clinical-trials-临床试验方案 PPT课件

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