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Pharmacoeconomics and therapeutic drug monitoring

Article  in  International Journal of Clinical Pharmacy · September 1997

DOI: 10.1023/A:1008634318875 · Source: PubMed

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 Pharmacoeconomics and therapeutic drug monitoring
Articles

• J . Ly l e B o o t m a n a n d D o n a l d L . H a r r i s o n

Introduction
In recent years, the reality that resources for health
care are clearly limited has led to significant changes
in the development, implementation, and reimburse-
ment of pharmacy and related services. These influ-
ences have convinced policy makers in health care
that innovative health programs should be cost-justi-
fied in order to exist in the future. This continues to
be crucial to the expansion of pharmaceutical services
and the adoption of new health technologies.
Application of economic evaluations is not new to the
health care sector [1-3]. As health care expenditures
have escalated over the past two decades, the appli-
cation of the techniques has increased. A new disci-
pline, pharmacoeconomic analysis, has emerged to
identify, measure, and compare the costs and conse-
quences of pharmaceutical products and services.
Pharmacoeconomic research is becoming increasing-
ly critical in the evaluation of new drug therapies and
pharmaceutical services. Essentially, economic meth-
ods are used to weigh the costs and benefits of phar-
J. Lyle Bootman and Donald L. Harrison. Pharmacoeconomics
macy service programs. The purpose of this article is and therapeutic drug monitoring.
to provide an overview of pharmacoeconomics and Pharm World Sci 1997;19(4): 178-181.
its application to the evaluation of therapeutic drug
© 1997 Kluwer Academic Publishers. Printed in the Netherlands.
monitoring.
J. Lyle Bootman (correspondence): Professor and Dean,
College of Pharmacy, The University of Arizona, PO Box
210207, Tucson, Arizona 85721-0207, U.S.A.
An overview of pharmacoeconomics Donald L. Harrison: MAJ, US Army, Clinical Investigation
Over the past decade, pharmacoeconomics has Regulatory Office, ATTN: MCCS-GCI, 1608 Stanley Road,
Building 2268, Ft. Sam Houston, Texas 78234-6125, U.S.A.
become an important consideration in drug develop-
ment and marketing by the pharmaceutical industry Keywords
[1 4]. Pharmacoeconomic evaluation
Cost-effective
Pharmacoeconomic studies attempt to identify,
Cost-Benefit
measure, and compare the costs in terms of resources Therapeutic drug monitoring
consumed and consequences in terms of outcomes of
Abstract
pharmaceutical products and services [1-4].
The ever increasing rate of inflation and the reality that
Pharmacoeconomic research methods include a resources for medical care are limited has led to significant
variety of methods including cost-minimization, cost- changes in the reimbursement for health care services. These
influences have convinced health care policy makers to close-
effectiveness, cost-benefit, cost-of-illness, cost-utility,
ly evaluate innovative health services in terms of the benefits
decision analysis, and quality of life assessments. This and costs. New pharmaceutical services must be economical-
new emerging discipline is being adopted as a health ly justified in order to exist in the future. This is crucial to the
expansion and adoption of pharmaceutical services.
science discipline by the pharmaceutical industry,
Application of economic evaluations is not new to the
academic pharmaceutical scientists, and pharmacy health care sector. Until recently, there were no incentives to
and medical practitioners throughout the world. It is transfer this interest into widespread use. As health care
expenditures have escalated over the past two decades, the
proposed that this emerging discipline will have a
number of applications of these techniques has increased.
dramatic influence on the delivery and financing of Especially significant are cost-benefit and cost-effectiveness
health care throughout the world. evaluations of medical practice, pharmaceuticals, and other
health care technologies.
During the early 1960s, pharmacy began evolving
Pharmacoeconomic analysis is an important tool to assist
as a clinical discipline within the health care system. It in the evaluation of new pharmaceutical services and tech-
was during this time that pharmaceutical science dis- nologies. Essentially, economic analytical methods are used
to weigh the positive and negative consequences of alterna-
ciplines, such as pharmaceutics, clinical pharmacy,
tive courses of action. The usefulness of pharmacoeconomic
drug information, and pharmacokinetics became a
Pharmacy World & Science

analyses is in resource allocation, with the purpose of achiev-

critical and integral part of pharmacy education, sci-
ence, and practice. Similarly, it was in the 1970s that
the discipline of pharmacoeconomics developed its
roots. The first application of pharmacoeconomics
was in the evaluation of pharmacokinetic and thera-
Volume 19 Nr. 4 1997
ing the highest return on investment or accomplishing a
given objective in the least costly manner. Unfortunately,
very few pharmacy programs have been evaluated using
pharmacoeconomic techniques. The purpose of this article is
to present various methods to assess the economic value of
therapeutic drug monitoring services in society and for spe-

