Sarah Walker – 新型试验设计速览 v1.pdf

1、A whistlestop tour of novel trial designsSarah WalkerProfessor of Medical Statistics&EpidemiologyParadigm of evidence-based medicine“One regimen to rule them all”“Standard of care”,SOC,“control”:simultaneously maximising good outcomes and minimising bad outcomes(toxicity)Recommended in guidelines,sh

2、ould be generally used in all/most patientsIteratively improve this“optimal regimen”through series of(generally two-arm)randomised controlled trials vs SOCLed to massive improvements in outcomes forTuberculosisCancer chemotherapyHIVInnovation“Platform”designs/master protocolsMulti-Arm Multi-Stage(MA

3、MS)Baskets UmbrellasFactorial Compare multiple new interventions vs SOC to iteratively improve SOC faster Maximise efficiency in trial operationsMAMS(Multi-Arm Multi-Stage)Multi-arm:Test many relevant agents within one protocolMulti-arm,Multi-stageT2T3T1CT4Phase IIPhase IIIMulti-arm,Multi-stageT2T3T

4、1CT4Phase IIPhase IIIMAMS(Multi-Arm Multi-Stage)Multi-arm:Test many relevant agents within one protocolMulti-stage:Ask if reasons to continue investigating a treatment?Stop arms early for lack of benefit(“pick the winners”)OR lack of sufficient activity(“drop the losers”)Based on an intermediate(sur

5、rogate)outcomeMulti-arm,Multi-stageT2T3T1CT4Phase IIPhase IIIMulti-arm,Multi-stageT2T3T1CT4Phase IIPhase IIIMAMS(Multi-Arm Multi-Stage)Multi-arm:Test many relevant agents within one protocolMulti-stage:Ask if reasons to continue investigating a treatment?Stop arms early for lack of benefit(“pick the

6、 winners”)OR lack of sufficient activity(“drop the losers”)Based on an intermediate(surrogate)outcomeMulti-arm,Multi-stageT2T3T1CT4Phase IIPhase IIIMulti-arm,Multi-stageT2T3T1CT4Phase IIPhase IIIOther types of platform trial Basket vs umbrella?Basket trials:same intervention evaluated on multiple di