Evaluation of Consistency Requirements in Multi-Regional Clinical Trials with Different Endpoints

Abstract

In recent years, there is an increasing trend to conduct multi-regional clinical trials (MRCT) for drug development in Pharmaceuticals industry. A carefully designed MRCT could be used in supporting the new drug’s approval in different regions simultaneously. The primary objective of an MRCT is to investigate the drug’s overall efficacy across regions while also assessing the drug’s performance in some specific regions. In order to claim the study drug’s efficacy and get drug approval in some specific region(s), the local regulatory authority may require the sponsors to provide evidence of consistency in the treatment effect between the overall patient population and the local region. Usually, the regional specific consistency requirement needs to be pre-specified before the study conduct and the consistency in treatment effect between the region(s) of interest and overall population will be evaluated at the final analysis. In this paper, we evaluate the consistency requirements in multi-regional clinical trials for different endpoints, i.e., continuous, binary and survival endpoints. We also compare the different consistency requirements of the same endpoint/measurement if multiple consistency requirements are enforced and our recommendations for each endpoint/measurement will be made based on the comprehensive consideration.