cific patient populations. Additionally, this article will review

peutic drug monitoring service programs. The first
article published in pharmacy literature occurred
when McGhan, Rowland, and Bootman introduced
178 the concepts of cost-benefit and cost-effectiveness
the previous attempts and various issues surrounding the
economic justification of therapeutic drug monitoring.
Accepted January 1997
analysis along with a theoretical model for evaluating
pharmacokinetic services [5]. Following this,
Bootman and colleagues published the first research
article in pharmacy literature in which cost-benefit
analysis was utilized to evaluate the outcomes of indi-
vidualizing aminoglycoside dosages in severely
burned patients with gram negative septicemia [6].
The actual term ‘pharmacoeconomics’ was not pro-
posed until a decade later when Townsend’s article
described this evolving pharmacy discipline [7]. This
was followed by Bootman, Townsend, and McGhan’s
effort to publish the first edited text devoted to the
basic concepts and principles of pharmacoeconomics
[8]. To date, much of the efforts in this discipline have
been directed toward the refinement of the research
methods and their application to researching specific
drug therapies and pharmaceutical care services.
Pharmacoeconomic research and pharma-
ceutical care
To date, most of the applications of pharmacoeco-
nomics have been dedicated to evaluating the costs
and consequences of specific drug therapies. In addi-
tion to evaluating drug therapies, it is equally impor-
tant to use these methods to evaluate innovative
pharmaceutical care services (e.g., Therapeutic Drug
Monitoring Programs, Patient Counseling Programs).
The profession of pharmacy continues to undergo
change and re-evaluation of its mission. There is gen-
eral consensus that the mission of pharmacy practice
is fulfilling the social need to assure the safe and effec-
tive use of drugs. To achieve this goal, there is agree-
ment that pharmacists need to assume greater
responsibility for the management of drug therapy in
order to ensure a patient’s positive therapeutic out-
come. Recently, the profession has adopted the provi-
sion of ‘pharmaceutical care’ as the paradigm for the
future practice of pharmacy [9 10].
Pharmaceutical care is the responsible provision of
drug therapy for the purpose of achieving definite
outcomes that improve a patient’s quality of life
symptoms [9 10]. Four outcomes have been identi-
fied: (1) cure of a disease, (2) reduction or elimination
of symptoms, (3) arresting or slowing of a disease
process, and (4) preventing a disease or symptoms
[9 10]. However, the potential does exist to decrease
a patient’s quality of life [9]. Pharmaceutical care
involves the process through which a pharmacist
cooperates with the physician and other professionals
in designing, implementing, and monitoring a thera-
peutic plan that will produce specific therapeutic out-
comes for the patient. This involves three major func-
tions: (1) identifying potential and actual drug-related
problems, (2) resolving actual drug-related problems,
and (3) preventing potential drug-related problems.
Because of the nature of drugs as dangerous chemi-
cals, the occurrence of drug-related problems (DRPs)
is common. The major function of the pharmacist is to
enhance the quality of drug therapy and, thus,
decrease the risk of drug-related morbidity [9].
Pharmacists must be committed to preventing and
resolving DRPs. Eight DRPs have been identified: (1)
untreated indication, (2) improper drug selection, (3)
subtherapeutic dosage, (4) failure to receive drugs, (5)
overdose, (6) adverse drug reactions, (7) drug interac-
tions, and (8) drug use without indication [9 10].
It is suggested that pharmacists must practice
pharmaceutical care to achieve not only safe and
effective therapy, but to enhance the cost-effective-
ness of drug therapy as well [1]. Additionally, the suc-
cessful implementation of pharmaceutical care will
come about only with sufficient pharmacoeconomic
research that adequately documents the magnitude
to which the benefits of pharmaceutical care out-
weigh the costs associated with the provision of those
services. In fact, the profession of pharmacy is unlikely
to succeed in its role of providing pharmaceutical care
without this critical body of knowledge. Further, phar-
macoeconomics will enable the profession to specify
which pharmaceutical care services are cost-effective
in relation to each other so to improve efficiency in
delivering such services. Finally, pharmacoeconomic
research may be helpful in establishing adequate
reimbursement for such services especially in capitat-
ed health care reimbursement schemes. In essence,
the success in implementing pharmaceutical care will
be based upon quality pharmacoeconomic research.
Pharmacoeconomics and drug-related
morbidity
Evidence suggests that a large proportion of drug-
related morbidity and mortality is preventable
through the provision of pharmaceutical care [10-12].
Drug-related morbidity and mortality can have signifi-
cant economic consequences to the health care
system [11-13]. Unfortunately, little pharmacoeco-
nomic research has documented this problem or has
successfully demonstrated that the pharmacist may
be a cost-effective alternative in resolving this prob-
