AUTHOR=Kameyama Natsuko , Hosaka Aoi , Maeda Hideki TITLE=Has risk management plan system influenced the speed of package insert revisions in Japan? JOURNAL=Frontiers in Medicine VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1465313 DOI=10.3389/fmed.2024.1465313 ISSN=2296-858X ABSTRACT=Introduction

The system of Risk Management Plan in Japan (J-RMP) is a relatively new system, implemented in 2013; thus, its effect on safety measures is still unclear. One of the purposes of J-RMP is to enhance the postmarketing safety measures to be ensured by publishing J-RMP and sharing information on risk management among healthcare professionals. We hypothesized that this might enable information about postmarketing adverse events to be accumulated rapidly, potentially accelerating the identification of adverse reactions (ARs). Herein, we focused on the speed of adding clinically significant ARs (CSARs) to package inserts (PIs) as an indicator of the rapidity of AR identification, investigated the impact of the J-RMP system on PI revisions.

Methods

We investigated the “Notice of Revision of Precautions” on the website of Pharmaceuticals and Medical Devices Agency (PMDA), targeting PI revisions with the addition of CSARs from April 2003 to March 2023, which corresponds to 10 years before and after J-RMP implementation in April 2013. We created an original database from public information of PMDA and investigated the speed of adding CSARs to PIs.

Results

Comparing the time lapse from drug approvals to PI revisions after J-RMP implementation (149 cases) to that before implementation (318 cases), the median value was 32 months for both. Regarding the time lapse when the additional CSARs were listed and unlisted as safety concerns at the time of approvals, it was 35 months vs. 32 months (14 cases vs. 126 cases, p = 0.7820), with no statistically significant difference. Conversely, there were significant differences within each AR and each drug therapeutic category.

Discussion and conclusions

This study revealed that the rapidity of risk identification as ARs was not affected by J-RMP, and it may be affected by the characteristics of each AR and each drug therapeutic category. It is expected that other J-RMP benefits, such as risk prevention before the occurrence, will be utilized to further develop strategies for the effective utilization of the J-RMP for safety measures in Japan.