临床试验设计的类型

LeaDrye,PhDJohnsHopkinsUniversityTypesofTrialDesignCopyright©2013JohnsHopkinsUniversityandLeaDrye.AllRightsReserved..

PhaseI:FirststageintestinganewinterventioninhumansUsually10-30peopleIdentifytolerabledose,provideinformationondrugmetabolism,excretion,andtoxicityOftennotcontrolled

PhaseII:Usually30-100peoplePreliminaryinformationonefficacy,additionalinformationonsafetyandsideeffects

PhaseIII:Usually100+peopleAssessefficacyandsafetyControlled,usuallyrandomized2Phasesoftrials.LectureOutline

DiscussvarioustrialdesigntypesParallelCrossoverGroupallocationFactorialLargesimpleEquivalencyNon-inferiorityAdaptive3.ComparisonStructure:Parallel,Crossover,andGroupAllocationDesignsSectionAThematerialinthisvideoissubjecttothecopyrightoftheownersofthematerialandisbeingprovidedforeducationalpurposesunderrulesoffairuseforregisteredstudentsinthiscourseonly.Noadditionalcopiesofthecopyrightedworkmaybemadeordistributed..ParallelDesign

Simultaneoustreatmentandcontrolgroups

Eachpersonisrandomlyassignedtoonetreatmentgroup

Randomizationremovestreatmentselectionbiasandpromotescomparabilityoftreatmentgroups

Statisticalcomparisonsmadebetweentreatmentgroups5.|P叫ωe G巾Randomized「占v1，白iJHSPH.ParallelDesignExample:NETTSource:NETTResearchGroup(1999).Chest1999;116:1750-61;NETTResearchGroup(1999).JThoracCardiovascSurg,118:518-528;Fishman,A.,&Martinez,F.,etal.(2003).NEnglJMed348:2059-73.

NationalEmphysemaTreatmentTrial(NETT)- PhaseIIItrial,unmaskedPopulationPeoplewithsevereemphysemaSamplesize1,200AllocationtotreatmentRandomizedTreatments—Lungvolumereductionsurgeryplusmedicaltherapy—Medicaltherapy(standardtherapycontrol)7.ParallelDesignExample:NETTSource:NETTResearchGroup(1999).Chest1999;116:1750-61;NETTResearchGroup(1999).JThoracCardiovascSurg,118:518-528;Fishman,A.,&Martinez,F.,etal.(2003).NEnglJMed348:2059-73.HypothesistestingSuperiorityOutcomes—Primary:mortality,exercisecapacity—Secondary:qualityoflife,symptoms,lungfunctionandmechanics,functionalcapacityFollow-upUpto7.5yearsNumberofrecruitingcentersMulti-center(17)8.CrossoverDesign

RandomizationoforderinwhichtreatmentsarereceivedABorBARandomizationpromotesbalancebetweentreatmentgroupsintimingofexposure

TestingofbothtreatmentsineachpatientEachpatientservesashis/herowncontrolVariabilityreducedbecauselessvariabilitywithinpatientthanbetweenpatients

Fewerpatientsneeded9.CrossoverDesignGraphWashoutGroup1,TxAGroup1,TxBGroup2,TxBGroup2,TxA10.CrossoverDesign:Disadvantages

Treatmentcan’thavepermanenteffectsorcures

Potentialcarry-overeffectsoffirst-periodtreatmenttosecondperiodWashoutneedstobelongenoughUnequalcarry-overeffectsTreatmentduringwashout

Testforperiodbytreatmentinteractionsnotpowerful

Dropoutsmoresignificant

Analysismaybemoredifficult11.CrossoverDesign:Uses

ConstantintensityofunderlyingdiseaseChronicdiseases—asthma,hypertension,arthritis

Short-termtreatmenteffectsReliefofsignsorsymptomsofdisease

Metabolic,bioavailability,ortolerabilitystudies12.CrossoverDesign:Examples

Evening-dosevs.morning-dosedtravoprostinopen-angleglaucomafor24-hourintraocularpressurecontrol

Montelukastvs.salmeterolasadjuvanttoinhaledfluticasoneforexercise-inducedasthmainchildren

Topicaloilvs.placeboforneuropathicpain13.GroupAllocationDesign

Alsoknownas“clusterrandomization”

Randomizationunitisagroupofindividuals(community,school,clinic)

IndividualrandomizationandinterventionisnotfeasibleorisunacceptableTrackingContamination

Ifthereisacorrelationintheresponseswithinagroup,designlosessomeefficiency(moreindividualsrequired)14.lα[Ij川臼Randomized〈〈.GroupAllocationExample:SommerVitAtrial16Lancet.1986May24;1(8491):1169-73

PopulationPreschoolchildreninnorthernSumatrain1982-83

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