COI declarations and off-label drug use
Conflict-of-interest statements made by physicians and scientists in their medical journal articles after they had been allegedly paid by pharmaceutical manufacturers as part of off-label marketing programs are often inadequate, highlighting the deficiencies in relying on author candidness and the weaknesses in some journal practices in ensuring proper disclosure, according to a study by international researchers published in this week’s PLOS Medicine. Off-label marketing is the promotion by a manufacturer of a drug for use in a condition or age group, or in a dose or form of administration that has not been specifically approved by a drugs regulatory body; it is illegal in the United States.
In an analysis led by Aaron Kesselheim from Brigham and Women’s Hospital in Boston, the authors from the US and Australia found that overall, only one in seven authors reported by whistleblowers to be involved in off-label marketing activities fully disclosed their conflict of interest in published articles.
The authors reached these conclusions by examining 26 whistleblower complaints of illegal off-label promotion and identified the 91 doctors and scientists recorded as being involved in this practice. The researchers found 39 (43%) of these 91 experts had authored 404 publications related to the drugs at issue in the complaints. However, only 62 (15%) of these articles had adequate disclosures. Among the articles without adequate disclosures, 43% (148) had no disclosure at all, 4% had statements denying any conflicts of interest, 40% had disclosures that did not mention the drug manufacturer, and 13% had disclosures that mentioned the manufacturer but inadequately conveyed the nature of the relationship between author and drug manufacturer reported in the complaint.
The authors argue that such failures in relation to off-label marketing schemes are especially troubling because off-label use is an area of clinical practice in which opinion is likely to be divided about appropriate care and there is no guidance from regulatory authorities. Therefore, high-profile ”opinion leaders” may exert considerable influence on prescribing practices through their publications. The authors argue: “More adequate disclosure of financial ties in these situations would give readers an opportunity to weigh the potential for bias.”
The authors conclude: “Our findings suggest that approaches to controlling the effects of conflicts of interest that rely on author candidness and variable policing by journals have fallen short of the mark. Readers are left with little choice but to be sceptical.”
Funding: ASK is supported by a career development award from the Agency for Healthcare Research & Quality (K08HS18465-01), and a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared the following competing interests: ASK was co-chair of a conference entitled Conflicts of Interest in the Practice of Medicine: A National Symposium sponsored by the American Society of Law, Medicine, and Ethics, the Highmark Foundation, the Jewish Healthcare Foundation, and the University of Pittsburgh; ASK was paid a small honorarium for his effort. In 2008-2009, ASK served as an expert witness for the state of Texas in a case against Merck alleging inappropriate promotion of rofecoxib (Vioxx), and ASK served as an expert witness for a class of individual plaintiffs in a case against AstraZeneca alleging inappropriate promotion of esomeprazole (Nexium). All other authors have declared no competing interests.
Citation: Kesselheim AS, Wang B, Studdert DM, Avorn J (2012) Conflict of Interest Reporting by Authors Involved in Promotion of Off-Label Drug Use: An Analysis of Journal Disclosures. PLoS Med 9(8): e1001280. doi:10.1371/journal.pmed.1001280
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CONTACT: Aaron S. Kesselheim Brigham and Women’s Hospital and Harvard Medical School Massachusetts, United States of America email@example.com