1、Phase I:-First stage in testing a new intervention in humans-Usually 10-30 people-Identify tolerable dose,provide information on drug metabolism,excretion,and toxicity-Often not controlledPhase II:-Usually 30-100 people-Preliminary information on efficacy,additional information onsafety and side eff
2、ectsPhase III:-Usually 100+people-Assess efficacy and safety-Controlled,usually randomized2Phases of trialsLecture OutlineDiscuss various trial design types-Parallel-Crossover-Group allocation-Factorial-Large simple-Equivalency-Non-inferiority-Adaptive3Comparison Structure:Parallel,Crossover,and Gro
3、upAllocation 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 copies of the copyrighted work may be made or distributed
4、.Parallel DesignSimultaneous treatment and control groupsEach person is randomly assigned to one treatment groupRandomization removes treatment selection bias and promotes comparability of treatment groupsStatistical comparisons made between treatment groups5|P叫eG巾Randomized占v1，白iJHSPH6Parallel Desi
5、gn 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.National Emphysema Treatment Trial(NETT)-Phase III trial,unmaskedPopulationPeople with severe emphysemaS
6、ample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy(standard therapy control)7Parallel Design Example:NETTSource:NETT Research Group(1999).Chest 1999;116:1750-61;NETT Research Group(1999).J Thorac Cardiovasc Surg,118:518-528;Fis
7、hman,A.,&Martinez,F.,et al.(2003).N Engl J Med 348:2059-73.Hypothesis testingSuperiorityOutcomesPrimary:mortality,exercise capacitySecondary:quality of life,symptoms,lung function and mechanics,functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center(17)8Crossover DesignRa
8、ndomization of order in which treatments are received-AB or BA-Randomization promotes balance between treatment groups intiming of exposureTesting of both treatments in each patient-Each patient serves as his/her own control-Variability reduced because less variability within patient thanbetween pat
9、ientsFewer patients needed9Crossover Design GraphWashoutGroup 1,Tx AGroup 1,Tx BGroup 2,Tx BGroup 2,Tx A10Crossover Design:DisadvantagesTreatment cant have permanent effects or curesPotential carry-over effects of first-period treatment to second period-Washout needs to be long enough-Unequal carry-
10、over effects-Treatment during washoutTest for period by treatment interactions not powerfulDropouts more significantAnalysis may be more difficult11Crossover Design:UsesConstant intensity of underlying disease-Chronic diseasesasthma,hypertension,arthritisShort-term treatment effects-Relief of signs
11、or symptoms of diseaseMetabolic,bioavailability,or tolerability studies12Crossover Design:ExamplesEvening-dose vs.morning-dosed travoprost in open-angle glaucoma for 24-hour intraocular pressure controlMontelukast vs.salmeterol as adjuvant to inhaled fluticasone for exercise-induced asthma in childr
12、enTopical oil vs.placebo for neuropathic pain13Group Allocation DesignAlso known as“cluster randomization”Randomization unit is a group of individuals(community,school,clinic)Individual randomization and intervention is not feasible or is unacceptable-Tracking-ContaminationIf there is a correlation
13、in the responses within a group,design loses some efficiency(more individuals required)14lIj川臼Randomized15Group Allocation Example:Sommer Vit A trial16Lancet.1986 May 24;1(8491):1169-73Population-Preschool children in northern Sumatra in 1982-83Treatments-Vitamin A supplementation during study-Vitamin A supplementation after studyClusters-Villages(450)selected using survey sampling method-Each randomly allocated to one treatment此课件下载可自行编辑修改，仅供参考！此课件下载可自行编辑修改，仅供参考！感谢您的支持，我们努力做得更好！感谢您的支持，我们努力做得更好！谢谢谢谢!
