Medical Device Daily Washington Editor

The FDA has a plentiful supply of critics giving voice to outrage over the details of the agency's operations, and the recent publication of a journal article on conflicts of interest among advisory committee members has spurred a legislative proposal that would ban such committees from taking on members with such conflicts.

But public concerns over such arrangements are not restricted to the FDA. According to the web site for the Center for Science in the Public Interest (Washington), similar concerns exist regarding the Environmental Protection Agency and the National Academies of Science.

Going unaddressed in the current debate is the question of why legislative interest seems to always zero in on the FDA and to ignore these sister agencies.

The article serving to boost current interest in this controversy appeared April 26 in the Journal of the American Medical Association, penned by a team headed by Peter Lurie, MD, director of the health research group at Public Citizen (Washington).

The article offers a survey of advisory committee meetings between 2001 and 2004, with “a total of 221 meetings held by 16 advisory committees” reviewed. The survey found 73% of these had “at least one . . . member or voting consultant [who] disclosed a conflict.”

Further, the study found that only 1% of the 28% who disclosed such conflicts of interest were recused by the agency (rounding presumed to account for the apparent total of more than 100%).

Interestingly, Lurie and colleagues acknowledge that only “a weak relationship between certain types of conflicts and voting behaviors was detected,” and that the exclusion of those with potential conflicts “would not have altered the overall vote outcome at any meeting studied.”

The legislation of interest, the FDA Improvement Act of 2005, authored by Rep. Maurice Hinchey (D-New York), would bar any scientists with any conflict of interest at all from participating in advisory committees. On his congressional web site, Hinchey observes that “[i]n 2001, fees paid by drug companies funded 32% of the FDA's budget for drugs. Today, that figure is nearly 50% and it is expected to grow higher.”

“Plain and simple, if a doctor or a scientist has a personal financial stake in a drug, they should not be allowed to sit on an FDA advisory panel” to review that product, Hinchey said. He described the agency's use of conflict-of-interest waivers as a “rampant” practice that has “for far too long endangered the safety of the American people.”

Jeff Lieberson, the director of communications at Rep. Hinchey's office, told Medical Device Daily it is “baseless” that the FDA “can't find enough people without conflict of interest. If they can find 72%, they can look a little harder and find the other 28%.”

Lurie, however, suggested that he does not favor a legislative fix for the problem, at this point.

“They should literally beat the bushes to find people with as few conflicts as possible. One thing is to look harder,” he said.

Details were not available on the most recent iteration of the FDA guidance in time for inclusion in this edition of Medical Device Daily. The previous version, published in January 2002, states that the public disclosure of conflicts of interest “will adequately enable a reasonable person to understand the nature of the conflict and the degree to which it could be expected to influence” votes.

The guidance also notes that the agency will generally exclude any members of standing committees from voting on a product if that member either enjoys royalties from patents and/or trademarks or has served as an expert witness.

In a prepared statement for the July 24 meeting of the Center for Science in the Public Interest (Washington), Scott Gottlieb, MD, the agency's deputy commissioner for medical and scientific affairs, pointed out that “Congress, in its wisdom, created [the advisory panels] in the first place,” adding that previous gripes about the FDA revolved around the perception that the agency's review procedures fed a widespread perception that it was “a black box.” According to his statements, advisory committees have been part of FDA practice for 30 years.

Gottlieb also made the case that “our drug review process is the most transparent in the world, bar none,” noting that Canadian and European committees “meet in secret.” He cautioned that “the value of these committee meetings could be eroded . . . if some current legislative proposals become law.”

“I think it is fair to say that there are few academic experts engaged in research who don't have some scientific ties to industry, especially since FDA defines what a 'tie' is so broadly,” Gottlieb remarked.

The constitution of these panels is that of a “standing advisory committee, with members recruited and appointed sometimes years in advance,” Gottlieb explained. Due to the need to appoint members in advance to ensure staffing, “it is impossible to tell who will eventually have relationships that could present” a potential conflict.

“If we err on the side of caution and appoint only members who have absolutely no associations of any kinds . . . we are going to be hard pressed to find people who have also been engaged in relevant” scientific work, Gottlieb insisted, adding that peer review journals bring in such experts “precisely because of their expertise.”

Gottlieb made the case that arguments “for barring certain people from these expert panels reinforces the unfortunate sense that only personalities and alleged motives count in modern public life when, in truth, it is the integrity and rigor of ideas that have lasting consequences.”

Asked about the findings by Lurie that no panel decisions were decisively influenced by the presence of members with potential conflicts of interest, Lieberson of Rep. Hinchey's office pointed out that the data only go up to 2004, and he cited Vioxx as an example of a “systemic problem.” He admitted that he is not aware of any indication that the Vioxx case is the rule rather than the exception.

Nonetheless, he argued that “[w]hen you have a quarter of panel members with a conflict, you have a systemic problem, because FDA has not demonstrated its commitment to filling its panels completely with conflict-free advisors.”