1、Lea Drye,PhDJohns Hopkins UniversityTypes of Trial DesignCopyright 2013 Johns Hopkins University and Lea Drye.All Rights Reserved.临床试验设计的类型Phase I:First stage in testing a new intervention in humansUsually 10-30 peopleIdentify tolerable dose,provide information on drug metabolism,excretion,and toxic
2、ityOften not controlledPhase II:Usually 30-100 peoplePreliminary information on efficacy,additional information onsafety and side effectsPhase III:Usually 100+peopleAssess efficacy and safetyControlled,usually randomized2Phases of trials临床试验设计的类型Lecture OutlineDiscuss various trial design typesParal
3、lelCrossoverGroup allocationFactorialLarge simpleEquivalencyNon-inferiorityAdaptive3临床试验设计的类型Comparison 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
4、 under rules of fair use for registered students in this course only.No additional copies of the copyrighted work may be made or distributed.临床试验设计的类型Parallel DesignSimultaneous treatment and control groupsEach person is randomly assigned to one treatment groupRandomization removes treatment selecti
5、on bias and promotes comparability of treatment groupsStatistical comparisons made between treatment groups临床试验设计的类型5|P叫eG巾Randomized占v1，白iJHSPH临床试验设计的类型Parallel Design Example:NETTSource:NETT Research Group(1999).Chest 1999;116:1750-61;NETT Research Group(1999).J Thorac Cardiovasc Surg,118:518-528;
6、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 emphysemaSample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy(standard t
7、herapy control)临床试验设计的类型7Parallel 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 testingSuperiorityOutcomesPrimary:mortality,exercise ca
8、pacitySecondary:quality of life,symptoms,lung function and mechanics,functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center(17)临床试验设计的类型8Crossover DesignRandomization of order in which treatments are receivedAB or BARandomization promotes balance between treatment groups
9、 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 needed临床试验设计的类型9Crossover Design GraphWashoutGroup 1,Tx AGroup 1,Tx BGroup 2,Tx BGroup 2,Tx A临床试验设计的
10、类型10Crossover Design:DisadvantagesTreatment cant have permanent effects or curesPotential carry-over effects of first-period treatment to second periodWashout needs to be long enoughUnequal carry-over effectsTreatment during washoutTest for period by treatment interactions not powerfulDropouts more
11、significantAnalysis may be more difficult临床试验设计的类型11Crossover Design:UsesConstant intensity of underlying diseaseChronic diseasesasthma,hypertension,arthritisShort-term treatment effectsRelief of signs or symptoms of diseaseMetabolic,bioavailability,or tolerability studies临床试验设计的类型12Crossover Design
12、: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 childrenTopical oil vs.placebo for neuropathic pain临床试验设计的类型13Group Allocation DesignAlso known
13、 as“cluster randomization”Randomization unit is a group of individuals(community,school,clinic)Individual randomization and intervention is not feasible or is unacceptableTrackingContaminationIf there is a correlation in the responses within a group,design loses some efficiency(more individuals requ
14、ired)临床试验设计的类型14lIj川臼Randomized临床试验设计的类型Group Allocation Example:Sommer Vit A trial16Lancet.1986 May 24;1(8491):1169-73PopulationPreschool children in northern Sumatra in 1982-83TreatmentsVitamin A supplementation during studyVitamin A supplementation after studyClustersVillages(450)selected using survey sampling methodEach randomly allocated to one treatment临床试验设计的类型
