Regulatory Focus™ > News Articles > Researchers Question Consistency of FDA’s Use of Surrogate Endpoints for Drug Approvals

Researchers Question Consistency of FDA’s Use of Surrogate Endpoints for Drug Approvals

Posted 30 November 2015 | By Zachary Brennan 

Researchers Question Consistency of FDA’s Use of Surrogate Endpoints for Drug Approvals

The US Food and Drug Administration (FDA) is not consistent with its use of surrogate endpoints in assessing the risks and benefits of treatments for some diseases, making it difficult to assess the treatments' actual clinical effects on outcomes important to patients, according to researchers from Johns Hopkins.

The researchers came to this conclusion after evaluating 58 FDA drugs approved between 2003 and 2012 for chronic obstructive pulmonary disease (COPD), Type 1 and 2 diabetes, glaucoma and osteoporosis, all of which commonly use surrogate endpoints in clinical trials.

Of the four diseases, the researchers found that most drugs for COPD (7/9, 78%), diabetes (26/26, 100%) and glaucoma (9/9, 100%) were approved based on surrogates while for osteoporosis, most drugs (10/14, 71%) were also approved for patient-centered outcomes (ie. survival, function, symptoms and health-related quality of life).

“If the use of surrogate outcomes is needed, assessing the validity of surrogate outcomes and considering the surrogate's usage in the treatment and population under study is necessary to inform a drug evaluation,” the researchers advise, noting the study demonstrates the agency still relies heavily on surrogates.

Surrogate Discussion

FDA’s rationale for using surrogates was discussed in 11 of the 43 (26%) drug approvals based on surrogates, but the agency’s lack of a consistent approach “makes it difficult to assess and interpret their actual clinical effects on outcomes important to patients,” the researchers say.

In addition, if FDA’s rationale was discussed, drug approvals for diabetes were more likely than others to contain a discussion of evidence demonstrating that treatment effects on surrogate outcomes predict effects on patient-centered outcomes, though the researchers conceded that not documenting the rationale for the use of a surrogate in an approval does not mean FDA didn’t have a rationale.

The researchers also seek to make clear that in order to formally validate a surrogate outcome, “it is necessary to have evidence from RCTs [randomized controlled trials] assessing whether the treatment effect on surrogates consistently predicts the treatment effect on patient-centered outcomes.”

And these Johns Hopkins researchers aren’t the first to question FDA’s use of surrogates in approvals. Last month, two doctors from the National Cancer Institute and Knight Cancer Center also raised questions about FDA’s use of surrogates in the approval of new oncology drugs.

“For evaluating new drugs, patient-centered outcomes should be chosen whenever possible. If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study,” the Hopkins researchers say.

BMJ Open


Categories: Regulatory News

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