Criminal Liability of Licensed Physician for 57. See e.g. OrganiLation and Delivery o f Scrviccs: Collah-
Unlawfully Prcscrihing or Dispensing “controlled sub- orativc Drug Therapy Management (98 12) and Collaborat-
stance’‘ or drug in violation of the Controllcd Substances ive Drug Therapy Management Activitics (9801) at
Act (21 U.S.C.S.fjs801 et seq). 33ALK Fed 220. www.ashp.org/bestpracticcs/Med~~lierapy/org/position/
40. Gulbus, V.M. Wrongful or excessive prescription of drugs position.pdf (accesscd April 30, 2001) or Pharmacists
as ground for revocation or suspension of physician’s or Finding Solutions Through Collaboration at www.accp.
dentist’s license to practice, I*awyers Cooperative Publish- com/postition/paperlO.pdf (accessed April 30, 2001).
ing Co., Rochcster, New York, 22ALR4th Supplement, 58. Brcu, I . M.Ds still give thumbs down to nonphysician
1983 and 1995; 669. prescribing practice. Drug Topics 20
PROFESSIONAL RESOURCES
tact atio
Editors, inviting important papers and directing the Becduw ot their h r c d commitment to improving thc
pivotal elements of their editorial life. science and practice of pharmacotherapy, and becau5e 01
their common long-term goals regarding thc professiondl
and scientific direction of the journal, Pharnzacotheiapy
and ACCP initiated an affiliation agreement in 1988
whereby Pharmacotherapy became the official journal
Pharmacothei-upy, The Journal qf Human Pharmacology of the American College of Clinical Pharmacy. This
and Drug Therapy, was founded in 1981 by Russell R. relationship continued lo strengthen and, in 1994, Phar-
iller, Pharm.D., Ph ., a young, fiery visionary who macothcrapy became part OS the ACCP family. Today,
conceptual izcd a jour 1 whose embrace would include Pharmacothcrapy continues to flourish and has become
all scientifically anchored aspects of clinical pharmacy one of the prceminent scientific journals in the area of
and clinical pharmacology. For several years previously, pharmacy and clinical pharmacology.
Dr. Miller had been a Column Editor for the American
Journal of Hospital Pharmacy, captaining a column pro-
phetically named by him, “Pharmacotherapy.” Armed
with this experience, his vision, and his famous energy
and laser focus, Dr. Miller dcveloped and brought Phur- The future directions Sor Pharmarothernpy can be
macotherupy to market nearly single-handedly. Early on, summed up in the preamble of our vision statement:
the value of the journal was recognized by William A. “Phurmucotherapy will become the preeminent journal
Gouveia, Director of Pharmacy at Tufts-New England in the broad field of pharmacotherapy and clinical phar-
Medical Center in Boston, who instrumentally and gra- macology by serving as a knowledgc source and pub-
ciously supported the journal and has provided hospital lication venue S Q ~all health disciplines committed to
space for the journal to nurture and grow optimizing drug therapy outcomes.” Further, Pharmaco-
The journal grew steadily under Dr. therapy will be the source of first choice by hculty when
hand and in 1985, he appointed Richard T. Scheife, teaching health profcssionals about drugs and therapeutics.
Pharm.D., FCCP, as Deputy Editor of Pharmucotherupy. Pharmacotherapy will fully utilize all rclevant forms
Since 1986, lollowing the untimely death QS Russell of media to allow the broadest accessibility to Pharnzu-
Miller, Richard Scheife has served as Editor-in-Chief. cotherapy ’s important and high-impact knowledge.
PROFESSIONAL RESOURCES
HIS
PSAP was initiated in 1991 with the goal of developing and PSAP is continuing to focus on innovations in the drug
distributing a high-quality, intensive, structured program treatment of diseases. Additional emphasis is being placed
for advanced-level clinical practitioners. Other objectives on the integration of alternative medicine into the
of the program included: 1) assisting other structured treatment plan and the role of genomics in the prevention
programs (e.g., staff development or residencies) in and treatment of diseases. Information is being provided
upgrading the clinical competence of clinical pharmacy on new ways that patients may choose to access the health
generalists; 2) assisting advanced-level clinical practi- care system, including home health care and telemedicine.
tioners in maintaining clinical competence; 3) emphasizing In addition, new sources of drug information are dis-
decision-making skills for complex clinical problems. cussed and described.
The goals and objectives of this program have been Consistent with the progressive nature of the PSAP
carried out consistently through the dedication and di- series. innovative formats for delivery of PSAP informa-
rection of the editorial boards (Table 2). the quality writ- tion are being elaluated. These will include a version
ing of leaders in the field of pharmacotherapeutics, and available on the Internet, starting with the fourth edition.
the input of skilled reviewers. Since the second edition of The online version of PSAP provides the same informa-
PSAP, the Board of Pharmaceutical Specialties acknowl- tion as the print version but with additional functionality.
edges its quality by recognizing participation in PSAP as including the ability to take the exams online. The online
a method of obtaining recertification as a Board Certified version also permits access by pharmacists in remote
Pharmacotherapy Specialist. areas of the world.
toring of chronic drug therapy, or management of the therapeutic recommendations or other aspects of
drug formulary. drug therapy to health professionals, peers, pa-
tients, the public, and health care managers.
Assessment factors 13. Assesses and participates in the management of
patients with drug overdose and patients exposed
1. Collaborates with other health professionals to to poisons.
make therapeutic decisions such as drug and drug 14. Performs basic cardiac life support, and assesses
product selection, therapeutic drug monitoring, and participates in drug therapy management
and drug dosing. during medical emergencies.
2. Participates in the planning and development of 15. In conjunction with licensed medical practitio-
patient treatment. ners, develops, manages, and assists in the im-
3. Investigates therapeutic alternatives and recom- plementation of pharmacotherapeutic protocols.
mends or initiates the management of patient- 16. Works with other health care providers and re-
related problems based on interpretation of rele- levant committees to develop programs for im-
vant literature and clinical experience. Com- proving drug use and quality of patient care.
municates the results of these investigations to 17. Documents the economic impact of clinical
health care practitioners in a manner appropriate pharmacy activities for use by organized health
to the training, skill, and need of that health care managers, practitioners, institutions, and
professional. providers.
4. Assists in the management, monitoring, and 18. Identifies therapeutic categories or individual the-
modification of drug therapy in patients with rapeutic agents warranting drug utilization eval-
chronic disease. uation. Develops and conducts drug utilization
5. Reviews patient records and orders regarding evaluation in these targeted areas.
drug therapy and recommends and initiates 19. Coordinates the timely, accurate delivery of
changes as appropriate. medications to patients in conjunction with other
6. Evaluates patients by means of interview and, pharmacy practitioners.
when appropriate, physical assessment to deter- 20. Utilizes pharmacokinetic principles in the for-
mine past medical history, previous medication mulation of therapeutic drug regimens.
use, present medical history, present medication 21. Coordinates the timing and collection of drug
use, present medical condition, and response to concentration samples in biologic fluids. in-
therapy. The pharmacotherapy specialist per- terprets drug concentration results, makes re-
forms accurate and reproducible physical exam- commendations to physicians regarding dosage
ination in accordance with their formal training adjustments, and monitors response to recom-
and experience. mended dosage regimens.
7 . Interprets laboratory and other patient-specific 22. Interprets patient-specific data, physical findings,
data to aid in determining treatment plans and medical history, and other pertinent information
monitoring response to therapy. to aid in designing treatment plans, and monitors
8. Solves therapeutic queries posed by physicians the patient’s response to the recommended dos-
and other health care providers. age regimen.
9. Identifies complications resulting from drug 23. Evaluates the biomedical literature to determine
therapy and recommends or initiates the neces- optimal therapeutic drug-monitoring strategies
sary treatment alternatives to minimize or ne- and population pharmacokinetic parameters.
gate them. 24. Interprets and applies population pharmacoki-
10. Utilizes available state-of-the-art knowledge and netic data to the design of patient-specific drug
technology to assess, improve, and monitor drug dosage regimens.
therapy regimens. 25. Determines patient-specific pharmacokinetic pa-
11. Establishes procedures for detecting significant rameters on the basis of measured drug concen-
drug-drug, drug-laboratory, drug-food, and drug- trations and prospectively applies these data to
herbal interactions, and develops the necessary dosage regimen design.
means to minimize adverse patient consequences 26. Educates health professionals, students, patients,
that might result from such interactions. and the public regarding the utility of clinical
12. Effectively communicates oral and/or written pharmacokinetics.
730 Phar~acotherapySpecialists, Practice Guidelines for (ACCP)
lack 1. Chen
Western University of Health Sciences, Pomona, California, U.S.A.
also focus on nonpharmacologic (e.g., dietary or lifestyle adept, and possess mature interpersonal skills that are
changes). in addition to pharmacologic (e.g., medication required to successfully participate in collaborative de-
education), issues. The pharmacotherapy specialist may cision making.
also be invited to speak at community health sympo-
siums to educate the public on a variety of pharmaco- ertif ication
therapy-related issues (e.g., preventative health medica-
tions used to treat various conditions, medication safety). According to the Board of Pharmaceutical Specialties,
eline Five: The pharmacotherapy specialist the prirnav purpose of specialization in anj health care
continually develops his or her knowledge and skills in profession is to improve the qualih of care individual
applicable practice areas, and demonstrates a commit- patients receive, to increase the chances of positive
ment to continued professional growth by engaging in a treatment outcomes, and ultimately, to improve the
lifelong process. As new pharmacotherapeutic agents are patient's qualit) of life. Specialties evolve in response to
the development of new knowledge or technology that can
introduced into the marketplace and as the practice of
affect patient care, and the resulting changes in patient-
pharmacotherapy evolves, the specialist must be capable
care needs. The rapid, dramatic advancement in clriig
of continually refining. improving, and expanding their therapy in recent decades has created a clear need for
advanced knowledge and skills. pharmacy practitioner:; who specialize in specific kinds oj
treatment and aspects of care. Special& certification is n
As conceptualized by Holland and Nimmo, pharmacy responsible, progressive initiative from the projession to
practice can be categorized into five interrelated practice ensure the best possible patient care.i31
models (see Appendix).'21 The five interrelated practice
models can be simplistically delineated as clinical Although not required, a pharmacotherapy specialist
pharmacy, distributive pharmacy. drug information, phar- may become a Board Certified Pharmacotherapy Spe-
maceutical care, and self-care. The value-added functions cialist (BCPS) through a process established by the
of a pharmacotherapy specialist often depend on the Board of Pharmaceutical Specialities (BPS). In addition
successful utilization of knowledge and skills derived to pharmacotherapy, the BPS certifies pharmacists in
from three of the five basic practice models-clinical several other specialties (e.g.. nuclear pharmacy, nut-
pharmacy, drug information. and pharmaceutical care. rition support pharmacy, psychiatric pharmacy, onco-
Therefore, the pharmacotherapy specialist often has to logy pharmacy).
acquire additional training and education, beyond the Recall that licensure to practice as a pharmacist is
level of general licensed pharmacists, that will allow them attained through a government agency after an indi-
to provide specialized, value-added functions. vidual demonstrates a minimum degree of competency. It
does not indicate that the pharmacist has attained any
additional skills or knowledge that is required to prac-
ALlFlGATl tice as a pharmacotherapy specialist, However, success-
ful completion of BPS certification in pharmacotherapy
The pharmacotherapy specialist is a licensed pharmacist indicates that the pharmacist possesses a level of edu-
who has received specialized education andlor advanced cation, experience, knowledge, and skills that surpass
training in the biomedical, pharmaceutical, and clinical those required to obtain pharmacy licensure.
sciences. The pharmacotherapy specialist must also be Additional information on BPS certification can be
capable of using sound judgment when practicing phar- obtained from the Board of Pharmaceutical Specialties,
macotherapy. The appropriate knowledge. skills. and atti- 2215 Constitution Avenue, NW. Washington, DC, 20037-
tudes of a pharmacotherapy specialist are acquired through 2985 or online at www.bpsweb.org.
academic curricula (e.g., Doctor of Pharmacy program)
at an accredited college or school of pharmacy, post-
graduate training (e.g., pharmacy residency or fellowship),
and/or extensive pharmacy practice experiences.
The pharmacotherapy specialist is generally intelligent A growing body of literature has emerged that supports
and capable of resolving problems that may not have a the value of pharmacist-related activities in improving
clear right or wrong answer. They possess a strong sense of and promoting the safe. effective. and economical use
responsibility, are confident and conscientious, exercise of drugs.
practicality and logic, exhibit emotional stability and Researchers from the Harvard School of Public
persistence, are able to convey expertise, are socially Massachusetts General Hospital, and the Brigham and
734 Pharmacotherapy Specialty Practice
Women's Hospital conducted a study designed to measure Table 2 Hospital-based clinical pharmacy services associated
the effect of a single pharmacist's participation on medi- with reductions in health care costs
cal rounds on the rate of preventable adverse drug events Estimated annual
in an intensive care unit.[41 The participation of an Clinical pharmacy service cost savings"
experienced BCPS was associated with a 66% reduction
in preventable adverse drug events and approximately Adverse drug reaction monitoring $1,636,614,476
$270,000 in annual cost savings to the hospital. The Drug information services $5,309,746,272
BCPS was accepted as a member of the multidisciplinary Drug protocol management $1,757,282,145
Drug use evaluation $1,137,727,143
team, and the researchers noted that mutual cooperation
Medication admission histories $7,07537 1,493
and positive interpersonal relationships between the Participation on medical rounds $8,107,395,977
pharmacy and medical staff were vital criteria for suc-
*Based on 1016 hospitals that offer these clinical pharmacy services.
cessful pharmacist interventions.
(From Ref. [7].)
In another study, services provided by a pharmaco-
therapy specialist (e.g., participation on rounds and re-
viewing of patients' medications) in internal medicine cotherapy practice.[*] This document may also be viewed
and intensive care units was associated with significant online at http//:www.accp.com.
cost savings without negatively affecting the quality of The American Society of Health-System Pharmacists
care provided to patients. The drug cost savings alone (ASHP) supplemental standard and learning objectives for
was estimated at approximately $400,000 per year.[51 residency training in internal medicine and pharmacother-
On a daily basis, pharmacotherapy specialists are often apy are published annually by the Accreditation Services
involved with many types of clinical pharmacy services Division of the ASHP in the Residency Directory, Volume
and functions associated with added value to patients and Two. These documents may also be viewed online at:
the health care system. For example, involvement in car-
diopulmonary resuscitation teams, clinical research, drug http://www.ashp.org/public/rtp/IMSUPPST.html
for
information services, and medication admission histories internal medicine and at
is associated with a significant number of lives saved in http://www.ashp.org/public/rtp/PHTHSUPP.html
for
hospitals within the United States (see Table 1). Six types pharmacotherapy practice
of clinical pharmacy services-adverse drug reaction
reporting, drug information services, drug protocol man-
agement, drug use evaluation, medication admission his-
tories, and participation on medical rounds-are asso-
ciated with an estimated health care cost savings of
billions of dollars annually (see Table 2).[6,71
*Based on 1029 hospitals that offer these clinical services. The distributive pharmacy specialist requires strong
(From Ref. [6].) technical skills in the preparation and dispensing of pres-
~ h a ~ n i ~ ~ (Specialty
~ t ~ e Practice
r a ~ ~ 735
criptions, and communication skills to counsel patients on use or judgment lor referrals, and the ability to establish
the use and administration of medications. They enjoy trust with the patient, to convey expertise, and to com-
technical probleni solving and routine activities. Their municate clearly. Knowledge or nonpres-cription medi-
primary role is to ensure that the right medication gets cations and therapy of minor diseases is important. The
to the right patient at the right time. Common practice primary role of the seK-care specialist is to help patients
settings include the community pharmacy and the hos- make informed decisions about their own care. A suc-
pital pharmacy. cessful self-care specialist must en.joy technical problem
solving and a high degree of social interaction. A com-
ra mon practice site is the community pharmacy.
other members of the health care team. I. Bond. C.A.: Raehl, C.L.; Franke, T. Clinical pharmacy
services, pharmacy staffing, and the total cost of care in
United States hospitals. Pharmacotherapy 2 ~ ~ )20,0 , 609-
elf- 621.
X. ACCP Clinical Practice Affairs Committee. Subcommittee
The self-care specialist require\ strong skills in health R. l 998-2000. Practice guidelines for pharmacotherapy
screening, design and recommendation of drug therapy, specialists. Pharmacotherapy 2
PHARMACY PRACTICE ISSUES
ana
Tularik, Inc., South San Francisco, California, U.S.A.
various countries worldwide, further improving the steps icology studies, evolves through clinical testing, and ma-
toward global harmonization. tures with postmarketing experience. Pharmacovigilance
A number of the ICH guidelines were based on pro- groups within pharmaceutical companies take this ‘‘long
posals offered by the Council of International Organiza- view” of drug safety and put into place systems to ad-
tions for the Medical Sciences (CIOMS).[6’71Originally dress the monitoring and evaluation needs at each phase.
founded by the WHO and UNICEF to produce scientific The potential for a new drug or biologic to elicit un-
conferences, CIOMS has since matured into a “think toward effects is first examined in preclinical studies.[12’
tank” for addressing safety issues faced by both industry Single-dose and repeated-dose toxicity studies examine
and regulators. Like ICH, the CIOMS Working Groups are the pharmacodynamic effects in at least two mammalian
comprised of members from the pharmaceutical industry species. Genotoxicity studies examine the propensity of
and national regulators. Examples of the work of the the drug to cause mutations and chromosomal damage.
CIOMS group have been development of a common form Carcinogenicity studies assess the ability of the com-
for reporting individual cases and periodic summaries of pound to produce cancerous changes in cells. The toxic
adverse events, elements for electronic data transmission effects on reproductive organs and fertility is examined
of adverse events, a framework for determining attribut- in reproductive toxicity studies. Untoward effects may
ability of an adverse event to a drug, and a process for first be identified during these initial pharmacodyna-
weighing the risks and benefits of a drug product. mic studies. Safety pharmacology studies then seek to
further identify adverse effects across a series of organ
systems and to define the dose-response curve for these
adverse effects. This information forms the initial basis
for the scope of adverse effects that might be anticipated
Additional organizations have developed to foster drug in humans.
safety. The WHO Department of Essential Drugs and The first clinical trials of a new compound generally
Medicines (EDM), created in response to the thalidomide take place in healthy volunteers. These studies seek to
disaster, established the Drug Safety Programme to com- establish the initial safety profile in humans and obtain
municate information among member states on drug safe- pharmacokinetic information. Up until this point, the ex-
ty and efficacy, including the prompt transmission of trapolation of the adverse events identified from precli-
serious adverse event experiences.“] The Uppsula Mon- nical studies to humans remains theoretical. Even adverse
itoring Centre, through an agreement with WHO, oversees effects associated with other members of the drug class
a collaborative effort among 64 countries, as of January remain to be demonstrated for the product under study.
2000, to monitor drug safety w o r l d ~ i d e . [ ~The
, ’ ~ ~Cen- Emphasis is placed on the clinical investigator to closely
tre’s goals are to identify safety risks as soon as possible monitor the subjects for the development of any adverse
and communicate them to healthcare professionals and effects and to attempt to determine whether a causal rela-
the public in order to facilitate risk-benefit assessments. tionship exists between the event and the study drug.
The WHO program also supports the European pharma- The essential elements of pharmacovigilence during
covigilence Research Group (EPRG). The EPRG, estab- clinical trials of an investigational compound span from
lished in 1993, is comprised of members from academia adverse event identification through characterization and
and regulatory agencies from 10 European Union member Identification is focused on “treatment-
states.“ ‘I The group conducts research and investigations emergent” adverse events. These events can then be char-
into specific drug safety issues. acterized by incidence, prevalence, severity, seriousness,
and relationship to the study drug (causality). The data can
then be examined to identify potential risk factors and
CLI markers with which to anticipate the occurrence of an
adverse event.
The maturing of the field of pharmacovigilence has led Determination of a causal relationship between the use
industry and regulators to understand the evolutionary of a drug and the development of an adverse event can be
nature of safety surveillance. Whereas much of the im- difficult. A number of algorithms have been developed in
petus for promulgating regulations to ensure public safety an attempt to standardize this p r o c e ~ s . “ ~ -Although
~~’
was based on problems with commercialized products, a each employs elements that are generally accepted, none
greater appreciation has developed that understanding has been widely adopted in its entirety due to limitations
the safety profile of a medication begins before it reaches in reproducibility and predictive value. Over time, em-
the clinic. Safety surveillance begins with preclinical tox- phasis has shifted from attempting to assign causality at
738
A significant limitation when analyzing spontaneous fundamental process in clinical medicine. Unfortunately,
reports of adverse events is the inability to calculate fre- what appears to be a straightforward process has no ag-
quency rates. In a controlled clinical trial, the number of reed-on procedures or quantifiable statistics. Approaches
events (numerator) and the number of trial subjects (deno- to risk- benefit assessment during development have been
minator) are well known. A frequency rate for the adverse published,“6-”1 but little work has been directed toward
event can be calculated. However, in the postmarketing analysis of marketed drugs.
setting it must be assumed that all adverse events are The CIOMS Working Group addressed the task of
underreported: hence the numerator value is poorly known developing a common approach to risk-benefit analysis in
and the total number of patients exposed to the drug cannot its fourth guidance-CIOMS I Y ‘ ~ ]In addition to provid-
be definitively established, rendering the denominator ing a standardized methodology for risk assessment, the
value unclear. At best, postmarketing data can be de- guidance describes concepts and procedures for determin-
scribed as reporting rates that cannot be directly compared ing the magnitude of a safety problem and deciding on
to the frequency rates arrived at in the clinical trials. appropriate actions. Although not a definitive set of algo-
A significant advance in the analysis of safety infor- rithms, the guidance offers pharmacovigilence personnel
mation for marketed drugs is the availability of large-scale, not only a common schema for approaching risk-benefit
record-linked databases. These are databases of patient assessment but also a recommendation that such common
demographics, prescription history, laboratory data, and approaches be utilized by industry and regulators alike.
clinical data that are linked. Health maintenance or-
ganizations and academic programs have been instru-
mental in the construction of these databases, e.g., Group
Health of Puget Sound, Kaiser Permanente. and General
Practice Research Database. Epidemiologists utilize these The momentum of international harmonization efforts
systems for case-control studies that can provide estimates will continue to improve the ability with which ad\erse
of relative and absolute risk. Based on a signal derived events are classified, analyzed and communicated. Paper-
from spontaneous reports, for example, pharmacoepide- based system will be replaced by electronic transmission
miologists can use these record-linked databases to explore of adverse event information. The WHO monitoring
the validity of this signal in a large patient experience. program will extend the Bayesian artificial neural net-
The application of epidemiological principles has been works for analysis of the large amounts of adverse event
a valuable development in the practice of pharmacov- data at its disposal.[301In the United States. efforts are
igilence.[*” The detection of new adverse reactions is underway at the FDA to improve the content and format
made difficult by their unanticipated nature, delayed pre- of product prescribing i n f ~ r m a t i o n . [ ~
sentation, infrequent occurrence, presence of multiple Pharmacogenomics will likely play an increasingly
concomitant drug treatments and/or other confounding important role in pharmacovigilence as genetic poly-
risk factors. The science of epidemiology brings to phar- morphisms become better understood. Genetic variation
macovigilence the concept of risk assessment, tools for can play a significant role in the safety profile of a drug.
making comparisons, and a vocabulary for describing The science of pharmacogenomics-the study of genetic
risk. Relative risk provides a measure of the size of an factors in drug response-has only recently become a
association between drug exposure and an adverse event, viable tool with the advent of sufficiently sophisticated
which is helpful for establishing associations. The ab- analysis Knowledge of genetic variations
solute or excess risk is an indicator of the extent to which in known polymorphic enzymes can help identify geiio-
an adverse event can be attributed to drug use. The epi- types at particular risk. An appreciation that terfenadine
demiologic principles of relative and absolute risk provide metabolism was dependent on a cytochrome P450 iso-
a basis on which these risks can be balanced against an- enzyme (CYP2D6) that was effectively absent in 6- 10%
ticipated benefits. of the Caucasian population may have altered the de-
velopment decisions for the compound or the target pop-
~ l a t i o n . [ Such
~ ~ ] examples of genetic polymorphisms of
FIT T genes associated with drug metabolism are among the
best studied to date. Genetic variants can give rise to un-
Once a safety signal is identified and analyzed. pharma- expected drug effects, e.g., hemolysis in glucose-6-phos-
covigilence personnel must determine whether it signifies phate dehydrogenase deficiency. and variants in the drug
a shift in the relationship between risks and benefits. target can alter the response and frequency of adverse
Weighing the risks and benefits of drug treatment is a effects, e.g., variants in the beta-adrenergic receptor can
740 Pharmacovigilence
alter the response to beta-agonists in asthmatics.r341Mu- 16. Hutchinson, T.A.; Leventhal, J.M.; Kramer, M.S.; Karch,
tations in membrane transporters involved in drug ab- F.E.; Lipman, A.G.; Feinstein, A.R. An algorithm for the
sorption can lead to substantial changes in bioavailability. operational assessment of adverse drug reactions. 11. De-
Transporter pharmacogenomics is a rapidly developing monstration of reproducibility and validity. JAMA, J. Am.
SOC.ASSOC.1979, 242 (7), 633-638.
field in its own right. As the field of pharmacoge-
17. Leventhal, J.M.; Hutchinson, T.A.; Kramer, M.S.; Feinstein,
nomics matures, it promises to afford a mechanism to
A.R. An algorithm for the operational assessment of adverse
improve the safety profile of a large number of drugs. drug reactions. 111. Results of tests among clinicians. JAMA,
The process of pharmacovigilence requires the con- J. Am. SOC.Assoc. 1979,242 (18), 1991-1994.
tribution of many healthcare professionals in industry, 18. Louik, C.; Lacouture, P.G.; Mitchell, A.A.; Kauffman, R.;
government, and clinical practice. With improved har- Lovejoy, F.H.; Yaffe, S.J.; Shapiro, S. A study of adverse
monization, more sophisticated analysis tools, and reactions algorithms in a drug surveillance program. Clin.
clearer communication, more patients will be able to Pharmacol. Ther. 1985, 38 (2), 183-187.
realize the benefits of drug therapy while minimizing the 19. Pere, J.C.; Begaud, B.; Haramburu, F.; Albin, H. Compu-
attendant risks. terized comparison of six adverse drug reaction assessment
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(7), 623-632. 2000, 105, 487-492.
PHARMACY PRACTICE ISSUES
Chip Robison
BeneScript Services, Inc., Norcross, Georgia, U.S.A.
Kimberly ~ @ ~ n a ~ ~ i o
Canton, Georgia, U.S.A.
dicate claims and the codes used to submit utilization data substantial savings by outsourcing the services of a PBM.
for formulary drug rebates. For example, a plan with 100,000 members who use
Diversified Pharmaceutical Services, Inc., with roots their benefit averaging 0.7 prescription claims per mem-
going back to the early 1970s, is credited for establishing ber per month at 60 cents per claim would be billed
maximum allowable cost (MAC) programs and mandat- $42,000 per month. Compare this with the cost of build-
ory generic drug programs.[31 It has been associated with ing a plan with an in-house pharmacy program staff,
SmithKline Beecham Healthcare Services and was once a which could run into the hundreds of thousands of dollars.
subsidiary of the United Healthcare Corporation, but is The question that must ultimately be answered before
now part of the Express Scripts network. contracting with a PBM is whether doing so will yield
Actual ownership of the PBMs varies. Some compa- drug cost savings. Managed care organizations consider-
nies are privateiy held corporations (e.g., National Pres- ing contracting for PBM services must compare the cost
cription Administrators). Some are publicly traded (e.g., of the potential PBM contact with the cost of building an
Express Scripts). Some are now or have been owned by internal pharmacy program. For many organizations,
managed care organizations (e.g., Pacificare's ownership purchasing the services of an established PBM (with its
of Prescription Solutions or Prudential's ownership of attached clinical expertise) makes better business sense
Integrated Pharmacy Solutions). They have also been than building one internally.
owned by retail pharmacy chains, as in the case of Rite In addition, PBMs can assist with many of the
Aid's ownership of PCS prior to its evolution into Ad- challenges facing managed care organizations in the
vance PCS. Pharmaceutical manufacturers have pur- administration of a prescription drug program. These
chased PBMs (e.g., Merck owns Medco and Lilly at challenges may include
one time owned PCS).
Administering multiple plan designs and copay-
ments. Managed care organizations will inher-
ently differ in the way their plans are designed.
For example, a step therapy program for the treat-
ment of hypertension may be part of one orga-
In the 1990s, both utilization and overall cost of phar- nization's design, but not anothers. An assertive
maceuticals increased drastically. This allowed cost PBM can set both prescribing protocols for the
containment programs and the PBM business to flourish. physicians as well as produce policies for pres-
The annual percent change in retail prescription prices cription processing with regard to copay levels.
rose significantly higher than the consumer price index.
Performing audits of contracted pharmacy pro-
Marketplace entry of new, higher-priced medications and
viders (e.g., i*etailpharnzacies contracted to pro-
direct to consumer marketing of medicines contributed
vide pharnzacy services). This is done to ensure
significantly to increased patient utilization. Analysis of
that both the PBM and the managed care orga-
the recent explosion of drug prices is beyond the scope of
nization (payer) are being charged properly by
this chapter; however, a sobering fact to note is that na-
the dispensing pharmacy for what is actually
tional health care expenditures for prescription drugs
dispensed to the patients.
totaled $91 billion in 1998. This is expected to reach
about $243 billion in 2008.[41 Adjudicating claims electronically. This refers to
The annual percentage increases in prescription expen- the actual transmission of a prescription claim
ditures have surpassed all other components of personal via telephone lines from the pharmacy to the
health care expenditures in the past decade. Yet, growth PBM database. Various benefit design rules are
in expenditures and prescription drugs still comprise a applied to the electronic claim as it is processed.
relatively small proportion of total health care costs. This processing or adjudication step is an ex-
pensive item and can be administered on a cost
per claim basis. Depending on the number of
covered patient lives within a prescription plan,
economies of scale may prevail, allowing for a
low cost per claim adjudication fee to be offered
Typically, PBMs charge a managed care organization by to large plans. As the reader may imagine, cost
the number of prescription claims administered. Plans per claim is a competitive area among marketers
with low to moderate levels of membership can realize of PBM services.
Pharmacy Benefit Management 743
4. Providing Drug Utilization Review (DUR) edits. 9. Ensuring competitive administrative fees asso-
These are electronic messages transmitted back ciated with prescription claims and management
to the dispensing pharmacist when filling a pre- reports. Competition in the marketplace puts
scription. These edits provide messages con- pressure on the PBM to offer a managed care
cerning many aspects of drug therapy, and can organization a fair and equitable rate on the
flag nonformulary drugs when attempts are made prescription claims processed by the PBM. As a
to fill them. The DUR message from most service not unlike others in health care, fees
PBMs alert the pharmacist to preferred drugs in charged by PBMs are negotiable and should
lieu of the nonformulary drug being considered provide value to the managed care organization.
for dispensing. The National Drug Code (NDC)
number flagging or blocking at the point of Once hired by a managed care organization, the PBM
dispensing is a common function of DUR edits. must also report utilization trends back to the organiza-
Other parameters may be programmed into tion. These reports must be meaningful in a way ?hat will
DUR edits by a PBM. For example, age limit provide the managed care organization with data from
parameters may be used for certain NDC num- which to draw informed conclusions as to how it is
bers. Cosmetic (e.g., retinoic acid) products or spending its prescription drug d ~ l l a r . ‘ ~ ’
attention-deficit disorder drugs may be excluded
from coverage in patients over a certain age.
Entire therapeutic category exclusions can be lTlES
managed by DUR edits as well. For example,
the oral contraceptive or fertility drug class pres- A number of products and services beyond the collection
criptions can be programmed for DUR flags. and processing of pharmacy prescriptions are offered to
However, DUR edits can be patient friendly. customers by PBMs. The following paragraphs, although
Drugs that require a prior authorization can be not complete, provide a listing of some of the many
logged into a patient’s drug coverage profile. services offered by PBMs.
Once authorization is complete for the initial
filling, subsequent refills can be approved elec-
tronically by means of DUR edits. ssira
5 . Introduce initiatives on behalf of drug manufac- A claim is a bill, generally submitted electronically in a
turers to support the goals of a managed care standardized NCPDP format (NCPDP), for products and
organization. This may take the form of unres- services rendered by retail pharmacies. Once received, the
tricted grants, promotion of internal health fairs, claim is audited via a series of programs that make up the
and wellness programs. For example, the ma- adjudication process. The information is scrutinized for
nufacturer of cholesterol medicine may support appropriate content, correctness, eligibility, pharmaceu-
health initiatives of a managed care organization tical, and benefit appropriateness. Real-time electronic
aimed at reducing heart disease. A PBM can often point-of-sale claims are adjudicated according to the plan
be a valuable conduit for this type of support. design of the patient’s benefit. The technology used
6 . Communicating prescription benefits, forin- allows for the data to be merged with eligibility and
ulary drug lists, utilization management, and di- pharmacy data pertaining to each member and plan. The
sease management initiatives to physicians and adjudication process also provides electronic messaging
to patients. for ease of prescription filling by the pharmacist. (The
message received is guided by the results of the various
7. Negotiating the contracted drug reimbursement adjudication programs.) The goal of this messaging is to
rates f o r network and mail sewice pharmacies. foster plan/formulary compliance and ultimately bring
Some PBMs use a MAC pricing schedule for about cost efficiency for payors.
generic drugs, limiting the pharmacist’s reim- There are 12 basic audit steps in the adjudication
bursement rates, and thereby containing cost for process (Fig. 1). They are as follows:
the health plan payor.
8. Maximizing cost savings by sharing savings 1. Submit claim-The pharmacy sends the claim
from pharmaceutical contracts with the nmn- electronically to the PBM responsible for proc-
aged care organization. essing, as indicated by the patient’s benefit card.
744 Pharmacy Benefit ~ a n a ~ e ~ e n t
1 3 4 5 6
12 11 10
2 . Format clain-Claim information is inserted program for agreement with the other compo-
into appropriate fields of the NCPDP stand- nents of the prescription information (e.g., drug
ard format. selection agrees with NDC number, drug agrees
with the dose, dose agrees with the dosing
3 . Member and group eligibility-The patient/
schedule, quantity agrees with day’s supply).
member information is checked against a current
list of patients eligible to receive a medical 7 . Beaefit[61-This indicates what medications are
benefit. The type and extent of the benefit covered and under what circumstances. The
received is indicated by the “group” to which benefit is defined by the degree to which the
the individual belongs (e.g., all employees of a patient will contribute to products and services
single company usually make up a “group”). via a copay. The entity that provides the benefit
quantitates and determines the benefit limits (e.g.,
4. Pharmacy eligibilitj-Not all medical benefits if the benefit is provided to the patient by the
include coverage of pharmaceuticals. The mem- employer, then the employer dictates the condi-
bedpatient information must be checked against tions of the benefit-for example, “lifestyle
a list of individuals eligible for a pharmacy be-
drugs” that offer cosmetic improvement may
nefit (e.g., currently medicare beneficiaries do not be covered in favor of covering critical
nor receive a pharmacy benefit; thus, no assist-
medications that treat disease).
ance is offered in the coverage of pharmaceuti-
cal costs). 8. Gopajs and deductibles‘61-These are the pre-
scribed dollar contributions that the patient must
5. M D eligibilit).-The prescribing physician is pay to receive a particular pharmacy product or
checked against a list of approved health service. The prevailing logic for copays is that
plan providers. increasing the patient’s share of the cost will
6. Prescription information check-Once the pre- encourage the patient to influence prescribing.
scription information is placed in the proper If the patient must pay a higher copay, then the
format, each piece of information is checked by a patient may influence the physician to seek
Pharmacy Benefit Management 745
lower copay (less costly to the health plan) electronically back to the pharmacy. Updating
drugs. Thus, copays are used indirectly to steer a patient file ensures a continuous, accurate
a physician’s prescribing habits. Copays are prescription record. This record can then be
also used to encourage patients to request the checked for compliance, drug interactions, com-
generic version of medications when available pared with medical claims to check for appro-
(e.g., a patient benefit may state a low copay of priateness of treatment. etc., all of which offer
$5 for a generic medication, $10 for a brand opportunity for the pharmacist, physician, or
name medication, and/or $25 for a nonformu- PBM to avoid an adverse event or improve a
lary medication). clinical outcome.
12. Forinat and send response-The adjudicated
9. D u g pricing-The prescription information is
claim is returned to the dispensing pharmacy.
matched with a listing of per unit price, as
The industry standard for claims communication
dictated by PBM purchase contracts with phar-
is National Council for Prescription Drug Prog-
maceutical companies.
ram (NCPDP) formatting. With this format, the
10. DUR-This process can take many forms de- various field containing characters and text are
pending on the goal to be accomplished. The standardized and easily recognizable to phar-
drug can be scrutinized against the existing pa- macies. This final link will clarify such para-
tient profile for drug interactions, accuracy of meters as:
dosing. and/or prescribing instructions or dupli-
city. The purpose is to ensure appropriate pre- 0 patient identification
scribing for the most common or majority use. m ingredient cost(s)
It is not intended to check appropriateness for 0 days supply of medication
clinical exceptions to “the rule.” Actions to be m copay due from patient
taken, if any, are relayed back to the pharmacy 0 dispensing fee
by an edit message. The edit message may in- 0 final amount reimbursed to the dispensing
dicate that the prescription will not be covered pharmacy
until discrepancies are corrected or further in-
formation is given. The DUR message is one of
the vital communications between the PBM and
the dispensing pharmacy. The actual DUR mes-
sage can suggest a preferred formulary drug for PBMs have contractual relationships with retail phar-
a particular nonformulary drug submitted. The macies and share a common electronic network. Through
DUR message may be in the context of an this common network, prescription claims can be sent to a
interaction warning or overdosage warning common point of collection (the PBM). Large PBM-
supplied by the logic of the PBM’s internal retail networks offer customers easy access to prescrip-
software. Discrepancies between quantity and tions throughout the United States. Network relationships
day’s supply violations may be communicated are less costly to PBM customers due to volume discount
back to the dispensing pharmacist as well. For and greater billing/payment efficiencies (e.g.. all phar-
example, a pharmacy may enter correct infor- macies that contract with the PBM are part of that PBM’s
mation for a birth control prescription. If the pharmacy network).
patient file indicates the patient is female and
that birth control is part of the allowable
benefit, then the prescription will be covered
with a copay. If the patient’s file indicates the
patient is male, a rejection code will be gen-
Providing volume discounts and less administrative cost
erated with an appropriate message sent back to
to the payer, by virtue of making payments to only one
the pharmacy.
business, makes mail order a cost-efficient alternative.
11. Update file and archive-The patient’s drug Patients are often incentivized to use mail order services
profile and the PBM’s data archive are updated with offerings of home delivery, discontinued multiple-
to reflect the latest information. The information month supplies of medication, and discounted copay-
necessary to complete the transaction is sent ments .‘6371
746 Pharmacy Benefit Management
PBM representatives act as liaisons with the purchaser of PBMs evaluate prescription data to identify drugldisease
pharmacy benefits for the purposes of exchanging in- patterns of use, and develop programs targeted to ensure
formation on benefit utilization, collaboration on health correct dosing, compliance, and maintenance of treatment
education or interventional programs, maintaining and standards are maintained. Disease management programs
updating the benefit as needed, and addressing patient may originate from within the PBM or may be outsourced
needs and satisfaction issues. PBM representatives and to a specialty company with this expertise. Generally,
purchasers also collaborate to ensure that quality phar- pharmaceutical manufacturers assist PBMs with their
maceuticals and services are delivered at minimal cost. disease management initiatives.
Good disease management translates into greater produc-
tivity and less absenteeism for the employer. Thus em-
ployers have a vested interest in improving the health of
their employees. An employer with a young covered po- PBMs offer aggregate reports from their prescription data
pulation-young men, women. and children-would have archives. These data are stripped of all patient-identifying
concerns that medications for diseases predominant in the information and are disseminated to physicians or em-
young, like asthma, would be adequately covered by the ployers for the purpose of enhancing patient outcomes.
benefit and used appropriately by patients. Account man- PBMs offer the expertise of clinical pharmacists to assist
agers work with employers to create ways to meet these in the interpretation of aggregate reports. Clinical phar-
health goals. macists help identify trends and goals to set for ma-
ximization of patient outcomes.
PBMs offer analysis of drug utilization patterns at both PBMs offer educational services to patients in many
individual and group levels. From these analyses, they forms. These may include newsletters, specialty pro-
may recommend an intervention, education, or course of grams, advice lines, consultation services, and internet-
action to ensure appropriate utilization and outcome. based information services, and so on.
DUWDUE edits also occur online as the prescription is
processed. If the prescription information does not match
program criteria for appropriateness, an edit message is
generated to the filling pharmacy. PBMs offer services to both customers and benefit
purchasers to ensure that questions are answered and
problems are resolved in a timely manner.
graphic parameters to include prevalence of disease, age close many of the loopholes through which medication
of the insured population, and cost limitations. errors often pass. By eliminating the handwritten word,
e-prescribing would significantly reduce errors in pre-
scription interpretation; can allow for real-time drug
B screening, formulary, and DUR checks; and streamline
the communication process between the HMO, pharma-
The business of medicine and of managed care is ever cist, and physician.
evolving. The PBM industry is continually challenged Baniers to electronic prescribing generally circulate
with issues surrounding the development of new treat- around issues of connectivity and ease-of-use issues with
ments and technologies. Listed here are a few of the PBM physicians, and the cost of implementing this tech-
trends of the future. nology in both physician practice and pharmacies. For
a seamless system to work, the prescribing physician
must have
A tiered benefit is a type of pharmacy benefit that has 1. Ready access to benefit irzformation. What is the
grown in popularity in recent years. Rather than follow the formulary, and what if any conditions must be met
“traditional” formulary process of selecting “best in for coverage?
class” medications for formulary inclusion, a tiered 2. The Benefit provider information. Who is the
benefit simply stratifies medications according to some HMO/PBM benefit provider?
basic parameters, usually efficacy, safety, and cost. This 3. A Common electronic interface. Will a single
design of benefit usually does not preclude the coverage program interface with all benefit providers? Will
of any given medication (as with the traditional closed it interface with all retail pharmacy providers?
formulary design) but rather allows for a greater cost How will the prescription information get to the
sharing by the patient. Medications in lower tiers are correct provider? What devices will physicians
usually available as generic, possess a clinical advantage use to interface with the system? Computers,
of some type, or are more cost-efficient. Medications handheld devices?
placed in higher tiers are usually those that offer no cli-
nical advantage, are more expensive, or are “lifestyle en- Although the benefits to the patient and the health care
hancing” in nature (e.g., medications for sexual per- marketplace would be tremendous, there are many
formance, cosmetic drugs, fertility agents, hair restoration obstacles to overcome. One market development holds
drugs, appetite suppressants, oral contraceptives). great promise for bringing the health care system one step
Traditionally, pharmacy benefits have been of three-tier closer to making e-prescribing a reality: On February 22,
design; each tier associated with an ever-increasing copay 2001, three of the largest PBMs. Advance PCS, Express
(e.g., 1st tier, $5; 2nd tier, $10; 3rd tier, $25) €or common Scripts, and Merck-Medco announced an agreement to
medications. Under this design a few select medications, establish a common utility for the collection of pre-
such as “lifestyle-enhancing” drugs, were either not in- scription information. The company, known as RxHub
cluded in the benefit or were severely restricted. LLC, will act as the central “conduit of information be-
Consumer demands for greater access to medications tween all parties” and .‘will provide a single stan-
has prompted the development of a fourth tier. This differs dardized channel of communication to link physicians
in that it introduces the concept of coinsurance, or per- through electronic prescribing software on their hand-
centage copay to consumers. Medications in this tier would held computer or practice management system to pharma-
be covered as a percentage of total medication cost as cies, PBMs and health plans.”‘81 The success of e-pres-
opposed to a set c o p y amount. For example, fertility me- cribing and of ventures like RxHub holds great promise
dications might be covered at 50% of their total cost. The for increasing efficiency.
patient would pay 50% and the pharmacy benefit would
pay 50%. Thus providing the consumer and the physician tenti~l tion
with an incentive to discuss considerations of cost.
Due to their inherent activities. PBMs are alleged to be
involved in the practice of pharmacy by some lobbying
groups. As a result, the National Association of Boards of
Electronic prescribing has been a much sought after goal Pharmacy has advised each state board of pharmacy to
by the health care industry. Electronic prescribing would evaluate and license PBMs in their area. The Academy of
748 Pharmacy Benefit Management
Managed Care Pharmacy disagrees with PBM licensure, 6. Stern. C. The history, philosophy and principles of
claiming that a very small percentage of PBM activity pharmacy benefits. J. Managed. Care Pharm. 1999, 5 (6),
could be defined as practicing pharmacy. Legislation has 525-531.
been proposed by various state legislatures to license 7. Copland. Employee Benefit Research Institute. 1999,
April, no. 208 (www.ebri.org).
PBMs as pharmacies. Licensing legislation most probably
8. http://www.express-scripts.com/other/rxhub/rxhub.html,
will take the form of a separate class of pharmacy li-
Press Release: February 22, 2001: New Venture to Jump-
censure. Separate licensing would in turn lead to potential start Electronic Link with Physicians and Pharmacies.
state regulation of PBMs. Georgia, for instance, has 9. Where We Stand, Therapeutic Interchange, Position Paper.
signed into law a bill that mandates the licensure of Revised by the AMCP Board of Directors; Academy of
pharmacy benefit managers doing business within the Managed Care Pharmacy: 100 North Pitt Street, Suite 400,
state. This licensure requirement allows for inspection of Alexandria, Virginia 22314. 1999, November (www.amcp.
pharmacy benefit managers by state inspectors. 0%).
Another regulatory issue is therapeutic interchange of
medications. PBM clinical departments often set up
internal protocols for alternate product substitution within
a therapeutic class. The National Association of Boards of
Pharmacy contends that therapeutic substitution is practi-
cing pharmacy. In one of its position papers, the Academy Web Sites
of Managed Care Pharmacy supports the use of thera- Academy of Managed Care Pharmacy web site: www.
peutic interchange programs. The Academy of Managed amcp.org
Care Pharmacy contends that this decision is ultimately Employee Benefit Research Institute web site: www.ebri.
that of the phy~ician.'~'
or g
Another form of regulation now facing PBMs is in the Medscape web site: www.medscape.com
form of the Health Information Portability and Account- National Council for Prescription Drug Programs web
ability Act. This enormous set of regulations, which is
site: www.ncpdp.org
expected to have full legal effect in the near future, would Pharmaceutical Care Management Association web site:
potentially affect not only the processing of confidential www.pcmanet.org
patient information, but also the administration of other Pharmacy Benefit Management Institute web site: www.
clinical programs (e.g., disease management, formulary pbmi.com
management, drug compliance programs, patient and Pharmscope news. articles, and editorials: www.
clinician education programs). pharmscope.com
RxHub LLC web site: www.rxhub.net
Wk
Jou rnals/Text
Paul Hueseman, PharmD, Medical Information Scientist,
National Accounts, AstraZeneca Pharmaceuticals, and Ben Drug Benefit Trends is published monthly by SCP/
Sloan, National Account Director, Salix Pharmaceuticals. Cliggott Communications, Inc., 330 Boston Post Road,
Darien, CT 06820-4027.
Healthplan is published bimonthly by the American
EFE S Association of Health Plans (AAHP). 1129 20th Street,
NW Suite 600, Washington, DC 20036-3421.
1. Navarro. R.P. Managed Care Pharmacy Practice; Aspen Journal of Managedcare Pharmacy is peer-reviewed and
Publishers: 1999; 223-231. published bimonthly by the Academy of Managed
2. The National Council for Prescription Drug Programs
Care Pharmacy, 100 North Pitt Street, Suite 400 Alex-
website: www.ncpdp.org.
andria, VA 22314.
3. Diversified Pharmaceutical Service, Internal Promotional
Document: 1998. Managed Care is published monthly by Managed Care,
4. Smith, S.. et al. The next decade of health spending: A new Medimedia USA. 275 Phillips Boulevard, Trenton, NJ
outlook. Health Aff. 1999, 94, JulyiAugust. 08618.
5. Sawyers, T. Test prospective PBM before signing contract. Navarro, Robert P., Managed Care Pharmacy Practice;
Managed Care 2000, March. Aspen Publishers: 1999.
PROFESSIONAL RESOURCES
1 1
The third Pharmacy in the 21st Century Conference[31 The fourth Pharmacy in the 21st Century C ~ n f e r e n c e , ~ ~ ]
was held October 7-10, 1994, in Lansdowne, Virginia. “Reengineering the Medication-Use System,” was held
This invitational conference was organized and spon- October 1-3, 1999, in Baltimore, Maryland. This
sored by the Joint Commission of Pharmacy Practi- invitational, interdisciplinary conference was organized
tioners, a consortium of national pharmacy associations and sponsored by the Joint Commission of Pharmacy
and liaison organizations. Members of JCPP included Practitioners and had 108 participants from pharmacy,
the Academy of Managed Care Pharmacy, the American medicine, and nursing. Also included were benefit man-
Association of Colleges of Pharmacy, the American agers and representatives from federal regulatory agen-
College of Apothecaries, the American College of cies, consumer advocacy groups, the pharmaceutical in-
Clinical Pharmacy, the American Pharmaceutical Asso- dustry, the information systems industry, and the health
ciation, the American Society of Consultant Pharma- insurance industry.
cists, the American Society of Health-System Pharma- Instead of focusing strictly on the pharmacy profes-
cists, the National Community Pharmacists Association, sion, the fourth conference addressed the quality of the
the National Association of Boards of Pharmacy, and entire medication-use system. The objectives were to
the National Council of State Pharmacy Association describe-and publicize-the extent of preventable
Executives. The conference had 131 participants, in- morbidity, mortality, and excess costs resulting from
cluding pharmacists and representatives from the spon- suboptimal medication use; to stimulate discussion of the
soring organizations, medicine, nursing, and public and social and economic impact of dysfunction in the me-
private agencies. dication-use system; to develop a reengineered system for
The objective of the conference was to understand and medication use that would optimize clinical, economic,
overcome the barriers to delivering pharmaceutical care and humanistic outcomes; to identify strategies that could
in all settings. The two keynote speakers were David A. be used to evaluate and implement the models developed;
Zilz, who presented “The Changing Health System: Im- and to foster greater interprofessional collaboration and a
plications for Pharmaceutical Care,” and Carl E. Trinca, shared commitment to optimal medication use.
who presented “The Pharmacist’s Progress Toward Im- Several keynote presentations set the stage for work-
plementing Pharmaceutical Care.” A panel of five shops focusing on opportunities for improving the me-
pharmacists representing hospital pharmacy, long-term dication-use system; recommendations for applying
and specialty care, managed care, and independent and technology and preventing human error; recommenda-
chain practice described the services they provided and tions for medicine, nursing, and pharmacy; and strategies
how they overcame obstacles to providing pharmaceutical for improving the medication-use system. The final
care. These presentations set the stage for work groups to exercise was the development of recommended strate-
identify barriers to implementing pharmaceutical care, the gies for reengineering the medication-use system. These
reasons for those barriers, and strategies for overcoming included improving the clinical decision-making process
the barriers and implementing pharmaceutical care in related to medication use; improving communication
community and ambulatory care, hospital and insti- among health professionals and between health profes-
tutional care, long-term care, home healthcare, and man- sionals and patients; ensuring safety in drug distribution,
aged care. dispensing, and administration; and educating individual
Work groups classified the barriers as economic, edu- patients and the public about responsible medication use.
cational. political and legal, technological, and social,
interprofessional, and intraprofessional. The work groups
also proposed strategies for addressing these problems in
each practice setting. It was concluded that pharmacists
should direct their attention to patients, acquire the skills Each Pharmacy in the 21st Century Conference had a
needed to provide pharmaceutical care, collect and share different focus yet each had a positive impact on the
patient information, document the services and care pro- profession and on healthcare. For instance, the concept of
vided, perform and participate in outcomes research on pharmaceutical care-a major milestone for pharmacy-
pharmacists’ interventions to demonstrate the clinical and was widely introduced as a result of the second con-
economic value of pharmaceutical care, and recognize ference. Since that time, pharmacists have been increas-
that new credentials will be developed for pharmacists ingly recognized for what they do: helping people make
providing high-quality patient care. the best use of medications.
Pharmacy in the 21st Century 751
The series of conferences helped the profession to Institute for Alternative Futures and Project HOPE:
evaluate pharmacy practice and move forward. In ad- Virginia, 1985.
dition, they provided a platform for pharmacy to work 2. Conference on Phurnicicy in the 21st Century, October I 1 -
include method of recruiting, the informed consent and receiving high-dose placebo may account for the de-
consenting process, procedures for blinding, vehicle de- creased response.
livery (brand of medication, capsule color, size, prepara- Placebo therapy in the treatment of ulcerative colitis
tion, consistency of the product, and equivalence to the has consistently shown a measurable benefit. Ilnyckyj et
medication being compared), and patient-specific factors al. reviewed the literature to determine the extent of
(preexisting conceptions and beliefs).[6-s1 placebo response in the treatment of acute ulcerative
The method of patient recruiting, consenting, and colitis.'"] Analysis of all double-blind, placebo-con-
blinding has been shown to influence patient beliefs and trolled trials of patients with active ulcerative colitis by
subsequent reporting of efficacy and safety of the medi- multiple reviewers ensured appropriate data extraction
cation.[41 Means and type of vehicle delivery appear to and a series of analysis were conducted on the various
affect patient perception of intervention strength, and ad- clinical, endoscopic, and histological endpoints. Remis-
verse events.['] One study found that increased confidence sion (10%) occurred less frequently than response (30%)
in the manufacturer appeared to supplement relief ob- with placebo therapy. Number of patient visits appeared
tained in both placebo and active medication groups.[61 to be related to placebo response (clinical, endoscopic,
Patient beliefs and attitudes have the most influence on and histologic) but not remission. Therefore, the authors
outcomes, and reporting of efficacy and adverse events. concluded that conditioned response with active inter-
When patients are provided with information, emotional vention may have a significant effect in placebo response.
support, and an intervention consistent with preexisting Understanding endogenous mechanisms may account
conceptions, a sense of control over their illness and po- in part for the placebo response in patients with pain. The
sitive response to therapy were achieved."' The expecta- release of endorphins (endogenous opiate-like substances)
tion from the drug had an influence on the magnitude of is believed to mediate the response to pain."'] Naloxone,
the r e ~ p o n s e . ~ ~ ' a pure opiate antagonist, should block the effect of en-
dorphin analgesia that is often quantified as placebo re-
sponse."21 Patients who received naloxone post dental
extraction experienced more pain compared to placebo
responders. The placebo response was attributed to en-
dorphin release."21
Over the past 50 years, placebo-controlled trials have The mechanism of placebo response in blood pressure
been used by practitioners and researchers to determine is not well understood. In a study of 1292 stage I and
the efficacy and safety for a variety of therapeutic inter- stage I1 hypertensive females, 30% responded to placebo
ventions. In all clinical trials regardless of disease state therapy."'] Response varied with age and ethnicity. The
(e.g., peptic ulcer disease, ulcerative colitis, dental pain response in elderly Caucasian females was greater than in
management, hypertension, hypercholesterolemia, mi- other age and race subgroups. 38% versus 23-27%, re-
graine) or therapy received (e.g., antacids, clofibrate) pa- s p e c t i ~ e l y . " ~Factors
] such as natural history of the dis-
tients exhibited placebo response (Table l). The extent of ease and regression to the mean have been suggested as
placebo response (subjective and objective measures) the basis for this placebo response.
varies between trials and disease states. Evaluation of the Placebos have been useful in determining the efficacy
literature demonstrates the extent and variety of factors of various therapies in decreasing mortality and morbi-
implicated in response. Faizallah et al. studied the effects dity. The Coronary Drug Project Research Group eva-
of high- and low-dose placebo versus high- and low-dose luated the efficacy and safety of several lipid-lowering
antacids in the treatment of peptic ulcer disease."'] Pa- drugs such as clofibrate on the long-term morbidity and
tients with more significant disease received high-dose mortality of patients with coronary artery disease."41
placebo versus high-dose antacid therapy. Those with less Subgroups defined by patient response were determined
severe disease were given low-dose placebo versus low- after randomization. Patient adherence of 80% or greater
dose antacid therapy. Response appeared to be dependent appeared to substantially lower five-year mortality in
on the agent received and extent of the underlying dis- both the clofibrate and placebo groups."41 Factors such
ease. Patients in the low-dose placebo group reported a as patient adherence, social and behavioral characteris-
35% response while those receiving high-dose placebo tics, and/or biochemical response appeared to influence
reported a 13% response to therapy."'] This suggested patient outcomes.
that patients with more severe disease were less likely to Route of administration may have a significant effect
demonstrate a placebo response. However, poor compli- on patient response. A meta-analysis of 22 acute migraine
ance (2/3 of the desired used volume) among the patients treatment trials showed greater effect associated with a
I54 Placebo Effects
parenteral than an oral route."51 Of those receiving oral number of study visits. Greater than three patient visits
placebo therapy, 25.7% experienced relief compared to demonstrated greater placebo response." 'I Response to
32.4% response in the subcutaneous placebo group."51 placebo in individuals suffering from panic disorder was
Future trials are necessary to determine the effect of other directly related to the severity of the underlying disease.
routes of administration on patient response. Those with extensive pathologic conditions responded
only to active therapy."71
Placebo response may be related to the Hawthorne
GTQ effect."'] As the practitioner provides more attention to
the patient's health, there is often an increased desire of
Numerous factors may explain the reason for placebo the patient to please the caregiver and to express appre-
response and identify patients most likely to respond to ciation for an effective intervention.
placebo. These include preconceived patient views of Many hypotheses have been proposed about the un-
disease severity, available treatment options, desire of derlying cause of placebo response such as the release
the patient to please the provider, biochemical release, of endogenous endorphins in response to painful sti-
and stress."61 muli. Patients experiencing postoperative pain after mo-
Preconceived patient views of illness, presence of an lar extraction responded to placebo due to the release
emotional support network, and practitioner response and of endorphins."*]
intervention influence the patient attitude about the dis- The percentage of patients responding to placebo in-
ease and its treatment.[16j Patients with acute severe creased when stress was associated with pain."] Patient
symptoms are more likely to have improvement in symp- anxiety appears to be a factor in determining response
toms, due to natural or spontaneous recovery, which may to placebo."']
be attributed to the placebo. Placebo response in the On reanalysis of 14 of the 15 clinical trials, the factors
treatment of acute ulcerative colitis was related to the accounting for the improvements in the placebo group
Placebo Effects 755
included spontaneous improvement. fluctuation of disease Is it ethical for physicians to prescribe placebos?
symptoms, effects of previous and/or concurrent treat- This question has been debated in the medical literature
ment and medication, conditional switching of placebo since the 19th century. Arguments for placebo use have
treatment, irrelevant response variables, answers given to focused on the Dositive effects noted in clinical
be polite but not truthful, experimental subordination, trials. [2.10.12.13,22-261
conditioned answers, and false assumption of toxic The primary arguments against placebo use without
placebo effect."'] Practitioner and patient expectations consent focus on the deception and manipulation in-
directly influence the results and may distort the data.[201 volved, and violation of the a priori moral rule that a
Recall bias, parental assessment, and context influence person deserves respect and should be treated as expected
expectations may affect reporting of subjective outcomes with an active drug."] It eliminates the patient's right to
and adverse events.[201 It is difficult to determine the make an informed decision about hidher care, diminishes
effects related to the treatment versus those related to the the patient's dignity, and results in decreased trust in the
supportive, confirming environment. physicianlpatient relationship. It also advocates the use of
Placebos have been found to have effects similar to medication for every ailment including those without
the active medication being compared.[211Many inves- medical justification or for which no treatment is avail-
tigators have attempted to quantify the placebo response. able. Placebo administration may further increase re-
Scales such as the placebo effect scale (PES) and the quests for treatment of symptoms, delay appropriate
side effect scale (SES) have been used to identify diagnosis and treatment, and result in the withholding of
patients likely to exhibit placebo effects. These scales established therapies.
determine possible predictors of placebo response such
as demographic variables, illness characteristics, and
diagnostic and symptom variables to identify patients at C I
increased benefit or risk of demonstrating a placebo
response."'] The need for routine use of such scales The current Declaration of Helsinki was revised in
prior to inclusion in clinical trials and implications of October 2000 to provide guidance to physicians and
identifying those most susceptible to placebo response other medical researchers on the issue of placebo controls
require further study. when effective agents are available. The changes reflect
the ethical concerns raised by the use of placebo controls
in pregnant HIV-infected females in Uganda and Thai-
land. Available agents such as zidovudine have been
shown to significantly decrease the incidence of trans-
There are numerous misconceptions or generalizations mission of HIV to the fetus when taken throughout the
about placebo response. Common misconceptions include pregnancy. The revisions stress that the well-being of the
but are not limited to the following: One-third of all human subject takes precedence over the interests of
patients respond to placebo therapy; response is brief; medical progress. Medical research is justified only if
certain demographic or personality factors predict re- the benefits to the patient outweigh the risks and the
sponse; those who respond to placebo therapy do not informed patient consents to participate. The efficacy
have medical problems; and giving placebo is equivalent and safety of the investigational product should be tested
to no In addition, placebo response in one against the best current treatment available. If no treat-
clinical trial or disease state does not ensure equivalent ment exists, placebo therapy or no intervention is ac-
placebo response in other disease ~ t a t e s . " ~ . ' ~ . ' ~ ' ~ ~ - ~ceptable.
~] It is important to realize that the Declaration
of Helsinki does not have legal power to enforce these
changes. These are guidelines for ethical conduct of me-
CTlC dical research. Institution-specific IRBs are responsible
for enforcing the rules and guidelines for human subject
Placebos employed in the course of general medical safety and research conduct.
practice may be given to patients believed to be expe-
riencing exaggerated symptoms or to those who were
unresponsive to current medical therapies. Such patients Y
are likely to receive placebo therapy when practitioners
are unable to determine the cause of disease or if inade- Placebos are used in clinical practice and research. Pla-
quate treatment is available.[27'2x1 cebo response has been demonstrated in a variety of
756 Placebo Effects
disease states. Despite the demonstrated efficacy of Placebo-associated blood pressure response and adverse
placebo therapy, the use of placebos in clinical practice effects in the treatment of hypertension: Observations from
may be considered unethical. Attempts by researchers to a Department of Veterans Affairs Cooperative Study.
determine the patient-specific characteristics responsible Arch. Intern. Med. 2000, 160, 1449-1454.
14. Influence of adherence to treatment and response of cho-
for placebo response have been unsuccessful. Patient,
lesterol on mortality in the coronary drug project. N. Engl.
practitioner, and environmental factors make it difficult J. Med. 1980; 303, 1038-1041.
to quantify placebo response. T h e Declaration of 15. de Craen, A.J.; Tijssen, J.G.: de Gans, J.; Kleijnen, J.
Helsinki has been revised to address the issue of Placebo effect in the acute treatment of migraine: Sub-
placebo use in clinical trials. If an effective agent is cutaneous placebos are better than oral placebos. J. Neurol.
available, the new agent should be tested for efficacy 2000, 247: 183-188.
against the available effective therapy, not the placebo. 16. Bernstein, C.N. Placebos in medicine. Semin. Gastrointest.
Further studies are needed to clearly understand the Dis. 1999, 10, 3-7.
reasons for placebo response in patients of various de- 17. Uhlenhuth, E.H.: Matuzas, W.: Warner, T.D.; Thompson,
mographic characteristics. P.M. Growing placebo response rate: The problem in
recent therapeutic trials? Psychopharmacol. Bull. 1997, 33,
31-39.
18. Shapiro, A.K.: Struening, E.L.: Barten, H.; Shapiro, E.
Correlates of placebo reaction in an outpatient population.
Psychol. Med. 1975, 5>389-396.
1. Beecher, H.K. The powerful placebo. JAMA, J. Am. Med. 19. Kienle, G.S.; Kiene, H. The powerful placebo effect: Fact
ASSOC.1955, 159, 1602-1606. or fiction? J. Clin. Epidemiol. 1997, 50, 131 1-1318.
2. Brody, H. The lie that heals: The ethics of giving placebos. 20. Swartzman, L.C.; Burkell, J. Expectations and the placebo
Ann. Intern. Med. 1982, 97, 112- 118. effect in clinical drug trials: Why we should not turn a
3. Gotrsche, P.C. Is there logic in the placebo? [see com- blind eye to unblinding, and other cautionary notes. Clin.
ments]. Lancet 1994, 344, 925-926. Pharmacol. Ther. 1998; 64; 1-7.
4. Kleijnen, J.; de Craen, A.J.; van Everdingen, J.: Krol, L. 21. Turner, J.A.; Deyo, R.A.; Loeser, J.D.; Von Korff, M.;
Placebo effect in double-blind clinical trials: A review of Fordyce, W.E. The importance of placebo effects in pain
interactions with medications. Lancet 1994. 344. 1347- treatment and research [see comments]. JAMA, J. Am.
1349. Med. Assoc. 1994: 271; 1609-1614.
5. Moerman, D.E. Cultural variations in the placebo effect: 22. Flaten, M.A.: Blumenthal, T.D. Caffeine-associated stim-
Ulcers, anxiety, and blood pressure. Med. Anthropol. Q uli elicit conditioned responses: An experimental model of
2000, 14. 51-72. the placebo effect. Psychopharmacology (Berlin) 1999,
6. Branthwaite, A,: Cooper, P. Analgesic effects of branding 145. 105-112.
in treatment of headaches. Br. Med. J. (Clin. Res. Ed.) 23. Shetty, N.; Friedman, J.H.; Kieburtz, K.; Marshall. F.J.;
1981. 282. 1576-1578. Oakes, D. The placebo response in Parkinson’s disease.
7. Kaptchuk, T.J. Powerful placebo: The dark side of the Parkinson study group. Clin. Neuropharmacol. 1999, 22,
randomised controlled trial. Lancet 1998.351, 1722- 1725. 207-212.
8. Buckalew, L.W.: Coffield, K.E. An investigation of drug 24. Dellemijn, P.L.: Vanneste, J.A. Randomised double-blind
expectancy as a function of capsule color and size and pre- active-placebo-controlled crossover trial of intravenous
paration form. J. Clin. Psychopharmacol. 1982, 2, 245- fentanyl in neuropathic pain. Lancet 1997, 349, 753-
248. 758.
9. Gracely, R.H.: Dubner, R.; Deeter, W.R.: Wolskee, P.J. 25. Massie, B.; Bourassa, M.; DiBianco, R., et al. Long-term
Clinicians’ expectations influence placebo analgesia [let- oral administration of amrinone for congestive heart
ter]. Lancet 1985, I , 43. failure: Lack of efficacy in a multicenter controlled trial.
I0 Fairallah. R.: De Haan, H A . ; Krasner. N., et al. Is there a Circulation 1985, 71, 963-971.
place in the United Kingdom for intensive antacid treat- 26. Jolley, A.G.: Hirsch, S.R.: McRink, A.: Manchanda, R.
ment for chronic peptic ulceration? Br. Med. J. (Clin. Res. Trial of brief intermittent neuroleptic prophylaxis for
Ed.) 1984, 289, 869-871. selected schizophrenic outpatients: Clinical outcome at one
11 Ilnyckyj, A,; Shanahan, F.: Anton, P.A.; Cheang, M.; year. BMJ 1989, 298, 985-990.
Bernstein, C.N. Quantification of the placebo response in 27. Goodwin, J.S.; Goodwin, J.M.: Vogel, A.V. Knowledge
ulcerative colitis [see comments]. Gastroenterology 1997; and use of placebos by house officers and nurses. Ann.
112. 1854-1858. Intern. Med. 1979, 91, 106-110.
12 Levine, J.D.: Gordon, N.C.: Fields, H.L. The mechanism 28. Berger, J.T. Placebo medication use in patient care: A
of placebo analgesia. Lancet 197 survey of medical interns. West. J. Med. 1999, 170, 93-
13 Preston, R.A.; Materson, B.J.; Reda, D.J.; Williams, D.W. 96.
PROFESSIONAL DEVELOPMENT
Edward P. Krenzelok
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
between 1750 and 1900-150 years; 1900-1950 saw 0 Development of public and professional education
information double again in only 50 years. From 1960- programs and materials.
1992, information doubled at least once every five years. * Collection and analysis of national poisoning data.
By 2020, it is estimated that information will double
every 73 days. Clinical pharmacists working in poison For more information or to join the AAPCC contact:
centers must proactively prevent the information explo- AAPCC, 3201 New Mexico Avenue, NW, Suite 310,
sion from incapacitating centers and must find ways to Washington, DC 20016; Tel.: 202-362-7217, Fax: 202-
filter the information to make it usable. Half of knowl- 362-8377, E-mail: aapcc@poison.org, Web site: www.
edge is knowing where to find data and information and aapcc.org.
then converting them to knowledge once you find them.
Twenty-five years ago, pharmacists working in a PIC
had a limited number of textbooks, a few hundred papers
from the medical literature, and a few pieces of Poi-
sindex microfiche as their information resources. Since Pharmacists who practice in a PIC or in private practice
that time hundreds of textbooks have been written to would benefit from membership in the American
address basic clinical toxicology and very specific topics Academy of Clinical Toxicology (AACT). The AACT
such as botanical toxins. (See Appendix 5 for a list of was established in 1968 as a not-for-profit multidis-
relevant textbooks.) The advent of the electronic data- ciplinary organization uniting scientists and clinicians
base era has made an incredible number of resources in the advancement of research, education, prevention,
available on general toxicology, hazardous materials, na- and treatment of diseases caused by chemicals, drugs,
tural toxins, and biochemical terrorism. (See appendix 5 and toxins. The founders of the AACT established the
for specific URLs.) Academy to:
a leading clinical toxicology journal and has published the For more information or to join the EAPCCT contact:
AACT/EAPCCT cutting-edge position statements on EAPCCT General Secretary, National Poison Informa-
gastrointestinal d e c ~ n t a m i n a t i o n , " ~The
~ ' ~ ~Academy is tion Service, Guy's & St. Thomas Hospital Trust,
also the host organization of the American Board of Ap- Medical Toxicology Unit, Avonley Road, London
plied Toxicology, which certifies nonphysicians as clinical SE14 5ER, U.K.; Tel.: 44-207-771-5310, Fax: 44-207-
toxicologists-a mandatory certification for PIC direc- 771-5309, E-mail: alex.campbell@gstt.sthames.nhs.uk,
tors. The AACT supports career development of mem- Web site: www. eapcct.org.
bers involved in toxicology research through financial Active participation in these societies and their annual
awards and sponsorship of fellowships and scholarships. meetings provides an excellent venue to learn about con-
Additionally, the Academy sponsors an electronic temporary issues in clinical toxicology and poison in-
bulletin board to foster collaborative clinical toxicology formation practice. All of the societies are interdiscip-
research among its members. linary and cater to the needs of people with an interest in
For more information or to join the AACT contact: clinical toxicology irrespective of the individual's health
AACT. 777 East Park Drive, PO Box 8820, Harrisburg, science training. Membership in one or all of the socie-
PA 17105-8820; Tel.: 717-558-7750, ext. 1467 Fax: 717- ties provides the best opportunity to network with clini-
558-7845, E-mail: aact@pamedsoc.org, Web site: cal toxicologists.
www.clintox.org.
entres T
P
The European Association of Poisons Centres and There are 54 RPICs serving the majority of the United
Clinical Toxicologists (EAPCCT) was founded in 1964 States. Clinical pharmacists who are looking for a career
by a group of physicians and scientists with the specific opportunity in poison information practice should contact
goal of advancing knowledge and understanding of the those centers for additional information. (A current list of
diagnosis and treatment of all forms of poisoning. The all PICs in the United States may be found at www.
Association's objectives are to: aapcc .org .)
6. Access for hearing-impaired individuals must must include at least one full-time equivalent of on-site
be provided. toxicological supervision and appropriate backup. These
7. A plan to provide poison center services in re- components must meet the specific criteria listed below.
sponse to natural and technological disasters must Each site of a certified poison center system must meet
be in place. the requirements for medical and managing direction.
Table 1 Time requirements for medical directions planning, and oversight of administrative func-
tions of programs, e.g., staff training, quality as-
No. of human
poison exposures 1QQ%BC hours Total tox hours surance, budgeting.
Managing direction may be provided by a single
25,000 10 20 managing director or may be provided by more
50,000 20 30 than one individual, each with the qualifications
75,000 30 40 identified below. If more than one individual is
100,000 40 50 involved in providing managing direction, one in-
125,000 50 60
dividual must be designated as managing director
(or comparable title), and that person is responsible
for coordinating managing direction activities.
the initial 25,000 human poison exposure cases. The managing director must be a nurse with a
Time applied to this total should conform to the baccalaureate degree, associate degree, or three-
following standards: year diploma; a pharmacist; or a physician or may
a. Up to 10 hours per week of the total time hold a degree in a life science discipline if a
applied to medical direction may consist of diplomate of the American Board of Applied
toxicology activities not directly related to Toxicology. If the managing director is also the
certified poison center operation, such as medical director, this person must have a full-time
clinical, academic, teaching, and research commitment to the poison center.
activities. No more than 10 percent of clinical The managing director with toxicological super-
time in emergency department, clinic, ward, or vision responsibilities must be board-certified or
intensive care unit service will apply to this board-prepared, as evidenced by a letter from the
total, unless specific documentation is pro- appropriate board indicating that the candidate
vided to verify that the additional time was will be allowed to sit for the next examination. For
directly related to toxicology. physicians this board can be the ABMT (pre-1994)
b. The remainder of the total time applied to or the ABMS subspecialty examination in medical
medical direction activities must consist of toxicology (post-1994). For all others, the board
poison center operational activities during the must be the American Board of Applied Toxico-
time that is 100 percent dedicated to on-site logy. Candidates for the board examination must
medical direction at each certified poison successfully complete the examination within two
center or site of a poison center system. consecutive administrations of the examination.
The time requirements for medical direction Individuals without board certification in applied
are summarized in Table 1. toxicology will be considered qualified as man-
5) Medical backup must be available. in a timely aging directors for the purpose of determining
manner, at all times. If not provided by the compliance with the current criteria i f 1) the in-
medical director, medical backup may be provided dividual served as managing director of a poison
by those providing medical direction or other center certified by AAPCC as of September 14,
individuals designated by the medical director. All 1998; and 2) the individual met the immediately
medical backup must be provided by board- previous AAPCC criteria for managing directors
certified or board-prepared medical toxicologists. on September 14, 1998.
Other individuals identified and qualified by the
medical director (e.g., fellows, managing director) 2. Specialists in Poison ~nf#r~atiQn.A Specialist in
may serve as immediate certified poison center Poison Information must be on duty in the certified poison
backup if timely secondary backup is provided at center, or at each functioning site of a poison center
all times by a board-certified or board-prepared system, at all times.
medical toxicologist. Direct clinical effort as
backup can be applied to item 4.A. above. Specialists in Poison Information must be: 1) a
nurse with a baccalaureate degree, associate de-
gree, or three-year diploma; a pharmacist; or a
physician; 2) currently certified by AAPCG as a
1) The managing director provides direct toxico- Specialist in Poison Information; 3) a diplomate
logical supervision of poison center staff, strategic of the American Board of Applied Toxicology; or
766 Poison Information Pharmacy Practice
ning, implementation, and evaluation, and/or an appro- B. The certified poison center or system must submit
priate educational background with which to provide all its human exposure data (except as noted in
public-oriented presentations about poison center aware- 1V.B.1.) to AAPCC’s Toxic Exposure Surveil-
ness and the value of the poison center, poison preven- lance System meeting specified submission dead-
tion, and first aid for poisoning. This role will be super- lines and quality requirements and including all
vised by the medical and/or managing director. required data elements.
1. The submission of human exposure data de-
rived from industry contracts is encouraged but
F. The certified poison center or system shall not required for certification.
have an ongoing quality improvement program 2 . Certified poison centers that withhold indus-
try-derived human exposure data must annu-
1. A certified poison center or system shall imple- ally submit the number of industry-derived
ment quality assurance activities which incorpo- human exposures that were withheld.
rate specific monitoring parameters and staff edu- C. The certified poison center or system shall tabu-
cation programs. late its experience for regional program evaluation
2. A certified poison center or system shall de- and hazard surveillance on at least an annual
monstrate that patient outcomes are monitored re- basis. This criterion will be considered to be met if
garding high-risk, high-volume, or problem-prone the center completes an annual report summar-
cases. The corrective actions taken to improve pa- izing its own experience.
tient care shall be documented. In addition, the D. The certified poison center shall monitor the
certified poison center should demonstrate mon- emergence of poisoning hazards and take specific
itoring of customer satisfaction and assessment of actions to eliminate poisoning hazards.
staff competency.
V. P r ~ f @ s s ~ oa ~ a l
i Iit ies
The certified poison center or system shall A The certified poison center or system shall pro-
identify the treatment capabilities of the vide information on the management of poison-
treatment facilities of the region ing to the health professionals throughout the
region who care for poisoned patients. This cri-
At a minimum, the certified poison center or system terion will be considered to be met if the certified
should: 1) identify emergency and critical care treatment poison center offers ongoing information about
capabilities within the region for adults and children; 2 ) poison center access and services and updates on
have a working relationship with all poison treatment new and important advances in poisoning man-
facilities in its region: 3) understand the analytical tox- agement to the health professionals throughout
icology facilities in the region and how to interface with the region.
them; 4) understand how the region’s prehospital trans- B. The certified poison center or system shall provide
portation system is structured and how to interface with it; a variety of public education activities targeting
and 5 ) know where critical antidotes are available within identified at-risk populations. The programs shall
the region and how they can be transferred between fa- address poisoning dangers, poison prevention
cilities when necessary. strategies, first aid for poisoning, and when and
how to access poison center services. These pro-
grams must be implemented throughout the cer-
tified poison center’s region.
governed by a board of directors elected by ABAT ical toxicology. Scholastic course work is not
membership from among its diplomates. considered to be professional experience.
All ABAT functions are undertaken in accordance with
ABAT bylaws and the bylaws of AACT; these bylaws and Because the American College of Medical Toxicology
all regulations and procedures are promulgated by ABAT. and the American Board of Veterinary Toxicology are
ABAT is a not-for-profit organization. No member of responsible for certification in their respective areas,
ABAT receives or derives any profit from the operation applicants holding the Doctor of Medicine, Doctor of
of ABAT and no part of the net income of ABAT be- Osteopathy, or Doctor of Veterinary Medicine degree
are not eligible to sit for the ABAT examination.
nefits any individual member. ABAT is not involved in
authorizing or designating any political lobby action.
The principal office of ABAT is usually established in 2. Applicants must complete at least 12 months of
the city of the residence of the president. postdoctoral training (i.e., residency or fellowship)
in clinical toxicology or a closely related field. Ap-
plicants without postdoctoral training must have a
minimum of at least three years of professional ex-
perience related to applied clinical toxicology after
ABAT was created as a not-for-profit organization for completion of their doctoral degree. To be prepared
the unique purpose of fostering the development of clini- for the examination, candidates should have con-
cal toxicology among the nonphysician, nonveterinarian siderable clinical experience and an understanding
members of the American Academy of Clinical Toxico- of the clinical and environmental factors associat-
logy by: ed with various types of toxicological problems.
Examples of activities related to the practice of
Advancing the science, study, and practice of clinical applied clinical toxicology include consulting with
toxicology. medical personnel on patient care issues; having
Improving the quality of clinical toxicology consul- administrative responsibility for a poison control
tation available to the public. center with consultative responsibilities; rendering
Establishing and maintaining standards of excellence opinions on product toxicity; teaching clinical to-
for nonphysician practitioners by developing and ad- xicology to students, practitioners, or colleagues;
ministering examinations, as well as other criteria, for collaborating with medical toxicologists; and con-
the certification and recertification of these practitio- ducting research in applied clinical toxicology.
ners in clinical toxicology. 3. Applicants must demonstrate experience in all the
Granting certificates and other forms of recognition to areas of clinical, research, and teaching activities
professionals who demonstrate exceptional ability in and leadership. An abundance of experience in
clinical toxicology. one area will not substitute for lack of experience
Maintaining a registry of ABAT diplomates and, upon in another.
request, furnishing lists of ABAT diplomates to the 4. Applicants holding a degree in a healthcare pro-
public, governmental agencies, healthcare profes- fession in which licensing is required must be in
sionals, and educational institutions. good standing with the appropriate jurisdictional
board and must be eligible for, or possess, a valid,
BAT Certification Examination unrestricted license to practice. A copy of the
license must accompany the application.
5 . Applicants must be members in good standing
Applicants must meet the following initial criteria to be- of the American Academy of Clinical Toxico-
come a candidate for examination: logy at the time of their application.
of ABAT will inform the candidate of the committee’s on poison control centers, $7 in medical costs are
decision, and if required. will list areas of improvement saved. The average cost of a poisoning exposure
the committee felt would allow the candidate to suc- call is $32, while the average cost if other parts
cessfully pass credential review on a subsequent submis- of the medical system are involved is $932. Over
sion. Once credentialled, an applicant must take the exam the last 2 decades. the instability and lack of
within two examination cycles. funding has resulted in a steady decline in the
number of poison control centers in the United
Iicat io s States. Within just the last year, 2 poison control
centers have been forced to close because of
A combined application and testing fee of $400, made funding problems. A third poison control center
payable to the American Board of Applied Toxicology, is scheduled to close in April 1999. Currently,
must accompany the application. If credentialling is there are 73 such centers.
denied for any reason, the $300 portion for the exam- (3) Stabilizing the funding structure and increasing
ination will be refunded. accessibility to poison control centers will in-
crease the number of United States residents who
have access to a certified poison control center,
and reduce the inappropriate use of emergency
T medical services and other more costly health-
care services.
finitio
At the second session In this Act, the term ‘Secretary‘ means the Secretary of
Health and Human Services.
Begun and held at the City of Washington on Monday,
the twenty-fourth day of January, two thousand
An Act
To provide assistance for poison prevention and to
stabilize the funding of regional poison control centers. (a) IN GENERAL-The Secretary shall provide co-
Be it enacted b j the Senate and House of Representa- ordination and assistance to regional poison
tives of the United States of America in Congress control centers for the establishment of a nation-
assembled, wide toll-free phone number to be used to access
such centers.
ec. ort Title (b) RULE OF CONSTRUCTION-Nothing in this
section shall be construed as prohibiting the es-
This Act may be cited as the ‘Poison Control Center tablishment or continued operation of any pri-
Enhancement and Awareness Act.‘ vately funded nationwide toll-free phone number
used to provide advice and other assistance for
poisonings or accidental exposures.
(c) AUTHORIZATION OF APPROPRIATIONS-
Congress makes the following findings: There is authorized to be appropriated to carry out
this section. $2,000,000 for each of the fiscal years
2000 through 2004. Funds appropriated under this
(1) Each year more than 2,000,000 poisonings are
reported to poison control centers throughout the subsection shall not be used to fund any toll-free
United States. More than 90 percent of these poi- phone number described in subsection (b).
sonings happen in the home. Fifty-three percent
of poisoning victims are children younger than 6
years of age.
(2) Poison control centers are a valuable national
resource that provide lifesaving and cost-effect- (a) IN GENERAL-The Secretary shall establish a
ive public health services. For every dollar spent national media campaign to educate the public and
Poison Information Pharmacy Practice 771
healthcare providers about poison prevention and State government as having in effect stan-
the availability of poison control resources in local dards for certification that reasonably provide
communities and to conduct advertising cam- for the protection of the public health with
paigns concerning the nationwide toll-free number respect to poisoning.
established under Section 4.
(b) CONTRACT WITH ENTITY-The Secretary (d) WAIVER OF CERTIFICATION
may carry out subsection (a) by entering into con- REQUIREMENTS-
tracts with 1 or more nationally recognized media
firms for the development and distribution of
monthly television, radio, and newspaper public (1) IN GENERAL-The Secretary may grant a
service announcements. waiver of the certification requirement of
(c) AUTHORIZATION OF APPROPRIATIONS- subsection (c) with respect to a noncertified
There is authorized to be appropriated to carry poison control center or a newly established
out this section, $600,000 for each of the fiscal center that applies for a grant under this
years 2000 through 2004. section if such center can reasonably
demonstrate that the center will obtain such
a certification within a reasonable period
of time as determined appropriate by the
secretary.
(a) REGIONAL POISON CONTROL CENTERS- ( 2 ) RENEWAL-The Secretary may only
The Secretary shall award grants to certified re- renew a waiver under paragraph (1) for a
gional poison control centers for the purposes of period of 3 years.
achieving the financial stability of such centers,
and for preventing and providing treatment recom- (e) SUPPLEMENT NOT SUPPLANT-Amounts
mendations for poisonings. made available to a poison control center under
(b) OTHER IMPROVEMENTS-The Secretary shall this section shall be used to supplement and not
also use amounts received under this section to- supplant other Federal, State, or local funds
provided for such center.
(1) Develop standard education programs; ( f ) MAINTENANCE OF EFFORT-A poison con-
( 2 ) Develop standard patient management pro- trol center. in utilizing the proceeds of a grant
tocols for commonly encountered toxic under this section, shall maintain the expendi-
exposures; tures of the center for activities of the center at a
(3) Improve and expand the poison control data level that is not less than the level of such ex-
collection systems; penditures maintained by the center for the fiscal
(4) Improve national toxic exposure surveillance; year preceding the fiscal year for which the grant
and is received.
( 5 ) Expand the physiciadmedical toxicologist (g) MATCHING REQUIREMENT-The Secretary
supervision of poison control centers. may impose a matching requirement with respect
to amounts provided under a grant under this
(c) CERTIFICATION-Except as provided in subsec- section if the Secretary determines appropriate.
tion (d), the Secretary may make a grant to a center (h) AUTHORIZATION OF APPROPRIATIONS-
under subsection (a) only if- There is authorized to be appropriated to carry
out this section, $25,000,000 for each of the fiscal
( I ) The center has been certified by a profes- years 2000 through 2004.
sional organization in the field of poison
control, and the Secretary has approved the
organization as having in effect standards for
certification that reasonably provide for the
protection of the public health with respect
to poisoning; or
(2) The center has been certified by a State gov- CHRIS: U.S. Coast Guard chemical hazard response
ernment, and the Secretary has approved the information.
772 Poison Information Pharmacy Practice
Dolphin Software: Over 160,000 material safety data RTECS from NIOSH: Registry of the toxic effects of over
sheets. 142,000 substances.
Drugdex: Extensive pharmaceutical information. Safetydex: Over 8000 hospital-specific material safety
data sheets.
Drug-Reax: Drug interaction information on over 8000
pharmaceuticals. Tomes: Medical and hazard information for chemicals.
HDSB from NLM: Health and environmental effects of Poisoning and Toxicology Compendium with Symp-
over 4500 toxic chemicals. toms Index, Jerrold B. Leikin, and Frank P. Paloucek;
Lexi-Comp, Hudson, Ohio, 1998.
Identidex: Tablet and capsule identification system Clinical Management of Poisoning and Drug Over-
dose, Third Edition; Lester M. Haddad, Michael W.
Index Nominum: International drug directory. Shannon, and James F. Winchester; WB Saunders,
Philadelphia, Pennsylvania, 1998.
Infotext: Environmental health and safety information Goldfrank’s Toxicologic Emergencies, Sixth Edition;
directed toward occupational hygienists. Lewis R. Goldfrank, Neal E. Flomenbaum, Neal A.
Lewin, Richard S. Weisman, Mary Ann Howland, and
IRIS: U.S. Environmental Protection Agency health risk Robert S. Hoffman; Appleton and Lange, Stamford,
assessment information for over 450 chemicals. Connecticut, 1998.
Toxicology of the Eye, Fourth Edition; W. Morton
LOLI: Environmental, international, and state regulations Grant, and Joel S. Schuman; Charles C Thomas,
on chemicals maintained by ChemAdvisor. Springfield, Illinois, 1993.
Casarett and Doull’s Toxicology, Sixth Edition; Curtis
NAERG: 1996 North American Emergency Response D. Klaassen; McGraw-Hill, New York, New York,
Handbook. 2001.
OHM/TADS: Physiochemical and toxicological informa- Sax’s Dangerous Properties of Industrial Materials,
tion on 1400 substances. Includes oils and other envi- Eighth Edition; Richard J. Lewis, Sr.; Van Nostrand
ronmental hazards. Reinhold, New York, New York, 1992.
Poisindex: Ingredient and clinical toxicology manage- Occupational, Industrial, and Environmental Toxicology;
ment information on over 1 million substances. Michael I. Greenberg, Richard J. Hamilton, and Scott D.
Phillips; Mosby, St. Louis, Missouri, 1997.
RegsLink: Access to federal and state chemical regulatory
information. Proctor and Hughes’ Chemical Hazards of the Work-
place, Fourth Edition; Gloria J. Hathaway, Nick H. Proc-
Reprorisk: Contains 4 databases on reproductive risk tor, James P. Hughes, and Michael L. Fischman; Van
information. Nostrand Reinhold, New York, New York, 1996.
Poison Information Pharmacy Practice 773
AMA Handbook of Poisonous and Injurious Plants; Ken- Chemical Warfare Agents; Satu M. Somani; Academic
neth F. Lampe and Mary Ann McCann; American Medi- Press, San Diego, California, 1992.
cal Association, Chicago, Illinois. 1985.
National Library of
Disposition of Toxic Drugs and Chemicals in Man, Internet Grateful Med
Fourth Edition; Randall C. Baselt and Robert H. Cra- http://igm.nlm.nih.gov/
vey; Chemical Toxicology Institute, Foster City, Cali- The Internet Grateful Med Web site provides a variety
fornia, 1995. of database accesses to a variety of searches including
MEDLINE, AIDS line, AIDS drugs, AIDS trials, Chem-
ical Identification, NIH Clinical Alerts, and a variety of
other very useful access sites.
Textbook of Military Medicine Part I-Medical Aspects of
Chemical and Biological Warfare; Russ Zajtchuk, Editor;
Department of the Army, Bethesda, Maryland, 1997. Library of Medicine
http://sis.nlm.nih.gov/ToxSearch.htm
Chemical Warjare Agents; Timothy C. Marrs, Robert L. This provides a variety of information on toxicology and
Maynard and Frederick R. Sidell; John Wiley and Sons, environmental health with searches and links to a variety
New York, New York, 2000. of important organizations.
774 Poison Information Pharmacy Practice
http://ecdin.etomep.net/Ecdin/E-hinfo.html
This is a factual database created by the European Com- http://www .mninter.net/-publish/
mission, Joint Research Centre at the Ispra (I) site. It This is a comprehensive collection of drugs of abuse.
contains a list of chemical information for each chemical Although the information is somewhat basic it is very
listed. One of its sections is PHATOX (Pharmacological comprehensive.
and Toxicological) data which includes health evaluations,
toxicological data, epidemiological data, and health
hazard evaluations. http://www.holisticmed.com/www
This is an interesting and very useful site that provides
o ~ s o n ~n~orrnatiQn
i~~ a lot of information on holistic medicines and alterna-
http://www.mic.ki.se/Diseases/c21.613.html tive therapies.
The site provides access to many links with detailed in-
formation on a variety of poison issues including: general; erreal
bites and stings; food poisoning; gas poisoning; plant http ://www .hyperreal.org
poisoning; lead, iron, mercury, cadmium. nickel, and drug Important site that includes drugs of abuse primarily in-
poisoning; and hazardous substances. There are many volving the “rave” scene.
pictures and multiple links.
ide-The Virtual
http://www.internets.com/mednets/stoxicology
.htm http://www-sci.lib.uci.edu/HSG/Pharmacy.html
This site provides a list of links to various toxicologi- Access to Martindales pharmacy center for drug
cal sites. information.
Poison Information Pharmacy Practice 775
Pharmacy (Medicine, Biosciences) This a searchable Web site that contains information
http://www.pharmacy.org and photographs of various fungi, both poisonous and
This site contains many links to pharmacy-related re- nonpoisonous.
sources, including schools of pharmacy, online journals,
CME, and societies. Medical Botany Library
http://www .floridaplants.com/mpois.htm
PharmWeb Information on poisonous plants and mushrooms from
http://www.pharmweb.net around the world.
This is a searchable site from the U.K. with information
for the patient and health professional.
Medicinal and Poisonous Plant
http://www .inform.umd.edu/EdRes/Colleges/LFSC/
X Drug Compendium Program
life-sciences/.plantbiology/Medicinals/medicinals,
htm
http://www 1.mosby.com/Mosby/PhyGenRx
Information and links on poisonous and medicinal plants
A comprehensive listing that is searchable for generic or
from the University of Maryland.
brand names and by drug category.
2. Botticelli, J.T.; Pierpaoli, P.G. Louis Gdalman, pioneer in 8. Hanison. D.L.; Draugalis, J.R.; Slack, M.K.; Langley, P.C.
hospital pharmacy poison information services. Am. J. Cost-effectiveness of regional poison control centers. Arch.
Hosp. Pharm. 1992, 49, 1445 1450. Intern. Med. 1996, 156, 2601- 2608.
3. Robertson, W.O. National organizations and agencies in 9. Van Buren, J.; Fishcr, L.L. Monroe County Poison
poison control programs: A commentary. Clin. Toxicol. Prevention I3emonstration Project: Final Report to U.S.
Consumer Product Sufety Commission; New York State
4. Youniss, J.; Litovitz, T.; Villaneuva, P. Characterization of Department of Health: Albany, New York, 1990.
U.S. poison centers: A 1998 survey conducted by the 10. Leikin, J.B.; Krenzelok, E.P. Poison Centers. Clinicul
American Association of Poison Control Centers. Vet. Toxicology, 1st Ed.: WB Saunders Company: Philadelphia,
Hum. Toxicol. 2000, 42 (l), 43 53. 2000; 11 1 - 114.
5 . Litovitz, T.L.; Klein-Schwartz, W.; White, S.; Cobaugh, 11. Krenzelok, E.P. Poison centers at the millennium and
D.J.; Youniss, J.; Drab, A,; Benson, B. 1999 Annual report beyond. J. Toxicol., Clin. Toxicol. 2000, 38 (2), 169 170.
-
of the American Association of Poison Control Centers 12. Krenzelok. E.P.; Vale, J.A. Position statements: Gut
Toxic Exposures Surveillance System. Am. J. Emerg. Med. decontamination. J. Toxicol., Clin. Toxicol. 1997, 35 (7),
2000, 18 ( 5 ) , 517-574. 695- 697.
6. Krenzelok, E.P. Do poison centers save money? What are 13. American Academy of Clinical Toxicology, European
the data? J. Toxicol., Clin. Toxicol. 2000,36 (6), 545 547. Association of Poisons Centres and Clinical Toxicologists
7. Miller, T.R.; Lestina, D.C. Costs of poisoning in the Position statements on gut decontamination. J. Toxicol.,
United States and savings from poison control centers. A Clin. Toxicol. 1997, 35 (7), 699 -762.
benefit-cost analysis. Ann. Emerg. Med. 1997, 29, 239- 14. Personal communication with the AAPCC, September 26,
245. 2000.
PHARiMACY PRACTICE ISSUES
I LL
Clinical pharmacy practice in Spain is very closely linked There are a few documents that include nearly all func-
to the concept of pharmaceutical care, as defined by Hep- tions developed by clinical pharmacists in Spain (see
ler and Strand:“] “Pharmaceutical care is the responsible Table 1). They are, in chronological order, as follows.
provision of drug therapy for the purpose of achieving
definite outcomes which improve a patient’s quality of aws
life.” So much so, in fact, that the term pharmaceutical
care already implies the concept of clinical pharmacy. The Orden por la que se regulan 10s Servicios Farmace‘uticos
evolution toward pharmaceutical care implies the step in de hospitales (Ministerio de Sanidad y Consumo,
which the pharmacist selects the therapy, taking respons- 1977).[61This is the law that primarily regulated hospital
ibility for it, instead of only suggesting it to the pharmacy services, defining for the first time some of the
Originally introduced in hospital pharmaceutical prac- clinical activities that the pharmacist must develop, such
tice, and although lack of human staff has prevented as drug information, clinical trials, or pharmacovigilance.
its consolidation at all hospitals, clinical pharmacy has
grown throughout Spain in recent years. Pharmaceutical Ley General de Saizidad (Ministerio de Sanidad y
care, introduced more recently, is the current trend in Consumo, 1986).17] This is a general law that regulates
hospital pharmacy, and is being increasingly adopted in most subjects health-related, including all health service
community pharmacy practice. structures and requirements for drug commercialization,
Indeed, clinical pharmacy has become so important as well as some of the pharmacist’s functions as a
to pharmacy as a whole that it has now been included healthcare provider.
as an obligatory subject in pharmaceutical teaching and
courses. Under the new educational plan, the second Ley del Medicainento (Ministerio de Sanidad y
cycle of the pharmacy licenciatura (roughly equivalent Consumo, 1990).[’] In force since 1990, it represents
to an honors degree) includes a central subject entitled the most important law in the drugs area. It regulates
“pharmacology and clinical pharmacy.’ ’[41 In 1984, a most clinical activities developed by pharmacists at any
new European Community Directive (EC Directive 84/ health institutions.
432) established that pharmacy undergraduate curricula
should contain a 6-month stage in a community or hos-
pital pharmacy. In the last year, the training period for oliey ents
hospital pharmacists has been increased by a year to a
total of 4 years, an extra year dedicated exclusively to Coloquios de aproximacidn a la farmacia clinica
in-house clinical pharmacy training (the pharmacist vi- (Asociacih Espaiiola de FarmacCuticos de Hospitales,
sits the patients with the physician at the ward).[5’ 1981).[91This document collects the conclusions of eight
The functions of the clinical pharmacist and the debates about clinical pharmacy in which participated 200
documents governing such activities in Spain are list- hospital pharmacists, including subjects such as drug
ed below. selection, drug information, and pharmacist integration in
Table 1 Clinical content in general laws and policy documents that guide clinical pharmacy in Spain
the healthcare team. The impact of this document reached tice recommendations to facilitate its members’ work and
Europe through the Eighth European Symposium on daily practice at hospital. They include some clinical
Clinical Pharmacy, held in Lyon, France. in 1979. areas such as pharmacokinetics, artificial nutrition, and
drug information (see below).
Farmacia hospitalaria (Sociedad Espaiiola de Farm-
acia Hospitalaria. 1990).“01 Edited in 1990, this book
compiles all activities, clinical and nonclinical, deve-
loped by an hospital pharmacist. Due to the success of
the first edition, two years later, the contents were re-
viewed, and a second edition was published, including
more details about clinical contribution of the pharmacist electio
on patient’s pharmacotherapy.
Law: Ley General de Sanidad. Ministerio de Sanidad y
Acreditacidn docente de sewicios de farmacia hospi- Consumo, 1986.”l
talaria (Sociedad Espafiola de Farmacia Hospitalaria, 5.5. “All people who work at health services
1991).[”l Elaborated by the National Speciality Commis- must collaborate in drug evaluation and control.. . .”
sion, this document contains the acreditation requirements
for a hospital pharmacy service to be able to train future Law: Ley del Medicamento. Ministerio de Sanidad y
specialists, as well as the program of hospital pharmacy Consumo, 1990.[81
specialization. In 2000, the program was revised to in- Art. $4.4. and 84.6. ‘‘Public Administration will
clude one more year dedicated exclusively to clinical proceed for primary and specialized care structures to
pharmacy training.[51 make a scientific drug selection and evaluation, through
Drug and Therapeutics Committee . . .” and “. . . will
Manual del residente de farmacia hospitalaria (Socie- promote the publication of drug formularies for healthcare
dad Espaiiola de Farmacia Hospitalaria, 1999).[l2I Elabo- professionals’ use.”
rated to by a consult handbook for future specialists, all Art. 91.2. “Hospital pharmacy services will take part
teaching hospitals participated in its creation; it contains in hospital commissions to participate in drug selection
most activities developed by the hospital pharmacist, with and evaluation according to evidence, and drug use.”
theory and practical cases.
olicy d ~ ~ ~ SEFH ~ e nRecommendations:
t ~ Drug
SEFH consensus statements, practice recomnzenda- forniular3; edition. Sociedad Espafiola de Farmacia Hos-
tions, and guidelines (Sociedad Espafiola de Farmacia pitalaria, 1994.[l3I
Hospitalaria). As any society, the Spanish Society of Through this document, the SEFH defines the concept
Hospital Pharmacy (SEFH) periodically publishes prac- of drug formulary and tries to give a guide in how to
Policy Documents and Laws That Guide Clinical Pharmacy Practice in Spain 781
elaborate it. It must contain the drugs selected by the 0 Passive information in response to enquiries will be as
Drugs and Therapeutics Committee with their basic in- objective, concise, useful, and clear as possible.
formation, institutional proceedings regarding drug pre-
scription, and practical drug information such as drugs in More complete details about a hospital pharmacist’s
pregnancy and lactation, dose adjustment in renal or he- activities concerning information on drugs and the func-
patic impairment, drug interactions, and so on. tions of the CIM are given in Chapter 2.4 of the book
Farmacia Hospitalaria (Hospital Pharmacy) by the
Further information provided by the SEFH about drug SEFH.“~]
selection in hospitals is compiled in Chapter 2.1 of the
book Farmacia H ~ s p i t a l a r i a . [ ‘ ~ ] Clinical P ~ a r m a c Q k i n ~ t ~ c s
A regular information procedure should be established Chapter 3.2 of Farmacia Hospitalaria (Hospital Phar-
on new developments in pharmacotherapy for the macy) contains a more detailed description of these ac-
pharmacy service staff and technical advice for the tivities.“’]
dispensation unit concerning any medication-related
problems detected. rtificiai Nutrition
a Priority should be given to aspects such as efficiency,
safety, and cost when technical reports to drug-se- Policy document: SEFH recommendations on artificial
lection committees are being prepared. nutrition (Sociedad Espaiiola de Farmacia Hospitalaria,
* Active information will be education- and training- 1997). 91
oriented and will be addressed to healthcare staff via The SEFH considers artificial nutrition to be multi-
bulletins and to patients. disciplinary in range and scope and, therefore, recom-
782 Policy Documents and Laws That Guide Clinical Pharmacy Practice in Spain
mends the creation of Artificial Nutrition Commissions, Law: Real Decreto establishing the requirements for
in which the pharmacy service should be always and performing clinical trials with drugs (Ministerio de Sa-
actively represented. The main task of these Com- nidad y Consumo, 1993).[211
missions is to establish an artificial nutrition protocol Heading 3 deals with CEIC. Art. 41.2 emphasizes that
that includes: the hospital pharmacist should be a member of the CEIC,
and Art. 42 describes the duties and functions of the CEIC:
* Records of enteric nutrition, peripheral parenteral nut- “. . .to evaluate the protocol and the research team,
rition, and central parenteral nutrition. evaluate the written information to be given to the subjects
0 Assessment of nutritional state. of the research, perform monitoring of trials.. . .”
* Calculation of calorie requirements.
* Administration routes. Policy document: Clinical trials (Sociedad Espafiola
* Biochemical monitoring. de Farmacia Hospitalaria, 1992).[221
* Standard formulas and regulations governing indi- Involving the pharmacist in the clinical trials may
vidual prescriptions. actually facilitate the work in some aspects, including:
In the SEFH’s view, the preparation and dispensation * Patient monitoring and follow-up, in which the phar-
of artificial nutrition is not the pharmacy services’ only macist collaborates with the researcher in the com-
activity, as they can also perform prescription and clinical pilation of analytical parameters.
monitoring. This already occurs at a number of Spanish 0 Registering and channeling any adverse reactions ob-
hospitals: the pharmacist prescribes and performs daily served and trying to establish the causal relation.
checkups on patients being fed artificially. 0 Conveying information to the patients to help them
comply properly with the protocol.
Policy document: Nutritional therapeutics (Sociedad
Espafiola de Farmacia Hospitalaria, 1992).[201
This chapter describes the activities performed by the
pharmacist as a member of the nutritional support team,
which involve a range of tasks from indications, assess- Law: Ley del Medicamento (Ministerio de Sanidad y
ment of nutritional state, and the preparation of artificial Consumo, 1990).“]
nutrition for adults and children to concepts on basic die- rt. 91.2. “To ensure the rational use of drugs the
tetics and mother-infant nutrition. Drug-nutrient inter- hospital pharmacy services.. . shall prepare reports on
action analysis is another duty. drug use.. . and perform any duties that lead to improved
drug use and control.”
Published by the SEFH in 1992, Farnzacia Hospitalaria An increasing number of Web pages of interest to the
covers other specific duties of the clinical pharmacist in clinical pharmacist are appearing on the Internet, in-
the health system, such as clinical toxicologyi261 and cluding the following in Spain:
clinical activities in hospital clinical units: infectious di-
seases, pediatrics, oncology, gynecology, surgery. geriat- Atenci6n Farmackutica (Pharmaceutical Care). Carlos
rics, clinical hematology, cardiovascular, intensive care I11 Health Institute, National Health School, http://
units, psychiatry, emergencies, e t ~ . ‘ ~ ~ ] www.isciii.es/unidad/Sgpcd/ens/atenfar/
paginaprincipal. htm.
Club de Atencidn Farmace‘utica (Pharmaceutical Care
Club), Pharmacy Faculty, University of Granada,
aw: Ley de regulacidn de sewicios de las oficinas de http://www.ugr.es/-atencfar/welcome.htm.
farmacia (Jefatura de Estado, 1997).‘28’ Ateizcidn Farmackutica (Pharmaceutical Care), Cinfa
Art. 1: Enumerates the functions and duties of laboratories, http://www,atencion-farmaceutica.com/.
pharmacists working in pharmacy offices, which include Unidad de Farmacia Clinica y Farinacoterapin (Cli-
‘ ‘information and follow-up of pharmacological treatment nical Pharmacy and Pharmacotherapy Unit), Pharmacy
of patients; collaboration on the control of individualized Faculty, University of Barcelona, http://www.ub.es/
use of drugs to detect any possible adverse reactions and farcli/wpO.htm.
inform the relevant pharmacovigilance bodies.” Fundacidn Pharmaceutical Care EspaAa, Barcelona,
Since the law came into effect, the community phar- http://www.pharmaceutical-care.org.
macist has evolved from a mere “pharmaceutical advi-
ser” to becoming involved in the launch of pharmaceu-
tical care programs.
ent: Granada Consensus on drug- The following are a few journals pertaining to phar-
related problems, 1998.[29’ maceutical care and clinical pharmacy:
On the assumption that the three basic objectives of
pharmaceutical care are to identify, solve, and anticipate Farmacia Hospitalaria (Farm Hosp). Sociedad Espa-
medicinal drug-related problems. the Consensus of Gra- fiola de Farmacia Hospitalaria. http://www.sefh.es/
nada established a classification of such problems based revistas/revistas.htm.
on the application of a systematic criterion of evaluation Atencidn Farnzace‘utica-European Journal of Clin-
of the requirements of pharmacotherapy : to be indicated, ical Pharmacy (Aten Farm). http://www.farmaclin.
effective, and safe. com.
784 ocuments and I,aws That Guide Clinical Pharmacy Practice in Spain
Pharmaceutical Carr ErpuZa (Phnrm Cure Esp). medicamentos. SEFH 1996; 20 (77), 15S20. http::,'www.
Fundaci6n Pharmaccutical Care Espafia. http:llwww. setli.es,'norinas~normay9.htm(accessed Oct. 2000).
pharmaceutical-carc.cs. 16. Airpuru, K.; Arrirabalaga. M.J.; Cao, C . Informacidn dc
Mcdicamcntos. In Farmaciu I-lospitrrlurin, 2nd Ed.;
SEFH: Madrid, 1992; 349 369.
17. Iiccomendaciones de la SEFH sobre FarmacocinCtica
clinica. SEFH 1997, 21 (XO), 10 1 I.http: '!www.scfh.es/
~
5. Programa Ojiciul de lorinacidiz en la Especializcrcidn 21. Real Decreto 561/1993, de 16 de abril, por el quc se
de I'czrmacia Hospitalaria; Sociedad Espaiiola de Farm- eatablecen 10s requisitoa para la realizacicin de ensayos
acia Hospitalaria. http://www.se~.es/residentes/programa/ clinicos con medicainentos. BOE no. 114, May 13, 1993.
programa.htm (accessed Mar 2001). 22. Idoate, A.J.; Cainzos, M.D.: Tdoipe, A. Ensayos clinicos. In
6. Ordcn de 1 de febrero de 1977 por la quc se regulan 10s Farinacia Hospitalaritr, 2nd Ed.; SEFH: Madrid, 1992;
servicios farmacCulicos dc hospitales. ROE no. 43, Feb 19, 645-691.
1977. 23. Altirniras, J.; Segu, J.L. Farmacoepidemiologia y Estudios
7. Ley I4/ 1986, de 2.5 de abril, Gencrdl dc Sanidad. BOE no. de Utilizacibn de Mcdicamcntos. In Fannucia Hospitala-
102, Apr. 29, 1986. ria, 2nd Ed.; SEFH: Madrid. 1992; 396- 435.
8. Ley 2.511990, dc 20 de diciembrc, del Mcdicamento. BOE 24. Chstro, I.; Altiiniras, J.; Mas, P.; Napal. V.; Olalla, J.F.;
no. 306, Dcc. 22; 1990. Pardo, C.; Rodriguez, J.M. Farmacovigilancia. In F~irm-
9. C0l0qrui0.~ de Aproximacidn u la Farinacia Clinica; acia Hospitalaria, 2nd Ed.; SEFH: Madrid. 1992; 601 -
A 3.0 150
B
u
gPP
5e m
v)
-0 w
c
u-
0
b
a
a
1 .G 50
0 .o 0
1979-1983 (3) 1984-1988 (4) 1989-1993 ( 2 ) 1994-1998* (2)
5-year approval period (number withdrawn in calendar years)
1
0Percentage of cohort withdrawn +Number of new molecular entities approved in calendar years I
Fig. 1 New molecular entity withdrawals. NME. new molecular entity; *Prescription Drug User Free Act years. (From Ref. [6].)
improve the understanding of the potential severity of MedWatch program, the FDA runs a program for adverse
previously anticipated risks, to detect events resulting events related to veterinary products and in conjunction
from drug interactions or drug effects in particular po- with the Center for Disease Control and Prevention, a
pulations, and to assess the potential for causal rela- program for adverse events with vaccines, the Vaccine
tionships.[61 The FDA’s primary mechanism for iden- Adverse Event Reports System (VAERS).
tifying serious ADEs is the spontaneous reporting system After determining that a problem exists through the
(SRS). Additional approaches include the use of large post-marketing surveillance process, the FDA has several
healthcare databases, cohort and case-control studies, and options. These options include medical alerts such as
product registries. “Dear Health Professional” letters or safety alerts pub-
In 1993, the FDA introduced a new streamlined SRS, lished in the FDA Medical Bulletin or on the MedWatch
MedWatch. MedWatch allows healthcare providers and web site, press releases, product labeling changes, boxed
patients to report ADEs to the FDA by several mecha- warnings, and product withdrawals. The FDA may also
nisms, including electronic and print media (Table 1). require a drug manufacturer to conduct post-marketing
The goals of the MedWatch program are to increase safety studies. It should be noted that the FDA is only able
awareness of drug- and device-induced disease, clarify to request that a manufacturer remove a product from
what should be reported to the FDA, simplify the re- the market.
porting process, and provide regular feedback to the
healthcare community about safety issues involving me-
dical products.“’]
Information received through the MedWatch program
is entered into the Adverse Event Reporting System Drug manufacturers may identify ADEs through several
(AERS) database. The AERS database is designed to means, including spontaneous reports by healthcare pro-
permit electronic or paper submission of reports, comply viders or patients, clinical studies, and reviews of the
with international standards and terminology, and facil- medical literature. Once the company is aware of an
itate pharmacovigilance screening. In addition to the ADE, the data are evaluated, the seriousness and ex-
Post-Marketing Surveillance
Fig. 2 Post-marketing surveillance process. An ADE is serious if the outcome is death; life-threatening: requires an intervention to
prevent permanent impairment or damage; or results in hospitalization, disability. or congenital anomaly. AERS. Adverse Ebent
Reporting System. (From Ref. [16].)
Table 1 Contacts for adverse event reporting healthcare provider who may be able to more accurately
assess the ADE."']
Method Contact
MedWatch
Direct mail MedWatch
The FDA medical products
reporting program
Food and Drug Administration
5600 Fishers Lane The current post-marketing surveillance system involves
Rockville, MD 20852-9787 multiple processes and interactions. A breakdown in any
Facsimile 1-800-FDA-0178 one of these processes or interactions could lead to a
Internet https:llwww.accessdata.fda.govl weakness. Several weaknesses of the current system have
scriptslmedwatchl
been identified. The first is the identification of an ADE.
Modem I-800-FDA-7737
Telephone 1-800-822-1088
Identification of an ADE is subjective and imprecise.['*]
A study to evaluate how accurately ADEs are identified,
VAERS" found less than a 50% agreement between clinical phar-
Internet http:ll~~ww.fda,gov/cber/vaers/ macologists and treating physician^."^] A second weak-
vaers.htm ness of the current system is underreporting of ADEs. The
Telephone 1-800-822-7967 FDA estimates that only 1- 10% of ADEs are reported.[*']
A third weakness is the introduction of bias. ADEs re-
Veterinary Products ported through the SRS are not subjected to the same
Telephone 1-888-332-8387 rigorous standards as those determined through controlled
"VAERS = Vaccine Adverse Event Reports System clinical studies. These reports are therefore subjected to a
number of biases, including the length of time a product
has been marketed, reporting environment, detailing time,
atients and quality of data.[211A fourth weakness is the inability
to estimate population exposure to the drug. The FDA
The role of the patient is also vital to the post-marketing attempts to overcome this weakness by forming coope-
surveillance process, particularly in identifying an ADE in rative agreements with outside research organizations.
an outpatient setting. Although patients may report se- Unfortunately, these data still need to be interpreted
rious ADEs directly to the FDA or any ADE to the drug cautiously because drug prescribing may not equal drug
manufacturer, it is suggested that they work through a usage.[221The fifth weakness of the current system is the
300000
M
ii n
2 250000
* 200000
a2
L
0
b 150000
a
50000
0
85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
Year
Expedited 0Direct
Fig. 3 Number of periodic, expedited, and direct reports received by the FDA for the years 1985-1999. (From Ref. [14].)
~ o s t - M a r ~ e t Surveillance
in~ 789
quality of reports submitted to the FDA. Often the poor In addition to those items developed by the FDA, the
quality of information received does not allow the FDA to creation of an independent center for assessing phar-
adequately evaluate the report and be proactive in maceutical effectiveness has been proposed."3273281 This
protecting the public.'61 The final weakness of the cur- center would be an independent agency that would assist
rent system is the lack of effect of the FDA's action. A in developing answers to issues that face healthcare pro-
study documented that the prescribing habits of cisapride viders and patients after a drug has been marketed, in-
did not change after the FDA expanded the black box cluding therapeutic differences and safety issues.
warning, issued a press release, and had the manufac-
turer distribute 800.000 ''Dear Health Professional"
letters."31
In spite of these limitations, the current system does
have some strengths. For example, it covers large num- The current post-marketing surveillance system in the
bers of diverse patients. Reports generated through the United States is a multifaceted, international process in-
SRS reflect everyday use of the drug. A second strength volving the FDA, drug manufacturers, healthcare pro-
of the system is the ability to monitor ADEs in an in- viders, and patients. Whereas the FDA is strengthening
expensive manner. The current system is relatively inex- the current system, its success will still rely heavily on the
pensive compared with an observational event monitoring submission of spontaneous reports. Therefore, healthcare
system.'241 The last strength of the current system is its providers need to be continually reminded of the value of
ability to generate hypotheses and signals. Currently, the reporting ADEs.
FDA is in the process of determining what constitutes a
signal: this strength is only beginning to be fully used.
00: Available at: http://www.citizen.org/hrg/publicatioiis/ matter of opinion. Clin. Pharmacol. Ther. 1976, 19 ( 5 Pt. I),
FDAsurvey/FDAsurvey.htm. Accessed 2/6, 200 1. 489 492.
10. Tufts Center for the Study o f Drug Development. User 20. Major Management Challenges and Program Risks. In
Fees Credited with 5 1% Drop in Average Approval Times United Slate.r General Accounting Ofizcc~;January, 200 I ,
Since 1993. In Tufts Center j o r the Study of Drug Deve- Available at: http://frwebgate.access.gpo.gov/cgi-bin/
lopment hnynct Report: June 1999, Available at: http:// useftp.cgi‘!IPaddrcss=162.140.64.2 1&fileiiame=dO 1247.
www.tufts.edulmed/csdd/impact 12.pdP. Accessed 2/22, pd~&dircctory=/diskb/wais/data/gao.Accessed 2/23, 200 I .
2001. 21. Sachs, R.M.; Bortnichak. E.A. An evaluation of spontan-
11. Joint Commission on Accreditation of Healthcare Organi- eous adverse drug reaction monitoring systems. Am. J.
zations. Cnrnprehensivr Accreditation Manual ,f&r Hospi-
tals: Joint Commission o n Accrediation of Healthcare 22. Scrradell, J.; Bjornson, I1.C.; Hartmna, A.G. Drug
Organizations: Oakbook Terrace, Illinois, 2001. utiliLation study methodologies: National and international
12. ASHP guidelines on adverse drug rcaetion monitoring and perspectives. Drug Intell. Clin. Pharm. 1987, 21 (12),
reporting. Am. J. Health-Syst. Pharrn. 1995; 52, 417 419. 994 1001.
13. Curran, C.F.; Engle, C. An index of United States Federal 23. Smalley, W.; Shatin, D.; Wysowski, 11.K.; Gurwitz, J.;
Regulations and Guidelines which cover safety surveil- Andrdde, S.E.: Goodman, M.; Chan, K.A.; Platt, I<.;
lance of drugs. Drug Inf. J. 1997. 31. 833-841. Schech. S.D.; Ray, W.A. Coiitraindicatcd use of cisapride:
14. and QA/QC S o f i d y Bvuluation lni- Impact of food and drug administration regulatory action.
tiatives in OPDRA /Slide Pre.smtution]; 07/03/00, Avail- JAMA: .I.Am. Med. Assoc. 2000, 284 (23), 3036-3039.
able at: http://www.fda.gov/cder/prescnt/dia-62000/opdra/ 24. Flctcher, A.P. Spontaneous adverse drug reaction reporting
sld040,htin. Accessed 2/22, 2001. vs event monitoring: A comparison. J . R. Soc. Med. 1991,
1s. US Food and Drug Administration. MedWatch, The FDA 84 (6), 341L344.
M ~ d i c a Products
l 1icJporting Program; Available at: http:// 25. Scott, H.D.; Thacher-Renshaw, A.; Rosenbaum, S.E.;
www.fda.gov/medwatch/what.htm. Accessed 2/22, 200 I . Waters, W.J.; Green, M.; Andrews, L.G.; Faich, G.A.
16. US Food and Drug Administration. The FDA k s k Guide Physician reporting of adverse drug reactions. Results of the
,for Adverse Event and Prodiic,t Proh1c.m Reporting; Rhode Island Adverse Drug Reaction Reporting Project.
Available at: http://www.fda.gov/rnedw~~tch/rep(~rt/desk/ JAMA, .I.Am. Med. Assoc. 1990, 263 (13), 1785 1788.
tpcfiiial.htm#toc. Accessed 2/22. 200 1. 26. Hamrcll, M. Current regulations and practiccs for adverse
17. Henltel, J. M(dWuic1z: FDA’s “Heud.s 1Jp” on Medical event reporting: Implications for labeling. Drug Inf. J.
Product Sofety; Available at: http://www.Sda.gov/Sdac/ Z ~ ~ 34,
( ~97s
0 ~ 980.
features/1C)OX/69X-med.html. Acccsscd 02/26, 2001. 27. Wood, A.J.; Stein, C.M.; Woosley, R. Making medicines
18. Koch-Weser, J.: Sellers, E.M.; Zacest, R. The ambiguity o f safer-the need for an independent drug safely board. N.
adverse drug reactions. Eur. J . Clin. Pharmacol. 1977, 11 Engl. J. Med. 19998, 3 3 Y ( 2 3 , 1851-1854.
