Abstract
The Japanese regulatory guideline “Basic Principles in Global Clinical Trials,” issued in September 2007, serves to encourage the participation of Japan in international phase 3 clinical trials and, as such, is very much welcome, helping to avoid repeat, stand-alone trials in Japanese patients that are often underpowered. However, the guideline raises a concern regarding the consistency of outcomes in the subset of Japanese patients and the total trial population and offers two alternative criteria to determine the fraction of Japanese patients that should be recruited. The first criterion requires that sufficient Japanese patients are entered such that, if the treatment effects in the Japanese and overall populations are truly the same, there is an 80% chance that the effect in Japanese patients will be shown to be at least half of the effect in the total trial population. The second criterion requires that sufficient patients be entered per geographical region included in the trial such that, if there is a true effect in the overall population, the probability that each region (including Japan) will also show a positive effect is 80%. The purpose of this article is to explore the implications of these criteria in terms of overall power and the fraction of the Japanese patients that need to be recruited to satisfy them and to consider some potential alternative criteria that might offer advantages over those stated in the guideline.