FDA accelerated drug reviews need fixing

Sep 29, 2015

The FDA’s accelerated drug reviews skip some important research methods – they typically do not use trials with active comparators or clinical outcome measures, according to two new studies.

FDA’s accelerated drug reviews skip some important research methods – they typically do not use trials with active comparators or clinical outcome measures, according to two new studies.

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Published in the September 23, issue of BMJ, the first study was led by Aaron Kesselheim, MD, with Harvard's T.H. Chan School of Public Health. The second study was also led by Kesselheim and Bo Wang, PharmD, a Harvard medical student and pharmacist.

FDA’s fast-track reviews have increased around 3% annually since 1987. However, the researchers noted, the trend was driven mainly by applications involving drugs that were not first-in-class and/or were for expanded indications of already approved products (supplemental NDAs).

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"Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative," Dr Kesselheim wrote in the first study.

Given the increased likelihood of post-approval changes in the prescribing information for the expedited approval drugs, “regulators may want to ensure that the provisional nature of these drugs is well communicated to patients and physicians,” Dr Kesselheim wrote. “Currently, only drugs approved through accelerated approval have this information integrated into their official labels.”

In addition, FDA may want to consider new guidance on advertising practices to ensure that all advertisements prominently feature the limited nature of the data supporting agents approved through these pathways, Dr Kesselheim wrote.

In the first study, the researchers noted that FDA approved 774 drugs since 1987, and priority review was the most common approval process at 43%. Accelerated approvals were the least common at 9%.

The second study examined the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs’ originally approved indications.

Thirty percent of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% of modified use approvals and 11% of approvals expanding the patient population, almost all of which related to pediatric patients.

“Although we do not conclude that any of these approvals were mistaken, pediatric patients have unique physiologies and pharmacokinetic characteristics that may require more rigorous trials to confirm both the efficacy and the safety of drugs previously approved only for use in adults,” Dr Kesselheim wrote.

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