title: Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements.
abstract: OBJECTIVE
  Randomized controlled trials (RCTs) with dichotomous outcomes may be analyzed with or without adjustment for baseline characteristics (covariates). We studied type I error, power, and potential reduction in sample size with several covariate adjustment strategies.
  
  
  METHODS
  Logistic regression analysis was applied to simulated data sets (n=360) with different treatment effects, covariate effects, outcome incidences, and covariate prevalences. Treatment effects were estimated with or without adjustment for a single dichotomous covariate. Strategies included always adjusting for the covariate ("prespecified"), or only when the covariate was predictive or imbalanced.
  
  
  RESULTS
  We found that the type I error was generally at the nominal level. The power was highest with prespecified adjustment. The potential reduction in sample size was higher with stronger covariate effects (from 3 to 46%, at 50% outcome incidence and covariate prevalence) and independent of the treatment effect. At lower outcome incidences and/or covariate prevalences, the reduction was lower.
  
  
  CONCLUSIONS
  We conclude that adjustment for a predictive baseline characteristic may lead to a potentially important increase in power of analyses of treatment effect. Adjusted analysis should, hence, be considered more often for RCTs with dichotomous outcomes.
authors.affiliation: Center for Clinical Decision Sciences, Department of Public Health, Erasmus Medical Center, P.O. Box 1738, Rotterdam 3000 DR, The Netherlands. a.hernandez@erasmusmc.nl
authors.forename: Adrián V
authors.initials: AV
authors.lastname: Hernández
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: J Dik F
authors.initials: JD
authors.lastname: Habbema
mesh_terms: D003627:Data Interpretation, Statistical; D006801:Humans; D016015:Logistic Models; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome