US FDA standards demand that surrogate end points used in clinical trials be “reasonably likely to predict” survival for accelerated approval, or be established proxies for survival for traditional approval. However, surrogate end points used to support most new cancer drug approvals in the United States frequently lack formal study.1
“In cancer clinical trials, surrogate end points, such as tumor shrinkage or slowed tumor growth, may be used as proxies for outcomes that matter to patients, living longer or better, in order to gain earlier approval of new drugs,” said Vinay Prasad, MD, MPH, a hematologist at Oregon Health & Sciences University, Portland, Oregon, and lead author of this study.
Researchers examined 55 drugs granted FDA-approval on the basis of surrogate end points between January 2009 and December 2014. Of these drugs, 25 received provisional, accelerated approval, and 30 drugs received full, traditional approval.
This study could not find any formal analyses assessing the strength of the surrogate-survival correlation for 14 drugs (56%) granted accelerated approval or for 11 drugs (37%) granted traditional approval.
Among the drugs granted accelerated approval, a level 1 analysis (the most robust analysis) was performed on 4 drugs. A level 1 analysis was performed on 15 drugs granted traditional approval, only 3 of which found a strong correlation.
“The present study suggests that the use of surrogate end points for drug approval often lacks formal empirical verification,” said Prasad.
Prasad recognized that the FDA could have used unpublished studies to justify the use of surrogates.
“If so, I would urge the FDA to publish these studies to allow independent researchers to judge their work,” Prasad suggested.
“If the surrogates are valid that would be great news. But, if there are limitations to the analyses, it would benefit patients to know.”
The FDA previously published such analyses. The FDA approval process needs to find a balance between speed of approval and safety of drugs to best serve patients with cancer.
1. Kim C, Prasad V. Strength of validation for surrogate end points used in the US Food and Drug Administration’s approval of oncology drugs [published online May 10, 2016]. Mayo Clin Proc. doi:10.1016/j.mayocp.2016.02.012.