title: Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury.
abstract: OBJECTIVE
  We aimed to determine to what extent covariate adjustment could affect power in a randomized controlled trial (RCT) of a heterogeneous population with traumatic brain injury (TBI).
  
  
  METHODS
  We analyzed 14-day mortality in 9,497 participants in the Corticosteroid Randomization After Significant Head Injury (CRASH) RCT of corticosteroid vs. placebo. Adjustment was made using logistic regression for baseline covariates of two validated risk models derived from external data (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury [IMPACT]) and from the CRASH data. The relative sample size (RESS) measure, defined as the ratio of the sample size required by an adjusted analysis to attain the same power as the unadjusted reference analysis, was used to assess the impact of adjustment.
  
  
  RESULTS
  Corticosteroid was associated with higher mortality compared with placebo (odds ratio=1.25, 95% confidence interval=1.13-1.39). RESS of 0.79 and 0.73 were obtained by adjustment using the IMPACT and CRASH models, respectively, which, for example, implies an increase from 80% to 88% and 91% power, respectively.
  
  
  CONCLUSIONS
  Moderate gains in power may be obtained using covariate adjustment from logistic regression in heterogeneous conditions such as TBI. Although analyses of RCTs might consider covariate adjustment to improve power, we caution against this approach in the planning of RCTs.
authors.affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. elizabeth.turner@lshtm.ac.uk
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Turner
authors.forename: Pablo
authors.initials: P
authors.lastname: Perel
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.forename: Phil
authors.initials: P
authors.lastname: Edwards
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Hernández
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Haleema
authors.initials: H
authors.lastname: Shakur
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D001930:Brain Injuries / Q000188:drug therapy / Q000401:mortality*; D003627:Data Interpretation, Statistical; D015600:Glasgow Coma Scale / Q000706:statistics & numerical data; D006801:Humans; D057194:Intention to Treat Analysis; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012025:Reflex, Pupillary / Q000502:physiology; D018401:Sample Size; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D010919:Placebos