Japan’s PMDA publishes perspective on RWD/RWE utilization for postmarketing drug safety assessment

In a new Commentary published in Pharmacoepidemiology and Drug Safety, authors from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) reflect on the experience gained in recent years utilizing real-world data/evidence for regulatory decision-making on drug safety.

Real-world data (RWD) and real-world evidence (RWE) are becoming increasingly valuable for global regulatory agencies in postmarketing drug safety assessment, offering insights to understand the performance and safety of new treatments under real-world conditions. As these agencies seek to refine the use of RWD and RWE in their decision-making, many are sharing their experience gained to enhance the understanding and improve regulatory practices. In a new article title ‘PMDA Perspective on RWD/RWE Utilization for Regulatory Purposes Including Assessment on the Impacts of Regulatory Actions and Safety Risk of a Drug at Postmarketing Stage,’ published in Pharmacoepidemiology and Drug Safety, the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan offers its own perspective and insights on this evolving field.

In Japan, PMDA uses RWD from two types of RWD database, chosen depending on the purpose of the study and following feasibility assessment. Whilst smaller, collecting data from around 8 million Japanese patients, the Medical Information Database Network (MID-NET) includes detailed laboratory test results in addition to electronic medical record, claims, and diagnostic procedure combination data. In contrast, the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is the largest health-related database, with coverage of electronic health insurance claims and specific health check-up data from almost 125 million people in Japan. Detailed lab results, which offer critical insights into the overall understanding of a drug’s safety profile in real-world use, are lacking.

The authors share several case studies demonstrating how the PMDA has effectively leveraged RWD in pharmacoepidemiological research for regulatory decision-making. During the COVID-19 pandemic, RWD played a crucial role in monitoring the safety of newly approved drugs under emergency conditions. MID-NET data, for instance, has been used to track the use and safety of anti-COVID-19 drugs.

The PMDA also considers using RWD to evaluate the impacts of regulatory action in clinical practice by assessing changes before and after safety-related regulatory action as crucial for promoting more efficient and timely regulatory decisions. For example, the impact of regulatory changes on metformin use was examined using MID-NET data. This study showed no increase in lactic acidosis cases following a change in metformin’s label, indicating the revised guidelines were effective.

Despite its usefulness, the authors caution that several challenges in using RWD persist, such as covering a wide range of medicines, selecting relevant outcome measures, and addressing confounding factors. They also recognize the need for better integration of RWD sources to allow longer follow-up and more comprehensive data analysis; for instance, by linking the NDB with the nursing care database.

They also emphasize the need for international cooperation and harmonization, noting worldwide collaboration as “indispensable for increasing trust in RWD utilization and facilitating the regulatory acceptance of RWE on a global basis.”