In this study, we focused on whistleblower complaints, the only publicly accessible data that reveal the details of off-label marketing arrangements between pharmaceutical manufacturers and physicians. All of the relationships we identified were alleged by whistleblowers with special knowledge of company practices, although none of the complaints were subject to full trial and evaluation by a judge or jury. We found that, of 91 authors who had financial relationships with pharmaceutical companies in the context of off-label drug marketing, 39 authored 404 related articles in the three years following their engagement. However, only two-thirds of those articles contained any type of disclosure statement, one-quarter contained a disclosure statement that mentioned the relevant pharmaceutical company, and one in seven made disclosures that adequately described their relationship with the manufacturer. Adequate disclosure was no more or less likely in articles that discussed off-label uses. A majority of the most productive authors made adequate disclosures some of the time.
The rate of adequate disclosure we observed is markedly lower than rates detected in previous studies. For example, Okike et al. examined orthopedic surgeons with financial ties to hip and knee prosthesis manufacturers who presented or served as a committee or board member at an annual professional meeting, and found that 75% disclosed payments directly or indirectly related to their research (80% for the 208 directly related presentations, 50% for the 32 indirectly related presentations) 
. Chimonas et al. examined publications from a subset of these orthopedic surgeons and identified disclosures in 50% of directly related and indirectly related articles published in the year following the payments (50% of the 52 directly related articles, 50% of the 34 indirectly related articles) 
. The much lower rate of disclosure we observed may be due to consideration of authors from a range of clinical specialties, or our focus on ties with the pharmaceutical industry. Additionally, part of the difference may be attributable to the targeted nature of our study: authors who are paid by industry to support off-label uses may be especially poor disclosers.
Where does responsibility for this alarmingly high rate of inadequate disclosure lie? These failures spanned many articles and publications, pointing to authors themselves. Authors may be ignorant about what is required, may misunderstand the relatedness of the paper to their financial entanglement, or may be forgetful. The systematic nature of the non-disclosure, and context in which these failures occurred—suspect marketing activities that authors were paid to be a part of—suggest that embarrassment or willful hiding may explain at least some of the missing disclosures. However, this hypothesis is contradicted by the fact that physicians who are involved in off-label marketing activities tend not to face punishment by the DOJ or state medical boards 
, or to view their participation as inappropriate 
It is clear that that journal practices play a role in inadequate disclosure, because we found that some authors, including the most prolific ones, made adequate disclosures in some articles but not in others. It is unlikely that so many authors would engage in this type of behavior on their own, since it creates a public record of spotty disclosure that could be ascertained by searching and cross-referencing the medical literature 
. To systematize practices, the ICMJE promulgated disclosure standards in 2009, including a template that requires authors to disclose direct support for the research, personal financial relationships, and other interests 
. Yet journals still diverge in their disclosure requirements, and even in how they define a “conflict of interest” 
. Journals also may inconsistently apply disclosure requirements to non-data-driven commentaries, as compared to reports of studies or trials. Indeed, our results reinforce other research that has found low rates of adequate disclosure among commentaries 
. Our results, collected before the ICMJE standards were published, show some of the consequences of variable oversight by editors of biomedical journals.
Solutions to inadequate conflict of interest disclosure are not straightforward. Some have called for civil liability 
, and a few journals have threatened restriction of future publication 
. Academic medical centers and universities have been a primary locus of attempts at reform, with many developing conflict of interest rules of varying intensity 
. The Department of Health and Human Services has proposed requiring all universities and medical schools to disclose financial arrangements that could influence the work of government-funded researchers on their faculties 
, although this policy appears unlikely to be fully implemented 
While efforts by academic medical centers may enhance disclosure by authors of medical journal articles, we found that 57% of the physicians in the whistleblower complaints published no articles during the study period. Thus, manufacturers' off-label marketing strategies may often involve payments to physicians who have influence in their local communities, rather than those who engage in research or write articles related to practice. It is also notable that non-authors were more often provided with gifts or honoraria, while authors were more often paid as speakers on behalf of the company. The different types of financial inducements may reflect varying marketing roles played by physicians who contribute to the medical literature and those who do not. If academic medical centers tighten their policies about receipt of payments from manufacturers, more companies considering an off-label marketing strategy may continue to seek out such non-academically affiliated experts. The Patient Protection and Affordable Care Act will require manufacturers to report their physician payments to the government starting in 2013. This may promote transparency of financial relationships among all physicians, but its effectiveness will depend on the government's ability to make disclosures available in a timely and user-friendly fashion, and to prevent “laundering” of funds through seemingly neutral third-party corporations.
Our study has certain limitations. Our analysis is based on authors identified from whistleblower cases concerning off-label drug promotion. Rates and patterns of disclosure in this population may spotlight a “worst” end of the spectrum. Nonetheless, these authors are still capable of influencing prescribing practices, and the citation rate of their articles and the prestige of some of the journals in which their work was published deepen concerns that they have done so. In addition, while our results suggest deficiencies at both the author and journal level, our data cannot precisely define the fraction of deficiencies attributable to improper reporting by the author, as compared to administrative error, policies, or other reasons arising from the journal. This can be attributed in part to the fact that we did not obtain information on the disclosure requirements of each journal in the year of publication, nor did we have access to the specific disclosure-related communications between the journals and the authors. Finally, nearly all of the whistleblower complaints were focused on making out a case of fraud by the companies, not alleging or proving illegal activities on the part of the individual physicians or scientists that formed the focus of our study. Thus, the full range of payments to and interactions with individual physicians and scientists may not have been disclosed, rendering our account of these payments and interactions a lower bound on their true extent.
This study documented substantial deficiencies in the adequacy of conflict-of-interest disclosures made by authors who had been paid by pharmaceutical manufacturers. That such failures occurred in relation to off-label marketing schemes is especially troubling. Because off-label use is an area of clinical practice in which opinion is likely to be divided about appropriate care, the views of high-profile “opinion leaders” may exert considerable influence on prescribing practices 
. Disclosure of financial ties in these situations would give readers an opportunity to weigh the potential for bias. 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 skeptical.