An Analysis of Japanese Patients Enrolled in Multiregional Clinical Trials in Oncology

Abstract

The Japanese regulatory agency, the Ministry of Health, Labour and Welfare, requires sponsors to enroll a specific number or proportion of Japanese patients in multiregional clinical trials (MRCTs) in order to allow for the appropriate statistical evaluation of the efficacy and safety of an investigational drug in the Japanese population. This means the actual proportion of Japanese patients to the total sample size would need to be determined by taking into account the proportion of patients in other regions as well as the appropriate statistical considerations. Determining the proportion of Japanese patients that satisfies the regulatory agency's statistical requirement, along with taking into account the practical limitations of patient enrollment, would be difficult for sponsors. We believe that recent studies about the proportion of Japanese patients enrolled in MRCTs provides sponsors with useful information about partitioning sample size into individual regions for MRCTs in oncology. In this study, we investigated the proportion of Japanese patients in MRCTs and further compared the efficacy results from the overall population to that of the Japanese population. The proportion of Japanese patients averaged approximately 10.9%, but the proportion varied depending on the drug type. The results of the primary endpoints in Japanese patients were similar to those of the overall population, regardless of the proportion of Japanese patients.

Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma

“…3 The approval of oncological drugs and indications based solely on a single-arm trial has also increased in Japan. 4 Such trials often use the response rate as the primary efficacy endpoint and a fixed sample size, determined based on the well-known frequentist manner. Specifically, the sample size of single-arm trials with a binary response rate is determined based on the frequentist method that specifies a and b error rates.…”