Editorial: The Incompetence Of The FDA

As a journalist and editor who’s covered the cardiovascular arena for more than 25 years I’ve tried as much as possible to avoid taking positions on the major controvesies that have appeared over the years. I’m proud that during the “TPA wars” I remained on good terms with not only Eric Topol, Rob Califf and Eugene Braunwald, but Peter Sleight, Charlie Hennekens, and Gianni Tognoni. More recently, as we’ve been engulfed by the Vioxx, Vytorin, and COURAGE controversies, among others, I’ve been pleased to maintain good working relationships with all the mainstream protagonists.

I have no intention of breaking this tradition over prasugrel. The players in this drama are all far smarter about this kind of stuff than I could ever hope to be, and the subtle statistical and clinical issues are extremely difficult to evaluate and assess. But there is one aspect of the prasugrel story that I do feel competent to comment upon.

The FDA handling of this hearing was breathtakingly incompetent. Let me explain:

As first reported here previously, less than 48 hours before the advisory committee hearing new member Sanjay Kaul was “uninvited” from the meeting. Now I’m no expert on the criteria for serving on FDA advisory committees, and it’s possible that Kaul’s previous statements represented a legitimate reason for excluding him, but there is absolutely no reason for this to have been done immediately prior to the meeting. It’s not like Kaul was hiding anything. Any reasonable exercise of due diligence– just google “Kaul and prasugrel” and you’ll see what I mean– would have revealed his outspoken position. Since Kaul was removed so close to the meeting, and after publication of the roster, FDA officials need to publicly apologize to Kaul and to provide a full explanation for the reasons for his dismissal, and in fact provide an account for the entire sequence of events leading to this last minute debacle.

It’s also not clear what constitutes “intellectual conflict of interest.” But even if there were general agreement that Kaul’s previous positions disqualified him to vote, wouldn’t the committee have benefited from his expertise as a nonvoting member? Other outspoken experts have criticized the FDA hearing for having the atmosphere of an auto financing party at a “family picnic.” At the very least, inclusion of someone like Kaul in the proceedings would have allowed the FDA to escape the charge of cronyism and disregard for dissent.

I’m also surprised that there has been little public discussion about the FDA briefing document, which contained apparently redacted content that was easily recovered in the PDF document originally posted on the FDA website. One important point here: some of the redacted content in the document, which appeared to contain information that might have identified patients in clinical trials, or genuine trade secrets, was fully scrubbed from the PDF document and was not recoverable. The recoverable content was more “political” in nature, and appeared to represent a last minute, incompetently executed attempt by top managers at the FDA to stifle opposing views. This pathetic effort to create a sense of unity appears to be typical of the type of managerial problems that have beset the FDA in recent years.

I can’t say for sure whether the prasugrel hearing is a demonstration of intellectual dishonesty or corruption. But I think I can say for sure that it is certainly a clear demonstration of incompetence.


  1. The FDA seems to be about politics, not science. That seems to me to be more and more true, the more I read about their activities.

    Politics has no place in this process. Let the scientific chips fall where they may. That does not mean a complete abandonment of common sense when looking at treatments for patients.

  2. Greg Gilbert says

    From the different reports I have read, it seems to be the publics opinion that the FDA does what it wants and NOT what is best for the American public.

    Take, for example, the Provenge story. On March 29, 2007, the Advisory Committee voted 17-0 for its safety and 13-4 for efficiency. Two out of the four ‘no’ votes were from doctors with strong conflicts of interest. (Can you believe a doctor who vote with their wallet instead of their sworn duty to extend lives?) Even with this strong vote, the FDA issued a ‘Complete Response Letter’ to Dendreon on May 8, 2007. Provenge would have helped over 50,000 men with PCa had the FDA done their job and approved this new therapy. Incompetent, no. Conflicted, YES.

    The American people need new leadership at the FDA if we are to approve new drugs that extend lives without the horrible side effects of chemo.

