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 design
• Brownian motion
• Conditional power
• Markov process
• Sample size re-estimation
• Sequential design
• Transition 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.