This has been a tough and confusing time for anyone who prescribes painkillers, especially COX-2 inhibitors. The decision about what to prescribe was not made easier by the voluntary withdrawal in 2004 of rofecoxib (Vioxx) by Merck; because one trial found an increased risk of cardiovascular side effects. Then it was reinstated in February this year when an Food & Drug Administration (FDA) advisory panel concluded that the benefits outweighed the risks.
Confounding that turnaround was an analysis, conducted at the request of The New York Times by the Center for Science in the Public Interest (CSPI), a Washington-based consumer advocacy organization that focuses on health and nutrition. They found that 10 of the 32 FDA panel members who approved returning the painkillers to the market had financial ties to manufacturers of COX-2 inhibitors; 17 other members also had links to the manufacturers, but not in connection with COX-2 inhibitors.
The Center concluded that the advisory board would have voted against approval for the drugs if conflicts of interests had excluded members from participating in the decision.
Whether they regard painkillers or any other drugs neurologists might use, concern about conflicts of interests has moved beyond the academic and practice corridors to the halls of Congress. An amendment to the 2006 FDA appropriations bill, passed by Congress and signed by the President in November, aims to put to rest an issue that has long dogged the agency: conflicts of interest for members of advisory committees.
RULES FOR ADVISORY PANEL
The FDA's 30 advisory committees are responsible for reviewing drugs and products, although final decisions rest with the FDA. The amendment to the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act (HR 2744) requires the FDA to publish on its Web site all conflict-of-interest waivers given to its panel members at least 15 days before any advisory panel meeting.
If the FDA learns of a conflict of interest less than 15 days before the meeting, the agency must disclose that as soon as possible and no later than the date of the meeting. In addition, the FDA Commissioner is required to make quarterly reports to the Health and Human Services Inspector General and the House and Senate Appropriations Committees on the efforts the agency has made to find qualified panel members with minimal or no conflict of interest.
Figure. Dr. Lily Jun...Image Tools
This legislation is a watered-down version of an amendment offered by Congressman Maurice Hinchey (D-NY) that would prohibit the practice of issuing waivers altogether. Senate and House conferees chose to include this less stringent amendment during negotiations on the FDA appropriations bill.
SKEPTICISM ABOUT THE AMENDMENT
Critics claim that while it was a step in the right direction, the amendment will not prevent physicians and scientists with ties to drug, device, or food manufacturers from sitting on panels responsible for approving those companies' products. “What this final version essentially says to the FDA is if you want to continue using doctors and scientists with conflicts of interest go right ahead, just let us know about it,” Congressman Hinchey said in a published news statement.
According to FDA policy, the agency may grant a waiver to a panel member when the official responsible for the appointment determines that the need for the employee's services outweighs the potential conflict of interest created by the employee's financial interest. Under the current system, waivers are only released when an individual files a Freedom of Information Act request, which according to a statement by CSPI Integrity in Science Project Director Merrill Goozner, can take years. However, all conflicts of interest are announced at the beginning of every FDA advisory committee meeting and transcripts of those discussions can be found on the FDA Web site, www.fda.gov/ohrms/dockets/ac/acmenu.htm.
Some claim that expunging the FDA of all conflicts of interest is an unrealistic and impractical goal. FDA advisory members are selected precisely because of their expertise in a certain field. Because of the nature of the industry, this expertise often involves prior consulting work with pharmaceutical and biotechnology companies, Murray Sagsveen, Esq., AAN General Counsel, said.
“If you appoint people with no conflicts of interest at all, they might not know anything about the issue,” he said.
Rather, it is the degree of the conflict of interest that makes a difference, he said. For example, it is acceptable that a panel member might have accepted an honorarium for a speaking arrangement from a pharmaceutical company many years ago, as long as that information is disclosed. On the other hand, an expert who has a continuing $100,000 consulting contract with a pharmaceutical company should not be appointed to an FDA panel, he said.
INFORMATION IS AVAILABLE TO PUBLIC
Figure. Congressman ...Image Tools
AAN member Lily Jung, MD, who was recently appointed Consumer Representative to the FDA Peripheral and Central Nervous System Drugs Advisory Committee, said the amendment is unnecessary because all information about advisory meetings is made public.
“Everything is in the public record, if you say something that is not scientifically based, it will come back to bite you,” she said.
A more serious issue, she said, is conflicts of interest among higher-ups at the agency. She pointed out that in December 2003 an FDA committee had recommended that the morning-after pill Plan B be approved by for over-the-counter use; but that recommendation was later rejected by the agency's executive board – a decision, she said, that could have been the result of political pressure.
Dr. Jung, a neurologist at the Seattle Neuroscience Institute and Swedish Medical Center, has so far served as a non-voting member in one FDA meeting, which took place this August. During the meeting, committee members declined to approve a new migraine drug because they felt that additional safety data was needed, according to meeting notes posted by the FDA. Dr. Jung, also Clinical Associate Professor at the University of Washington, disclosed at the meeting that she received a waiver for ownership of stock valued from $5,001 to $25,000 in a competing firm. She said FDA financial disclosure forms are more extensive than many others she has seen.
“If a portion of your financial portfolio is based upon your ownership of [healthcare related] stock – I think the average panel members have little day-to-day interest in that – maybe I'm naïve, but I don't think it interferes with how you manage your profession or your work,” she said.
FUNDING INFLUENCES DECISIONS
Sheldon Krimsky, PhD, Professor at the Department of Urban and Environmental Policy and Planning at Tufts University in Medford, MA, and author of the book Science in the Private Interest (Rowman & Littlefield, 2003) argues that studies have shown that private funding does influence scientific decisions. Waivers of conflict of interest have been abused and should be discontinued, he said in an e-mail to Neurology Today. Although this would limit the FDA's ability to recruit, it won't prevent or make it impossible for the agency to recruit qualified panel members. “The longer the non-waiver policy is in place, the easier it will be to recruit,” he said. “Scientists will begin to recognize that being an advisor is a privilege.”
Congressman Hinchey plans to reintroduce legislation banning conflict of interest waivers during next year's appropriations process. In addition, in September Senators Richard Durbin (D-IL), Mike Enzie (R-WY), and Edward Kennedy (D-MA), asked the Government Accountability Office to review the FDA's waiver policy.
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Dr. Krimsky welcomes such efforts. “If the waivers are permitted it will reinforce the idea that there is no hope for achieving disinterested advice; there would be no reason for scientists to remain ‘clear of conflicts’ since the norm suggests they are multi-vested,” he said.
ARTICLE IN BRIEF
✓ An amendment to the 2006 FDA appropriations bill, passed by Congress and signed by the President in November, aims to put to rest an issue that has long dogged the agency: conflicts of interest for members of advisory committees. But critics of the amendment contend that it will not prevent physicians and scientists with ties to drug, device, or food manufacturers from sitting on panels responsible for approving those companies' products.