{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:26:22Z","timestamp":1792765582631,"version":"4.5.0"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"\n Importance<\/jats:title>\n The 2007 US Food and Drug Administration (FDA) Amendments Act (FDAAA) expanded its safety-related regulatory authorities, including enhanced postmarketing safety surveillance and new clinical study requirements. However, whether FDAAA has been associated with differences in the frequency and timing of postmarket safety-related actions remains poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess whether FDAAA was associated with differences in time to first FDA postmarket drug safety\u2212related action, and to assess whether therapeutic and regulatory characteristics were associated with differences in time to these actions post-FDAAA implementation.<\/jats:p>\n <\/jats:sec>\n \n Design and Setting<\/jats:title>\n This was a cross-sectional study of all novel therapeutics approved by FDA between January 1, 2001, and December 31, 2019, and followed up through December 31, 2024. Approvals were categorized as pre- or post-FDAAA (before or after March 25, 2008). Post-FDAAA therapeutic and regulatory characteristics included drug class, therapeutic area, orphan status, special regulatory pathway, and presence of a boxed warning or FDAAA-mandated postmarket study requirement at approval.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Time to first FDA postmarket drug safety\u2212related action, a composite of withdrawals due to safety concerns, incremental boxed warnings, and safety-related communications.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 560 novel therapeutics approved, FDA took postmarket safety-related actions for 130 (23.2%) during a median (IQR) follow-up of 12.1 (7.8-18.2) years. These comprised actions within 5 years of approval for 34 of 164 therapeutics (20.7%) approved pre-FDAAA, and 57 of 396 (14.4%) approved post-FDAAA (rate ratio,\u20090.69; 95% CI, 0.47-1.02;\n P<\/jats:italic>\n \u2009=\u2009.06). Compared to pre-FDAAA approvals, after accounting for therapeutic and regulatory characteristics, there was no statistically significant difference in time to first postmarket safety-related action for post-FDAAA approvals (time ratio, 0.40; 95% CI, 0.15-1.07;\n P<\/jats:italic>\n \u2009=\u2009.07). However, among therapeutics with postmarket safety-related actions within 5 years of approval, median time to first action was shorter post-FDAAA (median [IQR], 3.1 (2.0-4.2) years for pre-FDAAA vs 1.8 [1.3-2.5] years post-FDAAA;\n P<\/jats:italic>\n \u2009=\u2009.004). Among 260 novel therapeutics approved post-FDAAA, after the October 2013 enactment of breakthrough therapy designation, the following therapeutic and regulatory characteristics were associated with time to first postmarket safety-related action: small molecule type (time ratio, 0.24; 95% CI, 0.07-0.81;\n P<\/jats:italic>\n \u2009=\u2009.02), orphan designation (time ratio,\u20098.29; 95% CI, 2.43-28.27;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), fast track (time ratio, 0.22; 95% CI, 0.08-0.64;\n P<\/jats:italic>\n \u2009=\u2009.005), breakthrough therapy designation (time ratio,\u20090.10; 95% CI, 0.03-0.32;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), prolonged regulatory review time (&amp;gt;400 days; time ratio,\u20090.16; 95% CI, 0.03-0.73;\n P<\/jats:italic>\n \u2009=\u2009.02), and FDAAA-mandated postmarket study requirements at approval (time ratio,\u20090.35; 95% CI, 0.15-0.80;\n P<\/jats:italic>\n \u2009=\u2009.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cross-sectional analysis found that the enhanced safety-related regulatory authorities of FDAAA were not associated with differences in time to first postmarket safety-related action. However, among therapeutics with postmarket safety-related actions within 5 years of approval, median time to first action was shorter post-FDAAA implementation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamainternmed.2025.6566","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:01:12Z","timestamp":1765209672000},"page":"233","source":"Crossref","is-referenced-by-count":6,"title":["Postmarket Drug Safety\u2212Related Actions Before and After the US Food and Drug Administration Amendments Act"],"prefix":"10.1001","volume":"186","author":[{"given":"Harry","family":"Doernberg","sequence":"first","affiliation":[{"name":"Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Wallach","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, 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