Abstract
This study uses transcripts from the Peripheral and Central Nervous System Drug Advisory Committee of the US Food and Drug Administration to evaluate the association of conflicts of interest for public speakers at committee meetings with the speakers’ statements.
The Peripheral and Central Nervous System Drug Advisory Committee (PCNSDAC) of the US Food and Drug Administration (FDA) makes recommendations for the approval or denial of drugs that treat nervous system diseases. Before issuing recommendations, the PCNSDAC hears public testimony about these drugs in an open forum.1 For example, eteplirsen, a treatment for Duchenne muscular dystrophy, was approved after 52 public speakers provided testimony at the PCNSDAC meeting.2 After approval of eteplirsen, critics spoke out against its approval, citing weak evidence from a 12-patient trial based on a surrogate end point.3 Because public speakers overwhelmingly spoke in favor of eteplirsen,3 critics raised concerns regarding the influence of public testimony on FDA drug approval.4
In the interest of all patients, conflicts of interest (COI) among public speakers must be mitigated to ensure the ethical approval of drugs. Without addressing public speaker COIs, the integrity of new drug approvals may be compromised. Recent evaluations of public speaker COIs reported that pharmaceutical companies often pay traveling and lodging expenses for them.5,6 The aim of this study was to evaluate public PCNSDAC speakers to determine the proportion with an industry COI and the association of those COIs with the speaker’s statements about the drug.
Methods
We based our methods on previous studies.5,6 A total of 19 publicly available meeting transcripts for PCNSDAC meetings from January 7, 2009, to September 18, 2017, were analyzed. The following data were extracted in duplicate by masked investigators (W.A., J.A.): the public speaker’s name, the organization that he or she represented, the drug being discussed, whether the speaker had the disease for which the drug was indicated, whether the speaker took the drug, the speaker’s disclosed COIs, and whether his or her statements about the drug were positive, neutral, or negative. This study used publicly available data and was therefore exempt from institutional review board approval. Logistic regression was used to examine the association between declaring a COI and having the disease for which the drug is indicated and positive statements about the drug. We attempted to include a third variable (whether the speaker took the drug) but were not able to because no patients who took the drug spoke negatively. Stata statistical software, version 15.1 (StataCorp) was used for data analysis.
Results
We identified 226 public speakers from 17 meetings (Table 1 and Table 2). Of the 226 speakers, 129 (57.1%) disclosed a COI, 42 (18.6%) denied COIs, and 55 (22.3%) did not mention COIs. A total of 89 of the 129 public speakers (69.0%) were reimbursed for their travel. A total of 125 (96.9%) spoke positively, 2 (1.6%) spoke negatively, and 2 (1.6%) were neutral. Speakers with a COI were more likely to give favorable remarks about a drug compared with speakers with no COIs (adjusted odds ratio, 4.80; 95% CI, 1.48-15.50). Having the disease was not associated with positive remarks (adjusted odds ratio, 2.60; 95% CI, 0.56-12.08). All patients who took the drug spoke positively.
Table 1. Conflicts of Interest Disclosures From Speakers.
| Variable | No. (%) of Speakers (N = 129) |
|---|---|
| Reimbursed for travel | 89 (69.0) |
| Represented an organization that has received money from pharmaceutical drug company | 13 (10.1) |
| Was or has been a consultant to the pharmaceutical drug company | 13 (10.1) |
| Has received a grant from the pharmaceutical drug company | 5 (3.8) |
| Donated money to research for the drug in question | 4 (3.1) |
| Was an investigator in the drug’s trial | 3 (2.3) |
| Owns stock in pharmaceutical drug company | 1 (0.7) |
| Pharmaceutical representative who wants to represent the drug | 1 (0.7) |
Table 2. Company, Drug Name, and Speaker Information From PCNSDACa.
