Professional Documents
Culture Documents
USP Veterinary Clinical Drug Information Monograph Development Process
USP Veterinary Clinical Drug Information Monograph Development Process
USP Veterinary Clinical Drug Information Monograph Development Process
Committeememberswoulddecidewhich therapeuticcategories,and drugswithineachcategory,wereof greatestneed tothepractitioner.For the antimicrobials,22monographscovering63selectedmedicationswerecreated. OncedrugswereselectedbyVMIformonographdevelopment,astaff veterinarianobtainedpublicly availableinformationonthedrugsforreview,including USAandCanadianlabelinformation,FDAFreedomofInformationdocuments,foreign druglabels,andpeerreviewedjournalarticles.Carefulattention waspaidtospecies specificinformation.Thisinformation wasthenarrangedintoa common template containing:brandnames,categoryofdrug,indications,regulatoryconsiderations, chemistry,pharmacology andpharmacokinetics(i.e.,mechanismofaction/effect, absorption,distribution,proteinbinding,biotransformation,elimination),precautionsto consider,side/adverseeffects,overdoseinformation,clientconsultation,veterinary dosinganddosageformsinformation. Certain sections,suchaschemistryandregulatoryconsiderations,werenot contentious. Allreliablepharmacokineticinformationfoundwasadded,regardlessof species.Theindication anddosingrecommendations,however,requiredthegreatest
effort, andVMIappliedthemostintensiveevidencebasedapproachtoreachaconsensus onthesetwosections. Foreach extralabelindication,andanylabelindicationthatwasviewedas contentiousbyan ExpertCommitteemember,aspeciesspecificevidencetable summarizedallpertinentitemsofliterature. The tablewouldcontainthecitation information,thetypeofstudy[e.g.,casereport(s),clinicaltrial,diseasemodel,invitro study,metaanalysis,pharmacokineticstudywithoutsurrogateendpoints, pharmacokineticstudywithsurrogateendpoints], methodof randomization,typeof controlused(e.g.,positive,negative,uncontrolled),andthetypeofmaskingused(e.g., singlemasked,doublemasked,nonmasked).Asynopsisoftheclinicalmethodsused, dosesanddurationoftherapystudied,results,authorconclusions,andlimitationsnoted by theUSPstaff veterinarianwereincluded.Aportionofanexampleevidencetableis giveninFigure1. When all oftheevidencetablesforaparticulardrugorfamilyofdrugshadbeen constructed,theywereintegratedintoamonographballotprovidedtoVMIExpert Committeemembersandthirdparty adhocreviewersforinitial discussion.Therefore, reviewershadaccesstotheevidencetablesandallotherinformation compiledforthat drug(includinglabeledindications,pharmacokineticandsafetydata)duringthedecision makingprocess. Onceapreliminary consensusontheindicationsthatwouldbeincludedinthe monograph wasreached,aspeciesspecificstatementforeachindicationtobeincluded wasdraftedandplacedintooneofthreecategories.Acceptedindicationswerethose thathadsubstantialdatasupportingthemandwereincommonuse.Themajorityofthese
wereindicationsincludedincurrentproductlabeling,butextralabelindicationsalso wereincludediftheyrosetotherequiredlevelofevidence.ThePotentiallyeffective category (alsoknownasAcceptancenotestablishedintheolderUSPinformation monographs)includedindicationswithmoderateevidencetosupportaparticularuse, oftenaddressinganunmetclinicalneed.Lastly,anindicationmay havebeen deemed Unaccepted,meaningthedrugshouldnotbeusedforagivenpurpose.Thislatter categorization wasmostoftenappliedtoolderdrugsthatnewertreatmentshadrendered obsoleteduetoimprovedsafetyand/orefficacy.Inaddition,beginningin2005,allnew monographsandrevisionsofoldermonographsincludedevidenceratingsforeach indication.EachratingwascomposedofoneoverallEvidenceQualityindicatorandone