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Lea Drye, PhD,Johns Hopkins University,Types of Trial Design,Copyright 2013 Johns Hopkins University and Lea Drye. All Rights Reserved.,Phase 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 side effectsPhase III:Usually 100+ peopleAssess efficacy and safetyControlled, usually randomized2,Phases of trials,Lecture Outline,Discuss various trial design typesParallelCrossoverGroup allocationFactorialLarge simpleEquivalencyNon-inferiorityAdaptive,3,Comparison Structure: Parallel, Crossover, and Group,Allocation Designs,Section A,The 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.,Parallel Design,5,Simultaneous 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 groups,|,P,叫,eG,巾,Randomized,占v,1，白,6,iJHSPH,Parallel Design Example: NETT,Source: 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.,7,National Emphysema Treatment Trial (NETT)-Phase III trial, unmasked,Parallel Design Example: NETT,Source: 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.,8,Crossover Design,9,Randomization of order in which treatments are receivedAB 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 needed,Crossover Design Graph,Washout,10,Group 1, Tx A,Group 1, Tx B,Group 2, Tx B,Group 2, Tx A,Crossover Design: Disadvantages,11,Treatment 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 significantAnalysis may be more difficult,Crossover Design: Uses,12,Constant intensity of underlying diseaseChronic diseasesasthma, hypertension, arthritisShort-term treatment effectsRelief of signs or symptoms of diseaseMetabolic, bioavailability, or tolerability studies,Crossover Design: Examples,13,Evening-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,Group Allocation Design,14,Also known 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 required),l,Ij川臼,15,Randomized,Group Allocation Example: Sommer Vit A trial,16,Lancet. 1986 May 24;1(8491):1169-73,PopulationPreschool children in northern Sumatra in 1