clinical trials 临床试验方案.ppt

NY/VIAETC,UnderstandingClinicalTrials,DevelopedbySaraBack,NPBronx-LebanonHospitalCenter,NY/VIAETC,Overview,PurposeofResearchStudiesClassificationsofEpidemiologicalResearchBasicResearchTerminologyFeaturesofClinicalTrialsDesign/ProtocolPhasesofaStudyEthicsProtectionofParticipantsContributionsofClinicalTrialsParticipatinginaTrialConclusionothers=controlsProtocol:Studydesign-instructions,Blinded:ParticipantsdonotknowifinexperimentalorcontrolgroupDoubleBlinded:ParticipantsANDstaffdonotknowgroupassignmentPlacebo:Inactivepillw/notherapeuticvalue,NY/VIAETC,ComponentsofClinicalTrialProtocols,Investigatingtwoormoreconditionssohavetwo(+)groupsEx:drugvs.placebo;medicinevs.surgery;lowdosevs.highdoseSpecificinclusion/exclusioncriteriaSamplesize&powercalculationsPlanre:potentialbiasesPlanre:handlingofattrition/losstofollowup,NY/VIAETC,StudyParticipantRecruitment,IdentifyeligibleparticipantsExplainstudyProvideinformedconsentReassesseligibilityAssigntoonegroup,Participantsshouldbetold:Mayhavesideeffects(adverseeffects)TimecommitmentBenefits&risksMaywithdrawatanytimeEnrollment100%voluntary,NY/VIAETC,PhasesofClinicalTrials,Mosttrialsthatinvolvenewdrugsgothroughaseriesofsteps:#1:Experimentsinthelaboratory#2:Oncedeemedsafe,gothrough1-4phases,NY/VIAETC,PhasesofClinicalTrials,PhaseI:Smallgroup20-80for1sttimetoevaluatesafety,determinesafedosagerange&identifySEPhaseII:Rx/txgiventolargergroup100-300toconfirmeffectiveness,monitorSE,&furtherevaluatesafety,NY/VIAETC,PhasesofClinicalTrials(cont.),PhaseIII:Rx/txgiventoevenlargergroup1,000-3,000tofulfillallofPhaseIIobjectives&compareittoothercommonlyusedtxs&collectdatathatwillallowittobeusedsafelyPhaseIV:Doneafterrx/txhasbeenmarketed-studiescontinuetotestrx/txtocollectdataabouteffectsinvariouspopulations&SEfromlongtermuse.,NY/VIAETC,SummaryofPhasesI-III,NY/VIAETC,EthicsofClinicalTrials:ProtectionofParticipants,3ethicalprinciplesguideclinicalresearch:RespectforPersons:TreatmentofpersonasautonomousBeneficence:Issuere:potentialconflictbetweengoodofsocietyvs.individualJustice:Treatmentofallfairly&allequallysharebenefits&risks,NY/VIAETC,EthicalNormsofClinicalTrials,Soundstudydesignstakeintoaccount:RandomizationorsharingofrisksProperuseofplaceboProcessestomonitorsafetyofrx/txCompetentinvestigatorsInformedconsentEquitableselectionofparticipantsCompensationforstudyrelatedinjuries,NY/VIAETC,EthicalIssues:ProtectionofHumanSubjects,RelyonintegrityofInvestigatorbutoutsidegroupsalsohaveoversightParticipantsrightsprotectedbyInstitutionalReviewBoardsIRBsAnIRBisdefinedas:anyboard,committeeorothergroupformallydesignatedbyaninstitutiontoreview,toapprovetheinitiationof,andtoconductperiodicreviewofbiomedicalresearchinvolvinghumansubjects,NY/VIAETC,HumanSubjectsProtection,IRBresponsibleforsuchtasks:ReviewresearchtoensurethatpotentialbenefitsoutweighrisksDevelopandissuewrittenproceduresReviewresearchforrisk/benefitanalysis&properprotectionofsubjectsIssuewrittennoticeofapproval/disapprovaltotheInvestigatorReviewandrespondtoproposedprotocolchangessubmittedbytheInvestigator,NY/VIAETC,HumanSubjectsProtection,Reviewreportsofdeaths,andseriousandunexpectedadverseeventsreceivedfromtheInvestigatorConductperiodiccontinuingreviewofthestudy,studyrisks,selectionofsubjects,privacyofsubjects,confidentialityofdata,andtheconsentprocess,IRBResponsibilities(continued):,NY/VIAETC,HistoricalMinute:OriginofIRBs&HumanSubjectCode,AttentiontoprotectingparticipantsbeganafterWWIIw/theNurembergTrials(1947)Outofthosetrials,keypointswerecodified,NY/VIAETC,HistoricalMinute:10KeyPoints,VoluntaryinformedconsentExperimentmustbeforthegoodofsociety,&resultsnotobtainablebyothermeansExperimentshouldbebaseduponprioranimalstudiesPhysical&mentalsuffering&injuryshouldbeavoidedNoexpectationthatdeath/disablinginjurywilloccurfromtheexperimentRiskvs.benefitProtectsubjectsagainstinjury,disability,ordeathOnlyscientificallyqualifiedpersonstobeinvolvedSubjectcanterminateher/hisinvolvement,NY/VIAETC,HistoricalMinute:OriginofIRBs&HumanSubjectCodes,Since1947,additionalsubjectprotectionrequirementsdeveloped&implementedLatestadditions:Year2000-PresidentClinton&DHHSSecretaryShalalaannouncedadditionalstudyrequirementsrelatedto:informedconsenttrainingreq.adverseeventsconflictofinterestcivilmonetarypenaltiesimprovedmonitoringofPhaseI&IItrials,NY/VIAETC,InformedConsent:APartofHumanSubjectProtection,ObjectivesofInformedConsentToEnsure:VoluntarinessComprehensionInformationToDemonstrateThat:PersonfreelygaveconsenttoparticipateConsentgivenbyacompetentpersonPersonhasbeengivenallinformationPersonknowsthisisresearchnottreatment,NY/VIAETC,ComponentsofInformedConsent,MustIncludetheFollowingInformation:Whyresearchbeingdone?WhatresearcherswanttoaccomplishWhatwillbedoneandforhowlongRisks&benefitsoftrialOthertreatmentsavailableCanwithdrawfromtrialwheneverdesireCompensationforunexpectedinjuries,NY/VIAETC,VulnerablePopulations,Groupsthoughtnottohaveautonomytogiveinformedconsent:childrenmentallyimpaired,individualswithdementiaPrisonersORWhomaybeundulyinfluencedtoparticipate:studentssubordinatespregnantwomen(actually,thefetuses)patients(care-givervs.researcher),NY/VIAETC,VulnerablePopulations,Tosafeguardthesegroups,specialrequirementssuchas:OnlyparentcanconsentforminorConsentsmustbeinsubjectsnativelang.Prisoners:onlysometypesofresearchallowed,NY/VIAETC,InclusioninClinicalTrials,NIHRevitalizationActof1993:Guidelinesthatrequireinclusionofwomen&minoritiesinclinicalstudiesNewguidelinesstipulatethat:Women&minoritiesaretobeincludedinallhumansubjectresearchTheyaretobeincludedinPhaseIIItrialstoallowsufficientpowertonotedifferencesCostcannotbeabarrierOutreachactivitiesmusttakeplacetoinclude&followthesegroups,NY/VIAETC,InclusioninClinicalTrials,Historicallywomenwereexcludedifofreproductiveage(ages18-45)FearofharmtopotentialunbornchildInessence,excludedMAJORITYofwomenNewguidelineseliminatesthisstipulation,NY/VIAETC,IssuesinClinicalTrials:UseofPlaceboTrials,Oninternationalrealm,1999“DeclarationofHelsinki”revisedtoaddressuseofplacebos:PlacebosnotethicalinvirtuallyallstudiesthatinvolvediseaseswithPROVENtxRemainethicalintrialswherenoproventxRevisionsduetocontroversyoveruseofplacebosinattemptingtofindeasy/cheapwaytoreduceHIVperinataltransmission1998studyinIvoryCoast,Uganda,&Thailand:HIV+pregnantwomengiveneitherplaceboorshortercourseofAZT,NY/VIAETC,ParticipationinClinicalTrials,WhySomeParticipate:GivebacktosocietyExhaustedallothertxsHealthcareservicesPayment&incentivesSupportOthers?,WhySomeDoNot?MistrustofstudiesDonotwanttobe“guineapig”DonotmeetcriteriaCannotgiveuptimeforstudyvisitsBarriers:lang.,distance,NY/VIAETC,TakingPartinResearchStudies:QuestionstoAsk,Whatisstudyabout?Whatarethegoals?Studysponsor?Participantinputintoprotocols?Inclusioncriteria?Benefits&risks,Isthereanincentive?Howprotectedfromharm?Whatisrequired:#studyvisit&whatoccurs?Whathappensafterstudyisover?Howresultswillbediss