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

ABSTRACT

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. CONCLUSION: 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.