Modification of Sample Size in Group Sequential Clinical Trials

TLDR

In group sequential clinical trials, sample size reestimation can be complicated when the change is influenced by the observed sample path. The authors develop a new group sequential test procedure by modifying the weights used in the traditional repeated significance two‑sample mean test. The procedure modifies these weights and its generalization is discussed. Simulations show that increasing sample size based on interim estimates inflates type I error, yet the new test preserves the target error rate and yields substantial power gains with larger sample sizes. Summary.

Abstract

Summary. In group sequential clinical trials, sample size reestimation can be a complicated issue when it allows for change of sample size to be influenced by an observed sample path. Our simulation studies show that increasing sample size based on an interim estimate of the treatment difference can substantially inflate the probability of type I error in most practical situations. A new group sequential test procedure is developed by modifying the weights used in the traditional repeated significance two‐sample mean test. The new test has the type I error probability preserved at the target level and can provide a substantial gain in power with the increase of sample size. Generalization of the new procedure is discussed.