Surrogate endpoint

The appeal is practical. Waiting years to measure mortality or disease recurrence is slow and costly, whereas a biomarker can be read in weeks or months. Regulators sometimes grant approval on surrogates for this reason. The danger is that a surrogate is only valid if changing it reliably changes the true outcome, and many do not clear that bar.

History is littered with cautionary tales. Antiarrhythmic drugs suppressed the surrogate of irregular heartbeats yet increased deaths, and some cancer therapies improve progression-free survival without extending life. A valid surrogate must lie on the causal pathway and capture the treatment's full effect on the real outcome, a demanding condition rarely proven.

When reviewing a study built on a surrogate, ask whether the surrogate has been validated against hard outcomes for this intervention and population, and whether the authors overstate patient benefit that only the true endpoint could establish.