Understanding how the primary endpoint impacts the interpretation of trial results: The Japanese Adult Moyamoya...

The meaning of a clinical trial depends to a large extent on the choice of the primary outcome measure, which can be explanatory or pragmatic.

We review the Japanese Adult Moyamoya (JAM) trial, that compared surgical extracranial to intracranial (EC-IC) bypass and medical management of hemorrhagic moyamoya disease. We also review some principles which guide the selection of the primary trial endpoint.

The main component of the primary outcome measure in JAM was rebleeding, a surrogate outcome that allowed investigators to demonstrate that surgical bypass had causal efficacy. However, the number of patients with a poor outcome, defined as those with a modified Rankin score (mRS)>2, would have been a more pragmatic choice. Unfortunately, the trial was too small to show that patients benefited from surgery.

The JAM trial showed that EC-IC bypass can decrease rebleeding in moyamoya patients, but whether patients have better outcomes with surgery remains uncertain. Hard pragmatic clinical primary outcome measures are necessary to guide surgical care.