  3. In the matter of Dendreon’s Provenge, on May 9, 2007, the FDA denied approval for Provenge, a promising, safe, and effective treatment for men with androgen independent prostate cancer (AIPC); this is the very, very late stage of the disease. This denial came despite a March 29, 2007, recommendation of the FDA’s own Advisory Committee (AC) that Provenge be approved. That panel comprised 17 members who are recognized experts in the field. They voted 17-0 that Provenge is safe and 13-4 that it demonstrates substantial evidence of efficacy, the Congressionally mandated FDA standard.

    Events during and following the AC meeting were, to say the least, bizarre. The AC’s members represented two competing organizations within the FDA: the Center for Drug Evaluation and Research (CDER, which includes the FDA’s Office of Oncologic Drugs (OOD) and the Center for Biologics Evaluation and Research (CBER). The latter was selected to take the lead on the review of Provenge, something that was bitterly contested by OOD head Dr. Richard Pazdur. Two members of the AC represented CDER; Howard I. Scher, M.D., and Maha Hussain, M.D. Both were outspoken critics of Provenge at the AC meeting – some even have said that they dominated the AC meeting – and based on comments received in real time from several observers in the audience, they continually badgered and intimidated other members of the committee. Regrettably, though both had requested and received conflict of interest (COI) waivers, neither probably would have been allowed to vote, much less participate, under new draft guidelines now being considered by the FDA. (Dr. Scher, for example, is on Novacea’s scientific advisory board as lead investigator of the Asentar Phase III clinical trial in the same stage of prostate cancer as Provenge. He is also lead investigator on a clinical trial investigating the chemotherapy drug Taxotere in early-stage prostate cancer – a trial some in the prostate cancer community believe would be adversely affected by Provenge approval. How he ever was able to participate in the first place is puzzling.)

    In the days that followed the AC, two members of the AC – Drs. Scher and Hussain – and a third practitioner, Dr. Thomas Fleming (who is often chosen by Dr. Pazdur to participate in OOD-sponsored advisory committees but did not participate in this AC) wrote letters, ostensibly to the FDA, protesting the AC’s recommendation to approve Provenge. All three of these letters were “leaked” to The Cancer Letter, a newsletter about oncology drug approvals that also played a key role in the Erbutix scandal. Dr. Scher has told colleagues he did not volunteer to write the letter but was asked. Additionally, substantial portions of it were written by other people. The leak and subsequent publication of the three letters was seen within the medical community as an aggressive “public relations” campaign intended to sink the approval of Provenge, despite the very favorable safety and efficacy votes of the AC. We know now, of course, that the FDA delayed the approval of Provenge by issuing a Complete Response letter, which effectively delays approval for 1-2 years. During this time, 30,000—60,000 men will die of prostate cancer, many of whom might otherwise have benefited from Provenge, which even the FDA’s own advisory committed found safe and effective.

  4. Thanks for writing this article. Having seen the FDA’s handling of Dendreon’s Provenge, this story about Kaul doesn’t surprise me at all. The FDA is corrupt….and incompetent.

  5. Thanks for the kind words, everyone, but I would respectfully request that all non-cardiology related discussions be moved elsewhere. I have enough trouble trying to keep track of what’s going on in cardiology without having to worry about oncology too!

    Larry Husten (CardioBrief)

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    right here, really like what you’re saying and the way in which you are saying it. You make it entertaining and you still take care of to stay it smart. I can’t wait
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  1. […] meeting (click to see our initial story that first reported his absence and our subsequent editorial about some serious questions raised by the advisory committee meeting), an FDA spokesperson has provided an explanation for Kaul’s […]

  2. […] to develop between government and industry. One only has to look to the FDA’s recent challenges at separating themselves from industry influence to see the potential for […]

  3. […] removed without explanation from the prasugrel (Efient, Lilly) advisory panel (as recounted here, here, here, and here), provoking considerable controversy and two congressional […]

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