Disadvantages of surrogate endpoints

Therapeutic interventions have multiple effects that often are not reflected by a single surrogate outcome.

In particular, the surrogate outcome may not measure drug safety. For example, patients given Flecainide following a heart attack were found to have their ventricular ectopics suppressed. However, this did not lead to the expected reduction in mortality. In fact, there was an increase in cardiac arrests.

There are many examples in medicine where over-reliance on surrogate outcomes has been misleading and sometimes harmful.