lem.
Most of the research to date has focused on rates of
hospitalization attributed to adverse drug effects or
medication noncompliance; however, few have eval-
uated the economic impact of drug-related morbidity
and mortality. Sullivan and colleagues estimated that
noncompliance accounted for 5.3% of hospitaliza-
tions, resulting in estimated direct medical costs of
$8.5 billion annually [14]. The authors further esti-
mated an additional $17-$25 billion annually in indi-
rect costs due to noncompliance. Additionally,
Manasse estimated total costs of noncompliance to
be more than $100 billion [11 12]. While noncompli-
ance and hospitalizations are certain to account for a
large proportion of drug misadventuring and asso-
ciated direct medical costs, limiting the analysis to the
issue of noncompliance alone underestimates the true
extent of drug-related morbidity and mortality.
The most comprehensive study to date was pub-
lished by Johnson and Bootman [13]. The authors
estimated that the annual direct costs associated with
DRPs in the ambulatory care setting in the United
States was approximately $76 billion. They developed
a conceptual model of therapeutic outcomes result-
Pharmacy World & Science
ing from drug therapy in the ambulatory setting and
estimated the magnitude of drug-related morbidity
and mortality in the United States. Most importantly,
they further estimated that the provision of pharma-
ceutical care by pharmacists would reduce the direct
Volume 19 Nr. 4 1997
costs of DRPs by 59.6% (to $45.6 billion) with over
119 000 deaths avoided. This is an excellent example
of how pharmacoeconomic research can assist in the
justification of pharmaceutical care as a practice para-
179
 digm. Given this analysis, pharmaceutical care servic-
es may be viewed as cost-effective in reducing the
incidence and prevalence of DRPs. However, pharma-
coeconomic research into DRPs should not be con-
fined to the ambulatory care setting; it must be
expanded to all pharmaceutical care settings. The
model proposed by Johnson and Bootman has been
incorporated into research currently underway at The
University of Arizona designed to estimate the eco-
nomic impact of consultant pharmacists on drug-
related morbidity and mortality in long-term care
facilities.
Therapeutic drug monitoring and pharma-
coeconomics
The model proposed by Johnson and Bootman pro-
vides an excellent framework for the pharmacoeco-
nomic evaluation and assessment of therapeutic drug
monitoring (TDM) services. Therapeutic drug moni-
toring programs can be viewed as a tool to monitor
and prevent drug-related problems in any setting
where drug therapy is provided. Therapeutic drug
monitoring provides a more accurate response to
drug therapy since plasma drug concentration is a
better predictor of therapeutic response than the
dose. In terms of preventing and resolving drug-relat-
ed problems, TDM is most helpful in the diagnosis of
noncompliance; monitoring the impact or presence
of adverse effects and/or drug interactions; evaluating
proper dosage and effectiveness of drug therapy; and
possibly determining improper drug selection if the
patient is not responding to therapy (therapeutic fail-
ure). Therefore, the link between TDM, pharmaceuti-
cal care, and pharmacoeconomics is important in the
planning of future pharmacy services. A survey con-
ducted in 1992 by the American Society of Health
Systems Pharmacists (ASHP) indicated that TDM ser-
vices have become a mainstay in the institutional set-
ting, with 57% of the hospitals in the United States
providing pharmacokinetic consultations [15]. A sub-
sequent survey demonstrated that 47% of those insti-
tutions without TDM services were planning to
initiate them in the near future [16].
Though the trends indicate that the growth in
TDM services continues, relatively few attempts have
been made to rigorously evaluate TDM services using
pharmacoeconomic methods to further expand such
services [17 18]. Recently, Murphy and colleagues
published the results of their survey indicating that
only 7% of those offering TDM services are conduct-
ing pharmacoeconomic evaluations relative to patient
outcomes [16]. As with other innovative services
aimed at achieving pharmaceutical care, TDM servic-
es will require rigorous cost justification for continua-
tion within any setting where drug therapy is provid-
ed.
The initial study conducting any level of pharma-
Pharmacy World & Science
coeconomic analysis was that reported by Bootman
and colleagues in 1979, in which cost-benefit analysis
was used to measure the impact of therapeutic drug
monitoring in burn patients treated with aminoglyco-
sides for gram negative infections [6]. This study,
Volume 19 Nr. 4 1997
using the classical economic method of cost-benefit
analysis, demonstrated that pharmacokinetic TDM
services in the acute care setting relative to treating
gram negative septicemia were very beneficial when
180
compared to the cost incurred during the provision of
that service. This study was further validated by the
results published by Moore and colleagues, who
found a significant association between peak concen-
trations of aminoglycoside antibiotics and therapeutic
success in patients with gram negative pneumonia
[19].
In 1980, Elenbaas and colleagues published the
