{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:18:33Z","timestamp":1787768313454,"version":"build-2784847793"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The 21st Century Cures Act (2017) was enacted during a period of evolving FDA flexibility in evidentiary standards for drug approval. To examine trends before and after implementation, we independently reviewed all novel drugs approved between 2016 and 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We constructed a database of all novel FDA approvals from January 1, 2016, through December 31, 2024. Each study linked to an approved drug (N\u2009=\u20096,763) was cataloged by study number, sponsorship, and timing of results reporting relative to completion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Since 2016, the number of studies supporting approval has steadily declined. Beginning in 2017, the modal number of studies per approval fell to one. Industry sponsorship increased while NIH-supported studies decreased. Average time to public posting of results exceeded the one-year statutory limit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the post-2016 period, FDA approvals were supported by fewer studies and by a greater proportion of industry-sponsored studies. Although this may accelerate access to new therapies, it raises concerns about the strength of evidence for safety and effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0342878","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:25:21Z","timestamp":1787765121000},"page":"e0342878","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in evidence used for FDA Novel Drug Approvals: 2016-2024"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2427-6445","authenticated-orcid":true,"given":"Aditya","family":"Narayan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica L.","family":"Irvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-4695","authenticated-orcid":true,"given":"Amanda J.","family":"Koong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5742-4667","authenticated-orcid":true,"given":"Sujin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"5","key":"pone.0342878.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0177546","article-title":"Awareness and trust of the FDA and CDC: Results from a national sample of US adults and adolescents","volume":"12","author":"SD Kowitt","year":"2017","journal-title":"PLoS One"},{"issue":"6","key":"pone.0342878.ref002","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1215\/03616878-10041093","article-title":"Trends in the Quality of Evidence Supporting FDA Drug Approvals: Results from a Literature Review","volume":"47","author":"BL Brown","year":"2022","journal-title":"J Health Polit Policy Law"},{"key":"pone.0342878.ref003","first-page":"315","volume-title":"The 21st Century Cures Act: pharmacoeconomic boon or bane?","author":"RL Mendoza","year":"2017"},{"issue":"6","key":"pone.0342878.ref004","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/cpt.208","article-title":"The 21st century cures act: Opportunities and challenges","volume":"98","author":"A Sarpatwari","year":"2015","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"pone.0342878.ref005","first-page":"677","article-title":"The Potential Effect of the 21st Century Cures Act on Drug Development","volume":"24","author":"JA Goble","year":"2018","journal-title":"J Manag Care Spec Pharm"},{"issue":"6","key":"pone.0342878.ref006","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1001\/jama.2016.20640","article-title":"New \u201c21st Century Cures\u201d Legislation: Speed and Ease vs Science","volume":"317","author":"AS Kesselheim","year":"2017","journal-title":"JAMA"},{"issue":"2","key":"pone.0342878.ref007","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMp1615745","article-title":"The 21st Century Cures Act - A View from the NIH","volume":"376","author":"KL Hudson","year":"2017","journal-title":"N Engl J Med"},{"key":"pone.0342878.ref008","volume-title":"How FDA Used Its Accelerated Approval Pathway Raised Concerns in 3 of 24 Drugs Reviewed","author":"GOV O"},{"issue":"15","key":"pone.0342878.ref009","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJMhpr1713338","article-title":"The FDA Breakthrough-Drug Designation - Four Years of Experience","volume":"378","author":"JJ Darrow","year":"2018","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0342878.ref010","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1001\/jama.2019.20288","article-title":"FDA Approval and Regulation of Pharmaceuticals, 1983-2018","volume":"323","author":"JJ Darrow","year":"2020","journal-title":"JAMA"},{"issue":"8","key":"pone.0342878.ref011","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.27650","article-title":"Review of Evidence Supporting 2022 US Food and Drug Administration Drug Approvals","volume":"6","author":"RM Kaplan","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"2","key":"pone.0342878.ref012","article-title":"Food and Drug Administration novel drug decisions in 2017: transparency and disclosure prior to and 5 years following approval","volume":"1","author":"RM Kaplan","year":"2023","journal-title":"Health Aff Sch"},{"key":"pone.0342878.ref013","doi-asserted-by":"crossref","DOI":"10.1001\/jamahealthforum.2021.1306","volume-title":"In a first, FDA warns company to remedy failure to post clinical trial results","author":"J Stephenson","year":"2021"},{"key":"pone.0342878.ref014","first-page":"10","article-title":"FDA and NIH let clinical trial sponsors keep results secret and break the law.","author":"C Piller","year":"2020","journal-title":"Science"},{"issue":"10221","key":"pone.0342878.ref015","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0140-6736(19)33220-9","article-title":"Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study","volume":"395","author":"NJ DeVito","year":"2020","journal-title":"Lancet"},{"key":"pone.0342878.ref016","author":"Reps","year":"2024"},{"issue":"16","key":"pone.0342878.ref017","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1001\/jama.2023.2351","article-title":"Comparison of Availability of Trial Results in ClinicalTrials.gov and PubMed by Data Source and Funder Type","volume":"329","author":"JT Nelson","year":"2023","journal-title":"JAMA"},{"issue":"18","key":"pone.0342878.ref018","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1056\/NEJMp2200203","article-title":"Designing Cures 2.0 - 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