临床试验设计的类型(1)

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 to

2、xicity-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 d

3、esign types-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 ed

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

5、oves treatment 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 Cardiova

6、sc Surg, 118: 518-528; Fishman, 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 plu

7、s medical therapyMedical therapy (standard 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: 2059-73.8Hypothe

8、sis testingSuperiorityOutcomesPrimary: mortality, exercise capacitySecondary: 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-A

9、B or BA-Randomization promotes balance between treatment groups intiming 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 GraphWasho

10、ut10Group 1, Tx AGroup 1, Tx BGroup 2, Tx BGroup 2, Tx ACrossover Design: 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 fo

11、r period by treatment interactions not powerful D ropouts more significant 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

12、olic, bioavailability, or tolerability studiesCrossover Design: Examples13 Evening-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.

13、placebo for neuropathic painGroup Allocation Design14 Also known as “cluster randomization” 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 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 nort