临床试验设计的类型.pptx

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1、Lea Drye,PhDJohns Hopkins UniversityTypes of Trial DesignCopyright 2013 Johns Hopkins University and Lea Drye.All Rights Reserved.P h a s e I:-First stage in testing a new intervention in humans-Usually 10-30 people-Identify tolerable dose,provide information on drug metabolism,excretion,and toxicit

2、y-Often not controlled P h a s e II:-Usually 30-100 people-Preliminary information on efficacy,additional information onsafety and side effects P h a s e III:-Usually 100+people-Assess efficacy and safety-Controlled,usually randomized2Phases of trialsLecture Outline D i scuss various trial design ty

3、pes-Parallel-Crossover-Group allocation-Factorial-Large simple-Equivalency-Non-inferiority-Adaptive3Comparison 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 p

4、urposes 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 Design5 S i m u ltaneous treatment and control groups Each person is randomly assigned to one treatment group R a n d omization removes treatme

5、nt selection bias and promotes comparability of treatment groups S t a t i stical comparisons made between treatment groups|P叫 eG巾Randomized占v1，白6iJHSPHParallel Design Example:NETTSource:NETT Research Group(1999).Chest 1999;116:1750-61;NETT Research Group(1999).J Thorac Cardiovasc Surg,118:518-528;F

6、ishman,A.,&Martinez,F.,et al.(2003).N Engl J Med 348:2059-73.7 N a t i onal Emphysema Treatment Trial(NETT)-Phase III trial,unmaskedPopulationPeople with severe emphysemaSample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy(stand

7、ard therapy control)Parallel 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 348:2059-73.8Hypothesis testingSuperiorityOutcomesPrimary:mortality,exercise capaci

8、tySecondary:quality of life,symptoms,lung function and mechanics,functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center(17)Crossover Design9 R a n d omization of order in which treatments are received-AB or BA-Randomization promotes balance between treatment groups intim

9、ing of exposure Testing of both treatments in each patient-Each patient serves as his/her own control-Variability reduced because less variability within patient thanbetween patients Fewer patients neededCrossover Design GraphWashout10Group 1,Tx AGroup 1,Tx BGroup 2,Tx BGroup 2,Tx ACrossover Design:

10、Disadvantages11 Treatment cant have permanent effects or cures Potential carry-over effects of first-period treatment to second period-Washout needs to be long enough-Unequal carry-over effects-Treatment during washout Test for period by treatment interactions not powerful D ropouts more significant

11、 Analysis may be more difficultCrossover Design:Uses12 C onstant intensity of underlying disease-Chronic diseasesasthma,hypertension,arthritis S h ort-term treatment effects-Relief of signs or symptoms of disease M e t a b olic,bioavailability,or tolerability studiesCrossover Design:Examples13 Eveni

12、ng-dose vs.morning-dosed travoprost in open-angle glaucoma for 24-hour intraocular pressure control M ontelukast vs.salmeterol as adjuvant to inhaled fluticasone for exercise-induced asthma in children Topical oil vs.placebo for neuropathic painGroup Allocation Design14 Also known as“cluster randomi

13、zation”R a n d omization unit is a group of individuals(community,school,clinic)I n d i vidual randomization and intervention is not feasible or is unacceptable-Tracking-Contamination I f there is a correlation in the responses within a group,design loses some efficiency(more individuals required)l

14、I j 川 臼15RandomizedGroup Allocation Example:Sommer Vit A trial16Lancet.1986 May 24;1(8491):1169-73 P o p u l a tion-Preschool children in northern Sumatra in 1982-83 Treatments-Vitamin A supplementation during study-Vitamin A supplementation after study C l u sters-Villages(450)selected using survey sampling method-Each randomly allocated to one treatment