The New York Times
February 19, 2005
Yesterday's action by a panel of experts advising the Food and Drug Administration made it abundantly clear that the value of a widely used class of painkillers remains mired in confusion. Even after months of controversy, experts are sharply divided over the safety of some of the cox-2 inhibitors and uncertain about how these newer drugs compare in effectiveness and safety with many older painkillers.
The panel of 32 experts agreed unanimously that the two cox-2 drugs still being sold in the United States - Celebrex and Bextra, both made by Pfizer - and Vioxx, a cox-2 drug that was recently pulled from the market by Merck, all raise the risk of heart attack or stroke in some patients. That puts the lie to assertions that Vioxx was uniquely dangerous and makes it clear that all drugs in the class pose at least some cardiovascular risk.
But the panelists apparently considered the risks relatively small or at least tolerable. By an overwhelming vote of 31 to 1, the panel recommended that Celebrex, the most widely sold drug in the class, remain on the market. The only disagreement was over how strong the warning label should be, and whether Pfizer should be forced to continue its voluntary cessation of advertising directed at consumers.
The panel issued a much closer verdict on Bextra - 17 experts judged it fit for marketing, 13 disapproved, and 2 abstained - mostly because the smattering of data on Bextra suggests that it is riskier than Celebrex.
Then, in a surprising squeaker of a vote that galvanized the stock markets, the panel decided, 17 to 15, that Vioxx could be revived. Merck had already suggested that it might seek to reintroduce that medication, given the evidence that all drugs in the class pose some cardiovascular risk, not just Vioxx. Now a bare majority of the panel has agreed, even though many felt that Vioxx looked substantially riskier than the other two drugs.
That judgment may prove less valuable to Merck in the marketplace than in the courtroom. Plaintiffs who seek to prove that Merck was irresponsible in keeping Vioxx on the market after signals of danger emerged will now have to confront the fact that 17 expert advisers think it is safe enough to put back in circulation.
The underlying problem with these drugs is that they have been heavily promoted and thus prescribed promiscuously to patients who did not need to take them. The presumed advantage of the cox-2 drugs is that they may provide the same pain relief as older painkillers like ibuprofen without causing the gastrointestinal bleeding and ulcers that occur in a minority of patients taking the older remedies. Although there are doubts that the drugs actually do cut the rate of bleeding and ulcers (only Vioxx has shown that ability to the F.D.A.'s satisfaction), the panelists clearly felt that they benefit some patients, if for no other reason than that different patients respond well to different drugs. Some experts also complained that there was too little safety information available on the alternative painkillers.
In making its final decision on the cox-2 class, the F.D.A. ought to ensure that the drugs are aimed only at the patients most likely to benefit and least likely to be harmed, and are taken in doses and for durations that limit the unavoidable risk. For the long run, the agency needs to find better ways to assess the safety of drugs once they are on the market.
An F.D.A. plan to mine the databases of Medicare and other government or private health plans would be a good start. But the agency also needs the power and resources to sponsor, or compel the drug industry to sponsor, needed studies. There would be less confusion on the cox-2 dilemma if the risks and benefits of all the relevant drugs were more securely understood.