(2), 75-78. 28. Ray, W.A.; Griffin, M.R.; Avorn, J. Evaluating drugs after
19. Kareh, F.E.; Smith, C.L.; Kerzner, B.; Mazzullo, J.M.; their approval Sor clinical use [see comments]. N. Engl. J.
Weintraub, M.; Lasagna, L. Adverse drug rcactions-a Med. 1993, 329 (27), 2 0 2 9 ~ ~ 2 0 3 2 .
PHARMACY PRACTICE ISSUES
I
(responsible for managing drug programs for seniors and
Prescriptions foy Health, commonly referred to as the those on social assistance).
Lowy report after its chairman, was initiated by a pro- Recommendations are directed at government, med-
vincial government after noting astronomical rises in its icine, hospitals, nursing, and the public; the following is a
health care expenses on prescription drugs (20% annually synopsis of those recommendations involving pharmacy:
and 500% over the past decade). The report contains 147 4.22: The continuation of drug interchangeability
recommendations, many directed at government, but whereby pharmacists provide the generic equivalent (de-
many also directed at the health professions, the health fined) of the lowest-cost product acceptable to govern-
science centers, the pharmaceutical manufacturers, dis- ment. This is followed by a number of other recom-
tributors, and the public. The report was produced by a mendations regarding drug pricing and the development
committee appointed by the Ontario Ministry of Health. of the concept of “best available price.”
Its members were F. Lowy (Chair), M. Gordon, R. Moul-
ton, R. Spunt, J. Thiessen, D. Webster, and W. Wensley. : That unit-dose/IV admixture be the system of
(Members Thiessen and Wensley are pharmacists.) choice for institutional drug delivery in hospitals and that
the Ministry aid hospitals in the costs of conversion.
7.4: That physicians and pharmacists jointly study the
appropriateness of the quantity of drugs on a prescription
and prepare guidelines.
The committee found that Ontarians receive “excellent
treatment involving prescription drugs” and that they 7.7: That postmarketing surveillance studies be es-
were safe, available, and affordable through insurance tablished involving large numbers of family physicians
plans and government-supported programs for the aged and others.
and those receiving social welfare. However, the com-
7.9: That “Choice of Medications-1990’ ’ be made
mittee went on to note some problem areas:
available to all physicians and pharmacies and that it con-
tain guidelines and objective information on drug pre-
Some products paid for by the government plan were
scribing.
suboptimally effective or had unfavorable benefit/
risk ratios. 7.11 and 7.12: That the hospital formulary system be
Physicians are not well prepared educationally for fostered and that the concept be extended to group clinics,
prescribing the many agents available, especially for nursing and old age homes, health maintenance organiza-
the elderly; CE programs were found lacking. tions, and comprehensive health organizations.
Pharmacists were “not meeting their full professional
7:13: That generic names be on all prescription labels.
potential as members of the health care team.”
Some citizens do not have access to these drugs, be- 7.15: That a pilot project be established to test the
cause they are the “working poor” without insurance Harvard model of academic detailing.
or have extraordinary drug costs because of cata-
7.18: That physicians and pharmacists establish for-
strophic illness.
mal mechanisms on the issues of patient counseling
and communication.
The committee found less than adequate cooperation
between the federal government (responsible for approv- 8.1: That the role of pharmacy assistants be defined
ing new drugs on the market) and provincial governments and ensure that they perform product-oriented tasks while
pharmacists concentrate on patient-oriented tasks such as 2 0 : That drug information programs be supported
monitoring drug therapy and providing advice to patients and expanded.
and other health professionals.
2 2 : That a second faculty of pharmacy, with a five-
8.2: That information management systems be estab- curriculum, be established.
lished to ensure optimal access to patient profiles and
2 2 : That the present faculty of pharmacy (U.
adverse drug interaction programs.
Toronto) increase its curriculum to five years with more
8.3 and 8.4: That standards for original packaging instruction on patient counseling, therapeutics, drug in-
dispensing be developed. formation, pathophysiology, and geriatrics.
.5: That auxiliary labels and other printed information 2 4 : That the practical training period be restructured.
on prescription drugs along with verbal be increased, with 8.25: That a PharmD program be established in two
reinforcement by the pharmacist. years.
.6: That pharmacists pay particular attention to the 8.26: That joint teaching occur in medicine and phar-
visually handicapped when labeling. macy on patient-oriented services, including therapeutics,
.7: That pharmacists label in the language of the monitoring techniques, and patient counseling.
patient, with verbal reinforcement. : That pharmacy services to long-term institutions
be improved.
: That a campaign be aimed at seniors to pick one
pharmacy for all services. 8.31: That pharmacy and nursing work out their roles
in counseling.
.9: That patient profiles be required in all commu-
nity pharmacies. 3 6 : That mechanisms be put in place to ensure
appropriate patient education regarding treatment plans
: That portable patient medication records such as
prior to discharge.
the “smart card” be developed.
8.37: That all hospital pharmacies require patient
8.11: That guidelines be developed to ensure the profiles.
pharmacist has access to the patient’s diagnosis(es).
.39: That mechanisms be established to compensate
8.12: That a campaign be launched to make the public itals providing pharmacy services to outpatients.
more aware of the services to be expected of a phar-
macist, especially those related to the provision of in- 8.41: That funding be increased for hospital phar-
formation on proper use. macy residencies.
8.13: That all pharmacies have a private and comfort- 42: That standards and ethically appropriate me-
able consultation area. s of cost containment be established for investiga-
tional drugs.
8.14 and 8.15: That pharmacists exert more control
over the sale of nonprescription drugs.
8.45: That community programs for patient compli-
ance be funded.
8.16: That pilot projects be established to assess alter-
.3: That drug utilization review programs be inte-
native reimbursement for the provision of pharmaceutical
grated into medical CE.
services not based on the sale of a drug.
9.4: That the provincial adverse drug reaction program
.17: That linkages involving the patient be deve-
be supported.
d between the medication profile in hospital and in
the community. 9.6: That approaches be researched to reduce use of
hypnotics, sedatives, and tranquilizers.
: That the clinical role of pharmacists be en-
couraged and expanded in monitoring and intervention 11.1: That liquid formulations be provided to the
as necessary. elderly with swallowing difficulties.
8.19: That pilot projects of community drug therapy 11.2: That smart cards be introduced to facilitate
committees be established, modeled on institutional monitoring and that pharmacy computer systems be
settings. programmed to handle problems of the elderly.
793
11.5: That guidclincs be developed to limit hypnotics, Thc report is as relevant today as it was a decade ago.
sedatives, and tranquilizers for the shortest possible time It recognized the valuable work of clinical pharmacists
with no repeats. in institutions and recommended that it be extended not
only in institutions but into thc community as well. The
devclopment of the PharmD programs at the University
of Toronto (in Ontario) and thc University of British
Columbia (farthcst western province) has provided fur-
Elevcn years later, many of the recornmendations have thcr stimulus to this effort. Standards (hospital accred-
been carried out, at least partially. Others have not moved itation, hospital pharmacy, and community pharmacy)
significantly sincc the report’s publication. Probably the also seem to have been influenced or minimally have
most important aspect of the report was the laundering paralleled the recommendations of this report.
of thc province’s medication system in public, with res- Because Ontario is Canada’s most populated province,
ponsibilities being levied at our government, our m i - events that occur there are often considered by othcr
versities, and our professions. Yet, although the high- provinces or in national efforts. It is therefore fair to
lights of this report may have hit thc lay press for a day suggest that thc Lowy report probably had significant
or two, particularly the aspects of drug pricing, thcre is influence beyond thc boundaries of Ontario.
little long-term cffcct. The provincial pharmacy associa-
tions have taken the report seriously and have initiated
many of its recornmcndations.
Thc initial concern of the government and the com-
mittee, namely, a rapidly climbing total drug bill, has All in all, we would do well do rcvijit these iecominenda-
only been partially addressed. Efforts have been made to tions, particularly tho\e dealing with sedmlc<\ Lare and
control drugs such as omcpraLolc through the “limited computerized record\. The patient orientation urged by
use” requirement, which places additional (unpaid) work Lowy for pharmacists has certainly spurred the clinical
on pharmacists. Significant efforts have also been made movement in this part of the world
in some pilot prqjccts on antibiotic prcscribing: thc model
involves joint educational efforts for community physi-
cians and pharmacists and joint eIforts to follow guide-
lines on a variety of infectious diseases. In areas where
thcse efforts havc been started, antibiotic costs have Prescriptions for Health/Reeommanclations pour la sant6. Report
fallen by 10-20%. However, overall in the province, the of’ the Pharmaceutical Tnquiry/Rapport du ComitC enyuctc de
drug budget continues to gallop ahead at the rate of 12% I‘Ontario sur les produits pharmaceutiques. Government of’
per year. Ontario, I u l y 1990.
PROFESSIONAL DEVELOPMENT
"
factors: agent, environment, and host
Sufficient n sological
stage
symptoms disease
PERIOD
PROMOTION RECOVERY
chemoprophylaxis
Fig. 1 Natural history of disease and levels of prevention. (From Ref. (91.)
thogenic period, and the resultr9' (Fig. 1). This division is It should be noted that the existence of a close sta-
of great interest, as we see later in the article with regard tistical relationship between a risk factor and a disease
to the levels of prevention. does not mean that all individuals with the risk factor
will necessarily develop the disease, or that the absence
of this risk factor is any guarantee that the disease will
not develop.
The prepathogenic period is characterized by the presence
of factors that favor or determine the development of the
disease. These factors may be environmental (infectious,
physical, chemical agents, etc.) and behavioral (over- The pathogenic period has two stages: the presympto-
consumption of fats or carbohydrates, sedentary lifestyle, matic stage and the clinical disease stage. During the
smoking, excess consumption of alcohol, use of illegal presymptomatic period, there are no symptoms or clini-
substances, etc.), and they affect the endogenous genetic cal signs but, as a result of the causal stimulus, the
predispo~ition[*~' toward developing the disease. anatomical and pathological changes responsible for the
Some of these factors are necessary (but not sufficient) disease (arteriosclerosis in the coronary arteries, pre-
for the onset of the disease. The clearest example is that of malignant disorders in the tissues, etc.)"ol are already
the agents of infectious diseases (bacteria, viruses, etc.). under way.
At other times, the factors are not absolutely necessary for In the clinical stage, the changes in the organs and
disease onset, as this can occur in their absence, although tissues are already important enough for signs and
their presence implies an increased likelihood of the symptoms of the disease to appear in the patient."']
condition arising. Such is the case with the risk factors for Finally, the result is the last period in the natural
chronic diseases (high blood pressure, obesity, smoking, history of the disease and reflects the end of the process:
hypercholesterolaemia, etc.).[241 death, disability, chronicity, or recovery.
796 Preventive Medicine
Pharmaceutical Association, proved the viability of Table 3 What can health promotion offer to the
health education in both the therapeutic and health pro- community pharmacy?
motion spheres. Three hundred pharmacists took part a Increase impact and effectivessnes of pharmacotherapy
in the experiment in Barcelona, the educative sessions o Increase impact and effectivessnes of counseling and health-
being attended by around 10,000 people. The evaluation related advice
proved the value of exercise as it helped to significantly e Increase job satisfaction by job enrichment:
increase the knowledge of those attending about the - By fostering liaison with users
matters discussed. - By improving cooperation with other providers
Also to be noted are the two health education plans - By making visible “the cognitive service” information,
drawn up in Spain by the Consejo General de Colegios advice, and counseling
e Make the contribution of community pharmacy evident
FarmacCuticos (General Council of Pharmaceutical As-
- In the management of drug therapy
sociations), with the collaboration of the provincial
- As an important place for health-related service
associations: the Plan de Educacidn Nutncional (Plan for a Support the integration of community pharmacy into the
Education on Nutrition)[*” and the Plan de Educacidn primary health care team
sobre el medicamento (Plan for Education on Drugs).[221
(From Ref. [23].)
1. Give priority to activities that, in healthy adults, Applying health promotion principles could be a
have shown to be effective in the population; that means to further develop the professional role (Table 3).
is, they have provided some health benefit for the
community and constitute a framework of ref-
erence that makes it clear which preventive ac-
tivities should be carried out at the pharmacy.
2. Adapt the joint development of these activities to Health promotions activities in primary health care, in
the needs and programs established for each basic general practice and in community pharmacy, is not yet
heaith area. The idea resulting from all this is that well documented or evaluated with sufficiently high
there has to be coordination between all the agen- quality standards. There seems to be a wide variance in
cies and professionals involved in primary health the degree to which health-promoting services, projects,
care, and the appropriate supports and mechanisms and programs are documented, evaluated, and evidence
for achieving this coordination. based. In particular, there seems to be need for further
work concerning lifestyle counseling, health education,
In practice, to carry out the preventive activities de- and interventions for health development.[231
fined, the pharmacist will have to take into account the The need to be able to evaluate the effectiveness of the
need for the following: activities is obvious. Therefore, it will be essential to
specify, during the process of implementing health
Reinforcing knowledge, skill, and attitude through promotion at the pharmacy, what the particular objectives
accredited, continued training. are and which activities must be carried out, while
Creating an atmosphere and place for these ensuring that the former are attainable and the latter
activities. feasible on the basis of the resources available. It will be
Having the necessary measuring equipment and necessary to plan a careful implementation strategy that
resources for the activities. will ensure the participation of as many professionals as
Setting a good example, both the pharmacist and possible while also permitting evaluation of the repercus-
the other personnel, to reinforce the aforemen- sions, on the population’s health, of the integration of
tioned healthy atmosphere. health promotion activities into the pharmacist’s practice.
Preventive Medicine 799
P ~ N D I X1
I u M
From pharmacy 0
primary care centre 0
(full name and address)
telephone number
Patient’s data
1st surname 2nd surname name
NCR paper
800 Preventive Medicine
der primary care, a provider or provider team is the pri- clinics. These settings would include family practice of-
mary source of a patient’s care, and the place that a patient fices, general medicine clinics, or pediatric clinics.
turns to for health care information and support.”[41
The key feature of primary care clinicians is that they
handle a wide range of medical conditions. They serve as ESTABLISH IN^ N AMBULATORY CARE OR
the entry point into the health care system and decide on PRIMARY CARE PRACTICE
referral or triage to secondary or tertiary levels of care.
Specialty clinics provide ambulatory care, and, in many Obtaining Clinical Privileges
cases, some primary care. Most specialists (e.g., cardio-
logy, neurology, nephrology, etc.), however, are consid- Prior to any patient intervention, it is essential that the
ered secondary levels of care. These secondary and tertiary clinical pharmacist has in place a document that outlines
levels of care should be utilized when a problem is beyond specifically the practitioner’s scope of practice.[’] It is
the expertise of the primary care clinician. The typical important that the scope of this document be sufficient to
family practice physician or general internist cares for well allow the clinical pharmacist to function as a member of an
over 90% of problems that present to them. There is a interdisciplinary primary care team. This document could
small percentage of problems that would require referral to be in the form of clinical privileges or a scope of practice
secondary or tertiary care. Even when a patient is referred statement (Appendix 1). This approach could be used for
for a specific problem, the primary care clinician should developing a practice for a new practitioner or used for a
maintain overall care for the patient and coordinate all previous clinician who has not formally obtained scope of
other aspects of care. This continuity implies chronic care practice privileges. If the facility is an organized health
and preventive care that are more conducive to long-term care center (hospital or managed-care organization), it
assessments of patient outcomes than can be achieved with would be worthwhile to review the facility’s guidelines for
acute illness managed in the inpatient setting.[31 clinical privileges granted to the physician’s assistants and/
Clinical pharmacists and pharmacotherapy specialists or nurse practitioners if these are available. Depending on
provide care in a wide variety of ambulatory care and the institution, approval is required by the Chief of
primary care settings.”*21There are two major types of Pharmacy, Chief of Staff, Clinical Executive Board, and
practice that are very distinct. While currently more com- the Institutional Director. Once these privileges are es-
mon in structured settings such as hospitals and health tablished, only then can the clinical pharmacist provide
maintenance organizations, primary care is increasingly primary patient care (e.g., in pharmacist-managed clinics).
being provided in many settings including community In the past, formal guidelines to obtain clinical pri-
pharmacies. The first type of practice is one in which the vileges were often not commonly developed in private
pharmacist is independently responsible f o r providing practice or other settings such as outpatient family practice
primary care, typically between regularly scheduled phy- settings. However, clinical pharmacists in private practice,
sician visits. This includes conducting complete histories; community pharmacies, family practice residencies, and
obtaining objective information including physical assess- health maintenance organizations should develop these
ment and ordering laboratory tests; starting, stopping, or guidelines for their clinical pharmacy practitioners to
changing drug therapy; and determining the appropriate ensure quality and evaluate performance. For clinicians in
timing of follow-up visits. These activities are common in these settings, it is less likely that formalized arrangements
pharmacist-managed clinics in the Indian Health Service, for scope of practice privileges exist with physicians or
medical centers, and VA hospitals, including hyperten- other health professionals. However, similar templates as
sion, diabetes, hyperlipidemia, anticoagulation, and phar- those for institutions (Appendix 1) could be used and mo-
macy service clinics. These activities are in contrast to dified for these settings.
those provided by other professionals such as physician The application form in Appendix 1 also requests data
assistants or nurse practitioners who may perform func- on whether the clinical pharmacist is board certified in
tions traditionally performed by a physician. pharmacotherapy or another specialty. Board certification
The second type of setting is an interdisciplinaiy team should be considered strongly desirable, if not required.
approach to care of the patient where the pharmacist sees At the present time, the most appropriate specialty
patients with physicians. Pharmacists who work in such certification process for ambulatory or primary care
teams assist with care at the same time other health pharmacists would be certification in pharmacotherapy.
professionals see the patient. In this setting, they may have This would be analogous to physician certification in the
independent patient care activities but these would not be broad-based specialty of family practice. Board certifica-
as extensive as are generally seen in pharmacist-managed tion in pharmacy will be increasingly important and it
Primary Care, Clinical Pharmacy Services in (ACCP) 803
should be achieved by all ambulatory care/primary care factors to address if patient satisfaction is being assessed.
pharmacy practitioners who provide the services outlined Providing these personal services is not new but it is
in this report. increasingly important when patient satisfaction drives
third-party contracts in managed care. Pharmacists must
provide these personal levels of care if they truly are
delivering pharmaceutical care.
such as the American College of Physicians, the Ame- Force wanted to highlight optimum methods for docu-
rican Medical Association, the BlueCross Blueshield menting positive outcomes of clinical pharmacy inter-
Association, and other specialty societies are developing ventions. To keep in step with health care reform, a
new treatment guidelines. good method of assessing the impact of therapy on a
It is important to note that AHCPR is not a regulatory specific chronic disease is health-related quality-of-life
agency and is not involved with reimbursement. Applica- (HRQL) outcome measures. The pharmaceutical indus-
tion of the guidelines is not enforced by the government. try, the medical profession, and governmental agencies
Using these guidelines that were prepared by multidis- have shown increasing interest in assessing new mea-
ciplinary panels of experts may allow primary care pro- sures of a drug's overall effectiveness. Quality of life
viders to deliver scientifically sound care to the patient. (QOL) will be considered as seriously as safety and ef-
There are also medical-legal issues pertaining to ficacy when evaluating response to therapy.
clinical practice guidelines developed by specialty soci- Even when primary care providers follow accepted
eties. The general counsels who are involved with these clinical practice guidelines, there is no assurance of a
issues, private practice attorneys, and the counsel of the favorable outcome. That is why it is important for the
American Medical Association generally believe that fol- clinical pharmacist to understand and use appropriate,
lowing established clinical practice guidelines would be a clinically relevant outcome measures to quantify the
strong defense in malpractice cases. However, if a prac- impact of their interventions."21 Bungay and Wagner
titioner deviated widely from these guidelines, he or she argue that HRQL outcome measures should assess phy-
would need to have a strong rationale, documented in the sical, social, and role functioning; emotional distress and
patient's record, to support the use of an alternate regimen. well-being; general health perceptions; and energy and
A major issue that needs to be addressed is what f a t i g ~ e . " ~They
] also stress that the assessment of health
standards or methodologies should be followed when status must be integrated into the care of patients. HRQL
guidelines are developed."01 A structured, systematic, measures can be used to assess a population with a specific
science-based approach should be used whenever devel- disease, or as a research method to examine how changes in
oping these guidelines. The Institute of Medicine has process affect outcomes."41 The current challenge is to
identified the necessary characteristics which would en- develop tools and operations that can be used in the office
hance a guideline's effectiveness: sensitivity, specificity, setting to evaluate care, and hopefully direct treatment for
patient responsiveness, readability, minimal intrusiveness, individual patients. It is critical, however, that these as-
feasibility, and computer compatibility." 1312' If guideline sessments be performed while considering the patient mix,
development followed these scientific methods, it would timing of data collection (timing during the evolution of a
be difficult to criticize the process. disease process), patient characteristics, and measurement
In contrast to good guideline development, the de- properties. The reader is referred to a more comprehensive
termination of whether guidelines are useful depends discussion of these issue^."^.'^^ We will briefly discuss the
upon their readability, computer compatibility, and other importance of HRQL outcomes, the types of instruments
factors. Outcomes management takes the results of the available, and how to choose a specific instrument for a
outcomes research and incorporates them into clinical specific patient population.
practice guidelines to theoretically help ensure all patients Quality of life includes many issues occurring in a
receive the most effective treatment available." 13121 person's life, such as health status, job satisfaction, family
issues, and overall Since these are
nonspecific, this measurement may not be the best in-
dicator of positive or negative pharmacotherapeutic inter-
Another objective of this report is to determine the best ventions made by a clinical pharmacist. Health-related
method to measure the impact of pharmacotherapeutic quality-of-life assesses those aspects of a patient's life
decisions made by clinical pharmacists on patient out- specifically related to physical and mental well-being.
comes. There are several approaches that can be used to "Hard data" such as treadmill time in patients with heart
assess outcomes. These include disease- or treatment- failure may be of interest to clinicians, but is of little value
related outcomes (e.g., blood pressure, seizure frequency, to the patients. Frequently, "hard data" correlate poorly
medication adherence, target serum concentrations). The with the patient's actual functional status. An additional
Task Force felt that it was not appropriate for this report reason to add HRQL instruments to clinical outcomes
to delineate specific clinical outcomes such as level measurements pertains to the phenomenon that patients
of blood pressure control or serum drug concentrations. with the same medical condition often respond differently
While these are important outcome measures, the Task to therapy. HRQL is a complementary method of meas-
Primary Care, Clinical Pharmacy Services in (ACCP) 805
uring the impact of therapy on chronic disease. Thus, The Health Outcomes Institute has developed and
HRQL might be used in tandem with explicit or implicit validated several outcome instruments that can be used to
quality assurance review that is measuring the process of evaluate patient outcomes following interventions by
delivering care along with clinical outcome measures pharmacist^."^] These include hypertensiodlipids, angina,
(e.g., blood pressure for hypertension or peak flow mea- asthma, chronic obstructive pulmonary disease, chronic
sures for asthma).[61 sinusitis, hip replacement, hip fracture, depression, low
Primary care providers, patients, and health care ad- back pain, osteoarthritis, alcohol abuse, stroke, rheumatoid
ministrators are interested in HRQL outcomes because arthritis, and prostatism (Appendix 4). The Health Out-
they are a method to measure the impact of therapy on the comes Institute is located at 2001 Killebrew Drive, Suite
disease process. Hospital administrators and other policy 122, Bloomington, MN 55425; telephone (612) 858-9188.
makers have a high stake in these issues because payers
are beginning to use HRQL data in their reimbursement Example
It is imperative that clinical pharmacists involved in If pharmacists were providing primary care for hyper-
providing primary patient care have a good working know- tensive patients and wanted to compare the results of an
ledge of HRQL instruments and are competent in choosing intervention, they should first provide interventions based
the appropriate methods to assess their interventions. upon established therapeutic guidelines for treating
Generic instruments and disease-specific instruments are hypertension such as those outlined by the Fifth Joint
the two general means by which HRQL can be measured. National Committee on Detection, Evaluation, and
The first modem health status questionnaires were very Treatment of Hypertension (JNC-V). With each patient
long, but their results were well validated. The Sickness encounter, they would collect the data in Appendix 2.
Impact Profile (SIP) is an example of an early profile. It These two procedures would ensure that the pharmacist is
includes a physical dimension and a psychosocial dimen- providing an appropriate process of care.
sion."4-1'1 A dimension is a quality or aspect that is a Prior to the intervention, the pharmacist would assess
component of health. The SIP also includes five independ- health outcome measures such as blood pressure, current
ent categories including sleep, rest, eating, work, and home medication adherence, and forms such as a general form
management, as well as recreation and pastimes. More (e.g., SF-36) and a disease-specific form (e.g., Hyperten-
recently, shorter profiles have been developed such as the s i o d i p i d Form 5.1) (Appendix 4). After the pharmacist
Nottingham Health Profile and the Medical Outcomes intervention, a predetennined period of time must elapse
Study (MOS) 36-Item Health Survey (SF-36) (Appendix 4). before these questionnaires can be repeated (e.g., 6- 12
The other approach in assessing HRQL is to focus on mo). The questionnaires and blood pressure assessments
the aspects of health status that are specific to a particular are then repeated and it is determined whether the
area of interest or disease. By narrowing the area being intervention had any effect on the patient outcome.
observed, it is possible to gain increased responsiveness to
changes in therapeutic interventions. Responsiveness
relates to the instrument's ability to detect changes in Recommendations
the patient's status over The instrument may
be specific to a particular disease state (e.g., angina or When appropriate, generic assessment measures
arthritis), or to a population (e.g., the frail elderly), or to a should be used to develop methods to evaluate
physiologic problem (e.g., pain). In addition to respon- overall patient outcomes after pharmacists' inter-
siveness, these disease-specific instruments evaluate areas ventions. However, since these may not be the
routinely addressed by primary care providers.r171 most appropriate techniques for specific pharma-
Most generic and specific HRQL measures used today cotherapy interventions, disease-specific methods
have been validated, but not in all populations. If an should also be considered.
instrument is valid, it has been statistically determined to Centers or individuals who want to evaluate pa-
measure what it is intended to measure. Compendia of tient outcomes that result from pharmacists' inter-
available measures, including critical reviews, can faci- ventions should utilize instruments that have been
litate the choice of an instrument for a specific setting or developed and evaluated by experts.
purpose."'] Appendix 4 contains some generic health When appropriate, patient outcomes after pharma-
profile instruments that can be used for various disease cists' interventions and primary care activities
states, and, where possible, a disease-specific instrument should be assessed with disease-specific instru-
was listed. ments that have been validated appropriately.
806 Primary Care, Clinical Pharmacy Services in (ACCP)
4. The choice of generic andlor disease-specific primary care functions, the contractual arrangement
instrument(s), should be made by the multidiscipli- should be viewed as being with the patient.
nary team when patient care is being assessed.
T e r m i n a t ~ nthe
~
TH
If a pharmacist-patient relationship exists and it is to be
terminated. the pharmacist must give the patient suf-
Since primary care often involves an interdisciplinary
ficient notice so that he may secure other professional
team. many health care professionals provide care to the
care.[211Even though the pharmacist’s powers in ter-
patient. Clinical pharmacists need to understand the legal
minating the relationship are limited, the patient has
implications of the care they provide, or of their patient
broad powers in terminating the relationship. The patient
interventions. Some of the medical-legal concepts that
is free to unilaterally terminate the relationship at any
need to be addressed include: what establishes a pro-
time. From the moment the pharmacist is dismissed or
fessional relationship, how to terminate this relationship,
discharged, he is relieved of all future professional res-
abandonment, and harmful neglect. These issues are rooted
ponsibility to the patient.
in both tort and contract law. In actions of negligence, four
legal elements must be addressed: duty, breach of this
duty, damage, and causation.‘201In determining a phar-
macist’s duty, the central question is whether a particular
conduct is a standard of pharmaceutical care. This is often Once established, the pharmacist-patient relationship
quite controversial in that there may be certain activities, imposes a duty of care upon the pharmacist that continues
such as duty to warm, that are not accepted by all courts as as long as attention is required, unless the pharmacist
a standard of care for pharmacists. If it is decided that the gives sufficient notice of termination or is discharged.[211
action is not a standard of care, the pharmacist cannot While this case law currently only applies to physicians,
be held negligent. If it is, then the issues are whether pharmacists who assume a caregiver role would also be
the pharmacist breached that duty (standard of care), subject to this duty. To recover on the theory of aban-
whether the patient was harmed (and to what extent), donment. the plaintiff must prove the following:
and whether the breach of duty caused the harm.
The essence of primary care is taking responsibility for a) Existence of a pharmacist-patient relationship.
the care of the patient to improve outcomes. Therefore, b) Unilateral severance by the pharmacist without
the following discussion is essential for the pharmacist- reasonable notice and without providing an ade-
patient relationship in primary care. quate substitute.
c) Necessity of continuing pharmaceutical attention.
d) Proximate cause.
e) Damages.
It is the pharmacist-patient relationship that gives rise to
the pharmacist’s duty to care.[211The pharmacist-patient A pharmacist is immune from the abandonment charge
relationship usually involves an expressed or implied when the patient voluntarily chooses not to return or
contractual agreement whereby the pharmacist offers to discharges the pharmacist.
treat the patient with proper professional skill and the Abandonment may thus occur in two ways: through
patient agrees to pay for such treatment. The pharmacist explicit withdrawal from a case or failure to attend the
has the responsibility for practicing all facets of the patient with due diligence. If the pharmacist fails to attend
profession competently. This could involve, for example, the patient with due diligence, he may also be liable under
drug distribution. providing primary care, patient mon- negligence principles. If he prematurely terminates the
itoring. patient and provider consultationleducation, and relationship despite the patient’s continued need for care,
other activities. As a result, the legal principles govern- he may also have abandoned the patient. The pharmacist
ing contract formation apply to the establishment of has a definite right to withdraw from the case provided he
the pharmacist-patient relationship. At issue, however, gives the patient reasonable notice so that a patient may
is whether this contractual arrangement really exists secure other attention. Failure by the patient to cooperate
between the pharmacist and the patient or whether it is with the pharmacist may justify termination of the
between the pharmacist and some other entity such as professional relationship by the pharmacist. The phar-
the physician. The answer may depend on what the macist is not justified in abandoning the patient unless
pharmacist is actually doing. If the pharmacist provides the patient obstinately refuses treatment. Differences of
Primary Care, Clinical Pharmacy Services in (ACCP) 807
opinion on the factors surrounding a case may occur. comparative negligence where blame is essentially
Therefore, it would be prudent for the pharmacist to apportioned between the plaintiff and defendant.
document carefully events and to offer to obtain a sub- In summary, pharmacists’ decisions regarding follow-
stitute clinician for the patient, and even then alternative up care are subject to legal scrutiny. As standard guide-
care arrangements must be made. lines concerning the appropriate frequency of follow-up
visits for outpatient management of most diseases are not
routinely available, clinicians are vulnerable to actions for
harmful neglect. Lacking such standards, a jury of lay-
Decisions concerning frequency of patient visits are an persons listens to “expert testimony” and decides whether
important medical-legal issue. Pharmacists can be held appropriate care was given. Busy workloads of pharma-
liable for harmful neglect, an act of negligence involving cists who service a large number of patients are not
nondiligent care of the patient. Courts have ruled, “A considered a defense against harmful neglect. If a prac-
physician is not chargeable with neglect on account of the titioner cannot provide adequate care to each patient, an
intervals elapsing between visits, where the injury equally competent substitute must be named. Finally, it is
requires no attention during the intervals, but is negligent essential to remember that the patient has obligations in
where attention is required.”[221 the management of his own health. To document ap-
The establishment for “proximate” or “legal” causa- propriate pharmacists’ advice to patients, written instruc-
tion is the first step.[231A factual link between the phar- tions should be provided that clearly and specifically
macist’s conduct and the patient’s injury and whether the outline what the patient should do during intervals be-
pharmacist could have foreseen the harm must be deter- tween visits, and full and appropriate records of patient
mined. The plaintiff must compare what did occur with visits must be maintained.
what would have occurred if contrary-to-fact conditions
existed. As an example, in a case involving a pharmacist, if
the pharmacist had provided more frequent visits, would a
more favorable outcome have resulted? The plaintiff
would have to prove, by a preponderance of the evidence, This Task Force report is designed to provide adminis-
that the infrequency of visits was the cause of damages to trators and pharmacy practitioners with recommendations
him. In addition, even if it is established that the phar- that assist them in establishing and evaluating pharmacy
macist’s conduct caused the patient’s injury, a question of services and assessing patient outcomes in ambulatory/
forseeability may be raised. In general, unless the phar- primary care. Each setting will have unique features re-
macist could have foreseen that harm would occur, there quiring specific processes be tailored to that institution
will be no liability. The issue of foreseeability would most or clinic. By utilizing the outcome instruments, practice
likely be part of the determination of duty. Many of the guidelines, and other materials listed in this report, the
consensus statements and guidelines included in this paper clinician should be able to establish a valuable practice
describe appropriate intervals of follow up that, if in most primary care settings.
followed, might reduce the liability of clinical pharmacists.
The jury would be instructed not to consider a pharma-
cist’s workload as a legitimate determination of frequency
of follow-up care. Pharmacists should be aware that having
more patients than time allows does not relieve them of This article was written in collaboration with Joseph L.
their responsibility to provide proper follow-up care. Fink 111, JD, and Francis B. Palumbo, PhD, JD, who
Pharmacists do not carry the sole burden of what assisted with the legal discussions and Kathleen M.
happens to their patients during intervals between appoint- Bungay, PharmD, and Eleanor Perfetto, PhD, who
ments. Patients also have responsibilities with regard to provided significant guidance and advice with the health
the management of their illnesses. The Supreme Court care process and outcomes sections.
of Maine ruled “it is the duty of a patient to follow the The article was written by the following ACCP Task
reasonable instructions and submit to the reasonable Force on Ambulatory Care Clinical Pharmacy Practice:
treatment prescribed by his physician or surgeon.’’[241 If William Linn, Pharm.D. (Chair), Barry L. Carter,
the patient fails in his duty and his conduct directly Pharm.D., FCCP, BCPS (Board Liaison); Betsy Carlisle,
contributes to the injury, he may be precluded from or Pharm.D.; Allan Ellsworth, Pharm.D., BCPS; Timothy
limited in seeking damages. Some state laws provide for Ives, PharmD., BCPS; Susan Maddux, Pharm.D., BCPS;
contributory negligence where any negligence by the Patricia Taber, Pharm.D, BCPS. Approved by the ACCP
plaintiff completely bans recovery. Other states have Board of Regents on May 4, 1994.
808 Primary Care, Clinical Pharmacy Services in (ACCP)
The following are the clinical scope of practices granted to you as a member of the staff of the Hospital (Clinic),
located in (city).
~ (state?. These determinations were made through a thorough review of your education,
training, and experience, and demonstrated competence by the Professional Standards Board and approved by the Director. If you
change positions and/or if your duties change (i.e., a geriatric clinical pharmacist moves to medical oncology), then you must
reapply for practices specific to that area
Areas of Practice:
A = Ambulator). Care
‘4.Routine duties: Routine duties are defined as those duties that are performed on a regular, repetitive basis.
(1) Category A-1. Routine duties that require review by the physician supenisor who will note concurrence or addendum as
indicated Countersignature of the medical record is required within 2 4 hours.
Requested
taking and recording verbal orders from physicians A
(2) Category A-2: Routine duties that do not require review by the physician supenisor unless so indicated These duties v.4 be
remewed by the physician supervisor on a regular basis rhrough a random sampling process. Results of this
review wll be discussed with the clinical pharmacist as appropnate.
Requested
* provision of formal wntten consultations upon request
in the areas of pharmacotherapy and pharmacokinetics A
* provision of written initial assessments in the progress notes A
provision of follow-up notes within the progress notes A
* taking medicatiodtherapeutic histones A
* measuring ma1 signs and performing physical examinations
of relevant organ systems for the purpose of monitoring
drug therapy A
* collecting laboratory specimens (i.e., drawing blood) A
* order the followng noninvasive tests:
(a) iaboratory tests (e.g., PT, CBC)
(b) EKGs
( c ) Holter monitors A
(d) PFTs A
(e) echocardiograms A
(0x-rays (e.g., CXR) A
* order appropriate consultations from the following services:
(a) dental A
(b) dietetics A
(c) medical specialties A
(d) psychiatry A
(e) psychology A
(0 radiology
(& social work A
(h) surgical specialties (old problems) A
(Continued)
Primary Care, Clinical Pharmacy Services in (ACCP) 809
B. Non-RoutineJNon-Emergency Duties:
Requested
* authority to m t e prescriptions for medication refills for
medical problems that are stable in patlents followed in
outpatient clinics, The clinical pharmacist is not authorized
to write prescriptions that are used to initiate any form of
drug therapy. A
* authority to make adjustments in dosage as clinically
indicated for a period of up to 3 months between
physician visits using the following classes of drugs:
1. antihistamine drugs
2 antiinfective agents A
3 . antineoplastic agents {indicates not applicable to this ambulatory care
pharmacist)
4. autonomic drugs A
5. blood formation and coagulation A
6. cardiovascular drugs A
7. central nervous system agents A
8. gastrointestinal drugs A
9. hormones and synthetic substitutes
10. respiratory smooth muscle relaxants
0 limited authorization to approve the use of restricted or
nonformulary medications when the use of such agents
is within the established guidelines or approved cntena
for use at this facility (i.e., antibiotics, chemotherapy) A
C. Emergency Duties: Carried out for patients in life-threatening situations where a physician is not immediately available The
clinical pharmacist initiates this activlty but makes every effort to summon a physician as soon as possible
(i,e,,cardiopulmonary resuscitation, and, if advanced cardiac life support-certified, electrodefibrillation).
D. Miscellaneous Duties: Those duties that do not fall into the first category.
0conduct clinical research protocols A
I do hereby request the above outlined scope of practices. 1 have read and agree to abide by the bylaws of the
Hospital.
Signature of applicant Date
Signature of physician supervisor Date
Chief, Pharmacy Service Date
Chief of Staff Date
Director Date
Medical Records will be reviewed on a quarterly basis. Twenty-five charts will be randomly selected and reviewed for the
following items:
1. Progress notes written in an appropriate S.O.A.P. format.
2. Determine if the subjective and objective information is consistent with the assessment and plan.
3. Past medical history and family history is obtained at least once for each patient.
4. Social, diet, and exercise history is recorded at least every 4 months.
5. Medication history recorded at least once.
6. Current prescription and nonprescription medication recorded on each visit.
7. Compliance is assessed on each visit.
8. Each visit contains thorough questioning concerning disease control, signs or symptoms of disease progression or new
complications, and signs or symptoms of adverse reactions.
9. Each visit documents appropriate objective information such as laboratory, physical assessment data, vital signs, etc.
10. All patient counseling concerning drug therapy, compliance, diet. exercise, and other lifestyle factors are recorded.
(Continued)
810 Primary Care, Clinical Pharmacy Services in (ACCP)
A ~ ~ e 2n ~Evaluating
~ x process of care: Example quality assurance in primary care (Continued)
Hypertension guidelines
1. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch
Intern Med 1993; 153: 154-83.
2. Frohlich ED, Apstein C, Chobanian AV, et al. The heart in hypertension. N Engl J Med 1992; 327: 998-1008.
3. National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group report on
hypertension and chronic renal failure. Arch Intern Med 1991; 151: 1280-7.
4. National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group report on
primary prevention of hypertension. Arch Intern Med 1993; 153: 186-208.
5. National High Blood Pressure Education Program Working Croup report on the heart in hypertension. National High Blood
Pressure Education Program. U.S. Department of Health and Human Services. NIH Publication No. 91-3033. September 1991.
6. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working
Croup report on hypertension in the elderly. Hypertension 1994; 23: 275-85.
7. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working
Group report on hypertension in diabetes. Hypertension 1994; 23: 145-58.
8. Bussey HI, Hawkins DW. Hypertension. In: Carter B, Angaran D, Sisca T, eds. Pharmacotherapy self-assessment program, 1st
edition. Kansas City: American College of Clinical Pharmacy, 1991: 1-26.
9. Bussey HI, Hawkins DW. Hypertension. In: Carter BL, Angaran DM, Lake KD, Raebel MA, eds. Pharmacotherapy self-
assessment program, 2nd edition. Kansas City: American College of Clinical Pharmacy, In press.
Diabetes guidelines
10. Lebovitz HE, Clark CM, DeFronzo RA, et ai., for the American Diabetes Association Clinical Education Program. Physician’s
guide to non-insulin-dependent (type 11) diabetes. Diagnosis and treatment, 2nd edition. American Diabetes Association, 1990.
11. American Diabetes Association. Clinical practice recommendations, 1992- 1993. Diabetes Care 1993; 16 (suppl 2): 1-113.
12. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development
and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-86.
13. Bartels DW. Diabetes mellitus. In: Carter B, Angaran D, Sisca T, eds. Pharmacotherapy self-assessment program, 1st edition.
Kansas City: American College of Clinical Pharmacy, 1993: 145-167.
14. Bartels DW. Diabetes mellitus. In: Carter BL, Angaran DM, Lake KD, Raebel MA, eds. Pharmacotherapy self-assessment
program, 2nd edition. Kansas City: American College of Clinical Pharmacy, In press.
Hyperlipidemia guidelines
15. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel 11). JAMA 1993; 269: 3015-23.
16. Israel MK, McKenney JM. Hyperlipidemias. In: Carter B, Angaran D, Sisca T, eds. Pharmacotherapy self-assessment program,
1st edition. Kansas City: American College of Clinical Pharmacy, 1991: 27-47.
17. Israel MK. Hyperlipidemias. In: Carter BL, Angaran DM, Lake KD, Raebel MA, eds. Pharmacotherapy self-assessment program,
2nd edition. Kansas City: American College of Clinical Pharmacy, In press.
(Continued)
812 Primary Care, Clinical Pharmacy Services in (ACCP)
46 Rodvold KA, Erdman SM Thrombosis In Carter BL. Angaran DM, Lake KD, Raebel MA. eds Pharmacotherapy self-
assessment progiam, 2nd edition Kansas City American College of Clinical Pharmacy, In press
Depression guidelines
55. Clinical practice guidelines. Depression in primary care, volume 1. Detection and diagnosis. U S . Department of Health and
Human Services. Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 93-0550, April
1993.
56. Clinical practice guidelines. Depression in primary care. volume 2. Treatment of major depression. US.Department of Health
and Human Services. Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 93-0550,
April 1993.
57. American Psychiatric Association. Practice guidelines for major depressive disorders in adults, 2nd edition. Washington, DC,
1993.
58. Crimsley SR. Depression. In: Carter B, Angaran D, Sisca T, eds. Pharmacotherapy self-assessment program, 1st edition. Kansas
City: American College of Clinical Pharmacy, 1992: 127-50.
Generic tools
1. Stewart AL, Ware JE Jr, eds. Measuring functioning and well-being: the medical outcomes study approach. The Rand
Corporation. Durham. NC: Duke University Press, 1992.
2. Parkerson GR, Gehlbach SH. Wagner EH: et al. The Duke-UNC health profile: an adult health status instrument for primary care.
Med Care 1981; 19: 806-28.
3. 'Hunt SM,McEwen J. McKenna SP. Measuring health status: a tool for clinicians and epidemiologists. J R Coll Gen Pract 1985;
35: 185-8.
4. Nelson EC, Wasson JH. Kirk JQ. Assessment of function in routine clinical practice: description of the COOP chart method and
preliminary findings. J Chronic Dis 1987; 40 (suppl 1): 55s-63.
5 . Stewart AL, Hays RD, Ware JE. The MOS short-form general health survey: reliability and validity in a patient population. Med
Care 1988; 26: 724-35.
6. Ware JE, Snow K; Kosinski M, et al. SF-36 health survey manual and interpretation guide. Boston: Nimrod Press, 1993.
7. Bergner M, Bobbitt RA, Carter WB. et al. The sickness impact profile: conceptual formulation and methodology for the
development of a health status measure. Int J Health Serv 1976; 6: 393-415.
The Nottingham Health Profile
Diabetes outcomes
11. Given CW. Measuring the social psychological health states of ambulatory chronically ill patients: hypertension and diabetes as
tracer conditions. J Comm Health 1984; 9: 179-95.
12. Hanestad BR, Polit RN. Perceived quality of life in a study of people with insulin-dependent diabetes mellitus using the
Hornquist model. Qua1 Life Res 1994; 3: 79.
13. Hanestad BR, Homquist JQ, Albreksten G. Self-assessed quality of life and metabolic control in persons with insulin-dependent
diabetes mellitus (IDDM). Scand J SOCMed 1991; 19: 57-65.
14. Kaplan SH. Patient reports of health status as predictors of physiologic health measures in chronic disease. J Chronic Dis 1987;
40: 278-35.
15. Marquis KH, Ware JE, Johnston R, et al. Appendix B to summary report: an evaluation of published measures of diabetes self-
care variables. Publication No. N-1152-HEW. Santa Monica, CA: The Rand Corporation, June 1979.
16. Nerenz DR, Repasky DP, Whitehouse FW,et al. Ongoing assessment of health status in patients with diabetes mellitus. Med
Care 1992; 30 (suppl 5): MS112-24.
17. Testa MA, Simonson DC. Measuring quality of life in hypertensive patients with diabetes. Postgrad Med J 1988; 64 (suppl3): 50-8.
18. The Diabetes Control and Complications Trial (DCCT) Research Group. Reliability and validity of a diabetes quality-of-life
measure for the Diabetes Control and Complications Trial. Diabetes Care 1988; 11: 725-32.
19. Wenneker MB, Mchorney CA, Kieszak SM, et al. The impact of diabetes severity on quality of life: results from the medical
outcomes study [abstr]. Clin Res 1991; 39: 612A.
Hyperlipidemia outcomes
20. Flack JM. Grimm RH. HypertensionLipid Form 5.1. Bloomington, MN: Health Outcomes Institute, 1993. (200 Killebrew Dr..
Suite 122, Bloomington, MN 55425).
(Conrinued)
814 Primary Care, Clinical Pharmacy Services in (ACCP)
(Continued)
Primary Care, Clinical harmacy Services in (ACCP) 815
Rheumatologic outcomes
74. Bombardier C, Ware J, Russell J, et al. Auranofin therapy and the quality of life in patients with rheumatoid arthritis. Am J Med
1986; 81: 565-78.
75. Blair PS, Silman AJ. Can clinical trials in rheumatology be improved? Cum Opin Rheumatol 1991; 3: 272-9.
76. Bjelle A. Functional status assessment. Curr Opin Rheumatol 1991; 3: 280-5.
77. Bakker CH, Rutten-van MM, Van Doorslaer E, et al. Health related utility measurement in rheumatology: an introduction.
Patient Educ Counsel 1993; 20: 145-52.
78. Meenan RF. Gertman PM, et al. Measuring health status in arthritis: the arthritis impact measurement scales. Arthritis Rheum
1980: 23: 146-52.
Depression outcomes
79. Alden D, Austin C, Sturgeon R. A correlation between the geriatric depression scale long and short forms. J Gerontol 1989; 44:
124-5.
(Continued)
816 Primary Care, Clinical Pharmacy Services in (ACCP)
80. Borson S, McDonald GJ, Gayle T, et al. Improvement in mood, physical symptoms, and function with nortriptyline for
depression in patients with chronic obstructive pulmonary disease. Psychosomatics 1992; 33: 190-201.
81. Brooks W, Blair J, John S, et al. The impact of psychologic factors on measurement of functional status: assessment of the
sickness impact profile. Med Care 1990; 28: 793-804.
82. Given C, Stommel M, Given B. et al. The influence of cancer patients’ symptoms and functional states on patients’ depression
and family caregivers’ reaction and depression. Health Psychol 1993; 12: 277-85.
83. GrCgoire J, de Leva1 N, Mesters P, et al. Validation of the quality of life in depression scale in a population of adult depressive
patients aged 60 years and above. Qual Life Res 1994; 3: 51-2.
84. Gurland B, Golden RR, Teresi JA, et al. The short-care: an efficient instrument for the assessment of depression, dementia and
disability. J Gerontol 1984; 39: 166-9.
85. Lambert MJ, Hatch DR, Kingston MD, et al. Zung, Beck and Hamilton rating scales as measures of treatment outcome: a meta-
analytic comparison. J Consult Clin Psychol 1986; 54: 54-9.
86. Light RW, Merrill EJ, Despars JA, et al. Prevalence of depression and anxiety in patients with COPD: relationship to functional
capacity. Chest 1985; 87: 35-8.
87. Norris JT, Gallagher D. Wilson A, et al. Assessment of depression in geriatric medical outpatients: the validity of two screening
measures. J Am Geriatr SOC1987; 35: 989-95.
88. Prusoff BA, Klerman GL, Paykel ES. Concordance between clinical assessments and patients’ self-report in depression. Arch
Gen Psychiatry 1972: 26: 546-52.
89. Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. J Appl Psychol Meas 1977; 1:
385 -401.
90. Revicki DA, Turner R, Brown R, et al. Reliability and validity of a health-related quality of life battery for evaluating outpatient
antidepressant treatment. Qual Life Res 1992; 1: 257-66.
91. Stewart AL, Sherbourne CD, Wells KB, et al. Do depressed patients in different treatment settings have different levels of well-
being and functioning? J Consult Clin Psychol 1993; 6: 849-57.
92. Stoker MJ, Sunbar GC, Beaumont G. The SmithKline Beecham ’quality of life’ scale: a validation and reliability study in
patients with affective disorder. Qual Life Res 1992; 1: 385-95.
93. Tambs K, Moum T. How well can a few questionnaire items indicate anxiety and depression? Acta Psychiatr Scand 1993; 87:
364-7.
94. Tanaka JS, Huba GJ. Confirmatory hierarchical factor analyses of psychological distress measures. J Pers SOCPsychol 1984; 46:
621-35.
95. Tanaka-Matsumi J, Kameoka VA. Reliabilities and concurrent validates of popular self-report measures of depression, anxiety,
and social desirability. J Consult Clin Psychol 1986; 54: 328-33.
96. Wells KB. Commentary: assessment of psychological morbidity in primary care. J Chronic Dis 1987; 40 (suppl 1): 81s-3.
97. Wells KB, Stewart A, Hays RD, et al. The functioning and well being of depressed patients. JAMA 1989; 262: 914-19.
98. Wells KB, Hays RD, Burnam MA, et al. Detection of depressive disorders for patients receiving prepaid for fee-for-service care:
results from the medical outcomes study. JAMA 1989; 262: 3298-3302.
99. Radloff LS. The CES-D scale: a self reported depression scale for research in the general population. Appl Psychol Meas 1977; 1:
385-401.
Research: A View from Inside the Agency for Health Care 16. Guyatt, G.H.; Feehey, D.H.; Patrick, D.L. Measuring
Policy and Research. In U S . Department of Health and health-related quality of life. Ann. Intern. Med. 1993, I /a,
Human Services, Public Health Service, AHCPR Pub. No. 622 629.
91-002.5, June; 1991. 17. Bungay, K.M.; Ware, J.E. Measuring and Monitoring
9. Agency for Health Care Policy and Research. Clinical Health-Related Quality of Life. In Current Concepts; The
Practice Guideline Development. In U S . Department of Upjohn Company: Kalamazoo, 1993.
Health and Human Services, Public Health Service, 18. Palmer, R.H.; Banks, N.; Edwards, J.; Fowles, J.; Neeent,
AHCPR Pub. No. 93-0023, August; 1993. D.; Zapka, J. Interim Report: External Rpview Peiform-
10. Woolf, S.H. Practice guidelines: A new reality in medi- unce Measurement qf Medicare HMOs/CMPs; Delmarva
cine. 11: Methods of developing guidelines. Arch. Intern. Foundation for Medical Care, Inc.: New York, 1994;
Med. 1992, 152, 946-952. February.
11. Ware, S.E., Jr. Standards for validating health measures: 19. Health Outcomes Jnstitute. Outcomes Management System
Definition and content. J. Chronic Dis. 1987, 40,473-480. (OMS), Bloomington, Minnesota; 1993.
12. Woolf, S.H. Practice guidelines: A new reality in medicine. 20. Pharmacy L a w Digest, Facts and Comparisons; Fink, S.L.,
111: Impact on patient care. Arch. Intern. Med. 1993, 153, 111, Marguardt, K.W., Simonsmeier, L.M., Eds.; Facts and
2646 2655. Comparisons: St. Louis, Missouri, 1994.
13. Bungay, K.M.; Wagncr, A.K. Comment: Assessing the 21. Perdue, J.M. The Law of Texas Medical Malpractice. In
quality of pharmaceutical care. Ann. Pharmacother. 1993, Houston IAW RevicJw, University of Houston Luw Center,
27, 1542 1543. 2nd Ed.; University or Houston Law Center: Houston, 198.5;
14. Greenfield, S.; Nelson, E.C. Recent developments and 2-20.
future issues in the use of health status assessment measures 22. v. Aiken, T., et al., 101 N.W. 769 (Iowa 1904).
in clinical settings. Med. Care 1992, 30 (Suppl. 5 ) , 23-41. 23. Kecton, W.P. Prosser and Keetnn on the L a w of Torts, 5th
15. Patrick, D.L.; Erickson, P. Health Status and Health Policy: Ed.; Wcst Publishing Company: St. Paul, 1984; 263
Quality oJ Life in Health Care Evaluation and Resource 321.
Allocation; Oxford University Press: Mew York, 1993. 24. v. Odiorne, M., 94 A. 753 (Maine 1915).
PROFESSIONAL DEVELOPMENT
P s
Association Foundation Leads the not-for-profit, Research training and grants programs;
Executive, Director of charitable arm of professionwide research; fund-raising.
Research Institute the association.
Attorney Legal counsel Resource for staff, board, and officers in
for association. matters of nonprofit or antitrust law; personnel
and copyright issues; legal disputes.
Chapter Relations. Primary association liaison Programs and services for chapters
Manager of with chapters. and other affiliates.
Chief Executive Oversees all aspects of the Strategic direction; “the big picture.’‘
Officer, Executive association; reports to the
Director, Executive elected governance of
Vice President the association.
ComputerM anagement Computer support systems. Database development; membership
Information Systems, database management; web site
Manager of development and maintenance.
Deputy Chief Executive, Responsible for major Specific projects of importance
Associate Executive Director projects; often works to the association.
with personnel issues.
Education, Development and delivery Scientific abstracts; meeting standards
DirectorNice President of educational programming, for continuing pharmaceutical education;
or Manager including certificate programs development of program content; working
and other training programs. with speakers: delivery of live, printed,
and online programming; educational grants.
Finance, Director Oversees financial Accounting; management of short-,
of/Controller management of intermediate-, and long-term investments;
the association. financial reporting to chief executive officer
and governing board.
Government Relations Leads association’s Lobbying; tracking legislative initiatives
(often paired with advocacy efforts to to alert membership of important issues;
Professional Affairs), government, legislative, writing suggested legislation; interaction
Directormice President of and regulatory bodies. with representatives of government bodies.
Human Resources, Personnel management. Hiring and firing; employee policies;
Manager of employee benefits.
Marketing, Promotion of the association. Promotion of membership, meetings,
DirectorNice President publications.
or Manager
Meetings and Planning for conventions Meeting logistics; site selection;
Expositions, of the association. audiovisual requirements; exhibits
Directormice President program; vendor contracts.
or Manager
Member Services, Membership recruitment Dues notices; recruitment of new members;
Directormice President and retention. services for members; promotional materials;
or Manager member complaints.
Professional Affairs Primary contact with other Development of professional policies; attends
(often paired with professional associations. meetings of other related associations;
Government Relations), offers comment on behalf of association
Directormice President regarding position statements of other
associations; collaboration with other
associations regarding mutual interests.
(Continued)
820 Professional Associations, Clinical Pharmacy Careers in
number of years, and were active in the association as a curricula. Those thinking of careers in associations should
volunteer, through committee work, attendance at meet- keep their eyes open to issues and events, the actions of
ings, presentation of scientific abstracts, or elected office, other related groups, and the opinions of colleagues. They
By becoming known as a reliable volunteer, they set the need to pay attention to the business and the politics of the
stage for movement into association employment. This profession and be informed about them.
path is advantageous in providing the association with an Finally, training in how to manage projects, people,
employee whom they know and who understands the and finances can be very helpful for association managers.
membership and the profession. However, a disadvantage Many of the skills necessary to be an excellent clinical
of this path is that clinical pharmacists have rarely re- pharmacist are opposite those required to be an excellent
ceived the management training and experience necessary manager. Training and experience in this area are crucial
for association work. to excelling in an association career.
Others who identify association work as their career
objective early in their training may enter this type of
work through summer internships, experiential clerkships ENEFITS
and externships, and executive residencies, or by accept-
ing their first postgraduate job with an association and There are many benefits of association work. Working
then advancing though various positions and departments. within an association provides increased opportunities to
Many of these opportunities are listed in a document be involved with the discipline of clinical pharmacy. For
prepared by the member organizations of the Interorga- someone who has practiced patient care, conducted re-
nizational Council on Student Affairs.[31 search, or taught, this can provide an exciting new di-
Regardless of the career path chosen, preparation for a rection with new challenges and new skills to learn. Those
career in association management should ideally include who have been members of the association before work-
several elements. Exposure to association work can be ing for it often appreciate the opportunity to work for a
obtained through an internship, a clerkship, or an execu- group having a mission they believe in and from which
tive residency. These experiential activities provide ex- they have benefited as a member.
cellent opportunities for exposure to what it might be Association work necessarily involves communication
like to work for an association. with its members. Those working in this field have many
Experience as a practicing member of the profession more acquaintances among their peers and with repre-
can be an excellent way to prepare for association work. sentatives of the pharmaceutical industry. Establishing
Through spending time in actual patient care, research, and maintaining contacts is an important part of this work.
and teaching, prospective association pharmacists can Those who enjoy interacting with people will especially
learn firsthand what members do and what their struggles enjoy this aspect of association life.
are. Furthermore, by becoming involved with associations A clinical career within an association can be an op-
on a volunteer basis, it is possible to experience how the portunity for continued learning and professional growth.
association works. Volunteering also provides an oppor- Association managers often need to enhance their skills
tunity to showcase an applicant’s talents and dependabi- in business management, public relations, marketing, pro-
lity to the association. Choosing to work for employers ject management, advocacy, politics, personnel manage-
who will allow time and support for association work is ment, legal issues, and many other areas, depending on
also beneficial. the scope of their responsibilities. Adopting the attitude
Other areas of preparation that are very helpful involve of a lifelong learner is essential, as the profession and
skills aside from those taught in traditional pharmacy the world change rapidly. It is necessary to constantly
Professional Associations, Clinical Pharmacy Careers in 823
learn new knowledge and skills to keep up with these When working with speakers, authors, and commit-
rapid changes. tees, who by definition are performing volunteer work,
Working for an association opens many career oppor- association executives must be prepared to help members
tunities in related fields, with other associations, with the meet their deadlines, through reminders, clear commun-
pharmaceutical industry, in other management jobs, and ication, and advance planning. Missed deadlines by mem-
in private consulting. The skills gained through associa- bers have the potential to result in periods of great stress
tion work are widely transferable to other professions, as for association staff who in turn have printing or other
well as back to clinical practice. deadlines that cannot be changed. As this can be a source
Clinical pharmacists within associations have many of great stress, it is essential to have the personal fortitude
opportunities to work on new projects pertaining to the to deal with the unexpected and uncontrollable.
membership and the profession. They can be creative not Because associations must function as businesses,
only in developing a project, but also in funding, imple- serving as stewards of their members’ resources, there is
menting, and promoting it. Association work provides a less freedom for association employees to function as
wide variety of opportunities to practice clinical phar- independently as they might in an academic environment.
macy in ways that, although different from traditional Budgets must be developed and adhered to, and per-
roles, affect patient care and the profession. formance targets established and met. Also, because the
Many of the knowledge and skills taught in clinical elected officers change regularly, the direction of the
pharmacy curricula are applicable to association work. For association and the style of the governing board can
example, those working with educational programs often change frequently. Clinical pharmacists working within
draw on their pharmacy backgrounds to help members associations must be flexible, as issues and responses
design better educational offerings. Also, research techni- can change, may not always agree with their personal
ques learned in academic training are applicable to asso- opinions, and are often outside their control.
ciation research.
