Futility stopping in clinical trials, optimality and practical considerations.

Stopping for futility is a useful tool in a clinical trial. It is widely used in single-arm trials in oncology and in many two-arm trials. We review three stopping rules for futility. We give recommendations for the optimal timing of futility looks in two-stage trials in terms of the information fraction and the probability of stopping under the alternative hypothesis. We discuss futility stopping in trials with substantial uncertainty about the variability of the outcome and in crossover trials.