The withdrawal last week of the painkiller Vioxx was a bombshell, taking a huge bite out of the stock price of the pharmaceutical giant Merck & Co. Inc.

Aside from the obvious reminder that investing in the stock market can be perilous, consumers, physicians and regulators can take many lessons from the largest prescription-drug withdrawal in history.

A new drug is not necessarily a better drug. When cox-2 inhibitors, the class of drugs to which Vioxx belongs, were first approved in early 1999, they were touted as a "super Aspirin." There was a widespread assumption that cox-2 inhibitors worked better than over-the-counter medications. That is not true. Ibuprofen (sold as Advil, Motrin) and naproxene work as well as expensive cox-2 inhibitors, though they may have different side effects.

All drugs have side effects. The big selling point of cox-2 inhibitors, like Vioxx and its competitor Celebrex, is that they are less likely to cause gastric bleeding. But the study that showed these wondrous results turned out to be questionable: Researchers published results only from their first six months of data because the data at the one-year mark were less positive. While gastric bleeding is less likely with cox-2 inhibitors, this risk has to be balanced against another, greater danger -- an increased risk of heart disease.

Beware of hype. Vioxx and its main competitor, Celebrex, are among the most heavily advertised drugs ever. The marketing was brilliant, the wooing of physicians masterful, and the media did more than their share of early swooning. Doctors who relied purely on the marketing bumph and not research failed their patients.

Pay attention to new research. A study published in the New England Journal of Medicine in 2000 showed a clear association between taking Vioxx and an increased risk of heart disease. Subsequent research confirmed the association. Yet, the company did not act until a fourth study, which was meant to determine if Vioxx could prevent colon cancer, found an increased risk of heart attack and stroke.

The first media reports questioning the merits of cox-2 inhibitors appeared as far back as 1999. So the information was out there.

Doctors should prescribe with caution. Cox-2 inhibitors such as Vioxx should be prescribed to people with chronic pain only if they have ulcers or other digestive-tract problems, a condition that applies to only about 10 per cent of arthritis patients. But the drugs have been prescribed indiscriminately, for various conditions for which they have not been tested.

Clinical trial results are not the final word. Vioxx was initially approved on the basis of a study of 8,076 patients who took the drug for up to 13 months. But that research focused on reduced gastric bleeding among those on the drug, and did not look at heart disease. History and common sense tell us that as more people take a drug in real-life circumstances, and for longer periods of time, side effects become more clear.

Regulators need to be more far-sighted. Approving a drug for sale should be the beginning of the regulatory process, not the end. As evidence mounted about the cardiovascular risks of Vioxx, Health Canada sat on its hands; it requested only a small change to the label to tell users of the risks. One in five Canadians over the age of 65 takes a cox-2 inhibitor. They need better assurances that the drugs they are taking are safe.

Absence of evidence is not evidence of safety. It's troubling to hear stories of many physicians switching their patients to two other cox-2 inhibitors, Celebrex and Mobicox, in the wake of the Vioxx withdrawal. It's not known if these drugs also raise the risk of heart problems, because the research has not been done. If we want safe, effective drugs we need to invest more in independent research, and in monitoring.

Don't be wooed by numbers. The Vioxx example reminds us that drugs that are very expensive and provide only a marginal benefit can be deemed "successful." Bear in mind that, to be approved, most new drugs need only provide more benefit than a placebo -- in other words, that they are better than nothing. The profitability and popularity of a drug should not be confused with its clinical importance. In fact, they are often inversely related.

The success of Vioxx was a triumph of marketing over science: It racked up more than $2.5-billion (U.S.) annually in sales before science took the upper hand once more. It remains to be seen if we have learned our lesson, or if we will be seduced again when the next "newer" and "better" drug comes along.

apicard@globeandmail.ca