Understanding the importance of the primary trial hypothesis: The randomized trial on the timing of ruptured aneurysm surgery.

ABSTRACT

BACKGROUND AND PURPOSE: The primary hypothesis of a trial must be explicitly formulated. The primary hypothesis is essential for the proper interpretation of trial results. METHODS: We review the seminal Finnish randomized trial on the timing of aneurysm surgery, and re-examine how trial results could have been interpreted at the time had a precise primary hypothesis been pre-specified. Finally, we compare the power of this single center randomized trial with the multicenter International Cooperative (observational) Study that examined the same clinical problem. RESULTS: Had the Finnish authors worked under a pragmatic hypothesis in favor of early surgery (within 3days) versus delayed surgery, the trial results could have been interpreted as conclusive. The randomized trial was more appropriate, more ethical, and more efficient than the inconclusive International Cooperative study. CONCLUSION: The randomized trial on the timing of aneurysm surgery was a landmark in neurovascular research. A precise pragmatic primary hypothesis is a crucial step in trial design and interpretation.