Sample Size Re-Estimation for Adaptive Sequential Design in Clinical Trials

Abstract There is considerable interest in methods that use accumulated data to modify trial sample size. However, sample size re-estimation in group sequential designs has been controversial. We describe a method for sample size re-estimation at the penultimate stage of a group sequential design that achieves specified power against an alternative hypothesis corresponding to the current point estimate of the treatment effect. Key Words: Adaptive designBrownian motionConditional powerMarkov processSample size re-estimationSequential designTransition function ACKNOWLEDGMENT The authors had helpful discussions with Tommy Fu. Notes Spending rule = O′Brien–Fleming, P 1 = 0.1, P 2 = 0.065, N 1 = N 2 = 1044, Power = 80%, Total α = 0.025 one-sided. ACR=Adjusting the Final Critical Region method; CHW=Cui, Hung, and Wang method; MS = Müller and Schäfer method.