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Merck, the FDA, and Vioxx

The October 7 online issue of the New England Journal of Medicine ($$) includes two accounts of Merck's September 30, 2004 decision to withdraw the anti-inflammatory drug Vioxx from the market.

As the articles describe, Vioxx was the largest prescription-drug withdrawal in history. More than 80 million patients had taken the drug, many to treat symptoms of arthritis, and sales were in excess of $2.5 billion. Merck spent more than $100 million per year in direct-to-consumer advertising for Vioxx.

Vioxx was so commercially successful because it had a lower incidence of gastrointestinal complications (such as stomach ulcers) when compared with other anti-inflammatory drugs. But almost immediately after the drug had been approved by the FDA, studies began to suggest that Vioxx might pose an increased risk of cardiovascular complications such as heart attacks and strokes.

The data from these studies were inconclusive. It was only after the results of another study designed to assess the drug's effect on colonic polyps conclusively demonstrated that Vioxx increases the risk of potentially fatal cardiovascular events that Merck decided to stop selling the drug.

The Vioxx story leaves both Merck and the FDA smelling bad:

  • The FDA knew for years that Vioxx might increase the risks of cardiovascular events, but it (a) never required any studies to investigate this specific possibility, and (b) never required Merck to stop advertising the drug directly to the public. Thus, the FDA largely failed in its duties to protect the public health.
  • Merck knew that Vioxx might increase the risk of stroke and heart attacks, but instead of conducting a study that might have decided the issue, it chose to aggressively market the most favorable explanation of several plausible ones for the increased cardiovascular risks that other studies were suggesting. More to the point, Merck chose willful blindness.

    There's been some discussion elsewhere about the possibility that by suing Merck over Vioxx, overzealous trial lawyers will lead the FDA and the drug companies to become too hesitant to put beneficial new drugs on the market (see Nick Genes, Chris Rangel, Trent McBride). This should be a real worry. When the FDA abdicates its responsibility to the public, and the drug companies bury their heads in the sand to protect their sales numbers, trial lawyers pursuing their own self-interests can sometimes lead to "reforms" that aren't in the public's best interest, either.

    Nevertheless, we shouldn't confine our criticisms to trial lawyers (this applies to the "malpractice crisis" as well). Instead, we ought to be asking whether specific regulatory reforms might prevent another Vioxx episode in the future:

  • Should drug companies continue to be allowed to advertise directly to the public? Would it be wise to prohibit drug companies from using superficial TV ads to induce demand for an arthritis treatment that might increase the risk for fatal complications? Might it be better to require that drug companies promote their drugs in ways that allow more communication of the possible tradeoffs that the use of the drug entails?
  • Should we demand that the FDA be more proactive when reasonable suspicions arise that a drug like Vioxx might cause excess deaths from severe complications? Merck withdrew Vioxx on the fortuitous results of a trial that was not designed to assess the cardiovascular risks of the drug. If that trial had never been done, the question about cardiovascular risk might not have been answered for years. Merck was certainly not asking the question; it was aggressively spinning suggestive data in its favor instead. No one else had any obvious incentives to ask the question. Except, of course, for the public, whose representatives in the FDA were asleep at the wheel (see Kevin, M.D. for more on the FDA).

    See Matthew Holt and Donald E. L. Johnson for discussions about the overall state of the pharmaceutical industry following the withdrawal of Vioxx.