FDA May Not Be Following Procedure for Surrogate Endpoints

Many drugs approved from 2009 to 2014 did not have formal analyses of the surrogate-survival correlation.

Findings from a recent study suggest that surrogate endpoints supporting the approval of new cancer drugs are often missing formal study.

According to a study published in Mayo Clinic Proceedings, these findings call into question whether the FDA is adhering to standards that surrogates are “reasonably likely to predict” or “established” to be used in grant approvals.

"In cancer clinical trials, surrogate endpoints, 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 lead author Vinay Prasad, MD, MPH.

Researchers examined 55 drugs that gained FDA approval due to a surrogate endpoint between January 2009 and December 2014. There were 25 drugs that received accelerated approval and 30 that received traditional approval.

According to the FDA, surrogates for accelerated approval have to be “reasonably likely to predict” an increased lifespan. Surrogates for traditional approval have to be “established.”

The researchers, however, were unable to find formal analyses of the surrogate-survival correlation for 56% of the drugs that received accelerated approval and 37% of drugs that received traditional approval, according to the study.

The most extensive analysis, a level 1 analysis, was done on just 4 drugs that received accelerated approval. Only 15 drugs that received traditional approval were granted this type of analysis, but a strong link was found in just 3 of the drugs.

"The present study suggests that the use of surrogate endpoints for drug approval often lacks formal empirical verification," Dr. Prasad said.

Researchers said that there may be unpublished studies that support these surrogates.

"If so, I would urge the FDA to publish these studies to allow independent researchers to judge their work," Dr Prasad concluded. "If the surrogates are valid that would be great news. But, if there are limitations to the analyses, it would benefit patients to know."