Department of Biostatistics and Bioinformatics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Center for Data Science, Yokohama City University, Yokohama, Japan.
Ther Innov Regul Sci. 2020 May;54(3):528-533. doi: 10.1007/s43441-019-00084-4. Epub 2020 Jan 6.
Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue.
The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017.
Thirty-five companies based in Japan and 12 companies based in other countries, 47 companies in total, responded to the survey. The terms co-primary endpoints, secondary endpoint, and composite endpoint were used in a variety of ways. An endpoint for a clinically most important event that is expected to occur rarely differed between regions. Although the Pharmaceuticals and Medical Devices Agency did not demand multiplicity adjustment, it was considered in clinical trials with multiple endpoints for approval in Japan.
The use of terminology differed from the definition in the Food and Drug Administration guidance and the European Medicines Agency guideline. There remain challenges on a clinically most important event that is expected to occur rarely and multiplicity adjustment in clinical trials with multiple endpoints.
本次调查了涉及多个终点的临床试验中的两个问题：（1）多个终点的术语、罕见事件与终点的关系以及不同地区之间多重性调整的差异；（2）目前多重性调整和样本量计算的实践情况。本文总结了第一个问题的调查结果。
本次调查于 2017 年 10 月至 11 月在日本制药商协会的 63 名成员中进行。
共有 35 家日本国内公司和 12 家国外公司，总计 47 家公司对调查做出了回应。共同主要终点、次要终点和复合终点等术语的使用方式多种多样。预计很少发生的临床最重要事件的终点在不同地区有所不同。虽然药品和医疗器械管理局没有要求进行多重性调整，但在日本，对于涉及多个终点的临床试验，为了获得批准，会考虑进行多重性调整。
术语的使用与美国食品和药物管理局指南和欧洲药品管理局指南的定义不同。在涉及罕见事件且需要进行多重性调整的临床试验中，仍存在挑战。
