Surrogate Endpoints: When Shortcuts Mislead

Surrogate endpoints like bone density, PVC suppression, or HDL changes promise faster, smaller trials. Sometimes they work, as with LDL and blood pressure.

Sometimes they kill, as CAST showed with encainide and flecainide. The lesson is that surrogates must be validated against real outcomes, death, stroke, function, before driving treatment decisions.

Many expensive drug failures trace back to unvalidated surrogates..