Use of an adaptive approach to design and evaluation on multi-regional clinical trials with multiple endpoints

Abstract

For accelerating the development of new drugs and shortening their approval time, multi-regional clinical trials (MRCTs) have been considered widely in recent years. In this approach we focus on the scenario that the primary endpoints between two regions are correlated but different. For each region, the authority concentrates only on its own endpoint; that is, the tests are separately. Moreover, two-stage adaptive designs based on interval estimators are used for early stopping due to futility in the interim analysis. The proposed design then allows that, when the region with larger sample size fails to continue, a prespecified sample size adjustment is applied to the remaining. This leads to a reduction of sample size for the situation. Simulation studies show the proposed design is able to provide sufficient power. Keywords: multi-regional clinical trial; two-stage adaptive design; sample size determination