A Consumer Advocate at the FDA

February saw an unprecedented three-day FDA advisory committee meeting of outside experts called to consider the fate of the blockbuster arthritis drugs, Vioxx, Celebrex and Bextra. Vioxx was suddenly withdrawn by its maker Merck last September because it was found to increase the risk of heart attack and stroke. Although similar concerns about Celebrex and Bextra were confirmed in studies published early in 2005, their maker, Pfizer, decided not to withdraw the drugs.

Despite the growing evidence of life-threatening adverse reactions, a majority of the combined Arthritis Drug and Drug Safety and Risk Management Advisory Committees (I am a member of the latter) advised the FDA that all three brands were safe enough to remain on the market. Perhaps the most unexpected outcome was the committee’s vote (17 to 15) for the return of Vioxx. The group voted to keep Bextra on the market by almost as slim a margin. But Celebrex received a resounding 31 votes in favor of continued availability. I cast the lone vote against that drug remaining on the market.

My vote against Celebrex (as well as Bextra and Vioxx) was based on my conclusion from the available evidence that the increased risk of heart attack and stroke was probably a class effect* – meaning that any drug whose action is similar to Vioxx was likely to present similar risks. This was confirmed, by the way, in our discussions by many of my fellow panel members. I thought the committee’s vote bordered on the irrational given the general agreement that serious cardiovascular risks could be expected with all three drugs.

The committee members were obviously impressed by the emotional power of the patient anecdotes– more than 40 patients testified that one or another of the three drugs were the only treatment that brought relief. And, the rheumatologists on the committee for the most part argued (using anecdotal experience as well) that these drugs should remain available because they worked in some patients when all else failed. But, in fact, there is no scientific evidence that Vioxx, Celebrex or Bextra are any more effective in relieving pain than the older drugs taken for arthritis pain.

Perhaps more ominous than the fact that the anecdotes apparently trumped science in the voting, was the revelation after the meeting that a third of the advisory committee members had troubling conflicts of interest. This raised the specter that financial ties to industry, especially Merck and Pfizer, might have influenced the committee’s votes on Bextra and Vioxx.

Prior to the meeting, the newly appointed Secretary of Health & Human Services, Michael Leavitt , and the FDA Commissioner-nominee, Dr. Lester Crawford, assured the public that the agency would be more transparent in the future. Yet the FDA knowingly included scientists and physicians with direct conflicts of interest in the February advisory committee process. And, adding insult to injury, the FDA chose to forgo publically identifying the conflicted committee members. Normally the agency presents a conflict of interest statement at the start of each advisory committee session which identifies conflicted members. The statement also specifies the nature of their conflict, including the dollars involved, and declares whether the member has been granted a waiver to participate or has been recused . For this meeting, the agency inexplicably concluded that, because the discussion was not about a drug approval, such transparency was unnecessary.

Congress continues to draft legislation to deal with FDA’s shortcomings. What is needed is real reform – not marginal changes that are more scenic than substantive. The Center for Medical Consumers, working with other national consumer and patient advocacy organizations, is trying to make sure that whatever legislation is passed will meaningfully improve the ability of the FDA to protect the public from harm. To be effective, Congress must provide more money and grant more legal authority for the FDA to monitor and enforce drug safety. Congress should also insist that the agency’s decision-making be completely transparent to the public it serves.

* Older arthritis drugs, such as ibuprofen and naproxen, are not included in this class because they have a somewhat different action.

Arthur A. Levin, MPH, Center for Medical Consumers ©, April 2005.