Nonparametric Approach for Calculating Japanese Sample Size in Multi-regional Clinical Trials

Abstract

In planning a multi-regional clinical trial including Japan, the sample size for Japanese subjects is often considered based on the probability of obtaining consistent results between Japanese subpopulation and the overall study population, as recommended in the Japanese guideline ‘Basic Principles on Global Clinical Trials.’ Some methods have been proposed for calculating the sample size for Japanese subjects in multi-regional clinical trials based on the guideline, but no such methods have been proposed for trials where nonparametric methods are used for comparing two treatments. In this paper, we propose a method for calculating the Japanese sample size for a study where a nonparametric method is used. The proposed method uses the area under the ROC curve (AUROC) as an effect-size measure. This idea is justified by the fact that the AUROC is equivalent to Mann-Whitney’s U statistics. The AUROC is subdivided into parts according to Japanese/non-Japanese subpopulations and their variance and covariances are derived to construct a formula for calculating the probability of obtaining consistent results between the overall study population and Japanese subpopulation. Investigation by simulation suggests that the accuracy of the method is sufficiently high for practical use.