TY - JOUR
T1 - Covariate adjustment increased power in randomized controlled trials
T2 - An example in traumatic brain injury
AU - Turner, Elizabeth L.
AU - Perel, Pablo
AU - Clayton, Tim
AU - Edwards, Phil
AU - Hernandez, Adrian V.
AU - Roberts, Ian
AU - Shakur, Haleema
AU - Steyerberg, Ewout W.
PY - 2012/5
Y1 - 2012/5
N2 - 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). Study Design and Setting: 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. Conclusion: 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.
AB - 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). Study Design and Setting: 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. Conclusion: 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.
KW - Covariate adjustment
KW - Power in clinical trials
KW - Prognostic targeting
KW - Relative sample size
KW - Strict selection
KW - Traumatic brain injury
UR - https://www.scopus.com/pages/publications/84861170204
U2 - 10.1016/j.jclinepi.2011.08.012
DO - 10.1016/j.jclinepi.2011.08.012
M3 - Artículo
C2 - 22169080
AN - SCOPUS:84861170204
SN - 0895-4356
VL - 65
SP - 474
EP - 481
JO - Journal of Clinical Epidemiology
JF - Journal of Clinical Epidemiology
IS - 5
ER -