Participants in past meetings of the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) think changes to FDA advisory committee procedures announced in August will add credibility to those committee votes.
The FDA announced a series of changes on August 4 that will affect who can vote during meetings of its advisory committees and how those votes will be recorded. The “headline” changes affect conflict of interest rules, which were, in part, driven by provisions in the FDA’s Amendments Act (FDAAA) passed by Congress in 2007. That bill had a “conflict of interest” section. Congress had been concerned for years that votes by academic researchers who sit on advisory committees may be influenced —either in reality or hypothetically—by payments they receive from pharmaceutical companies.
The new FDA rules state that any committee member with more than a $50,000 personal financial interest in any of the companies (or its competitors) that may be affected by a particular meeting cannot vote. If the member’s interest is less than $50,000, FDA officials may, in certain situations, grant a waiver to the committee member—but will do so only if they determine that there is an essential need for the advisor’s particular expertise. The FDAAA also established limits on the number of waivers the FDA can grant across its advisory committees in a given year, a percentage that decreases over time.
The FDA’s previous rules prohibited participation in advisory committee meetings and votes if a vote would have “a direct and predictable effect on a financial interest attributable to him or his employer.” But unlimited waivers were allowed, and granted.
Another important change in the FDA’s August 4 package of reforms is that advisory committee votes will be simultaneous, instead of in roll-call fashion. David Shaffer, MD, professor of child psychiatry at Columbia University, New York State Psychiatric Institute, said that the simultaneous vote “is one of the excellent things about the new policy.” Shaffer attended a February 2008 meeting of the PDAC to discuss Eli Lilly and Company’s new drug application for Zyprexa Adhera (olanzapine pamoate depot). He was a voting consultant. “I think there was a certain amount of following the leader,” Shaffer explained, referring to advisory committee meetings in general. “Everybody is subject to group process, and people vary a great deal in their self-perceived rank and expertise.”
The advisory committee had voted 10-0 in favor of FDA approval of Zyprexa Adhera—a long-acting form of Zyprexa for schizophrenia—that could be injected every 2 or 4 weeks. The product would be administered in a doctor’s office.
At that February meeting, Shaffer and 2 other members of the advisory committee were given waivers to participate. Those 2 members who got waivers were Andrew C. Leon, PhD, professor of biostatistics in psychiatry and professor of public health at Weill Cornell Medical College, and Andrew Winokur, MD, PhD, director of the neuropsychopharmacology treatment, research, and training center in the Department of Psychiatry at the University of Connecticut Health Center. Neither man is on the current roster of the PDAC.
The waiver given to Winokur noted that he had received remuneration for participation in a study for a competing product for an unrelated indication and had earned less than $100,000 for his efforts. Leon had received payments of less than $50,000 a year for his participation on 3 separate data safety monitoring boards organized by a company or companies—how many companies is not clear—with a competing product.
Leon noted that although his 4-year term ended June 30, 2007, he attended the February 2008 meeting and a second one in July 2008 as a voting consultant. He agreed with Shaffer that at times there can be a tendency for committee members to “follow the leader” in voting, but he explained that more often than not he voted in the minority.
Leon called the $50,000 ceiling for voting “reasonable.” But while acknowledging the public perception that academics with consulting contracts “create an opportunity for biased evaluation,” he noted that “if you look at my votes over the past 6 years, I probably don’t look like a friend of industry.” The waiver request, submitted by Igor Cerny, director of advisors and consultants staff at the FDA’s Center for Drug Evaluation and Research, noted that any financial conflicts Leon might have were “not so substantial as to preclude Dr Leon’s participation.” In addition, his participation was needed because he was the “only biostatistician participating in the Psychopharmacologic Drugs Advisory Committee meeting” and “a biostatistician with expertise in psychiatric drugs, which makes him even more vital for the required analysis of clinical trial data in this meeting.”
Shaffer agreed with Leon that the new conflict of interest policy helps deal with the appearance of conflicts, which is what caused most of the concern.
Daniel S. Pine, chairman of the PDAC and a researcher with the NIMH, declined to comment on the potential impact of the changes.
However, some aspects of the changes disappointed interested parties on both ends of the spectrum. For example, public interest groups had wanted the FDA to “look back” 3 years to see whether an advisory committee member had received more than $50,000 in payments from a drug company. The FDA decided on a 1-year look back period. That disappointed Roy Baranello Jr, assistant vice president of global regulatory policy and operations for Wyeth Pharmaceuticals too. He had argued that disallowing a vote by an advisory committee member who sold stock “many months”—be it 10, 8, 6, or whatever—before the meeting would deprive “the committee and the FDA of that member’s expertise without any real justification.”