Advisory Panel Conflict Waivers To Stay; FDA Will Provide Clarity On Process

FDA's plan for improving its advisory committee member selection process focuses on increasing the transparency and consistency of the existing process rather than an overhaul of its practices.

"We will be revising the guidance document that governs how we give out waivers to people with potential conflicts of interest," FDA Deputy Commissioner for Medical & Scientific Affairs Scott Gottlieb said during a recent panel discussion at the National Press Club.

"To the extent that we codify more of these kinds of assessments in writing, it can inspire more consistency [and] more transparency on our process," he explained.

The panel was convened July 24 at the National Press Club to discuss a report on conflicts of interests in National Academies' advisory committees.

In a same-day release, FDA issued a five-point plan to strengthen its advisory panel processes comprising electronic notifications of committee meeting schedules, a more streamlined system to appoint members to drug-related panels and three new guidances.

The guidances will revise and expand upon FDA's 2000 guidance document concerning the management of conflicts of interests for panel members, Gottlieb said.

One guidance will attempt to provide more clarity on the procedures for granting waivers, another will specify when briefing documents become publicly available and a third will outline when waivers for conflicts of interest will be available to the public.

Since the 2000 guidance, changes in the marketplace -and in FDA's thinking - necessitate certain clarifications and adjustments to conflict of interest guidelines, Gottlieb said. "We're going to ask a lot of hard questions - whether certain relationships even require a waiver or whether certain relationships should be granted a waiver."

Advisory committee members have expressed concern about the lack of clarity around FDA's waiver policy in the past.

Gottlieb described FDA's conflict of interest determinations as qualitative and made on a case-by-case basis.

Under the current system, FDA ranks the extent of the conflict by monetary amount and the nature of the involvement (for example speakers' bureau participation, stock holding, working with sponsors versus competitors) on a scale of one to three.

"People who have a level-one conflict will often get waivers. Those who have a level-two conflict will be looked at very closely and sometimes they won't [get a waiver]. People who have a level-three conflict will sometimes get a waiver," he said.

In the future, FDA hopes to be "much more transparent about the waivers that we bring and about the potential associations that our panel members might have," Gottlieb said.

"The reality right now is there is inconsistency in how we disclose this information and it's also difficult to follow the logic of the issue," he acknowledged.

"We post redacted waiver documents on our website. Anyone who has looked at that knows they are hard to follow," he noted.

"We think we can develop templates and a more routine approach to disclose why we made certain decisions about granting a person a waiver."

FDA implemented a new conflict disclosure policy at an August 2005 meeting; however, adherence to the policy at subsequent meetings has been inconsistent.

While improving transparency and consistency in FDA's practices is a priority, Gottlieb emphasized that the agency must safeguard its ability to issue conflict of interest waivers for expert panel members in order to uphold the advisory committees' significance in informing the agency's drug regulatory decisions.

"We feel we need to preserve our ability to maintain our primary criteria for selecting people to our advisory committees - their clinical experience [and] their expertise."

"This means that we need to preserve the process by which we grant waivers to the people who have relationships that could present the appearance of a conflict of interest," he said.

According to Gottlieb, the "vast majority" of waivers issued by FDA are for university department chairs who supervise a large faculty, some of whom may be involved in industry-funded research.

Doing away with the waiver system, as some critics have suggested, would hamper the advisory committee process and bring less clarity to the agency's reasoning behind its drug decisions, he suggested.

"The bottom line is, if we didn't have that ability, we would have far fewer advisory committee meetings," Gottlieb said. "It would probably be...less valuable in some respects to the agency. We would probably bring far fewer drug decisions to these meetings, cutting down on the transparency that they afford."

Gottlieb also emphasized that the lack of compensation and the political scrutiny has made it harder to recruit advisory committee members. "To the extent that they're becoming more political targets to serve in advisory panels, with their reputation potentially being besmirched, people shy away from it," he said.

The contribution of advisory committees to FDA regulatory decisions goes beyond the binary "yes" or "no" vote for drug approvals, he emphasized.

In cases where the data is clear, "the advice that the agency gets from the advisory panel isn't necessarily should we approve the drug," Gottlieb said, "but there are significant questions around the scope of the approval, [such as] what the label should look like [and] an appropriate risk management plan."

Gottlieb held up the Vaccines & Related Biological Products Advisory Committee's recent review of Merck's human papillomavirus vaccine Gardasil as an example of a situation where the committee provided valuable recommendations even when it was widely felt in advance that the product would be approved.

For this type of "nuanced" advice, FDA seeks advisory committee panelists from a "band of heavy clinical trialists," which Gottlieb described as "really a narrow group of people in this country."

"People who are heavy clinical trialists are going to have relationships that could present the appearance of a conflict of interest," he noted. In an effort to strike a balance, FDA defines conflicts of interest broadly to "capture all potential conflicts," but then issues more waivers.

Gottlieb agreed with FDA Office of Medical Policy Director Robert Temple's recent comments to the New York Times that committee members who participate in industry-sponsored drug safety monitoring boards should not require a waiver. "Those are the very best people, and they are anything but patsies," he said.

Temple has previously said that participating in a speakers' bureau for a company poses a greater conflict of interest concern than conducting a trial.

Gottlieb also noted that FDA convenes standing advisory committees, sometimes years in advance of meetings, making it impossible to predict whether potential members will have conflicts with regard to a specific meeting topic.

Standing committees have a number of advantages, he noted, such as allowing panel members to learn the process and become familiar with other panel members' expertise.

During the Press Club discussion, Cleveland Clinic's Steven Nissen, a former chair of FDA's Cardio-Renal Advisory Committee, maintained that "there are a lot of people who aren't conflicted that can be found for panels."

While Nissen did not object to the inclusion of individuals who participate in steering committees for trials funded by academic institutions, he said that speaking on behalf of a company "should be an absolute reason for recusal."

Several panelists at the event noted that the presence of intellectual conflicts also is problematic, but harder to gauge. Nissen said that intellectual conflicts are not "as pervasive" as financial ties, but panelists who have "opined publicly in a very strong way...should either recuse themselves or be recused."

Nissen has been an outspoken critic of FDA's advisory committee oversight.

"Unfortunately, we're in an era when public trust in the FDA is at an all time low, so the appearance of a conflict of interest is as serious as the conflict itself, because it undermines the public's trust," he added.

[Editor's note: This story was contributed by "The Pink Sheet," your source for prescription drug news. For more information call 1-800-332-2181.]