臨床試驗設計的類型課件

LeaDrye,PhDJohnsHopkinsUniversityTypesofTrialDesignCopyright?2013JohnsHopkinsUniversityandLeaDrye.AllRightsReserved.臨床試驗設計的類型

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

PhaseII:Usually30-100peoplePreliminaryinformationonefficacy,additionalinformationonsafetyandsideeffects

PhaseIII:Usually100+peopleAssessefficacyandsafetyControlled,usuallyrandomized2Phasesoftrials臨床試驗設計的類型LectureOutline

DiscussvarioustrialdesigntypesParallelCrossoverGroupallocationFactorialLargesimpleEquivalencyNon-inferiorityAdaptive3臨床試驗設計的類型ComparisonStructure:Parallel,Crossover,andGroupAllocationDesignsSectionAThematerialinthisvideoissubjecttothecopyrightoftheownersofthematerialandisbeingprovidedforeducationalpurposesunderrulesoffairuseforregisteredstudentsinthiscourseonly.Noadditionalcopiesofthecopyrightedworkmaybemadeordistributed.臨床試驗設計的類型ParallelDesign

Simultaneoustreatmentandcontrolgroups

Eachpersonisrandomlyassignedtoonetreatmentgroup

Randomizationremovestreatmentselectionbiasandpromotescomparabilityoftreatmentgroups

Statisticalcomparisonsmadebetweentreatmentgroups5臨床試驗設計的類型|P叫ωe G巾Randomized「占v1，白iJHSPH臨床試驗設計的類型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臨床試驗設計的類型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臨床試驗設計的類型CrossoverDesign

RandomizationoforderinwhichtreatmentsarereceivedABorBARandomizationpromotesbalancebetweentreatmentgroupsintimingofexposure

TestingofbothtreatmentsineachpatientEachpatientservesashis/herowncontrolVariabilityreducedbecauselessvariabilitywithinpatientthanbetweenpatients

Fewerpatientsneeded9臨床試驗設計的類型CrossoverDesignGraphWashoutGroup1,TxAGroup1,TxBGroup2,TxBGroup2,TxA10臨床試驗設計的類型CrossoverDesign:Disadvantages

Treatmentcan’thavepermanenteffectsorcures

Potentialcarry-overeffectsoffirst-periodtreatmenttosecondperiodWashoutneedstobelongenoughUnequalcarry-overeffectsTreatmentduringwashout

Testforperiodbytreatmentinteractionsnotpowerful

Dropoutsmoresignificant

Analysismaybemoredifficult11臨床試驗設計的類型CrossoverDesign:Uses

ConstantintensityofunderlyingdiseaseChronicdiseases—asthma,hypertension,arthritis

Short-termtreatmenteffectsReliefofsignsorsymptomsofdisease

Metabolic,bioavailability,ortolerabilitystudies12臨床試驗設計的類型CrossoverDesign:Examples

Evening-dosevs.morning-dosedtravoprostinopen-angleglaucomafor24-hourintraocularpressurecontrol

Montelukastvs.salmeterolasadjuvanttoinhaledfluticasoneforexercise-inducedasthmainchildren

Topicaloilvs.placeboforneuropathicpain13臨床試驗設計的類型GroupAllocationDesign

Alsoknownas“clusterrandomization”

Randomizationunitisagroupofindividuals(community,school,clinic)

IndividualrandomizationandinterventionisnotfeasibleorisunacceptableTrackingContamination

Ifthereisacorrelationintheresponseswithinagroup,designlosessomeefficiency(moreindividualsrequired)14臨床試驗設計的類型lα[Ij川臼Randomized〈〈臨床試驗設計的類型GroupAllocationExample:SommerVitAtrial16Lancet.1986May24;1(8491):1169-73

PopulationPreschoolchildreninnorthernSumatrai