title: Exploration of time-course combinations of outcome scales for use in a global test of stroke recovery.
abstract: BACKGROUND
  Clinical trials for acute ischemic stroke treatment require large numbers of participants and are expensive to conduct. Methods that enhance statistical power are therefore desirable.
  
  
  OBJECTIVE
  We explored whether this can be achieved by a measure incorporating both early and late measures of outcome (e.g. seven-day NIH Stroke Scale combined with 90-day modified Rankin scale).
  
  
  METHODS
  We analyzed sensitivity to treatment effect, using proportional odds logistic regression for ordinal scales and generalized estimating equation method for global outcomes, with all analyses adjusted for baseline severity and age. We ran simulations to assess relations between sample size and power for ordinal scales and corresponding global outcomes. We used R version 2·12·1 (R Development Core Team. R Foundation for Statistical Computing, Vienna, Austria) for simulations and SAS 9·2 (SAS Institute Inc., Cary, NC, USA) for all other analyses.
  
  
  RESULTS
  Each scale considered for combination was sensitive to treatment effect in isolation. The mRS90 and NIHSS90 had adjusted odds ratio of 1·56 and 1·62, respectively. Adjusted odds ratio for global outcomes of the combination of mRS90 with NIHSS7 and NIHSS90 with NIHSS7 were 1·69 and 1·73, respectively. The smallest sample sizes required to generate statistical power ≥80% for mRS90, NIHSS7, and global outcomes of mRS90 and NIHSS7 combined and NIHSS90 and NIHSS7 combined were 500, 490, 400, and 380, respectively.
  
  
  CONCLUSIONS
  When data concerning both early and late outcomes are combined into a global measure, there is increased sensitivity to treatment effect compared with solitary ordinal scales. This delivers a 20% reduction in required sample size at 80% power. Combining early with late outcomes merits further consideration.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Fraser C
authors.initials: FC
authors.lastname: Goldie
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Fulton
authors.forename: Jesse
authors.initials: J
authors.lastname: Dawson
authors.forename: Erich
authors.initials: E
authors.lastname: Bluhmki
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003198:Computer Simulation; D016208:Databases, Factual; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D020127:Recovery of Function; D018401:Sample Size; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis / Q000628:therapy*; D013997:Time Factors; D055815:Young Adult
keywords: combinations; global outcomes; outcomes; scales; stroke; stroke recovery