Ten Years after the Implementation of the Risk Management Plan in Japan: The Impact of Risk Management Plan on Package Insert Revision

It has been 10 years since the Japanese Risk Management Plan (RMP) was implemented in 2013. However, the impact of the Japanese RMP (J-RMP) system on drug safety measures is unclear. Herein, we investigated the impact of the J-RMP system on package insert (PI) revision, focusing on the rapidity of identification of clinically significant adverse reactions (ARs) as an effect indicator of the J-RMP system in drug safety measures. We created an original database from public information of the Pharmaceuticals and Medical Devices Agency and investigated the speed of adding clinically significant ARs to PIs. Comparing the time lapse from drug approvals to PI revisions after the implementation of the J-RMP system to that before implementation, the median value was 32 months vs. 32 months (149 vs. 318 cases), and no significant difference was observed. We also compared the time lapse from drug approvals to PI revisions when additional ARs had been included as safety specifications at the time of drug approvals and when they had not been included, and the median value was 35 months vs. 32 months (14 cases vs. 126 cases, p = 0.7820), and no statistically significant difference was observed. Therefore, it was suggested that the J-RMP system did not affect PI revision and its speed. It should be considered how to effectively utilize J-RMP for safety measures in Japan.