#### Abstract

Collaborative double robust targeted maximum likelihood estimators represent a fundamental further advance over standard targeted maximum likelihood estimators of causal inference and variable importance parameters. The targeted maximum likelihood approach involves fluctuating an initial density estimate, (Q), in order to make a bias/variance tradeoff targeted towards a specific parameter in a semi-parametric model. The fluctuation involves estimation of a nuisance parameter portion of the likelihood, g. TMLE and other double robust estimators have been shown to be consistent and asymptotically normally distributed (CAN) under regularity conditions, when either one of these two factors of the likelihood of the data is correctly specified.

In this article we provide a template for applying collaborative targeted maximum likelihood estimation (C-TMLE) to the estimation of pathwise differentiable parameters in semi-parametric models. The procedure creates a sequence of candidate targeted maximum likelihood estimators based on an initial estimate for Q coupled with a succession of increasingly non-parametric estimates for g. In a departure from current state of the art nuisance parameter estimation, C-TMLE estimates of g are constructed based on a loss function for the relevant factor Q_0, instead of a loss function for the nuisance parameter itself. Likelihood-based cross-validation is used to select the best estimator among all candidate TMLE estimators in this sequence. A penalized-likelihood loss function for Q_0 is suggested when the parameter of interest is borderline-identifiable.

We present theoretical results for "collaborative double robustness," demonstrating that the collaborative targeted maximum likelihood estimator is CAN when Q and g are both mis-specified, providing that g solves a specified score equation implied by the difference between the Q and the true Q_0.

This marks an improvement over the current definition of double robustness in the estimating equation literature.

We also establish an asymptotic linearity theorem for the C-DR-TMLE of the target parameter, showing that the C-DR-TMLE is more adaptive to the truth, and, as a consequence, can even be super efficient if the first stage density estimator does an excellent job itself with respect to the target parameter.

This research provides a template for targeted efficient and robust loss-based learning of a particular target feature of the probability distribution of the data within large (infinite dimensional) semi-parametric models, while still providing statistical inference in terms of confidence intervals and p-values. This research also breaks with a taboo (e.g., in the propensity score literature in the field of causal inference) on using the relevant part of likelihood to fine-tune the fitting of the nuisance parameter/censoring mechanism/treatment mechanism.

#### Disciplines

Statistical Methodology | Statistical Theory

#### Suggested Citation

van der Laan, Mark J. and Gruber, Susan, "Collaborative Targeted Maximum Likelihood Estimation" (April 2009). *U.C. Berkeley Division of Biostatistics Working Paper Series.* Working Paper 246.

https://biostats.bepress.com/ucbbiostat/paper246