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

BACKGROUND/

aimsThere 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.

methodsWe 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.

resultsFrom 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.

conclusionsReal-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.