臨床試驗(yàn)設(shè)計(jì)的類型課件

1、Lea Drye, PhDJohns Hopkins UniversityTypes of Trial DesignCopyright 2013 Johns Hopkins University and Lea Drye. All Rights Reserved.臨床試驗(yàn)設(shè)計(jì)的類型Lea Drye, PhDJohns Hopkins UniPhase I:First stage in testing a new intervention in humansUsually 10-30 peopleIdentify tolerable dose, provide information on dr

2、ug 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 randomized2Phases of trials臨床試驗(yàn)設(shè)計(jì)的類型Phase I:Phases of

3、 trials臨床試Lecture OutlineDiscuss various trial design typesParallelCrossoverGroup allocationFactorialLarge simpleEquivalencyNon-inferiorityAdaptive3臨床試驗(yàn)設(shè)計(jì)的類型Lecture OutlineDiscuss variComparison Structure: Parallel, Crossover, and GroupAllocation DesignsSection AThe material in this video is subject

4、 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.臨床試驗(yàn)設(shè)計(jì)的類型Comparison Structure: ParallelParallel DesignSimultaneo

5、us 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臨床試驗(yàn)設(shè)計(jì)的類型5Parallel DesignSimultaneous|P叫eG巾Randomized占v1，白iJHSPH臨床試驗(yàn)

6、設(shè)計(jì)的類型|P叫eG巾Randomized占v1，白iJHSPHParallel 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.National Emphysema Treatment Trial (NET

7、T)-Phase III trial, unmaskedPopulationPeople with severe emphysemaSample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy (standard therapy control)臨床試驗(yàn)設(shè)計(jì)的類型7Parallel Design Example: NETTSParallel Design Example: NETTSource: NETT R

8、esearch 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 capacitySecondary: quality of life, symptoms,lun

9、g function and mechanics, functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center (17)臨床試驗(yàn)設(shè)計(jì)的類型8Parallel Design Example: NETTSCrossover DesignRandomization of order in which treatments are receivedAB or BARandomization promotes balance between treatment groups intiming of

10、 exposureTesting of both treatments in each patientEach patient serves as his/her own controlVariability reduced because less variability within patient thanbetween patientsFewer patients needed臨床試驗(yàn)設(shè)計(jì)的類型9Crossover DesignRandomizatiCrossover Design GraphWashoutGroup 1, Tx AGroup 1, Tx BGroup 2, Tx BG

11、roup 2, Tx A臨床試驗(yàn)設(shè)計(jì)的類型10Crossover Design GraphWashoutGCrossover 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

12、 treatment interactions not powerfulDropouts more significantAnalysis may be more difficult臨床試驗(yàn)設(shè)計(jì)的類型11Crossover Design: DisadvantageCrossover Design: UsesConstant intensity of underlying diseaseChronic diseasesasthma, hypertension, arthritisShort-term treatment effectsRelief of signs or symptoms of

13、diseaseMetabolic, bioavailability, or tolerability studies臨床試驗(yàn)設(shè)計(jì)的類型12Crossover Design: UsesConstCrossover 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 exercis

14、e-induced asthma in childrenTopical oil vs. placebo for neuropathic pain臨床試驗(yàn)設(shè)計(jì)的類型13Crossover Design: ExamplesGroup Allocation DesignAlso known as “cluster randomization”Randomization unit is a group of individuals (community, school, clinic)Individual randomization and intervention is not feasible o

15、r is unacceptableTrackingContaminationIf there is a correlation in the responses within a group, design loses some efficiency (more individuals required)臨床試驗(yàn)設(shè)計(jì)的類型14Group Allocation DesignAlsolIj川臼Randomized臨床試驗(yàn)設(shè)計(jì)的類型lIj川臼Randomized臨床試驗(yàn)設(shè)計(jì)的類型Group Allocation Example: Sommer Vit A trial16Lancet. 1986 May 24;1(8491):1169-73PopulationPreschool children in northern Su