Free Advice for the FDA

As safe as aspirin is safe enough

Headlines have been screaming recently about dangerous drugs and supplements being pulled off the market by the U.S. Food and Drug Administration. Last year the FDA banned the dietary supplement ephedra, which millions of Americans took to control their weight and boost their energy. Ephedra is derived from a Chinese herb, Ma Huang, that has been used for centuries. This year, the FDA asked Pfizer to stop selling the prescription pain reliever Bextra. Bextra belongs to a class of painkillers called COX-2 inhibitors which are supposed to be gentler on the stomachs of patients. COX-2 inhibitors are particularly popular with people who suffer from the chronic pain of arthritis.

FDA regulators justified their actions on the grounds that the overall risk versus benefit profile for these remedies is unfavorable and thus they are not safe enough for consumers to take. Activists claimed that ephedra use was responsible for 155 deaths between 1993 and 2003. During that time some 12 to 17 million Americans ingested 3 billion doses of ephedra. Before the FDA ordered Bextra off the market, the pharmaceutical company Merck voluntarily withdrew its COX-2 inhibitor, Vioxx, last September. The claim is that Vioxx might be responsible for between 28,000 and 55,000 heart attack deaths since the FDA approved it in 1999. The FDA has now also required "black box" warnings on non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil), naproxen (Aleve), and ketoprofen (Orudis). Black box warnings are the strongest form of required labeling, alerting consumers that all NSAIDs may increase the risk of cardiovascular disease.

In April, a federal judge in Utah overturned the FDA's ban on ephedra, agreeing with supplement maker Nutriceuticals that the FDA had failed to meet the scientific burden of proof that ephedra is unsafe. >

Meanwhile, our solons on Capitol Hill have not been idle. Senators Charles Grassley (R-IA) and Christopher Dodd (D-CT) have just introduced legislation that would create a new Center for Postmarket Drug Evaluation and Research at the FDA. The new center would have the power to withdraw approval of a drug, require labeling changes, restrict distribution and require physician and consumer education. Currently, the center that approves new drugs must negotiate recalls or labeling changes with the drug companies. The center could also require manufacturers to conduct post-market clinical studies if there are questions about safety of a drug once it's on the market.

And dietary supplements may also come under increased FDA scrutiny. In 1994, Senator Orrin Hatch (R-UT) was instrumental in passining the Dietary Supplement Health and Education Act, which essentially exempted supplements from FDA drug approval regulations. Now Senators Hatch and Richard Durbin (D-IL) evidently plan to propose legislation that would establish some form of post market monitoring of dietary supplements. The draft bill would require that adverse events be reported by "a manufacturer, packer, distributor, or retailer the name of which appears on such labeling of the dietary supplement or non-prescription drug." The FDA would scrutinize supplement adverse event reports and have the power to request more detailed information from supplement makers and sellers.

So if the FDA is about to subject popular medications to heightened postmarket scrutiny, what's the point at which the agency should decide to jerk them off the market? The day that Bextra was pulled from the market, Dr. Joshua Prager from the California Pain Medicine Center at UCLA was asked by National Public Radio anchor Michelle Norris if he'd advise patients currently taking Bextra to switch to aspirin. Dr. Prager responded, "Well, the first thing I would say about aspirin is if aspirin went through the FDA scrutiny that all these other drugs go through now in trying to come to market in the year 2005, it probably would not get FDA approved."

I know that the number of people who are estimated to die from gastrointestinal bleeding as a result of taking NSAIDS and aspirin range from 3,500 to 16,500 per year. Even the analgesic alternative acetaminophen (Tylenol) kills 450 people per year through liver toxicity. But consider that tens of millions of Americans take these medicines every week and manage to survive. (In surveys, 17 percent report taking aspirin the previous week, 17 percent ibuprofen, and 23 percent acetaminophen.)

Of course, drug and supplement manufacturers and the FDA should warn people of any previously unknown dangers that become manifest over time. But since aspirin was patented by Bayer in 1899, more than 1 trillion tablets have gulped down and today the world gobbles 50 billion tablets annually. The point is not that aspirin is absolutely "safe." No medicines are. But aspirin is safe enough. The history of aspirin's use shows that patients and physicians can learn to manage the risks posed by medications that have similar benefit-risk profiles. Given my aspirin safety standard, the FDA certainly overreacted when it banned ephedra. Even Vioxx's risk profile is not obviously worse than that of current widely available NSAIDs.

Would we be better off had the FDA been around to ban aspirin back in 1899? Clearly not. Thus my simple solution to the allegedly complex problem of drug safety—if a remedy is as safe as aspirin, it should stay on the market.