The-Investigator’s-Brochure

7.1IntroductionTheInvestigator’sBrochure(IB)isacompilationoftheclinicalandnonclinicaldataontheinvestigationalproduct(s)thatarerelevanttothestudyoftheproduct(s)inhumansubjects.Itspurposeistoprovidetheinvestigatorsandothersinvolvedinthetrialwiththeinformationtofacilitatetheirunderstandingoftherationalefor,andtheircompliancewith,manykeyfeaturesoftheprotocol,suchasthedose,dosefrequency/interval,methodsofadministration:andsafetymonitoringprocedures.TheIBalsoprovidesinsighttosupporttheclinicalmanagementofthestudysubjectsduringthecourseoftheclinicaltrial.Theinformationshouldbepresentedinaconcise,simple,objective,balanced,andnon-promotionalformthatenablesaclinician,orpotentialinvestigator,tounderstanditandmakehis/herownunbiasedrisk-benefitassessmentoftheappropriatenessoftheproposedtrial.Forthisreason,amedicallyqualifiedpersonshouldgenerallyparticipateintheeditingofanIB,butthecontentsoftheIBshouldbeapprovedbythedisciplinesthatgeneratedthedescribeddata.ThisguidelinedelineatestheminimuminformationthatshouldbeincludedinanIBandprovidessuggestionsforitslayout.Itisexpectedthatthetypeandextentofinformationavailablewillvarywiththestageofdevelopmentoftheinvestigationalproduct.Iftheinvestigationalproductismarketedanditspharmacologyiswidelyunderstoodbymedicalpractitioners,anextensiveIBmaynotbenecessary.Wherepermittedbyregulatoryauthorities,abasicproductinformationbrochure,packageleaflet,orlabellingmaybeanappropriatealternative,providedthatitincludescurrent,comprehensive,anddetailedinformationonallaspectsoftheinvestigationalproductthatmightbeofimportancetotheinvestigator.Ifamarketedproductisbeingstudiedforanewuse(i.e.,anewindication),anIBspecifictothatnewuseshouldbeprepared.TheIBshouldbereviewedatleastannuallyandrevisedasnecessaryincompliancewithasponsor’swrittenprocedures.Morefrequentrevisionmaybeappropriatedependingonthestageofdevelopmentandthegenerationofrelevantnewinformation.However,inaccordancewithGoodClinicalPractice,relevantnewinformationmaybesoimportantthatitshouldbecommunicatedtotheinvestigators,andpossiblytotheInstitutionalReviewBoards(IRBs)/IndependentEthicsCommittees(IECs)and/orregulatoryauthoritiesbeforeitisincludedinarevisedIB.Generally,thesponsorisresponsibleforensuringthatanup-to-dateIBismadeavailabletotheinvestigator(s)andtheinvestigatorsareresponsibleforprovidingtheup-to-dateIBtotheresponsibleIRBs/IECs.Inthecaseofaninvestigatorsponsoredtrial,thesponsor-investigatorshoulddeterminewhetherabrochureisavailablefromthecommercialmanufacturer.Iftheinvestigationalproductisprovidedbythesponsor-investigator,thenheorsheshouldprovidethenecessaryinformationtothetrialpersonnel.IncaseswherepreparationofaformalIBisimpractical,thesponsor-investigatorshouldprovide,asasubstitute,anexpandedbackgroundinformationsectioninthetrialprotocolthatcontainstheminimumcurrentinformationdescribedinthisguideline.7.2GeneralConsiderationsTheIBshouldinclude:7.2.1TitlePageThisshouldprovidethesponsor’sname,theidentityofeachinvestigationalproduct(i.e.,researchnumber,chemicalorapprovedgenericname,andtradename(s)wherelegallypermissibleanddesiredbythesponsor),andthereleasedate.Itisalsosuggestedthataneditionnumber,andareferencetothenumberanddateoftheeditionitsupersedes,beprovided.AnexampleisgiveninAppendix1.7.2.2ConfidentialityStatementThesponsormaywishtoincludeastatementinstructingtheinvestigator/recipientstotreattheIBasaconfidentialdocumentforthesoleinformationanduseoftheinvestigator’steamandtheIRB/IEC.7.3ContentsoftheInvestigator’sBrochureTheIBshouldcontainthefollowingsections,eachwithliteraturereferenceswhereappropriate:7.3.1TableofContentsAnexampleoftheTableofContentsisgiveninAppendix27.3.2SummaryAbriefsummary(preferablynotexceedingtwopages)shouldbegiven,highlightingthesignificantphysical,chemical,pharmaceutical,pharmacological,toxicological,pharmacokinetic,metabolic,andclinicalinformationavailablethatisrelevanttothestageofclinicaldevelopmentoftheinvestigationalproduct.7.3.3IntroductionAbriefintroductorystatementshouldbeprovidedthatcontainsthechemicalname(andgenericandtradename(s)whenapproved)oftheinvestigationalproduct(s),allactiveingredients,theinvestigationalproduct(s)pharmacologicalclassanditsexpectedpositionwithinthisclass(e.g.advantages),therationaleforperformingresearchwiththeinvestigationalproduct(s),andtheanticipatedprophylactic,therapeutic,ordiagnosticindication(s).Finally,theintroductorystatementshouldprovidethegeneralapproachtobefollowedinevaluatingtheinvestigationalproduct.7.3.4Physical,Chemical,andPharmaceuticalPropertiesandFormulationAdescriptionshouldbeprovidedoftheinvestigationalproductsubstance(s)(includingthechemicaland/orstructuralformula(e)),andabriefsummaryshouldbegivenoftherelevantphysical,chemical,andpharmaceuticalproperties.Topermitappropriatesafetymeasurestobetakeninthecourseofthetrial,adescriptionoftheformulation(s)tobeused,includingexcipients,shouldbeprovidedandjustifiedifclinicallyrelevant.Instructionsforthestorageandhandlingofthedosageform(s)shouldalsobegiven.Anystructuralsimilaritiestootherknowncompoundsshouldbementio