skip to main content

Title: Nonparametric causal mediation analysis for stochastic interventional (in)direct effects
Summary Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary exposures and static interventions and (ii) direct and indirect effect decompositions have been pursued that are only identifiable in the absence of intermediate confounders affected by exposure. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the exposure and mediators. In contrast to existing proposals, our causal effects can be evaluated regardless of whether an exposure is categorical or continuous and remain well-defined even in the presence of intermediate confounders affected by exposure. Our (in)direct effects are identifiable without a restrictive assumption on cross-world counterfactual independencies, allowing for substantive conclusions drawn from them to be validated in randomized controlled trials. Beyond the novel effects introduced, we provide a careful study of nonparametric efficiency theory relevant for the construction of flexible, multiply robust estimators of our (in)direct effects, while avoiding undue restrictions induced by assuming parametric models of nuisance parameter functionals. To complement our nonparametric estimation strategy, we introduce inferential techniques for constructing confidence intervals and hypothesis tests, and discuss open-source software, the $\texttt{medshift}$  $\texttt{R}$ package, implementing more » the proposed methodology. Application of our (in)direct effects and their nonparametric estimators is illustrated using data from a comparative effectiveness trial examining the direct and indirect effects of pharmacological therapeutics on relapse to opioid use disorder. « less
; ; ;
Award ID(s):
Publication Date:
Journal Name:
Sponsoring Org:
National Science Foundation
More Like this
  1. Identification of causal direction between a causal-effect pair from observed data has recently attracted much attention. Various methods based on functional causal models have been proposed to solve this problem, by assuming the causal process satisfies some (structural) constraints and showing that the reverse direction violates such constraints. The nonlinear additive noise model has been demonstrated to be effective for this purpose, but the model class is not transitive--even if each direct causal relation follows this model, indirect causal influences, which result from omitted intermediate causal variables and are frequently encountered in practice, do not necessarily follow the model constraints; as a consequence, the nonlinear additive noise model may fail to correctly discover causal direction. In this work, we propose a cascade nonlinear additive noise model to represent such causal influences--each direct causal relation follows the nonlinear additive noise model but we observe only the initial cause and final effect. We further propose a method to estimate the model, including the unmeasured intermediate variables, from data, under the variational auto-encoder framework. Our theoretical results show that with our model, causal direction is identifiable under suitable technical conditions on the data generation process. Simulation results illustrate the power of the proposed method in identifyingmore »indirect causal relations across various settings, and experimental results on real data suggest that the proposed model and method greatly extend the applicability of causal discovery based on functional causal models in nonlinear cases.

    « less
  2. Summary It is important to draw causal inference from observational studies, but this becomes challenging if the confounders have missing values. Generally, causal effects are not identifiable if the confounders are missing not at random. In this article we propose a novel framework for nonparametric identification of causal effects with confounders subject to an outcome-independent missingness, which means that the missing data mechanism is independent of the outcome, given the treatment and possibly missing confounders. We then propose a nonparametric two-stage least squares estimator and a parametric estimator for causal effects.
  3. Summary A common concern when trying to draw causal inferences from observational data is that the measured covariates are insufficiently rich to account for all sources of confounding. In practice, many of the covariates may only be proxies of the latent confounding mechanism. Recent work has shown that in certain settings where the standard no-unmeasured-confounding assumption fails, proxy variables can be leveraged to identify causal effects. Results currently exist for the total causal effect of an intervention, but little consideration has been given to learning about the direct or indirect pathways of the effect through a mediator variable. In this work, we describe three separate proximal identification results for natural direct and indirect effects in the presence of unmeasured confounding. We then develop a semiparametric framework for inference on natural direct and indirect effects, which leads us to locally efficient, multiply robust estimators.
  4. Causal effects are often characterized with averages, which can give an incomplete picture of the underlying counterfactual distributions. Here we consider estimating the entire counterfactual density and generic functionals thereof. We focus on two kinds of target parameters. The first is a density approximation, defined by a projection onto a finite-dimensional model using a generalized distance metric, which includes f-divergences as well as Lp norms. The second is the distance between counterfactual densities, which can be used as a more nuanced effect measure than the mean difference, and as a tool for model selection. We study nonparametric efficiency bounds for these targets, giving results for smooth but otherwise generic models and distances. Importantly, we show how these bounds connect to means of particular non-trivial functions of counterfactuals, linking the problems of density and mean estimation. We go on to propose doubly robust-style estimators for the density approximations and distances, and study their rates of convergence, showing they can be optimally efficient in large nonparametric models. We also give analogous methods for model selection and aggregation, when many models may be available and of interest. Our results all hold for generic models and distances, but throughout we highlight what happens formore »particular choices, such as L2 projections on linear models, and KL projections on exponential families. Finally we illustrate by estimating the density of CD4 count among patients with HIV, had all been treated with combination therapy versus zidovudine alone, as well as a density effect. Our results suggest combination therapy may have increased CD4 count most for high-risk patients. Our methods are implemented in the freely available R package npcausal on GitHub.« less
  5. This study investigates appropriate estimation of estimator variability in the context of causal mediation analysis that employs propensity score‐based weighting. Such an analysis decomposes the total effect of a treatment on the outcome into an indirect effect transmitted through a focal mediator and a direct effect bypassing the mediator. Ratio‐of‐mediator‐probability weighting estimates these causal effects by adjusting for the confounding impact of a large number of pretreatment covariates through propensity score‐based weighting. In step 1, a propensity score model is estimated. In step 2, the causal effects of interest are estimated using weights derived from the prior step's regression coefficient estimates. Statistical inferences obtained from this 2‐step estimation procedure are potentially problematic if the estimated standard errors of the causal effect estimates do not reflect the sampling uncertainty in the estimation of the weights. This study extends to ratio‐of‐mediator‐probability weighting analysis a solution to the 2‐step estimation problem by stacking the score functions from both steps. We derive the asymptotic variance‐covariance matrix for the indirect effect and direct effect 2‐step estimators, provide simulation results, and illustrate with an application study. Our simulation results indicate that the sampling uncertainty in the estimated weights should not be ignored. The standard error estimationmore »using the stacking procedure offers a viable alternative to bootstrap standard error estimation. We discuss broad implications of this approach for causal analysis involving propensity score‐based weighting.

    « less