| Drug | Company | Date of Meeting | No. of Speakers | People Who Spoke Positively/Total Who Disclosed a COI (%) | People Who Spoke Positively/Total With the Disease (%) | People Who Spoke Positively/Total Who Took the Drug (%) |
|---|---|---|---|---|---|---|
| Corticotropin injection (Acthar) | Questcor Pharmaceuticals | 5/6/10 | 20 | 15/15 (100) | 2/2 (100) | 2/2 (100) |
| Ataluren | PTC Therapeutics Inc | 9/28/17 | 29 | 26/26 (100) | 6/6 (100) | 6/6 (100) |
| Drisapersen | BioMarin Pharmaceutical Inc | 11/24/15 | 24 | 16/18 (88.9) | 2/2 (100) | 2/2 (100) |
| Etelpirsen | Sarepta Therapeutics Inc | 4/25/16 | 52 | 30/30 (100) | 7/7 (100) | 7/7 (100) |
| Ezogabine (Potiga) | Valeant Pharmaceuticals | 8/11/10 | 1 | 0/0 | 0/0 | 0/0 |
| Fampridine (Ampriva) | Acorda Therapeutics Inc | 10/14/09 | 11 | 5/5 (100) | 5/6 (83.3) | 3/3 (100) |
| Fingolimod | Novartis Pharmaceuticals Corporation | 6/10/10 | 6 | 1/1 (100) | 4/4 (100) | 2/2 (100) |
| Luflupane (DaTSCAN) | GE HealthCare | 8/11/09 | 3 | 3/3 (100) | 0/0 | 0/0 |
| Lamictal XR | SmithKline Beecham Corporation | 3/10/11 | 1 | 1/1 (100) | 0/0 | 0/0 |
| Lemtrada | Genzyme Corporation | 11/13/13 | 10 | 5/5 (100) | 8/8 (100) | 6/6 (100) |
| Phenytoin-fosphenytoin | Pfizer Inc | 11/3/10 | 1 | 1/1 (100) | 0/0 | 0/0 |
| Florbetapir | Avid Radiopharmaceuticals | 1/20/11 | 8 | 3/4 (75) | 0/0 | 0/0 |
| Rasagiline (Azilect) | Teva Neuroscience Inc | 10/17/11 | 7 | 4/4 (100) | 1/1 (100) | 1/1 (100) |
| Suvorexant | Merck Sharp & Dohme Corp | 5/22/13 | 3 | 1/1 (100) | 0/0 | 0/0 |
| Tafamidis meglumine (Vyndaqel) | FoldRx Pharmaceuticals, Inc | 5/24/12 | 15 | 2/2 (100) | 8/8 (100) | 1/1 (100) |
| Tasimelteon (Hetlioz) | Vanda Pharmaceuticals Inc | 11/14/13 | 11 | 7/8 (87.5) | 3/4 (75) | 1/1 (100) |
| Vigabatrin | Ovation Pharmaceuticals | 1/7-8/09 | 24 | 5/5 (100) | 2/2 (100) | 1/1 (100) |
| Total | NA | NA | 226 | 125/129 (96.9) | 48/50 (96.0) | 32/32 (100) |
Abbreviations: NA, not applicable; PCNSDAC, Peripheral and Central Nervous System Drug Advisory Committee.
Some speakers declared a conflict of interest, had the disease, and took the drug and may be counted more than once in the last 3 columns.
Discussion
Our results suggest that public speakers at PCNSDAC meetings are more likely to provide positive statements about a drug if they have an industry COI or take the drug in question but not more likely if they have the disease for which the drug is indicated. These findings are consistent with previous studies.5,6 This study is limited by the use of only publicly available meeting transcripts. Thus, our analysis may exclude potential confounding variables.
Given the proportion of patients who disclosed a COI and the association between COIs and positive statements, the acceptability of industry influence in gathering public speakers should be questioned. Of note, a significant portion of speakers did not mention COIs at all. Given the possibility that public speakers are capable of swaying approval committee opinion about a drug, declaring or denying COIs should be required.
References
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