{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:58:36Z","timestamp":1772161116248,"version":"3.50.1"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Recent court decisions have thrown into question the Food and Drug Administration\u2019s rules limiting manufacturer promotion of prescription drugs for unapproved uses. We assessed how providing pro forma disclosures or more descriptive evidence context about the data supporting an off-label claim affected physicians\u2019 beliefs about drug efficacy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              In online and mailed surveys, we randomized national samples of board-certified, clinically active cardiologists, internists, and endocrinologists to receive 1 of 3 information scenarios about a hypothetical drug derived verbatim from excerpts on the website for Vascepa, a prescription fish oil for which Food and Drug Administration specially permitted off-label promotion after a manufacturer lawsuit. The scenarios presented information about the approved on-label indication (severe hypertriglyceridemia), off-label claim + pro forma disclaimers (suggestive but not conclusive evidence for use as an add-on to a statin for patients reaching low-density lipoprotein goal but with persistent moderate hypertriglyceridemia), and off-label claim + evidence context (eg, reports on 3 trials failing to demonstrate cardiovascular benefit of other triglyceride-lowering drugs for such patients). Among 686 respondents (48% response rate), 29% reported receiving off-label information about Vascepa (ie, use as an add-on to a statin) from the manufacturer, and 16% had prescribed it off-label for this purpose. Off-label prescribing was 5 times higher among physicians who received such off-label information (38% versus 7%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). For the hypothetical drug, the proportion of physicians endorsing the unproven claim that the drug reduced cardiovascular risk was similar among those randomized to the on-label and off-label claim + pro forma disclaimers scenarios (35% versus 37% [95% CI, \u22126% to 11%]), but substantially lower among those randomized to the off-label claim + evidence context scenario (21% [95% CI, \u221224% to 7%]).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Physicians who received company information about the unapproved use of Vascepa were more likely to report prescribing it off-label. Supplementing off-label claims with evidence context improved the prescribers\u2019 knowledge and reduced enthusiasm for the unproven, off-label indication of reducing cardiovascular risk.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circoutcomes.119.006073","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T10:02:10Z","timestamp":1573466530000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Randomized Study of Providing Evidence Context to Mitigate Physician Misinterpretation Arising From Off-Label Drug Promotion"],"prefix":"10.1161","volume":"12","author":[{"given":"Lisa M.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH (L.M.S., S.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Woloshin","sequence":"additional","affiliation":[{"name":"Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH (L.M.S., S.W.)."},{"name":"The Lisa Schwartz Program for Truth in Medicine (S.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Lu","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 in Boston, MA (Z.L., F.A.T., A.S.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn M.","family":"Ross","sequence":"additional","affiliation":[{"name":"American Board of Internal Medicine, Philadelphia, PA (K.M.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frazer A.","family":"Tessema","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 in Boston, MA (Z.L., F.A.T., A.S.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris","family":"Peter","sequence":"additional","affiliation":[{"name":"The Center for Outcomes Research &amp; Evaluation (CORE), Yale-New Haven Hospital, New Haven, CT (D.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 in Boston, MA (Z.L., F.A.T., A.S.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMhle1506365"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1611755"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.12045"},{"key":"e_1_3_4_5_2","first-page":"1539","article-title":"Prospects for regulation of off-label drug promotion in an era of expanding commercial speech protection.","volume":"92","author":"Kesselheim AS","year":"2014","unstructured":"Kesselheim, AS, Mello, M. Prospects for regulation of off-label drug promotion in an era of expanding commercial speech protection. University of North Carolina Law Review. 2014;92:1539\u20131604.","journal-title":"University of North Carolina Law Review"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-720X.2009.00408.x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.6058"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001978"},{"key":"e_1_3_4_9_2","unstructured":"Amarin Pharma Inc. v. US FDA. No. 15 Civ. 3588 (PAE) 2015 WL 4720039 (SDNY Aug. 7 2015)."},{"key":"e_1_3_4_10_2","unstructured":"U.S. Food and Drug Administration. Memorandum: Public health interests and first amendment considerations related to manufacturer communications regarding unapproved uses of approved or cleared medical products. January 2017. Available at http:\/\/www.ascrs.org\/sites\/default\/files\/FDA_Memorandum\u2013Public_Health_Interests_and_First_Amendment_Considerations_Related_to_Manufacturer_Communications_Regarding_Unapproved_Uses_of_Approved_or_Cleared_Medical_Products_Jan_2017%20%281%29.pdf. Accessed August 22 2018."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812792"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001282"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300955"},{"key":"e_1_3_4_15_2","unstructured":"Zhang Y Guille R. A longitudinal analysis of certification trend and performance on dual certification in hematology and medical oncology. Presented at: American Educational Research Association Meeting April 2011."},{"key":"e_1_3_4_16_2","unstructured":"Weng W Gray B Lipner RS. Racial disparity in the quality of diabetes care: do physicians treat minority patients differently or do minority patients receive care from different types of physicians? Presented at: AcademyHealth Annual Research June 2010."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-018-4688-z"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.8121"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.5205"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0895-4356(97)00126-1"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1214926"},{"key":"e_1_3_4_22_2","first-page":"124","article-title":"The statutory case against off-label promotion.","volume":"83","author":"Cortez N","year":"2016","unstructured":"Cortez, N. The statutory case against off-label promotion. University of Chicago Law Review Online. 2016;83:124\u2013142.","journal-title":"University of Chicago Law Review Online"}],"container-title":["Circulation: Cardiovascular Quality and Outcomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCOUTCOMES.119.006073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:06:49Z","timestamp":1715573209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCOUTCOMES.119.006073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":21,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1161\/CIRCOUTCOMES.119.006073"],"URL":"https:\/\/doi.org\/10.1161\/circoutcomes.119.006073","relation":{},"ISSN":["1941-7713","1941-7705"],"issn-type":[{"value":"1941-7713","type":"print"},{"value":"1941-7705","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"2019-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e006073"}}