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# Surrogate Marker Treatment Effects Can Vary: Study
- URL: https://www.fdaweb.com/surrogate-marker-treatment-effects-can-vary-study/
- Published: 2018-03-21T12:00:00.000Z
- Updated: 2026-09-14T23:54:24.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5141038

Treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease are often larger than the treatment effects observed among post-approval trials using surrogate markers as trial endpoints, specifically for non-continuous surrogate markers, according to a [study](https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1023-9?ref=fdaweb.com) published online in *BMC Medicine*. Yale University researchers say that new proposals for increased reliance on smaller and shorter trials with surrogate markers carry the risk of demonstrating larger, and potentially exaggerated, treatment effects, which may ultimately lack reproducibility or generalizability.

“Policymakers, doctors, and patients should interpret treatment effects based on surrogate markers of disease as primary endpoints with caution, and in the absence of clinical outcomes, regulators and payers should focus on those surrogate markers that have been validated,” the researchers say.

The study found that the treatment effects based on non-continuous surrogate markers in pivotal trials are larger than, and may overestimate, the treatment effects based on the exact same non-continuous surrogate markers when used in post-approval trials. It also found that many post-approval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection.