• Elizabeth L Turner, Pablo Perel, Tim Clayton, Phil Edwards, Adrian V Hernández, Ian Roberts, Haleema Shakur, Ewout W Steyerberg, and CRASH trial collaborators.
• Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. elizabeth.turner@lshtm.ac.uk
• J Clin Epidemiol. 2012 May 1;65(5):474-81.

ObjectiveWe 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).Study Design And SettingWe 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.ResultsCorticosteroid 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.ConclusionModerate 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.Copyright © 2012 Elsevier Inc. All rights reserved.

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