A Statistical Issue About a Phase III Multi-regional Trial for the Survival Data under Accelerated Failure Time Model with Unrecognized Heterogeneity

For the time-to-event outcome, current methods for sample size determination are based on the proportional hazard model. However, if the proportionality assumption fails to capture the relationship between the hazard time and covariates, the proportional hazard model is not suitable to analyze survival data. The accelerated failure time model is an alternative method to deal with survival data. In this article, we address the issue that the relationship between the hazard time and the treatment effect is satisfied with the accelerated failure time model to design a multi-regional trial for a phase III clinical 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 sample size to each region.