Drugs approved by the Food and Drug Administration just before their deadlines were much more likely to have later safety problems than medications approved at other times, a study by Harvard scientists revealed.

Daniel Carpenter, Ph.D., of the Harvard University Department of Government and colleagues reported in the March 27 issue of the New England Journal of Medicine that, from 1993 to 2004, drugs approved in the final two months of the review period allowed under the Prescription Drug User Free Act were far more likely to be withdrawn for safety reasons than drugs approved at other times.

The study identified the date of approval for all new drugs approved since 1993 relative to their PDUFA review deadlines. Of these, 100 were approved within the two months before the deadline, and 218 were approved at other times. Seven of the 100 drugs approved just before the deadline were subsequently withdrawn, versus four of 216 approvals at all other times. Moreover, ten of the late approvals were later slapped with a black-box warning, compared with four of the other approvals. And 18 of the late-approved drugs later had a dosage form discontinued, versus 8.8% of the other approvals.

“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,” Dr. Carpenter said in his study.

He also offered some examples of drugs approved close to deadline whose problems drew regulators’ attention after they were on the market. These drugs include Baycol, a cholesterol drug that Bayer voluntarily withdrew after 31 deaths, Vioxx, a pain reliever ordered off the shelves after a clinical trial showed triple the rate of heart deaths, and Rezulin, a diabetes drug that was withdrawn from the UK market for toxic effects on the liver.

Dr. Carpenter suggested that the problem might not lie with the deadlines themselves, but rather with the FDA’s resources for conducting speedy reviews.

On the other hand, Dr. Janet Woodcock, director of the FDA Center for Drug Evaluation and Research denied Dr. Carpenter’s findings saying: “FDA won’t approve a drug if we are not ready. The timeframes established by PDUFA are guidelines, and we have the flexibility to miss a PDUFA date if we’re not certain about the safety of a drug and want more time to review it. And we have the option of denying approval altogether if there is any question about safety,” the Boston Globe reports.

The Robert Wood Johnson Foundation, the National Science Foundation, and Harvard University funded the Dr. Carpenter’s study.