Surrogate Endpoint

Definition

A surrogate endpoint is a clinical trial endpoint used as a substitute for a direct measure of how a person feels, functions, or survives. It does not measure the clinical benefit of primary interest directly, but is expected to predict that benefit based on biological, clinical, epidemiological, or therapeutic evidence. [1] [2]

Why It Matters in Ageing Research

Surrogate endpoints matter because many important ageing outcomes, such as disability, dementia, multimorbidity, or mortality, can take many years to observe directly. Ageing trials may therefore study shorter-term measures such as biomarkers, functional tests, disease-risk indicators, or composite outcomes, but these measures need strong validation before they can stand in for meaningful clinical benefit. [1] [3] [4]

Common Confusion

• A surrogate endpoint is not automatically valid just because it is correlated with ageing or disease risk.
• A biomarker can be used as a surrogate endpoint only when there is enough evidence that it predicts clinical benefit.
• Changing a surrogate endpoint does not always mean an intervention improves how people feel, function, or survive.

Related Reading

• Clinical Endpoint
• Composite Endpoint

References

1. FDA-NIH Biomarker Working Group. (2016). BEST (Biomarkers, EndpointS, and other Tools) Resource. https://www.ncbi.nlm.nih.gov/books/NBK326791/
2. U.S. Food and Drug Administration. (2018). Surrogate Endpoint Resources for Drug and Biologic Development. https://www.fda.gov/drugs/development-resources/surrogate-endpoint-resources-drug-and-biologic-development
3. Prentice, R. L. (1989). Surrogate endpoints in clinical trials: Definition and operational criteria. https://doi.org/10.1002/sim.4780080407
4. Moqri, M., Herzog, C., Poganik, J. R., et al. (2023). Biomarkers of aging for the identification and evaluation of longevity interventions. https://doi.org/10.1016/j.cell.2023.08.003