Discussion

We investigated whether COIs were associated with public speakers providing favourable testimonies at PDAC meetings. Our results showed that disclosing a COI was associated with increased odds of public speakers providing a favourable testimony for the recommendation of psychiatric drugs. At these meetings, more than one-third of the 145 public speakers disclosed a COI and more than three-fourths of these speakers provided a positive testimony with travel and lodging being the most prominent. Speakers who had the condition in question were not more likely to provide a positive statement than those who did not. Additionally, we found that 24 out of the 145 public speakers did not mention their COI, and among these speakers, nearly half of them provided a positive testimony. The implications of these findings are concerning since COIs have the potential to skew public speaker’s testimonies at these meetings and persuade committee members to look beyond the evidence and approve a drug through the acquisition of non-evidence-based information.

Our primary finding—disclosing a COI was associated with increased odds of public speakers giving a positive testimony—aligns with previously published research from three previous investigations. Abola and Prasad7 found that 31 out of 103 public speakers reported financial COI at Oncologic Drug Advisory Committee (ODAC) meetings and all of these associated speakers provided positive remarks regarding the drug in question. The authors stated that committee members should keep these financial associations in mind when listening to the speaker’s testimonies during open public hearings due to the possible effects that these COIs may have on the speaker’s testimonies. Additionally, McCoy et al 2 found that almost 25% of speakers at Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) meetings contained COIs but nearly 20% of these speakers did not properly disclose their conflicts. In addition, the authors found that these COIs significantly increased the speaker’s chances of providing support for approval of a drug and concluded that sponsor-related bias may be in effect at these meetings. Finally, Arthur et al 6 found that 126 out of 129 speakers who disclosed a COI at Peripheral and Central Nervous System Drug Advisory Committee meetings gave a positive testimony about the drug in question. These authors concluded that given the influence that industry-related COIs may have on the nature of public speaker’s testimonies at these meetings, further precautions should be implemented to prevent the future persuasion of committee members endorsing a drug like eteplirsen, whose approval may have been influenced by emotionally charged tactics.5 Thus, our study’s findings provide additional support to the belief that COIs may influence the nature of public speaker’s testimonies at FDA meetings. Our findings do not provide support that speakers who had the disease for which the drug was indicated or who took the drug were more likely to recommend the drug. These circumstances have been described as non-financial COIs and have been a source of debate in the published literature. Some authors argue that financial COIs should be the primary consideration, as financial ties have been extensively studied and are known to contribute to bias.8–12 Other authors warn that non-financial COIs may be problematic and that medical bias could possibly have an effect on the assessment of evidence by scientists or others.13 Currently, the FDA only considers COIs that are financial in nature to be necessary for disclosure.14

We recommend pharmaceutical companies not be allowed to handpick the patients they want to speak during open public hearings, but rather random video diaries from patients involved in the drug’s clinical trial phases be played at these hearings instead to promote transparency and validity regarding the approval process, as suggested by Hayes and Prasad.15 For example, patients involved in these trials may be preselected to record video updates regarding their experience and viewpoint of the drug throughout the clinical trial phase and a random selection of these video diaries be played for the panel during committee meetings to provide representative patient testimony. This implemented process may help ensure non-emotionally charged testimonies are presented to the committee and potentially reduce the risk of bias regarding the approval of psychiatric drugs. Additionally, we acknowledge that public speakers are not the only parties who present with COIs at FDA advisory meetings, and these COIs may also affect committee recommendations regarding drug approval; hence, we decided to briefly discuss them as follows.

Lammers et al 16 reviewed 35 ODAC meetings between 2011 and 2015 and found that 35 out of 38 experts (US healthcare professional with an MD degree) who spoke at these meetings had received industry payments with a mean income of $39 316. In addition, this study found a strong correlation among these expert’s payments and their degree of academic success. Thus, the higher number of publications or citations ascribed to these experts, the greater the amount of industry payments they received. A 2006 study investigated the voting patterns of advisory committee members from 221 meetings held by 16 different committees over a 4-year period. This study found that 73% of meetings contained at least one committee member with a financial obligation and these financial associations exceeded $100 000 in select cases.17 Graham et al 18 sought to examine the relationship between industry and patient-consumer representatives serving on the FDA drug advisory committees by investigating all 167 FDA advisory committee meetings between 2009 and 2012. This study found COIs to be present in one-third of these meetings with half of the COIs to be valued at $50 000 or more. The authors concluded with recommendations to the FDA to change the way they evaluate COIs for patient and consumer representatives; specifically, a revision to their guidelines was suggested regarding the requirement of advisory committee members to list their financial relationships between industry and organisations (form 3410). Thus, evidence from the body of literature on COIs and FDA committees coupled with results from the present study support the notion that the FDA’s drug approval process may lack transparency and is subject to possible bias created by financial associations between pharmaceutical companies and public speakers, expert speakers and advisory committee members.

We recognise that disclosure of COIs alone is not sufficient to mitigate bias. We agree with the recommendations by McCoy and Emmanuel19 who suggest that, in addition to stronger disclosure rules for public speakers, additional procedures should be considered for implementation by the FDA regarding COIs, namely stricter management of COIs or prohibition. Management practices might include limiting the number of speakers who have COIs, whereas prohibition would eliminate public speakers with COIs altogether. Whether one or more of these procedures are employed, we believe that these alternatives would help the FDA accomplish its mission for ‘protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices…’.20

This study has strengths and limitations. Key strengths include the fact that our methodology was modelled after prior studies, all of which have been peer-reviewed in distinct areas of medicine.2 6 Additionally, our pilot-tested, double-blinded data extraction helps mitigate bias and adds to the validity of our results. Our study has limitations. This study was cross-sectional, which may restrict its generalisability. Even though we extensively searched throughout the FDA’s website, we were unable to find two transcripts from PDAC meetings, which may have contained public speakers that could have altered our results. In addition, we were forced to discard another meeting due to poor transcription quality during the session.