临床试验设计的类型课件1

1、临床试验设计的类型课件1Phase I:First stage in testing a new intervention in humansUsually 10-30 peopleIdentify tolerable dose, provide information on drug metabolism,excretion, and toxicityOften not controlledPhase II:Usually 30-100 peoplePreliminary information on efficacy, additional information onsafety and

2、 side effectsPhase III:Usually 100+ peopleAssess efficacy and safetyControlled, usually randomized2Phases of trialsPhase I:Phases of trialsLecture OutlineDiscuss various trial design typesParallelCrossoverGroup allocationFactorialLarge simpleEquivalencyNon-inferiorityAdaptive3Lecture OutlineDiscuss

3、variComparison Structure: Parallel, Crossover, and GroupAllocation DesignsSection AThe material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional co

4、pies of the copyrighted work may be made or distributed.Comparison Structure: ParallelParallel DesignSimultaneous treatment and control groupsEach person is randomly assigned to one treatment groupRandomization removes treatment selection bias and promotes comparability of treatment groupsStatistica

5、l comparisons made between treatment groups5Parallel DesignSimultaneous|P叫eG巾Randomized占v1，白iJHSPH6|P叫eG巾Randomized占v1，白iJHSPHParallel Design Example: NETTSource: NETT Research Group (1999). Chest 1999; 116: 1750-61; NETT Research Group (1999). J Thorac Cardiovasc Surg, 118: 518-528; Fishman, A., &

6、Martinez, F., et al. (2003). N Engl J Med 348: 2059-73.National Emphysema Treatment Trial (NETT)-Phase III trial, unmaskedPopulationPeople with severe emphysemaSample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy (standard thera

7、py control)7Parallel Design Example: NETTSParallel Design Example: NETTSource: NETT Research Group (1999). Chest 1999; 116: 1750-61; NETT Research Group (1999). J Thorac Cardiovasc Surg, 118: 518-528; Fishman, A., & Martinez, F., et al. (2003). N Engl J Med 348: 2059-73.Hypothesis testingSuperiority

8、OutcomesPrimary: mortality, exercise capacitySecondary: quality of life, symptoms,lung function and mechanics, functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center (17)8Parallel Design Example: NETTSCrossover DesignRandomization of order in which treatments are receive

9、dAB or BARandomization promotes balance between treatment groups intiming of exposureTesting of both treatments in each patientEach patient serves as his/her own controlVariability reduced because less variability within patient thanbetween patientsFewer patients needed9Crossover DesignRandomizatiCr

10、ossover Design GraphWashoutGroup 1, Tx AGroup 1, Tx BGroup 2, Tx BGroup 2, Tx A10Crossover Design GraphWashoutGCrossover Design: DisadvantagesTreatment cant have permanent effects or curesPotential carry-over effects of first-period treatment to second periodWashout needs to be long enoughUnequal ca

11、rry-over effectsTreatment during washoutTest for period by treatment interactions not powerfulDropouts more significantAnalysis may be more difficult11Crossover Design: DisadvantageCrossover Design: UsesConstant intensity of underlying diseaseChronic diseasesasthma, hypertension, arthritisShort-term

12、 treatment effectsRelief of signs or symptoms of diseaseMetabolic, bioavailability, or tolerability studies12Crossover Design: UsesConstCrossover Design: ExamplesEvening-dose vs. morning-dosed travoprost in open-angle glaucoma for 24-hour intraocular pressure controlMontelukast vs. salmeterol as adj

13、uvant to inhaled fluticasone for exercise-induced asthma in childrenTopical oil vs. placebo for neuropathic pain13Crossover Design: ExamplesGroup Allocation DesignAlso known as “cluster randomization”Randomization unit is a group of individuals (community, school, clinic)Individual randomization and

14、 intervention is not feasible or is unacceptableTrackingContaminationIf there is a correlation in the responses within a group, design loses some efficiency (more individuals required)14Group Allocation DesignAlsolIj川臼Randomized15lIj川臼Randomized15Group Allocation Example: Sommer Vit A trial16Lancet. 1986 May 24;1(8491):1169-73PopulationPreschool children in northern Sumatra in 1982-83TreatmentsVitamin A supplementation during studyVitami