Twice this week, we have learned that members of the FDA advisory panel convened to review the safety of the Avandia diabetes pill had relationships with drugmakers that had something at stake. One panelist, David Capuzzi, has an ongoing relationship with GlaxoSmithKline as a speaker, although he apparently spoke only once about the diabetes drug (see here). And Abraham Thomas has, in the past, given talks about Actos, a rival pill sold by Takeda Pharmaceuticals ( see here).
The FDA is now investigating the episode surrounding Capuzzi and expects to have some decision by the end of the week. A finding that warrants further inquiry could be sent to the HHS Office of Inspector General. The agency, however, may not probe Thomas, because his speaking engagements for Takeda took place more than 12 months prior to last week's advisory panel meeting. The panel, by the way, voted 20-to-12 to allow Avandia to remain on the market.
Meanwhile, we asked a few other members of the panel what they thought of this development, given that Capuzzi voted in favor of allowing Avandia to remain on the market, while Thomas was one of the 12 panelists who voted to remove the pill. Would they have voted differently had they known about the relationships between their colleagues and the drugmakers? To what extent, if any, should the FDA take this into consideration as the agency now decides what to do with Avandia? Here are their thoughts...
Elaine Morrato, assistant professor, Departments of Health Systems, Management & Policy Clinical Pharmacy and Pediatrics at the University of Colorado-Denver (who voted to allow Avandia to stay on the market with restrictions): "I really rely on the FDA's assessment of conflicts of interest, so I'm going to have rely on their judgment. For me, personally, I'm not influenced by what they said or how they voted. So it woulldn't have changed how i would have voted...
"They encourage us to err on overdisclosing...I do think the FDA has really increased the transparency of prior disclosures. As I fill out these forms, they do ask us to disclose anything in your past that may have relevance.. For example, I worked for a pharmaceutical company nine to 10 years ago. I know they do a critical evaluation and a determination of what might be relevant.
"I would agree the agency needs to follow through with investigation they're planning...I think the agency emphasized in the meeting the vote is important and the discussion is as important, if not more so...They can look at tthe flow of the conversation to determine or not whether it affects the investigation."
Sanjay Kaul, professor, David Geffen School of Medicine at UCLA, Division of Cardiology, Cedar Sinai Medical Center (he voted to allow Avandia to remain on the market but with warnings): "Don't they cancel each other out? Your guess is as good as mine (concerning what the FDA will do). I think, as a rule, all conflicts of interest or potential conflicts should be disclosed...I just don't know whether this is really what it's made out to be. I really want to give people the beneift of the doubt. I can see how other people may make somehing of it...I don't think the panelists were perusaded by any one individual panel member's opinions about the data. I feel there are two types when they look at the data - if it fits preconceived notions, they're convinced. If not, they're not convinced.
"I realize the FDA COI process can be confusing. Sometimes, they say only disclose COI for the past 12 months, but what if you had something going back two or three or four years. Some people are literate, some disclose everyhing and let the FDA make the decisions.
"If I recall correctly, I think (Capuzzi) said, generally, he is skeptical of the class (of drugs) and so even tnough he does not prescribe Avandai, he felt making a decision based on data presented would have a chilling effect on innovation. I think he was coming from philosophical point of view rather than being a fan of (the class of drugs)...
"I can assure you the panelists came prepared and had very strong opinions and won't be easily swayed by other people's opinions unless they're very compelling...I don't know how this would impact...I don't think the FDA just counts the votes...The FDA focuses on discussions around the vote...The numbers don't mean much to me, or most of the panelists or the FDA. "But it's an important lesson for all of us to learn - when in doubt, alll information should be disclosed in transparent fashion...If it turns out there are other others also conflicted, than the process was not working...Should the FDA start auditing everyone's COI perhaps? At some point, the FDA has to trust the disclosed conflicts." Michael Proschan, mathematical statistician, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (he abstained): "To me, my thinking is based on all the data i reviewed...It's true, certainly, what people on the panel say has some impact. To me, my decison is based virtually entirely on the data I reviewed, so Ii don't think itwould have much infuence at all...Remember, there were two different advisory committees combined, so there two out of however many? It's is still not very many.... And I think the FDA is going to weigh what everyone said. I don't know whether they'll make any adjustment in their minds, but I kind of doubt it. I think they needed to hear what everyone thought of the data, but i don't think it should have much of an effect...If you found out one member was paid off to vote a certain way, it would be a different story...I don't think it's that serious... In an ideal world, it'd be great to never have any conflicts...Unfortunately, to get an expert who's never had any dealing with any of the companies is almost impossible, but in the real world, I just don't think that's practical."