On the analysis and interpretation of outcome measures in stroke clinical trials: lessons from the SAINT I study of NXY-059 for acute ischemic stroke.

BACKGROUND AND PURPOSE A variety of primary end points have been used in acute stroke trials. We focus on the modified Rankin Scale, a reliable and valid ordinal outcome measure that assesses disability on a 7-point scale. METHODS We provide an abbreviated discussion of analytical methods for ordinal scales, and related effect size measures; we illustrate these methods and their interpretation with outcome data from the SAINT I study of NXY-059 in acute ischemic stroke. RESULTS The nonparametric Mann-Whitney statistic provides a straightforward method for analysis of the modified Rankin Scale, and incorporates associated measures of effect size. These measures are directly related to the concepts of Number Needed to Treat and Number Needed to Harm. CONCLUSIONS Our re-examination of the outcome data from the SAINT I study provides little evidence for the purported efficacy of NXY-059. More broadly, analysis and interpretation of ordinal outcome scales based on ascribed numerical values to the steps of the scale should be done cautiously. Statistical treatment of multiple primary outcome measures in acute stroke clinical trials should be established before analysis. Lastly, conflating statistical and clinical significance should be avoided.