Posted by Michael Wonder on 01 Sep 2016
The primary outcome fails — what next?
31 August 2016 - A well-designed clinical trial derives its credibility from the inclusion of a pre-specified, a priori hypothesis that helps its authors avoid making potentially false positive claims on the basis of an exploratory analysis of the data.
Nevertheless, an unreasonable yet widespread practice is the labeling of all randomized trials as either positive or negative on the basis of whether the P value for the primary outcome is less than 0.05. This view is overly simplistic. P values should be interpreted as a continuum wherein the smaller the P value, the greater the strength of the evidence for a real treatment effect.
In a review article in the New England Journal of Medicine, Pocock & Stone outline the thought processes to follow when the primary outcome of a trial is first perceived as negative. They illustrate their points with examples from clinical trials — primarily from the cardiovascular disease area, but the underlying issues apply to the whole of medicine.
