USA – Researchers Call on FDA to Rethink Guidance Allowing Use of Surrogate Outcomes

The US Food and Drug Administration (FDA) needs to reconsider its use of surrogate outcomes in some guidance documents on developing treatments for infectious diseases, researchers from Harvard and George Washington University School of Medicine wrote in a review published Tuesday in JAMA Internal Medicine.

The review evaluated 22 FDA guidance documents, which included recommendations for pivotal clinical trials in 27 disease indications. For six indications (22%), only direct clinical outcomes were specified as primary endpoints, while for the other 21 indications, guidance documents recommended surrogate outcomes as sole primary endpoints or as part of composite primary endpoints.

“None of the recommendations for the use of surrogate measures matched the regulatory and scientific conditions favoring indirect outcomes in place of clinical outcomes,” they wrote.

While the researchers noted that surrogate outcomes can be appropriate as primary endpoints in anti-infective clinical trials (e.g. “the biomarker of HIV viral load has been shown to be a valid surrogate outcome in a chronic life-threatening disease predicting risk of clinical progression or death”), the researchers stressed that surrogates should only be used as primary endpoints in the correct setting (e.g., chronic, life-threatening disease) and when there is strong evidence that the effects on the surrogate are informative for clinical outcomes…