Unsafe at Any Dose?

My apologies to Ralph Nader for knocking off the famous title of his book on car safety, but I wanted something bold to catch your eye even if I transformed an uncompromising assertion into a tentative question. Drug safety is a topic of overriding importance and something that all healthcare providers must consider in their work. Ever since Hippocrates said to “do no harm,” safety has been up front in physicians’ minds.

In the yin–yang of medical treatment, safety is on the opposite side of efficacy. Just as advances in the treatment and prevention of musculoskeletal disease should excite us, their potential for harm should frighten us. We should worry that danger lurks and that agents that produce startling results in diseases like rheumatoid arthritis will exact a price in toxicity. That price may not be here today, but it could be here tomorrow.

Are we watching closely to ensure that the benefits of the drugs we prescribe outweigh the risks?

Ralph Nader is a smart, clever man, and he made product safety a national focus. He could act as a scold and an outsider, but he has a prophet’s charisma. He does not smile much nor crack jokes but, then again, prophets are not famous for their easy way or sense of humor. Whatever he lacks in charm, Nader gets the job done.

The poster child for Nader was the Corvair, a popular Chevrolet that had a profitable run in the 1960s. The Corvair had a rear engine and a complicated suspension that required different inflation pressures for the front and rear tires. Unless the tires were filled with air just right, the Corvair was subject to “tuck under,” whatever that is. (Sorry, Wikipedia failed me on this one.)

The need to keep more than a 10-psi difference in the front and rear tires was hidden in the owner’s manual and the “tucking under” effect caused accidents. In addition to sounding the alarm on the Corvair, Nader unmasked other car problems such as chrome dashboards whose glare in the sun blinded drivers and engines that spewed noxious fumes. The outcome of Nader’s exposés was to increase safety regulations from Congress and spur industry to build safety into their vehicles.

Safety a Challenge for Drugs, Too

My title is obviously exaggerated (this is a magazine after all), and cars are not drugs. Furthermore, unlike new car models, new drugs undergo long and elaborate testing in animals as well as people. Monitoring by the Food and Drug Administration (FDA) is rigorous and should root out the bad apples that develop in industry’s orchards. Even if phase 3 testing looks good, postmarketing surveillance programs can keep a bright light shining on the thousands of products that comprise today’s medicine chest.