{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T04:05:42Z","timestamp":1794283542381,"version":"4.9.0"},"reference-count":37,"publisher":"BMJ","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013362","name":"Swiss Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"accepted":{"date-parts":[[2023,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyze the therapeutic value of supplemental indications compared with first indications for drugs approved in the US and Europe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>New and supplemental indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) between 2011 and 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Proportion of first and supplemental indications rated as having high therapeutic value using ratings from the French and German national, independent health authorities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort study included 124 first and 335 supplemental indications approved by the FDA and 88 first and 215 supplemental indications approved by the EMA between 2011 and 2020; the largest subset was for cancer disorders. Therapeutic ratings were available for 107 (86%) first and 179 (53%) supplemental indications in the US and for 87 (99%) first and 184 (86%) supplemental indications in Europe. Among FDA approved indications with available ratings, 41% (44\/107) had high therapeutic value ratings for first indications compared with 34% (61\/179) for supplemental indications. In Europe, 47% (41\/87) of first and 36% (67\/184) of supplemental indications had high therapeutic value ratings. Among FDA approvals, when the sample was restricted to the first three approved indications, second indication approvals were 36% less likely to have a high value rating (relative ratio 0.64, 95% confidence interval 0.43 to 0.96) and third indication approvals were 45% less likely (0.55, 0.29 to 1.01) compared with the first indication approval. Similar findings were observed for Europe and when weighting by the inverse number of indications for each drug.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The proportion of supplemental indications rated as having high therapeutic value was substantially lower than for first indications. When first or supplemental indications do not offer added therapeutic value over other available treatments, that information should be clearly communicated to patients and physicians and reflected in the price of the drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmj-2022-074166","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T20:00:12Z","timestamp":1688587212000},"page":"e074166","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Therapeutic value of first versus supplemental indications of drugs in US and Europe (2011-20): retrospective cohort study"],"prefix":"10.1136","volume":"382","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-7384","authenticated-orcid":false,"given":"Kerstin N","family":"Vokinger","sequence":"first","affiliation":[{"name":"Institute of Law, University of Zurich, Zurich, Switzerland"},{"name":"Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Innovation and Regulation Initiative, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille E G","family":"Glaus","sequence":"additional","affiliation":[{"name":"Institute of Law, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S","family":"Kesselheim","sequence":"additional","affiliation":[{"name":"Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquel","family":"Serra-Burriel","sequence":"additional","affiliation":[{"name":"Institute of Law, University of Zurich, Zurich, Switzerland"},{"name":"Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S","family":"Ross","sequence":"additional","affiliation":[{"name":"National Clinical Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA"},{"name":"Section for General Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA"},{"name":"Center for Outcomes Research and Evaluation, Yale-New Haven Health System, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Hwang","sequence":"additional","affiliation":[{"name":"Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Innovation and Regulation Initiative, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Division of Urological Surgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"2025110102163733000_382.jul05_10.e074166.1","unstructured":"US Food and Drug Administration. 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