ormoreEvidenceTypeindicators(seeExamples1and2).Themonographidentified intowhichofthethreecategoriesanindicationfell,combinedwiththedrugproducts evidenceratings,providinganevidentiarybasistosupportanindicateduse. Theevidencetablescreatedforextralabel indicationswerealsousedaspartof thediscussionsforcorrespondingdosagerecommendations.Inafewcases,tableswere specificallycreatedtoaddressadosagecontroversy.Bothextralabelindicationsand dosingwereassignedadesignationtodifferentiatethem fromlabeledrecommendations ineachmonograph. Theinitialballotallowedcommentsonanyportionofthemonograph,inaddition torequestingdecisionsonindicationsanddosing.Itwastypicallyfollowedbyatleast oneballotsummarizingtheinitialresponsestoissuesonwhichaconsensuswasnot reached. DraftmonographrevisionandExpertCommitteereviewcontinueduntila consensuswasreachedonallpreviouslycontentioussections. Themonograph wasthen
listedforpublicreviewonUSPswebsite,duringwhichtimecopiesofdrafttextwere madeavailabletothemanufacturersofthedrug,theCenterforVeterinaryMedicine/U.S. FoodandDrugAdministration,andall otherinterestedpartiesforreviewandcomment. Followingpublicreviewthemonograph wasfinalized,becamepartof USPsauthorized text(notFDAenforceable),andwaspublished.Monographsunderwentperiodic updates,asneeded. USP monographsweretheonlydruginformationsourcein veterinarymedicinewhichunderwentsuchextensiveevidencebasedevaluationcoupled withexpertpanelreview,aprocessbywhichthescientificcredibilityoftheinformation wasmaintained. InDecemberof2008,USPunderwentasignificantstaffreductionwitha concomitantreductionoreliminationofcertaininformationprograms,duetothe worldwideeconomicdownturn.Thereisnolongeraveterinarianonstafftoworkwith theVMIExpertCommitteetodevelopandupdatethemonographsandevidencetables. Mostofthemorethan100evidencetablescreatedduringdevelopmentofthisevidence basedinformationarenotpubliclyavailable.InSeptember2009,theVeterinaryClinical DrugInformationmonographsweretransferredtotheAmericanAcademyofVeterinary PharmacologyandTherapeuticsandcanbeaccessedonthewebsiteat http://www.aavpt.org/USPmonographs.shtml.Thefuturedevelopmentofthisdrug informationresourceisbeingdiscussedwithintheAAVPTandtheAmericanCollegeof VeterinaryClinicalPharmacology.
Example2.EvidenceratingsandIndicationStatement EvidenceQuality A.Goodevidencetosupportarecommendationforuse B.Moderateevidencetosupportarecommendationforuse C.Insufficientevidencetosupportarecommendationforuse D.Moderateevidencetosupportarecommendationagainstuse E.Goodevidencetosupportarecommendationagainstuse EvidenceType 1. Speciesspecificevidencefromatleastonelargerandomizedandcontrolledtrial (RCT)ormultiplesmallRCTs 2. SpeciesspecificevidencefromasmallRCT,diseasemodels,largecasestudies, pharmacokineticstudiesusingsurrogateendpoints,orevidencefromwelldesigned trialsinadifferentspeciesthatisconsideredappropriateforcomparison. 3. Dramaticresultsfromeitherwelldesigned,speciesspecifictrialswithoutcontrols, controlledtrialswithoutrandomization,orsmallcasestudies. 4. Pharmacokineticstudieswithoutsurrogateendpointsorwelldesigned pharmacodynamicstudiesinhealthyanimals 5. Invitrostudies 6. Opinionsofrespectedauthoritiesonthebasisofclinicalexperienceorreportsof expertcommittees.
Exampleofanindicationstatementinthemonograph Dogs Accepted US,CAN EL EL *Perioperativeinfections(prophylaxis) Cefazolinis usedinthepreventionofinfectionsassociatedwithsurgery, includingbonesurgery,andcausedbysusceptibleorganisms, whentheriskofinfectionishighorpotentiallyseverelydamaging (Evidencerating:A1,2).{R1268283} *ELUS,CAN indicatesanextralabelindicationintheU.S.andCanada.