Seven-day NIHSS is a sensitive outcome measure for exploratory clinical trials in acute stroke: evidence from the Virtual International Stroke Trials Archive.
OBJECTIVE
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 >80% 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.
Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK. k.r.lees@clinmed.gla.ac.uk
Daniel M
DM
Kerr
Rachael L
RL
Fulton
Kennedy R
KR
Lees
D004185:Disability Evaluation; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D009316:National Institutes of Health (U.S.); D017063:Outcome Assessment, Health Care / Q000592:standards*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator