Drug tests: too speedy - or safe enough?

Prescription drugs pulled from the market. Drug ads voluntarily yanked from TV and print. "Black box" warning labels placed on some medicines, and safety doubts raised about others.

As Americans try to figure out how suspect drugs got into their medicine cabinets - and who is to blame - two startling facts are coming to the fore: 1) The consumption of all medications involves some risk and 2) The bar for establishing their safety is set much lower than many people think. Furthermore, some experts say, these risks are almost impossible to avoid.

"People need to understand that all drugs by definition are poisons and need to be used appropriately and selectively where you anticipate the benefit to exceed the risk," says Steven Weisman, a pharmacologist at Innovative Science Solutions in Morristown, N.J., and a consultant to drug companies conducting clinical trials.

The seeds of the current crisis were planted more than a decade ago when Congress, under public pressure, directed the federal Food and Drug Administration (FDA) to make speedy approval of new drugs, rather than safety testing, its priority.

"It's a common misperception that the FDA approves drugs that are safe and effective," says Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development, a nonprofit research group affiliated with Tufts University in Boston. "The FDA actually approves drugs where the expected benefits outweigh the expected risks of that drug. It's always a risk-benefit analysis."

In the 1970s and '80s, the FDA had an "overly cautious approach to drug approval," in the view of Dr. Kaitin. Research by his center at Tufts showed the United States trailed behind other countries in developing new drugs, a so-called "drug lag."

The AIDS epidemic of the late '80s helped stir public thought to demand rapid drug development, he says, and Congress responded by giving the FDA new latitude to speed up the process, including fast-track approvals.

Today no new epidemic is causing a widespread public outcry so the pendulum has swung back toward safety concerns, Kaitin says.

"You can't have it both ways," says Mr. Weisman. That means choosing between a long approval process or bringing valuable new drugs quickly to the market, he adds.

Responding to criticism, acting FDA commissioner Lester Crawford asked the respected Institute of Medicine (IOM) in November to report back with recommendations on how the FDA could better detect dangerous side effects of drugs both before and after they reach the market.

But even before the IOM can report, Congress may take action. Sen. Charles Grassley (R) of Iowa, chairman of the Senate Finance Committee, held hearings this fall on dangers of certain drugs and plans to continue them in the new session. He also plans to introduce bills that would create an independent office of drug safety and require drug companies to register the results of all their clinical trials in a public database. Last week the British Medical Journal printed an article alleging that Eli Lilly and Co. knew that its antidepressant drug Prozac had "troubling side effects" as early as the 1980s and failed to publish the information. A group of editors of leading medical journals has said their publications will no longer accept articles about drugs unless all of their clinical trials have been publicly published.

Critics of the safety of the drug-approval system are advocating these and other reforms, including a ban or at least tougher limits on direct-to-consumer advertising.

But even they agree that it would be difficult to change the current system of clinical trials to ensure that every drug that reaches the marketplace is absolutely safe and has no dangerous side effects.

Even Phase III clinical trials, which usually involve several hundred to 3,000 volunteer subjects, are unlikely to reveal every adverse effect. That's because they still don't represent the vast differences among potential users. People may be taking combinations of other drugs that will react unfavorably, or have differences of age, gender, race, or even genetic ability to absorb drugs that the trials simply won't reveal. They also may take the drug in an incorrect dosage or for a longer period of time than is recommended.

Page: 1 | 2