Japanese Patient Enrollment in Multi-regional Clinical Trials for New Drug Applications in Japan: Current Status and Related Factors.

Multi-regional clinical trials (MRCTs) have become the standard approach for new drug development in Japan. However, no standardized methodology exists to determine the appropriate number of Japanese patients for MRCTs, and factors associated with Japanese patient enrollment remain unclear. In this study, new drugs approved in Japan between January 2006 and December 2024 using clinical data packages including MRCTs were examined. For the targeted products, the proportions of Japanese patients (JP ratio) in the MRCTs were calculated, and their associations with potential explanatory variables were analyzed. Among the 1621 newly approved drugs, 453 met the inclusion criteria. The median JP ratio was 8.9%, which was substantially lower than the 15-20% recommended in the Japanese guidance documents. Higher JP ratios were observed in studies with smaller sample sizes and fewer participating countries. Multivariable logistic regression analysis revealed significant associations between the JP ratio and several factors, inclucing approval year, company type, orphan drug designation status, and number of participating countries. MRCTs are an established approach for new drug development in Japan, and marketing authorization has been obtained even when JP ratios are below guidance recommendations. Nevertheless, barriers to conducting MRCTs in Japan remain unresolved and may continue to reduce the motivation of emerging biopharmaceutical companies to pursue development in Japan. Japan has traditionally evaluated evidence from Japanese populations on a country-specific basis, in addition to evidence from the overall population. Greater clarity regarding the acceptance of more flexible development strategies would be beneficial in preventing future drug lag and drug loss.