Accurate p-values for adaptive designs with binary endpoints

Abstract

Adaptive designs encompass all trials allowing various types of design modifications over the course of the trial. A key requirement for confirmatory adaptive designs to be accepted by regulators is the strong control of the family-wise error rate. This can be achieved by combining the p-values for each arm and stage to account for adaptations (including but not limited to treatment selection), sample size adaptation and multiple stages. While the theory for this is novel and well-established, in practice, these methods can perform poorly, especially for unbalanced designs and for small to moderate sample sizes. The problem is that standard stagewise tests have inflated type I error rate, es..