Premarket and postmarket real-world evidence studies supporting U.S. Food and Drug Administration regulatory decision-making, 2016-2024.

Abstract

Background/aims: There is growing interest in leveraging real-world data, such as electronic health records, administrative claims data, and patient registries, to generate real-world evidence studies that support the U.S. Food and Drug Administration's premarket and postmarket regulatory determinations of effectiveness and/or safety for novel therapeutics. We examined the frequency and characteristics of real-world evidence studies used by the U.S. Food and Drug Administration to support premarket determinations of effectiveness and/or safety, as well as those required or requested by the U.S. Food and Drug Administration to be conducted postmarket after approval.

Methods: We identified all novel therapeutics approved by the U.S. Food and Drug Administration between 2016 and 2024, using action packages from the Drugs@FDA database. Product labels, approval letters, and review documents were used to identify real-world evidence studies supporting premarket determinations of effectiveness and/or safety, as well as all postmarketing requirements or commitments outlined at the time of approval. Outcomes included the number of novel therapeutics approved with premarket and/or postmarket real-world evidence studies and characteristics of these studies, including study design, data source, and primary objectives.

Results: From 2016 to 2024, the U.S. Food and Drug Administration approved 400 novel therapeutics for 543 indications, of which 43 (10.8%) had at least one real-world evidence study that supported premarket determinations of effectiveness and/or safety (64 unique studies), and 138 (34.5%) had at least one real-world evidence study required or requested by the U.S. Food and Drug Administration to be conducted postmarket after approval (208 unique studies). Among the 64 unique premarket real-world evidence studies, the most common study designs were non-interventional (observational) studies (35, 54.7%) and externally controlled trials (17, 26.6%); 38 (59.4%) studies utilized electronic health or medical records, and 47 (73.4%) provided evidence on effectiveness. Among the 208 unique postmarket real-world evidence studies, the most common study design was non-interventional (observational) studies (159, 76.4%); 61 (29.3%) studies identified registries as the proposed data source, and 197 (94.7%) were designed to provide evidence on safety alone. The proportion of therapeutics approved with at least one postmarket real-world evidence study increased over time from 2 of 20 (10.0%) in 2016 to 23 of 47 (48.9%) in 2024; however, only 7 (3.4%) of these studies were classified by the U.S. Food and Drug Administration as fulfilled or submitted as of May 2025.

Conclusions: Real-world evidence studies are infrequently used to support the U.S. Food and Drug Administration's premarket determinations of effectiveness and/or safety but have been increasingly required or requested by the U.S. Food and Drug Administration to be conducted postmarket after approval; however delays in completing postmarket real-world evidence studies may limit their regulatory impact.