Celebrex lessons

THE MORE the public learns about the harmful side effects of many arthritis painkillers, the more evident it is that drug companies knew about these problems early on and did nothing to protect their customers from them. The latest revelation about an early warning of heart problems linked to Pfizer's Celebrex strengthens the case for reforming the process of approving drugs and monitoring them once they are on the market.

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Celebrex is in a family of painkillers called cox-2 inhibitors that were developed in the 1990s to relieve joint pain without causing gastrointestinal pain or bleeding. Scientists have long been concerned that they might also cause heart attacks and strokes in longterm users.

Evidence of this side effect in one cox-2 inhibitor, Vioxx, led Merck to pull the drug off the market last fall. In December, the National Cancer Institute halted a study using Celebrex when data showed high doses of the drug were linked to 3.4 times greater risk of cardiovascular problems. Now it turns out that Pfizer had done a study five years ago that also showed a link between Celebrex and heart problems, but did not follow up on it.

Pfizer has said the study was flawed, because the sample group taking the drug happened to have more health problems than the sample taking the placebo. That might be so, but Pfizer should still have interpreted the study as a warning sign, and started a bigger, more carefully organized trial to determine if Celebrex did cause heart problems.

The Food and Drug Administration also was lax. Pfizer says it provided the 1999 study to the agency in June 2001, which should have prompted the FDA to require more tests.

But the FDA's underfunded office for monitoring the safety of drugs once they are on the market did not take that step.

Taken together, the regulatory failures surrounding both Vioxx and Celebrex make a strong argument for changes in the approval process. Drugs like these that are not lifesaving and will be taken for chronic conditions should be subjected to longer preapproval testing to show they are safe over the long term. Drug makers should be required to reveal publicly all studies on new drugs as soon as they are done, and the FDA should police drug ads more aggressively. Finally, the office that monitors drug safety on the market should be better-funded. The office should have enough autonomy that its staff is not influenced by FDA decision-makers who give the initial green light to new drugs. Without changes of this kind, more drugs with harmful side effects will find their way into Americans' medicine cabinets.