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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.
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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 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.
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- Award ID(s):
- 2102840
- PAR ID:
- 10341676
- Date Published:
- Journal Name:
- Biostatistics
- ISSN:
- 1465-4644
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/biostatistics/kxac002
