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Lee, Kim May ; Robertson, David S. ; Jaki, Thomas ; Emsley, Richard

The benefits of covariate adjustment for adaptive multi-arm designs

Lee, Kim May, Robertson, David S., Jaki, Thomas and Emsley, Richard (2022) The benefits of covariate adjustment for adaptive multi-arm designs. Statistical Methods in Medical Research 31 (11), pp. 2104-2121.

Date of publication of this fulltext: 29 Sep 2025 11:09
Article
DOI to cite this document: 10.5283/epub.77851


Abstract

Covariate adjustment via a regression approach is known to increase the precision of statistical inference when fixed trial designs are employed in randomized controlled studies. When an adaptive multi-arm design is employed with the ability to select treatments, it is unclear how covariate adjustment affects various aspects of the study. Consider the design framework that relies on pre-specified ...

Covariate adjustment via a regression approach is known to increase the precision of statistical inference when fixed trial designs are employed in randomized controlled studies. When an adaptive multi-arm design is employed with the ability to select treatments, it is unclear how covariate adjustment affects various aspects of the study. Consider the design framework that relies on pre-specified treatment selection rule(s) and a combination test approach for hypothesis testing. It is our primary goal to evaluate the impact of covariate adjustment on adaptive multi-arm designs with treatment selection. Our secondary goal is to show how the Uniformly Minimum Variance Conditionally Unbiased Estimator can be extended to account for covariate adjustment analytically. We find that adjustment with different sets of covariates can lead to different treatment selection outcomes and hence probabilities of rejecting hypotheses. Nevertheless, we do not see any negative impact on the control of the familywise error rate when covariates are included in the analysis model. When adjusting for covariates that are moderately or highly correlated with the outcome, we see various benefits to the analysis of the design. Conversely, there is negligible impact when including covariates that are uncorrelated with the outcome. Overall, pre-specification of covariate adjustment is recommended for the analysis of adaptive multi-arm design with treatment selection. Having the statistical analysis plan in place prior to the interim and final analyses is crucial, especially when a non-collapsible measure of treatment effect is considered in the trial.



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Details

Item typeArticle
Journal or Publication TitleStatistical Methods in Medical Research
Publisher:Sage
Open Access Type:CC-License
Volume:31
Number of Issue or Book Chapter:11
Page Range:pp. 2104-2121
Date25 July 2022
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1177/09622802221114544DOI
KeywordsAdaptive design, covariate adjustment, multi-arm, treatment selection, UMVCUE
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-778517
Item ID77851

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