Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr 23:15:139.
doi: 10.1186/1745-6215-15-139.

The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies

Brennan C Kahan  1 , Vipul Jairath, Caroline J Doré, Tim P Morris
Affiliations

The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies

Brennan C Kahan et al. Trials. .

Abstract

Background: Adjustment for prognostic covariates can lead to increased power in the analysis of randomized trials. However, adjusted analyses are not often performed in practice.

Methods: We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas. We assessed (1) how large an increase in power can be expected in practice; and (2) the impact of adjustment for covariates that are not prognostic.

Results: Adjustment for known prognostic covariates led to large increases in power for most outcomes. When power was set to 80% based on an unadjusted analysis, covariate adjustment led to a median increase in power to 92.6% across the 12 outcomes (range 80.6 to 99.4%). Power was increased to over 85% for 8 of 12 outcomes, and to over 95% for 5 of 12 outcomes. Conversely, the largest decrease in power from adjustment for covariates that were not prognostic was from 80% to 78.5%.

Conclusions: Adjustment for known prognostic covariates can lead to substantial increases in power, and should be routinely incorporated into the analysis of randomized trials. The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so, and so should also be considered.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Simulation results for ‘underpowered’ trials. Change in power through covariate adjustment as compared with unadjusted analysis for ‘underpowered’ trials (where an unadjusted analysis gives 50% power).
Figure 2
Figure 2
Simulation results for ‘adequately powered’ trials. Change in power through covariate adjustment as compared with unadjusted analysis for ‘adequately powered’ trials (where an unadjusted analysis gives 80% power).
See this image and copyright information in PMC

References

    1. Hernandez AV, Eijkemans MJ, Steyerberg EW. Randomized controlled trials with time-to-event outcomes: how much does prespecified covariate adjustment increase power? Ann Epidemiol. 2006;16(1):41–48. doi: 10.1016/j.annepidem.2005.09.007. - DOI - PubMed
    1. Hernandez AV, Steyerberg EW, Butcher I, Mushkudiani N, Taylor GS, Murray GD, Marmarou A, Choi SC, Lu J, Habbema JD, Maas AI. Adjustment for strong predictors of outcome in traumatic brain injury trials: 25% reduction in sample size requirements in the IMPACT study. J Neurotrauma. 2006;23(9):1295–1303. doi: 10.1089/neu.2006.23.1295. - DOI - PubMed
    1. Hernandez AV, Steyerberg EW, Habbema JD. Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements. J Clin Epidemiol. 2004;57(5):454–460. doi: 10.1016/j.jclinepi.2003.09.014. - DOI - PubMed
    1. Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med. 2002;21(19):2917–2930. doi: 10.1002/sim.1296. - DOI - PubMed
    1. McHugh GS, Butcher I, Steyerberg EW, Marmarou A, Lu J, Lingsma HF, Weir J, Maas AI, Murray GD. A simulation study evaluating approaches to the analysis of ordinal outcome data in randomized controlled trials in traumatic brain injury: results from the IMPACT project. Clin Trials. 2010;7(1):44–57. doi: 10.1177/1740774509356580. - DOI - PubMed

MeSH terms

LinkOut - more resources