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The International Journal of Biostatistics

Ed. by Chambaz, Antoine / Hubbard, Alan E. / van der Laan, Mark J.

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An Application of Collaborative Targeted Maximum Likelihood Estimation in Causal Inference and Genomics

Susan Gruber / Mark J. van der Laan
Published Online: 2010-05-17 | DOI: https://doi.org/10.2202/1557-4679.1182

A concrete example of the collaborative double-robust targeted likelihood estimator (C-TMLE) introduced in a companion article in this issue is presented, and applied to the estimation of causal effects and variable importance parameters in genomic data. The focus is on non-parametric estimation in a point treatment data structure. Simulations illustrate the performance of C-TMLE relative to current competitors such as the augmented inverse probability of treatment weighted estimator that relies on an external non-collaborative estimator of the treatment mechanism, and inefficient estimation procedures including propensity score matching and standard inverse probability of treatment weighting. C-TMLE is also applied to the estimation of the covariate-adjusted marginal effect of individual HIV mutations on resistance to the anti-retroviral drug lopinavir. The influence curve of the C-TMLE is used to establish asymptotically valid statistical inference. The list of mutations found to have a statistically significant association with resistance is in excellent agreement with mutation scores provided by the Stanford HIVdb mutation scores database.

Keywords: causal effect; cross-validation; collaborative double robust; double robust; efficient influence curve; penalized likelihood; penalization; estimator selection; locally efficient; maximum likelihood estimation; model selection; super efficiency; super learning; targeted maximum likelihood estimation; targeted nuisance parameter estimator selection; variable importance

About the article

Published Online: 2010-05-17

Citation Information: The International Journal of Biostatistics, Volume 6, Issue 1, ISSN (Online) 1557-4679, DOI: https://doi.org/10.2202/1557-4679.1182.

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