Surrogate Endpoint
A laboratory measurement or physical sign used as a substitute for a direct clinical outcome when the true outcome would take too long to measure. HbA1c is a validated surrogate for long-term diabetes complications. Regulatory agencies may grant accelerated approval based on surrogate endpoints.
Technical Context
Surrogate endpoint validation requires demonstrating that the surrogate lies on the causal pathway of the disease, that changes in the surrogate reliably predict changes in the clinical outcome, and that treatment effects on the surrogate predict treatment effects on the outcome. HbA1c is a validated surrogate for diabetes complications based on decades of outcome data (DCCT, UKPDS trials). Body weight change as a surrogate for cardiovascular outcomes is becoming better validated (SELECT trial provided evidence that weight loss with semaglutide reduces cardiovascular events). The FDA's accelerated approval pathway allows approval based on surrogate endpoints reasonably likely to predict benefit, with confirmatory trials required post-approval.