results of their research aimed at estimating the costs
associated with a clinical pharmacokinetic service, fur-
ther demonstrating that pharmacists’ involvement
was shown to decrease health care costs associated
with such a service [20]. Since those initial studies in
the late 1970s and early 1980s a variety of studies
have been published that have utilized various eco-
nomic methods demonstrating that the benefit to
cost ratio for TDM services is positive [21-25].
Unfortunately, these studies were limited by the lack
of prospective randomization as well as a somewhat
narrow approach, failing to incorporate the wide
range of both direct and indirect costs.
The only prospective randomized studies attempt-
ing to evaluate TDM services have been published in
recent years [26-30]. However, these studies were
also quite narrow in their approach in that most of
them examined aminoglycosides as opposed to sev-
eral classes of drug therapy and did not use sophisti-
cated economic methods in their overall evaluation
[3]. Additionally, these studies have been narrow in
terms of costs considered in they did not consider
indirect costs nor quality of life. Complete pharma-
coeconomic analyses require that at least two alterna-
tives be considered and that all relevant costs and
therapeutic outcomes be included.
Few studies have been undertaken to economically
justify TDM services in the ambulatory care setting.
This is a serious shortcoming, given the potential for
DRPs and their economic impact demonstrated by
Johnson and Bootman [13]. Most studies in ambula-
tory care centered on the demand for TDM services in
the ambulatory setting and none have used pharma-
coeconomic methods in the economic justification of
these services. In 1989, Einarson and colleagues eval-
uated patient willingness to pay for TDM services in
an ambulatory setting [31]. On average, patients
were willing to pay $12.46 for the service, therefore it
was shown to be cost-effective from a willingness to
pay perspective. In 1994, Wade and McCall described
the economic advantages of pharmacists providing
continuous quality improvement (CQI) for the moni-
toring of digoxin therapy [32]. The researchers
reported a savings of approximately $16,000 over a
four-month period after interventions by clinical phar-
macists. However, this study is seriously limited by its
failure to assess patient outcomes, the full range of
costs, and to compare costs to patient outcomes. In
summary, there is a lack of quality studies using phar-
macoeconomic methods to economically justify the
provision of TDM services in the ambulatory care set-
ting. What is needed are comprehensive pharma-
coeconomic studies designed to compare all relevant
costs of a TDM service in the ambulatory care setting
to the outcomes or benefits of the service.
Conclusions
The delivery of health care in the United States and
the world has been changing rapidly during the past
two decades. The rising cost of health care has been
the major concern. As we approach the year 2000
there appears to be more of an attempt to balance
the outcomes of care with the cost so that cost-effec-
tive decisions can be made relevant to various medi-
cal interventions such as drug therapy. As a result of
these changes, a new discipline in pharmacy referred
to as pharmacoeconomics has evolved. Pharmacists
must apply such research to decisions related to drug
therapy as well as to justify innovative pharmacy ser-
vices.
The United States is spending over $900 billion
dollars on health care and unfortunately little is
understood of what outcomes are being attained for
that expenditure. Outcomes research and pharma-
coeconomics are the most important mechanisms to
learn more about the effective and efficient way to
provide accessible quality care at reasonable costs.
Additionally, pharmacoeconomics will be a key deter-
minant in enabling pharmacy to completely fulfill and
justify its social responsibility of delivering pharma-
ceutical care. Pharmaceutical scientists have consis-
tently sought to apply their abilities to create new
knowledge that supports the contemporary practice
of pharmacy. The application of pharmacoeconomics
to clinical practice and pharmaceutical care will be
crucial to pharmacy’s success in the future health care
delivery system. Pharmacoeconomics provides a
theoretical framework for the evaluation and justifica-
tion of such services. Overall, few studies have used
pharmacoeconomic methods to rigorously assess
TDM services. Further, there is a complete lack of
pharmacoeconomic studies concerning the provision
of TDM services in the ambulatory care setting.
Clearly, what is needed are comprehensive pharma-
coeconomic studies designed to compare all relevant
costs of a TDM service to the outcomes or benefits of
the service. Finally, it is crucial that these studies be
undertaken in all possible drug therapy settings.
Note: The views of the authors are their own and do
not purport to reflect the position of the Department
of the Army or of the Department of Defense.
A portion of the material contained in this manuscript
was presented at the E.S.C.P. 24th European
Symposium on Clinical Pharmacy in Prague, Czech
Republic, October 10-13, 1995.
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