Causal mediation in cluster-randomized trials with multiple mediators: spillover-aware decomposition, identification, and semiparametric efficient inference

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Autori principali: Tong, Jiaqi, Cheng, Chao, Li, Fan
Natura: Preprint
Pubblicazione: 2026
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author Tong, Jiaqi
Cheng, Chao
Li, Fan
author_facet Tong, Jiaqi
Cheng, Chao
Li, Fan
contents Causal mediation analysis in cluster-randomized trials (CRTs) is complicated by the presence of multiple mediators, intracluster correlation, and within-cluster interference. Existing mediation methods often fall short in accommodating these features simultaneously, and semiparametric efficient estimators that fully address them remain unavailable. We develop a unified framework that defines a class of mediation effect estimands, including exit indirect effects, exit spillover mediation effects, and their interaction effects, to investigate causal mechanisms in CRTs with an arbitrary number of mediators under an unknown causal structure. We introduce a set of interpretable causal assumptions for point identification of each estimand. For optimal inference, we first derive the efficient influence functions for the proposed estimands and construct corresponding one-step and debiased machine learning estimators. In particular, to flexibly model the joint mediator density, we employ an elliptical copula marginal regression model that combines a nonparametric marginal regression with an interpretable association structure. We assess the finite-sample performance of the proposed estimators through simulation studies and illustrate the methodology by reanalyzing the PPACT CRT data with three causally unordered mediators.
format Preprint
id arxiv_https___arxiv_org_abs_2604_10710
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Causal mediation in cluster-randomized trials with multiple mediators: spillover-aware decomposition, identification, and semiparametric efficient inference
Tong, Jiaqi
Cheng, Chao
Li, Fan
Methodology
Causal mediation analysis in cluster-randomized trials (CRTs) is complicated by the presence of multiple mediators, intracluster correlation, and within-cluster interference. Existing mediation methods often fall short in accommodating these features simultaneously, and semiparametric efficient estimators that fully address them remain unavailable. We develop a unified framework that defines a class of mediation effect estimands, including exit indirect effects, exit spillover mediation effects, and their interaction effects, to investigate causal mechanisms in CRTs with an arbitrary number of mediators under an unknown causal structure. We introduce a set of interpretable causal assumptions for point identification of each estimand. For optimal inference, we first derive the efficient influence functions for the proposed estimands and construct corresponding one-step and debiased machine learning estimators. In particular, to flexibly model the joint mediator density, we employ an elliptical copula marginal regression model that combines a nonparametric marginal regression with an interpretable association structure. We assess the finite-sample performance of the proposed estimators through simulation studies and illustrate the methodology by reanalyzing the PPACT CRT data with three causally unordered mediators.
title Causal mediation in cluster-randomized trials with multiple mediators: spillover-aware decomposition, identification, and semiparametric efficient inference
topic Methodology
url https://arxiv.org/abs/2604.10710