Toward Better Practice of Covariate Adjustment in Analyzing Randomized Clinical Trials
Publication Date
2022Journal Title
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
ISSN
0162-1459
Publisher
Informa UK Limited
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Ye, T., Shao, J., Yi, Y., & Zhao, Q. (2022). Toward Better Practice of Covariate Adjustment in Analyzing Randomized Clinical Trials. JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION https://doi.org/10.1080/01621459.2022.2049278
Abstract
In randomized clinical trials, adjustments for baseline covariates at both
design and analysis stages are highly encouraged by regulatory agencies. A
recent trend is to use a model-assisted approach for covariate adjustment to
gain credibility and efficiency while producing asymptotically valid inference
even when the model is incorrect. In this article we present three
considerations for better practice when model-assisted inference is applied to
adjust for covariates under simple or covariate-adaptive randomized trials: (1)
guaranteed efficiency gain: a model-assisted method should often gain but never
hurt efficiency; (2) wide applicability: a valid procedure should be
applicable, and preferably universally applicable, to all commonly used
randomization schemes; (3) robust standard error: variance estimation should be
robust to model misspecification and heteroscedasticity. To achieve these, we
recommend a model-assisted estimator under an analysis of heterogeneous
covariance working model including all covariates utilized in randomization.
Our conclusions are based on an asymptotic theory that provides a clear picture
of how covariate-adaptive randomization and regression adjustment alter
statistical efficiency. Our theory is more general than the existing ones in
terms of studying arbitrary functions of response means (including linear
contrasts, ratios, and odds ratios), multiple arms, guaranteed efficiency gain,
optimality, and universal applicability.
Keywords
stat.ME, stat.ME
Sponsorship
Isaact Newton Trust
Embargo Lift Date
2023-03-26
Identifiers
External DOI: https://doi.org/10.1080/01621459.2022.2049278
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334744
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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