Perhaps the greatest benefit of association work is the
ability to represent the association’s members, seeking to c
improve their practices and opportunities, and to make a
difference in the profession. Working as a pharmacist within a professional asso-
ciation is a challenging, yet rewarding way to practice
clinical pharmacy. This career choice should be strongly
TI considered by those who seek to serve their colleagues and
the profession by helping them manage and adapt to ever-
Those choosing to practice clinically within a profession- changing issues in clinical pharmacy.
al association must have excellent organizational and
time management skills. They will experience many pres-
sures from various directions and must be skilled at prio-
ritizing their activities. Excellent written and verbal com- EFERE
munications skills are also essential.
Association executives must find a balance between 1. Casteuble, T. What today’s association executives earn.
being a member of the association and serving on the Assoc. Manage. 1997, 49 (4),53-61.
staff. An attitude of servanthood is absolutely essential. It 2. American Association of Colleges of Pharmacy. 1999-
is also critical to find a balance between listening to mem- 2000 Profile of Pharmacy Faculty. In Institutional Re-
search Report Series; American Association of Colleges of
bers and responding to their needs versus taking the lead
Pharmacy: Alexandria, Virginia, 1999.
and establishing the direction of the association. The most 3. Interorganizational Council on Student Affairs. Znterorga-
responsive associations are typically ‘‘member driven,” nizational, Financial, and Experiential Information Docu-
meaning that the association staff take their lead from ment; Interorganizational Council on Student Affairs,
the elected officers of the organization, with a focus on American Pharmaceutical Association: Washington, DC,
implementing, rather than establishing policy. 2000.
PROFESSIONAL DEVELOPMENT
Julie A. Dopheide
University of Southern California, Los Angeles, California, U.S.A.
It is estimated that 25--50% of patients in long-term the practitioner. Model practice settings in hospitals and
care facilities suffer from neuropsychiatric disorders that several clinics are discussed in the following paragraphs.
are functionally impairing.'"] At least 26% of incarcer-
ated adults"21 and 52% of children in the juvenile justice
Hospital
system meet criteria for a DSM-IV-TR disorder.[13] When
substance abuseldependency is included in the adult pop-
Psychiatric pharmacy specialists in hospitals provide a
ulation, the incidence rises to 7 1%.[12] Psychiatric phar-
wide range of services, including participation in multi-
macist specialists can provide consultation on optimizing
disciplinary treatment planning, medication education
drug therapy for patients in these settings.
groups for patients, therapeutic drug monitoring, dis-
Half of the homeless suffer from mental illness, and
charge counseling, and quality a s ~ u r a n c e .201
' ~ Model
rely on community outreach, missions, and government-
practices exist across the United States for the acute care
run clinics to provide service.[143151 A psychiatric phar-
psychiatric pharmacist; however, the scope of practice is
macist is uniquely qualified to manage the coordination of
variable based on staffing, institutional support. and in-
medication follow-up for these patients. Developmentally
terest of the practitioner. Through the years, a patient-
disabled individuals are often treated for a combination of
focused model has evolved using the principles of phar-
neurologic and psychiatric problems and, therefore, have
maceutical care whereby the pharmacist develops a
unique drug interaction considerations and communica-
professional relationship with the patient in addition to
tion obstacles. Psychiatric pharmacists currently serve as
staff and takes responsibility for health outcomes.
consultants and members of multidisciplinary treatment
Psychiatric pharmacy in the acute care setting involves
teams to optimize the care of these
patient interviews for initial assessment and follow-up
Quality of care for individuals with psychiatric illness
monitoring. The pharmacist obtains a medication history
has come under scrutiny with several studies documenting
to facilitate treatment plan development, in addition to
a need for improvement in medication management.['7-191
participating in multidisciplinary rounds for exchange of
Psychiatric pharmacists have the opportunity to improve
information and therapeutic decision making. The inpa-
care through quality assurance surveysldrug-use evalua-
tient psychiatric pharmacist conducts therapeutic drug-
tions, patient and staff e d u c a t i ~ n , [ ~and
. ~ ~ direct
I medi-
level monitoring of lithium and anticonvulsants. Con-
cation management."] Psychiatric pharmacist specialists
ducting medication education groups and individual
are an important community resource for consumer advo-
medication counseling sessions are standard functions of
cacy groups such as NAMI, also known as the National
the inpatient psychiatric pharmacist.[251
Alliance for the Mentally
In addition, psychiatric pharmacists have opportunities
for involvement in treatment guideline development for Primary Care
psychiatric disorders. The American Pharmaceutical
Association recruited psychiatric pharmacy specialists to In the primary care setting, there are several practice
develop their guidelines for psychiatric disease state models for pharmacy-run clinics. Typically, patients are
management. [221 evaluated by a psychiatrist and referred to the psychiatric
Dr. Lynn Crismon's work in developing the Texas pharmacist for medication management and ongoing
Medication Algorithms for treatment of depression in assessment.[261The Veteran's Administration (VA) health
children and adults and the treatment of attention-defi- care system was one of the first to use psychiatric phar-
cit hyperactivity disorder in ~ h i l d r e n ' ~ , laid ~ ~ , ~the
~] macy specialists in mental hygiene clinics in the 1970s.
groundwork for psychiatric pharmacists to work with Currently, the VA health care system supports psychiatric
psychiatrists, psychologists, other health care professio- pharmacist specialist involvement in several psychiatric
nals, and consumer groups to develop and implement clinics, including the cognitive disorders, mood disor-
national therapeutic guidelines. ders, psychiatry emergency, geropsychiatry, and cloza-
pine ~ l i n i c s . [ ~ ~ , ~ ~ ]
Extent of involvement varies across VA systems. For
example, at the VA clinic in La Jolla, California, a
psychiatric pharmacist's scope of practice includes: 1)
assessing clinical response to medication via mental status
An attractive feature of psychiatric pharmacy is that it exam and psychiatric interviewing techniques; 2 ) asses-
offers creativity in developing a practice that is indivi- sing development of adverse drug reactions; 3) ordering
dualized to the setting and patient population of interest to and evaluating appropriate laboratory tests to assess cli-
824 Psychiatric Pharmacy Specialty Practice
nical response, assess development of adverse drug re- based on decreased clinic visits and decreased prescrip-
actions, and evaluate therapeutic drug levels; 4) making tions of $22,241.25 over 3 months.[301
changes in psychotropic drug therapy using the physician One prospective study from Australia analyzed clinical
order form or through direct order entry into the com- pharmacy interventions on an inpatient psychiatric unit
puter; 5) assessing patient compliance with medications over a 6-month period. Two hundred and four inter-
by analyzing computer dispensing records and quantities ventions were proposed for 69 patients, 91.7% of which
of medications dispensed versus doses remaining; 6) were accepted. Some of the interventions (20.3%) were
documenting findings, actions, and plans in the patient’s estimated to be of major clinical significance, with added
medical records on the progress notes form or through cost savings of 24,700 based on cutting 38 days of in-
direct progress note entry into the computer; 7) providing patient care at $ 6 5 0 / d a ~ . [ ~ ~ I
prescriptions for all medications with enough medications
to last until the patients’ next appointment; 8) providing
patient medication education, including methods of TOOLS
coping with certain side effects, recognizing symptoms
of toxicity, and emphasizing the importance of compli- Psychotropic drug therapy expertise, interview technique,
ance, and when appropriate, providing written informa- and the mental status exam are the most used tools of
tion; and 9) rescheduling patients for follow-up appoint- the psychiatric pharmacist. Validated psychiatric rating
ments with an appropriate clinician. In a VA clinic in scales are also used and allow objective measurement of
Waco, TX, a psychiatric pharmacist specialist has similar drug therapy outcomes. Psychiatric pharmacists develop
scope of practice but is assessed quarterly, in writing, by expertise in using standardized rating scales such as the
the supervising psychiatrist. Hamilton-Depression Rating Scale and the Monitoring of
Scott and White hospital in Texas is an example of Side Effects Scale (QSES).[32,331American Psychiatric
a pharmacy-run women’s health clinic. In this model, Association rating scales and online references, such as
the obstetrics-gynecology physician or nurse identifies Clinical Pharmacology,[341are available on CD-rom and
patients at risk for mood disorders, including premen- make the information easily retrievable in settings with
strual syndrome and premenstrual dysphoric disorder, and computer capabilities. Clinical psychiatric pharmacists
refers them to the pharmacist for further evaluation, treat- use portable laptop or notebook computers and personal
ment, and drug therapy monitoring. Patient approval ra- data assistants, or PDAs, to keep track of patient profiles,
tings were 96% excellent.[291 drug therapy recommendations, and outcomes.
industry
NETWORKING
Psychiatric pharmacy specialists are vigorously recruited
by industry to serve as medical science liaisons, neuro- Networking can be accomplished by participating in
science managers, members of advisory boards, and national meetings where psychiatric pharmacy specialists
resources of drug information for physicians and other gather to exchange ideas, participate in neuropsychiatric
health care professionals.“] educational programming, and discuss professional issues
such as residency training, reimbursement, and health
care policy. These national meetings include the College
BENEFITS OF SPECIALTY PRACTICE of Psychiatric and Neurologic Pharmacists,“] ASHP’s
Section of Clinical Specialists in Psychiatric and Neuro-
Several U.S. studies report improved care, improved level logic Pharmacy,[71and the American College of Clinical
of functioning, and economic savings attributed to psy- Pharmacy’s (ACCP’ s) central nervous system practice-
chiatric pharmacist intervention^;[^] however, the studies related network.[351 The “psypharm” listserv has ap-
are small, generally retrospective in nature, and most lack proximately 400 participants (George Foose, personal
rigorous controls. One chart review of 60 clinic patients communication) and is an effective tool for “rapid-res-
compared pharmacist prescribing with psychiatrist pre- ponse” networking with national and international psy-
scribing and determined pharmacist prescribing was as chiatric pharmacists. To become a member of psypharm
good as or better than physician prescribing.[261 The and/or of the College of Psychiatric and Neurologic
largest study was a chart review in some 4700 patients, Pharmacists (CPNP) listserv, log on to the CPNP web site
which documented that 66% of pharmacist recommenda- or contact Dr. George Foose via e-mail at gfoose@msn.
tions were implemented with an extrapolated cost savings Com.[s,361
Psychiatric Pharmacy Specialty Practice 825
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39 (7), 908-927. 54 (23), 2717 2718.
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26. Stimmel, G.L.; McGhan, W.F.; Wincor, M.Z. Compar- 31. Alderman, C.P. A prospective analysis of clinical phar-
ison of pharmacist and physician prescribing for psychi- macy interventions on an acute psychiatric inpatient unit.
atric inpatients. Am. J. Hosp. Pharm. 1982, 39, 1483 I . Clin. Pharm. Ther. 1997, 22 (l), 27-31.
1486. 32. Sajatovic, M.; Ramirez, L.F. Rating Scales in Mental
27. Defilippi, J.L. Perronal Communication on Approvc.rl Health; Lexi-comp Inc.: Hudson, Ohio, 2001, copyright
Scope of Psychiatric Pharmacy Pructice in the Veteran’s 200 1.
Administration Mental Hygiene Clinic, Waco, Texas; May 33. American Psychiatric Association ( M A ) Rating Scales;
2001. 2000, copyright 2000.
28. Dishman, B. Personal Communication on Approved Scope 34. Clinical Pharmacology; www.clinicalpharmacology.com.
of Practice for Psychiatric Clinical Pharmacy Specialist at 35. American College of Clinical Pharmacy (ACCP). www.
the Veterun’s Administration Healthcare system, La Jollu, accp.org.
Calf(irnia; J ~ l y200 1 . 36. Psypharm listserv. psypharm@listscrv.unc.edu.
29. Jermain, D.M.; Sulak, P.J.; Woodward, B.W.; Knight, 37. United Kingdom Psychiatric Pharmacy Group (UKPPC).
A.C. Psychopharmacy medication clinic in a managed care www.ukppg.org.uk (accessed July 2001).
PROFESSIONAL DEVELOPMENT
Organizations exist as long as they are able to produce 1. Who are the customers of the pharmacy service?
services that are of interest to someone-this someone Patients, their relatives, physicians, nurses, society,
being customers. Pharmacists create small organizations managers and administrators, politicians, students,
(e.g., hospital pharmacy services, community pharmacies, and so on are the customers. They do not always
ambulatory settings) that are located within other or- share the same values and can even have con-
ganizations (e.g., hospitals, primary care, home care), flicting interests. This is due to agency relation-
which in turn are integrated into what we may consider ships, so frequent in healthcare.
the healthcare system organization.
The final customers of the healthcare service are 2 . Which are the services offered by the pharmacy
patients and their families, and the final product is health. service? This question does not refer to what
Health as a product is not easy to define and measure. A pharmacists do, how they invest their time, or
way to measure the product of healthcare systems is to what their tasks are-all that is well known. We
look at their outcomes. Today, the outcomes of healthcare know what is done, but it is more difficult to
systems are considered to be economic, clinical, and prove what it is for; that is, what is the useful-
humanistic in nature. ness for the patient? The question refers to what
Pharmacists participate in the healthcare system and in clients receive from pharmacy services, from their
its final product. Sometimes they directly access the own point of view. As stated previously, what
patient, and other times, they indirectly access the patient customers get is what makes sense to pharmaceu-
through other health professionals (doctors, nurses), tical organizations.
providing them with what belongs to us-our knowledge
of drugs. Drugs are widely used as resources in all It is strategic for clinical pharmacy services to identify
healthcare systems. Our objective would be to achieve a and segment customers to meet their expectancies and
safer and effective medication-use process. needs. It results in good customer management.
However, the healthcare system is only furnished with As a profession, the services we offer are not fully
limited resources, facing endless new technologies and agreed upon or conceptualized, but delivery of medica-
growing service demand by the population. All this tions, and manufacture and handling, are. These services
translates into tremendous economic pressure on health- are our baseline services. It is far more difficult to
care professionals. consensuate and conceptualize the pharmacists' cognitive
This is the starting point in the development of the services and their added value to health process, yet there
subject of quality assurance in pharmacy services. have been some attempts.[u1 The reason is likely to be
that we are not paid to do that,[71 so we do not feel
obligated to do so, unlike other professions with a great
LlTV knowledge load.
We should find a way to accomplish it and offer a
There are many definitions of quality;"331 however, we portfolio of services. This portfolio of pharmaceutical
reduce the concept to the bare bones. That is, quality is services should be patient oriented and customer focused.
doing things right, or better said, allowing our customers There are some works in the literature that describe the
to receive good service because they, precisely, are the needs assessment with different customers (patients,
ones who rate the quality of the service (Fig. 1). healthcare teams, et~.).[~-"]
ECONOMICAL
HUMANISTIC
PHYSIC1.4N PHYSICIAN
NURSE
PATIEUT PATIENT
ADMINISTRATORS ADMINISTRATORS
THIRD-PARTY-PAYERS THIRD-PARTY-PAYERS
STUDEYTS STUDENTS
SOCIETY SOCIETY
The next step is to define what the characteristics are them. The production of services takes place by means of
of each service we offer in this portfolio. By these processes (Fig. 2). To obtain high-quality services,
characteristics, we are defining the variables of quality processes need to be very well defined, and to be known
itself. Quality would also include, besides technical and accepted by those performing them. A good way to
aspects, those aspects related to communication skills, define them is using flowcharts.
which are quite valued in customer satisfaction. The Quality should never be improvised; quality is
cognitive, behavioral, and emotional aspects of commun- planned. Service production processes should be well
ication are thus considered. defined. Those performing them should known them, and
In working toward quality, there are several steps and be well prepared and trained for this objective of quality.
different tools: People want to work properly, so organizations should
prepare the ground, clearly stating what it is expected
e Certification. from them, training them adequately, and commending
a Accreditation. that is done well.
0 Self-evaluation. In this normalization of processes, the activities to be
performed should be defined, as well as their sequence
and who does it and h o ~ . " ~ This. ' ~ ~is a good time to
Certificati incorporate technologies such as information system,
robotics, communication systems, and so
The object of certification is to ensure that what is done is In the definition stage of this process, it is essential to
what was said would be done. In certification, we nor- be flexible, to have an open and imaginative mind, and to
malize both processes and procedures. A process is a question everything-what is done, why, for what reason,
sequence of activities performed to provide a service. The and for whom (in these steps, some tasks are often found
activity is what is done, whereas a procedure is the to be unnecessary and can be left undone because they
documentation that describes how to perform a process (a provide nothing to the final service or are repeated; some
set of activities). A service is what the patient gets, and activities are done just because it has always been that
the outcome is the result of the service. way). It is good to have a variety of people with different
To provide our customers with these services, we are points of view, and it is advisable that the staff involved
furnished with material and human resources that produce in the process also participate in it, whatever their train-
Quality Assurance of Clinical Pharmacy Practice 829
r ECONOMICAL
OUTCOME
HUMANISTIC
I NEEDS I PRODUCTION
PROCESSES
ing, because they are the ones who know their work best Accreditation
and know how to improve it. It has the advantage of
facilitating empowerment, homogenizing criteria, and Although certification ensures the homogeneity in the
forcing the culture of quality to develop. quality of organizations, accreditation is based on the
Once the process is defined, it simply has to be creation of quality standards in service quality and in the
performed as described. The objective of this is to avoid comparison among several organization^."^.^^^ Accredi-
variability in its execution and thus in its quality, de- tation is granted by external organizations, which set the
pending on the person who performs it. criteria and standards that are used as indicators of health.
Everything should be normalized: process controls, Before undergoing external accreditation. it is essential to
equipment servicing, staff training, quality control (few know the requirements and to specifically prepare for
indicators on critical points), frequency of the process them. An external accreditation is an acknowledgmenr
review, and definition of responsibilities. The documenta- that the quality requirements established by that organ-
tion of these activities should also be ization are fulfilled. Actually, quality is predefined by
Processes normalization is distinct in each organiza- means of indicators and standards. Accreditations may
tion, because each organization is unique. This should be include structure, processes, and results standards. The
the second step toward quality. Defining our customers current trend is toward the assessment of results,
and our service portfolio is the first step. Each service whenever possible.
should have a well-defined and normalized elaboration
process, with a clear beginning and end. Self-Evaluation
So far we have discussed the operative processes-that
is, the service production processes-but there are other In self-evaluation, organizations enter a constant circle
equally relevant processes, such as support services (not of questioning what they are doing. how, for whom, and
perceived by the customer, but also essential, e.g., how they can improve it. It involves an important degree
maintenance, purchases, etc.) and strategic services (they of dynamism and maturity throughout the organization.
orient the whole organization; Fig. 3). The quality of all with a clear, decided focus on the customer and society.
these processes is susceptible to evaluation. It is a path toward excellence: the continuous culture of
830 Quality Assurance of Clinical Pharmacy Practice
ECONOMICAL
OUTCOME CLINICAL
HUMANISTIC
er
~~~~~~~~
i
I
IIWOVATION MAh’AGEMENT
Strategic Processes
V
U
PRODUCTION I I
PROCESSES SERVICES
Wefative’Prod&s&3 I I
MAINTENANCE
PURCHASES 11 INFORMATION
SYSTEM
Support Processes
quality. Their common feature is a proactive approach to example of adaptation to the environment is the very
quality. It deals with double-checking that what the concept of pharmaceutical care meant a great innovation
organization designs is what customers really want and for the profession,[251 and the contribution of the
need, and if that it is precisely what the organization is pharmacist in the detection and prevention of therapeu-
actually providing. tical errors, designing specific programs for it.[269271
At this level, we introduce concepts that are in vogue In the healthcare sector, innovation is closely related to
such as benchmarking and innovation. Both look for research and scientific evidence. We should increase our
improvements in services and/or processes. The first con- research on quality and also make it b e t t e ~ - . [ ~ ’ Then,
- ~ ~ ] it
cept does so by searching for better ways of working in has to be published and d i ~ s e m i n a t e d . ‘ This
~ ~ ] should be
other organizations; the second concept does so by means done with high scientific level works, producing scientific
of imagination and creativity. evidence of quality. The study question should be less
Benchmarking was first introduced in business science “how am I doing it?” (pharmacist oriented) and more
as an efficient and effective way of optimizing compan- “how do I improve the care offered to the patient?”
ies. It deals with looking for practices that proved (patient oriented).
successful in other companies, and implementing them
into one’s own company, or in plain words, copying the
best one^.[^^-'^] KEY POINTS
Innovation is the key to the future. It means to be alert
as to how society, the healthcare system, and the macro- Conceptualization and measurement are the key points.
and micro-context in which we live, will evolve. An Quality management is achieved by the management of
Quality Assurance of Clinical Pharmacy Practice 831
customers, people, and processes. It is essential to follow These services are of an intangible nature, so it is
a strategy because quality is not improvised. Conceptua- sometimes positive to introduce elements to make in-
lization is what gives congruity to the whole system. In visible operations visible (e.g., to develop a physical
practice, this implies the following tactic. support allowing the customer to see it clearly). Ours is a
multidisciplinary job, and this must be reflected not only
in our research, but also in our attitude and daily work,
as full patient-focused members of the healthcare
team. [35,361
Defining the portfolio of services and the level of We have to be readily accessible, both in terms of
quality of each service. Knowing the needs before space and time. We have to leave pharmacy offices and
designing and performing the service. Besides expressed go to the patient and the healthcare team.[371We must
needs (demand), we have to explore the hidden, or not clearly and firmly lead all those activities related to drugs
expressed, needs. We should know what services and because this is the knowledge field of our profession.
with what characteristics of quality are of interest to our Leadership has a lot to do with effectively communicating
customers, avoiding unnecessary efforts in services that to influence others’ actions, attitudes, beliefs, and so on.
will not be valued or that will be useless to us (although Pharmacy services must relocate themselves strategically
our unit may consider them interesting). In this section, as proactive agents in the healthcare team.
qualitative research is a tool to consider. This is a
strategic step.
issemination
In an automated, natural manner, but in different service effectively fulfills its mission (considering its
settings from the strictly pharmaceutical, clinical phar- three dimensions: economic, clinical, and humanistic,
macists integrate clinical research and publications, along with patient satisfaction). In practice, this means to
together with other professionals. This involves dissem- measure. Pharmaceutical services have to be measurable
inating the services that clinical pharmacy has to offer. to be self-evaluated, corrected, and improved.
Actually, all healthcare professionals should learn that We can measure quality in our activities and in the
the center of the healthcare system is the patient, and services we p r o d ~ c e , [ ~as~ ’well
~ ~ ]as the impact of our
rather than classifying the patients’ functions, what is contribution to the outcomes of the healthcare system in
important are those processes that provide an added value terms of qualityr421(Fig. 4).
to the patients’ health, and those who lead them. It means For economic outcomes, we can use pharmacoecon-
establishing alliances between members of the healthcare omy as the main tool.[431There is a great variety of cli-
team. Perhaps we should start viewing the members of nical indicators that we can relate to drugs efficacy and
health teams as being coresponsible for care, and even safety. These clinical indicators, obtained with designs
incorporate patients themselves into the team, with a first- from clinical epidemiology (observational and experi-
line role, taking active part in decisions. The clinical are excellent to measure clinical outcomes.
pharmacists’ goal is for patients to see them as an ally, To obtain indicators for humanistic outcomes, such as
someone on whom they can rely. satisfaction and quality of life, we have different tools,
such as surveys, and different qualitative research meth-
ods (interviews, focus groups, e t ~ . ) . [ ~ ~ ~ ~ ]
easure Measuring wastes some resources, and the concept
of cost-opportunity makes us cautious when tempted
It is important to have a discussion with the customer after to measure whatever is at hand. We should measure
delivering our service to ensure that, once started, this little, and just what is critical (even monitoring and
Structure
Indicators
1 Indicators
Process I
Services
Indicators
Economic
ECONOMIC PHARMACOECONOMICS
Indicators
,
CLINICAL
CLINICAL EPIDEMIOLOGICAL
METHOD
(OBSERVATIONAL &
,D HUMANISTIC
measuring at a preestablished frequency) a n d o r im- with time. Quality is dynamic because the environment is
portant and significant. Before deciding to measure, dynamic. We must continuously adapt ourselves to the
we must be sure that we are using the best indicator environment and innovate. What now is a gold standard
as possible to reach our objective. We must know why will perhaps be a minimum tomorrow.
and for what we are measuring-it is not the same Quality is evaluated by measuring relevant indicators.
to obtain a certification, make a decision, or research Outcomes indicators (economic, clinical, and humanistic)
and publish. will be the major importance in the future for clinical
The same criteria should be applied for technical pharmacist services. Clinical pharmacist services must
questions of internal interest and for the clinical aspects of relocate themselves strategically as a proactive agent and
interest to the patient and the rest of healthcare staff. In lead drug therapy in the healthcare team.
this case, the language should be common to the rest of The challenge will be the economic evaluation of
the healthcare staff, and indicators should be clinical pharmacy services. Once the products of pharmaceut-
indicators. This information, both positive or negative, ical services and its outcomes are defined, considering
has to be disseminated, clarified, and shared. We must economic, clinical, human outcomes, and once the mi-
insist on the use of clinical and satisfaction indicators, as nimal or standard quality if the services (both basic
well as of economic ones. and value-added services, with high degree of know-
ledge), then we must know its In the context
of healthcare systems, where they are currently im-
mersed, with huge economic pressure, it is necessary to
prove that the resources used by pharmaceutical ser-
Quality is something one pursues in an active manner. vices are cost effective for the healthcare system and
Once we start the path toward quality, we cannot abandon the patient. In other contexts, and maybe in the future,
it: it just becomes part of our daily routine. it will be important to price these pharmaceutical ser-
vices that our patients are going to receive.r503511 By
orienting our services through quality, they will pro-
bably be more effective, because we will not incur in
the cost of nonquality.
In this article, it was our intent to present a pers- We need to develop methods for measuring and
pective on this topic, providing different tools to meeting customers’ expectations (needs and demands)
approach the quality of pharmaceutical services. These to provide both baseline and value-added services, suc-
have been placed in a context where the concepts of cessful in kind and in quality. It is said we are in the age
limited resources, cost-opportunity, and efficacy are of knowledge. We pharmaceutics are well versed on the
implicit. The concept has been abstracted so it can be medications-use process. Let this knowledge be useful for
applied to the public or private sectors, to hospital or our customers and society. Let us convey it in a clear,
ambulatory settings, and to different societies, with effective way. It is just quality.
different values.
As for the external quality systems, we deliberately
avoided the description of official quality systems, such as EF s
the Joint Commission on Accreditation of Healthcare
Organizations (accreditation), International Standariza- 1. Deming, W.E. Calidad, productividad y competitividad.
tion Organization (certification), and European Federation In La salida de la crisis; Diaz de Santos S.A.: Madrid,
for Quality Management (self-evaluation), because it 1989.
would have been impossible to cover them all. Instead, we 2. Juran, J.M. El liderazgo para la calidad. In Manual para
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3. Crosby, P. La calidad no cuesta; Compaiiia Editorial
quality systems will probably assume most of the things
Continental S.A.: Mexico DF, 1990.
discussed in this article.
4. Ellis, S.L.; Billups, S.J.; Malone, D.C.: Carte, B.L.; Covey,
Quality is planned and evaluated. In other words, D.; Mason, B.; Jue, S.; Carmichael, J.; Guthrie, K.B.S.;
quality is managed; it cannot be detached from man- Sintek, C.D.; Dombrowski, R.; Geraets, D.R.; Amato, M.
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PROFESSIONAL DEVELOPMENT
Donald E. Letendre
American Society of Health-System Pharmacists,
Bethesda, Maryland, U.S.A.
TYPES OF ~ E § I ~ E N ~ ~ E S
A pharmacy residency is an organized, directed, post- There are two types of residency programs: pharmacy
graduate training program in a defined area of pharmacy practice and specialized. Pharmacy practice residencies,
practice. Residencies exist primarily to train pharmacists often referred to as “general” residencies, are intended
(called “residents” during the training program) by to provide training and education in the fundamentals of
providing them the opportunity to accelerate their growth exemplary contemporary pharmacy practice. Areas in
beyond entry-level professional competence in direct which the resident typically receives training are acute
patient care and in practice management, and to further patient care, ambulatory patient care, drug information
the development of leadership skills that can be applied and drug-use policy development, and practice manage-
in any position and in any practice setting. Pharmacy ment. Because pharmacy practice residencies are offered
residents acquire substantial knowledge required for in a variety of practice settings (e.g., hospitals, health
skillful problem solving, refine their problem-solving systems, home care programs, long-term care facilities,
strategies, strengthen their professional values and atti- managed care environments, community practice sites),
tudes, and advance the growth of their clinical judgment, the relative time that the resident might spend in each
a process begun in the clerkships of the professional area of practice will likely vary depending on the nature
school years but requiring further extensive practice, of the site and the types of patients being served, as
self-reflection, and shaping of decision-making skills well as the particular practice interests of the resident.
based on feedback on performance. The residency Fundamentally, pharmacy practice residencies are inten-
provides a fertile environment for accelerating growth ded to produce a well-grounded general clinical phar-
beyond entry-level professional competence through macy practitioner.
supervised practice under the guidance of model Specialized residencies are offered in a wide variety of
practitioners. Residents are held responsible and accoun- specialty practice areas and are intended to build upon the
table for pursuing optimal medication therapy outcomes practice experience gained through completion of a
in patients. pharmacy practice residency. The following is a list of
The residency also provides a fertile environment for specialized areas of practice in which American Society
accelerating the growth of residents’ leadership skills. of Hospital Pharmacists (ASHP)-accredited residency
Each residency offers the opportunity to exercise lea- programs are offered:
dership under the watchful eye of effective leaders.
Examples of leadership skills and traits that may be * Critical care
enhanced during a residency include trustworthiness and 0 Drug information
integrity. comfort with ambiguity, organizational com- * Emergency medicine
mitment, cross-cultural sensitivity, internalization of the * Geriatric
role of service to patients and other customers, recogniz- 0 Infectious diseases
ing the need for change, change management, persuasive 0 Internal medicine
communication, team-building, confidence in one’s abi- * Managed care
lity to lead. and realistic self-assessment. To ensure 0 Nuclear
continuous development of future leaders in pharmacy
practice, it is widely accepted that leadership skill de-
velopment be an integral part of pharmacy practice re-
.,
0
0
Nutritional
Oncology
Pediatric
sidency training. 0 Pharmacotherapy
0 Pharmacy practice management adopted (replacing the term “internship”) and partici-
Primary care pants agreed on a set of standards that would be used to
. Psychiatric
Subspecialities (e.g., cardiology, pulmonary, renal)
conduct the first accreditation site surveys in the spring
of 1963.
Throughout the early years, postgraduate pharmacy
training, as reflected in the standards, focused primarily
on the manufacture and preparation of pharmaceutical
products and on systems that could be implemented to
help ensure the integrity of those products up to the point
ASHP, in cooperation with its professional association
of administration. Moreover, substantial effort was placed
partners, administers the only process that grants
on providing trainees with the skills needed to pursue
accreditation status to practice sites conducting residen-
leadership roles in the hospital pharmacy community. The
cies. ASHP’s authority to grant accreditation is recog-
standards used to guide postgraduate training in insti-
nized by the Health Care Financing Administration
tutional settings during the early years were reflective of
(HCFA). The accreditation process requires that each site
practice at that time in that they focused heavily on the
demonstrate compliance with established standards of
“product” side of the profession with little mention of the
practice and offer a residency that meets the requirements
end user, the patient.
for training.
The process of accreditation ensures that accredi-
ted programs are peer reviewed and that requirements
Clinical ~ h a ~ ~ a c y
for providing a state-of-the-art practice environment
are fulfilled.
In the late 1960s and early 1970s, a few residency
programs began to place greater emphasis on patient care.
Clearly, these programs provided a philosophical shift
VOLUTI away from product-focused training and toward a greater
emphasis on pharmacist participation in patients’ drug
therapy management. They also helped facilitate the
“clinical pharmacy” movement that was emerging by
One of the fundamental issues that led to the founding of providing training to many of the early would-be clinical
the ASHP in 1942 was the need to train practitioners for pharmacy pioneers. The rapidity with which change was
hospital pharmacy. This segment of practice was largely occurring is perhaps best reflected in the Clinical Services
ignored by pharmaceutical education. The first proposed segment of the Qualifications of the Pharmacy Service
standard for postgraduate pharmacy training was pub- section of the revised Accreditation Standard for Phar-
lished for comment in ASHP’s The Bulletin in 1948.“] macy Residency in a Hospital that was approved in
Since then, the requirements for training, as reflected in November 1974:[31
the accreditation standards that have evolved throughout The functions which comprise clinical services are
the years, have always attempted to challenge programs to difficult to identify, partly because there is no common
be at the vanguard of practice. agreement among practitioners as to the definition of
The initial pharmacy residencies-or “internships’ ’ a clinical service, partly because there are “clinical”
as they were called-were established in the 1930s, first components associated with most, if not all, of the service
at the University of Michigan Hospital in Ann Arbor functions of the hospital pharmacy department, and partly
under the direction of Harvey A. K. Whitney and because, in current practice, no clear distinction has been
Edward C. Watts. Other early programs were at the made between clinical teaching activities and clinical
University of California Hospital in San Francisco, Duke service activities. What are frequently purported to be
University Hospital, and St. Luke’s in Cleveland. By the service activities are, more often than not, teaching (or
early 1950s, it was estimated that at least a dozen learning) activities. For this reason, in evaluating clinical
hospitals offered hospital pharmacy internship training.[*] service activities, only those services. . .which are con-
In December 1962, preceptors of the programs in exist- tinuously performed even in the absence of students and
ence at the time and other hospital pharmacy leaders trainees, are considered.
convened a meeting that in retrospect helped set the This document marked the first time that require-
framework for the accreditation process that is in use ments for clinical pharmacy services in postgraduate
today. At that meeting, the term “residency” was first training programs were addressed. Nonetheless, over the
Residencies 839
next few years, it became increasingly more difficult to creditation standard. Hence, providing programs
evaluate the growing number of “clinical residencies” with sufficient time to establish these services
that were emerging against the hospital pharmacy ac- under the direction of clinically competent prac-
creditation standard. In those programs, the scope of titioners was a key factor in maintaining both
clinical services provided to patients grew substantially the hospital and the clinical tracks in resi-
and the attendant requirements for residency training to dency training.
assist in the delivery of those services were not ad-
dressed adequately in the accreditation standard-it
was like trying to fit the proverbial square peg in a
round hole. Hence, in 1980, ASHP approved the first
The training of clinical specialists and pharmaceutical
Accreditation Standard for Residency Training in Cli-
scientists took hold in the 1970s and progressed
nical
throughout the 1980s, paralleling advances in drugs
Maintaining accreditation standards for both hospital
and drug delivery systems. Outgrowths of this movement
and clinical residencies throughout the 1980s was
included the birth of the Board of Pharmaceutical
beneficial for a variety of reasons. Among them were
Specialties and the American College of Clinical
the following:
Pharmacy (ACCP). and the establishment of the ASHP
Special Interest Groups (SIGs). Throughout this period,
1. The profession’s diffeerentiated workforce needs.
it became increasingly more accepted in the profession
Many staff pharmacist positions in organized
that pursuing optimal drug therapy in patients, particu-
health care settings required a blend of the ad-
larly when extremely complex drug regimens were
ministrative and clinical skills that graduates of
involved, often required a more sophisticated level of
general hospital residencies received, whereas
service than was typically provided by a general phar-
most management positions required graduates to
macy practitioner. Spurred on by the increasing need
complete hospital residencies that focused prim-
for more highly trained individuals, in 1980, ASHP
arily on honing a resident’s administrative skills
approved the first Accreditation Standard for Specialized
(most often these were tied to MS degree prog-
Pharmacy Residency Trainingrs1 (frequently referred to
rams). However, graduates of clinical residencies
as the specialized “umbrella” standard) and the Sup-
typically pursued faculty appointments and clini-
plementary Standard and Learning Objectives for
cal practice positions that provided greater oppor-
Residency Training in Psychiatric Pharmacy Practice,[61
tunities to deal directly with patients‘ drug the-
which had been developed by the SIG on psychophar-
rapy issues.
macy practice. Since then, supplemental standards have
2. A n insufficient level of residency candidates
been approved for 16 specialized areas of pharmacy
holding advanced degrees. A prerequisite to
practice. Two of these standards, pharmacotherapy and
pursuing a clinical residency was the completion
infectious diseases, were developed jointly with the
of the PharmD degree or a commensurate level
ACCP and the Society of Infectious Disease Pharma-
of life experience to satisfy this requirement.
cists, respectively.
Although the number of pharmacy school gra-
duates holding the PharmD degree continued to
increase throughout the 1980s, several clinical re- eneies
sidencies struggled early on to obtain only can-
didates who had satisfied this prerequisite. This ASHP approved the Long-Range Position Statement on
situation was particularly noteworthy for programs Pharmacy Manpower Needs and Residency Training17] at
that were in regions where there was a paucity of the same time as the clinical residency standard. The
PharmD graduates. position statement intended to guide the thinking of
3. Qualifications of the pharmacy service. Virtually members about the categories of professional and tech-
all departments of pharmacy that offered general nical pharmacy workforce needed in organized health
hospital residency training in the 1980s provided care settings and the types of training programs required
some level of clinical pharmacy services. How- to meet that need. It also acknowledged that over time the
ever, for the majority of these programs, the distinction between a “generalist” and a “clinical prac-
level of clinical services provided-particularly titioner” would diminish and that, at some point in the
during the early 1980s-was inadequate to meet future, the need to maintain both clinical and hospital
the requirements of the clinical residency ac- residency standards would no longer exist.
840 Residencies
Consistent with this thinking, practitioners at the 1985 reason, applicants to this type of program should have
Hilton Head Conference on “Directions for Clinical completed a comprehensive clerkship and externship
Practice in Pharmacy’”’] and the 1989 National Re- program such as is required in contemporary clinically
sidency Preceptors Conference[’] offered several recom- based pharmacy curricula. For pharmacy practice resi-
mendations to merge the hospital and clinical residency dencies, there is no absolute requirement concerning the
standards. In particular, participants at these conferences type of pharmacy degree the applicant must possess.
noted that, due to revisions in the hospital and clinical However, it is clear that the PharmD degree provides the
residency standards, major segments of both documents, applicant with the level of knowledge and skills needed
especially those that relate to requirements in depart- to meet the requirements for training in a pharmacy
mental services, were now virtually identical. Moreover, practice residency and that, over time, this degree is
it was also noted that portions of the requirements in the expected to become an absolute prerequisite for appli-
general hospital standard-notably, the training objec- cants. In all cases, it is the residency program director’s
tives for the clinical and drug information services responsibility to assess each applicant’s baseline know-
areas-approached the clinical standard more closely ledge and skills, and to ascertain overall qualifications for
than in the past. Hence, in 1991, following more than 2 admission. The applicant should bear in mind that it is
years of development that included a series of open permissible for programs to establish more stringent
forums to receive input from residency preceptors on all entry-level requirements; hence, applicants must take
proposed segments of the document, the first Ac- responsibility for contacting programs directly to deter-
creditation Standard for Residency in Pharmacy Practice mine specific entry requirements.
was approved.“’] Prerequisites for entry into a specialized residency may
Adoption of the term “pharmacy practice” in the vary depending on the type of program. In all instances,
new standard was significant. Clear consensus was es- however, completion of the PharmD degree (or other
tablished that the time had come to no longer distinguish advanced degree in pharmacy) is required, except in
between “clinical pharmacy practice” and “pharmacy unusual cases (e.g., BS degree graduate who has been
practice” as the practice of pharmacy is inherently in practice several years). Although completion of a
clinical.[”] As of July 1, 1992, all ASHP-accredited pharmacy practice residency is required typically for
general hospital and clinical residencies were converted admission to a specialized program, some programs may
to residencies in pharmacy practice. Since then, three accept an applicant without residency training provided
separate standards governing pharmacy practice residen- that the individual has a comparable level of profes-
cies have emerged: ASHP Accreditation Standard for sional practical experience. The reason for this require-
Residencies in Pharmacy Practice (approved April 25, ment is that a specialized program requires the applicant
200 1); Accreditation Standard and Learning Objectives to have a sound foundation in general practice skills that
for Residency Training in Pharmacy Practice (with the pharmacy practice residency provides. Applicants
Emphasis in Community Care), prepared jointly by interested in pursuing specialized residency training are
ASHP and the American Pharmaceutical Association; urged to contact programs directly to determine the
and Accreditation Standard and Learning Objectives for specific requirements for application.
Residency Training in Managed Care Pharmacy Practice,
prepared jointly by ASHP and the Academy of Managed
Care Pharmacy. IN s
There are a number of ways to learn about residencies.
G However, the avenues that will likely provide potential
applicants with the most information are the ASHP
In all instances, the applicant to a residency must be a Residency Directory, the ACCP Directmy of Residencies
highly motivated pharmacist who desires to obtain and Fellowships, and the ASHP Residency Showcase.
advanced education and training, leading to an enhanced The ASHP Residency Director3 is a two-volume series:
level of professional practice. The applicant must be a Volume I covers pharmacy practice residencies and
graduate of a college of pharmacy accredited by the volume I1 covers specialized residency programs. This
American Council on Pharmaceutical Education or be series is available through most colleges of pharmacy’s
otherwise eligible for licensure. departments of pharmacy practice and can be obtained
A residency in pharmacy practice is predicated on directly following application to the ASHP Resident
prior clerkship and externship experiences. For this Match Program. The ACCP Directory of Residencies and.
Residencies 841
Fellowships is likewise available through most colleges of program information, as well as ask program representa-
pharmacy and can be obtained directly by contacting tives about the overall strengths and weaknesses of their
ACCP. Both directories provide interested individuals program. Frequently, the best assessment of what a
with a wealth of pertinent program information. Indivi- program has to offer is through communication with
duals interested in learning more about the residency residents currently in the program.
resources offered by these associations are encouraged
to visit the following web sites: www.ashp.org and
www.accp.com. Moreover, the following web sites offer
specific information about community-based and ma-
naged care residencies, respectively: www.aphanet.org Virtually all pharmacy practice residencies are required to
and www.amcp.org. participate in the Resident Matching Program (RMP). The
All students who are in their last year of pharmacy only exception is those programs offered through the
school and are interested in residency training are en- military and public health services. Hence, it is essential
couraged to attend the ASHP midyear clinical meeting that potential applicants to these programs register for the
in December of each year to participate in the Residency match. Applicants to specialized programs are not
showcase. The showcase is an area set up in booth required to participate in the RMP.
format that enables representatives of the various prog- ASHP contracts with the National Matching Service
rams to meet personally with prospective residency can- (NMS) to operate the RMP. The RMP ensures that each
didates to address any questions they might have about pharmacy practice residency program is matched with
a program. Among other things, it provides applicants the preferred individuals who have applied and who have
with the best opportunity to meet preceptors and resi- selected the program as an acceptable site in which to
dents from each program, learn first hand about specific train. To apply for the match, applicants must contact
elements of each program, and gain insights into prog- NMS directly (595 Bay Street, Suite 300, Toronto.
rams that are often difficult to obtain through the direc- Ontario, Canada; telephone: 416-977-3431 or fax: 416-
tories. Because virtually all programs require candidates 977-5020). There is a modest application fee, and the
to participate in on site interviews, participation in the applicant agreement form must be received by January
showcase can help a prospective candidate better iden- 15. Once NMS has received the agreement form. the
tify those programs of greatest interest, which will help applicant will be sent a personalized match number (this
minimize unnecessary travel expenses that might have number will be required by all pharmacy practice
otherwise been incurred traveling to a less desirable residencies to which the student graduate applies) and,
program. It is important to note that more than 98% of under separate cover, a copy of the ASHP Residency
all ASHP-accredited residencies typically participate in Directory. As noted previously, the Directory pro\ ides
the showcase. descriptions of all accredited programs, including im-
Before searching for a residency, the pharmacist portant contact information. After consulting the Direc-
graduate must determine his or her career objectives. tory and identifying programs of interest. the student
Because programs vary in terms of their relative degree of graduate must request applications forms directly from
emphasis in the areas in which training is provided, it is the individual residency program directors. not from
particularly important for the applicant to determine, to ASHP. Most programs require the applicant to participate
the extent possible, the area(s) that are most suited to in an on-site interview; hence. student graduates are
achieving career objectives. For example, an individual advised to check directly with programs about applica-
interested in some dimension of ambulatory care would tion procedures as policies governing application do \ ary
be wise to pursue programs that offer a broad range of among programs.
experiences in this area of practice.
It is not uncommon for career objectives to change
following experience in the many areas of practice
typically provided in residencies. Hence, for applicants
who are unsure about future professional goals, the best
1. Fiske. R., et al. Standards for internships in hospital phar-
advise is to pursue training in a practice site that provides macies. The Bulletin § e ~ t e m ~ e ~ / O c ~ o
a solid grounding in patient care because many of the 233-234.
skills a resident will acquire are transferable across most 2. Zellmer, W.A. Twenty-Five Years of Pharmacy Residency
areas of pharmacy practice. To this end, it is essential that Accreditation-Part I. Early Efforts to Establish the
potential applicants allow adequate time to review Program (Unpublished manuscript).
842 Residencies
3. Accreditation standard for pharmacy residency in a hospital. of an invitational conference conducted by the ASHP
Am. J. Hosp. Pharm. February 1975, 32, 192-198. Research and Education Foundation and the American
4. ASHP accreditation standard for residency training in Society of Hospital Pharmacists. Am. J. Hosp. Pharm.
clinical pharmacy. Am. J. Hosp. Pharm. September 1980, June 1985, 42, 1287-1342.
37, 1223 1228. 9. Directions for postgraduate pharmacy residency training.
5. ASHP accreditation standard for specialized pharmacy Proceedings of the 1989 National Residency Preceptors
residency training. Am. J. Hosp. Pharm. September 1980, Conference conducted by the American Society of Hospital
37, 1229-1232. Pharmacists. Am. J. Hosp. Pharm. January 1990,47, 85-
6. ASHP supplementary standard and learning objectives for 126.
residency training in psychiatric pharmacy practice. Am. J. 10. ASHP accreditation standard for residency in pharmacy
Hosp. Pharm. September 1980, 37, 1232- 1234. practice. Am. J. Hosp. Pharm. January 1992, 49, 146-
7 . ASHP long-range position statement on pharmacy man- 153.
power needs and residency training. Am. J. Hosp. Pharm. 11. Letendre, D.E. Reflections on the future of pharmacy
September 1980, 37, 1220. residency programs: An ASHP perspective. Am. J. Pharm.
8. Directions for clinical practice in pharmacy. Proceedings Educ. Fall 1992, 56, 298-300.
PHARMACY PRACTICE ISSUES
role of investigator in clinical trials. Nevertheless, be- clinical trial was described. The average time spent per
cause of the pharmacist knowledge of the principles trial was 91 hours, the average cost per trial was $1766,
governing therapeutics, together with the intense rela- and the average cost per patient was $174.[271Although it
tionship that they maintain with all the departments within is clear that clinical research activities should be funded
the hospitals, the hospital pharmacist is a valuable asset by specific economic resources, this consideration is not
for the design, development, review, and collaboration for always taken into account. Likewise, costs other than
preparation of the protocol, as stated before.[241 those of the investigator, such as the costs of pharmacist
Different surveys on the status of the role of the activities, are usually not taken into account when the
clinical pharmacist in clinical trials have been pre- total cost of a clinical trial is calculated. Even, if these
~ e n t e d . [ ~ . ~The
' , ~ ~average
] number of clinical trials costs are considered, they are fixed by people who are not
started per year and hospital is 9.6, and there is a wide familiar with the pharmacy. Consequently, the current
range of variation (up to 70 trials per year in large sources for funding used to support the pharmacists' par-
hospitals). However, the latest data indicate a dramatic ticipation in clinical trials are not homogeneous, ranging
increase in activity (around 100-150 trials per year). To from fees charged to investigators (usually reimbursed
summarize the results, it can be stated that, in 76.2% of through the funds the investigator receives from the
hospitals, the pharmacy is the receiving site for investiga- sponsor) to the covering of the costs assumed by the
tional drugs, and 90.4% give written acknowledgment of institution as part of the cost of participating in a research
receipt. Direct dispensing to the patient is executed in program. This picture does not differ essentially from that
59.5% of centers, whereas dispensing to the investigator described by Rockwell et al. in their survey.[261
was executed in 29.2% of hospitals.[31 Inventory control The economic impact of drug studies on the pharmacy
of samples for investigation is intensively observed in budget should be considered. Spanish regulation^"^] give
85.7% of institutions. If the point of view of the industry responsability to the sponsor for providing evaluated
is taken into account,[251similar results are obtained; that drugs free of charge. Along these lines, two reports mea-
is, distribution of the investigational drug is performed sured the savings resulting from the development of cli-
by the pharmacy service in 82.8% of centers. In addition, nical trials. In one case, 23 clinical trials saved almost
the pharmacy's role of dispensing drugs facilitates the 0,30 million € , during the period 1994-1996.[2*1 In a
monitor's task in 71 % of cases. Interestingly, sponsors second study, of the 105 clinical trials conducted in our
recognize that pharmacists are investigators in 12% of hospital during January 2000, 36 were evaluated. and the
clinical trials, and that almost all of them (94% of spon- results indicated a total savings of 1,65 million € ; from
sors) consider that the presence of pharmacist on the the rest of the studies, 55 therapies were evaluated with-
ethics commitee of clinical research is essential for eva- out an established treatment, 2 were sponsored by the own
luating protocols. The value of the pharmacists' activity hospital, and 9 added, not substituted, the investigational
in clinical trials is essentially not different from those drug to the conventional treatment.[291These savings are
obtained in surveys developed in other countries.[261 consistent with those corresponding to two pharmacy-
Regarding human resources in this field, most centers based investigational drug services in the United States
manage clinical trials by assigning one or more part-time for fiscal period 1996- 1997.[301
pharmacists or technicians who also work on traditional From the institutions point of view, the Spanish So-
activities such as drug delivery and drug information. ciety of Hospital Pharmacy [Sociedad Espafiola de Far-
Therefore, it is difficult to estimate the number of pro- macia Hospitalaria (SEFH)] considers the clinical trials a
tocols that can be managed by one full-time employee. matter of interest. As proof of this fact, there was a
Only centers developing more than 70 clinical trials per meeting organized in the early 1990s in which more than
year are able to have one full-time employee dedicated for 50 experts described and analyzed the role of the hospital
clinical research.[31 This fact is linked to another ex- pharmacists in the growing world of clinical trials.[311
tremely important issue: The revenue for pharmacy costs Furthermore, the reference text Farmacia Hospitalaria
is associated with research. In the current context of hos- dedicates an entire chapter to the clinical trials issue.[321
pital operating costs, the structural resources and time Nevertheless, whereas different associations (e.g. Amer-
spent by the hospital pharmacy service for clinical trial- ican Society for Health-System Pharmacists, Joint Com-
related activities are difficult to justify. As it has been mittee on Accreditation of Healthcare Organizations)"]
pointed only by carefully quantifying the costs for have edited guidelines oriented to establish and define the
providing this service and demonstrating that the benefits rules of the clinical pharmacist in clinical trials, the SEFH
outweight the costs, can the pharmacy justify a new has still not taken the step. Regarding educational pro-
expansion program. In this way, a model for estimating grams for residents, there are no standardized guidelines
and evaluating the cost of pharmacy activity for any given for rotations in investigational drug services, and each
846 Role of the Clinical Pharmacist in Clinical Trials (Spain)
hospital acts according to its own criterion. Moreover, the reporting incidences considered serious for the clinical
recent edition of the resident's manual[331does not con- trial follow-up.
sider specifically the issue of clinical trials.
As mentioned previously, the role of the clinical The description of the basic activities (in chronological
pharmacist in clinical trials in Spain must be considered in order) are as follows:
three main ways: the participation in the development of
protocols by managing the dispensing and drug account- * Reception and study of protocol
ability by means of the pharmacy-based investigational
drug services; the contribution of the clinical pharmacist, Opening protocol file
according to its condition of permanent member, to the Checking preceptive documentation
ethics commitee of clinical research; and the direct role as Protocol study
investigators, conducting clinical trials. Meetings with monitors and/or investigators
Evaluating pharmacy participation
Opening computerized record
INV L Establishing dispensing procedures
Information activities
a Patient information and training (especially in the case two main programs: TRIALS[381designed by a working
of outpatients) party of the SEFH; and the recently updated GECOS,
0 Destruction of the returned or unused drug samples designed in our pharmacy
through a suitable procedure
8 Evaluation of the patient’s and investigator’s adher-
ence to protocol
For the adequate management of the investigational The ethics commitee of clinical research is the insti-
samples in the context of the activity of the pharmacy, it is tutional entity at the local institution that is responsible
necessary to consider the following: for protecting the rights of human.[‘51 It plays a similar
role to the institutional review board in other
e Integrating the pharmacy-based investigational drug The main functions of this entity are to examinate the
activity within the pharmacy service, making use of methodological, ethical, and regulatory issues of each
common settings and facilities protocol proposed for development in the hospital.
m Establishing a differentiated flow to manage samples In detail, the commitee must evaluate, among other
for investigation within the pharmacy service things, the following:
e Storing the investigational drugs in a specific, unique
place, far from the conventional drugs The appropriateness of the protocol related to the aim
e Establishing measures to keep the samples safe and of the study, its scientific efficiency, and the balance
guaranteeing their integrity (i.e., locks in shelves, between the expected risks and benefits of the new
temperature alarms) therapy
e Relaying on trained and specialized pharmacists and The appropriateness of the investigator and the
technicians, even full-time employees, if the number research team responsible for developing the clinical
and complexity of clinical trials requires it trial within the hospital
0 Defining an individual and concrete prescription sheet, The informed consent document to be given to the
essential for dispensing the investigational drug patients, from the point of view of the respect for
a Keeping all documents and activity records in separate human rights
files for each clinical trial The clinical trial follow-up, from the beginning of the
0 Computerizing all the clinical trial development, using study to the receiving of the final report
available software programs (purchased software or
developed in-house systems) The ethics commitee is composed of members with or
0 Establishing safety measures to guarantee the confid- without a background in health care and research. At least
entiality of the protocol and the patients, to include one clinical pharmacist must be a member of the ethics
protecting investigational samples, files, and computer commitee. According to a survey,[31 the pharmacist is
programs president of the commitee in 4.8% of cases, secretary in
e Elaborating suitable standard operating procedures for 36.5% of cases, adviser in 12.1% of cases, or voting
all activities related to the clinical trial performance member in 46.6% of cases. Thus, it is understood that
clinical pharmacists have the knowledge and the re-
It is important to define the reimbursment process for sponsability to evaluate and monitor a diversity of cli-
providing the investigational drug services. There are two nical, methodological, and ethical aspects relating to
main procedures: a fixed reimbursement per trial for clinical trials.
traditional services and a variable reimbursement esti- For this reason, it is remarkable that, in many cases,
mated per clinical trial for other services;[361and a fee clinical pharmacists lead the follow-up process for the
structure (fixed and variable) in which each activity clinical trials. It was in a pharmacy-promoted audit that a
involved in a clinical trial is In our case, we serious deviation in GCP recommendations was detected.
use the first procedure because of its simplicity. Never- In this study, it was concluded that compliance was ade-
theless, a new fee questionnaire describing the cost of quate in 50% of protocols, so-so in 25% of cases, and
each pharmacy-related activity is under evaluation. poor in the remaining 25%. Surprisingly, in 13% of the
As stated previously, a specifically defined computer patients, the informed consent document was not signed;
program is essential for maintaining inventory control and in 15% of the cases, the patient’s clinical records did not
accountability. There are different software programs reflect that the patients were included in a clinical
available, but beside conventional databases, there are In a different way, a long-term follow-up detected that
848 Role of the Clinical Pharmacist in Clinical Trials (Spain)
only 32% of clinical trials previously evaluated by the cists according to their background (i.e., pharmacoki-
local ethics commitee was finally published at the end of netics, pharmacoeconomics).
the protocol. Moreover, the sponsor sent the final report In the near future, within the context of our changing
of the clinical trial to the ethics commitee in only 33 of health care environment and research environment, there
135 finished clinical trials.[431 is a need for multidisciplinary approaches. The clinical
The role of the clinical pharmacist in the surveillance pharmacist should demonstrate, according to their expert-
of ethics principles and the maintenance of the rights of ise in the principles governing therapeutics. that they are
human can also be notorious, especially when referring to able to participate fully in this expanding process within
written information and the patient’s informed the research environment. Thus, a hospital pharmacist
The most relevant study undertaken in Spain that eva- would be valuable in the design, development, review,
luated the quality of the written information provided to and preparation of the protocol and, finally, in evaluating
patients was carried out by pharmacists involved in qua- and reporting results.
lity assurance and/or ethics ~ommitees.‘~’] The main out-
come of this study was to confirm that most of the written
information to patients (65.3% of clinical trials) required
high-level studies to be completely understood by the pa-
tients. As far as we know, a more ambitious, multicentric
1. Ministerio de Sanidad y Consumo. Ensayos Clinicos en
study is currently under development on the true compre- Espaiia (1982- 1988); Monografias TCcnicas: Madrid,
hension and awareness that patients have of the clinical 1990: Vol. 17.
trials in which they are involved. 2. Vlasses, P.H. Clinical research: Trends affecting the
As a whole, the pharmacist‘s presence in ethics com- pharmaceutical industry and the pharmacy profession.
mitees allows the pharmacy service to solve practical Am. J. Health-Syst. Pharm. 1999. 56, 171-174.
problems related to the execution of the clinical trial, prior 3. Quevedo, A,; PCrez. L.; Fernindez, A. Participacion del
to the approval of the protocol. Moreover, by evaluating farmackutico de hospital en la investigation clinica. Farm.
methodological aspects of protocols, the clinical phar- HOSP.1999, 23, 24-41.
macist is asked to develop future protocols, linking with 4. Idoate, A,; Girildez, J.; Idoipe, A. Trials: Aplicacidn
informiitica para la dispensacion y control de medicamen-
pharmacist’s role as clinical researcher.
tos en fase de investigacih clinica. Farm. Hosp. 1995, 19,
24-30.
5 . Data not published. Pesonal communication. Agencia
Espafiola del Medicamento. Ministerio de Sanidad y
Consumo.
6. Vizquez. J.R.; Moncin, C.; Huarte, R.; Idoipe, A.; Palomo,
It is clearly understood that pharmacy services and cli- P.: Marco, R. Ensayos clinicos: Participacion del servicio
nical pharmacists should play an important role in cli- de farmacia. Farm. Clin. 1995, 12, 178-188.
nical research.[461In this sense, a survey noticed that a 7. Escoms, M.C.; Novoa, C.; Jodar. R.J.; SuiiC, J.M. Perfil de
10s ensayos clinicos evaluados en un hospital general
clinical pharmacist was the investigator in 12% of cli-
durante quince afios: Utilidad de un programa informiitico.
nical trials.[31 Nevertheless. the percentage of protocols
Farm. Clin. 1997, 14, 341-347.
in which a pharmacist is integrated into the research 8. Lunik, M.C. Clinical research: Managing the issues. Am. J.
team is higher. Health-Syst. Pharm. 1999, 56, 170-171.
