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Adjustment for Baseline Characteristics in Randomized Clinical Trials

To identify the key insights or developments described in this article
1 Credit CME

The purpose of randomization in clinical trials is to ensure that there are no systematic differences between treatment groups with respect to measured and unmeasured baseline characteristics that could influence the outcome of interest.1 In a randomized clinical trial (RCT) without selection or information bias, an unadjusted analysis (ie, an analysis that does not take baseline characteristics into account) will provide unbiased estimates of treatment effects.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Lars W. Andersen, MD, MPH, PhD, DMSc, Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Nørrebrogade 44, Aarhus, NA 8000, Denmark (lwandersen@clin.au.dk).

Published Online: November 17, 2022. doi:10.1001/jama.2022.21506

Conflict of Interest Disclosures: None reported.

Disclaimer: Dr Anderson is a statistical reviewer for JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance.

References
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US Food and Drug Administration. Adjusting for covariates in randomized clinical trials for drugs and biological products. Accessed November 8, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adjusting-covariates-randomized-clinical-trials-drugs-and-biological-products
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European Medicines Agency. Guidelines on adjustment for baseline covariates in clinical trials. Accessed November 8, 2022. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-adjustment-baseline-covariates-clinical-trials_en.pdf
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Kahan  BC , Jairath  V , Doré  CJ , Morris  TP .  The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies.   Trials. 2014;15:139. doi:10.1186/1745-6215-15-139PubMedGoogle ScholarCrossref
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