Toward Better Practice of Covariate Adjustment in Analyzing Randomized Clinical Trials

Ting Ye, Jun Shao, Yanyao Yi and Qingyuan Zhao

Journal of the American Statistical Association, 2023, vol. 118, issue 544, 2370-2382

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: (a) guaranteed efficiency gain: a model-assisted method should often gain but never hurt efficiency; (b) wide applicability: a valid procedure should be applicable, and preferably universally applicable, to all commonly used randomization schemes; (c) 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 that includes all covariates used 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. Supplementary materials for this article are available online.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
http://hdl.handle.net/10.1080/01621459.2022.2049278 (text/html)
Access to full text is restricted to subscribers.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:taf:jnlasa:v:118:y:2023:i:544:p:2370-2382

Ordering information: This journal article can be ordered from
http://www.tandfonline.com/pricing/journal/UASA20

DOI: 10.1080/01621459.2022.2049278

Access Statistics for this article

Journal of the American Statistical Association is currently edited by Xuming He, Jun Liu, Joseph Ibrahim and Alyson Wilson

More articles in Journal of the American Statistical Association from Taylor & Francis Journals
Bibliographic data for series maintained by Chris Longhurst ().