Speaker
Description
When estimating the treatment effect after a group sequential test or a more complex adaptive design, the maximum likelihood estimate is liable to be biased. The ICH E20: Guideline on Adaptive Designs for Clinical Trials has “reliability of estimation” as a key topic. Methods have been developed to reduce the bias in estimators after group sequential and adaptive designs – or even eliminate bias completely. Proposals include Whitehead’s bias-adjusted estimator and Rao-Blackwell unbiased estimators. The resulting estimators have been compared in terms of bias, variance and mean square error. However, these results do not tell the whole story. We shall look more closely at some of these estimators, make recommendations, and note areas where future research is required.