{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:38:09Z","timestamp":1788489489828,"version":"build-2803163510"},"reference-count":40,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100014848","name":"Arnold Ventures","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Aims:<\/jats:title>\n                    <jats:p>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\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Real-world evidence studies are infrequently used to support the U.S. Food and Drug Administration\u2019s 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745251415190","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:33:11Z","timestamp":1770294791000},"page":"363-374","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Premarket and postmarket real-world evidence studies supporting U.S. Food and Drug Administration regulatory decision-making, 2016\u20132024"],"prefix":"10.1177","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1398-9698","authenticated-orcid":false,"given":"Louis Y","family":"Li","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Section of General Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9218-3320","authenticated-orcid":false,"given":"Joseph S","family":"Ross","sequence":"additional","affiliation":[{"name":"Section of General Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale University School of Medicine, New Haven, CT, USA"},{"name":"Department of Health Policy and Management, Yale School of Public Health, and Center for Outcomes Research and Evaluation, Yale-New Haven Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-6905","authenticated-orcid":false,"given":"Joshua D","family":"Wallach","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA"},{"name":"Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"U.S. Food and Drug Administration. Providing clinical evidence of effectiveness for human drug and biological products https:\/\/www.fda.gov\/media\/71655\/download (1998 accessed 8 May 2025)."},{"key":"e_1_3_3_3_2","unstructured":"U.S. Food and Drug Administration. Demonstrating substantial evidence of effectiveness for human drug and biological products https:\/\/www.fda.gov\/media\/133660\/download (2019 accessed 8 May 2025)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.3284"},{"key":"e_1_3_3_5_2","unstructured":"U.S. Food and Drug Administration. Demonstrating substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence https:\/\/www.fda.gov\/media\/172166\/download (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_6_2","unstructured":"Food and Drug Administration Modernization Act of 1997 Pub L No. 105-115 111 Stat 2296 https:\/\/www.congress.gov\/bill\/105th-congress\/senate-bill\/830 (1997 accessed 8 May 2025)."},{"key":"e_1_3_3_7_2","article-title":"Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study","volume":"351","author":"Kesselheim AS","year":"2015","unstructured":"Kesselheim AS, Wang B, Franklin JM, et al. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study. BMJ 2015; 351: h4633.","journal-title":"BMJ"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/1740774518770648"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.282034"},{"key":"e_1_3_3_10_2","unstructured":"U.S. Food and Drug Administration. Expedited programs for serious conditions\u2014Drugs and biologics https:\/\/www.fda.gov\/media\/86377\/download (2014 accessed 8 May 2025)."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/2168479019873918"},{"key":"e_1_3_3_12_2","unstructured":"Califf R. Realizing the promise of real-world evidence https:\/\/www.fda.gov\/news-events\/fda-voices\/realizing-promise-real-world-evidence (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_13_2","unstructured":"U.S. Food and Drug Administration. Real-world evidence https:\/\/www.fda.gov\/science-research\/science-and-research-special-topics\/real-world-evidence (2024 accessed 8 May 2025)."},{"key":"e_1_3_3_14_2","unstructured":"U.S. Food and Drug Administration. Framework for FDA\u2019s real-world evidence program https:\/\/www.fda.gov\/media\/120060\/download (2018 accessed 8 May 2025)."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40290-022-00456-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.6230"},{"key":"e_1_3_3_17_2","unstructured":"U.S. Food and Drug Administration. FDA\u2019s sentinel initiative https:\/\/www.fda.gov\/safety\/fdas-sentinel-initiative (2022 accessed 8 May 2025)."},{"key":"e_1_3_3_18_2","unstructured":"U.S. Food and Drug Administration. Submitting documents using real-world data and real-world evidence to FDA for drug and biological products https:\/\/www.fda.gov\/media\/124795\/download (2022 accessed 8 May 2025)."