October 26

FDA’s Double Standard Re: Advisory Committee Membership

FDA’s Double Standard Re: Advisory Committee Membership

Mon, 15 Nov 2004

FDA’s inexplicable actions–the latest being the removal of Dr. Curt Furberg from an FDA advisory committee for alleged "intellectual conflict of interest" – demonstrate hypocracy and intellectual dishonesty.

Dr. Furberg independently analyzed the scientific data, concluding: "The result is [Bextra] looks like Vioxx, and we need to be careful. Pfizer is basically saying ‘Our drug is safe until we have more information,’ and my position is the opposite. I am saying we need to know it is safe before we use it on a large scale."

FDA’s action against Dr. Furberg contrasts sharply with the agency’s record of tolerance of major financial conflicts of interest of its advisory panel members. See press release from Science for the Public Interest. Our own example is of a more recent vintage: from FDA’s Feb 2, 2004 advisory committee that deliberated about the safety of SSRI antidepressants for children and adolescents – in particular the suicidal risk linked to these drugs.

Dr. Andrew Leon was a member the FEB 2 advisory panel. However, Dr. Leon was also a member of the American College of Neuropsychopharmacology (ACNP) Task Force that issued an unsubstantiated pronouncement, January 21, 2004, reassuring the public at a publicized press briefing that antidepressants were proven "safe and effective" for youth.

The ACNHP pronouncement was in the form of an Executive Summary without any substantiating data. It was made available only through ACNP’s public relations firm, GYMR. Underscoring the commercial nature of the ACNP pronouncement at a publicized press briefing, GYMR notes:

"Our media events are successful because we have a nose for news. We know how to take the language of science and medicine and transform it into the more understandable language of health. We advise clients of the best dissemination strategy for their news and make sure that the message they deliver is compelling, documented and contributes to other national dialogues in a real and meaningful way."

In addition to Dr. Leon, Dr. David Shaffer, also of the ACNP Task Force was an invited FDA presenter.

Below is an excerpt from FDA’s advisory committee meeting transcript:


p. 17

17            In addition, FDA would also like to note

18 that one member of the Psychopharmacologic Drugs

19 Advisory Committee, Andrew Leon, and an FDA

20 speaker, David Shaffer, were members of the

21 American College of Neuropsychopharmacology ACMP

22 Task Force that has recently issued a preliminary

23 report on SSRIs and suicidal behavior in youth.

24 This task force reviewed published and

25 unpublished data from controlled trials in youth,

p. 18

1 data from epidemiological studies, and data from

2 autopsy studies.

3 Based on their preliminary review, they

4 concluded that the available evidence does not

5 suggest that SSRIs increase the risk of suicidal

6 behavior in youth and with depression, however,

7 they acknowledge that their conclusions are

8 preliminary and they recommend that the pertinent

9 data available to pharmaceutical companies and FDA

10 be rapidly made available to ACMP and others, so

11 that they may be independently evaluated.

12 In the event that the discussions involve

13 any other products or firms not already on the

14 agenda for which FDA participants have a financial

15 interest, the participants’ involvement and their

16 exclusion will be noted for the record.

17 With respect to all other participants, we

18 ask in the interest of fairness that they address

19 any current or previous financial involvement with

20 any firm whose product they may wish to comment

21 upon.

Contact: Vera Hassner Sharav

November 15, 2004


Center for Science and the Public Interest

The Food and Drug Administration advisory committee that met last September to consider approving AstraZeneca’s new anti-clotting drug Exanta had two major issues on its agenda. Did it work and did the occasional case of liver poisoning make Exanta unsafe?

A key expert sitting on that panel was Dr. Paul Watkins, a liver toxicity expert at the University of North Carolina. He took part in the discussion, but could not vote. The FDA limited his role because he sits on the advisory boards of two competing firms, one of which paid him more than $50,000 a year, according to a transcript of the meeting posted on the FDA website.

Watkins was not alone. Of the 14 members holding the fate of Exanta in their collective hands that day (the FDA almost always follows the advice of its advisory committees), ten disclosed relevant conflicts of interest at the meeting. None of the other nine were denied a vote.

They ranged from chairman Dr. Jeffrey Borer, who serves on the steering committee of a competitor, to University of Minnesota heart specialist Dr. Alan Hirsch, who listed eight corporate consulting and speaking relationships, several of which were with AstraZeneca’s competitors. "That was about the longest conflict of interest statement I can remember," joked Borer, whose day job is at the Weill Medical College of Cornell University.

