title: The added value of ordinal analysis in clinical trials: an example in traumatic brain injury.
abstract: BACKGROUND
  In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial.
  
  
  METHODS
  We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics.
  
  
  RESULTS
  Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively.
  
  
  CONCLUSIONS
  Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects.
authors.affiliation: Department of Neurosurgery, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium. b.roozenbeek@erasmusmc.nl
authors.forename: Bob
authors.initials: B
authors.lastname: Roozenbeek
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Pablo
authors.initials: P
authors.lastname: Perel
authors.forename: Phil
authors.initials: P
authors.lastname: Edwards
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Murray
authors.forename: Andrew Ir
authors.initials: AI
authors.lastname: Maas
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D001930:Brain Injuries / Q000188:drug therapy*; D005260:Female; D023261:Glasgow Outcome Scale / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D012107:Research Design; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones