Mid-trial design reviews for sequential clinical trials

Abstract

When sequential clinical trials are conducted by plotting a statistic measuring treatment di erence against another measuring information, power is guaranteed regardless of nuisance parameters. However, values need to be assigned to nuisance parameters in order to gain an impression of the sample size distribution. Each interim analysis provides an opportunity to re-evaluate the relationship between sample size and information. In this paper we discuss such mid-trial design reviews. In the special cases of trials with a relatively short recruitment phase followed by a longer period of follow-up, and of normally distributed responses, mid- trial design reviews are particularly important. Examples are given of the various situations considered, and extensive simulations are reported demonstrating the validity of the review procedure in the case of normally distributed responses. Copyright ? 2001 John Wiley & Sons, Ltd.