Surrogate endpoint

A surrogate endpoint is a measurement used in place of how a patient feels, functions or survives, on the assumption that moving it will move those things too. The US Food and Drug Administration defines it as a clinical trial endpoint used as a substitute for a direct measure of exactly those three things.

Almost every result in longevity research is a surrogate. Nobody has waited out a human lifespan to see whether a compound extends it, so trials measure something faster instead: a blood marker, an inflammation score, an estimate of biological age. The finding is then reported as progress towards living longer, and the substitution is rarely spelled out.

The regulator itself grades these measurements, and the grade is a statement about evidence. A validated surrogate endpoint is supported by a clear mechanistic rationale and by clinical data giving strong evidence that an effect on it predicts a specific benefit. A reasonably likely surrogate endpoint has the mechanistic or epidemiological rationale, but not enough clinical data to show that it predicts anything. Both are used in drug development; only one has been demonstrated to stand in for the thing it replaces.

The practical question to ask of a longevity claim is which of the two is in play, and the answer is usually the second. That does not make the research worthless. It makes the distance between the measurement and the promise worth stating, which is the part most coverage leaves out.