Targeted Maximum Likelihood Estimation using Exponential Families

Targeted maximum likelihood estimation (TMLE) is a general method for estimating parameters in semiparametric and nonparametric models. Each iteration of TMLE involves fitting a parametric submodel that targets the parameter of interest. We investigate the use of exponential families to define the parametric submodel. This implementation of TMLE gives a general approach for estimating any smooth parameter in the nonparametric model. A computational advantage of this approach is that each iteration of TMLE involves estimation of a parameter in an exponential family, which is a convex optimization problem for which software implementing reliable and computationally efficient methods exists. We illustrate the method in three estimation problems, involving the mean of an outcome missing at random, the parameter of a median regression model, and the causal effect of a continuous exposure, respectively. We conduct a simulation study comparing different choices for the parametric submodel, focusing on the first of these problems. To the best of our knowledge, this is the first study investigating robustness of TMLE to different specifications of the parametric submodel. We find that the choice of submodel can have an important impact on the behavior of the estimator in finite samples

Non-agency interventions for causal mediation in the presence of intermediate confounding

Recent approaches to causal inference have focused on causal effects defined as contrasts between the distribution of counterfactual outcomes under hypothetical interventions on the nodes of a graphical model. In this article we develop theory for causal effects defined with respect to a different type of intervention, one which alters the information propagated through the edges of the graph. These information transfer interventions may be more useful than node interventions in settings in which causes are non-manipulable, for example when considering race or genetics as a causal agent. Furthermore, information transfer interventions allow us to define path-specific decompositions which are identified in the presence of treatment-induced mediator-outcome confounding, a practical problem whose general solution remains elusive. We prove that the proposed effects provide valid statistical tests of mechanisms, unlike popular methods based on randomized interventions on the mediator. We propose efficient non-parametric estimators for a covariance version of the proposed effects, using data-adaptive regression coupled with semi-parametric efficiency theory to address model misspecification bias while retaining $\sqrt{n}$-consistency and asymptotic normality. We illustrate the use of our methods in two examples using publicly available data

Second-Order Inference for the Mean of a Variable Missing at Random

We present a second-order estimator of the mean of a variable subject to missingness, under the missing at random assumption. The estimator improves upon existing methods by using an approximate second-order expansion of the parameter functional, in addition to the first-order expansion employed by standard doubly robust methods. This results in weaker assumptions about the convergence rates necessary to establish consistency, local efficiency, and asymptotic linearity. The general estimation strategy is developed under the targeted minimum loss-based estimation (TMLE) framework. We present a simulation comparing the sensitivity of the first and second order estimators to the convergence rate of the initial estimators of the outcome regression and missingness score. In our simulation, the second-order TMLE improved the coverage probability of a confidence interval by up to 85%. In addition, we present a first-order estimator inspired by a second-order expansion of the parameter functional. This estimator only requires one-dimensional smoothing, whereas implementation of the second-order TMLE generally requires kernel smoothing on the covariate space. The first-order estimator proposed is expected to have improved finite sample performance compared to existing first-order estimators. In our simulations, the proposed first-order estimator improved the coverage probability by up to 90%. We provide an illustration of our methods using a publicly available dataset to determine the effect of an anticoagulant on health outcomes of patients undergoing percutaneous coronary intervention. We provide R code implementing the proposed estimator