Seven-Day NIHSS Is a Sensitive Outcome Measure for Exploratory Clinical Trials in Acute Stroke

Abstract

Background and Purpose-Clinical trials in stroke typically measure outcome after 90 days. Earlier outcome assessment would reduce costs and may increase power. We aimed to compare the sensitivity of 4 end points (modified Rankin Scale [mRS] at 30 and 90 days, and National Institutes of Health Stroke Scale (NIHSS) at 7 and 90 days, analyzed as ordinal measures) to detect the established treatment effect of recombinant tissue-type plasminogen activator (rtPA). Methods-Within the Virtual International Stroke Trials Archive, we compared rtPA-treated patients with untreated control subjects using a multiple resampling approach. From our total sample we drew 10 000 random samples of unique patients, constraining the sample sizes in treated and untreated groups to be equal. In each of these samples we tested for the treatment effect of rtPA by each of the 4 studied end points. The percentage of samples yielding significant results approximates the power of each end point at a given sample size. This process was repeated across a range of sample sizes, to determine the relationship between sample size and power for each of the 4 end points. Results-For our 4 end points of mRS at 30 and 90 days, and NIHSS at 7 and 90 days the smallest sample sizes required to generate statistical power Ͼ80% were 620, 480, 370, and 420, respectively, making 7-day NIHSS the most sensitive end point. These results were supported by dichotomized analyses. Conclusions-Seven-day NIHSS score appears a sensitive end point that should be validated in randomized trial datasets for use in exploratory stroke trials.

Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects

“…For example, change in NIHSS, infarct volume, and 24-hour NIHSS have been shown to be the strongest predictors of subjects' 90-day stroke outcomes. [7][8][9] Repeated assessments of stroke severity are routinely collected in stroke research studies providing an opportunity to assess longitudinal data on subjects' postdischarge functional outcomes.…”

Prestroke Modified Rankin Stroke Scale Has Moderate Interobserver Reliability and Validity in an Acute Stroke Setting

“…2 Construct validity of mRS is suggested by correlation with various markers of stroke severity 3,4 and correlation with other functional assessment scales. 5,6 There are inherent limitations in standard mRS assessments, for example the potential for interobserver variability in grading. 7 In stroke intervention trials, traditional statistical analyses assess numbers achieving a good functional outcome.…”

Serial Alberta Stroke Program Early Computed Tomography Score From Baseline to 24 Hours in SWIFT

“…Clinical measures, such as National Institutes of Health Stroke Scale (NIHSS) score or even modified Rankin Scale itself, are more predictive of final outcome the later they are first measured. [2][3][4] Hospital care can be influenced by clinical examination and investigation findings and by their effect on perceived prognosis. In the SWIFT study, there was a striking difference in NIHSS at 90 days between treatment groups: median 4.5 (interquartile range, 1-12.5) among Solitaire patients and 30.0 (interquartile range, 2-42) among Merci patients.…”

“…However, they tested their score only against baseline measures and did not consider alternatives, such as 24-hour or 7-day NIHSS, or 7-or 30-day modified Rankin Scale that have been validated among larger samples. [2][3][4] Why were alternative post-treatment predictors of late outcome discounted? NIHSS scores differed markedly at 90 days; would early clinical examination have revealed as large an advantage among patients who had reperfused?…”