The Watkins case is the most significant, however, because it highlights inconsistencies in how the FDA evaluates conflicts of interest and bias among the scientists sitting on its dozens of advisory panels. Industry critics are being held to a higher standard than physician-scientists who frequently consult for industry.

Last week, the agency bounced Dr. Curt Furberg of Wake Forest University from a meeting that will take place next February to evaluate whether all Cox-2 pain relievers cause the same heart problems that forced Merck to withdraw Vioxx from the market. Furberg, a well regarded drug safety expert and a frequent industry critic, had been quoted in the New York Times a day earlier suggesting his analysis of Pfizer’s Bextra trials showed it may cause the same heart problems as Vioxx.

The FDA’s acting chief for drug evaluation, Sandra Kweder, in ordering his removal claiming Furberg’s comment indicated he was "biased." Adding insult to injury, she invited Furberg to present his evidence to the committee, but precluded him from taking part in the discussion.

The agency’s treatment of Furberg stands in stark contrast to its treatment of Watkins only two months earlier. Watkins has a long history of bringing an industry-oriented bias to FDA proceedings.

Watkins is typical of many of the physician-scientists who sit on FDA committees. When he sits on a committee, he has his numerous conflicts of interest waived. And whether he’s sitting on the committee or appearing before it as an expert witness, he brings a distinct point of view to the committee’s deliberations.

In March 1999, for instance, Watkins, then at the University of Michigan, appeared before an FDA advisory panel as an expert witness to argue that the liver toxicities associated with the diabetes drug Rezulin were rare and usually associated with other conditions. One of the two patients who died in clinical trials drank 12 beers a day, he pointed out. "It’s reasonable to assume that both patients probably had underlying liver disease that reduced their ability to survive the drug related injury," he said.

The client sponsoring his appearance before the committee was the drug’s manufacturer, Warner-Lambert. A year and over 60 deaths later, the FDA pulled the drug from the market.

Watkins stuck to his theme of individual susceptibility during the September meeting considering AstraZeneca’s anti-clotting drug Exanta, whose generic name is ximelagatran. Claiming that 13 of 16 drugs withdrawn by the FDA in recent years for safety problems involved potentially predictable susceptibilities, Watkins told his fellow committee members that the liver problems that popped up in the ximelagatran trials "suggest to me a genetic component.

"I would applaud any efforts the company would do either retrospectively or prospectively to get genomic DNA to help us get some of the answers to these questions," he said. At the end of the day, the committee ­ its voting members, that is ­ elected to send the drug back for more data after concluding its toxicities outweighed its benefits.

Meanwhile, the FDA’s action in Furberg’s case went beyond the requirements of the law. The Federal Advisory Committee Act prohibits scientists with conflicts of interest from serving on the more than 200 science advisory committees sprinkled across the federal government. The law does allow agencies to waive those conflicts when a scientist’s expertise is needed to fill out the committee. That exemption is routinely invoked by the FDA.

There is nothing in the law, however, that prohibits "biased" scientists from serving on advisory committees. It only requires that scientists who have strong points of view be balanced by someone reflecting an alternative perspective.

"FACA requires that federal advisory committees be fairly balanced in terms of the points of view and the functions to be performed, and the courts have interpreted this requirement as providing agencies with broad discretion in balancing their committees," the Government Accountability Office wrote in a report last April. "It is important that committees are perceived as balanced in order for their advice to be credible and effective."

Ironically, Furberg and Watkins have served on an FDA advisory panel together. In 2002, both men played important roles on a committee evaluating whether unintentional overdoses of some over-the-counter pain killers like acetaminophen cause liver problems. At the outset of the meeting, its chairman waived a reading of all the participants’ conflicts of interest. "Because general topics impact so many institutions, it is not prudent to recite all potential conflicts of interest as they apply to each participant," Louis Cantilena, chairman of the nonprescription drugs advisory committee, said.

Indeed, the law covering conflicts of interest is much less strict when it is applied to advisory committees that are discussing broad issues rather than individual companies’ products. But that technicality seems to have been overlooked in the Furberg case.

The FDA’s drug safety committee that meets in February will be evaluating the safety of all Cox-2s, not just Vioxx or Bextra, which was the subject of Furberg’s most recent study. A close reading of Furberg’s comments in the original Times story indicates he was only referring to one drug ­ not the entire class. "Basically, we showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information," Furberg was quoted as saying after reporting his study’s results to an American Heart Association meeting in New Orleans.

Furberg sounded a conciliatory note after Kweder announced his removal. He wouldn’t object "if it’s the same rule they apply to others.”

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