Analysis of decades of drug approvals by a Harvard Research team, published in the March 27th New England Journal of Medicine, provides the first scientific evidence of what many have come to suspect. Congress-mandated deadlines that control the FDA review of new medications may have “spurred a dangerous rush to judgment.”
Looking at drugs that have been recalled (taken off the market) ie: Vioxx, Bextra, Rezulin, Baycol and others, Harvard researchers found a disturbing pattern: Medicines approved right on deadline by the Food and Drug Administration are more likely to cause safety problems than those cleared with more time to spare.
The study has generated calls to reexamine the balance between speed and safety. “The article is a wake-up call,” said Dr. Steven Nissen, the Cleveland Clinic’s influential cardiology chief who helped sound the alarm on the risks of some of those ultimately doomed drugs.
“It puts the FDA in a very difficult situation when they’re trying to make complex decisions under these very, very tight deadlines,” he added. “We’ve got to reevaluate now whether that’s good public policy.”
Deadlines were first imposed on the FDA by a 1992 law that allowed drug makers to pay millions of dollars in fees directly to the cash-strapped agency so it could hire more reviewers and clear a backlog of pending drug applications.
In return, the FDA had to make a decision – either approve or reject – on 90% of all drug candidates within 12-months of their application, or lose money. The deadline was 6 months for drugs so novel or potentially lifesaving to be classified high-priority.
Congress tightened the deadline for most drugs to 10 months in 1997.
Amid concern about risky drugs, Harvard professor, Daniel Carpenter, took a closer look at the impact. First, he found approval is 3.4-times as likely in the two months leading up to the user-fee deadline as at any other time.
Drugs approved in that just-before-deadline period had a four- to fivefold higher rate of being withdrawn or requiring serious safety warnings, compared with drugs approved faster – presumably slam-dunks – or those that miss the deadline, Carpenter concluded.
The FDA argued the findings weren’t accurate, rushing out its own statistics that showed somewhat more withdrawals among drugs approved just before the deadline but not enough to be statistically significant.
“FDA won’t approve a drug if we are not ready,” said agency chief Dr. Janet Woodcock. “And we have the option of denying approval altogether if there is any question about safety.”
But the Harvard researchers in turn rechecked their statistics, which had passed review by the medical journal, and said they were standing by the findings.
Sources: Associated Press
New England Journal of Medicine 03/27/08
