National Institutes of Health Stroke Scale as an Outcome in Stroke Research: Value of ANCOVA Over Analyzing Change From Baseline.

Abstract

National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).