In fact, it is not rare that pharmacists collaborate 9. Phillips, M.S. Clinical research: ASHP guidelines and
in activities that are not considered to be routine drug future directions for pharmacists. Am. J. Health-Syst.
management. The pharmacists may be responsible for Pharm. 1999, 56, 344-346.
randomization of the patients in treatment groups. If the 10. Cipywnyk, D.M. A survey of pharmacy-coordinated
study is double-blind, pharmacists can calculate do- investigational drug services. Can. J. Hosp. Pharm. 1991,
sages, keeping the investigator unaware of treatment 44; 183-188.
assignments. Nevertheless, the main field in which a 11. Giraldez, J.; Idoate, A,; Jimenez-Torres, N.V.; Ribas, J.;
Rodriguez-Sasiain, J.M. Aspectos Pricticos de la Partici-
clinical pharmacist can expand is with the institutionally
paci6n del Servicio de Farmacia en 10s Ensayos Clinicos
sponsored research of off-label treatments. Such re-
del Hospital. In Sociedad Espafiola de Farmacia Hospi-
search may involve an existing drug product, a new talaria. Jornadas de Actualizacidn Sobre Ensayos Clini-
formulation, a new method or route of administration, cos: Madrid, 1990; 65-118.
or any combination of these that is not covered by the 12. American Society of Health-System Pharmacists. ASHP
Spanish Medicine Agency-approved labeling; as well as guidelines on clinical drug research. Am. J. Health-Syst.
clinical trials that involve activities familiar to pharma- Pharm. 1998, 55: 369-376.
Role of the Clinical Pharmacist in Clinical Trials (Spain) 849
13. Ley 14/1986, de 25 de abril, general de sanidad. Ministerio Impact of Clinical Trials 1994-1996. In 3rd Congress of
de Sanidad y Consumo. B.O.E. no. 78, de 27 de abril de the European Association Hospital Pharmacists; Edim-
1986. burgh: UK, 1998.
14. Ley 25/1990, de 20 de noviembre, del medicamento. 29. ValdCs, 6.; SuiiC, M.P.; Montoro, J.B. Impact0 econdmico
Ministerio de Sanidad y Consumo. B.O.E. no. 306, de 22 de 10s ensayos clinicos en un hospital general: Ahorro en
de diciembre de 1990. costes farmacCuticos. Farm. Hosp. 2000, 24, 93-94, (Esp.
15. Real Decreto 561/1993, de 16 de abril, por el que se Congr.).
establecen 10s requisitos para la realizacidn de ensayos 30. McDonagh, M.S.; Miller, S.A.; Naden, E. Costs and
clinicos con medicamentos. Ministerio de Sanidad y savings of investigational drug services. Am. J. Health-
Consumo. B.O.E. no. 114, de 13 de marzo de 1993. Syst. Pharm. 2000, 57, 40-43.
16. Real Decreto 414/1996, de 1 de mayo, por el que se 31. Sociedad Espanlola de Farmacia Hospitalaria. Jomadas
regulan 10s productos sanitarios. Ministerio de Sanidad y de Actualizacio'n Sobre Ensayos Clinicos: Madrid, 1990;
Consumo. B.O.E. no. 99, de 24 de abril de 1996. 300 pp.
17. Declaracidn de Helsinki: recomendaciones para orientar a 32. Idoate, A.J.; Cainzos, M.D.; Idoipe, A. Ensayos Clinicos.
10s mCdicos en 10s trabajos de investigacidn biomCdica con In Farmacia Hospitalaria; Bonal, J., Dominguez-Gil, A.,
sujetos humanos. Adoptada por la 18" Asamblea MCdica Eds.; Editorial MCdica Intemacional SA: Madrid, 1993;
Mundial (Tokio, Japdn, octubre de 1975), por la 35" 645 -691.
Asamblea MCdica Mundial (Venecia, Italia, 1983) y por la 33. Bermejo, T.; Cuiia, B.; Napal, V.; Valverde, E. Manual del
41" Asamblea MCdica Mundial, Somerset West, Repdblica Residente de Farmacia Hospitalaria; Sociedad Espaiiola
de Sudifrica, octubre 1996. de Farmacia Hospitalaria, 1999; 917 pp.
18. Organizacidn Mundial de la Salud (International Confer- 34. Jddar, R. Los ensayos clinicos constituyen una seccidn con
ence on Harmonization of technical requirements for personalidad propia en el Servicio de Farmacia (entre-
registration of pharmaceuticals for human use) Good vista). El FarmacCutico Hospitales 1994, 52, 6-8.
Clinical Practice: Consolidated Guideline. Documento 35. Gdmez, B.; Codina, C.; Ribas, J. In Clinical Trials Agency,
no. E6GCPD12WP6. ICH Secretary. Ginebra, may 1996. ASHP Annual Meeting, Orlando, Florida, 1999, poster
19. Ordovas, J.P.; Jimenez-Torres, N.V. El Servicio de Farm- presentation, Intl-5 1.
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Tarea Cooperativa; Barlett, A,, Serrano, M.A., Torrent, J., 37. Anandan, J.V.; Isopi, M.J.; Warren, A.J. Fee structure for
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Barcelona, 1992; Vol. 13; 27-35. 50, 2339-2343.
20. Rodilla, F.; Magraner, J.; Fuentes, M.D.; Ferriols, F. 38. Idoate, A,; Ciraldez, J.; Idoipe, A,; Garrido-Lestache, S.
Ensayos clinicos y su repercusidn en un servicio de TrialsE:Aplicacidn informfitica para dispensacidn y con-
farmacia hospitalaria. Farm. Hosp. 1994, 18, 249-254. trol de medicamentos en investigacidn clinica. Farm. Hosp.
21. Sacristan, J.A.; Bolaiios, E. Papel de 10s servicios de 1995, 19, 24-30.
farmacia en la realizacidn de ensayos clinicos: Punto de 39. Gecos v1.1. Programa Multiusuario de Gestio'n de
vista de la industria farmackutica. Farm. Hosp. 1995, 19, Ensayos Clinicos Desarrollado para Servicios de Farm-
364- 367. acia Hospitalaria; Grifols SA: Barcelona, Spain, 2000.
22. Ferrer, M.I. El control de 10s medicamentos de ensayo 40. Oliveras, J.; Jddar, R.J.; SuiiC, J.M. Programa informatico
clinico: Perspectivas y necesidades actuales. El Farm- aplicado a1 control de ensayos clinicos. Farm. Hosp. 1990,
ackutico Hospitales 1994, 52, 38-39. 14, 83-87.
23. York, J.M.; Alexander, J.G.; Barone, J.A. The value of the 41. Wermelling, D.P. Clinical research: Regulatory issues.
clinical pharmacist in the drug development process. Clin. Am. J. Health-Syst. Pharm. 1999, 56, 252-256.
Res. Pract. Drug Regul. Aff. 1998, 6, 23-39. 42. De la Llama, F.; Gutierrez, P. Auditoria sobre ensayos
24. Gouveia, W.A. Regulatory Authority affecting american clinicos. Farm. Hosp. 1996, 20, 114- 117.
drug trials: Role of the hospital pharmacist. Drug Inf. J. 43. Monzd, M.; Pla, R. Seguimiento de 10s ensayos clinicos
1993, 27, 129-134. finalizados y sus posteriores publicaciones. Farm. Hosp.
25. Gallastegui, C.; Ascunce, P.; Divila, C.; Boado, A. 2000, 24, 107-108, (Esp. Congr.).
Servicios de farmacia y ensayos clinicos: Encuesta a la 44. Ordovis, J.P. Consentimiento informado del paciente en
industria farmackutica. Farm. Hosp. 1999, 23, 231 -237. 10s ensayos clinicos (editorial). Farm. Hosp. 1999, 23,
26. Rockwell, K.; Bockheim-McGee, C.; Jones, E.; Kwon, 267-270.
I.W.G. Clinical research: National survey of U.S. phx- 45. Ordovis, J.P.; Ldpez, E.; Urbieta, E.; Torregrosa, R.;
macy-based investigational drug services-1997. Am. J. JimCnez-Torres, N.V. Anilisis de las hojas de informacidn
Health-Syst. Pharm. 1999. 56, 337-344. a1 paciente para la obtencidn de su consentimiento
27. Idoate, A,; Ortega, A.; Carrera, F.J.; Aldaz, A.; GirBldez, J. informado en ensayos clinicos. Med. Clin. (Barc.) 1999,
Cost-evaluation model for clinical trials in a hospital 112, 90-94.
pharmacy service. Pharm. World Sci. 1995, 17. 172-176. 46. Ordovis, J.P. Investigacidn clinica en Espafia y servicios
28. Barroso, E.; Ferrer, M.I.; Jbdar, R. Direct Economical de farmacia hospitalaria. Farm. Hosp. 1996, 20, 189-191.
PROFESSl 0NAL ORGAN IZATIONS
I Federal councilors
Executive BERSHI
Helen Dowling, Federal President SHPA currently represents over 1,500 pharmacists and
Naomi Burgess, Federal Vice President pharmacy technicians working in hospitals and related
Helen Matthews, Federal Treasurer institutions. This represents over 80% of Australian
Sue Kirsa hospital pharmacists.
[41
TIV Australian Drug Information Procedure Manual.
151
Drug Usage Evaluation-Starter Kit.
issi ent Directory of Hospital Pharmacy and Pharmaceutical
[61
Organisations.
SHPA is committed to promoting the quality use of
medicines through the ongoing development, application,
and implementation of leading-edge pharmacy practice in s
hospitals and other healthcare organizations.
These newsletters keep members up-to-date with news
oak and views at a national and local state level.
SHPA Practice Standards and Definitions."' The recently completed Clinical Pharmacy Intervention
Australian Injectable Drugs Handbook.'21 Study['] was commissioned by SHPA to quantify the be-
[31
Clinical Pharmacy-A Practical Approach. nefits of clinical pharmacist's interventions. Eight teach-
Society of Hospital Pharmacists of Australia, The 853
ing hospitals were involved in the study, the first multi- Annual general meeting
site cost-benefit analysis of clinical pharmacy interven-
tions in Australia. The results showed that over A$4 November 2001: Hobart, Tasmania
million per annum were saved by the hospitals because of
the direct intervention of clinical pharmacists in drug
treatments. The study will form a key component of a
campaign to increase awareness of the important role
hospital pharmacists have in ensuring safe, high quality,
and cost-effective healthcare and of maintaining adequate 1. Practice Standards and Definitions; Johnstone, J.M.,
levels of clinical pharmacy services. Vienet, M.D., Eds.; The Society of Hospital Pharmacists
of Australia: Melbourne, Australia, 1996, ISBN 0 9588944
With the rapidly aging Australian population in mind,
9 3.
SHPA signed an agreement with the internationally re- 2. Australian Injectable Drugs Handbook, 2nd Ed.; Morris,
cognized commission for certification in Geriatric Phar- N., Ed.; The Society of Hospital Pharmacists of
macy in 2000. The agreement sees the two organizations Australia: South Melbourne, Australia, 1999, ISBN 0
teaming up to offer the first examination-based compet- 9586881 17.
ency assessment for Australian pharmacists. SHPA has 3. Clinical Pharmacy-A Practical Approach; Hughes, J.,
negotiated with the Australian Government for CCGP- Donnelly, R., James-Chatgilaou, Eds.; Macmillan Edu-
credentialed pharmacists to access funding for clinical cation Australia Pty Ltd.: South Yarra. Australia, 1998,
services provided to patients in both hospitals and com- ISBN 0 7329 4719 7.
munity settings. 4. Australian Drug Information Procedure Manual; Foran, S.,
Provision of quality educational services in pharmacy Ed.; The Society of Hospital Pharmacists of Australia:
South Melbourne, Australia, 1996.
and related areas is one of the core businesses of SHPA
5. Australian Drug Usage Evaluation Starter Kit; SHPA
and an area of ongoing expansion and development. In Drug Usage Evaluation Committee of Specialty Practice,
recent times, the focus of these services has broadened Ed.; The Society of Hospital Pharmacists of Australia:
from predominantly addressing the needs of hospital phar- South Melbourne, Australia, 1998.
macists, to incorporating nursing and community phar- 6. Directory of Hospital Pharmacy and Pharmaceutical
macist education. With the inclusion of pharmacy tech- Organisations; Vernon, G., Thomson, W.A., Eds.; The
nicians in our membership starting in 2000, educational Society of Hospital Pharmacists of Australia: South
needs of this group will be more formally addressed. Melbourne, Australia, 2001.
SHPA’s most recent strategic planning cycle began in 7. Allen, K.M.; Dooley , M.J. ; Doecke, C.J.; Galbraith, K.J.;
February 200 1. Taylor, G.R.; Bright, J.; Carey, D.L. A prospective
multicentre study of pharmacist initiated changes to drug
therapy and patient management in acute care government
funded hospitals, in press.
8. Dooley, M.J.; McLennan, D.N.; Galbraith, K.J.; Burgess,
N.G. Multicentre pilot study of a standard approach to
Biennial Clinical Pharmacy Conference document clinical pharmacy activity. Aust. J. Hosp. Pharm.
2000, 30 (4), 150-157.
October 2000: Gold Coast, Queensland 9. Burgess, N. The National Pharmacy Casemix Bridging
October 2002: Sydney, New South Wales Study-Report to the Commonwealth Department of
Health and Family Services; The Society of Hospital
iennial Federal CQn~erence Pharmacists of Australia: Adelaide, Australia, 1998.
10. Howitt, K.; Burgess, N.; Brooks, C. The Refinement and
Application of PharmGroup Classifications as a Manage-
November 2001: Hobart, Tasmania ment Tool f o r Competitive Neutrality in the Health
November 2003: Canberra, Australian Capital Territory Industry; Report to The Society of Hospital Pharmacists
of Australia: Melbourne, Australia, December 2000.
tate Branch Conferences
new headquarters also in Madrid and more suited to Finally, a brief mention of our annual Congress (first
their requirements. held in Madrid in 1955) is in order. The Congress has
Created in 1997, the Fundaci6n Espafiola de Farmacia accompanied and evolved together with the society itself.
Hospitalaria (Spanish Foundation for Hospital Pharmacy) This year we held the 45th Congress, the latest in a
is also closely linked to the SSHP. virtually uninterrupted series that provides a meeting place
Over the years, the SSHP has given top priority to its for Spanish hospital pharmacists and that has now be-
educational and publications areas. With regard to the come a highlight on the international health care circuit.
educational area, this special interest has resulted in a This year, the 47th meeting of Congress is to take place in
substantial number of courses, grants, prizes, and aids to Barcelona from October 1 to October 4 2002.
research. Efforts have been made to diversify so that Besides the Congress, approximately 20 zoned scien-
courses oriented toward residents have coexisted along- tific meetings are held every year, although the venues
side others directed toward the staff, in an attempt to for the coming year have not yet been decided. These
cover the needs and requirements of the whole group. events keep the society alive and have helped it to grow
Substantial aids are also available to ensure research from the 50 or so associates who attended the first Gene-
projects lead to complete, fully defined developments in ral Meeting in 1955 to the current membership of 1850.
highly contemporary areas and subjects, often achieved
by multidisciplinary and multicentric teams chosen with
a view to encouraging scientific and professional ex- VERNlN
changes. Aid is also available to outstanding young train-
ees, giving them access to specific knowledge in other residents of Honor
countries in lines of work that may or may not be directly Felipe Gracia; Juan Manuel Reol; Manuel Ruiz-Jarabo;
linked with our areas, but that are certain to provide a Joaquim Bonal de Falgas
wealth of new knowledge that can then be passed on
to the group as a whole. President
Among the more than 130 publications issued by the Eduardo Echarri Arrieta
SSHP’s publications area are a series of regularly revised
and updated monographs, general compendia, and regular ~i~e-~residen~
journal publications. The most outstanding of these is Ma. Cinta Gamundi Planas
undoubtedly the SSHP journal Farmacia Hospitalaria
(Hospital Pharmacy), which, over 20 years or so, has Secretary
provided a platform for some of the major landmarks in David Garcia Marco
the group’s story, collaborating closely in diffusion and
the training of Spanish and foreign professionals. The Treasurer
SSHP Infomzation Bulletin is another regular publication Rafael Molero G6mez
that has also accompanied us in our e€forts.
Activities undertaken by the area of institutional re- Member Zone 1
lations intensified in 1988, after the society’s 1987 entry as Ma. Jose Martinez Vizquez
full member in the European Association of Hospital
Pharmacists, to which it had previously belonged as an Member Zone
associate member. This was then accompanied by a Felipe de la Llama Vizquez
series of agreements with our institutions, including the
1989 Pharmacovigilance Agreement, the approval giv- Member Zone 3
en in 1993 of the SSHP’s Narcotics Computer Control Carmen Lacasa Diaz
Programme, and the more recent official blessing for the
calculation of specific pharmacy weights in GRD, and the Member Zone 4
Spanish Medicines Agency itself, with which we have Manuel A16s Almiiiana
collaborated in a wide-ranging series of task forces in our
acknowledged role as experts in medicine and drugs. e r 5
M e ~ ~ Zone
Fully aware of this role, the society promotes and de- Luis de la Morena del Valle
velops a range of studies, reports, and projects over a
range of contemporary and future health issues via the M e ~ ~ Zone
e r
foundation of the same name. Esperanza Quintero Pichardo
856 Spanish Society of Hospital Pharmacy
Member Residents
Cristina L. Crespo Martinez Due to its long existence and experience, the SSHP now
has a very well-developed structure and is considered as a
solid reference within the health field. The society has
eight commissions, work groups, and task forces, more
than 130 publications, a bimonthly scientific journal, an
Eduardo Echarri Arrieta information bullctin, and educational activities (prizes,
Ma. Cinla Camundi Planas courses, grants). This and the high degree of membcrship
Rafael Molero Gdmcz among the pharmacist’s professionals make this society
David Garcia Marco an important and representative organization within the
Felipe de la Llama VBzquez medical field.
Luis de la Morena del Valle
Farmaciu Hospitalaria: Esteban Valvcrde Molina Boletin Informativo Extraordinario. Memoria 1991 -1909;
SSHP Infiwmation Bulletin: David Garcia Marco Sociedad Espafiola de Farmacia Hospitalaria, 1999.
Historiu de la Sociedad EspaAolu de Farmacia Hospitalaria.
Tomo I; Sociedad Espafiola de Farinacia Hospitalaria,
1995.
Historiu cle la Sociedad E.ypaAola de Farmacin Hospitalaria.
Tomo II; Sociedad Espafiola de Farmacia Hospitalaria,
General Technical Secretary: Isabel Crespo Gonzglcz 1995.
ClerkA: Ma. Luisa Avila Fernlindez; Manuela Florencio Sociedad Espafiola de Farmacia Hospitalaria. Anuario; Meciitex,
Scrrano 1997.
PHARMACY PRACTICE ISSUES
TGL’s mission statement is promoting quality use of The Guidelines are derived from the best available scien-
medicines through the preparation, publication, and sale tific evidence, but the experience, insight and opinions of
of independent, authoritative, up-to-date, problem-orient- Australian experts are an essential element of the writing
ated information. process, with the final text reflecting independent and
expert interpretation.
Because the Guidelines cover all common disorders
and not just those for which there is a body of evidence,
there are many instances where trial data are not availa-
The key objectives of TGL are: ble, where published data fail to answer questions rele-
vant to prescribers, or where research findings may not
To encourage the use of Therapeutic Guidelines by be relevant to local practice. To resolve gaps in the
health professionals to assist them in making thera- evidence, recommendations for reasonable therapy are
peutic decisions to facilitate optimum healthcare. developed, with criteria such as a drug’s adverse effect
To encourage the use of Therapeutic Guidelines in- profile, long-term safety data, and cost being taken
ternationally through licensing agreements with appro- into consideration.
priate organizations.
To preserve the integrity of the organization through
strict policies for Directors, staff, and members of the eview and Endorsement
writing groups, on issues such as conflict of interest.
To maintain financial independence. Critical steps in the development of the manuscripts are
To establish strategic alliances with other organiza- an extensive external review process, reconciliation of
tions to further the objectives of the organization. text with that of other relevant therapeutic guidelines, and
To increase the range of products, e.g., information for endorsement by national or peak bodies such as The
consumers. Royal Australian College of General Practitioners and the
To allocate funds for research and development. National Prescribing Service.
859
arc
The evaluation unit liaises with a network of approxi- Research 1s an integral part of the organization and
mately 250 users (general practitioners, specialists, phar- the major focus of TGL research is on improving ac-
macists, and students) to actively solicit feedback on the cess to the Guidelines at the point of clinical decision
various texts. Participants in the network are provided making and increasing integration of the Guidelines with
with all titlcs free-of-charge, and staff visit these users other information sources, prescribing modules, and pa-
regularly to discuss and record comments. tient databases.
Beforc any new edition is commenced, accrued fecd- TGL is an industry partner in a major research project,
back on the previous edition is collated and passed on which provides one postdoctoral and two doctoral
to the writing group for consideration in the revision of scholarships to further develop and optimize the produc-
the text. tion of electronic Therapeutic Guidelines, including the
integration of Therapeutic Guidelines with prescribing,
dispensing, and medical record management software.
Pharmacy and Therapeutics (P&T) Committee. The first change and substitution in the outpatient setting. The
guidelines describing a formulary system were published Public Advocate for the City of New York contended
jointly in the early 1930s by the Journal of the American that the use of formularies and therapeutic interchange in
Medical Association and the Journal of the American ambulatory care settings resulted in inappropriate, or less
Pharmaceutical A~sociation.'~~ In 1965, the Joint Com- appropriate, drug therapy.I7] Furthermore, this inappro-
mission on Accreditation of Hospitals (JCAHQ) man- priateness in drug therapy occurs in great part because
dated that hospitals develop f~rmularies.'~]In 1959, financial considerations-much more than clinical con-
efforts by the American Society of Hospital Pharmacists siderations-drive formulary decisions in managed care
(ASHP) and the American Hospital Association (AHA) organization^.^^] In a published comparison evaluating
were directed at providing a description of the role of the the utilization of ambulatory services for patients in a
P&T Committee. Based on the recommendations of the health maintenance organization (HMO), the use of for-
two organizations, the P&T Committee was established as mularies and therapeutic interchange was found to in-
the major committee within the health care organization crease the utilization of health care resources.[81 Propo-
for determining which medications should be routinely nents of formularies and therapeutic interchange in the
used in the hospital. Data from the American Medical outpatient settings argue that these criticisms are un-
Association (AMA) suggest that 90% of hospitals have founded. The Academy of Managed Care Pharmacy
some type of formulary.[61Historically, P&T Committees (AMCP) states that a well-developed and maintained
have determined which medications were selected to the medication formulary decreases patients costs and im-
formulary based on the safety, efficacy, and acquisition proves patient care.[']
cost of the medications. In the inpatient setting, therapeutic interchange has
The function of the P&T Committee has evolved been accepted by a number of medical and pharmacy
secondary to greater pressures caused by managed care, organizations. These organizations include the AMA
costly medications, and expedited Food and Drug Ad- American Society of Health-Systems Pharmacists, and
ministration (FDA) review processes. Modern P&T the American College of Physicians.[21 These organiza-
Committees must consider the cost of therapy instead tions support therapeutic interchange within the estab-
of simplistically evaluating solely the acquisition cost of lished guidelines of a formulary system to meet the
the medication when deciding formulary status. Until therapeutic and institutional goals for the ultimate benefit
recently, cost effectiveness information was not a of patient care.
routine component of data submitted to the FDA during In general, there are three mechanisms by which
the drug approval process. In addition, shorter FDA therapeutic interchange can occur.[1o1 The first mech-
evaluations of new drugs mandate that hospitals, through anism consists of a system whereby pharmacists inde-
P&T Committees, constantly review information regard- pendently substitute medications on the basis of their
ing clinical outcomes, medication errors, and adverse
drug effects long after the medication has been approved
for use. Table 1 Therapeutic interchanges at SJHA
Low molecular weight heparins
RCHA SS Extended spectrum penicillins
First-generation cephalosporins
Second-generation cephalosporins
The term therapeutic interchange is often used inter-
Third-generation cephalosporins
changeably with therapeutic substitution. There are Proton pump inhibitors
important differences between the two methods of H2 blockers
formulary management; therefore, the terms should not 5HT3 inhibitors
be used in this manner. Based on the list of definitions Fluroquinolones
previously presented, the major difference between these Oxazolidinones/streptagramins
methods of formulary management is whether the pre- Parenteral amino acids
scribing physician has given approval of the interchange Sedative hypnotics
of one medication for another or received notification Enteral feedings
that the interchange occurred. In an effective therapeutic Insulins
IV immunoglobulins
interchange system, physicians are informed before the
Narcotic analgesics
alternative medication is dispensed and administered. A
Multivitamins
great deal of controversy surrounds therapeutic inter-
862 Therapeutic Interchange
own professional judgment, without the consent of the institution’s computer system to activate the therapeutic
prescribing physician. This mechanism is highly discour- interchange. The last mechanism involves obtaining phy-
aged by the majority of professional organizations and is sician approval prior to each therapeutic interchange.
considered illegal in several states. The second mech- Although effective in some situations, this mechanism can
anism is the most commonly accepted. In this mech- be time consuming for pharmacists, physicians, nurses,
anism, medications are automatically interchanged with and patients.
prior physician approval based on established institu- A survey published in 1992 by the American Society
tional protocols. These protocols are established through of Health-Systems Pharmacists suggested that only 6 1%
the hospital’s P&T Committee or through HMO poli- of the hospitals participating in the survey had well-
cies. In most instances, this mechanism relies on the controlled formulary systems.“ ’] Of these hospitals, 69%
had formulary systems based on the concepts of thera-
peutic interchange. Common medication classes involved
in therapeutic interchanges were antimicrobials, antacids,
Table 2 Guidelines for implementing a therapeutic and multivitamins. The medication class of antimicro-
interchange program bials is particularly suitable for therapeutic interchange.
Step I : Identify the feasibility of a therapeutic interchange Antimicrobials represent a pharmacologic class with mul-
based on medication class usage trends, patient outcomes, tiple therapeutic redundacies.‘” This pharmacologic class
clinical trial data, medication error trenddpotential, adverse represents approximately 10-40% of a typical hospital’s
reaction information, cost benefits, or resistance patterns. drug expenditures.[21
Saint Joseph’s Hospital of Atlanta (SJHA) is a 348-
Step 2: Determine the purpose of the therapeutic interchange.
If after determining that two agents are therapeutically bed, tertiary care, nonprofit hospital that specializes in
equivalent, cost savings can become an important factor of interventional cardiology, oncology, cardiac surgery, vas-
the therapeutic interchange. cular surgery, orthopedics, and neurology. The hospital
currently has a drug budget of approximately $10 million.
Step 3: Obtain support for the therapeutic interchange Therapeutic interchange has been used extensively to
from the P&T Committee, Antibiotic Subcommittee, and
manage the pharmacy drug budget. It is estimated that
any medical staff sections that would be involved in the
therapeutic interchange. a well-managed formulary system based on therapeutic
interchange avoids $800,000 to $1 million annually based
Step 4: Communicate the proposed therapeutic interchange to on medication acquisition costs. Table 1 contains a listing
members of the medical and hospital staffs. In general, input of therapeutic interchanges by medication class.
should be obtained from members of the laboratory, nursing One of the most recent medication classes reviewed
staff, administration, risk management, key physician groups,
for potential therapeutic interchange was the fluroqui-
and quality improvement staffs.
nolone antibiotics. A listing of the procedures involved
Step 5: Once approved, advertise the therapeutic interchange in the process is provided in Table 2. This listing should
to the medical, nursing, administrative, and pharmacy staffs. serve as a guide for implementing a therapeutic inter-
Communication can be in the form of medical staff change. Other guidelines have also been
newsletters, pharmacy newsletters, mailings, inservices,
and posters.
Step 6 Implement the interchange. Physicians are generally
more accepting of therapeutic interchange programs if they CONCLUSION
know that nonformulary medications can be obtained if
indicated. At SJHA, a nonformulary medication will not be When used appropriately, therapeutic interchange has
interchanged if “brand necessary” or “do not substitute” is proven to be an extremely effective method of medication
designated by the physician on the medication order.
cost management. An active and well-organized P&T
R e p 7: Monitor the program for positive or negative impacts. Committee is essential to the success of any therapeutic
This is perhaps the most important aspect of developing a interchange program. As the focus on the costs involved
therapeutic interchange program. Feedback regarding the with medication therapy in health care organizations
program should be continuously obtained from members of increases, P&T Committees will have to become even
the medical, nursing, discharge planning, and laboratory staffs more creative in methods used to promote, evaluate, and
and, in some instances, from patients. Be prepared to modify
monitor the effects of therapeutic interchange. The
the program, if necessary.
evaluation of quality of life issues, pharmacoeconomics,
863
clinical outcomes, and humanistic/behavioral outcomes ambulatory care settings. Am. J . Hosp. Pharm. 11994, S / ,
will become increasingly important."' 180% 18 10.
7. Green, M.; Vasisht, R.; Martin, J. Compromiying Your
Drug Choice: How HMOs are Dictating Your Nexl Pres-
cription; Public Advocate: New York, 1996.
8. Horn, S.D.; Sharkey, P.D.; Tracy, D.M.; Horn, C.E.;
James, B.; Coodwin, F. Intended and unintended con-
1. Massoomi, F. Formulary managcment: Antibiotics and sequences of HMO cost-containment strategies: Results
therapeutic interchange. Pharm. Pract. Manage. Q 1996, from managcd care outcomes project. Am. J. Manage. Care
I6 ( 3 ) , 11 18. 1996; TI ( 3 ) , 253-264.
2. American Socicty of Hospital Pharmacists. ASHP guide- 9. Managed Care Pharmacy ~act.c.heet-Therap~~uti~ Suhsti-
lines on formulary system management. Am. J. Hosp. tutian; Academy of Managed Care Pharmacy: Alcxandria,
Virginia, 1997.
3. d therapeutic interchange: The 10. Abood, R.K. Legal issues confronting the therapeutic
health care setting makes a diffcrcncc. Am. J. Health-Syst. substitution of drug products. Clin. Trends Pharm. Practice
Pharm. 1999, 56, 467 471. 1995, 9, 1-11.
4. Dillon, M.J. Drug F~ii-tnularl).Management in Managed 1 I. Crawford, S.Y.; Myers, C.E. ASHP national survey of
Care Pharmacy Practice: Navarro, R.P., Ed.; Aspen hospital-based pharmaceutical services 1992. Am. .I.Hosp.
Publishers, Inc.: Gaithersburg, Maryland, 1999; 145- 165. Pharm. 1993, .50, 1371 1404.
~~
5. Wade, W.E.; Spruill, W.J.; Taylor, A.T.; Longe, R.L.; 12. Wall, D.S.; Abel, S. Therapeutic-interchange algorithm for
Hawkins. D.W. The expanding role of Pharmacy and multiple drug classes. Am. J. Health-Syst. Pharm. 1996,
nd beyond. Pharma- 53, 1295- 1296.
13. Scsin, G.P. Therapeutic decision-making: A model for
6. American Medical Association. AMA policy on drug formulary evaluation. Drug Tntcll. Clin. Pharm. 1986, 29,
formularies and therapeutic interchange in inpatient and 581 583.
PHARMACY PRACTICE ISSUES
mission to interchange medications, the physician can on behalf of the patient.”[lol They define therapeutic
either give or withhold permission, or provide a new interchange as ‘‘the interchange of various therapeutically
prescription order (verbal order). This new prescription equivalent drug products by pharmacists under arrange-
order can override the therapeutic interchange policy and ments between pharmacists and authorized prescribers
therefore negate its effectiveness. who have previously established and jointly agreed upon
Although it has not published a position statement or conditions for interchanges.’ ’I1‘I They believe that an
paper on the topic, the AMA does not support the use of advisory committee should develop these policies, that
therapeutic interchange in any setting. Their position is the policies should be reviewed and revised over time,
evident when reviewing policies 23.023, 23.033, 23.035, and that prescribers should have the prerogative to over-
23.057, and 23.060 from their current Policy Compen- ride therapeutic interchange on behalf of patients. In
d i ~ m . [ These
~] policies state firm opposition to the in- addition, ASHP recommends that pharmacists enacting
terchange of “(1) . . . a drug product that is administered therapeutic interchange monitor affected patients to
in the same route and which contains the same phar- “identify and prevent any unexpected or untoward pa-
maceutical moiety and strength, but which differs in the tient response.’”’’] Similarly, physicians should be
salt or dosage form; and (2) . . . a drug product con- notified when a therapeutic interchange policy has been
taining a different pharmaceutical moiety but which is of enacted and be provided with educational materials sup-
the same therapeutic and/or pharmacological class.” At porting it when appropriate.
their June 1990 annual meeting, the AMA House of The APhA House of Delegates and the AACP support
Delegates debated and adopted Resolution 161, which ‘‘the concept of therapeutic interchange of various drug
states opposition to the establishment of a system at the products by pharmacists under arrangements in which
federal or state level for therapeutic interchange. The pharmacists and authorized prescribers interrelate on
resolution states that this “will inevitably interfere with behalf of the care of patient^.""^"^] The AACP further
the ability of the patient’s physician to assure that the “views initiatives to prohibit therapeutic interchange to
medication prescribed is dispensed to the patient,” and be counterproductive and confusing because this criticism
thus individuality of patient care can be lost. strikes at an important element of the clinical practice of
Of note is the difference between therapeutic inter- pharmacy. ’’ [13’ They believe that pharmacy students are
change policies endorsed by individual health care or- adequately trained to participate in the clinical envi-
ganizations, and regulations required by federal or state ronment, and to assist in the development and process of
laws. Federal or state regulations could be misinterpreted therapeutic interchange. To this end, AACP is committed
as being blanket policies that grant pharmacists authority to training pharmacists who are competent to perform
to interchange medications across all classes and cate- these activities.
gories. Such regulations might also inappropriately sug- The GPIA “supports the practice of therapeutic in-
gest that pharmacists be given the authority to override terchange in institutional or ambulatory settings where
a physician’s prescription without their knowledge. a functioning P and T committee and a formulary system
Therapeutic interchange policies should not grant are in place and where there is active consultation on
prescribing authority to pharmacists. Patients can be behalf of the patient between physicians and pharma-
assured of getting the best care possible only when a c i s t ~ . ’ ” ’The
~ ~ GPIA also “supports an ongoing drug
pharmacist acts in collaboration with a physician to utilization evaluation process for regular review of
provide an optimal drug product. therapeutic interchange policies and formularies, and for
Thus, both parties must endorse therapeutic inter- providing information and education to prescribers.’ ’[14]
change policies before such policies can be used effec- The PMA (representing pharmaceutical manufacturers
tively. Some states have enacted or proposed legislation marketing brand name drugs) opposes therapeutic inter-
that requires physicians to be involved in the development change. Its policy statement concerning drug selection
and management of therapeutic interchange guidelines, states that it ‘‘supports those public policies which retain
whereas other states have proposed legislation that seeks the authority and responsibility for prescription drug se-
to prohibit pharmacists from enacting a unilateral inter- lection exclusively with the individual attending physi-
change. The proposed or enacted legislation agrees with cian, dentist or podiatrist.. .. Specifically, PMA believes
ACCP’s definition in that physician involvement is pa- that inappropriate drug selection policies such as phar-
ramount to the successful development of guidelines maceutical or therapeutic substitution: (1) may adversely
for therapeutic interchange, and pharmacists should not affect a patient’s health, (2) raises serious legal questions,
make unilateral substitution of a drug. (3) may result in increased cost for medical services
The ASHP supports “therapeutic interchange by and (4) are highly inefficient and intrusive.’ ’[151 The
pharmacists when a pharmacist and a physician interrelate policy states, however, that it “is not intended to address
866 Therapeutic Interchange, Guidelines (ACCP)
the manner in which hospital pharmacy practices are system and Pharmacy and Therapeutics Committee or
implemented in an inpatient care situation. Direct phy- equivalent advisory committee.
sician involvement in determining the hospital formulary
distinguishes such formulary practices from therapeutic Rationale
and pharmaceutical substitution. Additionally, it is clear
that the inpatient care environment is a highly controlled The success of any therapeutic interchange program is
setting where patients are constantly being monitored related to the effectiveness of the Pharmacy and Thera-
and, consequently, is much different than the outpatient peutics Committee or its equivalent body, and the drug
care situation.”“’] formulary system. This committee, representing both the
The view of many research-based pharmaceutical pharmacy and medical staffs, must develop, implement,
manufacturers is based on the economic impact thera- review. and change policies and procedures to ensure
peutic interchange may have on their organizations. optimum patient care while containing costs. Similarly, it
Although this is an important consideration for their should recommend and assist in educating professional
welfare, we believe that the manufacturers should join staff regarding current therapeutic interchange policies,
physicians and pharmacists in the quest to provide ex- the success of such policies, and any approved exceptions
cellent medical care at reasonable costs, especially in to them.
light of the federal, state. and local regulations directed The Pharmacy and Therapeutics Committee should
at achieving this goal. Such a commitment would foster establish or assign a committee or department to monitor
a better relationship among the represented communities. the effectiveness of the interchange policies. Audits or
The ACCP believes that if physicians and phar- reviews should be conducted according to set policies.
macists communicate, collaborate, and jointly agree on Criteria should be developed and used to determine when
the purpose for and appropriate monitoring of therapeu- and why the therapeutic interchange policies may be
tic interchange policies, many of the opposing view- ineffective (see Guideline 11).The issues identified should
points outlined above can be brought together in an ef- be addressed and the professional staff notified of
fort to provide state-of-the-art therapeutics and optimal resulting changes to policies and procedures.
patient outcomes. The specific types of institutional or ambulatory set-
tings for which therapeutic interchange policies are most
likely to be effective are those that have drug formularies
with a functioning Pharmacy and Therapeutics Committee
or its equivalent. This may include, but is not limited to,
hospice settings, health maintenance organizations, com-
The ACCP supports therapeutic interchange policies munity hospitals, university teaching hospitals, and am-
when pharmacists and physicians collaborate to develop bulatory clinics affiliated with a hospital. If the policies
policies designed to provide patients with the best dictate that laboratory or medical record data should be
possible care at the best overall price. These policies readily available to pharmacists prior to dispensing a
should result from a synergistic combination of the therapeutic alternative, the setting must provide access to
expertise and knowledge of pharmacists and physicians this information. Regardless of the setting, pharmacists
whose common goal is to ensure optimum patient care. and physicians must have a good working relationship and
They should not be interpreted as “bestowing prescribing a mutual goal to provide excellent medical care while
authority on pharmacists.’’ Although the policies may containing costs appropriately.
vary in complexity, most involve the interchange of one
drug for another that is therapeutically equivalent. Thus,
they should not be viewed as or become blanket policies Guideline II
allowing pharmacists to choose an alternative agent from
an entire class or category of drugs. A continuous drug use evaluation process must be in
The ACCP supports the following guidelines for im- place for regular review of endorsed therapeutic inter-
plementing therapeutic interchange policies within health change policies and procedures.
care organizations.
Rationale
eline I
Drug use evaluation (DUE) reviews the types of me-
Therapeutic interchange is appropriate in institutional and dications prescribed within an institution. This process
ambulatory settings that have a functioning formulary could identify prescription orders to which therapeutic
Therapeutic Interchange, Guidelines (ACCP) 867
interchange policies apply. Once these orders are iden- professional staff regarding the rationale, procedures, and
tified, the success of the policies could be further monitoring criteria for therapeutic interchange. These
evaluated, reviewed, and reported. For example, one methods may include, but should not be limited to,
would have to identify whether an approved alternative newsletters, fliers, departmental meetings, meeting min-
agent was dispensed in place of the one originally pres- utes, and publication of therapeutic interchange policies,
cribed. The DUE could also determine if appropriate such as in an organization’s formulary. Physicians should
patient monitoring occurred following the interchange, be informed of the policies prospectively, and a list of
and whether the interchange resulted in an altered res- active policies should be readily available to the pro-
ponse. Results of these evaluations should be presented fessional staff. Concerns or problems regarding the poli-
to the Pharmacy and Therapeutics Committee or its equi- cies should be addressed to the Pharmacy and Thera-
valent to determine if changes or exceptions to existing peutics Committee.
policies are indicated, or if additional educational endea-
vors should be made available to participating profes- eline V
sional staff.
The therapeutic interchange policies should define a
Guideline III mechanism that enables authorized prescribers to disallow
therapeutic interchange.
Therapeutic interchange, as defined herein, may be exe-
cuted by pharmacists if the authorized prescriber is no- Rationale
tified either verbally or in writing within a reasonable
time frame, and if the pharmacists have access to medical Therapeutic interchange may not be applicable to all
records and appropriate laboratory or other test results as patients. For example, a patient’s preference may play a
required by the therapeutic interchange policy. Exceptions role in a physician’s decision to override a policy. An
to this procedure must be stated clearly in the policy. acceptable method of overriding must be made available
to authorized prescribers. Ideally, it would allow one to
Rationale capture information regarding decisions to override policy
so that the data can be reviewed easily by an advisory
Therapeutic interchange policies and procedures should committee. This could, for example, be accomplished by
describe in detail the conditions and processes for in- asking the physician to complete a brief survey or request
terchanging medications. These should include who has form for disallowing therapeutic interchange. The phy-
authority to enact the interchange, special exceptions to a sician would have to notify the pharmacist either in
policy or procedure, criteria to be evaluated before and writing or verbally regarding the desire to override the
after the interchange occurs, and the definition of “a existing policy.
reasonable time frame” for notifying the physician. For
example, the policy may not require that a physician be
notified for interchange of certain drugs, such as multi-
vitamins. As another example, a reasonable time frame
for notification of the physician when therapeutic in- The guidelines were written by the following subcom-
terchange has occurred may be defined as within 24-72 mittee of the 1990-1991 ACCP Clinical Practice Affairs
hours when the interchange involves antibiotics. Committee: Terri Graves Davidson, Pharm.D.; Mary Beth
O’Connell, Pharm.D.; Ryon Adams, Pharm.D.; Veronica
uideline IV Moriarty, Pham.D.; Anthony Ranno, Pharm.D.; Nathan
Schultz, Pharm.D.; Barry Carter, PharmD., FCCP, Chair;
The Pharmacy and Therapeutics Committee or its equiv- and Marsha Raebel, Pharm.D., FCCP. Other members of
alent should ensure that professional staff are educated the committee were Richard Berchou, Pharm.D., Dennis
regarding the rationale, policies, and procedures for the- Clifton, Pharm.D., Joseph F. Dasta, M.S., FCCP; Carl
rapeutic interchange. Hemstrom, Pharm.D.; Donald Kendzierski, Pharm.D.;
Bruce Kreter, Pharm.D.; Louis Pagliaro, Pharm.D.;
Rationale Richard Ptachcinski, Pharm.D.; Christine Rudd,
Pharm.D., FCCP; and Dominic Solimando, Jr., Pharm.D.
Proper educational methods should be developed, imple- Staff editor is Toni Sumpter, Pharm.D. Approved by the
mented, reviewed, and revised as necessary to inform the Board of Regents on November 3, 1992.
868 ‘I’herapeutic Interchange, Guidelines (ACCP)
From Pharmacotherupy 1993, 13(6):252-256, with 7. Oh, T.; Franko, T.G. Implementing therapcutic interchange
permission of the Amcrican Collcge of Clinical Pharmacy. of inlravcnous Fdmotidine for cimctidine and ranitidine.
Am. J. Hosp. Pharm. 1990, 47, 1547 1551.
8. American College of Physicians. Therapeutic substitution
and formulary systems. Ann. Intern. Med. 1990, 113 (2),
160- 163.
9. American Medical Association. AMA Policy Compen-
I. American Society of Hospital Pharmacists. Statement on dium. In Current Policies of the AMA House of Delegates
thc pharmacy and thcrapcutics committee. Am. J. Hosp. Through the I989 Interim Meeting; Chicago, 1990; 63-64,
Pharm. 1984, 41, 1621. 67.
2. Green, J.; Chawla, A.K.; Pong, P.A. Evaluating a res- 10. American Society of Hospital Pharmacists. Therupeutic
trictive formulary system by assessing nonformulary-drug Interchange; Bethesda, Maryland, 1982.
requests. Am. J. Hosp. Pharm. 1985, 42, 1537 1541. 11. American Society of Hospital Pharmacists. Guidelines on
3. Sesin, G.P. Thcrapcutic decision-making: A model for formulary system managcmcnt. Am. J. Hosp. Pharm. 1992,
formulary evaluation. Drug Intell. Clin. Pharm. 1986, 20, 49, 648-651.
581-583. 12. American Pharmaceutical Association. Position of the
4. Butler, C.D.; Manchester, R. The P&T cominittec: dcs- American Pharmaceutical Association on the Issue oj
criptive survey of activities and time requirements. Hosp. Th(,rupeutic.Interchange; Washington, DC, 1987.
Formul. 1986, 21, 90 99. 13. American Association of Colleges of Pharmacy. Perspect-
5. Weintrauh, M. Effective functioning of the PXLT com- ive on Therapeutic Interchange; Alcxandria, Virginia,
mittee: Onc chairpcrson’s view. Hosp. Formul. 1977, 12, 1987.
260 263. 14. Generic Pharmaceutical Industry Association. Policy on
6. Martin, LA.; Watkins, J.B.; Green, S.A., et al. Procedural Therapeulic Interchange; New York, 1992.
compliance and clinical outcome associated with thera- IS. Pharmaceutical Manufacturers Association. Policy State-
peutic interchange of cxtcnded-spectrum penicillins. Am. ment Concerning Drug Selection; Washington, DC, I 99 I;
J. Hosp. Pharm. 1990,47, 1551-1554. 1-6.
PROFESSIONAL DEVELOPMENT
Marwan S . Absuljoud
Henry Ford Hospital, Detroit, Michigan, U.S.A.
OPP [TIES
Transplantation of human tissues is one of the most Since the mid 1990s, the Food and Drug Administration
important medical achievements of the 20th century. (FDA) has approved various potent immunosuppressive
Transplantation began in 1902, with work of vascular drugs for use in transplantation. Currently, there are four
surgeon Alexis Carrel, who established many of the major classes of immunosuppressive drugs available:
vascular anastomosis techniques that led to effective corticosteroids, antilymphocyte, antimetabolites, and cal-
transplantation. A century later, transplantation has be- cineurin inhibitors (Table l). These immunosuppres-
come a life-saving procedure for a variety of irreversible sants are known to cause short-and long-term com-
acute and chronic diseases for which no other therapy is plications, including infections, cardiovascular disease,
available. Nearly every thoracic and abdominal organ and malignancy (Table 2).12-@ In addition, solid organ
may now be successfully transplanted. In 1999, a total of transplant recipients may have their care further com-
21,516 solid organ transplants were performed at centers plicated by preoperative conditions. The majority of pa-
throughout the United States, of which 16,802 were tients have chronic end-stage illnesses that are inevitably
cadaveric and 4,714 were from a living donor."] fatal and necessitate their transplant. As a result, post
Increased experience and advances in surgical tech- transplantation most patients are on complex prophy-
niques, tissue preservation and posttransplant care have lactic and therapeutic multidrug regimens, leading to
helped to improve the overall success of transplantation. many drug-related complications that may compromise
In 1988, the 1-year graft survival of renal transplants transplant outcomes and significantly increase the cost
using cadaver grafts was 76%, but by 1999, the 1-year of transplantation.
cadaver graft survival rose to 89%. Results of living From its inception, organ transplantation has been
donors also improved from 89% to 94% for the same approached in an extraordinarily multidisciplinary man-
time period. Improvement in survival have also been ner. The transplant team has historically included sur-
achieved for other solid organ transplants with ap- geons, immunologists, pathologists, internists, nurses,
proximately 70% to 80% of grafts functioning at 1-year dietitians, social workers, and spiritual representatives.
after transplantation. [ With continued success of transplantation and the im-
The success of any organ transplantation is due munsuppression-related complications, opportunities have
largely to control of the immune system by immu- been created for many of the pharmacists that are now
nosuppressive therapy to avert rejection of the allo- members of various transplant teams throughout the Uni-
graft. Immunosuppressive treatment strives to prevent ted States. As part of the team, transplant pharmacists
allorecognition and subsequent destruction of the trans- provide direct patient care in a variety of settings, espe-
planted tissues. As a result, transplant recipients rely cially because they have the understanding of transplant
on lifelong immunosuppressive drug therapy for pre- immunology and the immunosuppressants used to pre-
venting rejection and maintaining their graft. Phar- serve the graft.
macists, as experts on immunosuppressive drugs have Appropriately trained transplant pharmacotherapy
a vital role in optimizing pharmacological therapy to specialists may practice in traditional clinical roles or
enhance transplant outcomes and minimize drug-rela- they may fill positions outside the usual sphere of
ted complications. pharmacy practice. Many positions include a clinical
suppression of rejection and immunosuppressive drug lacking, only that it has not reached the standardization
toxicities. The fulcrum should always be adjusted to the and review procedures achieved in other specialties.
requirements of the individualized patient. For example, Guidelines and consensus statements regarding the
with older transplant recipients in whom the immune optimal management of transplant recipients have not
response is dampened, it may be more appropriate to been established because there are few circumstances in
select a lower-intensity immunosuppressive regimen to which the support of one treatment over another is
decrease side effects. In contrast, African Americans are overwhelming. This is probably due to the large sample
considered immunologic high-risk recipients with in- size required to show statistically significant differences
creased risk for rejection and, therefore, will require more and the variability of patients in regard to demographics,
intense immunosuppression to ensure successful thera- socioeconomics, and other risk factors. Most of the
peutic outcome^.[^^.^^^ Certain patients may be predis- resources currently available to aid in the selection of
posed to abnormalities that are part of their disease or a specific medications are publications from the primary
result of the transplant. and a particular immunosuppres- literature. National and international conferences play a
sive drug may exacerbate or worsen them. To prevent significant role in disseminating information concerning
jeopardizing the allograft or further complications in these advances in therapy and new ideas. Symposia provide
patients, it may be necessary to modify the doses of cer- another way to learn of contemporary practices, usually in
tain immunosuppressants or avoid them entirely. a setting that fosters networking while addressing in-
Once a particular regimen is chosen, pharmacists will dividual practice issues. They also provide more oppor-
frequently perform pharmacokinetic and pharmacody- tunity to discuss cases with colleagues, draw upon the
namic evaluations for immunosppressants, antibiotics, experience of others, and learn innovative ways that other
and other agents. Many of the immunosuppressants such centers address common problems. This puts a greater
as cyclosporine, tacrolimus. and sirolimus have signific- onus on the transplant pharmacist to continuously review
ant intra- and interpatient differences that may lead to the current literature, as well as to evaluate it based on its
suboptimal blood c~ncentrations.['""~~ Therapeutic drug merit and relevance to one's own practice setting and
monitoring of immunosuppressive drugs is essential to specific population. Again, this provides an opportunity
make accurate predictions for appropriate drug therapy. for pharmacist involvement with the transplant team.
Furthermore, many of the drugs used in the management Evaluation of the literature from transplant and non-
of transplant recipients are extensively metabolized by transplant sources becomes important. At times, one will
the cytochrome P-450 enzyme system. Drugs, foods, or need to extrapolate information from nontransplant pa-
nutrients that induce, inhibit, or compete for the same tients to overcome certain voids of information concern-
isoenzyme could effect blood concentrations of these ing transplant patients. Of course, experience and clinical
immunosuppressive agents (Table 3)."6.171Drug interac- training will determine when this extrapolation is ap-
tions that increase blood concentrations could expose propriate and when it is not. Herein lies part of the at-
transplant recipients to serious adverse effects, whereas traction of transplant pharmacy; one must possess very
drug interactions that decrease blood concentrations may specific knowledge on how to manage a unique group of
cause rejection episodes and possible loss of the graft as patients, namely organ transplant recipients, while being
a result of inadequate immunosuppression. Pharmacists able to deal with a multitude of medical issues, each of
can prospectively review the patient's medication profile which also requires specialist knowledge.
including over-the-counter (OTC) medications, herbs,
and dietary supplements to predict such interactions and
to help reduce adverse outcomes. Table 4 Useful web resources
http://thedrugmonitor.com
http://transweb.org
TQCOL s http://fujisawa.codmedinfo/cont_educ/tran-tmd/
http://transplantation.medscape.com/Home/Topics/
It has been suggested that there are as many transplant transplantatiodtransplantation.htm1
drug protocols for managing patients as there are htm
http://tpis.upmc.edu/tpis/immuno/compre.
transplant centers. This situation has been created by the http://ntpr.registry@ mail.tju.edu
fact that in the area of transplantation, there is an absence http://stadtlander.codtransplant/
of consensus statements and guidelines in the manage- http://mdconsult.com
http://clinicaltrials.gov
ment of immunosuppressive therapy. This is not to imply
http://unos.org
that adequate literature addressing transplant issues is
872 Transplantation Pharmacy Practice
Table 4 outlines various transplant web resources that a treat themselves with any of the numerous OTC medi-
pharmacist specializing in transplantation may find use- cations. The pharmacists may also develop a variety of
ful. Although some of these web sites include information educational tools to enhance patient learning.“’] This
for patients, others are for health care providers working could take the form of recording audio instructions for
with the transplant recipients. visually impaired diabetic patients, creating daily medi-
cation logs, and providing written information in lan-
guage appropriate for patient understanding.
EDUCATION Patient noncompliance to immunosuppressive therapy
is a significant cause of graft f a i l ~ r e . [ ’ ~ Some
- ~ ~ ] inves-
Transplant pharmacists are considered unbiased resources tigators have reported rates ranging from 2% to a high of
for drug information that promotes better patient care. 43% in pediatric renal transplant recipients.[231In addition
This service may be provided to a variety of individuals to the complexity of the drug regimen, other factors may
and disciplines, such as patients, caregivers, and health lead to drug noncompliance. These include concerns in
care providers, as well as medical residents, new phar- physical appearance due to the side effects of immuno-
macists, and pharmacy students. suppressants, poor provider-patient communication (e.g.,
During the first year after transplant surgery, the dosage change that is not fully explained), depression or
average drug regimen of a transplant recipient consists of anxiety, dissatisfaction with medical care, cost of drugs,
at least 10 different medications with variable time and misconceptions that missing doses will not cause
schedules for administration. For many patients, the r e j e ~ t i o n . [ ~Potential
~ , ~ ~ ] health and economic consequen-
significant number of medications and their complex ces of noncompliance to immunosuppressive therapy in-
schedules can be overwhelming. This creates the potential clude cost of initial and additional prescriptions, physician
for errors and drug noncompliance at a time when the visits, clinic or emergency department visits, hospitaliza-
patient’s condition makes them especially vulnerable to tion, diagnostic costs and additional care such as dialysis
the results of subtherapeutic phannacologic treatment. in case of renal transplant recipients.[261
Pharmacists can educate patients on indications for Pharmacists can provide various strategies for main-
immunosuppressive therapy, appropriate use of drugs, taining drug compliance. They can help patients to select
anticipated adverse effects and expected outcomes a reminder or “cue” such as clock times, meal times, or
(Table 5). Drug regimens must be simplified and made daily rituals or activities to assist with medication ad-
relevant to a patient’s individual needs. As time passes ministration. Meeting with patients more frequently to
after transplantation, the risk of graft rejection will de- assess compliance also reinforces the drug regimen.
crease. As a consequence, patients have frequent altera- Intervention programs using support groups and partner-
tions in therapy as their risk for infections and other ships between the recipient, family, and transplant team
complications decreases with the reduction of their im- have also been shown to be effective strategies to increase
munosuppressive therapy. Patients must be kept aware compliance.[271Increased emphasis on patient counseling
of these changes, and teaching opportunities during each and education about the drug regimen can lead to im-
admission and clinic visit should not be missed. Because proved compliance.
of the potential for drug interactions with immunosup- A major role of all pharmacists in hospitals and
pressants, pharmacists usually counsel patients not to outpatient clinics encompasses education for medical and
nursing staff, as well as other colleagues. Understanding
the various immunologic pathways that can be modified
Table 5 Common educational needs transplant pharmacists is essential to understanding the role of the various
address with patients immunosuppressive medications and their subsequent
Signs and symptoms of infection effects. Knowledge regarding identification and treat-
Medication adverse effects ment of complications, such as infections, hypertension,
Management of adverse events diabetes, hyperlipidemia, osteoporosis, renal insuffi-
Drug-drug and drug-food interactions ciency, depression, and cancer, just to name a few, is
Blood glucose control and insulin requirements crucial when caring for transplant recipients. As these
Pain management patients live longer and become healthier, new issues
Over-the-counter medication use arise as they contemplate such possibilities as conceiving
Alternative medicine use
children, concepts that would not have been entertained
Nutritional requirements
previously. Although at one time management of trans-
Drug compliance
plant recipients may have revolved around surgical care
Transplantation Pharmacy Practice 873
and immunosuppression, it now includes every discip- velopment, approval from the institution's Investigational
line from internal medicine to obstetrics and gyne- Review Board, budget analysis, patient recruitment, ob-
cology and all the pharmacologic issues that go along taining informed consent, data gathering, data analysis,
with each specialty. Each of the professionals contrib- drawing conclusions, and finally submission for presenta-
uting to the care of the patient needs to have some un- tions and publication.
derstanding of the transplant pharmacotherapy treatment Since the infancy of transplantation, the goal of drug
used. This will undoubtedly affect their differential diag- therapy has been to create an agent that can promote true
nosis, how they treat the patient, and what kind of immunologic tolerance, defined as graft acceptance with-
problems need to be brought to the attention of the trans- out immunosuppression. As a result, the National Ins-
plant team, who often continues to care long-term for the titutes of Health, various pharmaceutical companies, and
patient in some many independent scientists have all taken this into
Education may be provided through informal in-ser- developments to foster investigation into strategies that
vice programs about new drugs, new drug indications, might help to discover such a compound. Some phar-
and countless other topics. Tailoring these educational macists are currently performing such translational re-
programs to each discipline may pose a challenge to the search in the hope of eventually crossing paths with
presenter because of the varied background and needs clinical practice.
of the many people involved in the care of a transplant Emphasizing cost containment while achieving ratio-
patient. For example, educational needs of a surgeon nal pharmacotherapy has become an important feature of
are often different from those of a medical specialist many formulary decisions. A transplant pharmacist may
such as a nephrologist or hepatologist or those of a also develop pharmacoeconomic studies that examine
nurse or pharmacist. the financial impact associated with different immuno-
Pharmacists may also perform formal presentations at suppressive regimens. Such analysis extends beyond
professional meetings and symposia. Drug information comparison of the acquisition costs of the individualized
can be regularly disseminated in a form of drug mo- immunosuppressive agent. Other charges, such as the
nographs, newsletters, and continuing education articles. costs of organ procurement, room and board, laboratory
In addition, many transplant pharmacy specialists have tests, operating room, nuclear medicine, and physician
didactic teaching responsibilities, provide clinical rota- and surgeon professional fees, must also be included
tions for pharmacy students in transplantation, and serve because they may substantially add to the total cost of
as preceptors. transplantation. Feasibly, a more expensive immunosup-
pressant agent or regimen may prove to be more cost
effective than cheaper agents if graft survival is increased
ESEARCH or the incidence of morbidity is de~reased.'~'] A panel of
investigators drawn from major transplant centers and
The development of newer immunosuppressive drugs has representatives of the pharmaceutical industry drafted
promoted a need for investigating their safety and efficacy standards for economic and quality-of-life studies. This
to ensure appropriate use. Research on various approved panel recommended specific guidelines for the design and
or investigational immunosuppressants continues to be conduct of trials for economic analysis of transplantation.
executed at an accelerated rate. Many transplant pharma- These recommendations serve as a template for better
cists have established precedents for successful drug design of pharmacoeconomic trials to evaluate the cost
research practice^."^'^^'^^^ Most work with clinically effectiveness of transplantation in the future.
relevant trials in areas such as drug pharmacokinetics, The field of transplantation, therefore, is fertile ground
pharmacodynamics, and patient outcomes. This provides for numerous pharmacist-driven research projects of
the transplant pharmacist with additional avenues to significant clinical and experimental relevance. The
demonstrate to the team his or her unique suitability at results of such research can serve to guide protocol
coordinating and conducting such research. As is recog- decisions to improve patient outcomes and, ultimately,
nized by the FDA, the role of a person with a doctorate improve patient's quality of life.
degree in pharmacy can be to serve as primary inves-
tigator in collaboration with physicians. This is due to the
recognition that pharmacists have the appropriate training
and the clinical perspective to participate or manage
clinical drug research. Pharmacists may be involved in all Although the available number of transplant-related
aspects of the research project, including protocol de- industry practice positions is relatively small, some
874 Transplantation Pharmacy Practice
pharmaceutical companies offer medical or scientific Transplantation Network: Transplant Data; U S . Depart-
liaison positions well suited to pharmacists with prior ment of Health and Human Resources and Services
transplant experience. These positions require the indi- Administration: Richmond, Virginia, 2000.
vidual to interact with physicians, nurse coordinators, 2. Jindal, R.M.; Sidner, R.A.; Hughes, D.; Pescovitz, M.D.;
Leapman, S.B.; Milgrom, M.L.; Lumeng, L.; Filo, R.S.
and other pharmacists regarding issues of research and
Metabolic problems in recipients of liver transplants. Clin.
education, Coordination of multicenter studies and faci- Transplant. 1996, 10, 213-217.
litating communication among centers through symposia, 3. Kasiske, B.L.; Guijarra, C.; Massy, Z.A.; Wiederkehr,
continuing education programs, and advisory boards are M.R.; Ma, J.Z. Cardiovascular disease after renal trans-
especially vital in the transplant discipline. Many trans- plantation. J. Am. SOC.Nephrol. 1996, 7, 158-165.
plant practitioners rely heavily on these sources for up- 4. Epstein, S.; Shane, E.; Bilezikian, J.P. Organ transplanta-
to-date clinical information. Advances in transplantation tion and osteoporosis. Curr. Opin. Rheumatol. 1995, 7,
pharmacotherapy are happening with increasing fre- 255-261.
quency each year to the point where there is no standard 5. Carson, K.L.; Christine, M.H. Medical problems occumng
of practice. Much reliance is placed on “experts in the after orthotopic liver transplantation. Dig. Dis. Sci. 1997,
field,” often identified by industry professionals who tra- 42, 1666-1674.
