Person:

Kesselheim, Aaron

Background: Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author. Methods and Findings: We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996–2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02–0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥25 articles disclosed in about one-third of articles (range: 10/36–8/25 [28%–32%]). Conclusions: One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is a much lower rate of adequate disclosure than has been identified in previous studies. The non-disclosure patterns suggest shortcomings with authors and the rigor of journal practices.

Background: Policymakers and regulators in the United States (US) and the European Union (EU) are weighing reforms to their medical device approval and post-market surveillance systems. Data may be available that identify strengths and weakness of the approaches to medical device regulation in these settings. Methods and Findings: We performed a systematic review to find empirical studies evaluating medical device regulation in the US or EU. We searched Medline using two nested categories that included medical devices and glossary terms attributable to the US Food and Drug Administration and the EU, following PRISMA guidelines for systematic reviews. We supplemented this search with a review of the US Government Accountability Office online database for reports on US Food and Drug Administration device regulation, consultations with local experts in the field, manual reference mining of selected articles, and Google searches using the same key terms used in the Medline search. We found studies of premarket evaluation and timing (n = 9), studies of device recalls (n = 8), and surveys of device manufacturers (n = 3). These studies provide evidence of quality problems in pre-market submissions in the US, provide conflicting views of device safety based largely on recall data, and relay perceptions of some industry leaders from self-surveys. Conclusions: Few studies have quantitatively assessed medical device regulation in either the US or EU. Existing studies of US and EU device approval and post-market evaluation performance suggest that policy reforms are necessary for both systems, including improving classification of devices in the US and promoting transparency and post-market oversight in the EU. Assessment of regulatory performance in both settings is limited by lack of data on post-approval safety outcomes. Changes to these device approval and post-marketing systems must be accompanied by ongoing research to ensure that there is better assessment of what works in either setting.

Background: Medical device innovation remains poorly understood, and policymakers disagree over how to incentivize early development. We sought to elucidate the components of transformative health care innovation by conducting an in-depth case study of development of a key medical device: coronary artery stents. Methods and Findings: We conducted semi-structured interviews with the innovators whose work contributed to the development of coronary artery stents who we identified based on a review of the regulatory, patent, and medical literature. Semi-structured interviews with each participant covered the interviewee’s personal involvement in coronary artery stent development, the roles of institutions and other individuals in the development process, the interplay of funding and intellectual property in the interviewee’s contribution, and finally reflections on lessons arising from the experience. Transcripts were analyzed using standard coding techniques and the constant comparative method of qualitative data analysis. Conclusions: We found that the first coronary artery stents emerged from three teams: Julio Palmaz and Richard Schatz, Cesare Gianturco and Gary Roubin, and Ulrich Sigwart. First, these individual physician-inventors saw the need for coronary artery stents in their clinical practice. In response, they developed prototypes with the support of academic medical centers leading to early validation studies. Larger companies entered afterwards with engineering support. Patents became paramount once the technology diffused. The case of coronary stents suggests that innovation policy should focus on supporting early physician-inventors at academic centers.

Aaron Kesselheim discusses Natalie Vernaz and colleagues' paper on the effects on health care costs of “evergreening” strategies pursued by drug manufacturers. Please see later in the article for the Editors' Summary