FDA under fire over accelerated approval data demands

Robert Califf
Ex-FDA commissioner Robert Califf defended the FDA's accelerated approvals.

Researchers have raised concerns about the level of evidence needed to win accelerated approval from the FDA. Regulators stand accused of waving through drugs on the basis of slight data and then failing to ensure confirmatory postapproval trials validate the decision.

The study, details of which were published in the Journal of the American Medical Association, looked at the 22 drugs that won accelerated approvals in 24 indications between 2009 and 2013. About two-thirds of the trials that generated data to support these approvals lacked control arms, reflecting the FDA’s then-emerging willingness to greenlight cancer drugs on the basis of single-arm studies. 

Most of the drug labels noted the limitations of the data. And the FDA asked for 38 postapproval studies to confirm the efficacy, long-term outcomes and safety and pharmacokinetics of the drugs. As of April of this year, about 80% of these studies were either on track or already completed. The others were either running a year or more behind schedule or had been canceled altogether.

This is a cause for concern among the authors of the study.

“We have found numerous situations in which required confirmatory studies with rigorous designs and outcomes are not pursued or are not completed in a timely fashion, and in these cases, we are concerned that regulators appear to accept data that would not otherwise meet FDA standards,” Huseyin Naci, Ph.D., one of the authors of the paper, told Reuters.

The paper was published alongside an editorial by Robert Califf, M.D., whose short stint as the head of the FDA covered part of the period in which the fast-tracked drugs were supposed to be going through confirmatory studies. Califf thinks the paper raises “issues that merit deeper study and discussion within the FDA and in the clinical and payer ecosystems affected by the agency’s standards.” But he also defended the FDA and the accelerated approval pathway.

“In general, the current approach is acclaimed by those with the most at stake—patients and their families,” he wrote.

Those patients and their families have helped swing the pendulum away from caution and toward faster approvals based on less conclusive evidence. And, unless a safety scandal drives it back the other way, it is currently hard to see the FDA reversing course and facing down the backlash that would likely follow.