6. Bennett, W. The nephrotoxicity of immunosuppressive
vel between centers.
drugs. Clin. Nephrol. 1995. 43 (I), S3-S7.
7. Shaefer, M.S. Current topics in immunotherapy and the
role of the pharmacist on solid organ transplant service.
Pharmacotherapy 1991, I 1 (6), 136s-141s.
8. Hilbrands, L.B.; Hoitsma, A.J.; Koene, R.A. Costs of drugs
Pharmacists working with transplant patients are continu- used after renal transplantation. Transplant Int. 1996,9 (l),
ing to define their practice model to meet the phar- S399 - S402.
9. Barlow, C.W.; Moon, M.R.; Green, G.R.; Gamberg, P.;
maceutical and primary care needs of all transplant
Theodore, J.; Reitz, B.A.; Robbins, R.C. Rabbit antilym-
patients throughout the spectrum of care. The role for
phocyte globulin versus QKT3 induction therapy after
transplant pharmacists will continue to expand as the field heart-lung and lung transplantation: effect on survival,
of organ transplantation becomes a viable option for more rejection, infection, and obliterative bronchiolitis. Trans-
patients. In a relatively short period of time, for example, plant Int. 2001. 14, 234-239.
kidney transplantation has gone from being an experi- 10. Nashan, B.; Moore, R.; Amlot, P.; Schmidt, A.G.;
mental procedure in the 1950s to being a cost-effective Abeywickrama, K.; Soulillou, J.P. Randomised trial of
treatment for end-stage renal failure. The type of practice basiliximab versus placebo for control of acute cellular
one chooses does not need to be limited to any one of the rejection in renal allograft recipients. Lancet 1997, 350,
possibilities listed here. A transplant pharmacist position 1193-1198.
can involve different combinations of these responsibil- 11. Brethauer, B.; Devine, B.; Jue, M.; Quan, D.; Louie, C.
Cost-benefit analysis of a clinical pharmacist’s presence on
ities and others, as necessary, tailored to the preferences
a post-liver transplant service. Hosp. Pharm. 2000,35 (1 l),
of the practitioner and the needs of the center. As
1197-1202.
transplantation of other organs becomes more attractive, 12. Vasquez, E.M.; Benedetti, E.; Pollak, R. Ethnic differ-
the need for qualified pharmacists as part of the transplant ences in clinical response to corticosteroid treatment of
team will continue to increase. The field of transplanta- acute renal allograft rejection. Transplantation 2001, 71,
tion provides numerous opportunities for pharmacists, 229 -23 3.
many of which can still be individualized to suit the 13. Zetterman, B.K.; Belle, S.H.; Hoofnagle, J.H.; Lawlor,
strengths and preferences of the practitioner. Of all the S.; Wei, Y.; Everhart, J.; Wiesner, R.H.; Lake, J.R. Age
reasons that demonstrate the need for transplant pharma- and liver transplantation. Transplantation 1998, 66, 500-
cists, none is as convincing as the needs of the patient. 506.
The patient’s needs define what roles are available to 14. Johnston, A.; Holt, D.W. Therapeutic drug monitoring of
immunosuppressant drugs. Br. J. Clin. Pharmacol. 1999,
pharmacists and how valuable those services are to the
47, 339-350.
transplant community and society in general.
15. Yatscott, R.W.; Aspeslet, L.J. The monitoring of immu-
nosuppressive drugs: A pharmacodynamic approach. Ther.
Drug Monit. 1998, 20, 459-463.
16. Anaizi, N. Drug interactions involving immunosuppressive
agents. Graft 2001, 4 , 232-247.
1. 2000 Annual Report. In U.S. Scientific Registry of 17. Levy, G.A. Long-term immunosuppression and drug
Transplant Recipients and the Organ Procurement and interactions. Liver Transplant 2001, 7, S53-S59.
75
18. Partovi, N.: Chan, W.; Nimmo, C.R. Evaluation of a 25. Swanson. M.A.; Palmeri, P.; Vossler, E D . ; Bartus, S.A.;
patient education program for solid organ transplant Hull, D.; Schweizer, R.T. Noncoinpliance in organ
patients. Can. J. Hosp. Phann. 1995, 48 (2), 72-78. transplant recipients. Pharmacothcrapy 1991, 11 ( h ) ,
19. Bittar, A.E.; Keitel, E.; Garcia, C.D.; Bruno, R.M.; 173s-174s.
Silviera, A.E.; Messias, A.; Garcia, V.D. Patient noncom- 26. Whiting, J.F.; Martin, I . ; Zavala, E.; Hanto, D. The in-
pliance as a cause of late kidney graft failurc. Transplant. fluence of clinical variables on hospital costs after ortho-
Roc. 1992, 24, 2720-2721. topic liver transplantation. Surgery 1
20. Dunn, J.; Golden, D.; Ran Buren, C.T.; Lewis, R.M.; 27. Kiedar, R.; Katz, P.; Nakache, R. “Living again”:
Lawen, J.; Kahan, B.D. Causes of graft loss beyond two Heterogcneous support group for transplant patients and
years i n the cyclosporine era. Transplantation 19 their families. Transplant. Proc. 2001, 33, 2930-293 1.
349-353. 28. McCashland, T.M. Posttrnnsplantation care: Role of the
21. Matas, A. Chronic rejection in renal transplants-risk transplant center. Liver
factors and correlates. Clin. Transplant. 1994, 8, 332-335.
22. Douglas, S.; Blixen, C.; Bartucci, M.R. Relationship 29. ay, D.K.; Gaber, L.W.;
between pretransplant noncompliance and posttransplant Gaber, A.Q. Randornizcd double-blind study of standard
outcoines in renal transplant recipients. J. Transplant versus low-dose OKT? induction therapy i n renal allograft
Coord. 1996, 6, 53-58. recipients. Am. J. Kidney Dis. 1993, 22 (I), 36-43.
23. Beck, D.E.; Fennell, R.S.; Yost. R.L.; Robinson, J.D.; 30. Hcbcrt, M.F.; Ascher, N.L.; Lake, J.R.; Emond, J.; Nikolai,
Geary, D.; Richards, G.A. Evaluation of an educational B.; Linna, J.; Roberts. J.P. Four-year follow-up of
programme on compliance with medication regimens in mycophciiolate moreti1 for
paediatric patients with renal transplants. J. Pediatr. 1980, recipients. Transplantation
96, 1094. 31. Sullivan, S.D.; Garrison, L.P.; Best, J.H. The cost
24. Rodin, G.; Abbey, S . Kidney Transplantation. In effectiveness of mycophenolate mofetil i n the first year
Psychiutric Aspects of‘ Organ Trunsplantation; Craven, after primary cadaveric transplant. U.S. renal transplant
J., Rodin, G.M., Eds.; Oxford University Press: Oxford, mycophcnolate moreti1 study group. J. Am. Soc. Nephrol.
1992; 145- 163. 1997, 8 (lo), 1592 1598.
PHARMACY PRACTICE ISSUES
E!S nv
Yasmin Khaliq
Rochester, Minnesota, U.S.A.
INTRODUCTION further emphasis on the need for accuracy and full ob-
jective disclosure regarding the proposed research. It is
The Tri-Council Policy Statement is a Canadian docu- important that the researcher maintain the right to pursue
ment that has been adopted, in 1998, as the standard of knowledge freely but with responsibility. This means en-
ethical conduct in Canada when performing research suring the highest scientific and ethical standards includ-
involving human subjects. It reflects the desire to promote ing honesty and accountability. The law regulates re-
research conducted according to the highest ethical stan- search standards with respect to areas such as privacy,
dards. The Policy was developed by three groups: the equality, property, and competence. With the continuing
Medical Research Council of Canada, the Natural advances in knowledge, technology, and areas of con-
Sciences and Engineering Research Council of Canada, troversy, ethics will likely play a role in defining the law
and the Social Sciences and Humanities Research in the future.
Council of Canada in an effort to aid and support re- The Policy acknowledges that principles and guide-
search in Canada. The three councils are aware that lines require flexibility and exceptions to the rule. There
issues regarding ethical conduct are complex and con- can be many approaches to an ethical problem and debate
tinually evolving and therefore intend to update this do- regarding the answers will likely always occur. This will
cument regularly. ensure continued thought and evolution in applying ethi-
cal principles to research with humans.
This summary of the Policy is divided into ten sections
similar to the original document: ethics review; free and
informed consent; privacy and confidentiality; conflict of
The Policy attempts to address the responsibilities of re- interest; inclusiodexclusion of populations; aboriginal
searchers, institutions, and Research Ethics Boards (REBs) peoples; clinical trials; human genetics research; research
to their subjects. Ethical principles are shared across di- involving human gametes, embryos, or fetuses; and hu-
sciplines such that subjects should expect equal rights as man tissue.
well as benefits and risks across all fields. The Policy
provides a framework of common procedures by which the
ethics review process may be standardized. The Policy ETHICS REVIE
continues to recognize the diversity of various fields, but
promotes the sharing of general ethical principles. Thus, Research requiring ethics review is that which includes
this document can lend itself to many areas. The Policy is living human subjects as well as human remains, ca-
not intended to address specific ethical dilemmas but to davers, tissues, biological fluids, embryos, or fetuses. The
provide guiding principles and standards as well as pro- REB is mandated by its institution to approve, reject,
mote thought regarding areas of controversy. modify, or terminate submitted research proposals to
The Policy describes ethics as using morally accept- be conducted within the institution or by its members.
able means to attain morally acceptable ends. Guiding The REB is to have five members: two with knowl-
principles are found in Table 1. It is critical that the edge in research, one in ethics, one in law (specifically
subjects’ interests are primary when conducting research, biomedical research), and one without affiliation to the
and that it is understood that benefit and harm are not institution who is from the community.
viewed by the subject in the same manner as the re- The exposure of a subject to minimal risk is thought to
searcher. Trust by the subject or hope for cure places be equivalent to that encountered in everyday life. Greater
Table 1 Guiding principles for ethics formed by the REB of the institution that employs the
researcher(s) as well as by any REB with jurisdiction over
0 Respect for human dignity
0 Respect for free and informed consent the location of the research.
0 Respect for vulnerable persons
Minimizing harm
0 Maximizing benefits
restricted or dependent subjects and under such circum- press their wishes in a meaningful way, e.g., children,
stances must be judged in context. patients with Alzheimer’s disease. Their dissent pre-
REB review is generally necessary for studies of cludes participation.
naturalistic observation. However, studies observing
participants in rallies, demonstrations, or meetings, for Research in Emergency Health Situations
example, do not require REB approval, although issues of
privacy must be considered. Research that is to be performed on an individual without
his or her consent is subject to all legislation and regu-
Informing Potential Subjects lations as pertinent, and may be allowed by the REB i f
Consent may not be obtained without full disclosure of all A serious threat exists requiring immediate interven-
information that may affect consent and an opportunity tion and research offers a possibility of benefit when
for discussion. Obtaining consent includes: no standard therapy exists.
* Risk is not greater than with standard care or that
Invitation. benefits justify risk.
Indication of the research purpose. * Third party authorization cannot be secured despite
Identity of the investigator(s). diligent efforts.
Nature of the study and time commitment. No prior directive by the subject is known to exist.
Procedures.
Foreseeable harms and benefits. This is an uncommon situation that may occur if a
Alternatives to the research or consequences of subject has lost consciousness or competence. Additional
nonparticipation. safeguards to protect the subject’s rights and interests
Assurance that one is free to not participate or may may include additional scientific/medical/REB consul-
decide at a later time or date. tation, procedures to identify subjects in advance to
obtain consent prior to occurrence of an emergent si-
The likelihood of publication of the findings and any tuation, monitoring procedures by safety boards, and
conflicts of interest by the investigators, institution, or careful REB review for assessment of harms and benefits
sponsors must be indicated. Other information may be of participation.
necessary to include for select projects, such as subject
responsibilities, confidentiality as to subject identity, and
anticipated use of the data.
and informed consent is necessary. REB approval is not society should bear an unfair share, nor be unfairly
necessary for access to public information or materials. excluded in research participation. Vulnerable subjects
REB approval requires consideration of the purpose and have been excluded to avoid the issue of exploitation yet
type of data, limits on its use, safeguards for confiden- have thus also been denied the potential benefits of
tiality, modes of observation that may identify the subject, participation. Researchers shall not exclude potential
anticipated secondary uses of the data, and anticipated research subjects based on culture, religion, race, mental
linkage with other data. Subjects must be informed who or physical disability, sexual orientation, ethnicity, gen-
will have access to any identifying information, e.g., go- der, or age, unless a valid reason applies. Women must
vernment or agencies, research sponsors, or the REB, and not be excluded on the basis of gender or reproductive
must provide consent for such access to occur. capacity although harms and benefits must be consid-
ered. Incompetent subjects must not be excluded from
econdary Use of Data research that may be beneficial to themselves or the group
they represent.
When data are used for purposes other than the research
for which they were collected, REB approval must be
sought if individuals are identifiable. Researchers must
O R I ~ I N A LPEOPLES
demonstrate that knowledge of the subjects’ identities is
necessary for the current use, that confidentiality will be
The aboriginal peoples are recognized as having a unique
maintained and that the involved individuals have not
culture and history and perspective in life. Research
objected. If deemed appropriate, the REB may require
regarding their customs and community has in some cases
either informed consent from those who contributed the
been respectful; however, there has also been inaccurate,
data, an appropriate strategy for informing subjects, or
insensitive research conducted causing stigmatization and
consultation with representatives of those who contributed
thus apprehension with respect to future research pro-
the data. REB approval is also required for situations
posals. Thought must be given to language differences
when a researcher wishes to contact individuals to whom
and different ideas about public and private life. Involve-
data refers. Linkage of databases where research subjects
ment of academic or community members from this group
may be identifiable requires REB approval.
is essential for appropriate ethics review. The needs and
concerns of the people along with respect for their pro-
perty, culture, traditions, and unique viewpoints must be
considered by investigators. The community must also be
given the opportunity to respond to findings prior to com-
With increasing concern for conflicts of interest, such
pletion of research reports.
issues must be identified by the researcher, institution, and
REB for professionalism, to maintain public trust, and for
accountability. All conflicts, whether actual, perceived, or
potential, must be disclosed to the REB and addressed.
They must also be disclosed to the subject during consent.
For the REB to identify and best address conflicts, it Clinical trials are addressed in the context of biomedical
should be provided with details of the research project, research. Research can include case studies, cohort stu-
budgets, commercial interests, consultative relationships, dies, randomized controlled trials, or multicenter trials.
and other information as relevant. REB members must While the methodology of these studies is greatly varied,
withdraw from the discussion and decision-making when the guiding ethical principles and procedures remain the
their own research is under review. Methods to address same. To begin research there must be clinical equipoise,
and resolve conflicts must be developed. REBs must be or a reasonable uncertainty warranting pursuit of an
given the authority and financial and administrative answer. Such an approach should ensure bias is mini-
independence from the institution to fulfill their duties. mized in all therapeutic arms and that participation is not
considered disadvantageous. Research is generally cate-
gorized into four phases as found in Table 3.
ULATlON Research with new medical devices must be carefully
evaluated to ensure free and informed consent can be
Choice of inclusion into research studies should follow obtained. REBs must aid researchers to prevent conflicts
the principle of distributive justice, i.e., no member in of interest. This could be concerning subject selection or
880 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans
I Dose-finding studies of new These studies warrant close REB review with continuous
medications to determine monitoring independent of the trial sponsor. This is especially
acute toxicity. important as more of these trials include patients refractory to
Healthy subjects or patients. standard therapy, and with the increasing number of new medications.
Unexpected adverse events are a major concern.
I1 Determination of short-term Phase I and I1 studies must be carefully examined for free and
pharmacologic toxicity, informed consent procedures. An independent continuous review
some degree of efficacy. may be necessary.
Patients with specific diseases.
I11 Determination of pharmacologic Phase I1 and I11 often include placebos to assess toxicity of a
efficacy to increase survival or new agent. Use of placebo must be justified and minimization of
quality of life, some toxicity. harm ensured.
Patients with specific diseases.
IV Determination of long-term efficacy These studies are often conducted in private practice for postmarketing
and toxicity of marketed drugs. with a per-capita fee paid to assess side effects and patient acceptance.
Postmarketing surveillance studies. Such payments can create bias. REBs must assess the science and ethics
of these studies as much as with the other phases.
payment by sponsors to the investigators. Safety stan- information will be used and interpreted are unknown,
dards of new devices must be assured. Continued pro- requiring prudence in pursuing research in genetics.
vision of therapy beyond the trial termination must also An individual may feel hisher identity and self-worth
be examined. are threatened, not to mention any associated stigma
If research is to be used for regulatory approval of a that may occur toward the group to which the indivi-
drug, the International Conference on Harmonization dual belongs.
(ICH) guidelines that have been adopted by Canada must Important considerations are as follows:
be followed. Budgets must be evaluated to ensure no
conflicts of interest exist. Placebo-controlled studies are Consent is critical in genetics research, and concern
not considered acceptable when effective standard the- that the individual’s family may be coercive and that
rapies or interventions are available. Investigators must information may affect other members in the family
inform subjects as to why placebos are necessary when should be considered.
used, and, if any treatment is to be withdrawn and the Results of genetic tests must be protected from any
associated impact. Although sponsors may obtain prelim- third party access unless free and informed consent
inary data for analysis, final analysis and interpretation is given. DNA banking allows family and clinical
should be by the researchers to ensure the accuracy and information as well as genetic material to be a re-
integrity of the work. source for other researchers; however, removal of
the subject’s and family’s identity is important. Any
potential harm must be disclosed to the REB as well
TICS RESEARCH as how it will be dealt with. For example, information
about an individual’s susceptibility to disease may
The study of genes that determine human traits is very provoke anxiety, particularly if effective therapy or
topical and not without controversy. Identification of prevention is not available.
genes that comprise the human genome, their function, Genetic counseling must be available for subjects as
and their ability to predict disease or a predisposition to needed. The issue of cultural differences in the per-
disease is central to this research. However, because ception of this research must be accounted for.
genetic material in one individual is shared by bio- Gene alteration, including gene therapy, using human
logical relatives, privacy and confidentiality affect not germline cells or embryos, is not considered ethically
just the individual who may wish to consent to research acceptable. Gene alteration done for therapeutic rea-
participation. The effects of such research and how sons and using human somatic cells may be considered.
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans 881
Pat Murray
Royal Edinburgh Hospital, Edinbwgh, U.K.
The committee, which is made up of the Chairs of six * To push forward the debate on specialist pharmacists.
Practice Interest Groups and four General Committee To promote and support research within the field of
members, oversees the main educational events described critical care.
in the programme. It has a challenging job in co-ordi-
nating the main symposia while seeking to be visionary,
ducation and Training
to ensure the content of future symposia will attract par-
ticipants some 12 months in advance of the planned event.
Training is a component of most jobs: many people are
There is much to do with the planning, implementa-
expected to teach others, but many have had little
tion and review of each programme, which attracts up to
guidance on how to perform this key activity successfully.
350 participants.
The Education and Training Group of UKCPA aims to
Practice Interest Groups reflect the broad range of
share and promote good practice in the field, and to
interest and experience among members and provide a
support these individuals in their role.
network of support among members by maintaining a data
Training sessions are organized, either as part of the full
base of members and their area of expertise. Each group
UKCPA symposia, or as ‘stand alone’ days. For example, a
regularly contributes to ‘In Practice,’ reviewing current
recent study day on the topical issue of competency-based
researcNdevelopments in their field and training oppor-
training was held. The group has also written a guide for
tunities. The groups comprise:
good practice in education and training, as a short practical
aide memoir for consideration when planning an edu-
Care of the Elderly
cational event. Commissioned resource guides in key areas
Critical Care
such as teaching communication skills and assessment
Education and Training
have also been published.
Medicines Management in Primary Care
Quality Assurance
Surgery and Theatres ement in Primary
Infection Management Care Group
Each group sends a message.
The Medicines Management in Primary Care Group was
Care of the Elderly formed four years ago to provide support for the in-
creasing number of pharmacists developing a clinical
The aim of the group is to enhance the pharmaceutical role in Primary Health Care Teams. The objectives are to:
care of elderly people, within both primary and secondary
care. It does this by facilitating the continuing education Provide education and training for pharmacists to de-
and networking of its members. velop clinical pharmacy in primary care.
The Group organizes study days, mini-symposia and Facilitate liaison between primary and secondary
workshops. Topics have included the pharmaceutical care care pharmacists.
of patients with stroke, dementia and osteoporosis plus a Encourage communication between all pharmacists
day on ophthalmological problems. working in this area by providing a forum for ex-
change of ideas.
Critical Care Group Promote innovation and encourage practically applic-
able research.
The Group provides support for all pharmacists who have
an interest in the field of critical care, which includes Recent workshops have included patient perspectives,
intensive care, high dependency and coronary care. The therapeutic topics including cardiovascular and gastro-
groups core objectives are: intestinal systems, medicine resource management, med-
ication review and pharmacist-led clinics.
To continue to provide regular, objective and high
quality educational meetings.
To provide supportive documentation, especially for
those new to the field.
To promote the role of the critical care pharmacist The QA group was formed in the early days of UKCPA
within a multi-disciplinary setting through a closer when intervention monitoring was the flavor. Since then,
liaison with the Intensive Care Society. the Group’s focus has broadened to address a whole range
UK Clinical Pharmacy ~ ~ ~ s o ~ i a t ~ o ~ 885
of issues which are general to all clinical pharmacists, cists have introduced successfully. It also reviews the
managers including those in Primary Care. surgical and anaesthetic literature.
Recent examples of workshop topics at our two an- The Group also has a directory of members that allows
nual UKCPA symposia included sessions on compliance/ pharmacists to contact specialists in a particular area for
concordance, PILs, off-label use of medicines, medica- advice or information.
lion errors and ADR reporting. For the future, clinical The Group would like to see a member from all 700 +
governance and all its implications are high on the hospitals within the UK ensuring all hospitals have access
agenda and, to paraphrase the definition, we intend to to best practice.
hclp.. . .create an environment in which pharmaceutical
care will flourish.
Roger L. Williams
US. Pharmacopeia, Rockville, Maryland, U.S.A.
Standards established by the United States Pharmacopeia As a pharmacopeial organization, USP has certain unique
(USP) are accepted worldwide as the highest assurance of characteristics:
the quality of medicines and other products used to im-
prove the health of the public. We discuss the devel-
Non-governmental with statutory recognition: USP
opment of the publication and the organization, and its
is the world’s leading nongovernmental phar-
current and future initiatives toward promotion of world-
macopeia. According to the Federal Food, Drug,
wide health.
and Cosmetic Act, USP standards are enforce-
able by the Food and Drug Administration
(FDA) for all drugs manufactured and sold in
or imported into the United States. The standards
The first Pharmacopoeia of the United States, published in are also officially recognized in many other
1820 by USP, was an important milestone in American countries.
medicine and pharmacy. It was a compendium of about Volunteers lead the way: USP achieves its goals
217 of the best understood drugs and drug preparations and through the contributions of volunteer experts re-
a lexicon of standard drug names. Three medical visio- presenting pharmacy, medicine, and other health-
naries-Lyman Spalding and Samuel Mitchill from New care professions, as well as science, academia, the
York and Jacob Bigelow from Boston-were largely res- U.S. government, the pharmaceutical industry,
ponsible for this work. They intended the Pharmacopeia to and consumer organizations. Volunteers constitute
accomplish a degree of drug standardization and to faci- USP’s membership, Board of Trustees, and scien-
litate communication between physicians and pharmacists. tific decision-making committees. They are sup-
Today, USP publishes more than 3400 official standards ported by a staff of over 350.
monographs for drugs and other healthcare products. Standards set by a participatory process: USP
standards are developed by an exceptional process
of public involvement. The process gives those
who manufacture, administer, regulate, and use
therapeutic products the opportunity to comment
According to Roger L. Williams, M.D., USP’s Executive on the development and revision of standards used
Vice-president and Chief Executive Officer, USP pursues to measure the quality of these products.
its mission to promote public health through multifacet- Role that expands beyond standards: Unlike most
ed activities: of the world’s major pharmacopeias, USP’s role
is not limited to the establishment of written
* Establishing and disseminating officially recognized and chemical pharmacopeial standards. USP also
standards of quality for therapeutic products. helps to monitor and prevent medication error
* Collecting information from practitioners to help re- problems through reporting programs for health-
duce and prevent medication errors. care professionals. The valuable information and
* Educating healthcare professionals and patients on feedback obtained through these programs en-
the appropriate use of therapeutics and improving the ables USP to enhance the accuracy and utility of
health of special populations worldwide. its standards.
Man~~act~res,
Associations
Pharmacopeias
Fig. 1 USP convention membership. ‘a2002 The United States Pharmacopeial Convention, Inc. All rights reserved. Used
with permission.
888 United States Pharrnacopeia
Fig. 2 USP standards development. ‘c 2000 The United States Pharmacopeial Convention, Inc. All rights reserved. Used
with permission.
United States Pharmaeopeia 8S9
that a dietary supplement represented as conforming to rigorously and collaboratively tested in USP, FDA. and
the specifications of an official compendium shall be industry laboratories (see Fig. 3). USP currently has
deemed misbranded if it fails to do so. more than 1250 pharmaceutical Reference Standards-
one of the world’s largest collections-and about 500
Pharmacopeial Forum new items under development.
plement Verification
-
Fig. 3 Reference standards process. C. The United States
ew Mon
Pharmacopeial Convention, Inc. All rights reserved. Used with Currently, there are no public standards for about 35%
permission. of drugs in the U.S. market. USP seeks to develop public
890 United States Pharmaeopeia
quality standards for all therapeutic products in the Approaches to assure equivalence of complex ac-
market, especially for the top 200 prescribed drug pro- tive ingredients, including botanicals and dietary
ducts and active pharmaceutical ingredients. Increased supplements.
cooperation is being obtained from the pharmaceutical The application of modern biopharmaceutic principles
industry for a program to prepare and publish proposed to assure the equivalent performance of immediate-
standards monographs for newly approved drugs and and modified-release drug products.
drug products six years before patent expires. Compounded drug formulations for special populations.
Packaging, labeling, nomenclature, and dosage form
characteristics for medicines to reduce medication
errors.
Standardized imprint coding for all solid oral dosage
USP, through its participation in the Pharmacopeial Dis- forms.
cussion Group (PDC), is working closely with the Euro- Methods research on botanical ingredients.
pean and Japanese Pharmacopoeias to explore the har- Compounding guidelines for veterinary extra-label use
monization of pharniacopeial standards for cxcipicnts, of medications.
microbiological testing, general methods of analysis, and Education and training programs for health profes-
methods of analysis for biotechnology-derived products. sionals to support the appropriate use of the USP-NF
Several general test methods have already been harmo- and expand its use.
nized. USP serves on Quality Expert Working Groups at
the International Conference on Harmonization (ICH). It
also works through the Pan American Health Organiza-
tion and with individual countries around the world to
ensure drug quality.
The USP Convention membership meets once cvery 5
years to discuss the areas of healthcarc in which USP
should bc involved. These quinquennial meetings help
to define USP’s strategic focus and priorities for a 5-
The USP Convention membership, at its April 2000 Quin- year period.
quennial Meeting, adopted reyolutions directing USP to USP conducts open meetings as needed to invite the
explore in the ncxt 5 years: views of interested parties on issues of current signific-
ance in the pharmaceutical industry and the nature of
e The impact of applied genomics on drug discovery and USP’s involvement with these issues. Notices of open
development and therapeutic applications. meetings are posted on USP’s web site at www.usp.org.
PHARMACY PRACTICE ISSUES
rent
atric
Gene
University at Buffalo, Buffalo, New York, U.S.A.
As early as 1982, the Centers for Disease Control and Universal precautions are intended to supplement standard
Prevention (CDC) began issuing precautions for the infection control procedures and rely on the use of pro-
handling and care of laboratory specimens from patients tective barriers such as gloves, goggles, facemasks, as well
infected with the human immunodeficiency virus (HIV- as proper safety conduct, such as hand washing, avoiding
1). The goal was to minimize the risk of exposure to recapping of needles, and proper disposal of medical waste.
infectious blood and blood-containing body fluids. Al- The concept of universal precautions is based on the
though it was previously recognized that blood and underlying assumption that blood and certain body fluids
hypodermic needles posed a significant risk to the from all patients is potentially infectious for HIV, hepatitis
healthcare worker, this issue moved to the forefront of B virus (HBV), hepatitis C virus (HCV), methicillin-resis-
clinical practice with the recognition of the HIV/AIDS tant Staphylococcus aweus (MRSA), or any other blood-
epidemic, when it became clear that healthcare workers borne pathogen. In this context, potentially infectious body
would be at increased risk for exposure to HIV-1 and fluids include: cerebrospinal fluid, vaginal secretions, se-
other blood-borne pathogens. In 1987, the CDC issued men, pleural fluid, peritoneal fluid, pericardial fluid, and
guidelines that were designed to minimize the risk of amniotic fluid.“,’01 Universal precautions do not apply to
HIV- 1 transmission in the healthcare setting. These body substances such as feces, sweat, tears, urine, human
guidelines have since become known as the “universal breast milk, vomitus, nasal secretions, sputum, or saliva
precautions.”“] Universal precautions became mandat- unless visibly bloody; but this in no way lessens the need
ory in 1991 with the passage of the Occupational for practicing standard infection control procedures.“”01
Safety and Health Administration (OSHA) Blood-Borne The term “healthcare worker” is very broad and refers to
Pathogens Standard, which required healthcare employ- any person whose activities involve contact with patients or
ers to establish, at minimum, an exposure control plan with blood or other body fluids from patients in a health-
and offer training to employee^.[^-^] Since their care ~ e t t i n g . [ ~ ~An~ ~“exposure”
~~’’~ that places a health-
introduction, there have been numerous modifications care worker at risk for HIV or other blood-borne pathogens
of these guidelines by the CDC, Public Health Service and requires consideration for post-exposure prophylaxis is
(PHS), and OSHA. These modifications incorporate defined as any percutaneous injury, contact with mucous
new scientific knowledge and address additional con- membrane or nonintact skin (i.e., chapped, abraded, or skin
cerns that have arisen in the area of occupational with dermatitis), or contact with intact skin when the
exposure^.[^-'^] Recently, the Public Health Service duration of contact is prolonged (i.e., several minutes or
interagency working group, comprised of members of greater) or extensive with blood, tissue, or body fluids.””
the CDC, Food and Drug Administration (FDA), and
NIH, issued updated guidelines that consolidate re-
commendations regarding the management of health-
care workers who have experienced occupational ex-
posure to blood and other body fluids that may contain Given the HIV/AIDS epidemic, in addition to the increase
HIV .[IO1 in other viral infections such as HBV and HCV, the need
to adopt some form of protective measures, and thus the Table 1 Factors associated with an increased or decreased risk
rationale for universal precautions, is clear. It has been of occupational HIV transmission following an exposure
suggested that there are three main reasons for applying Increased risk Decreased risk
universal precautions.["] The first stems from the in- of transmission of transmission
ability to test and identify every patient to discern if they
are infectious. Therefore, it is most prudent to assume that Exposure to large quantity Use of gloves
all patients are infectious and thus act accordingly. The of blood
second reason is psychological in nature and takes into Exposure occured during Mucous membrane
placement of needle into exposure
account human behavior and performance regarding
artery or vein
identification and labeling practices. Lastly, there are ad- Exposure occurred during Prompt initiation of
ministrative and legal reasons that embrace OSHA's invasive procedure post-exposure prophylaxis
mandate for employers to provide a safe working envi- Deep injury Intact skin exposure
ronment for employees. Visible blood on needle/object
Source with increased viral load
The true risk of transmission following occupational ex- fluid, concentrated virus in laboratory, and one case was
posure is difficult to determine due to the high rate of unspecified. This data may not represent the true num-
underreporting of exposures and the underlying risk of ber of occupational HIV infections, because not all
healthcare workers being infected with HIV- 1 outside of workers are evaluated for HIV infection following oc-
the workplace. However, one prospective study deter- cupational exposure, not all workers with occupation-
mined that a percutaneous exposure to HIV-infected al exposurehnfection are reported, and an estimated
blood is associated with a 0.3% risk of transmission."21 40% or more of needlestick injuries may go unreport-
The risk is lower after a mucous membrane exposure at ed."s-171 Needlestick injuries, whether a consequence of
0.09%.[121The risk associated with HIV transmission recapping or improper disposal techniques, continue to be
after skin exposure has not been precisely defined, be- a frequent and important mode of HIV e x p ~ s u r e . " ~A]
cause presently, no HCW enrolled in any prospective large prospective surveillance study, the CDC Coopera-
study has seroconverted following an isolated skin ex- tive Needlestick Study, found more than 80% of all
posure: nonetheless, the risk is thought to be less than exposures were related to needlestick injuries.[18] Sur-
for mucous membrane e ~ p o s u r e . " ~ The
" ~ ~ risk of HIV veillance data indicates laboratory technicians, followed
transmission following exposure to bodily fluids other by nurses and physicians, represent the most common
than blood, such as cerebrospinal fluid, vaginal secre- occupations associated with occupational HIV transmis-
tions, semen, pleural fluid, peritoneal fluid, pericardial s i ~ n . " ~Some
] have argued that universal precautions
fluid, and amniotic fluid is not presently known. Factors may not significantly decrease exposure, as a glove can-
that increase or decrease the risk of HIV transmission not prevent a needlestick injury. However, there is evi-
following an occupational exposure are listed in Table 1. dence that despite the ability of needles to pass through
The increased risk resulting from exposure to blood latex gloves, there may be a substantially lower blood
from terminally ill AIDS patients likely reflects an innocula associated with the use of latex gloves, per-
increased viral In these instances, it has been haps suggestive of a reduced likelihood of occupation-
suggested that the risk of HIV transmission exceeds al infection.[20'2']
0.3%, but the practical utility of using HIV titers from
source patients as a marker for transmission is unknown,
and a low HIV titer does not rule out the possibility of POST-EXPOSURE PROPHYLAXIS FOR HIV
HIV tran~mission."~]
As of June 1997, documented HIV seroconversion Post-exposure prophylaxis, or the administration of phar-
temporally associated with occupational HIV exposure macological agents with the intent of preventing occu-
was reported in 52 healthcare workers.["] Forty-seven pational HIV transmission after exposure, may be useful
cases involved exposure to HIV-infected blood, 45 ex- in certain circumstances. The decision to use post-expo-
posures were percutaneous in nature, and most involved sure prophylaxis is complex and depends on a number of
a hollow-bore needle (91%)."01 The remaining five important factors, which should be evaluated on an in-
cases involved exposure to HIV-infected bloody body dividual, case-by-case basis. This decision should take
Universal Precautions and ~ o s t - ~ x ~ o § ~u r~e o ~ ~for~ l a x ~ § 893
into account the nature of the exposure, including volume tential hazards in deciding treatment duration, potential
of blood or body fluid involved. source of exposure and adverse effects of antiretroviral agents. viral resistance,
risk of transmission, time between exposure and start of and pregnancy. Fig. 1 outlines general considerations and
post-exposure prophylaxis, and documented efficacy of procedures that should be followed after an occupational
post-exposure prophylaxis. The potential benefits of post- exposure. Note that the algorithm is a suggested approach
exposure prophylaxis must be weighed against the PO- and does not represent all possible scenarios; each ex-
Fig. 1 General schematic of the considerations and procedures following an occupational exposure. This algorithm serves only as a
suggested approach; although it reflects the PHS guidelines, it is not meant to replace published guidelines. In addition, this algorithm
does not apply to other types of infectious exposures, such as sexual exposures. For specifics, please refer to the text and to the Public
Health Service guidelines."']
894 Universal Precautions and Post-exposure Prophylaxis for HIV
posure needs to be individualized on a case-by-case basis. negative for virus at the time of exposure, with no clinical
Additionally, this algorithm only pertains to occupational manifestations of HIV infection, then no further testing of
exposures and not to exposures differing in nature, such as the source is needed."'] Inevitably, there will be occa-
sexual exposures. sions where the source is unknown. In these instances, the
Because evidence suggests that systemic infection does Public Health Service recommends assessing the risk for
not occur immediately following primary HIV exposure, HIV transmission and the need for post-exposure pro-
there appears to be a period of time in which initiation of phylaxis based on integration of the nature of exposure
post-exposure prophylaxis promptly after occupational and epidemiological information."']
exposure may prevent or inhibit systemic infection by li-
miting viral replication and proliferation. The consensus is
that post-exposure prophylaxis should, therefore, be ini-
tiated as soon as possible following exposure, ideally
within a few hours of exposure, because some animal data Although there are some data in animals, there is limited
show a reduction in post-exposure prophylaxis efficacy information available that can be used to assess the ef-
with delayed initiation.[22.231Post-exposure prophylaxis ficacy of post-exposure prophylaxis in humans. This is a
may be beneficial even up to 36 hour after exposure, but manifestation of the infrequent rate of seroconversion of
the efficacy of post-exposure prophylaxis given this late is healthcare workers following exposure to HIV-infected
largely undetermined. The optimal duration of post-expo- blood and makes it doubtful that a prospective study with
sure prophylaxis is unknown, but presently, the Public adequate statistical power could be performed. The notion
Health Service guidelines recommend a 4-week regimen of using zidovudine as post-exposure prophylaxis was
of zidovudine and lamivudine with or without a protease addressed by the CDC in 1990 and has been shown to be
inhibitor."'] beneficial by a retrospective case-controlled study, which
Following an occupational exposure, it is vital that documented the risk for HIV infection among healthcare
healthcare workers are cognizant of institutional policies workers who used zidovudine as post-exposure prophy-
and procedures to allow for the timely and organized col- laxis reduced by 81%.[6,141However, there are at least 14
lection of data and initiation of post-exposure prophylaxis instances of zidovudine post-exposure prophylaxis failure,
if indicated. Institutions must have policies and procedures and there is growing concern regarding transmission of
in place to react quickly to occupational exposure to avoid zidovudine-resistant virus, especially if the source pa-
unnecessary delays in therapy. The date and time, details tient's HIV treatment regimen included z i d ~ v u d i n e . " ' ~ ~ ~ ~
pertaining to the type of activity being performed, nature Despite the fact that zidovudine has been shown to be
of the exposure (type, amount, severity, percutaneous, effective in reducing perinatal transmission, it cannot be
mucous membrane, time of contact, condition of skin), concluded that it is effective in reducing occupational
and details about the source (HIV infected, viral load, exposure HIV transmission, because the occupational ex-
history of antiretroviral therapy) should be recorded in the posure route is not similar to the mother-to-infant route of
healthcare worker's medical record. It is recommended
that skin sites or wounds that are contaminated should be
washed with soap and water."'] The use of antiseptics
may be considered, but application of caustic substances PTI TH
such as bleach is not recommended, as this would com-
promise the integrity of the skin barrier. Mucous mem- Because the treatment of HIV infection is rapidly evolving
branes should be flushed extensively with water."'] and takes into consideration multiple issues such as viral
Following each occupational exposure, proper assess- resistance and optimal drug combination regimens, there is
ment of the risk for HIV transmission should be per- growing concern over which drug or drugs should be used
formed by qualified personnel. If at all possible, the as the standard for post-exposure prophylaxis. Presently,
source patient should be evaluated for HIV, HBV, and there are no data available to assess whether the addition of
HCV status to help rule out viral infection."'] Information other antiretrovirals to zidovudine enhances the efficacy of
pertaining to intravenous drug use and other source risk post-exposure prophylaxis regimens, or whether the in-
factors relevant for consideration of post-exposure pro- creased prevalence of zidovudine resistance is an import-
phylaxis should be sought. If this information is un- ant factor for post-exposure prophylaxis regimen selection
available, the source person should be notified of the and efficacy. The CDC states that zidovudine should be
incident and consent sought to facilitate testing for sero- considered for all post-exposure prophylaxis regimens,
logic evidence for viral infection. If the source is sero- because it is the only agent that data supports efficacy for
Universal Precautions and Post-exposure Prophylaxis for HIV 895
post-exposure prophylaxis. Lamivudine should usually with zidovudine for treatment of HIV.[261The addition
be added for increased antiretroviral activity and acti- of protease inhibitor drugs such as indinavir, nelfinavir,
vity versus zidovudine-resistant viral strains."] The cur- and efavirenz are generally reserved for an expanded
rent Public Health Service guidelines maintain that it is post-exposure prophylaxis regimen following high-risk
reasonable to continue zidovudine as the drug of choice exposures in lieu of their additional toxicity and drug
in post-exposure prophylaxis regimens, and there has interactions. Nonnucleoside reverse transcriptase inhibi-
been no additional information to suggest altering lami- tors such as delavirdine and nevirapine are generally
vudine as the second agent for post-exposure prophyla- not included in post-exposure prophylaxis regimens.
xis."o1 Table 2 lists the commonly used antiretroviral The use of any drug, even as a prophylactic measure,
agents in post-exposure prophylaxis regimens, along may be associated with adverse effects. Adverse effects
with the usual dose and expected adverse effects. Other of antiretroviral medications are well-described in the
nucleoside reverse transcriptase inhibitors (NRTIs) that HIV population; however, there is sparse data about ad-
may be used with zidovudine for post-exposure pro- verse effects in the non-HIV-infected individuals. Be-
phylaxis are didanosine and zalcitabine, resulting large- tween October of 1996 and December of 1998, an HIV
ly from documented efficacy and use in combination post-exposure prophylaxis registry prospectively followed
healthcare workers receibing post-exposure prophylaxis Table 3 Available resources and registries for HIV
following occupational exposure and monitored them for post-exposure prophylaxis
adverse effects.[271Of the 250 healthcare workers who
Resource or registry Contact information"
completed a post-exposure prophylaxis regimen, and for
whom follow-up data was available, 76% reported some Centers for Disease Telephone: (404) 639-6425
symptoms or adverse events.'271 The most frequently re- Control (For reporting HIV
ported symptoms were nausea (57%), fatigue/malaise seroconversion in HCWs that
(38%), headache (IS%), vomiting (16%), and diarrhea received postexposure
(14%). Minor laboratory abnormalities were reported in prophylaxis)
or www.cdc.gov1hiv
8% of healthcare workers.[271Of those healthcare workers
(for general information)
who discontinued all post-exposure prophylaxis drugs. National Clinicians' Telephone: (888) 448-4911;
50% cited symptoms or adverse effects as the reason for Postexposure Hotline (888) 737-4448;
disc~ntinuation.[~~] (888) PEP4HIV
Little is known regarding the potential effects of an- Food and Drug Telephone: (800) 322-1088
tiretroviral drugs on the developing fetus. Although Administration (For reporting unusual or
carcinogencity or mutagenicty is evident in screening severe toxicity from PEP
tests for zidovudine and all other FDA-licensed NRTIs, regimens)
limited data on zidovudine use in the second or third Antiretroviral Telephone: (800) 258-4263
trimesters of pregnancy was not associated with serious Pregnancy Registry
adverse effects."' 25' Whether lamivudine is teratogenic UCSF On-line http:llarvdb.ucsf.edu
information (For information about
is unknown.['] This complicates the decision to provide
antiretroviral drugs)
post-exposure prophylaxis to pregnant women: however, National HIV/AIDS http:llwww.ucsf.edu/hivcntr
pregnancy should not preclude the use of optimal post- Clinician's Consultation
exposure prophylaxis, and post-exposure prophylaxis Center
should not be denied to a healthcare worker solely on HIVIAIDS Treatment http:/lwww.hivatis.org
the basis of pregnancy."" In these situations, the patient Information Service (ATIS) Telephone: (800) 448-0440
shall reserve the right to decline post-exposure prophy-
"Contact information is subject to change.
laxis after they have been informed about the risk of HIV
transmission given the nature of the exposure, limited
data regarding teratogenicity in various trimesters of preg- There are numerous factors to consider before and after
nancy, and the risks versus benefits of post-exposure pro- initiation of a post-exposure prophylaxis regimen, which
hylaxis therapy. may lead to providers and educators feeling overwhelmed
The impact that an occupational exposure can inflict on and unsure about some choices that need to be made. To
a healthcare worker and their family is enormous. Health- facilitate this process, Table 3 lists some available re-
care workers should receive post-exposure counseling and sources and registries that one may contact to aid in the
education. along with a detailed synopsis of what events decision process.
the healthcare worker may expect, including the need for
follow-up HIV antibody testing. Additionally, facts about
the risk for transmission and other issues such as the
choice, efficacy. adverse effects, and adherence of post-
exposure prophylaxis medications should be discussed. The practice of universal precautions is Federal Law in
Additionally, the possible need for sexual abstinence the United States, and it is the responsibility of every
or use of a condom to prevent secondary transmission to employer or institution that healthcare workers have the
their partners should be addressed in a manner allowing resources and training necessary to adhere to these safety
for questioning and feedback. Organ dysfunction, concur- precautions.[21 Additionally, support for continued prac-
rent disease states, and other medications the healthcare tice of universal precautions needs to come from all levels
worker was previously taking on a regular basis, and the of administration. Observations by Gershon et al. indicate
potential for drug interactions with post-exposure prophy- that one of the strongest correlates with compliance is the
laxis medications must be considered. Exposed healthcare institutional "safety climate.' '[''I This implies that if
workers should be reminded to refrain from donation of healthcare workers perceive their work environment to be
blood. plasma. organs, tissue. and semen donation, and conducive to practicing universal precautions, then they
to temporarily discontinue breastfeeding."'] will be more likely to do so.
Universal Precautions and Post-exposure Prophylaxis for HIV 897
Each occupational exposure needs to be considered on 7. Centers for Disease Control. Recommendations for pre-
a case-by-case basis. The risk of occupational HIV trans- venting transmission of human immunodeficiency virus
mission appears to be greatest if the exposure is percu- and hepatitis B virus to patients during exposure-prone
taneous in nature. In order to optimize post-exposure invasive procedure. Morb. Mort. Wkly. Rep. 1991, 40
(RR08), 1-9.
prophylaxis, the duration between exposure and initiation
8. Center for Disease Control. Provisional public health ser-
of therapy must be kept at a minimum: preferably within a vice recommendations for chemoprophylaxis after occu-
few hours. Despite the concern of viral resistance, post- pational exposurre to HIV. Morb. Mort. Wkly. Rep. 1996,
exposure prophylaxis regimens should include 4 weeks of 45 (22), 468-472.
zidovudine plus lamivudine, and under certain circum- 9. Centers for Disease Control. Guideline for infection con-
stances, a protease inhibitor. trol in health care personnel, 1998. Am. J. Infect. Control
Although the focus of this discussion emphasizes HIV 1998, 26, 289-354.
infection, healthcare workers must be aware that other 10. Centers for Disease Control. Public health service guide-
blood-borne pathogens such as HBV and HCV may also lines for the management of healthcare worker exposures
be of significant concern. The healthcare worker is en- to HIV and recommendations for post-exposure prop-
couraged to refer to alternative references for more de- hylaxis. Morb. Mort. Wkly. Rep. 1998, 47 (RR-7), 1-
28.
tailed discussions pertaining to these infection^.[^*'^^'
11. Hopkins, C.C. Implementation of universal blood and body
Unfortunately, healthcare worker exposure to infec- fluid precautions. Infect. Dis. Clin. North Am. 1989, 3 (4),
tious blood and body fluids will continue to be a reality. 747 762.
-
Hopefully, with the practice of basic infection control in 12. Ippolito, 6.; Puro, V.;De Carli, G. The Italian study
conjunction with universal precautions, this can be kept group on occupational risk of HIV infection. The risk of
at a minimum. Universal precautions will likely be an occupational human immunodeficiency virus infection in
evolving process considering the increased prevalence of health care workers. Arch. Intern. Med. 1993. 153, 1451-
viral resistance, and the continued emergence of new, 1458.
and more difficult to treat infectious entities. 13. Fahey, B.J.; Koziol, D.E.; Banks, S.M.; Henderson, D.K.
Frequency of nonparenteral occupational exposures to
blood and body fluids before and after universal precau-
tions training. Am. J. Med. 1991, 90, 145-153.
RE 14. Cardo, D.M.; Culver, D.H.; Ciesielski, C.A., et al. A case-
control study of HIV seroconversion in health care workers
1. Centers for Disease Control. Recommendations for pre- after percutaneous exposure. N. Engl. J. Med. 1997. 337,
vention of HIV transmission in healthcare settings. Morb. 1485-1490.
Mort. Wkly. Rep. 1987, 36 (Suppl. 2S), 1s- 18s. 15. Gershon, R.R.M.; Karkashian, C.; Felknor, S. Universal
2. Occupational Safety and Health Administration. Occupa- precautions: An update. Heart Lung 1994. 23 (4), 352-
tional exposure to bloodborne pathogen: Final rule. Fed. 358.
Regist. 1991, 56, 64004-640182. 16. Mangione, C.M.; Cerberding, J.L.; Cummings, S.R. Oc-
3. DeJoy, D.M.; Gershon, R.R.M.; Murphy, L.R.; Wilson, cupational exposure to HIV: Frequency and rates of
M.G. A work-systems analysis of compliance with univer- underreporting of percutaneous and mucocutaneous expo-
sal precautions among health care workers. Health Educ. sures by medical house staff. Am. J. Med. 1991, 90,
Q. 1996, 23 (2), 159-174. 85-90.
4. Center for Disease Control. Update: Universal precautions 17. Hamory, B. Underreporting of needlestick injuries in a
for prevention of transmission of HIV, HBV, and other university hospital. Am. J. Infect. Control 1983, I 1 (3),
blood-borne pathogens in health care workers. Morb. Mort. 174- 177, Centers for Disease Control and Prevention.
Wkly. Rep. 1988, 37, 229-234. HIV/AIDS Surveill. Rep. 1993, 5 (no.3), 13.
5. Centers for Disease Control. Guidelines of prevention of 18. Centers for Disease Control Cooperative Needlestick
transmission of human immunodeficiency virus and hepa- Surveillance Group. Surveillance of health care workers
titis B virus to healthcare and public-safety workers. A exposed to blood from patients infected with human im-
Response to P.L. 100-607. The Health Omnibus Programs munodeficiency virus. N. Engl. J. Med. 1988. 319, 11 18-
Extension Act of 1988. Morb. Mort. Wkly. Rep. 1989, 38 1123.
(S-6), 3-37. 19. Centers for Disease Control and Prevention. HIV/AIDS
6. Centers for Disease Control. Public Health Service state- Surveill. Rep. 1993, 5 (3), 13.
ment on management of occupational exposure to human 20. Wollowine, J.; Mast, S.; Gerberding, J. Factors Influ-
immunodeficiency virus, including considerations regard- encing Needlestick Infectivity and Decontamination
ing zidovudine post-exposure use. Morb. Mort. Wkly. Rep. Efficacy: An ex vivo Model. In 32nd Interscience Con-
1990, 39 (RR-l), 1-14. ference on Antimicrobial Agents and Chemotherapy,
898 Universal Precautions and Post-exposure Prophylaxis for HYV
Aizalzeirn, CA, American Society for Microbiology, 1992, 25. Connor, E.M.; Sperling, R.S.; Gelber, R., et al. Reduction
Abstract 11 88. of maternal-infant transmission of human immunodefi-
21. Mast, S.; Gerberding, J. Factors predicting infectivity fol- ciency virus type 1 with zidovudine treatment. N. Engl. J.
lowing needlestick exposure to HIV: An in vitro model. Med. 1994, 331, 1173-1180.
Clin. Rcs. 1991; 39, 58A. 26. Center for Disease Control. Guidelines for the use of
22. Martin, L.N.; Murphy-Corb, M.; Soike, K.F.; Davison- antiretroviral agents in HIV-infected adults and adoles-
Fairbum, B.; Baskin, G.B. Effects of initiation of 3’-azido, cents. Morb. Mort. Wkly. Rep. 1997, 175, 1051-1055.
3’deoxythmidine (zidovudine) treatment at different times 27. http://www.cdc.gov/ncido/hip/3lood/PEPRegistry.pdf
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ficiency virus. J. Infect. Dis. 1993, 168, 825-835. 28. Center for Disease Control. Immunization of healthcare
23. Shih, C.-C.; Kaneshima; H.; Rabin, L., et al. Post-exposure workers. Recommendations of the Advisory Committee on
prophylaxis with zidovudine suppresses human immu- Immunization Practices (ACIP) and the Hospital Infection
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time-dependent manner. J. Infect. Dis. 1991,163,625- 627. Mort. Wkly. Rep. 1997, 46, RR-18.
24. Tokars, J.1.; Marcus, R.; Culver, D.H., et al. Surveillance 29. Centers for Disease Control. Recommendation for preven-
of HIV infection and zidovudine use among health care tion and control of hepatitis C virus (HCV) infection and
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blood. Arch. Intern. Med. 1993, 118, 913-919. 1998, 4 7 (RRlg), 1--39.
DISTINGUISHED PERSONALITIES
Charles Walton has contributed substantially to the Charles Anthony Walton was born on April 3, 1926, in
development and maturation of clinical pharmacy. Auburn, Alabama, but was raised in Tallassee, which is
Among his most important contributions were the de- 35 miles northeast of Montgomery. He recalls how
velopment of drug information, the introduction of ra- people passing through his hometown accused the city
tional therapeutics into the pharmacy curriculum. and his fathers of leaving out the “ha” in spelling the name of
strong advocacy for a sustained clinical practicum as their town. Tallasseeans, according to Walton, are a noble
an essential component i n the training of competent cli- people and would tell such critics that they needed to
nical pharmacists. c: is regarded by many in the dis- travel further south into the panhandle of Florida if it was
cipline as the father or drug information training and one laughter they wanted.
of the founding fathers of the American College of Cli- Walton‘s interest in pharmacy began when he was a
nical Pharmacy. young lad and an avid listener of radio. Television had
899
900 Walton, Charles
not yet been invented. Walton was particularly interested ship. They were so enthusiastic and passionate about their
in radio commercials and some of their dramatic claims. ideas that often they would work well into the early
He remembers one mellifluous radio announcer saying morning hours generating new concepts and crafting plans
“Take Sal Hapitica for the smile of health and brush to expand the mission of pharmacy. These late-night
with Ipana for the smile of beauty.” But what really meetings were charged with so much creative energy that,
piqued his interest in drugs was the radio commercial the next days, neither man felt tired, but instead longed to
that advertised Carter’s Little Liver Pills. He found it in- get back together to continue their stimulating discus-
credible that such a small, round pill could produce such sions. Walton recalls one occasion when Parker invited
extraordinary and wonderful outcomes. In fact, he was him to his Lexington home to explore the idea of training
so intrigued with commercials that he decided that when pharmacists to provide rational drug information to hos-
he grew up he would pursue either a career in radio an- pital formulary committees and to physicians taking care
nouncing or in the study of drugs. His Southern drawl, of patients in the hospital. They worked tirelessly during
however, pretty much excluded a career in radio. the night, drafting a concept paper that outlined the es-
After graduating from Tallassee High School, Walton tablishment of a hospital pharmacy service that would be
enlisted in the United States Navy and served two years dedicated to the advancement of rational therapeutics.
during the Second World War. After completing his They called the new service initiative drug information.
tour of duty in the Navy, he enrolled as a freshman at They knew that their idea would be popular with the
Auburn University, where he would later study pharmacy. medical school’s chairman of medicine, Ed Pellegrino,
He was a good student of pharmacy and his interest and because Pellegrino was a pioneer and national leader in
curiosity in pharmacology continued to grow. However, the teaching and practice of rational drug therapy. A key
the faculty did not readily encourage his enthusiasm and development in the concept came about with the hiring of
desire to do postgraduate work in pharmacology and David Burkholder as the first director of the drug in-
suggested instead that he enter pharmacy practice where formation center. Working together, Burkholder and Pel-
he could earn a decent living. But there was one faculty legrino developed the first hospital formulary that was
member who learned of Walton’s desire to continue his based entirely on the principles of rational therapeutics.
education and pursue a graduate degree in pharmacology. (Today, we refer to rational therapeutics as evidenced-
She had a master’s degree in hospital pharmacy from based medicine.) The major underlying principle is that
Purdue University, and she alone urged Walton to follow no drug should be used in the hospital setting that has not
his dreams and enter graduate school. He did just that. been proven in proper studies to be safe and more effec-
After one year at Purdue, Walton was awarded a master of tive than alternative therapies.
science degree in pharmacology, and in 1950 he accepted The idea of melding drug information with pharmacists
a faculty position at the University of Kentucky School of monitoring drug therapy at the patient’s bedside came
Pharmacy in Louisville. from a drug information conference held in the early
Later on Walton took advantage of a part-time sab- 1960s at the Carnahan House, located on a horse farm
batical to begin work on a Ph.D. degree in pharmacology near Lexington. The conference was sponsored by the
at Purdue. He completed the program in 1956. Shortly American Society of Hospital Pharmacists (ASHP). At
after that, the University of Kentucky School of Pharmacy that conference, William Smith presented the so-called
moved to Lexington, and, in 1960, opened a medical ‘‘9th floor project” being conducted at the University of
school on this new Lexington campus. The presence of a California at §an Francisco. The marriage of drug in-
medical school on the same campus as the pharmacy formation to hospital pharmacists working at the bedside
school led Walton to dream about training pharmacy and gave birth to a new concept in pharmacy that the con-
medical students in the same educational environment. He ference delegates referred to as clinical pharmacy. Those
presented his idea to the two deans. The dean of the representing ASHP at the conference expressed some
medical school supported the idea, but the dean of the concern that a new competing organization might emerge.
pharmacy school had some reservations, and so Walton’s The conference attendees toyed with the idea of establish-
dream was temporarily suspended. ing an association of clinical therapologists. A delegate
Walton may have been dismayed but he was not from Canada quickly moved that the organization be
distracted. He soon became acquainted with the Director named the International Association of Clinical Therapo-
of Hospital Pharmacy at the University of Kentucky logists (IACT ). It was all in jest.
Medical Center-a very bright and energetic young man Walton became the director of the hospital pharmacy’s
who had some novel ideas of his own. Charles Walton and Drug Information Center in 1967. He also started working
Paul Parker rapidly developed a strong collegial relation- more closely with the hospital pharmacy residency pro-
Walton, Charles 901
gram directed by Paul Parker. He continued his tcaching faculty to help build the Pharm.11. program at Texas. The
of pharmacology in the pharmacy school but with a new program contained a strong didactic background in
different slant, incorporating in his lectures the principles the biomedical sciences and provided expericntial training
of rational therapeutics. At that time, James Doluisio, who in medicine, pediatrics, psychiatry, ambulatory care, and
had recently joined the pharmacy school faculty at the drug information.
