FDA has low efficacy threshold for approving cancer medicines


Background: Bevacizumab, for breast cancer, was fast tracked due to the findings of a single, small randomized controlled trial. 3 years later it was withdrawn by the FDA due to insufficient evidence showing an overall survival (OS) benefit of the drug in larger trials. Moreover, there have been discussions about making the fast track/accelerated approval process more demanding.

In light of this, the authors investigate whether the approval process has become more demanding by analysing drug approvals from 2002-2012. The study examines end points accepted by the FDA for regular and accelerated approval.

Findings: Between 2002 and 2012 the FDA granted approval to 65 oncology products for 127 indications. 64% of regular approvals were based on endpoints other than OS. For 16% difference in OS was reported to be not statistically significant.

While the majority of confirmatory trials for products granted accelerated approval have not yet been completed, 18 of the 42 indications granted accelerated approval between 2002 and 2012 have been converted to regular approval. As a percentage of approvals per year, OS indications have not increased. In 2010, 80% of regular approvals were based on OS; in 2011 and 2012, OS indications were reduced to 40% and 38%, respectively.


“We also found that extension of OS, while still considered the gold standard by the FDA, is by no means required for approval in oncology.”

“Our research shows that recent criticism of the FDA’s regulatory policy in oncology has been overstated. Approval trends over the past decade reveal that the agency has widely accepted the use of intermediate endpoints in the place of overall survival, consistently granted accelerated approvals, and, despite its outspoken resistance to single-arm trials in refractory populations, continued to grant accelerated approval to late-line therapies.”


Use of Multiple Endpoints and Approval Paths Depicts a Decade of FDA Oncology Drug Approvals, Michael B. Shea, Samantha A. Roberts, Jessica C. Walrath, et al.

Clin Cancer Res 2013;19:3722-3731. Published Online First May 10, 2013.




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