Comparison of the National Institutes of Health Stroke Scale with disability outcome measures in acute stroke trials

Background and Purpose - Acute stroke trials typically use disability scales as their primary end point. Neurologic impairment scales such as the National Institutes of Health Stroke Scale (NIHSS) are possibly more sensitive to change in patient status. We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points. Methods - We simulated a total of 6000 clinical trials, each with 1400 patients. We estimated statistical power for a range of NIHSS end points, including prognosis-adjusted and fixed dichotomized end points. These end points were compared with the BI and mRS dichotomized at 95 and 1, respectively. Results - The most powerful fixed end point was the NIHSS dichotomized at 1. For prognosis-adjusted outcome, we found greatest power if we defined success as achieving a score of <= 1 or improvement by at least 11 points from baseline. We are more likely to achieve a statistically significant result by using this prognosis-adjusted end point instead of NIHSS <= 1 (odds ratio, 2.8; 95% confidence interval [CI], 2.5 to 3.2). Use of the optimal NIHSS prognosis-adjusted end point rather than BI >= 95 could justify a reduction in sample size of approximately 68% (95% CI, 67% to 69%) without loss of statistical power. Conclusions - The NIHSS neurologic scale appears more sensitive than the BI or mRS, allowing smaller sample sizes or greater statistical power. The use of an NIHSS prognosis-adjusted end point could allow therapeutic effects from drugs to be more easily identified.