What does FDA approval really mean?

Patients and staff expect social workers to be able to field questions about pretty much any patient concern. With the recent highly publicized withdrawal of several popular drugs from the market, questions about drug safety are on the minds of many. What exactly does it mean when a drug wins Food and Drug Administration approval? Isn't it supposed to mean that the medication is absolutely safe? That the FDA knows all of its possible side effects? That it's better than older drugs on the market? The answers are: No, no and no. That doesn't mean that an FDA approval is worthless, consumer advocates say. But patients also shouldn't take it as an unconditional endorsement.

For one, the FDA's approval of a new drug doesn't necessarily mean that the drug is superior to drugs already on the market for the same condition, said Larry Sasich of the watchdog group Public Citizen. Many new drugs are never studied in head-to-head competition with older products to see if they're safer or more effective, Sasich said. Instead, drugs are often compared with a placebo in clinical trials.

But are they at least safe? The FDA would be the first to say that drugs are approved based on incomplete knowledge. Drugs are approved based on several rounds of clinical trials, but those trials may not uncover all risks. Clinical trials usually include no more than a few thousand people taking the drug for a limited period of time. The ultimate test comes when the drug is released to the market to be used for longer periods. "For any approved therapy, new and unexpected adverse events may occur that were not seen in clinical trials,'' the FDA said in a (recent) statement.

Dr. Jerry Avorn, a Harvard Medical School professor and author of the book "Powerful Medicines: the Benefits, Risks and Costs of Prescription Drugs" said some side effects only appear in patients with health conditions not represented in the trial group. Other adverse symptoms take years to develop. And some drugs cause damage only when used in combination with other medicines.

In addition, drug approval is an act of deciding whether the curative powers of a medicine are valuable enough to justify exposing a specific class of patients to the possible side effects. A drug with fairly severe side effects might be considered safe enough for patients with life-threatening conditions like cancer. But such risks would be unacceptable for a drug to treat the flu, for example.

Of greater concern in the eyes of critics like Avorn is the FDA's system for detecting serious new risks that surface after a drug is approved, and its record for getting the products off the market or beefing up their warning labels. Millions of patients continued to rely on the agency's approval of the three painkillers after evidence surfaced in 2000 that the drugs could boost the risk of heart attacks and strokes. The FDA didn't require definitive studies to nail down the extent of those risks, and discouraged its experts from speaking publicly about the danger. An FDA advisory panel recently found that all three drugs increase cardiovascular dangers, but concluded that the risks might be acceptable for a limited group of patients who don't have good treatment alternatives. In the middle of the controversy, the FDA asked for an outside evaluation of its drug surveillance program and undertook some safety reforms. Earlier this month, the agency told Congress it wants the power to strengthen drug warning labels unilaterally, without the need to negotiate with manufacturers.

According to Dr. Randall Stafford, an associate professor at Stanford University School of Medicine, "All these instances point to a need to be more conservative about new drugs,'' Stafford said. But physicians often follow exactly the opposite prescribing pattern, Stafford said. Pharmaceutical firms heavily promote new drugs to achieve the widest possible usage in a short period after their introduction to the market. "The drug industry has tended to focus on a strategy of developing blockbuster drugs,'' Stafford said. "It (the new drug) has to be used in ways that are beyond the boundaries of who we might want to use it -- where the drug is most useful and cost-effective.'' Harvard's Avorn is one of the doctors who believes in waiting a year or more before prescribing a newly approved drug, unless it offers breakthrough benefits for a serious condition. "It's particularly tragic when somebody has a potentially lethal side effect for a drug that was no better than other drugs around for years,'' Avorn said.

- Adapted from “HARD SELL: How Marketing Drives the Pharmaceutical Industry; What FDA approval means; Agency weighs benefits, risks before drugs get to market”, by Bernadette Tansey, San Francisco Chronicle, March 3, 2005.

03/2005