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Open Access Highly Accessed Methodology

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

Brennan C Kahan1*, Vipul Jairath2, Caroline J Doré3 and Tim P Morris4

Author Affiliations

1 Pragmatic Clinical Trials Unit, Queen Mary University of London, London E1 2AB, UK

2 Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK

3 Comprehensive Clinical Trials Unit, University College London, London WC1E 6BT, UK

4 MRC Clinical Trials Unit, University College London, London WC2B 6NH, UK

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Trials 2014, 15:139  doi:10.1186/1745-6215-15-139

Published: 23 April 2014

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.

Keywords:
Adjusted analysis; clinical trial; covariate adjustment; power; randomized controlled trial; regression