Analysis Suggests Additional Evidence Necessary for Surrogate Markers Used as Endpoints Used to Support FDA Drug Approvals
By Kelly Jordan
Clinical trials supporting the approval of drugs by the U.S. Food and Drug Administration (FDA) increasingly use surrogate markers, such as imaging findings or laboratory measures, as primary endpoints. Surrogate markers, which offer the advantage of reducing the duration and size of clinical trials, are expected to predict target clinical outcomes of interest that directly measure how people feel, function, or survive. In 2018, the FDA released an Adult Surrogate Endpoint Table of surrogate markers that may be used as primary endpoints in clinical trials that form the basis of FDA’s approval of drugs.
A recent investigation published in JAMA and led by Joshua Wallach, PhD, assistant professor of epidemiology, looked at the available research to support the use of 37 surrogate markers listed as potential primary endpoints in clinical trials for 32 chronic diseases (excluding cancer) in the FDA’s table. In particular, the authors conducted independent systematic reviews for each surrogate marker to identify meta-analyses of clinical trials quantifying the strength of association between the treatment effects measured using the relevant surrogate markers and any clinical outcome.
What They Found
The researchers’ analysis showed 22 of the 37 (59%) surrogate markers that may be used as endpoints in clinical trials to support FDA approval of drugs treating chronic diseases had no published meta-analyses examining the strength of their association with any clinical outcome. Furthermore, among those with at least one meta-analysis, few reported high-strength evidence of associations between the surrogates and target clinical outcomes.
“The development of the Adult Surrogate Endpoint Table was an important and necessary step for increasing the transparency around the surrogate markers that could be used to inform the approval of new drugs and biologics,” says Wallach. “However, our findings highlight the need for adding a summary of evidence supporting marker surrogacy for clinical benefit, or clarify when no studies are available.”
Why it Matters
These findings highlight the importance of making publicly available a summary of the evidence supporting surrogate endpoints that may be used to support FDA approval of drugs treating chronic disease.
“Ultimately, this can aid drug sponsors in choosing appropriate surrogate endpoints for trials and guide physicians and their patients in accurately interpreting the clinical benefit of drugs approved according to listed surrogate markers,” says Wallach.