University of Kentucky, was serving as chairman of the Walton strongly insisted that pharmacists engaged in
curriculum committee. Doluisio had been a key player in therapeutic decision making and pharmacothcrapy con-
thc development of the Pharm.D. Program at the sultations had to bc well-traincd clinicians who were
Philadelphia Collegc of Pharmacy and Science. Walton directly involvcd in the management of patients. The
was asked to chair a committee to develop a doctor of founders of thc American College of Clinical Pharmacy
pharmacy program at Kentucky. Working closely with (ACCP) were strongly influenced by Walton’s philosophy
Doluisio and Parkcr, Walton’s committee successfully on what constitutes a credible clinical pharmacy practi-
established a strong post-baccalaureate Pharm.D. program tioner as they dcvcloped the mission, goals, and purpose
dccply rooted in rational therapeutics and including a of the organization. In fact, Walton played a prominent
sustained clinical practicum through the hospital phar- role in the early development of the College not only as
macy residency program. Walton’s dream of pharmacy a source of encouragement, wisdom, and guidance but
students being educated and trained alongside medical also by serving ACCP as an advocate before the phar-
students had finally become a rcality. macy academy, particularly the American Association of
In 1973, Doluisio became Dean at the University of Colleges of Pharmacy. The major impetus of ACCP was
Tcxas College of Pharmacy in Austin. One of his first to strive for excellence. The new organization was cri-
administrative dccisions was to hirc Walton to develop a ticized by some as being composed of elitists. When
Pharm.D. program in Texas. Because there was no med- questioned about this, Walton said, “If striving for ex-
ical school in Austin, Doluisio negotiated an agrcement cellence makes me an elitist, then I am an elitist.” Be-
with the University of Texas Health Science Center in San cause of his important contributions to the development
Antonio to establish a jointly administered post-bacca- of the ACCP, Walton was inducted as the first honorary
laureate Pharm.D. degree program. And, because there fcllow of the College.
was no existing hospital pharmacy residency program at Charles Walton will forever be admired for his
the hcalth science center in San Antonio, a one-year sus- intellect, his humor, his wisdom, and his passion for
tained clinical practicum was incorporated as part of the excellence. To thc pioneers in clinical pharmacy and to
academic program. Walton was appointed associate dean many of those who followed in their footstcps, Charles
for clinical programs and recruited a young, dedicated Anthony Walton is a hero and bcloved friend.
DISTINGUISHED PERSONALITIES
pharmacy curriculum and to introduce medical students sisted international pharmacy leaders from scveral
and faculty to clinical pharniacists. countries in the design and implementation of clinical
relentless in his belief that clinically prepared pharmacists pharmacy programs. Throughout the late 1970’s and
could substantially improve the quality of hcalth care. 1980’s, Weaver served as an educational consultant
Under his leadership, in 1981 the Pharm.D. curriculum and advisor to numerous countries including
expanded from a two-year post B.S. program to a six-year University, Royal Danish Collcgc of Pharmacy, Wclsh
Pharm.D. degree. Weaver fclt that the curriculum should School of Pharmacy, Universities in Cairo, Tanta, Nai-
be designed to increase the clinical skills of all cntry- robi, Zimbabwe, Republic of South Africa, Amman Jor-
level pharmacists. The new curriculum featured courses dan, and the University of Sains Malaysia. In his role as
in pharmacokinctics and biopharmaceutics, as well as a Education Advisor to the University of Riyadh, Saudi
pathophysiology and therapeutics course sequence taught Arabia, Weaver assisted in the conversion of the cur-
for the first time entirely by clinical pharmacy faculty. riculum from the Europcan System to the credit system
Larry, as he is known by the thousands of students he and to the use of English as the language for teaching in
taught and mentored, brought a vision of improvcd pa- pharmacy. He worked with Saudi faculty to cstablish cli-
tient care through clinical pharmacy service that inspired nical pharmacy courses and initiated the first continuing
students and clinical faculty for over three decades. cducation program in pharmacy.
After 18 years as the Pharmacy Dcan, Weaver left Larry Weaver is one of pharmacy’s most well res-
academia to become the Vice President of Professional pected leaders due to his endless efforts to establish
Relations for the Pharmaceutical Manufacturers Asso- clinical pharmacy as the standard for American pharmacy
ciation (PMA). In his role as the Executive Director of education. He served in leadcrship roles including Pre-
the PMA Commission for Rarc Diseases, he championed sident and Vice President of both the Academy of Phar-
the goal of making orphan drugs available to patients maceutical Sciences of the APhA and the American
throughout the world who suffer from rare diseases. His Association of Colleges of Pharmacy. Hc also served as a
efforts have resulted in over 800 drugs, serums, and vac- member of first Board of Trustees of the Research
cines being designated as “orphans” by thc Food and Institute for the American College of Clinical Pharmacy.
Drug Administration. His continued efforts to help those
in need of orphan drugs required interaction with federal
agencies, pharmaceutical firms, researchers, practitioncrs,
and patients and their families. He has been described as a
peacemaker and a matchmaker who can bring industry, In 1994, Weaver was summoned back to the Deanship of
academia, and families together. the College of Pharmacy at the University of
He served in this capacity for two years and directed the
implementation of the new entry level Phar1n.D. curri-
culum. Since 1996, Dean Emeritus Lawrence C. Weaver
has been a mcmbcr of the Peters Institute of Pharmaceu-
tical Care, developing educational and rescarch programs
Larry Weaver is recogniad around the world for his in pharmaceutical care practice. Larry Weaver has had a
leaderrhip and advocacy for clinical pharmacy. He as- distinguished career in pharmacy.
PROFESSIONAL ORGANIZATIONS
ti
Patrice Trouiiler
University Hospital of Grenoble, Grenoble, France
MISSIONS
The World Health Organization (WHO) is a United Na- With 193 member states currently, WHO has a constitu-
tions specialized agency, which has 193 member coun- tional mandate to direct and coordinate international ef-
tries. Its objective is the attainment by all people of the forts in relation to health, to promote technical coopera-
highest possible level of health. WHO has four main tion among nations, to develop and transfer appropriate
constitutional functions: to act as the directing and co- health technology, and to set global standards for health.
operating authority on international health issues; to pro- Finally its overall mission is the ‘‘attainment by all people
vide assistance including maintaining epidemiological of the highest possible level of health,” with special em-
and statistic services; to promote research; and to develop phasis on closing the gaps within and among countries.
and promote international norms or standards. The work According to WHO, health is defined as “a state of com-
of WHO is carried out by the World Health Assembly, the plete physical, mental, and social well-being and not
Executive Board, the Secretariat, and six regional offices. merely the absence of disease or infirmity.” This ambi-
tious and idealistic objective was summarized by the
slogan ‘-Health for All by the Year 2000.’”’] In spite of
major achievements (e.g., smallpox eradication declared
in 1980; polio and guinea-worm disease on the threshold
of eradication; leprosy, lymphatic filariasis and neonatal
The origin of WHO dates from the need for international tetanus targeted for elimination), this “health for all”
preventive and control measures against epidemics such objective is currently challenged by the spread of the
as cholera and plague, particularly in the European region, HIV/AIDS pandemic; by the persistence of malaria and
during the nineteenth century. Later, different cooperation many other parasitic diseases; by tuberculosis, which is
arrangements were adopted and the International Agency still a major health priority since 1948; and increasing gap
for Public Hygiene was established in Paris (1907) to between least developing and developed countries (e.g.,
control epidemics and communicable diseases. Later the average life expectancy is 38.5 in Zambia and 79.5 in
Health Organization of the League of Nations was set up Sweden; 2 million children die each year from diseases
in Geneva (1919). During the San Francisco Conference, for which vaccines exist; etc.), and the growing impact of
which laid the foundations for the United Nations Orga- globalization on health issues.r21
nization (1945), it was decided to establish a permanent To carry out its missions, WHO is endowed with a
and autonomous international organization for health is- decentralized system including a central office (the Ge-
sues. In June 1946, an international health conference neva headquarters) and six regional offices. At the central
convened in New York by the UN Secretariat approved level, the World Health Assembly (WHA). a deliberating
the creation of WHO. Its specific Constitution, following body which represents the 193 member states, sets the
a ratification by 61 states, was set into place on April 7, policy, approves the budget, and passes agreements or
1948 (now marked as World Health Day). WHO, once the conventions (to be adapted by the member states). In ad-
main player, is now one of many UN and other orga- dition, it can issue international health regulations for
nizations or institutions concerned with health. The World technical matters (WHO normative functions) directly
Bank plays an increased financial and technical role, bi- and compulsorily applicable to member states. The WHA
lateral agencies and the private sector as well, such as the elects the Executive Board composed of 32 members and
non governmental organizations, make significant con- appoints a Director-General (DG) to give effect to the
tributions to international health.“’ decisions and policies of the Health Assembly and to
advise it. At the decentralized level, six regional offices tions if a national authority so desires, or they may form
have been created by the A to take local specificities the basis of national standards and technical regulations.
into account.
The funding for WHO comes from member countries clivi
and dues are based on their national economies and as
well on extra-budgetary funds allocated by countries or In support of its objectives, WHO develops a wide range
institutions earmarked for specific purposes or projects. of operational activities to provide appropriate technical
The total budget for W 0 was about $1.3 billion in 2000, assistance, to stimulate and advance work on prevention
and this amount has not increased in recent years despite and control of epidemic, endemic, and other diseases, and
increased demands on the organization. One problem has to cooperate with governments for strengthening health
been the persistent failure of some major funders to fully services. WHO works closely with other UN organiza-
pay their assessed dues and the fluctuation in member tions or programs [e.g., Food and Agricultural Organiza-
states’ voluntary contributions. tion (FAO), United Nations Children’s Fund (UNICEF),
United Nations Development Program (UNDP), and the
World Bank], and maintains working relationships with
bilateral agencies and intergovernmental and nongovern-
mental organizations (NGOs). In addition, nearly 1200
ar 8 health-related institutions are officially designated as
WHO collaborating centers. More than 50 affect the phar-
According to articles 2 and 21 of its Constitution, WHO maceutical sector, such as the Uppsala Monitoring Center
has a regulatory power for developing, establishing, and for pharmacovigilance issues.
promoting standards and nomenclature (International
Health Regulations). These regulations are limited to Communicable diseases
technical matters: health and international quarantine re-
gulations; health codification for international travels: in- Approximately, 56 million people died in 1999, of which
ternational nomenclature of diseases; nomenclature and 14 million died from infectious and parasitic diseases with
standards with respect to the safety, quality, and efficacy more than 90% occurring in developing countries. (In rank
for pharmaceutical, biological, and similar substances, order: acute lower respiratory infections, HIVIAIDS, di-
including their advertising and labeling: international arrhea, tuberculosis. malaria, measles.) To prevent and
standards for biological; international cooperation for control them, WHO developed and launched activities and
health statistics; food standards (through the joint WHO/ programs in the field such as the Expanded Programme on
F A 0 “Codex Alimentarius’’ Commission); and depend- Immunization (EPI) in collaboration with UNICEF (EPI
ence and misuse of drugs regulations. targets are poliomyelitis, measles, diphtheria, whooping
Numerous matters related to public health and bio- cough. tetanus and tuberculosis); the Onchocerciasis Con-
medical sciences can be the subject of Recommendations trol Programme; the global programs on AIDS; the “Roll
but without compulsory nature contrary to international Back Malaria” program; the Africa 2000 Initiative on
regulations. WHO Recommendations may be endorsed by water supply and sanitation issues; and others.
the WHA under article 23 or by the Executive
issued as resolutions (e.g., WHA 52.19 Resolu Noncommunicable diseases
revised drug strategy, 1999).
They may be issued by an individual WHO Expert Chronic diseases such as cardiovascular diseases, cancers,
Committee and included in their reports (e.g., WHO Ex- and respiratory diseases, affect both developed and deve-
pert Committee on specifications for pharmaceutical pre- loping countries. WHO’S priorities are an integrated and
parations, cal report number 863, 1996). or issued coordinated approach to prevent, treat, and cure through
as special publications under the authority of the disease-specific interventions, global campaigns to en-
DG (e.g., Globalization and access to drugs, health eco- courage healthy lifestyles (e.g., worldwide no-tobacco
nomics and drugs, 1998). Most of the WHO Recommen- day), and healthy public policies promotion.
dations are directed at developing countries (e.g.. the
“International Pharmacopoeia‘’). Emergency and humanitarian action
In practice, WHO standards, guidelines, and recom-
mendations serve as advice to member states. They can The emergency and humanitarian division of WHO/HQ
however, be adopted as legally binding national regula- plays an active role in assisting the member states in
906
tackling health emergencies. It relies on its emergency coordination with donors (through consolidated appeals),
preparedness and response programs, providing countries UN agencies (e.g., UNHCR, UNICEF, WFP) and other
timely support to tackle acute emergency and supporting entities involved (e.g., ICRC, NGOs). To face large
them during the reconstruction phase. WHO can assure movements or sudden influxes of refugees which create
National drug policy 0 Help countries formulate 0 Implementation and monitoring for
and imolement a national of NDP. developing a NDP.
drug policy (NDP) and 0 Health system development Indicators for monitoring
integrate the work into supported by essential drugs NDP, 1999.
their national health system policies and programs. Essential Drug List (EDL),
in ensuring commitment of 1lthlist, Nov 1999.
all stakeholders.
Access to essential 0 Ensure equitable 0 Access strategy and monitoring Standard indicators to
drugs availability and affordability for essential drugs (in particular measure equitable access.
of essential drugs. for priority health policies and Drug price information.
newly developed drugs). Operational principles
Financing mechanisms and for good pharmaceutical
affordable essential drugs. procurement, 1999.
0 National and local public Good drug donation
sector drug supply systems practices, 1999.
and supply capacity. The new emergency
health kit, 1998.
Quality and safety 0 Ensure the quality and 0 Norms, standards, and Norms, standards and
of drugs safety and efficacy of guidelines for pharmaceuticals guidelines developed
all medicines. and updated.
0 Put into practice 0 Drug regulation and QA systems. Quality control
regulatory and quality e Information support for specifications.
assurance (QA) srandards. pharmaceutical regulation. Drug nomenclature and
0 Guidance for control and use classification.
of psychotropics and narcotics. WHO certification
scheme on the quality
of pharmaceuticals.
Good manufacturing
practices (GMP).
Good laboratory practices
(GLP).
Good clinical practices
(GCP), 1995.
The International
Pharmacopoeia, 1994.
Rational use of drugs 0 Ensure therapeutically 0 Rational drug use strategy Guide to good
sound and cost-effective and monitoring through prescribing, 1994.
use of drugs by health national strategies. Medical products and
professionals (prescribers, the internet: a guide
nusses, and dispensers) 0 National standard treatment to finding reliable
and consumers. guidelines, EDLs, educational infomation, 1999.
programs. The use of essential
0 Independent and unbiased drugs. gth report of the
drug information system. WHO expert committee.
immediate needs for basic health services (e.g., Rwanda 3. Irrational prescribing and use: Up to 75% of
in 1994 and Kosovo in 1999), WHO has collaborated with antibiotics are prescribed inappropriately.
most international agencies and NGOs to developed a 4. Lack of pharmaceutical research and development
standard kit of essential medicines, medical supplies, and for tropical
basic equipment called the “New Emergency Health
Kit.” The same interagency group has developed guide- Reasons are complex and go beyond simple financial
lines for obtaining the maximum benefit from drug constraints. (In most developed countries, virtually 100%
donations through the “Guidelines for Drug Donations” of the population has health insurance; median coverage
de~elopment.[~’ is 35% in Latin America and less than 10% in Africa and
Asia.) Changes in the patterns of disease (e.g., rise of
HIV/AIDS, increasing drug resistance for malaria and
tuberculosis, increase in chronic diseases and diseases of
Research activities range from epidemiological surveil- the elderly) and drug demand also represent major
lance for new and re-emerging diseases, the tropical di- challenges and contribute to increased spending on drugs
sease research program (WHO/TDR in Geneva, Swit- and growing pressure on health resources. The potential
zerland) tackling epidemiological research, medicines impact of international trade agreements, such as the
research and development (on malaria, trypanosomiasis, World Trade Organization Agreement on trade-related
leishmaniasis, Chagas disease, etc.), cancer research aspects of intellectual property rights (WTO/TRIPS), is
(e.g., International Centre for Cancer Research in Lyon, also a matter of growing concern with relation to access to
France), and monitoring of the progress of genetic engi- new essential medicines (e.g., antiretroviral drugs, anti-
neering laboratories. biotics, second-generation vaccines).[s1 It highlights the
need for strengthened international cooperation and a
HO-Specific Activities in the stronger public health response.
Pharmaceutical Sector
atrice Trouillev
University Hospital of Grenoble, Grenoble, France
ponents being legislation, regulation and guidelines, ac- mentation and compliance], These problems are greatest
cess to essential medicines, quality assurance, rational use in low-income countries, but middle- and high-income
of medicines, research, and human resources develop- countries are also increasingly facing difficult therapeutic
ment). Usually, market approval of a pharmaceutical pro- and economic decisions.
duct is granted by drug regulatory authorities on the basis To ensure access to essential medicines, WHO has
of efficacy, safety. and quality, and rarely on the basis of defined a strategy by focusing on four key objectives:
comparison with other products already on the market or rational selection and use (through a strengthening of
cost. Different criteria are used for the selection of es- links between WHO EDL and standard therapeutic guide-
sential medicines; e.g., medicines with adequate evidence lines for priority diseases); affordable prices (through
of efficacy and safety; relative cost-effectiveness with good procurement practices and indicative cost informa-
comparisons between medicines (comparative efficacy tion policies, and TRIPS safeguards as parallel import and
and safety, meta-analysis) and considerations of the total compulsory licensing for new essential medicines); sus-
cost of the treatment; pharmacological criteria (e.g., phar- tainable financing, national spending on pharmaceuticals
macokinetic properties, bioavailability, galenic stability); varying from $2 to $400 per capita and per year (through
and formulations as single compounds, with fixed-ratio public funding and a health insurance scheme to maxi-
combination products being acceptable only when the mize risk-pooling and equity shifts); and reliable health
combination has a proven advantage (e.g., therapeutic ef- systems ensuring a proper diagnosis and treatment and a
fect, adherence to treatment improvement). responsible supply system.
There may still be oppositions to the use of the es- Despite the obvious medical and economic importance
sential medicines list. Physicians may see it as question- of essential medicines, there are still problems with lack
ing their prescription freedom, pharmacists may be wor- of access, poor quality, and irrational use. In many health
ried about the financial implications, while manufacturers facilities in developing and in developed countries, es-
may fear a market erosion, and consumers may think sential medicines are not used to their full p~tential.'~'
that they are being offered second-rate cheap medicines. While the EDL is regarded as a key aspect of global
These concerns must be considered and addressed, and health and economics, the WHO EDL is, for the past few
this is why the selection process should be consultative, years, at the center of debates with respect to access issues
and why education plays an important part. In fact, an (such as new essential medicines for HIV/AIDS, tuber-
essential medicines policy is nothing but an extension of culosis, and bacterial infections) and availability issues
the selective exercise carried out by the state, on behalf (such as the lack of pharmaceutical research and deve-
of the rights a community has to useful and safe pro- lopment for tropical diseases, most of the current tropical
ducts, to identify medicines that deserve marketing ap- pharmacopoeia having been driven by colonization re-
proval. The principle of convenience is under consid- quirements during the first part of the 20th ~ e n t u r y ) . ' ~In'
eration in an increasing number of countries, especially 2001, still one-third of the world's population (over 50%
as the pharmaceutical industry becomes more prolific, in the poorest part of Africa and Asia) does not have
more complex, and uses products that are increasingly regular access to the most vital essential medicines.
powerful and, consequently, more hazardous.
EF
AC ESSE
1. WHO. The WHO essential drugs list. URL: www.who.int/
Despite important achievements, the lack of regular ac- medicines/edl.html (accessed on Oct. 2000).
cess to essential medicines still remains a major health 2. WHO. The Use of Essential Drugs. In 6th Reporf of the
Expert Committee; WHO Technical Report Series, World
problem, recently highlighted by the magnitude of the
Health Organization: Geneva, 1995; Vol. 850.
HIV/AIDS pandemic [e.g., in the 11th EDL, while 15 3. WHO. WHO Medicines Strategy: Framework for Action in
drugs of importance to HIV-related opportunistic infec- Essential Drugs and Medicines Policy, 2000-2003; World
tions are present, only two antiretroviral drugs (ARVs) are Health Organization: Geneva, 2000, (WHO/EDM/2000.1).
listed for the prevention of mother-to-child infection, and 4. PCcoul, B.; Chirac, P.; Trouiller, P.; Pinel, J. Access to
no ARVs are listed for the HIV treatment itself because of essential drugs in poor countries. A lost battle? JAMA, J.
their high costs and prerequisites for treatment imple- Am. Med. Assoc. 1999, 281, 361-367.
AACl’. &e Anierican Aswctxion or Colleges .4cetohexamidc. adi,erse drug reaction, 30 resources for improving, 15
of Phnrmacy Acctylatorn, drug reaction, 29 sclf-efficacy, 14
Abbott ‘Total Quality Pain Maiiagcment. 643 ACE’. See Adtninistration for Children space considerations, 20
Abhrehiated New Drug Application, 380 m c l Families special populations, 14- 18
Aboriginal peoples. ethical issues. 879 ACPE. S c v Amet-ican Council 011 type 2 diabetes, 19
Abstracts. phat-maceutical. Arncrican Society of I’harniaceutical Education Adiniiiistration. drug, routcs of, 85
IIealth-Sy\teni I’hat-cnncists. 487 Acquired iinnitiIl[jdcficiency syndrome. Administration for Children and Families, 254
ACA. SW American Collegc of Apothecaries Src. AIDS Adiiiiiiistration on Aging, 254
Academia ActiMcd Lahoratorie\, 141 Advance Care, 141
carecrs options. clinical phal-macy Acyclot i l . 587 Advanced cardiac life support, 125
mentist. 179 Advanced professional educational programs,
clinical pharmacy careers in, I 5~
Adcnovirus. viral transfer techniques, 368 556
academic \ites, description of; 7. - 4 Adverse drug reactions. 2 3 -34
activities, 1 assessing, 12- 13
career ladder, 4 direct methods, I 2 cla\sii‘ication sy\tcma, 23-24
degree, 4 indirect rncthods. 12- 13 clinical pharmacy. economic analysis,
cxpcrieiice requil-ed, 4 children. 17- I8 307-321
rilctiity, 3 chi-onic d i x a s c s , 18-19 definitions, 23
options in, 1-3 coinmuiiity resources, 17 dr-ug-nulrient interactions, 30
r c w r d system, changes in. 2 cultural differciiccs and, 17 factors predisposing to, 24-28
tenut-e \ystern. changes in. 2 IlldcrCare Patient Ikhcation Series, 15 delivery system, 24
training, 4 elderly, 15- I6 diseases, influcncc of, 27
transition in academia. I -3 cognititc liinitations, 15 dosage form. 24
drug information phariiracy pi-actice in. 29 I limiteil iicce\s to health cat-c, I5 t h e , 24
Academy of Managed (’iirc Phai-macy. 6-7, phy\ical impairmcnts. 1; drug-related factors, 24-25
23 I . 270. 496 polyph;irmacy, 15 hypoalbuminemia. conditions associated
governance. 6 risk factor\ for nonadherence. 15 with, 26
initiatives. 7 ethnic minorities, 16- 17 inleractions between drugs, 24-25
meetings. 7 factors affecting. 13 patient-related factors. 25 -28
mission \t;itcincnt. 6 fear tactics, 14 concurrent diseases, 25
organir;~tionalstructure. 6 follolr-up, 14 gender. 28
vision \tatcrncnt, 6-7 hypertension. 18- 19 genetic factors. 26-28
Access to healthcare. 41 1 implement t-ewarti system. 14
Access to phai-inaccutical\, 35 infot-rncd tnctlication consumer, pateint a s , 14
Accidents, as cause of death, 404 lowliteracy patients, 16 herbal therapies usc, 28
Account manager. profesealiot1;rI National Council on Patient Infot-ni;ltion multidrug usc, 28
opportunities. SO2 and tiducation, I S nutrition, 28
American Collegc of Cliiiical iionadhcrence pediatrics, 25
Pharmacy as behavioral diwrder, 1 1 renal disease, 26
Accreditation defined. 10 1 1 pediatrics, 26
American Council on 2’h;it-ni;iceuiical patient-focused interventions for, 13- 14 genetic factors, 20
Education, 8 risk l‘actors for. 1 I gcriairic age-related changes,
defined, 224, 230 scope of prohlem, 10- I I pharrnacokinctic, 25
Accreditation of liealtli-Care Organi/ations. patient goal\. 14 herbal medicines. 3 I
Joint Corninission for, 493 -495 patient-centered adherence pnradigni. 1 I hutnan reliability
acci-editation process utmdards, 495 p q i n e n t for adhcrcncc scrvicm, 20 curve. 539
accreditation \tatus, 493 -495 Pediatric Mcdication Text. IS enhancing, 539-542
background. 493 Peter Lani). Ccntcr fot- Drug Thcrapy and incidencc. 24
Acctatninophen Aging, 15 manageable hehaviors
advcrsc drug reaction\, 29 phai-macothcrapy, enhancing adhcrencc to, at-risk behavior, 540- 54 1
cytochrome P450, 247 14-18 high-culpability behavior, 541 -542
911
912 Index
Adverse drug reactions (cont.) long-term opportunities, 40-41 Aniericaiz Journal of Health-System Pharmacy,
imperfect behavior, 540 salary range, 40 48-49, 57
Naranjo causality algorithm, 32 site description, 41 history. 48 -49
pharmaco-epidemiologic studies, 30-3 1 training, 40 objectives, 48
spontaneous reporting, 30-31 work settings. 39-40 American Journal of Pharmaceutical Education,
prevention, 32-33, 533-544 fellowships in, 356 50
manageable behaviors, 540 Ambulatory clinic, university-affiliated, clinical American Medical Informatics Association, 293
medication-use cycle. 533-535 phaimacy, economic analysis, American Pain Foundation, 643
outcomes-measurement approach, 538 -539 307 - 32 1 American Pain Society, 621, 643
preventable patient harm. scientific AMCP. See Academy of Managed Care Anzerican Pain Societ): Bulletin, 450
investigation, 536-539 Pharmacy American Pharmaceutical Association, 51 -52,
process-improvement approach. 536-538 American Academy of Clinical Toxicology, 231. 270, 496
role of pharmacist, 542-543 761-762 current major initiatives, 52
reporting systems, 28 -32 American Academy of Pain Management, 643 history, 51
screening methods, 30 American Academy of Pain Medicine, 643 meetings. 52
Affordability of health care services, elderly American Association of Colleges of Pharmacy, mission, 52
and. 15 210, 231, 270, 496 organizational structure, 5 1-52
Afiican Americans, Plzarnzacokiizetics and Drug appointed Commission to Implement Change, American Society for Clinical Pharmacology
Interactions in Elderly and Special 210 and Therapeutics. Pharmacokinetics
Issues in Elderly Aj%can-American Commission to Implement Change, 210 and Drug Metabolism Section,
Populations. 481 Janus Commission, 491 -492 166- 167
Agency for Health Care Policy and Research, history. 491 American Society of Addiction Medicine, 643
417 members of, 492 American Society of Anesthesiologists, 643
Agency for Healthcare Research and Quality, mission, 491 -492 American Society of Clinical Oncology, 621
35-38, 254. 417, 621 American Association of Phannaceutical American Society of Consultant Pharmacists,
Agency for Toxic Substances and Disease Scientists 53-55, 232, 270, 496
Registry, 254 Pharmacokinetics. Pharmacodynamics and advocacy. 54-55
Age-related changes Drug Metabolism Section, 166 consultant pharmacy practice, 53-54
geriatric, pharmacokinetic, 25 Population Pharmacokinetics and Pharmaco- education, 54
pharmacokinetics and, 25 dynamics Focus Group, 166 mission, 55
Age-related risk factors, pediatrics adverse drug American Association of Poison Control practice resources, 55
reactions, 26 Centers, 761 publications, 55
AHCPR. See Agency for Health Care Policy American Cancer Society, 621 senior care pharmacy, 53
and Research American Chronic Pain Association. 643 American Society of Health-System
AHRQ. See Agency for Healthcare Research American College of Apothecaries. 231, 496 Pharmacists. 56-57, 232, 270,
and Quality American College of Clinical Pharmacy, 43-44, 496, 621, 622
AIDS 188-198, 231, 270, 475, 496 American Journal of Health-System
as cause of death, 404 clinical pharmacist evaluation, 154- 160 Pharniacy. 57
Confronting AIDS: Direction f o r Public collaborative drug therapy management. best-practices documents, 79-81
Healtli, Health Care, and Research, 188-198 access to, 81
48 1 Commission to Implement Change in Clinical Practice Section, 293
No Time to Lose: Getting More from HIV Pharmacy Education, 210-213 clinical skills programs. 57
Prevention, 48 1 governance, 44 educational resources, 57
AIDS group. Cochrane collaborative. 183 organization, 43 Handbook on Injectable Drugs. 57
Airways group, Cochrane collaborative. 183 advocacy, 44 history, 56
Alaska, pharmacy practice legislation, 272 education. 44 International Pharmaceutical Abstracts, 57,
Albuterol, 671 membership, 43 487
Alcohol professional leadership, 44 Medication Teaching Maizual, 57
drug reaction with, 30 programs. 44 membership, 56-57
excipient in drug, 95 publications, 44 midyear clinical meeting, 475
Allergic reaction, to drug, 23 Pharmacokinetics Dynamics Practice publications, 57
Allergies, medication, 286-287 Research Network, 166 Supplemental Standard and Learning Objec-
All-inclusive care for elderly (PACE) programs, position statement, 188 tives for Residency Training, 166
managed care, clinical pharmacy American Council on Pharmaceutical Education, American Thoracic Society, 474
careers in, 504 8-9,45-47, 231, 270,496 American Zoo and Aquarium Association, 775
Allwin Data. software, 216, 218 accreditation, 8, 45 AMIA. See American Medical Informatics
Aloe, adverse reaction to, 31 continuing education accreditation program, Association
Alzheimer's disease, 588 45-46 Amikacin, AIDS, 442
gene therapy, 376 current initiatives, 47 Aminoglycosides
Amantadine, 585, 588 meetings, 47 AIDS, 442
Ambulatory care mission, 46-47 drug reaction, 27
clinical pharmacy careers in, 39-42 organizational structure, 46 Amphotericin B, AIDS, 442
degrees, 40 professional degree programs, 45 Amyotrophic lateral sclerosis, 585, 588
job activities, 39-40 "Standards 2000," 8-9 gene therapy. 376
Index 913
Bioal ailability, 92-93 health outcome, 109 clinical pharmacy opportunities, 61 1-614
bioequix alence. 97-98 model clinical practices. 108- 109 clinical research, 617-618
Bioequivalence. 97-98 clinical-based practice, 109 documented benefits, 618-620
Biopharmaceuticals. 82- 102 hematopoievis chart. 109- 110 drug administration policies, 613
bioavailability. 92 -93 networking. 110 drug handling, 612-613
bioequivalence, 97 -98 research-based practice, 108- 109 drug information, 614, 617
bioequivalence, 97 tools. 109- 110 education, 614
biowai1ers. 101 pharmacist’s responsibilities, 107 guidelines, 620-622
cell membrane passage BPS. See Board of Pharmaceutical Specialties inpatient care practice roles, 615-616
carrier-mediated transport, 88 Bradycardia. drug reactions and, 27 investigational drug use, 617
passive diffusion. 84-88 Breast cancer medication order review, 612
vesicular transport. 88 gene therapy trials, 374 model clinical practices, 614-618
classification system, 99- 101 screening, effectiveness of, studies, 565 outpatient care practice roles, 616-617
disintegration. 92-93 Breast cancer group, Cochrane collaborative, patient care problems, 613
dissolution. 101 183 patient care services. 620
formulation factors. dissolution, 95-96 British Committee for Standards in patient education, 613
generic drug products, 97-98 Haematology, guidelines, 67 patient monitoring. 613-614
oral drug absorption, 88-92 practice guideline development, 618-619
blood perfusion. gastrointestinal tract; reimbursement, 620
89-91 CA-A Cancer J014rnd f o r Clinicians, 623 resources for, 620-623
food, effect of. 91 -92 Caffeine, 754 roles. 612
gastric emptying time, 89 cytochrome P450, 247 specialist interventions, 619-620
gastrointestinal motility. 89 drug reaction with, 30 summary of interventions. 619
intestinal motility, 89 Calcineunn, 870 transitional patient care practice roles,
physiologic considerations. 88-92 inhibitors, drugs interacting with, 870 616
rate-limiting, 84 Calcium channel blockers: 588 Cancer Care Ontario. 621
particle size, 94 Calcium regulation. abnormality of, drug Cancer Chemotherapy and Biotherapy:
permeability class, I00 reaction, 29 Principles and Practice, 622
pH. 93-94 California Cancer Chemotherapy Handbook, 622
physiologic factors affecting. 84-88 pharmacy practice legislation. 272 Cancer Chemotherapy Pocket Guide, 622
cell membrane passage, 84-88 regulations governing prescribing, 190 Cancer Control Journal, 623
polymoiphic crystals, 94-95 Call center pharmacist, professional Cancer pain, Talarian map. 450
postapprobal change levels. 100 opportunities. 502 Cancer Principles and Practice of Oncology,
postapproval changes, 101 Cam Commerce Solutions, software. 216. 218 622
product design. 82-84 CAMIPR. See Consortium for Advancement of Cancer Therapy Evaluation Program. 622
scale-up. 101 Information Policy and Research Cancer Trials Support Unit of National Cancer
solubility. 93. 99- 100 Campus. National Institutes of Health, 576 Institute. 622
i n v i m dissolution testing. 96-97 Canada; health care systems, 390 Capsacian, 588
in iitro performance. 98-99 Canadian Cochrane Centre, 185 Capsule, oral administration of, processes
in vitro-it7 vivo correlation. 98-99 Canadian Hospital Pharmacy Residency Board, following, 86
Bioscanner 1000, cholesterol monitoring test. 111 Carbamazepine, 870
466 Canadian Pharmacists Association/Association adverse drug response. 29
Biotechnology industry, careers options, clinical des Pharmaciens du Canada, pediatric pharmacokinetic data, 665
pharmacy scientist, 179 112- 114 Carbidopa, 588
Biowaivers, 101 e-business, 113-114 Cardiac arrest. 115-118
Bipolar disorder, 585 initiatives. 113 - 114 Cardiology, 119- 126, 356. See also Cardiac
Bleeding. limiting antiplatelet drug use, 585 pharmacist shortage, 113 arrest
Bleeding disorders. drug reactions and. 27 prescribing authority, 113 acute care, 120-121
Blockers. cytochrome P450, 247 prib acy legislation, 113 acute coronary syndromes, 124- 125
Blood concentration curve. 381 third-party payer issues, 113 advanced cardiac life support, 125
Blood dqscrasia. 585 meetings. 114 antithrombosis. 122
Blood perfusion. gastrointestinal tract, 89-91 mission, 112-113 atrial fibrillation. 125
Blood pressure, controlling, effectiveness of. organizational structure, 112 chronic heart failure, 121- 122
studies, 565 Pharmacy Electronic Communications clinical pharmacy guidelines, 124- 125
Board certification. See Certification StandardDJational +Claims dyslipidemia, 121, 125
Board of Pharmaceutical Specialties. 103 - 105, Standard Initiative. 113 fellowships in, 356
228. 232. 270 publishing. 114 gene therapy clinical trials, 375
added qualifications. 104 Cancer heart failure, 125
certification. process, 104- 105 as cause of death, 404 home care. 442-443
mission. I03 - 104 gene therapy. 373 hypertension, 121, 125
specialties. 104 specialty pharmacy practice. 61 1-626 networking opportunities, 123- 124
Boehringer Mannheim Corp.. 141 anticancer therapy, outcomes related to, outpatient, 121 - 123
Bone marrou transplant, 106- 110 618 professional opportunities, 124
clinical pharmacy opportunities, 106- 108 chemotherapy order verification, 612 stable angina, 125
Index 915
Clopidogrel, 587 Commission for Certification in Geriatric Consumer behavior, health services research,
CMS. See Centers for Medicare and Medicaid Pharmacy, 229, 232. 270 412
Services Commission to Implement Change, 210-213 Consumers group, Cochrane collaborative, 183
CoaguChek PST, 141 Commissioned Officer Student Training and Contact information program, Drug
CoaguChek S Systems Test, Roche Diagnostics, Extem Program, 387 Enforcement Agency. 282
141 Committee involvement, medical information, Continuing education
Coccidiomycosis, with AIDS, 442 industry-based, labeling, defined, 231
Cochrane centers, 181-182 promotional review committee, 528 medical information, industry-based, 529
information on, 185- 186 Communication skills, scientist, clinical Contraceptives, drug reaction, 27
Cochrane Library, 181- 187 pharmacy, 178 Contract research organization, infectious
Cochrane centers, 181-182 Communications, medical, clinical pharmacy diseases, 471
Cochrane collaborative review groups, careers in, 519-524 Contracting. professional opportunities, 502
182-184 income, 519-521 Corn oil, excipient in drug, 95
Cochrane methods group, 184 training, 522-523 Coronary artery disease, 585, 814
collaboration structure, 181- 186 Community hospital Coronary syndromes, 124- 125
history, 181 clinical pharmacy, economic analysis, Corticosteroids, 870
steering group, 181 307 - 32 1 adverse drug reaction, 27
subscribing to, 184 university-affiliated, economic analysis, drug reaction, 27
Cochrane methods group, 184 307 - 32 1 COSTEP. See Commissioned Officer Student
Cognitive impairment group, Cochrane Community pharmacy Training and Extern Program
collaborative, 183 clinical pharmacy, economic analysis, Cost-minimization analysis, 307- 321
Cognitive limitations, in elderly, adherence and, 307-321 costs
15 diabetes care, 256-257 analysis, 307-321
Collaborative drug therapy management, 192 Community pharmacy practice, hyperlipidemia, anticoagulation therapy, 65
access to patients, 196 462-463 clinical pharmacy, economic analysis,
American College of Clinical Pharmacy, Community-based home care, 440 307-321
188-198 Competence clinical pharmacy services, evaluations of,
position statement, 188 defined. 230 301-325
collaborative relationships, defining, 195 ethical issues, 878 Spain, 459
compensation, 196- 197 Competency, defined, 23 1 Cranial nerves, 586
credentialing, 197 Compliance, counseling for, 650 Credential, defined, 224, 23 1
documentation of activities, 196 Computer links, hospice, 450 Credentialing, 223 -232
environment, 195- 196 Computer software, 214-222, 456 American College of Clinical Pharmacy. 197
federal government, regulations governing associated performance-enhancement tools, anticoagulation clinical pharmacy practice,
prescribing, 191 22 1 67
health care, evolving view of, 193- 194 clinical software attributes, 221 certificate training programs, 227
medical records, access to, 196 confidentiality, 222 certification, 228-229, 230
pharmacist prescribing in U.S., history of, documentation, 220 - 22 1 certification bodies, 232
188-192 hardware array, 215-220 certifying agencies, 228 -229
prescribing hospital pharmacy practice, 456 collaborative drug therapy management, 197
defined, 194 InfoWin, 456 Council on Credentialing in Pharmacy, 223
evolving view of, 194-195 point-of-care software, 220 defined, 224, 231
regulations governing pharmacist prescribing, privacy, 222 disease management, 268 -269
190-191 recommendations. 222 education, 230
requirements for, 195- 197 security, 222 entering practice, and updating professional
Collaborative partnerships, 693 Confidentiality knowledge and skills, 226
Collaborative practice agreements, 199-206 ethical issues, 878-879 fellowships, 227
current pharmacy practice environment, software, 222 importance of credentials. 224
199-201 Conflict of interest, ethical issues, 879 knowledge, enhancing, 226-227
definitions, 199 Confronting AIDS: Direction for Public Health, Millis Commission and, 557
types of, 201-206 Health Care, and Research, 481 multidisciplinary certification programs, 229
Collaborative relationships, defining, 195 Confusion, agents causing, 586 pharmacy supportive personnel, 229-230
College of Psychiatric and Neurologic Congestic heart failure, 754 preparing for pharmacy profession, 225-226
Pharmacists, 207-209 Consensus Conferences on Antithrombotic regulation, 230
initiatives, 208 Therapy, 67 residencies, 227
meetings, 208-209 Consensus Guidelines for Coordinated skills, enhancing, 226-227
membership, 208 Outpatient Oral Anticoagulation traineeships, 228
mission. 208 Therapy Management, 67 training, 230
organizational structure, 207-208 Consortium for Advancement of Information updating professional knowledge, 226
Colon, drug absorption in, 90 Policy and Research, 293 Credentials, U S . pharmacy, 225
Colon cancer, gene therapy trials, 374 Consortium of Academic Health Centers for Crime Drug Enforcement Task Forces, Drug
Colorectal cancer group, Cochrane Integrative Medicine, 484 Enforcement Agency, 282
collaborative, 183 Constipation, 585 Critical care, 837
ComCo Tec, software, 216, 218 Consumer, informed, pateint as, 14 fellowships in, 356
Index 917
Critical care pharmacy, 233-239, 240-245 Agency for Healthcare Research and Diffusion, molecules, 87
activities, 237, 242-244 Quality, 254 Digital Simplistics, software, 216, 218
challenges of, 237-238 Agency for Toxic Substances and Disease Digoxin, drug reaction, 27
components of, 235 Registry, 254 Diphtheria, 7 12
cuixnt practice, 234-235 Centers for Disease Control and Dipyridamole, 587
historical background, 240-241 Prevention, 252 Direct patient care, professional opportunities,
history of, 233-234 Food and Drug Administration, 251 -252 503
hospital services, 244 Health Resources and Services Directions in clinical practice in pharmacy
impact of, 236-237 Administration, 253 (Hilton Head Conference), 265-266
knowledge base, 235-236 Indian Health Services, 252-253 Disease management, 267-275
methods, 241-242 National Institutes of Health, 251 certification, 268-269
purpose, 241 Substance Abuse and Mental Health credentialing, 268- 269
research in critical care, 235 Services Administration, 253 -254 reimbursement, 269 - 27 1
Cryptococcosis, with AIDS, 442 human services operating divisions, 254 resources, 270
CTEP. See Cancer Therapy Evaluation Program Administration for Children and Families, scope of practice, 267-268
Cultural differences, adherence to medical care 254 Disease Management Association of America,
and, 17 Administration on Aging, 254 270
Curricula, pharmacy, design of, 555-556 Centers for Medicare and Medicaid Disease Management Purchasing Consortium
Cyclosporine, 870 Services, 254 and Advisory Council, 270
cytochrome P450. 247 Office of Secretary of Health and Human Disintegration, absorption and, 92-93
Cystic fibrosis Services, 254 Disposable IV equipment, pediatric dosing,
gene therapy, 373 Program Support Center, 254-255 667-668
home care, 442 Department of Veterans Affairs, careers in, 385 Dissolution, bioavailability and, 101
Cystic fibrosis group, Cochrane collaborative. Depression, 585, 815 Disulfiram
183 anxiety, neurosis group, Cochrane adverse drug reaction, 30
Cytochrome P450, 246-250 collaborative, 183 as cytochrome P450 inhibitor, 247
in drug-drug interaction, 248-249 Deutsches Cochrane Zentrum, 185 Diuretics, drug reaction, 27
gene polymorphism, drug response, Development, drug, team members Divalproex sodium, 588
differences, 246-248 nonscientific personnel, 130 Diversion control program, Drug Enforcement
isoenzymes, 246 pharmacists, 129- 130 Agency, 282
nomenclature, 246 physicians. 128- 129 DNA, viral transfer techniques, 368
noninvasive measurement of, 249 roles of, 128-130 Doctor of Pharmacy, 276-281
in systemic availability of drug, 248 scientists, 129 career opportunities, 280-281
Cytomegalovirus infection, with AIDS, 442 Developmental, psychosocial, learning pro- curriculum, 278-280
blems, Cochrane collaborative, 183 history of, 276-278
Dexamethasone, 870 Documentation
DAA Enterprises, software, 216, 218 DIA. See Drug Information Association diabetes care, 258
Daclizumab, 870 Diabetes, 256-259, 585, 586, 813 from hospice care providers, 452
Dairy products. drug reaction with, 30 assisted living facilities, 257-258 hyperlipidemia, 466
Dapsone as cause of death, 404 software, 220-221
adverse drug reaction, 29 clinics, 257 Dopamine agonists, 588
hydroxychloroquine, adverse drug reaction, community pharmacy, 256-257 Dopaminergic agents, 585
29 documentation forms, 258 Dosage form, adverse drug reactions and, 24
Data collection forms, patient drug history, 289 drug reactions and, 27 Dose, adverse drug reactions and, 24
Database manager, professional opportunities. effectiveness of, studies, 565 D.P. Hamacher, software, 216, 218
502 hospital pharmacy, 257 Drug Database at Pharmaceutical Information
Datdpopulation manager, professional managed care, 258 Association, 774
opportunities, 502 nursing homes, 257-258 Drug Enforcement Agency, 282-283
Declaration of Helsinki, 341-342, 755 physicians’ offices, 257 history, 282
Deep vein thrombosis, anticoagulation, 64 prescription drug benefit administrators, 258 programs, 282-283
Degrees private practice, 257 Drug history, 284-289
academic clinical pharmacy, 4 product sales, 258 compliance aids, 287
clinical pharmacy careers, 40 Dibasic calcium phosphate, excipient in drug, components of, 286-287
Dehydrogenase deficiency, drug reaction, 29 95 financial/insurance information, 286
Delerium, 586 Dietary Supplement Health and Education Act, patient, 284-289
Delivery system, adverse drug reactions and, 260-264 acute, chronic medical problems, 287-289
24 administration (Sections 8-13), 262-263 caregiver/family meinber, 285
Delphi, software, 216, 218 history of, 260 compliance, barriers to, 287
Dementia group, Cochrane collaborative, 183 introductory sections (Sections 1-4), 260-261 components of, 286-287
Dementia, 586 marketing, labeling of dietary supplements data collection forms, 289
Dental care, Medicaid usage. 516 (Sections 5-7), 261-262 healthcare providers, 285
Department of Health and Human Services, Dietary supplements, 774 immunizations, 287
251-255 categories of, 604 interviewing patient, 285 -286
agencies of, 25 1-254 drug regulation, comparison of, 261 medical records, 285
918 Index
Drug history (cont.) Echinacea, adverse reaction to, 3 1 Epilepsy, drug reactions and. 27
medication allergies. 286-287 Economic evaluations o f clinical pharmacy Epilepsy group, Cochrane collaborative, 183
medications, 287 services, 301 -325 Epoxide hydrolase, deficiency of, drug reaction,
patient data records, 284 analytic methods, 304 29
patients, 285 cost-justification studies, 303 Ergotamine. 588
pharmacy dispensing records. 285 methods, 301-302 drug reaction, 27
setting. 285 type of analysis, 302 Erythromycin
social history. 287 Economic value. o f clinical pharmacy services, as cytochrome P450 inhibitor, 247
sources of patient data, 285 307 -321 effect on group A streptococci, 60
special patient populations, 285-286 Edema, 585 Esophagus. drug absorption in, 90
types of data, 284-285 Education, 556 Essential Drug List, World Health Organization,
objective data, 285 home care, 437 908 -909
subjective data, 284-285 hyperlipidemia, 464-465 Estrogen replacement therapy. 815
pharmacist-conducted. rationale, 284 infectious diseases, 469 Ethanol, cytochrome P450, 247
Drug Information Association, 294 medical information. industry-based, 529 Ethical Conduct for Research Involving
Drug Information Framework, 360 Education, Pharmaceutical, American Council Humans. Tri-Council Policy
software, 360 on, 496 Statement. 876-881
Drug information pharmacy practice, 290-294 Eldercare Patient Education Series, 15 Ethical issues. 330-334
academic practice. 291 Elderly aboriginal peoples, 879
associations, 292 adherence to medical care, 15-16 classification of. 332-333
community. 290-291 cognitive limitations. 15 clinical evaluation, drugs, 136- 137
government, 292 physical impairments, 15 clinical trials. 879-880
industry, 291 -292 polypharmacy, 15 competence, 878
managed care, insurance companies, 292 risk factors for nonadherence. 15 conflict of interest, 879
model clinical practices. 290-292 flu shots, effectiveness of. studies, 565 data collection, 878- 879
networking opportunities, 293 -294 home care, 443 decision making and, 330-331
professional opportunities, 290 pain management, 641 definition of, 332
resources, 292-293 Pharinacokinetics and Drug Interactions discrimination, 333
Drug information specialist, professional in Elderly and Special Issues in disease management, 271 -273
opportunities, 502 Elderly African-American ethical problems. 331 -333
Drug Information-A Guide to Current Populations, 481 ethics review procedures, 877
Resources, 293 Electrolyte/nutritional status, neurology gene therapy, 376-377
Drug InformationPharmacoeconornics specialty pharmacy practice, 585 human genetics research, 880-881
Network, 293 Electronic prescribing, 326-329 inclusion/exclusion of populations, 879
Drug intolerance, defined. 23 advantages of, 327 informed consent. 877-878
Drug Price Competition and Patent Term description of, 326 informing potential subjects, 878
Restoration Act, 380 disadvantages of, 327-328 medication assistance programs, pharma-
Drug samples. 295-299 impact on practice. 328-329 ceutical company-sponsored, 532
alternatives to, 298 information available. 326-327 negative discrimination. 333
JCAHO criteria. compliance, 296 prescription destination, 327 personal interviews, 878-879
regulatory issues, 295 Emergency pharmacy services, 115-1 18 pharmaceutical outcomes. 704
Drug surveillance, Spain, 459 Emergency room. clinical pharmacy, economic pharmacotherapeutic decisions, 332
Dmg use evaluation, clinical pharmacy. analysis, 307-321 physician, pharmacist, patient, relationship
economic analysis, 307-321 EmergencyNET. 776 among, 33 1- 332
Drug-nutrient interactions, 30 Emerging Infections: Microbial Threats to positive discrimination, 333
Dry eyes, caused by anticholinergic medication Health in United States, 481 privacy, confidentiality, 878- 879
effect, 586 Employee education, medical information, rationing, 333
Duke University, health outcomes reasearce. industry-based, 529 relationship, between health professional,
36 ENA.C.T. Total Cholesterol Test, cholesterol patient, 330
Duodenum, drug absorption in, 90 monitoring test, 466 research, 335-343
Dutch Association of Hospital Pharmacists, 825 Encainide, cytochrome P450, 247 clinical trial design, 339-340
Dutch Cochrane Centre, 185 Encephalopathies, 586 Declaration of Helsinki, World Medical
Dynamics Practice Research Network, Endocrine disorders, drug reactions and, 27 Association, 341 -342
American College of Clinical Endocrine disorders group, Cochrane drug therapy, 337
Pharmacy Pharmacokinetics, 166 collaborative. 183 in emergency health situations, 878
Dyskinesias, 588 Endocrine system, neurology specialty historical perspective, 335 -336
Dyslipidemia, 121 pharmacy practice. 585 human subjects, protection of, 336
Enteral nutrition, 458 individual, vs. social interest, 339
drug reaction with, 30 informed consent, 336-337
Ear. nose, throat disorders group, Cochrane Environmental Chemicals Data and Information investigator independence, 340
collaborative, 183 Network, 774 moral principles, 337-339
Eatonform, software. 218 Environmental Protecton Agency, careers Nuremberg Code, 341
ECDIN. See Environmental Chemicals Data and options, clinical pharmacy scientific integrity, 340
Information Network scientist, 179 study volunteers, payment to, 337
Index 919
Ethical issues (cont.) Fear tactics, nonadherence in pharmaceutical Formulary systems, 362-365
secondary use of data. 879 care and, 14 drug selection, 363-364
unavailability of medication. 332-333 Federal Bureau of Prisons, careers in, 387 ethical issues. 364-365
Ethnic minorities, adherence to medical care, Federal government regulations governing formulary maintenance, 364
16- 17 prescribing, 191 history, 362-363
Ethosuximide, pediatric pharmacokinetic data, Fellowships, 355-357 history of. 860-861
665 applicant requirements, 356 medication use evaluation. 364
Etreby Computer, software, 216, 218 in clinical pharmacology, 356 positive. negative outcomes. 364
European Association of Poisons Centres and defined, 231 structure of, 363-364
Clinical Toxicologists, 762 definitions, 355 Foscamet, AIDS, 442
European Society of Clinical Pharmacy. experience of. 356 Freedom Data Systems, software, 216, 218
344 - 347 fellowship. defined, 355 Functional foods. 603-607
activities of, 345-346 guidelines, 355-356 categorizing, 605
calendar of events, 347 preceptor qualifications, 356 challenges facing. 604
clinical pharmacy, 345 resource, 356-357 examples. 603-604. 605
conferences, 345 training program requirements, 356 guidelines, 606-607
education. 345 FEMA Rapid Response Information healthful foods, categories of, 604
executive committee, 346 System, 776 Funding, National Institutes of Health. 576-577
general committee members, 346 Fertility group, Cochrane collaborative, 183 Fungi images on net. 775
goal, 344-345 Fertility regulation group, Cochrane Furosemide, drug reaction, 27
international office, 347 collaborative, 183 Future directions in clinical practice in phar-
members, 347 Financial information, patient drug history, 286 macy (Hilton Head Conference),
organization of. 346-347 Financing 265-266
related organizations, 345 -346 health care, 401-403 Future of Public Health, 481
research, 345 healthcare, 410-41 1
research and education committee. 347 First DataBank, Inc.. 358-361
special interest groups, 347 drug knowledge bases, 359 Gabapentin. 588
symposia, 345 drug interactions, 359 Gait, 586
Evaluating Drug Literature, 293 patient education, 359 Ganciclovir IV, AIDS, 442
Evaluation, clinical pharmacist. American prescriber order entry, 359 Garlic. adverse reaction to, 31
College of Clinical Pharmacy, Evaluations of Drug Interactions, 360 Gastric emptying time, 89
154- 160 future needs, 361 Gastrointestinal, pancreatic diseases group,
Evaluations of Drug Interactions, 360 integrated content software, 359-360 Cochrane collaborative. 184
Evidence-based practice, 348-354 Drug Information Framework, 360 Gastrointestinal absorption, drug, 25
applying evidence. 350 Rx InHand, 360 Gastrointestinal complaints, 588
challenges of, 351 RxWeb, 360 Gastrointestinal disease, drug reactions and, 27
clinical effectiveness, 35 1-352 locations, 361 Gastrointestinal motility, 89
criticisms of. 350-351 mission statement, 358-359 Gastrointestinal system
implementation, 352-353 Nutritionist Pro, software, 360-361 blood perfusion, 89-91
incomplete evidence, 35 1 reference products, 360 drug absorption in. 90-91
number needed to treat. 350 software, 216, 218 neurology specialty pharmacy practice, 585
pharmacist's role, 352 specialty software, 360-361 Gender, adverse drug reactions and, 28
relative risk, 349 Florida Gene therapy, 367-378
resources for, 352 pharmacy practice legislation, 272 cancer; 373
understanding evidence, 349 -350 regulations governing prescribing, 190 cardiology, clinical trials:, 375
web sites, 352 Flu, as cause of death, 404 cystic fibrosis. 373
Evolution. of academicians, 3 Flu shots, for older adults, effectiveness of. definition, 367-368
Excipients studies, 565 ethical issues. 376-377
effect on pharmacokinetics, 95 Fluid, neurology specialty pharmacy practice, gene therapy clinical trials, 373
in liquid drug products. 95 585 monogenic disorders, 373
solid drug products, 95 Fluvoxamine, as cytochrome P450 inhibitor, 247 severe combined immunodeficiency
Exclusion of populations. ethical issues, 879 Folic acid during pregnancy, 585 syndrome, 373
Expenditures for pharmaceuticals, reduction Follow-up. in adherence in pharmaceutical care, herpesvirus thymidine kinase, 373
of, 35 14 HSV-TK. 373-374
Experience required, in academic clinical Food; effect on absorption, 91-92 infectious disease. clinical trials, 375
pharmacy, 4 Food and Drug Administration, 251 -252, multidrug resistance. 376
785-786. 896 oncology, clinical trials, 375
careers. 179, 386 patient monitoring, 372-373
Faculty, academic clinical pharmacy, 3 policies, 148- 149 SCIDS. 373
Family environment, home care, 440 Food and Drug Modernization Act, 36 vector production and administration,
Family medicine, fellowships in, 356 Foodborne Pathogenic Microorganisms and 371-372
Family planning. Medicaid usage, 516 Natural Toxins Handbook, 775 vectors, 368-371
FDA. See Food and Drug Administration Formulary manager, professional opportunities, adenoviral vectors, 369-370
FDAMA. See Food and Drug Modernization Act 502 plasmid-based vectors, 371
920 Index
Health-systems, clinical pharmacy careers in HIV/AIDS Treatment Information cholesterol monitoring tests, CLIA waived
(cont.) Service, 896 status, 466
therapeutic drug monitoring service, 428 Holistic medicine, 774 clinic models, 463
sites. 430 Home care practice, 435-438. 502 communication, 466
work settings. 429 activities, 436-437 community pharmacy practice, 462-463
general clinical practice model. 429 career options, 437-438 documentation, 466
outpatient pharmacy. 429 education-related issues. 437 institutional pharmacy model. 464
Healthy People 2010. 432-434 Medicaid usage, 516 lipid management practices, 463
Heart attack, beta blocker treatment after, patient database, 436 lipid measurement devices, 466-467
effectiveness of, studies, 565 preadmission criteria, 436 outcomes, 813