},{"key":"e_1_3_3_19_2","unstructured":"U.S. Food and Drug Administration. Considerations for the design and conduct of externally controlled trials for drug and biological products https:\/\/www.fda.gov\/media\/164960\/download (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_20_2","unstructured":"U.S. Food and Drug Administration. Considerations for the use of real-world data and real-world evidence to support regulatory decision-making for drug and biological products: guidance for industry https:\/\/www.fda.gov\/media\/171667\/download (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_21_2","unstructured":"U.S. Food and Drug Administration. Data standards for drug and biological product submissions containing real-world data: guidance for industry https:\/\/www.fda.gov\/media\/153341\/download (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_22_2","unstructured":"U.S. Food and Drug Administration. Real-world data: assessing registries to support regulatory decision-making for drug and biological products https:\/\/www.fda.gov\/media\/154449\/download (2023 accessed 8 May 2025)."},{"key":"e_1_3_3_23_2","unstructured":"U.S. Food and Drug Administration. Real-world evidence: considerations regarding non-interventional studies for drug and biological products https:\/\/www.fda.gov\/media\/177128\/download (2024 accessed 8 May 2025)."},{"key":"e_1_3_3_24_2","unstructured":"U.S. Food and Drug Administration. Real-world data: assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products: guidance for industry https:\/\/www.fda.gov\/media\/152503\/download (2024 accessed 8 May 2025)."},{"key":"e_1_3_3_25_2","unstructured":"U.S. Food and Drug Administration. Integrating randomized controlled trials for drug and biological products into routine clinical practice: guidance for industry https:\/\/www.fda.gov\/media\/181871\/download (2024 accessed 8 May 2025)."},{"key":"e_1_3_3_26_2","unstructured":"U.S. Food and Drug Administration. Real-world evidence submissions to the center for biologics evaluation and research & the center for drug evaluation and research https:\/\/www.fda.gov\/science-research\/real-world-evidence\/real-world-evidence-submissions-center-biologics-evaluation-and-research-center-drug-evaluation-and (2024 accessed 8 July 2025)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_3_28_2","unstructured":"U.S. Food and Drug Administration. Drugs@FDA: FDA-approved drugs https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm (accessed 8 May 2025)."},{"key":"e_1_3_3_29_2","unstructured":"U.S. Food and Drug Administration. Search orphan drug designations and approvals https:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/ (accessed 8 May 2025)."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4932"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676-0"},{"key":"e_1_3_3_32_2","unstructured":"U.S. Food and Drug Administration. Postmarketing studies and clinical trials\u2014implementation of section 505(o)(3) of the Federal Food Drug and Cosmetic Act: guidance for industry https:\/\/www.fda.gov\/media\/131980\/download (2011 accessed 8 May 2025)."},{"key":"e_1_3_3_33_2","unstructured":"U.S. Food and Drug Administration. Postmarketing requirements and commitments: searchable database https:\/\/www.accessdata.fda.gov\/scripts\/cder\/pmc\/index.cfm (accessed 8 May 2025)."},{"key":"e_1_3_3_34_2","article-title":"Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis","volume":"361","author":"Wallach JD","year":"2018","unstructured":"Wallach JD, Egilman AC, Dhruva SS, et al. Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis. BMJ 2018; 361: k2031.","journal-title":"BMJ"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1344-3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2474"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13903"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/17407745211005044"},{"key":"e_1_3_3_39_2","unstructured":"U.S. Food and Drug Administration. FDA use of real-world evidence in regulatory decision making https:\/\/www.fda.gov\/science-research\/real-world-evidence\/fda-use-real-world-evidence-regulatory-decision-making (2025 accessed 7 October 2025)."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3688"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1177\/17407745251376620"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745251415190","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17407745251415190","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745251415190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T23:16:26Z","timestamp":1786230986000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17407745251415190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1177\/17407745251415190"],"URL":"https:\/\/doi.org\/10.1177\/17407745251415190","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}