Feature Archive

How Safe Are America's Medicines?

No. 1 of WebMD's Top 10 Stories of 2004: A series of drug removals and warnings opened up a floodgate of questions over the safety of drugs. What have we learned, and what can we expect in the future?

By Daniel DeNoon
WebMD Feature

Reviewed By Michael Smith

Are medicines safe for us and for our children? Americans once thought so. Now we aren't so sure.

It's been a shaky year for our faith in U.S. drug safety:

  • Heart safety questions led to the withdrawal of the arthritis drug Vioxx.
  • Vioxx's sister drugs Celebrex and Bextra are reported to have heart safety concerns. (In April 2005 the FDA asked that Bextra be pulled from the market because of heart, stomach and skin risks).
  • The FDA releases heart warnings about the over-the-counter pain reliever Aleve. (In April 2005 the FDA asked makers of over-the-counter anti-inflammatory drugs to revise their labels to include more specific information about the potential of ulcer, heart, and stroke risks.
  • Antidepressant drugs now carry a new "black-box" warning about suicide risk.
  • The ADHD drug Strattera is associated with -- in a very small number of patients -- serious liver damage.
  • A maverick FDA drug reviewer told Congress that several drugs now on the market may not be safe. He acknowledged he did not speak for the FDA, which finds the drugs safe when used properly. The drugs (Crestor, Bextra, Meridia, Accutane, and Serevent) remain on the market.
  • A three-year-old study of the FDA's drug review process surfaced late this year. It shows that nearly one in five FDA reviewers felt pressured to approve a drug, and that two out of three FDA reviewers lack confidence in how the FDA monitors the safety of a drug once it is approved. The report, from the Health and Human Service's inspector general's office, concludes that "these findings present a significant warning signal."

Is our drug-safety system broken? Exactly what does it mean for a drug to be "safe?" How can you find out whether medicines put you or your family at risk? WebMD takes a look at these questions.

What's a "Safe" Drug?

No drug on earth is totally risk free. Every time you take a medication, you take a risk.

So what's a safe drug? Balance, says William Comanor, PhD. Comanor is director of the UCLA program on pharmaceutical economics and policy and is professor of health services at UCLA and professor of economics at the University of California, Santa Barbara.

"Drug safety means finding the right balance," Comanor tells WebMD. "There is no other answer, unless you want to be an advocate or a politician."

By balance, Comanor means weighing a drug's risk against a drug's benefit. That's exactly how the FDA defines drug safety.

"The FDA's determination that a product is safe ... does not suggest an absence of risk," FDA spokeswoman Laura Alvey tells WebMD. "Rather, a product is considered to be safe if the clinical significance and probability of its beneficial effects outweigh the likelihood and medical importance of its harmful or undesirable effects. In other words, a product is considered safe if it has an appropriate benefit-risk balance for the intended population and use."

Large benefits make a large risk acceptable, says Marcia Angell, MD, for two decades the editor of The New England Journal of Medicine and now senior lecturer at Harvard University.

"When treating cancer we take all kinds of risk, because the benefits are so great," Angell tells WebMD. "Drug safety ought to be some relationship between benefit and risk. You ought to be able to take a risk that is commensurate with the benefit you get."

Note Angell's use of the word "ought." Drugs with very small benefits, she says, aren't worth any risk at all. Yet such drugs get approved as safe.

"If we are looking at drugs like Vioxx and Celebrex, neither should have been approved because they don't offer anything over pain relievers already sold over the counter," Angell says. "You don't want to accept any risk if there's no benefit over existing treatments."

But not everyone agrees with that stance. Safety concerns are exactly why arthritis specialist Stephen M. Lindsey, MD, says some patients truly need Cox-2 drugs such as Celebrex. (In April 2005, the FDA asked that Celebrex carry new warnings about the potential risk of heart attacks and strokes as well as potential stomach ulcer bleeding risks.) Lindsey heads the rheumatology department at the Ochsner Clinic Foundation in Baton Rouge, La.

"I don't think we should be telling people to stop taking Cox-2 drugs," Lindsey told WebMD in response to the news that Celebrex was linked to heart attacks and strokes. "There is a high risk of bleeding ulcers and death with traditional arthritis drugs. We forget that 17,000 people die each year with ulcers due to arthritis drugs. So if somebody has a high risk of a bleeding ulcer and has arthritis, they are safer on Celebrex -- unless they have serious heart disease, then all bets are off."