Financial Conflicts of Interest at FDA Drug Advisory Committee Meetings

This article systematically reviews published studies of the association of pharmaceutical industry funding and clinical trial results, as well a few closely related studies. It reviews two earlier results, and surveys the recent literature. Results are clear: Pharmaceutical company sponsorship is strongly associated with results that favor the sponsors' interests.

Objective To examine the association between payments made by the manufacturers of pharmaceuticals to physicians and prescribing by physicians within hospital referral regions. Design Cross sectional analysis of 2013 and 2014 Open Payments and Medicare Part D prescribing data for two classes of commonly prescribed, commonly marketed drugs: oral anticoagulants and non-insulin diabetes drugs, overall and stratified by physician and payment type. Setting 306 hospital referral regions, United States. Participants 45 949 454 Medicare Part D prescriptions written by 623 886 physicians to 10 513 173 patients for two drug classes: oral anticoagulants and non-insulin diabetes drugs. Main outcome measures Proportion, or market share, of marketed oral anticoagulants and non-insulin diabetes drugs prescribed by physicians among all drugs in each class and within hospital referral regions. Results Among 306 hospital referral regions, there were 977 407 payments to physicians totaling $61 026 140 (£46 174 600; €54 632 500) related to oral anticoagulants, and 1 787 884 payments totaling $108 417 616 related to non-insulin diabetes drugs. The median market share of the hospital referral regions was 21.6% for marketed oral anticoagulants and 12.6% for marketed non-insulin diabetes drugs. Among hospital referral regions, one additional payment (median value $13, interquartile range, $10-$18) was associated with 94 (95% confidence interval 76 to 112) additional days filled of marketed oral anticoagulants and 107 (89 to 125) additional days filled of marketed non-insulin diabetes drugs (P<0.001). Payments to specialists were associated with greater prescribing of marketed drugs than payments to non-specialists (212 v 100 additional days filled per payment of marketed oral anticoagulants, 331 v 114 for marketed non-insulin diabetes drugs, P<0.001). Payments for speaker and consulting fees for non-insulin diabetes drugs were associated with greater prescribing of marketed drugs than payments for food and beverages or educational materials (484 v 110, P<0.001). Conclusions and study limitations Payments by the manufacturers of pharmaceuticals to physicians were associated with greater regional prescribing of marketed drugs among Medicare Part D beneficiaries. Payments to specialists and payments for speaker and consulting fees were predominantly associated with greater regional prescribing of marketed drugs than payments to non-specialists or payments for food and beverages, gifts, or educational materials. As a cross sectional, ecological study, we cannot prove causation between payments to physicians and increased prescribing. Furthermore, our findings should be interpreted only at the regional level. Our study is limited to prescribing by physicians and the two drug classes studied.

Objective To explore a possible link between authors’ financial conflicts of interest and their position on the association of rosiglitazone with increased risk of myocardial infarction in patients with diabetes. Data sources On 10 April 2009, we searched Web of Science and Scopus for articles citing and commenting on either of two index publications that contributed key data to the controversy (a meta-analysis of small trials and a subsequent large trial). Data selection Articles had to comment on rosiglitazone and the risk of myocardial infarction. Guidelines, meta-analyses, reviews, clinical trials, letters, commentaries, and editorials were included. Data extraction For each article, we sought information about the authors’ financial conflicts of interest in the report itself and elsewhere (that is, in all publications within two years of the original publication and online). Two reviewers blinded to the authors’ financial relationships independently classified each article as presenting a favourable (that is, rosiglitazone does not increase the risk of myocardial infarction), neutral, or unfavourable view on the risk of myocardial infarction with rosiglitazone and on recommendations on the use of the drug. Results Of the 202 included articles, 108 (53%) had a conflict of interest statement. Ninety authors (45%) had financial conflicts of interest. Authors who had a favourable view of the risk of myocardial infarction with rosiglitazone were more likely to have financial conflicts of interest with manufacturers of antihyperglycaemic agents in general, and with rosiglitazone manufacturers in particular, than authors who had an unfavourable view (rate ratio 3.38, 95% CI 2.26 to 5.06 and 4.29, 2.63 to 7.02, respectively). There was likewise a strong association between favourable recommendations on the use of rosiglitazone and financial conflicts of interest (3.36, 1.94 to 5.83). These links persisted when articles rather than authors were used as the unit of analysis (4.69, 2.84 to 7.72), when the analysis was restricted to opinion articles (6.29, 2.15 to 18.38) or to articles in which the rosiglitazone controversy was the main focus (6.50, 2.56 to 16.53), and both in articles published before and after the Food and Drug Administration issued a safety warning for rosiglitazone (3.43, 0.99 to 11.82 and 4.95, 2.87 to 8.53, respectively). Conclusions Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors’ expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies. Although these findings do not necessarily indicate a causal link between the position taken on the cardiac risk of rosiglitazone in patients with diabetes and the authors’ financial conflicts of interest, they underscore the need for further changes in disclosure procedures in order for the scientific record to be trusted.