clinical trials 临床试验方案

NY/VIAETCUnderstandingClinicalTrialsDevelopedbySaraBack,NPBronx-LebanonHospitalCenterNY/VIAETCOverview•PurposeofResearchStudies•ClassificationsofEpidemiologicalResearch•BasicResearchTerminology•FeaturesofClinicalTrials•Design/Protocol•PhasesofaStudy•Ethics•ProtectionofParticipants•ContributionsofClinicalTrials•ParticipatinginaTrial•Conclusion&TakeHomeMessageNY/VIAETCOverviewtoResearchStudiesWhyDoResearchStudies?•Tocollectdataonusualandunusualevents,conditions,&populationgroups•Totesthypothesesformulatedfromobservationsand/orintuition•Ultimately,tounderstandbetterone’sworldandmake“senseofit”NY/VIAETCOverviewtoResearchStudies•Varioustypesofresearchstudies•Manyclassifiedas“EpidemiologicalStudies”Epidemiologyoftenisdefinedas:Thestudyofthedistributionofadiseaseorconditioninapopulationandthefactorsthatinfluencethatdistribution.NY/VIAETCClassificationsofResearchStudies:ThreeMainTypesObservationalStudies:•Groupsarestudied&contrastsmadebetweengroups•TheobserveddatacollectedareanalyzedAnalyticStudies:•AlsocalledExperimental•Studytheimpactofacertaintherapy•UltimatelytheinvestigatorcontrolsfactorbeingstudiedClinicalTrial:•Consideredthe“true”experimentalstudy•“GoldStandard”ofclinicalresearch•OftenaprospectivestudythatcomparestheeffectandvalueofaninterventionagainstacontrolinhumansubjectsNY/VIAETCAnotherClassificationSystem•Non-directedDataCapture•Ex:VitalStatistics•DirectedDataCapture&HypothesisTesting•Ex:CohortStudies,CaseControlStudies•ClinicalTrials•Ex:InvestigationofTreatment/Condition•Ex:DrugTrialsNY/VIAETCTheDifferentStudyDesigns•Case-control•Cohort•CaseReports•CaseSeries•OutcomesBased:•SurveyResearch:QualityofLifeQuestionnairesDecisionanalysisPollsEconomicAnalysisSurveys•MetaAnalyses•SurvivalAnalysis•RandomizedClinicalTrialNY/VIAETCBasicResearchTerminology•Retrospective:Referstotimeofdatacollection•Prospective:Referstotimeofdatacollection•CaseControlStudy:Personsw/disease&thosew/outarecompared•CohortStudy:Personsw/and/orw/outdiseasearefollowedovertimeNY/VIAETCTerminology(Cont.)•Cross-sectionalStudy:Presenceorabsenceofexposuretopossibleriskfactormeasuredatonepointintime.Prevalenceobtained.•Prevalence:The#ofnewcasesandexistingcasesduringspecifiedtimeperiod.•Incidence:The#ofNEWcasesperunitofapopulationatriskfordiseaseoccurringduringstatedtimeperiod.NY/VIAETCHistoricalMinuteFirst“ClinicalTrials”•ClinicalTrialshavealonghistory–evenifnotacknowledgedasClinicaltrials•Formalrecordofclinicaltrialsdatesbacktothetimeofthe“Trialists”:•Dr.VanHelmont’sproposalforatherapeutictrialofbloodlettingforfevers[1628]•Dr.Lind’s,ashipsurgeon,trialoforanges&limesforscurvy[1747]NY/VIAETCHistoricalMinuteFirst“ClinicalTrials”HistoricalHighlightsofDrugTrials•1909:PaulEhrlich-Arsphenamine•1929:AlexanderFleming-Penicillin•1935:GerhardDomagk-Sulfonamide•1944:Schatz/Bugie/Waksman–Streptomycin•By1950,theBritishMedicalRes.Councildevelopedasystematicmethodologyforstudying&evaluatingtherapeuticinterventionsNY/VIAETCCoreComponentsofClinicalTrials•Involvehumansubjects•Moveforwardintime•MosthaveacomparisonCONTROLgroup•Musthavemethodtomeasureintervention•Focusonunknowns:effectofmedication•Mustbedonebeforemedicationispartofstandardofcare•ConductedearlyinthedevelopmentoftherapiesNY/VIAETCCoreComponentsofClinicalTrials•Mustreviewexistingscientificdata&buildonthatknowledge•Testacertainhypothesis•Studyprotocolmustbebuiltonsoundðicalscience•Controlforanypotentialbiases•Moststudymedications,procedures,and/orotherinterventionsNY/VIAETCThePossibleWorldofClinicalTrialDesigns•Randomized/blindedtrial•Randomized/doubleblindedtrial•Non-randomizedconcurrentcontrolledtrial•Placebotrial•Historicalcontrolledtrial•CrossoverTrial•WithdrawaltrialNY/VIAETCSimplified•Randomized:SchemesusedtoassignparticipanttoonegroupoEx:Every3getshigherdose•Nonrandomized:AllwithHep.C=cases;others=controls•Protocol:Studydesign-instructions•Blinded:Participantsdonotknowifinexperimentalorcontrolgroup•DoubleBlinded:ParticipantsANDstaffdonotknowgroupassignment•Placebo:Inactivepillw/notherapeuticvalueNY/VIAETCComponentsofClinicalTrialProtocols•Investigatingtwoormoreconditionssohavetwo(+)groups•Ex:drugvs.placebo;medicinevs.surgery;lowdosevs.highdose•Specificinclusion/exclusioncriteria•Samplesize&powercalculations•Planre:potentialbiases•Planre:handlingofattrition/losstofollowupNY/VIAETCStudyParticipantRecruitment•Identifyeligibleparticipants•Explainstudy•Provideinformedconsent•Reassesseligibility•AssigntoonegroupParticipantsshouldbetold:•Mayhavesideeffects(adverseeffects)•Timecommitment•Benefits&risks•Maywithdrawatanytime•Enrollment100%voluntaryNY/VIAETCPhasesofClinicalTrials•Mosttrialsthatinvolvenewdrugsgothroughaseriesofsteps:–#1:Experimentsinthelaboratory–#2:Oncedeemedsafe,gothrough1-4phasesNY/VIAETCPhasesofClinicalTrials•PhaseI:Smallgroup[20-80]for1sttimetoevaluatesafety,determinesafedosagerange&identifySE•PhaseII:Rx/txgiventolargergroup[100-300]toconfirmeffectiveness,monitorSE,&furtherevaluatesafetyNY/VIAETCPhasesofClinicalTrials(cont.)•PhaseIII:Rx/txgiventoevenlargergroup[1,000-3,000]tofulfil