FDA deadlines may compromise drug safety by rushing approval

Some observers have suggested that these deadlines lead to the rushed approval of medications, a theory Carpenter tested by examining data on the timing of FDA approvals dating back to 1950. He found that the enactment of PDUFA in 1992 appeared to introduce a temporal discontinuity into FDA review cycles, with disproportionate approvals coming in the two months immediately before deadlines. Compared to drugs approved at a more measured pace in the months following the deadline, those approved right before the review clock expired were far more likely to require later regulatory intervention.

“Drugs rushed to approval just before the deadline are two to three times more likely to eventually be pulled off shelves due to safety concerns, two to seven times more likely to receive added label warnings known as ‘black box revisions,’ twice as likely to experience changes in manufacture, and two to seven times more likely to be voluntarily discontinued by manufacturers due to weak clinical demand,” says Carpenter.

In previous work, Carpenter developed a mathematical model to understand how government agencies “learn” and how deadlines affect organizational behavior. This model predicts the pattern of outcomes described in the New England Journal study.

Fifty years ago, the FDA approved most new medications within a few months of receiving applications from manufacturers. Over time, the process slowed as new review protocols were added in the wake of pharmaceutical missteps such as thalidomide, which led to the births of thousands of deformed babies in the late 1950s and early 1960s.

“Because of similarly high-profile regulatory mistakes in recent years, we will likely see greater congressional scrutiny in coming decades as these FDA deadlines come up for renewal every five years,” Carpenter says. “While we are not arguing that these deadlines should be abandoned, our research indicates that mechanisms other than strict deadlines may better balance the need for expeditious yet rigorous drug approval.”

The research was funded by the Robert Wood Johnson Foundation, the National Science Foundation, and Harvard’s Center for American Political Studies and Institute for Quantitative Social Science.