Heart disease. as cause of death, 404 Spain, 439-446 patient education, 466
Heart failure, drug reactions and, 27 advantages, 439 pharmacist education, 464-465
Heart group, Cochrane collaborative, 183 AIDS, 441 -443 practice models, 462-464
HEDIS. See Health Plan Employer Data and antibiotic therapy, cost savings, 441 reimbursement strategy, 467
Information Set classification, 439-440 screening programs, 462-463
Hematologic disease, drug reactions and, 27 community-based, 440 Hypersensitivity reaction, to drug, 23
Hematology: Basic Principles and Practice, 622 family environment, 440 Hypertension, 121, 754, 812
Hematology, home care, 442 home environment, 440 drug reactions and, 27
Hematology system, neurology specialty hospital-based, 439-440 nonadherence to medical care in, 18-19
pharmacy practice. 585 infections, 441 Hypertension group. Cochrane
Hematopoiesis chart. 109- 110 organization, 439-440 collaborative, 183
Hemophilia, drug reactions and, 27 parenteral antibiotics, 441 Hyperthyroidism. drug reactions and, 27
Hemorrhage, with routine medical care, vs. patient selection. 440-441 Hyperuricemia, drug reactions and, 27
pharmacist-managed type of interventions, 441 Hypoalbuminemia, adverse drug reactions
anticoagulation, 65 web sites. 444 and, 26
Heparin, 587 work environments, 435-436 Hypothyroidism, drug reactions and, 27
Hepatic disease, adverse drug reactions and. Home monitoring, 287
25 - 26 Hospice, 447-452
Hepatic system, neurology specialty pharmacy computer links, 450 ICAAC. See Interscience Conference for
practice, 585 documentation, from care providers, 452 Antimicrobial Agents and
Hepatitis A, 712 Hospice Foundation of America, 450 Chemotherapy
Hepatitis B. 712 Hospice Hands, web site, 450 ICC. See International Conference of
Hepato-biliary group, Cochrane managed care. clinical pharmacy Chemotherapy
collaborative, 183 careers, 504 ICMASKO. See International Conference
Herbal medicines, adverse drug reactions. 3 1 marketing pharmaceutical care, 45 1-452 on Macrolides, Azalides,
Herbal therapies. adverse drug reactions and, 28 National Hospice and Palliative Care Streptogramins, and Ketolides
Herpes simplex, with AIDS, 442 Organization, 450 Idaho, pharmacy practice legislation, 272
Herpes zoster, with AIDS, 442 Open Society Institute, Project Death in Idiosyncratic reaction to drugs, defined, 23
Herpesvirus thymidine kinase. gene America, 450 IDSA. See Infectious Diseases Society
therapy. 373 Palliative Medicine Program, 450 of America
High blood pressure, controlling, effectiveness professional opportunities, 449 Ileum, drug absorption in, 90
of, studies, 565 Purdue Pharma Pain and Palliative Care Imipramine, cytochrome P450, 247
Higher education. academic clinical Information, 450 Immunization practice. pharmacy-based, 56 1
pharmacy, 2 resources. 450 documentation, 561
Hilton Head Conference, directions in clinical Talarian map, cancer pain, 450 liability, 561
practice in pharmacy. 265 -266 Hospice Foundation of America, 450 reporting. 561
Hip fracture. gene therapy, 376 Hospice Hands, web site, 450 Immunosuppressants, 588, 870
Histamine-receptor antagonist, clinical phar- Hospice interdisciplinary team. 448 complications, 870
macy. economic analysis, 307-321 Hospital inpatient, Medicaid usage, 516 outpatient, Medicare Benefits and
Histoplasmosis, with AIDS, 442 Hospital outpatient, Medicaid usage. 5 16 Improvement Act of 2000, 530
History form. patient, 288 HRSA. See Health Resources and Services Medicare coverage under, 530
HIV, 586 Administration solid organ transplant, 530
Confronting AIDS: Direction f o r Public HSV-TK. See Herpesvirus thymidine kinase transplant facility. Medicare-
Health, Health Care, and Human genetics research, ethical issues, approved, 530
Research, 48 1 880-881 In vitro dissolution testing, 96-97
No Time to Lose: Getting More from HIV Human inmmunodeficiency virus. See HIV Incontinence group. Cochrane
Prevention, 481 Human subjects. protection of, 336 collaborative, 183
post-exposure prophylaxis. 891 -898 Huntington’s chorea, 585 Independent consultant, infectious
transmission, occupational, risk of, following Hydralazine, adverse drug response, 29 diseases, 47 1
exposure, 892 Hydrogenated vegetable oil, excipient in Indian Health Service, 252-253
universal precautions, 891 -898 drug, 95 careers in, 386
unlabeled indications, drug use for, 551 Hydroxypropylmethylcellulose, excipient in Indiana, regulations governing prescribing,
HIViAIDS group, Cochrane drug, 95 190
collaborative, 183 Hyperlipidemia, 461 -468, 585 Indinavir, 895
922 Index
Individual, vs. social interest, ethical issues. regulatory affairs, 528 Institute of Medicine, 480-481
339 safety reporting, 528 activities, 480-481
Industry, drug information pharmacy practice, sales, 527 Confronting AIDS: Direction f o r Public
291-292 labeling, promotional review committee, Health, Health Care, and
Infection 528 Research, 48 1
Emerging Infections: Microbial Threats to publications committee, 528 Emerging Infections: Microbial Threats to
Health in United States, 481 committee involvement, 528-529 Health in United States, 481
home care pharmacy, 441 global medical information, 528-529 To Err is Human: Building Safer Health Care
Infectious disease, 469-475, 837 labeling, promotional review committee, System, 480
board certification, 469 528 Future of Public Health, 481
books, 473 publications committee, 528 Growing Up Tobacco Free: Preventing
contract research organization, 471 daily work flow management, 526-527 Nicotine Addiction in Children and
education, 469 customer base, 526 Youths, 481
fellowships in, 357 documentation, 527 Halcion: A n Independent Assessment of
gene therapy clinical trials, 375 triage procedures, 527 Safety and Eficacy Data, 481
government, 47 1 volume, type of requests, 526-527 National Academy of Sciences, chartering
guidelines, 473-474 drug product information dissemination, by, 480
hospital practice, 470 525-526 No Time to Lose: Getting More from HIV
hospital setting, 471 -472 data on file, 526 Prevention, 481
independent consultant, 471 drug information resources, 525 -526 Pharmacokinetics and Drug Interactions in
industry consultantships. 475 guidelines, limitations, 525 Elderly and Special Issues in
journals. 472-473 package labeling, 525-526 Elderly African-American
model clinical practice settings, 471 -472 references, 526 Populations, 481
networking opportunities, 474-475 education, 529 Insurance companies, managed care, 292
outpatient practice, 470 academic rotation site, 529 Insurance information, patient drug history,
outpatient setting, 472 continuing education, 529 286
pharmaceutical industry, 470 employee education, 529 Integrative medicine, 482-486
postgraduate training, 469 internal support functions, 527-528 challenges to, 484-485
professional opportunities, 470-47 1 clinical research, 528 clinical model, 484
professional societies, 474-475 marketing, 527-528 Consortium of Academic Health Centers for
training, 469 quality assurance, 528 Integrative Medicine, 484
infectious Diseases Clinics of North regulatory affairs, 528 definition of, 483
Anzerica, 473 safety reporting, 528 future trends, 485
Infectious diseases group, Cochrane sales, 527 Intelligence program, Drug Enforcement
collaborative, 183 Information technology/database manager, Agency, 282
Infectious Diseases in Clinical Practice. 473 professional opportunities, 502 Intensive care unit, clinical pharmacy, economic
Infectious Diseases Society of America, 474 Informed consent, 336-337, 877-878 analysis, 307-321
Inflammatory bowel disease group, Cochrane InfoWin, 456 Interactions between drugs, 24-25
collaborative, 183 Inhalers, pediatric dosing, 675 Interactive patient counseling, 649
Influenza, 7 12 Injuries group, Cochrane collaborative, 183 Interactive Systems, software, 216, 218
Information, medical, industry-based, 525 -529 Innovation Associates, software. 216, 218 Interdisciplinary team, hospice, 448
careers in, 525-529 Institute for Safe Medication Practices, 476-477 Internal medicine, fellowships in, 357
committee involvement, 528-529 mission, 476 International Association for Study of Pain,
daily work flow management, 526-527 objectives, 476-477 643
customer base, 526 analysis-based ISMP initiatives, 476 international Association for Study of Pain
documentation, 527 communication-based ISMP initiatives, Newsletter, 450
triage procedures, 527 477 International Conference of Chemotherapy,
volume, type of requests, 526-527 cooperation-based ISMP initiatives, 477 475
drug product information dissemination, education-based ISMP initiatives, 477 International Conference on Macrolides,
525-526 knowledge-based ISMP initiatives, 476 Azalides, Streptogramins,
data on file, 526 Spain, 478-479 and Ketolides, 475
drug information resources, 525-526 future goals, 479 International Conference on Retroviruses, 475
guidelines, limitations, 525 medication errors reporting program, International Pharmaceutical Abstracts,
package labeling, 525-526 478-479 57, 487
references, 526 mission, 478 International Quality of Life Assessment
education, 529 Objectives, 478 Project, 422
academic rotation site, 529 projects, 479 International Society for Pharmacoeconomics
continuing education, 529 Institute for Safe Medication Practices-Spain, and Outcomes Research, 488-489
employee education, 529 478-479 International Society of Antiinfective
global medical information, 528 - 529 future goals, 479 Pharmacology, 474
internal support functions, 527-528 medication errors reporting program, 478 -479 International Technidyne Corp., 141
clinical research, 528 mission, 478 Internet Grateful Med, 582
marketing, 527-528 objectives, 478 Interscience Conference for Antimicrobial
quality assurance, 528 projects, 479 Agents and Chemotherapy, 474
Index 923
Interviewing patient, drug history, 285-286 accreditation status, 493-495 Leukemias, gene therapy trials, 374
communication, 285 background, 493 Levodopa, 588
setting. 285 Joint Commission of Pharmacy Practitioners, Lewy body disease, 585
special patient populations, 285-286 496-497 Liability, manufacturer, vaccines, 559 -560
Intestinal motility, 89 history, 496 Liberty Computer, software, 216, 218
Intramuscular administration, pediatric dosing, member organizations, 496-497 License, defined, 231
673-674 Academy of Managed Care Pharmacy, 496 Licensure, defined, 231
Intravenous administration, pediatric dosing, American Association of Colleges of Lidocaine, drug reaction, 27
666-670 Pharmacy, 496 Lifestream Technologies, 141, 466
Investigator, principle, clinical pharmacist as, American College of Apothecaries, 496 Lipid management practices, 463
144- 153 American College of Clinical Pharmacy Lipid measurement devices, 466-467
American College of Clinical Pharmacy, (American Association of Colleges Lipid monitoring form, 465
clinical pharmacist evaluation, of Pharmacy), 496 Lipid-lowering agents, 588
154- 160 American Council on Pharmaceutical Liposome, viral transfer techniques, 368
assessment methods, 154- 159 Education, 496 Liquid drug products, excipients used in, 95
budget, 151 American Pharmaceutical Association Literature search method, 303
current industry, 145- 148 (APhA), 496 Lithium, 585
FDA policies, 148- 149 American Society of Consultant Liver disease, as cause of death, 404
FDA regulations, 148- 149 Pharmacists, 496 Liver function tests, 588
history, 144- 145 American Society of Health-System Long-term care, clinical pharmacy careers in,
publication rights, 151- 152 Pharmacists, 496 498-499
qualifications, 152- 153 National Association of Boards of consultant pharmacist services, 498
access to patients, 153 Pharmacy, 496 history, 498-499
audits, 153 National Community Pharmacists job settings, 499
command of research process, 152 Association, 496 professional opportunities, 499
experience, 152 National Council of State Pharmacy role of consultant pharmacists, 498
human resources, 152 Association Executives, 496 training, certification requirements, 499
local leadership, 153 programs, 497 Louisiana, pharmacy practice legislation, 272
local resources, 152 Jouinal of Antimicrobial Chemotherapy, 472 Low plasma pseudocholinesterase, drug
responsibilities of, 149- 150 Journal of Infectious Diseases, 472 reaction, 29
template, 154, 155- 159 Journal of Infectious Diseases Low-density lipoprotein receptor, gene therapy,
Investigator independence, ethical issues, Pharmacotherapy, 473 375-376
research, 340 Journal of Pain, 450 Low-literacy patients, adherence with, 16
IQOLA Project. See International Quality of Journal of Pain and Palliative Care Lowy Report, Prescriptions forHealth, 791 -793
Life Assessment Project Pharmacotherapy, 450 Lung cancer group. Cochrane collaborative, 183
ISAP. See International Society of Antiinfective Journal of Pain and Symptom Lupus, drug reactions and, 27
Pharmacology Management, 450 LXN Corp., 141
Ischemic stroke, 587 LXN Duet Glucose Control Monitoring
prevention, 588 System. 141
Isoniazid, 870 Kansas, pharmacy practice legislation, 272 LXN Fructosamine Test System, 141
adverse drug response, 29 Karolinska Institute-Poisoning Information, 774 LXN IN CHARGE Diabetes Control
as cytochrome P450 inducer, 247 Kentucky System, 141
ITC Protime Microcoagulation System, 141 pharmacy practice legislation, 272 Lymphoma, gene therapy trials, 374
regulations governing prescribing, 190
Ketoconazole, as cytochrome P450
JAG Group, software, 216, 218 inhibitor, 247 Magnesium stearate, excipient in drug, 95
Janus Commission (American Association of Malignant pain, 639-640
Colleges of Pharmacy), 491 -492 Managed care, 506-5 11
history, 491 Labeling assertiveness, 507
members of, 492 dietary supplements, 261 -262 care, clinic coordinators, 507
mission, 491 -492 package, medical information, case studies
Japan, health care systems, 391-392 industry-based, 525 -526 all-inclusive care for elderly (PACE)
jASCorp, software, 216, 218 Laboratories program, Drug Enforcement programs, 504
JCAHO. See Joint Commission for Accredita- Agency, 282 hospice, 504
tion of Healthcare Organizations Laboratory tests, Medicaid usage, 516 specialty clinics, 504-505
JCPP. See Joint Commission of Pharmacy Lactose, excipient in drug, 95 utilization management, 504
Practitioners Ladder, career, academic clinical pharmacy, 4 clinical pharmacy careers in, 501 -505
Jejunum, drug absorption in, 90 Lamivudine, 895 case studies, 504-505
Johns Hopkins Center for Civilian Biodefense Language bamers, drug history-taking, 286 preparing for, 501-503
Studies, 777 LDL. See Low-density lipoprotein professional opportunities, 503 - 504
Johnson &Johnson, 141 Learning problems, Cochrane collaborative, 183 settings, 501
Joint Commission for Accreditation of Legislation, generic drugs, 379-380 skills, 503
Healthcare Organizations, 493 -495 Length of hospital stay, clinical pharmacy, communication, mediation skills, 507
accreditation process standards, 495 economic analysis, 307 - 32 1 diabetes care, 258
924 Index
Managed care (cont.) global medical information, 528-529 process-improvement approach, 536-538
disease management, 507-508 labeling, promotional review reporting program, Institute for Safe
drug information knowledge, 507 committee, 528 Medication Practices, 478-479
evaluating clinical, economic data, 508-509 publications committee, 528 role of pharmacist, 542-543
fellowships in. 357 daily work flow management, 526-527 Medication Teaching Manual. American Society
health, managing, 508 customer base, 526 of Health-System Pharmacists, 57
innovative positions, 507 documentation, 527 Medication use evaluation, 545-549
insurance companies, 292 triage procedures. 527 approaches to, 547-548
opportunities available. 506 -509 volume, type of requests, 526-527 goals of, 546
outcomes, measuring. 509 drug product information dissemination, limitations, pitfalls of. 548
skills, 506 525-526 priority setting, 546-547
strengths of pharmacy, 506 data on file, 526 process, 547
work in teams, ability to, 507 drug information resources. 525 -526 role of pharmacist, 546
Manager of clinical initiatives, professional guidelines, limitations. 525 scope, 546
opportunities, 502 package labeling. 525-526 tools, resources, 548
iWanaging Oral Anticoagulation Therapy, Clin- references, 526 value of, 548
ical and Operational Guidelines, 67 education, 529 Medication use for unapproved indications,
Manufacturer liability, vaccines. 559-560 academic rotation site, 529 550-553
Marijuana eradication program, Drug continuing education, 529 liability. 552
Enforcement Agency, 282 employee education. 529 patient safety, 550-552
Marketing internal support functions, 527-528 reimbursement, 552
dietary supplements, 261 -262 clinical research, 528 unlabeled indications, drug use for, 551
input, clinical evaluation, drugs, 135 marketing, 527-528 antineoplastics, 55 1
of pharmaceutical care, 451 -452 quality assurance, 528 antipsychotics, 551
Martindale Health Science Guide-Virtual regulatory affairs, 528 HIV, 551
Pharmacy Center, 774 safety reporting, 528 metoclopramide, 55 1
Masked facies. 586 sales, 527 ondansetron, 551
Matching program, resident, 841 Medical NBC Online Information Server, 776 MEDLINE, 580-581, 582, 773
Mayday Upper Peninsula Project, 643 Medical outcomes study, health status MEDLINEplus. 582
McKessonHBOC, software, 216, 218 assessment, 417 MedMARx, 889
MDR. See Multidrug resistance Medical records. access to, 196 MedNet, 774
Measles, 712 Medicare. 5 13 Melanoma, gene therapy trials, 374
Medicaid, 5 12-5 18 contact points, 512-514 Menstrual disorders, Cochrane collaborative, 183
administration of drug benefit, 515 description, 512-514 Mental health facility, clinical pharmacy,
clinical pathways, 5 15 and contact points, 512-514 economic analysis. 307-321
drug benefit coverage, 514-515 pharmaceutical programs, 5 12-5 18 Mental health scale, 423
drug coverage, 514-516 Medicare Benefits and Improvement Act of Mental status. 586
drug evaluation, 515 2000 for outpatient immunosup- Mentally retarded, Medicaid usage, 5 16
extending drug coverage, 514-515 pressive agents, 530 Mephenytoin, cytochrome P450, 247
financial conundrum. 514 Medicare coverage under, 530 Mesothelioma. gene therapy trials. 374
formulary coverage. 5 15 solid organ transplant, 530 Metabolic. endocrine disorders group, Cochrane
healthcare coverage options, 5 13-5 14 transplant facility. Medicare-approved, 530 collaborative, 183
history, 5 12-5 13 Medicare+Choice, 5 14 Metastatic cancer, gene therapy trials, 374
individuals utilizing, 5 16 drug step therapy, 515 Methemoglobin reductase deficiency, drug
Medicare, description, 512-514 Medication assistance programs, pharmaceutical reaction, 29
Medicare participation, 5 14 company-sponsored, 531 -532 Methyl propylparaben, excipient in drug, 95
Medicare program, 5 13 enrollment, 531 -532 Methylcellulose, excipient in drug, 95
original Medicare plan, 513-514 ethical issues, 532 Methylprednisolone, 587, 870
pharmaceutical care, disease management information frequently requested, 532 Metoclopramide, unlabeled indications, drug use
and, 515 internet sites, 531 for, 551
pharmacy benefit, tools to manage, 515 medication, 532 Metopronolol. cytochrome P450, 247
reimbursement, 516-518 pharmacists’ role. 532 Metrika, Inc.. 141
resource-based relative value system, Medication errors. 533-544 Metrika DRx HbAlc, 141
515-516 human reliability Metronidazole. adverse drug reaction, 30
Medical Botany Library. 775 curve, 539 Mexico, health care systems, 395
Medical College of Wisconsin Palliative Care enhancing, 539-542 Mexilitine, 588
Medical Program, 643 manageable behaviors, 540 Michigan
Medical communications, clinical pharmacy at-risk behavior, 540-541 pharmacy practice legislation, 272
careers in, 519-524 high-culpability behavior, 541 -542 regulations governing prescribing, 190
income. 519-521 imperfect behavior, 540 Microcrystalline cellulose, excipient in drug, 95
training, 522-523 medication-use cycle, 533-535 Micromedex, software, 216, 218
Medical information, industry-based, 525 -529 outcomes-measurement approach, 538 - 539 Midrin, 588
academic rotation site, 529 preventable patient harm, scientific Millis Commission, 554-557
committee involvement> 528-529 investigation, 536-539 clinical scientists, concept of, 556
Index 925
Millis Commission (cont.) Narcotic analgesics, drug reaction, 27 examination eligibility requirements. 573
credentialing. 557 Narrow-angle glaucoma NISPC DSM examinations. 573
graduate. advanced professional educational Cochrane collaborative, 27 organizational structure/meetings. 572 -573
programs, 556 drug reactions and, 27 National Institutes of Health, 25 1, 575 -579
organization, 554-557 Nasal administration, pediatric dosing, 675 campus, 576
pharmacy, defining, 555 National Academy of Sciences, chartering of facilities, 576
pharmacy curricula, design of, 555-556 Institute of Medicine, 480 careers, 179; 386-387
preparation of pharmacists. environment National Academy Press, 773 centers. 576-578
for. 556 National Association of Boards of Pharmacy, clinical studies, 577
providers of drug information, pharmacists as, 232: 270, 496 contracts, 578
554-555 National Association of Chain Drug Stores, 232, events. 579
Mini Mental Status Examination, 588, 741 -748 270 extramural research, 578
Minnesota. pharmacy practice legislation, 272 National Asthma Educator Certification Board, funding. 576-577
Minorities, adherence to medical care, 16- 17 American Lung Association, 232 general information, 579
Mission statement, Academy of Managed Care National Cancer Institute, 621 grants. 578
Pharmacy. 6 National Certification Board for Diabetes health information resources, 578-579
Mississippi Educators, 232, 270 institutes, 576-578
pharmacy practice legislation, 272 National Childhood Vaccine Injury Act of 1986, mission, 577
regulations governing prescribing, 190 559-563 offices, 576-578
Mitretek Systems, 776 adverse events, vaccine. 559 public health. contributions to, 575-576
Model clinical practices, managed care, childhood diseases, vaccination against. 559 research and research policy. 179
509-510 documentation, 561 scientific resources, 578
Health Plan Employer Data and Information historical advancements, 559 training, 577-578
Set. 510 immunization practice, pharmacy-based, 561 National Library of Medicine, 580-583, 773
Joint Commission on Accreditation of liability, 561 contacting, 583
Healthcare Organizations. 509 manufacturer liability, 559-560 databases, 582
National Committee for Quality Assurance, National Vaccine Injury Compensation ClinicalTrials.gov. 582
509 Program, 560-561 Internet Grateful Med, 582
networking opportunities, 510 protection under NCVIA, 561 MEDLINE, 582
Molecules, passive diffusion of, 87 reporting, 561 MEDLINEplus, 582
Monogenic disorders. gene therapy, 373 Vaccine Injury Act of 1986, 560-561 PubMed, 582
Montana, pharmacy practice legislation, 272 vaccine injury table, 560 PubMed Central, 582
Motor function, 586 National Chronic Pain Outreach Association, TOXNET, 582
Movement disorders group. Cochrane 643 electronic publishing, 583
collaborative, 183 National Clinicians’ Postexposure Hotline, 896 highlights of. 581
MTM Bioscanner 1000, 141 National Committee for Quality Assurance, history. 580
Multicenter. clinical pharmacy. economic model clinical practices, managed MEDLINE. 580-581
analysis, 307-321 care, 509 pharmacy practice. research, 581 -582
Multidrug resistance, gene therapy. 376 National Community Pharmacists Association, PubMed, vs. Internet Grateful Med, 582
Multidrug use. adverse drug reactions and, 28 232, 270, 496, 568-571 telemedicine, 583
Multiple sclerosis, 587. 588 governance. 569 National Vaccine Injury Compensation
Multiple sclerosis group, Cochrane historical overview, 568-569 Program. 560-561
collaborative. 183 initiatives, 569-571 NCBDE. See National Certification Board for
Muscle relaxants, adverse drug reaction, 29 mission, 569 Diabetes Educators
Musculoskeletal group. Cochrane collaborative, organizational structure. 569 NCCN. See National Comprehensive
183 National Comprehensive Cancer Network, 621 Cancer Network
Musculoskeletal injuries group. Cochrane National Council of State Pharmacy Association NCPA. See National Community
collaborative, 183 Executives, 496 Pharmacists Association
Musculoskeletal system, neurology specialty National Council on Patient Information and NCPIE. See National Council on Patient
pharmacy practice. 585 Education. 15 Information and Education
Myasthenia gravis, 586, 588 National Formulary, United States NCQA. See National Committee for
drug reactions and. 27 Pharmacopeia, 887-889 Quality Assurance
Mycobacterium. with AIDS, 442 National Foundation for Treatment of Pain, 643 NCSPAE. See National Council of State
Myocardial ischemia, drug reactions and, 27 National HIV/AIDS Clinician’s Consultation Pharmacy Association Executives
Center. 896 Nebraska, pharmacy practice legislation, 272
National Hospice and Palliative Care Neck cancer, gene therapy trials, 374
NABP. See National Association of Boards of Organization, 450 Nelfinavir, 895
Pharmacy National Institute for Clinical Excellence, Nephrology. fellowships in, 357
NACDS. See National Association of Chain 393-394 Networking opportunities
Drug Stores National Institute for Standards in Pharmacist anticoagulation, 68
Nafcillin, 870 Credentialing, 229, 232, 270, bone manow transplant, 110
Nalidixic acid, adverse drug reaction. 29 572-574 cardiology. 123- 124
Naranjo causality algorithm, adverse drug activities, 573-574 drug information pharmacy practice, 293-294
reactions, 32 exam registration process, 573 infectious diseases, 474-475
926 Index
Networking opportunities (cont.) NISPC. See National Institute for Standards in distance learning, 595
model clinical practices, managed care, 510 Pharmacist Credentialing Doctor of Pharmacy degree programs, 591
neurology specialty pharmacy practice, Nitrates, drug reaction, 27 prior learning, assessment of, 595-599
589-590 Nitrites, adverse drug reaction, 29 videotaped lectures, 594-595
specialty practice, clinical pharmacokinetics, Nitrofurantoin, adverse drug reaction, 29 web-based coursework, 595
166-167 No Time to Lose: Getting More from H N Nordic Cochrane Centre, 185
Neurological disorders, drug reactions and, Prevention, 481 North American Mycological Association, 775
27 Nonadherence in pharmaceutical care North Carolina, pharmacy practice legislation,
Neurological system, neurology specialty assessing, 12- 13 272
pharmacy practice, 585 direct methods, 12 North Dakota
Neurology, fellowships in, 357 indirect methods, 12- 13 pharmacy practice legislation, 272
Neurology specialty pharmacy practice, as behavioral disorder, 11 regulations governing prescribing, 191
584-590 children, 17- 18 Nuremberg Code, 341
cardiovascular system and, 585 chronic diseases, 18- 19 Nursing facility
educational opportunities, 589 -590 community resources, 17 diabetes care, 257-258
EENT, 586 cultural differences and, 17 Medicaid usage, 516
endocrine system and, 585 defined, 10- 11 Nutraceuticals, categories of, 604
fluid/electrolyte/nutritional status, 585 Eldercare Patient Education Series, 15 Nutrients, adverse drug reaction, 30
gastrointestinal system, 585 elderly, 15- 16 Nutrition
guidelines used in, 589 cognitive limitations, 15 adverse drug reactions and, 28
GU/reproductive system, 585 limited access to or affordability of health status, neurology specialty pharmacy practice,
hematology system. 585 care services, 15 585
hepatic system, 585 physical impairments, 15 support, home care, 443
inpatient neurology specialty practice, polyphannacy, 15 Nutritionist Pro, software, 360-361
586-587 risk factors for nonadherence, 15 Nystagmus, 586
musculoskeletal system, 585 ethnic minorities, 16- 17
networking opportunities, 589-590 factors affecting, 13
neurologic patient, approach to. 584 fear tactics, 14 Obstetric patients, home care, 443
neurological system, 585 follow-up, 14 Occupational HIV transmission, risk of,
outpatient neurology specialty practice, hypertension, 18- 19 following exposure. 892
587-589 implement reward system, 14 Octreotide, 870
pharmacotherapy history, 584 informed medication consumer, patient as. Ocular disease, drug reactions and, 27
psychological exam, 585 14 Oddis, Joseph A,, 609-610
pulmonary system, 585 low-literacy patients, 16 accomplishments, 609 - 6 10
renal system, 585 National Council on Patient Information and education, 609
review of systems, 584-586 Education, 15 influence on clinical pharmacy practice,
vital signs, 585 patient goals, 14 610
skin. 586 patient-centered adherence paradigm, 11 positions, 609
targeted neurological exam, 586 patient-focused interventions for, designing, professional involvement, 609
vital signs, 585 13-14 training, 609
Neuropathic pain, 641-642, 754 payment for adherence services, 20 Office of Secretary of Health and Human
Neuropathy, 586 Pediatric Medication Text, 15 Services, 254
Neurosis, Cochrane collaborative, 183 Peter Lamy Center for Drug Therapy and Ohio, pharmacy practice legislation, 272
Neutraceuticals, 603-607 Aging, 15 Omeprazole, cytochrome P450, 247
categorizing, 605 pharmacotherapy, enhancing adherence to, Omnicell, 456
challenges facing, 604 14-18 automated delivery, 456
examples, 603-604, 605 resources for improving, 15 OmniSYS, software, 216, 218
guidelines, 606-607 risk factors for, 11 OncoLink, 643
healthful foods, categories of, 604 scope of problem, 10- 11 Oncology, 61 1-626
Nevada self-efficacy, 14 anticancer therapy. outcomes related to, 618
pharmacy practice legislation, 272 space considerations, 20 chemotherapy order verification, 6 12
regulations governing prescribing, 191 special populations, 14- 18 clinical pharmacy opportunities, 61 1-614
New business developer, professional type 2 diabetes, 19 clinical research, 617-618
opportunities as, 502 Nonalignment pain, pain management, documented benefits, 618-620
New England Cochrane Center, 185 640-64 1 drug administration policies, 613
New Mexico Nonsteroidal anti-inflammatory drugs drug handling, 612-613
pharmacy practice legislation, 272 adverse drug reaction, 27 drug information, 614, 617
regulations governing prescribing, 191 clinical pharmacy, economic analysis, education, 614
Nicotine addiction, Growing Up Tobncco Free: 307 - 32 1 fellowships in, 357
Preventing Nicotine Addiction in Nontraditional Pharm.D, 591 -602 gene therapy clinical trials, 375
Children and Youths, 481 admission requirements for, 592-593, 594 guidelines, 620-622
Nifedipine, cytochrome P450, 247 background information, 591 -593 home care, 442
NIH. See National Institutes of Health degree transfer mechanisms, 591 inpatient care practice roles, 615-616
Nimodipine, 587 didactic instructional methods, 594-595 investigational drug use, 617
Index 927
Pediatrics (cont.) Personal interviews, ethical issues, 878- 879 Association of Pharmaceutical
endotracheal, 661 Peter Lamy Center for Drug Therapy and Aging, Scientists, 166
enzyme activity. 658 15 Pharmacokinetics and Drug Interactions in
gastric emptying, 658 Pew Health Professions Commission reports, Elderly and Special Issues in
gastric pH, 658 685-687 Elderly African-American
intramuscular, 658 -659 pharmacy, 686- 687 Populations, 481
intraosseous, 659 reports, 685-686 Pharmacokinetics and Drug Metabolism
percutaneous, transdermal, 659 -660 Pharmaceutical Abstracts, International, Section, American Society for
rectal. 661 (American Society of Clinical Pharmacology and
subcutaneous, 659 Health-System Pharmacists), 487 Therapeutics, 166- 167
administration techniques, 672-673 Pharmaceutical Benefits Scheme (Australia), Pharmacokinetics/Dynamics Practice Research
adverse drug reactions, 26 subsidies, 689-690 Network, American College of
adverse drug reactions and, 25, 26 Pharmaceutical care, 692-697 Clinical Pharmacy, 166
body composition, differences in, 661 -662 collaborative partnerships, 693 Pharmacopeia, United States, 886-890
central nervous system, drug penetration into. compensation, 695-696 Phartnacotherapy: Journal of Human Pharma-
662 follow-up evaluation, 694-695 cology and Drug Therapy, 124-725
density, 668 as generalist practice, 693 Pharnzacotherapy Self-Assessment Program
developmental physiologic changes, 657-658 history of landmark developments, 692 (American Association of Colleges
disposable IV equipment, 667-668 measuring outcomes, 695 of Pharmacy), 726-727
dosage forms, 670-671 patient assessment, 693-694 Pharmacotherapy specialty practice, 732-735
dosing regimens patient care process, 693-695 functions, 732-733
drug administration, mechanical system for, pharmaceutical care plan, 694 guidelines, 728-731
669 - 670 Pharmacist’s Workup of Drug Therapy, qualifications, 733
excipients, in medications, 664-666 693 supplemental information, 734
extemporaneous liquid preparations, 67 1 philosophy of, 693 value, 733-734
fellowships in, 357 practice management system, 695 Pharmacovigilance, vs. risk of treatment,
frequency, duration of drug administration, Pharmaceutical Care Spain Foundation, 736-740
669 698-700 clinical development, 737-738
hepatic metabolism, 662-663 Pharmaceutical company-sponsored, medication international organizations. 737
historical backgroung, 656-657 assistance programs, 531 -532 postmarketing environment, 738-739
inhalers, 675 enrollment, 531 -532 regulatory environment, 736-737
intramuscular administration, 673 -674 ethical issues, 532 risk-benefit assessment. 739
intravenous administration, 666-670 information frequently requested, 532 Pharmacy curricula, design of, 555-556
types of, 669-670 internet sites, 531 Pharmacy Electronic Communications
manual administration, 669 medication, 532 Standardmational e-Claims
metabolism, 662 - 663 pharmacists’ role, 532 Standard Initiative, 113
nasal administration, 675 Pharmaceutical outcomes: 702-706 Pharmacy technician, defined, 23 1
ophthalmic administration, 675 databases for, 703-704 Pharmacy Technician Certification Board, 232
oral absorption, 658 ethics, 704 Pharm.D. See Doctor of Pharmacy
oral liquids, 670-671, 672 limitations of evaluating, 703 Pharmex, software, 216, 218
oral medications, 670-673 organizations, 704- 705 PharmWeb, 775
oral solid dosage forms, 672-673 performance measures, 702 Phenelzine, adverse drug response, 29
osmolality, 668 resources, 704-705 Phenobarbital, 870
otic administration, 675 textbooks, 704 adverse drug response, 29
patient age, 660 web sites, 704-705 pediatric pharmacokinetic data, 665
percutaneous administration, 674 Phaimaciens Sans Frontieres, 707-709 Phenothiazines, drug reaction, 27
pharmacokinetics, 657-663 funding, 708 Phenytoin, 870
product selection, 671 -672 goal, 707 adverse drug reactions, 29, 30
protein binding, 662 history, 707-708 as cytochrome P450 inducer, 247
rectal administration, 674 human resources. 708-709 pediatric pharmacokinetic data, 665
renal elimination, 663 meeting, 709 Physical impairments. in elderly, adherence to
subcutaneous administration, 674 missions, 708 medical care and, 15
sustained-release preparations, 67 1-672 objectives, 707 Physician Data Query, 450
therapeutic drug monitoring, 663 -664 Pharmacist, physician, patient, relationship Physicians
sample size, 664 among, 331 Medicaid usage, 5 16
serum drug concentrations, 663 -664 Pharmacists without Borders, 707-709 pharmacist, patient, relationship among, 331
technical factors, 664 Pharnzacist’s Workup of Drug Therapy, 693 Physician’s GenRX Drug Compendium
tissue binding, 662 Pharmacoeconomics, fellowships in, 357 Program, 775
transdermal drug-delivery systems, 660-661 Pharmacoeconomics and Outcomes Research, Placebo effects, 752-756
Pentamidine, AIDS, 442 International Society for, 488-489 Declaration of Helsinki, 755
Peptic ulcer, drug reactions and, 27 Pharmacoepidemiology, fellowships in, 357 in diseases. 753-754
Peptic ulcer disease, 754, 815 Pharmacokinetics, fellowships in, 357 factors affecting, 754-755
Peripheral neuropathy, 585, 588 Pharmacokinetics, Pharmacodynamics and Drug misconceptions, 755
Permeability class, bioavailability and, 100 Metabolism Section, American use of placebos in clinical practice, 755
Index 929
Plantox, 775 Preadmission criteria, home care, 436 Program Support Center, Department of Health
Plasma pseudocholinesterase, drug reaction, 29 Prednisolone, 870 and Human Services, 254-255
Plasmapheresis, 587 Preparing Drug Ififormation Response, 293 Project Death in America, Open Society
Pneumocystis carinii. with AIDS, 442 Prescription drug benefit administrators, Institute, 450
Pneumonia diabetes care. 258 Propylene glycol, excipient in drug, 95
with AIDS, 442 Prescriptions for Health: Lowy Report, 791 -793 Prostate, and breast cancer, gene therapy trials,
as cause of death, 404 Preventive medicine, 794-800 374
Point-of-care software, 220 Primaquine, adverse drug reaction, 29 Prostatic cancers group, Cochrane collaborative,
Poison information, 757-778 Primary care: 39-42, 801-817 184
American Academy of Clinical Toxicology, degrees, 40 Protocol, clinical evaluation, drugs, 133- 134
761-762 job activities, 39-40 Pseudocholinesterase, drug reaction, 29
American Association of Poison Control long-term opportunities, 40-41 Psychiatric pharmacy specialty practice,
Centers, 761 salary range, 40 822 - 826
analytical toxicology, 773 site description, 41 benefits of specialty practice, 824
Certified Regional Poison Information training, 40 international, 825
Center, 762 work settings, 39-40 model practice settings, 823-824
clinical toxicology organizations, 761 -762 Primidone, 870 networking, 824
European Association of Poisons Centres and Principal investigator, clinical pharmacist as, tools, 824
Clinical Toxicologists, 762 144-153 Psychiatry, fellowships in, 357
information resources, 760-761 American College of Clinical Pharmacy, Psychological exam, neurology specialty
poison center, 760 clinical pharmacist evaluation, pharmacy practice, 585
Poisoning Information, Karolinska Institute, 154- 160 Psychometric theory, health status assessment,
774 assessment methods, 154- 159 417-418
Poisonous Plant Database, 775 budget, 151 PTCB. See Pharmacy Technician Certification
Poisonous Plant Guide, 775 current industqr, 145- 148 Board
Poisonous Plants Web Page, Cornell FDA policies, 148- 149 Ptosis. 586
University, 775 FDA regulations, 148- 149 PTS. See Polymer Technology Systems
Poliovirus, 7 12 history, 144- 145 PTS Bioscanner, 141
Polymer Technology Systems, Inc., 141 publication rights, 151- 152 Publication rights, principal investigator,
Polymorphic crystals, absorption, 94-95 qualifications, 152- 153 clinical pharmacist as, 151- 152
Polypharmacy, in elderly, 15 access to patients, 153 Publications committee, medical information,
Polysorbates, excipient in drug, 95 audits, 153 industry-based, 528
Polyvinyl pyrrolidone, excipient in drug, 95 command of research process, 152 PubMed, 582, 773
Postapproval changes, 101 experience, 152 vs. Internet Grateful Med, 582
Post-exposure prophylaxis, HIV, 891 -898 human resources, 152 PubMed Central, 582
Antiretroviral Pregnancy Registry UCSF local leadership, 153 Pulmonary, fellowships in, 357
On-Line information, 896 local resources, 152 Pulmonary diseases, as cause of death, 404
Centers for Disease Control. 896 responsibilities of, 149- 150 Pulmonary system, neurology specialty
definitions, 891 template, 154, 155-159 pharmacy practice, 585
Food and Drug Administration, 896 Principles and Practice of Biologic Therapy oj Purdue Pharma Pain and Palliative Care
HIV/AIDS Treatment Information Service, Cancer, 622 Information, 450
896 Principles and Practice of Gynecologic Pyxis, 456
Indinavir, 895 Oncology, 622 automated delivery, 456
Lamivudine, 895 Principles and Practice of Infectious Diseases,
National Clinicians’ Postexposure Hotline, 473
896 Principles and Practice of Supportive Oncology, QS/l Data Systems, software, 216, 218
National HIV/AIDS Clinician’s Consultation 450, 622 Quality assurance
Center, 896 Principles of Scientific Literature Evaluation: Clinical Laboratory Improvement
Nelfinavir, 895 Critiquing Clinical Drug Trials, 293 Amendments of 1988, 142
post-exposure prophylaxis for HIV, 892-894 Privacy clinical pharmacy practice, 827-835
rationale for, 891-892 ethical issues, 878-879 Quality Assurance, National Committee for,
regimens, prophylaxis, 895 software, 222 564 - 567
therapy, 894-896 Privacy legislation, 113 2000 NCQA Board of Directors, 566
transmission risk, 892 Privileging, defined, 231 accreditation, certification programs, 565 -566
Zidovudine, 895 Probenecid, adverse drug reaction, 29 accreditation survey, 564-565
Post-marketing surveillance, 785 -790 Procainamide, adverse drug response, 29 accreditation survey standards, classification
Food and Drug Administration, 785-786 Product design, 82-84 of, 565
future direction of, 789 biopharmaceutic considerations in, 83 antidepressant medication management, 565
justification of need, 785 Professional associations, 8 18-821 beta blocker treatment, after heart attack, 565
weaknesses, strengths of current system, Proficiency testing, Clinical Laboratory breast cancer screening, 565
788-789 Improvement Amendments of cervical cancer screening, 565
Potassium, drug reaction with, 30 1988, 142 comprehensive diabetes care, 565
Practice agreements, collaborative, 199-206 Program in Evidence-Based Care and Cancer effectiveness of care measures, examples of,
Practice Guidelines Initiative, 621 Care Ontario, 621 565
930 Index
Quality Assurance, National Committee for subject selection, 408-409 objectives, 478
(cont.) work force, 412 projects, 479
flu shots, for older adults, 565 research policy, careers options, clinical Salary range, clinical pharmacy careers, 40
HEDIS, 565 pharmacy scientist, 179 SAMHSA. See Substance Abuse and Mental
high blood pressure, controlling, 565 Research ethics, scientist, clinical pharmacy, Health Services Administration
NCQA contact information, 566 178-179 San Francisco Cochrane Center, 185
NCQA information, 566 Residencies, 837- 842 Sarin nerve gas. 777
NCQNHEDIS, pharmacy practice, 566 accreditation. 838 Satisfaction. of patient, 651 -655
quality compass, state of managed care evolution of, 838-840 tools to measure, 653
quality report, 566 information on, 840- 841 Saw palmetto, adverse reaction to, 31
Quality initiatives manager, professional prerequisites for training, 840 Schizophrenia, 585, 754
opportunities. 502 resident matching program. 841 Schizophrenia group, Cochrane collaborative,
Quality of healthcare, 41 1 types of, 837-838 184
Quinidine Residency. defined, 23 1 SCIDS. See Severe combined
adverse drug reaction, 29 Resistance immunodeficiency syndrome
as cytochrome P450 inhibitor, 247 pathways for. 59 Scientific integrity, ethical issues, research,
drug reaction, 27 variables involved in, 59 340
Quinine Respiratory disease, drug reactions and, 27 Scientist, clinical pharmacy, 174- 180
adverse drug reaction, 29 Respiratory infection group, Cochrane behavioral development, 178
drug reaction, 27 collaborative, 183 communication skills, 178
Respiratory insufficiency. drug reactions and, 27 definitions of, 176
Retail Mgmt. Products. software, 216, 218 literature tracking, evaluation, 177
Rapid acetylator, drug reaction. 29 Retail network manager, professional research ethics, 178- 179
Rectal administration, pediatric dosing, 674 opportunities, 502 scientific thinking, 177- 178
Rectum, drug absorption in, 91 Retrovims, viral transfer techniques, 368 skill sets, 177- 179
Rectum disease, gene therapy, 376 Reward system, in adherence in pharmaceutical technical proficiency. 178
Refampin. 870 care. 14 training, 175-177
Registered, defined, 23 1 Rheumatic disease, drug reactions and, 27 Scope of practice, defined, 23 1
Regulations governing pharmacist prescribing. Rheumatoid arthritis, gene therapy, 376 Scottish Pharmacists in Mental Health. 825
190-191 Rheumatology, fellowships in, 357 Screening methods, adverse drug reactions, 30
Regulatory environment, pharmacovigilance, Rhode Island, pharmacy practice legislation, ScripMaster, software. 216, 218
736-737 272 ScripPro, software, 216, 218
Reimbursement, disease management, 269-27 1 Rifampin, as cytochrome P450 inducer. 247 Scripworld Pharmaceutical News, 775
Renal disease Riluzole. 588 Search method, literature. 303
adverse drug reactions and. 26 Risk factors for nonadherence in pharmaceutical Security, software, 222
cell cancer, gene therapy trials. 374 care. 11 Sedation and/or confusion, agents causing, 586
gene therapy, 376 RMS. software, 216. 218 Seizure disorder. 815
Renal elimination, pediatric dosing, 663 RNA. software. 216, 218 Seizures, 587
Renal excretion. drugs, 25 Robert Wood Johnson Foundation. 643 prophylaxis. 587
Renal group, Cochrane collaborative, 184 Roche Diagnostics, 141 Selegiline, 588
Renal system, neurology specialty pharmacy RRIS. See FEMA Rapid Response Information Self-efficacy, nonadherence in pharmaceutical
practice, 585 System care and, 14
Reporting systems, adverse drug reactions, Rx InHand, software. 360 Serum drug concentration, clinical pharmacy,
28 - 32 Rx30. software. 216: 218 economic analysis, 307 -321
Reproductive system, neurology specialty RxList Internet Drug Name Category Cross Sesame oil, excipient in drug, 95
pharmacy practice, 585 Index, 775 Severe combined immunodeficiency syndrome,
Reprotox, 774 Rx-Net, Inc., software. 216, 218 gene therapy, 373
Republic of South Africa, health care systems, RxWeb. software. 360 Shortage, pharmacists, Canada, 113
390-391 Siberian ginseng, adverse reaction to, 31
Rescot Systems Group, software, 216, 218 Side effects, drug, defined, 23
Research Safe Medication Practices, Institute for, SIDP. See Society of Infectious Diseases
health services, 408-414 476 - 477 Pharmacists
access to healthcare, 41 1 mission, 476 Singapore Ministry of Health. Poison
clinical evaluation; 41 1-412 objectives, 476-477 Information Centre, 775
consumer behavior, 412 analysis-based ISMP initiatives, 476 Sirolimus, 870
data sources. 409 communication-based ISMP initiatives, 477 Skilled nursing facility, clinical pharmacy,
definition of, 408-409 cooperation-based ISMP initiatives, 477 economic analysis, 307 -321
financing of healthcare, 410-41 1 education-based ISMP initiatives, 477 Skin, neurology specialty pharmacy practice,
health policy, relationship between, knowledge-based ISMP initiatives. 476 586
409-410 Spain, 478-479 Skin group, Cochrane collaborative, 184
informatics, 412 future goals, 479 Slow acetylator. drug reaction: 29
quality of care, 41 1 medication errors reporting program, Slurred speech, 586
role of pharmacy profession in, 410-412 478-479 Smart Solutions. software, 216, 218
study setting, 408 mission, 478 Smoking cessation, 588
Index 931
Society of Hospital Pharmacists of Australia, central intravenous additive service. model clinical practices. 164
851-853 457-458 networking opportunities. 166- 167
Clinical Pharmacy Practice Guidelines. computer software, 456 professional opportunities, 161- 164
170- 173 drug dispensing/distribution, 455 -457 pharmacotherapy, 732-735
Society of Infectious Diseases Pharmacists, drug information, 458 functions, 732 -733
474 drug surveillance, 459 qualifications, 733
Sodium alginate. excipient in drug, 95 enteral, parenteral nutrition, 458 supplemental information, 734
Sodium carboxymethylcellulose, excipient in foreign drugs, 457 value, 733-734
drug. 95 future trends, 459 Spironolactone, adverse drug reaction, 30
Software. 214-222. 456 history of, 453 Spontaneous reporting, in pharmaco-epidemio-
associated performance-enhancement tools, management. 455 logic studies, 30-31
221 manufacture, 457 SRS, software. 216, 218
clinical software attributes, 221 medical devices, activities related to, 459 St. John's wort, adverse reaction to, 31
confidentiality, 222 pharmacoeconomics, 459 Stages in clinical evaluation of drugs: 130-133
documentation. 220-221 radiopharmacy, 459 "Standards 2000," American Council on
Drug Information Framework, 360 research drugs. 457 Pharmaceutical Education, 8-9
hardware array, 215-220 stocks in wards. 457 Standards in Pharmacist Credentialing, National
InfoWin, 456 therapeutic drug monitoring, 458-459 Institute for, 572-574
Nutritionist Pro: 360-361 training program, 454 activities. 573-574
point-of-care software, 220 transition in. 453-454 exam registration process. 573
privacy, 222 Institute for Safe Medication Practices, examination eligibility requirements, 573
recommendations. 222 478-479 NISPC DSM examinations, 573
Rx InHand, 360 future goals, 479 organizational structureimeetings, 572-573
RxWeb: 360 medication errors reporting program, Starch, excipient in drug. 95
security, 222 478-479 State Pharmacy Association Executives,
Solid drug products, excipients used in. 95 mission. 478 National Council of, 496
Solid organ transplant, Medicare Benefits and objectives, 478 State regulations governing pharmacist
Improvement Act of 2000. 530 projects. 479 prescribing. 190-191
Solubility Pharmaceutical Care Spain Foundation, Statement of continuing education credit,
absorption and, 93 698-700 defined, 224, 231
bioavailability and, 99- 100 policy documents. laws. clinical pharmacy Stearic acid, excipient in drug, 95
Sorbitol. excipient in drug, 95 practice, 779-784 Steroids. 587
Sources of patient data. 285 Spanish Society of Hospital Pharmacy, 854-856 Stimulants, 588
caregiver/family member, 285 directors of publications, 856 Stomach, drug absorption in, 90
healthcare providers. 285 governing body, 855-856 Stomatitis, 586
medical records, 285 permanent board, 856 Stool softeners, 587
patients, 285 Special populations. adherence in Street drugs, 774
pharmacy dispensing records, 285 pharmaceutical care, 14- 18 Stroke. 585, 586
South African Cochrane Centre. 185 Specialized Information Services of National as cause of death. 404
South Carolina, pharmacy practice legislation, Library of Medicine, 773 risk, 585
272 Specialty clinics, managed care, clinical Stroke group. Cochrane collaborative, 184
South Dakota pharmacy careers in, 504-505 Study volunteers. payment to, 337
pharmacy practice legislation, 272 Specialty practice Subarachnoid hemorrhage. 587
regulations governing prescribing, 191 clinical pharmacokinetics, 161- 169 Subcutaneous administration. pediatric dosing.
Spain American Association of Pharmaceutical 674
clinical pharmacist in clinical trials, 843- 849 Scientists Subfertility group, Cochrane collaborative, 183
home care pharmacy practice, 439-446 Pharmacokinetics, Pharmacodynamics Substance Abuse and iMental Health Services
advantages, 439 and Drug Metabolism Section. Administration, 253-254
AIDS, 441-443 166 Succinylcholine
antibiotic therapy, cost savings, 441 Population Pharmacokinetics and Phar- adverse drug reaction. 29
classification. 439-440 macodynamics Focus Group, 166 Sucrose. excipient in drug. 95
community-based, 440 American College of Clinical Pharmacy. Sugar-containing drugs, 671
family environment, 440 Pharmacokinetics/Dynamics Suicide. as cause of death, 404
home environment, 440 Practice Research Network, 166 Sulfadimidine, 870
hospital-based. 439-440 American Society for Clinical Pharma- Sulfaphenazole, as cytochrome P450 inhibitor,
infections. 441 cology and Therapeutics, Pharma- 247
organization, 439-440 cokinetics and Drug Metabolism Sulfasalazine. adverse drug response, 29
parenteral antibiotics, 441 Section, 166- 167 Sulfinpyrazone, 870
patient selection. 440-441 American Sociery of Health-System Phar- Sulfonamides, adverse drug reaction, 29
type of interventions, 441 macists, Supplemental Standard and Superficial solid tumors. gene therapy trials,
web sites, 444 Learning Objectives for Residency 374
hospital pharmacy practice, 453-460 Training, 166 Support services, Medicaid usage, 5 16
activities conducted in, 454-459 benefits of, 165- 166 Suremed, 456
automated delivery, 456 materials useful to, 166 automated delivery, 456
932 Index
Surveillance, post-marketing. 785 -790 as cytochrome P450 inducer, 247 access to health care, 403-405
Food and Drug Administration, 785-786 Tobutamide, cytochrome P450, 247 future of, 405-406
future direction of, 789 Tolazamide, adverse drug reaction, 30 health care financing, 401-403
justification of need, 785 Toxic reaction to drug, defined, 23 organization of, 399-400
weaknesses, strengths of current system, Toxicology Environmental Health Information trends in, 400-401
788-789 Program, 774 United States Pharmacopeia, 886-890
Sustained-release preparations, 67 1-672 TOXNET, 582 convention membership, 887
SymRx, software, 216, 218 TOXNET ToxLine, 774 history, 886
tPA, 587 initiatives, 889- 890
Tragacanth, excipient in drug, 95 dietary supplement verification program,
Tablet, oral administration of, processes Traineeship, defined, 23 1 889
following, 86 Training international, 890
Tacrine, 588 in academic clinical pharmacy, 4 meetings, 890
Tacrolimus, 870 anticoagulation clinical pharmacy practice, monograph development, 889-890
Talc, excipient in drug, 95 66-67 priorities, 890
Tears, artificial, 587 long-term care, clinical pharmacy careers in, MedMARx. 889
TechRx, software, 216, 218 499 mission, 886
TEHIP. See Toxicology Environmental Health National Institutes of Health, 577-575 National Formulary, 887-889
Information Program scientist, clinical pharmacy, 176 organizational structure, 887
Telemedicine, National Library of Medicine, Transcylcypromide. adverse drug reaction, 30 pharmacopeial forum, 889
583 Transition, in academic clinical pharmacy, 1-3 products, 887-889
Tenure system, academic clinical pharmacy, academicians, evolution of, 3 reference standards, 889
changes in, 2 higher education, 2 standards development, 888
Tetracycline, adverse drug reactions, 30 reward system, changes in, 2 statutory recognition, 888-889
Texas tenure system, changes in, 2 strengths, 886
pharmacy practice legislation, 272 Translational research, fellowships in, 357 Universal precautions, HIV, 891- 898
regulations governing prescribing, 191 Transplantation, organ Antiretroviral Pregnancy Registry UCSF
Theophylline, 93 facilities, Medicare-approved, 530 On-Line information, 896
adverse drug reaction, 27, 28 fellowships in, 357 Centers for Disease Control, 896
cytochrome P450, 247 Medicare Benefits and Improvement Act of definitions, 891
pediatric pharmacokinetic data, 665 2000, 530 Food and Drug Administration, 896
Therapeutic drug monitoring, 458-459 pharmacy practice, 869- 875 HIV/AIDS Treatment Information Service,
clinical pharmacy, economic analysis, Tri-Council Policy Statement: Ethical Conduct 896
307-321 f o r Research Involving Humans, indinavir, 895
Therapeutic Guidelines Limited (Australia), 876-881 lamivudine, 895
857-859 Tricyclic antidepressants, 588 National Clinicians’ Postexposure Hotline,
additional readings, 859 drug reaction, 27 896
current initiatives, 858-859 Triptans, 587, 588 National HIV/AIDS Clinician’s Consultation
history, 857 Twenty-first century, pharmacy in, 749-75 1 Center, 896
major directions, 859 Two Point Conversions, software, 216, 218 nelfinavir, 895
mission, 858 Type 2 diabetes, nonadherence to medical care post-exposure prophylaxis for HIV, 892- 894
objectives, 858 in, 19 rationale for, 891 -892
organizational structure, 857- 858 Tyramine, drug reaction with, 30 regimens, prophylaxis, 895
Therapeutic interchange, 860- 863 therapy, 894-896
formulary system, history of, 860-861 transmission risk, 892
guidelines, 864-868 U.K. Cochrane Centre. 186 Zidovudine, 895
process of, 861-862 Unapproved indications, medication use for, University hospital, clinical pharmacy,
Thiazide diuretics, drug reaction, 27 550-553 economic analysis, 307-321
Third-party payer issues. 1 13 United Kingdom, health care systems, 392-394 University of Alabama at Birmingham, health
Throat disorders group, Cochrane collaborative, United Kingdom Clinical Pharmacy outcomes research, 36
183 Association, 883-885 University of North Carolina at Chapel Hill,
Thromboembolism, with routine medical care, business management group, 883-885 health outcomes research, 36
vs. pharmacist-managed care of elderly, 884 University of Pennsylvania, health outcomes
anticoagulation, 65 critical care group, 884 research, 36
Thrombosis, anticoagulation, 64 education, 884 University of Texas Cancer Pain Page, 643
Thrush, 586 infection management group, 885 Unlabeled indications, drug use for, 551
Thyroid disorders, 585 primary care, 884 antineoplastics, 551
Ticlopidine, 587, 870 quality assurance group, 884-885 antipsychotics, 551
Titinium dioxide, excipient in drug, 95 surgery, 885 HIV, 551
TMT, software, 216, 218 United Kingdom Psychiatric Pharmacy Group, metoclopramide, 551
To Err is Human: Building Safer Health Care 825 ondansetron, 55 1
System, 480 United States Upper gastrointestinal, pancreatic diseases
Tobacco. See also Smoking causes of death in, 404 group, Cochrane collaborative, 184
addiction group, Cochrane collaborative, 184 health care systems within, 397-407 Urinary catheter, 585
Index 933
Urinary tract infections, 585 childhood diseases, vaccination against, 559 Volume expansion, 587
Urologic cancers group, Cochrane collaborative, documentation. 561 Von Hochstetter technique, ventrogluteal
I X4 historical advancements, 559 intramuscular injection, 674
U.S. Armed Serbices, careers in, 385-386 immunimtion practice, pharmacy-based, 56 1
U.S. Army Medical Kesearch Institute of liability. 561
infectious Diseases, 777 manufacturer liability, 550-560 Walton. Charlcr, 899-901
U.S. Army Rerearch Institute of Chemical National Vaccine Injury Cornpenration Warfarin, 587
DeSense. 777 Program, 560-56 1 adverse drug reactions, 30
1J.S. Army Soldier and Chemical and Biological protection undct- NCVIA, 561 cytochrorne P450. 247
Defense Command, 777 reporting, 561 Washington
U.S. Coast Guard. careers in, 387 Vaccine Injury Act of 1086. 560-563 pharmacy pi-actice legislation. 272
U.S. Public Hcalth Sct-vice, careers in, 386-387 vaccine injury table. 560 regulations governing prescribing, 19 1
USAMRICD. See U.S. Army Kescarch institute Valerian, adverse reaction to. 3 I Weaver. Lawrence, 902-903
of Chemical Defense Vdproic acid. 585 WHO Communicable Disease Surveillance and
IJSAMRIID. Soe U.S. Army Medical Kesearch pediatric pharniacokinetic data, 665 Response, 777
Institute of Infectious Disease\ Vanderbilt IJniversity, health outcomes Wi/liUf?7‘ S Hen?UlO/<Jg?, 622
lJse evaluation, of medication reseat-ch, 36 Wisconsin. pharinacy practice legislation, 272
approaches to, 547-548 Varicella, 712 Wisconsin Cancer Pain Initiative, 643
goals of, 546 v.r :
~ i ~ ~712
ax, Work force, health services research, 412
limitation\, pitfalls of. 548 Vascular etidothelial growth factor, gene Wo1.k settings. clinical pharmacy careers,
priority setting. 546- 547 therapy, 375 39--40
process, 547 Vaioconstrictors. drug reaction, 27 World Iiealth Organization, 904-907
role o f pharmacist. 540 Vectors, gene therapy, 368-371 Cancer Pain Kelease, 643
scope, 546 adenovit-a1 vcetors, 369-370 Essential Drug List. 908-909
tools, resources, 548 plasmid-based vectors. 37 1 functions, 905 -907
valuc of, 548 retroviral \ ectors, 368 - 360 history, 904
u.\C <Jff\tllihiOl;~S,473 Veegum, excipient in drug, 95 missions, 904-905
Utah. pharinacy practice legislation, 272 VEGF. S r r Vascular endothcli;il growth factor normative, harmonimtion functions, 905
Utilization management, managed care, clinical Ventriculat- drainage, 587 operational activities, 005-907
pharmacy careers in, 504 Ventrogluteal intrainuscular in.jection, von communicable diseases, 905
Utilization/case manager-, profe\sional Ilochstetter technique, 674 emergency. humanitarian action, 905 -907
opportunities. 502 Verapamil, cytochrorne 1’450, 247 health rerearch, 907
practice legislation. 272 iioncommunicable diseases, 905
Vcrtebrohasilar insufficiency. 587 in pharmaceutical \ector, 907
Vaccination programs, pharmacist-managed, Vertigo World Medical Association, Declaration of
7 1 0- 7 I7 medication induccd, 586 Helsinki, 341 -342
benefits of. 710-7! I Viral traiisfer techniques, compared. 368 Wounds group, Cochratie collaborative, I84
certificate program\. 7 10 Virginia, pharmacy practice legislation, 272 Wyoming, pharmacy practice legislation, 272
immunization opportunities. 71 1-712 Vi\ible Human Project, 774
inodel ph;irinacist-inanaged practices. Vision group, Cocht-me collaborative, 183
712-716 Vision statement, Academy of‘ Managed Care Xanthan gum, excipient i n drug, 95
networks, 7 I6 Pharmacy, 6-7 X-ray, Medicaid usage, 516
resources for vaccine information, 7 16 Vitamin R12 deficiency, 585
Vaccine In.jury Act, Childhood, 559-563 Vitamin K, drug reaction with, 30
advcrse events, vaccine, 559 Voice-lech, software, 216, 218 Zidovudine, 895
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