Riskier Drugs Tied to Faster U.S. Approval, Industry Financing

By Gene Emery | March 27, 2008

The U.S. Food and Drug Administration has sped up the approval process for new drugs since pharmaceutical firms began to help finance it, which has increased the number of recalls and unanticipated side effects, researchers said Wednesday.

The FDA adopted a system in which drug firms help finance approvals by paying user fees in 1992, when approvals had lagged because of a lack of staff.

But critics fret that the new system made the FDA too dependent on pharmaceutical companies. Manufacturers now fund more than half of the drug review budget and staff, according to the study published in the New England Journal of Medicine.

The issue has come to the forefront because of some drugs that have recently been pulled from the market for safety concerns, such as Merck’s Vioxx and Pfizer’s Bextra.

Withdrawals of drugs from the market are 5.5 times more common, dire “black box” warnings of very serious side effects are 4.4 times more likely, and the chance that at least one strength of a drug would be discontinued was 3.3 times greater when drugs are approved just before the deadline set by the user fee system, the researchers said.

“Deadlines may offer a blunt tool with which to accelerate review. But in keeping with reports from FDA scientists, our findings suggest that deadlines may also cause drugs approved under these constraints to have a higher likelihood of unanticipated safety problems once they are in widespread use,” said a team led by Daniel Carpenter of Harvard University.

To assess the impact of the system, the researchers tracked the timing of drug approvals before and after the Prescription Drug User Fee Act (PDUFA), going back as far as 1950.

They found that after PDUFA, approvals tended to be clustered very close to the deadlines set by the act. “You see all this piling ahead of the deadlines, and you have the piling of error,” Carpenter said in a telephone interview.

“The rate at which drug approvals were followed by post-marketing safety problems was significantly higher for produced approved in the two months before the PDUFA deadlines than for drugs approved at all other times,” the researchers said.

Carpenter said the study needs to be seen from the perspective that “the FDA is pretty flexible already. If a drug is a cancer drug with good pretty data, or a drug for a life-threatening disease, they give it a priority rating and rocket it on through.”

“What you have to call into question is why Vioxx got a priority rating. Every time you give something a priority rating you’re taking scarce resources away from other drugs.”

(Editing by Patricia Zengerle)

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