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Register a new userEstimating the natural indirect effect and the mediation proportion via the product method
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Chao Cheng
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
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The natural indirect effect (NIE) and mediation proportion (MP) are two measures of primary interest in mediation analysis. The standard approach for estimating NIE and MP is through the product method, which involves a model for the outcome conditional on the mediator and exposure and another model describing the exposure-mediator relationship. The purpose of this article is to comprehensively develop and investigate the finite-sample performance of NIE and MP estimators via the product method. With four common data types, we propose closed-form interval estimators via the theory of estimating equations and multivariate delta method, and evaluate its empirical performance relative to the bootstrap approach. In addition, we have observed that the rare outcome assumption is frequently invoked to approximate the NIE and MP with a binary outcome, although this approximation may lead to non-negligible bias when the outcome is common. We therefore introduce the exact expressions for NIE and MP with a binary outcome without the rare outcome assumption and compare its performance with the approximate estimators. Based upon these theoretical developments and empirical studies, we offer several practical recommendations to inform practice. An R package mediateP is developed to implement the methods for point and variance estimation discussed in this paper.
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As a classic parameter from the binomial distribution, the binomial proportion has been well studied in the literature owing to its wide range of applications. In contrast, the reciprocal of the binomial proportion, also known as the inverse proportion, is often overlooked, even though it also plays an important role in various fields including clinical studies and random sampling. The maximum likelihood estimator of the inverse proportion suffers from the zero-event problem, and to overcome it, alternative methods have been developed in the literature. Nevertheless, there is little work addressing the optimality of the existing estimators, as well as their practical performance comparison. Inspired by this, we propose to further advance the literature by developing an optimal estimator for the inverse proportion in a family of shrinkage estimators. We further derive the explicit and approximate formulas for the optimal shrinkage parameter under different settings. Simulation studies show that the performance of our new estimator performs better than, or as well as, the existing competitors in most practical settings. Finally, to illustrate the usefulness of our new method, we also revisit a recent meta-analysis on COVID-19 data for assessing the relative risks of physical distancing on the infection of coronavirus, in which six out of seven studies encounter the zero-event problem.
Causal mediation analysis aims to characterize an exposures effect on an outcome and quantify the indirect effect that acts through a given mediator or a group of mediators of interest. With the increasing availability of measurements on a large number of potential mediators, like the epigenome or the microbiome, new statistical methods are needed to simultaneously accommodate high-dimensional mediators while directly target penalization of the natural indirect effect (NIE) for active mediator identification. Here, we develop two novel prior models for identification of active mediators in high-dimensional mediation analysis through penalizing NIEs in a Bayesian paradigm. Both methods specify a joint prior distribution on the exposure-mediator effect and mediator-outcome effect with either (a) a four-component Gaussian mixture prior or (b) a product threshold Gaussian prior. By jointly modeling the two parameters that contribute to the NIE, the proposed methods enable penalization on their product in a targeted way. Resultant inference can take into account the four-component composite structure underlying the NIE. We show through simulations that the proposed methods improve both selection and estimation accuracy compared to other competing methods. We applied our methods for an in-depth analysis of two ongoing epidemiologic studies: the Multi-Ethnic Study of Atherosclerosis (MESA) and the LIFECODES birth cohort. The identified active mediators in both studies reveal important biological pathways for understanding disease mechanisms.
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Recent studies suggest that the microbiome can be an important mediator in the effect of a treatment on an outcome. Microbiome data generated from sequencing experiments contain the relative abundance of a large number of microbial taxa with their evolutionary relationships represented by a phylogenetic tree. The compositional and high-dimensional nature of the microbiome mediator invalidates standard mediation analyses. We propose a phylogeny-based mediation analysis method (PhyloMed) for the microbiome mediator. PhyloMed models the microbiome mediation effect through a cascade of independent local mediation models on the internal nodes of the phylogenetic tree. Each local model captures the mediation effect of a subcomposition at a given taxonomic resolution. The method improves the power of the mediation test by enriching weak and sparse signals across mediating taxa that tend to cluster on the tree. In each local model, we further empower PhyloMed by using a mixture distribution to obtain the subcomposition mediation test p-value, which takes into account the composite nature of the null hypothesis. PhyloMed enables us to test the overall mediation effect of the entire microbial community and pinpoint internal nodes with significant subcomposition mediation effects. Our extensive simulations demonstrate the validity of PhyloMed and its substantial power gain over existing methods. An application to a real study further showcases the advantages of our method.
Standard estimators of the global average treatment effect can be biased in the presence of interference. This paper proposes regression adjustment estimators for removing bias due to interference in Bernoulli randomized experiments. We use a fitted model to predict the counterfactual outcomes of global control and global treatment. Our work differs from standard regression adjustments in that the adjustment variables are constructed from functions of the treatment assignment vector, and that we allow the researcher to use a collection of any functions correlated with the response, turning the problem of detecting interference into a feature engineering problem. We characterize the distribution of the proposed estimator in a linear model setting and connect the results to the standard theory of regression adjustments under SUTVA. We then propose an estimator that allows for flexible machine learning estimators to be used for fitting a nonlinear interference functional form. We propose conducting statistical inference via bootstrap and resampling methods, which allow us to sidestep the complicated dependences implied by interference and instead rely on empirical covariance structures. Such variance estimation relies on an exogeneity assumption akin to the standard unconfoundedness assumption invoked in observational studies. In simulation experiments, our methods are better at debiasing estimates than existing inverse propensity weighted estimators based on neighborhood exposure modeling. We use our method to reanalyze an experiment concerning weather insurance adoption conducted on a collection of villages in rural China.
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