On the efficiency of adaptive designs for flexible interim decisions in clinical trials

It is shown that the optimal group sequential designs considered in Tsiatis and Mehta [2003. On the inefficiency of the adaptive design for monitoring clinical trials. Biometrika 90, 367-378] are special cases of the more general flexible designs which allow for a valid inference after adapting a predetermined way to spend the rejection and acceptance probabilities. An unforeseen safety issue in a clinical trial, for example, could make a change of the preplanned number of interim analyses and their sample sizes appropriate. We derive flexible designs which have equivalent rejection and acceptance regions if no adaptation is performed, but at the same time allow for an adaptation of the spending functions, and have a conditional optimality property. (c) 2005 Elsevier B.V. All rights reserved.