What is a 'safe' drug?
One of the most vivid lessons I learned in medical school came from an otherwise dry course in pharmacology. Our professor sobered a class of eager 20-somethings just aching to have prescription pads in their hands with his opening pronouncement: "Drugs are dangerous." If there's any lesson for the public in the current firestorm surrounding the recalled anti-inflammatory drug Vioxx, it should be that. Whether it's the century-old aspirin or the recently disgraced Vioxx--designed as a safer form of aspirin--all drugs come with unwanted and often unexpected side effects.
Vioxx did what it was designed to do. It blocks COX-2, an enzyme made when cells are injured, which triggers pain and inflammation. Vioxx ignores the always present COX-1 enzyme, which protects the lining of the stomach and intestines from being eaten alive by corrosive gastric acids. The selective COX-2 drugs--others include Celebrex and Bextra--are an advance over anti-inflammatories like aspirin, ibuprofen, or naproxen, which interfere with both the protective and the inflammatory enzymes, thus causing GI problems in at least 20 percent of chronic users. That means ulcers for some, but for over 16,000 arthritis sufferers each year, it means death from GI hemorrhage or intestinal perforation.
But gut protection carries risk, too. Some but not all studies of Vioxx show a small increase in heart attack and stroke after months of continual use. That may be acceptable for those facing debilitating arthritis but not for the millions of people who pop these pills frequently for minor aches and pains. This led Merck to abruptly pull its drug from the market. Overnight, Vioxx fell from glory to infamy.
Should Merck have instead worked with the Food and Drug Administration to strengthen the existing cardiovascular warnings and restrict the drug to those who have flunked other agents because of GI problems? That's a judgment call, the kind of informed call the FDA makes every day for the public, as do doctors for their individual patients. And the conundrum is that those judgments are not always obvious--and can change as new evidence accumulates.
Unfortunately, the public theater of Vioxx's demise omits such messy details. Within moments of the recall, media stories rushed to sing good riddance to a "bad drug," tort lawyers set out in hot pursuit of the injured "class," and critics assailed the drug maker for greed and deception and the FDA for lack of vigilance. Wall Street analysts wrapped the entire COX-2 drug class in black crepe. Would that it were this simple.
Nanoscalpels. Medicine is tough stuff. And it's made tougher because the public sees medicines as benign interventions, when in fact they are nanoequivalents of scalpels perturbing the mysterious and unique chemistry that makes up each person. Factors like age, sex, smoking, underlying illness, other drugs onboard, and genes influence the risk-benefit calculus. When we can identify the risk group, the drug becomes safer for everyone outside it. But that takes time. Birth control pills were found to cause a small but measurable increase in stroke and heart attacks; eventually it became clear that the risk was seen overwhelmingly in women who smoke. Such women should not use these pills, but that doesn't mean other women shouldn't.
I predict that the COX-2 inhibitors will survive. They are too important a tool to be dumped from the medicine chest. In addition to their pain-relieving capabilities, they show great promise in preventing and treating a wide array of deadly tumors, including those of the colon, lung, pancreas, stomach, brain, and breast. There's reason for this: To take hold and spread, some cancer cells have learned how to hijack the body's inflammatory pathways by producing overactive COX-2 genes. The COX-2 inhibitors offer a unique and targeted weapon against this banditry. Celebrex has already been approved for the prevention of colon cancer. Remember thalidomide? Once a notorious drug because it caused birth defects, it is now a lifesaver for those with certain cancers, like multiple myeloma.
Vioxx is no demon drug. And the FDA does not turn a blind eye to danger. Were safety the only measure, the agency's job would be easy--and our medicine chests would be empty. As we watch the Vioxx fallout, we should be wary of a scalping party that could leave us so safe we are not safe at all.
This story appears in the December 13, 2004 print edition of U.S. News & World Report.