A sick agency in need of a cure?
Recall of a popular pain drug has focused attention on government drug regulation
Part of the problem is that drug companies pay "user fees" to make up a portion of the FDA's costs for reviewing and approving drugs. Indeed, user fees now pay the salaries of about half of the more than 1,400 doctors, pharmacists, chemists, and other scientific personnel who decide if a new drug is safe and effective, according to a government report issued last year. This measure, first passed in 1992, was intended to provide the FDA with greater resources to reduce the time needed to evaluate new drugs, and it has. Where a new drug approval commonly took 27 months in 1993, it took 14 months in 2001. Ten months is now the goal.
"There's not a problem with speeding up the approval process," says Bruce Psaty, a drug safety expert at the University of Washington. "It just requires an additional commitment to drug safety. And that hasn't happened. It's like building up one set of muscles and ignoring the other." As the approval time has become shorter, the number of recently approved drugs withdrawn from the market has grown threefold.
Psaty feels this is one of many signs that more resources need to go into post-marketing surveillance of drugs, which is now limited primarily to self-reporting by physicians and drug companies (box, Page 36). Psaty reviewed the FDA documents on both Vioxx and Baycol, an ill-fated cholesterol-lowering statin that caused cases of muscle injury, kidney failure, and death. "The medical reviewers for FDA raised the correct issues," he says. "But what happens to these issues after they are raised?"
No one seems to have an answer, including the reviewers themselves. In a survey released last year by the Department of Health and Human Services' inspector general, 66 percent of FDA medical reviewers said they were somewhat or not at all confident that the FDA adequately monitors the safety of drugs once they are on the market. The same report found that out of some 2,400 post-marketing studies reviewers had asked companies to conduct, only 882 had been done.
What's more, some 40 percent of reviewers interviewed said that the review process had gotten worse in terms of allowing time for in-depth, science-based reviews. About a fifth said the work environment did not allow for the expression of differing scientific opinions, and 18 percent said they had felt pressure to approve or recommend approval of drugs, despite reservations about safety or effectiveness.
Graham believes part of the problem is philosophical. The pressure to approve drugs comes from the agency's position that potential for harm must be proven beyond doubt. When Vioxx was approved, the FDA medical reviewer questioned the drug's potential for risky clotting but said the agency could not answer "with complete certainty" whether the drug would lead to cardiovascular events. This demand for "complete certainty" that a drug is unsafe "is the heart of the scientific problem at FDA," says Graham.
This attitude leads to the approval of questionable drugs, which according to Graham include: Accutane, a potent acne drug that can cause birth defects; Crestor, a statin that has been associated with the same muscle-wasting disorder as Baycol, as well as kidney failure; and Bextra, like Vioxx another painkiller in the Cox-2 inhibitor class, which may increase cardiovascular risks in some people.
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