Flexible two-stage design with sample size reassessment for survival trials

Flexible trials with adaptive design modification at interim analyses have been recently proposed as an answer to cope with some limitations of traditional designs for phase III trials. Actually, the sample size and duration of fixed design trials strongly depend on the determination, prior to the study, of key parameters such as the expected treatment effect and the event rates. A misspecification of these parameters may result in an underpowered or overpowered trial. In the flexible framework, the remainder of a design can be modified at an interim analysis, while preserving the initially specified global error rates. In this work, we present a flexible design with sample size re-evaluation for survival trials and study its properties in practical settings. The results show that, if parameters are initially misspecified, the proposed method allows an improved power control with a reasonable increase in sample size, if any. Practical guidelines concerning the choice of the trial parameters are also given. (C) 2007 John Wiley & Sons, Ltd.