4th Summer Institute in Statistics for Clinical Research

Module 17: Adaptive Sample Size Re-estimation: Design and Inference

Session 5, Friday 8:30 AM - 5:00 PM: Fri Jul 28

Adaptive clinical trial designs have been proposed as a promising new approach that may help improve the drug discovery process. Recent statistical papers have introduced a variety of methods to allow unplanned interim modifications to the study design while preserving the type I error rate of the clinical trial. In particular, there is a large body of literature exploring designs with unplanned modifications to the sample size based on interim estimates of the treatment effect falling into a promising zone.

In this module we first present the impact such designs can have on the power of randomized clinical trials. We provide guidance on the adaptive rules that lead to the greatest benefit to study precision, and we present and compare methods for full statistical inference following the use of such designs.

We then provide some additional emphasis on the special issues that arise in the setting of censored time to event endpoints. We discuss how the changing censoring distribution during a sequential trial affects the analysis of distributions with crossing hazards and crossing survival curves, as well as issues that arise owing to the ancillary information about eventual event times that might be available on subjects who are censored at an adaptive analysis.