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Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach.

Publication ,  Journal Article
Tsiatis, AA; Davidian, M; Zhang, M; Lu, X
Published in: Stat Med
October 15, 2008

There is considerable debate regarding whether and how covariate-adjusted analyses should be used in the comparison of treatments in randomized clinical trials. Substantial baseline covariate information is routinely collected in such trials, and one goal of adjustment is to exploit covariates associated with outcome to increase precision of estimation of the treatment effect. However, concerns are routinely raised over the potential for bias when the covariates used are selected post hoc and the potential for adjustment based on a model of the relationship between outcome, covariates, and treatment to invite a 'fishing expedition' for that leading to the most dramatic effect estimate. By appealing to the theory of semiparametrics, we are led naturally to a characterization of all treatment effect estimators and to principled, practically feasible methods for covariate adjustment that yield the desired gains in efficiency and that allow covariate relationships to be identified and exploited while circumventing the usual concerns. The methods and strategies for their implementation in practice are presented. Simulation studies and an application to data from an HIV clinical trial demonstrate the performance of the techniques relative to the existing methods.

Duke Scholars

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Published In

Stat Med

DOI

ISSN

0277-6715

Publication Date

October 15, 2008

Volume

27

Issue

23

Start / End Page

4658 / 4677

Location

England

Related Subject Headings

  • Treatment Outcome
  • Statistics, Nonparametric
  • Statistics & Probability
  • Sampling Studies
  • Randomized Controlled Trials as Topic
  • Humans
  • Data Interpretation, Statistical
  • Algorithms
  • 4905 Statistics
  • 4202 Epidemiology
 

Citation

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Tsiatis, A. A., Davidian, M., Zhang, M., & Lu, X. (2008). Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach. Stat Med, 27(23), 4658–4677. https://doi.org/10.1002/sim.3113
Tsiatis, Anastasios A., Marie Davidian, Min Zhang, and Xiaomin Lu. “Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach.Stat Med 27, no. 23 (October 15, 2008): 4658–77. https://doi.org/10.1002/sim.3113.
Tsiatis, Anastasios A., et al. “Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach.Stat Med, vol. 27, no. 23, Oct. 2008, pp. 4658–77. Pubmed, doi:10.1002/sim.3113.
Journal cover image

Published In

Stat Med

DOI

ISSN

0277-6715

Publication Date

October 15, 2008

Volume

27

Issue

23

Start / End Page

4658 / 4677

Location

England

Related Subject Headings

  • Treatment Outcome
  • Statistics, Nonparametric
  • Statistics & Probability
  • Sampling Studies
  • Randomized Controlled Trials as Topic
  • Humans
  • Data Interpretation, Statistical
  • Algorithms
  • 4905 Statistics
  • 4202 Epidemiology