Drugs approved in the US since 1992, when user fees were introduced to expedite their approvals, have a one in three chance of acquiring a black box warning or being withdrawn for safety reasons within 25 years of approval, says new research.
The study, which appears in the current issue of Health Affairs, examines all drugs approved by the US Food and Drug Administration (FDA) over a 35-year period, comparing warning and withdrawal rates for products released before and after 1992, when the Prescription Drug User Fee Act (PDUFA) took effect. Since PDUFA, which allows FDA to collect user fees from industry, the average approval time for all drugs has fallen from 34 months to 16 months.
Very few of the 32 drugs withdrawn for safety reasons during the 35 years had clearly unique benefits at the time of approval, but all had unique risks that eventually led to their withdrawal, say the researchers. They report that drugs released post-PDUFA were more likely to be withdrawn or have a black box warning, with 26.7% receiving such a warning compared to 21.2% of those undergoing the longer pre-PDUFA approval process.
Half of all black box warnings appeared after a drug had been on the market for 12 years, and safety withdrawals have occurred as late as 30 years after a drug’s initial release, they say.
“Our findings raise concern that the FDA is rushing its review of new drugs and allowing potentially unsafe medicines onto the market. As a primary care doctor, I’m wary of prescribing brand-new drugs unless they’re really a breakthrough, since their full risks are often unknown,” said senior author Karen Lasser, associate professor of medicine at Boston University School of Medicine.
“By the time many drugs receive serious side effect warnings, millions of Americans have already been exposed to their side effects, which can sometimes be fatal,” added lead author Cassie Frank, an instructor in medicine at Harvard Medical School.
FDA resources for reviewing drugs have increased dramatically since PDUFA, amounting to $760 million this fiscal year from pharmaceutical companies, or about two-thirds of its drug review budget, noted co-author Sidney Wolfe, founder of Public Citizen’s Health Research Group.
“Since PDUFA, the review times for the drugs that are eventually banned have decreased enormously. From an average prior to PDUFA of about three years from receipt of the drug application to FDA approval, the interval has dropped sharply to about one year,” he said.