Surrogate Endpoints in Pivotal Clinical Trials for Drug Approval in Japan Compared to the United States.

Regulatory guidance documents exist on surrogate endpoints in the United States. In Japan, there are no established rules or guidance regarding the use of surrogate endpoints, and various aspects remain unclear. The aim of this study was to investigate the use of surrogate endpoints in Japan for drugs approved in Japan from 1999 to 2022, referring to the list established by the Food and Drug Administration. Precisely 2307 drugs were approved in Japan during the 24-year survey period. Of these, 1012 drugs (43.9%) were indicated for diseases for which surrogate endpoints were specified in the Surrogate Endpoint Table established by the Food and Drug Administration. After examining the endpoints used in clinical trials for 1012 drugs, 947 (93.6%) were approved based on the same surrogate endpoint as the Food and Drug Administration, whereas 65 (6.4%) were approved based on a different surrogate endpoint. In areas such as diabetes, there was a tendency to use surrogate endpoints established by the Food and Drug Administration, whereas for pharmaceuticals targeting pathogenic organisms, Japan's surrogate endpoints were typically used. Our findings demonstrate that several pharmaceuticals in Japan use surrogate endpoints similar to those of the Food and Drug Administration. These findings are expected to aid in the formulation of guidelines for the use of surrogate endpoints in clinical trials for future drug approvals in Japan.