Sample Size Determination and Rational Partition for A Multi- Regional Trial for Survival (Time-To-Event) Data with Unrecognized Heterogeneity that Interacts with Treatment

Abstract

To shorten the drug lag or the time lag for approval, simultaneous drug development, submission, and approval in the world may be desirable. Recently, multi-regional trials have attracted much attention from sponsors as well as regulatory authorities. Current methods for sample determination are based on the assumption that true treatment effect is uniform across regions. However, unrecognized heterogeneity among patients as ethnic or genetic factor will effect patients’ survival. In this article, we address the issue that the treatment effects with unrecognized heterogeneity that interacts with treatment are among regions to design a multi-regional trial. The log-rank test is employed to deal with the heterogeneous effect size among regions. The test statistic for the overall treatment effect is used to determine the total sample size for a multi-regional trial and the consistent trend is used to rationalize partition for sample size to each region.

Keywords:

• Heterogeneity
• Multi-regional study
• Regional sample size

Mathematics Subject Classification:

• Primary 62K99
• Secondary 62-07