A Re-examination of Japanese Sample Size Calculation for Multi-regional Clinical Trial Evaluating Survival Endpoint

In planning a multi-regional clinical trial including Japan, the sample size for Japanese patients is often considered based on the probability of obtaining a consistent result between Japanese subpopulation and the overall study population, as recommended in the Japanese guideline “Basic Principles on Global Clinical Trials.” We review the commonly used existing method for Japanese sample size calculation based on obtaining a consistent result for survival endpoint. Through simulations, we note that Japanese sample size based on the existing method tended to have less actual power than the nominal power for consistency, especially when there is a large treatment effect. We propose alternative methods based on the delta method and numerical integrations. Our proposed methods give similar Japanese sample sizes, and our simulation studies show that our proposed methods provide the actual power close to the nominal power for consistency.