Cumulative Natural Direct and Indirect Effects for Causal Mediation Analysis
因果中介分析中的累积自然直接效应与间接效应AI 解读 ↓
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Causal mediation analysis provides a fundamental framework for quantifying the contributions of different pathways from a treatment $X$ to an outcome $Y$ through a mediator. The natural direct and indirect effects (NDE and NIE) are widely used to decompose the total effect. In this paper, we observe that NDE and NIE can give rise to paradoxical interpretations due to their failure to satisfy two desirable properties of interpretable causal effects: skew-symmetry and additivity. To address these limitations, we introduce new measures of direct and indirect effects for continuous treatments, termed the cumulative natural direct and indirect effects (CNDE and CNIE), constructed by decomposing local causal effects $\mathbb{E}[\partial_xY_{x}]$ into local direct and indirect effects. CNDE and CNIE yield a decomposition of the total effect that preserves both skew-symmetry and additivity. We further extend this framework to ordinal treatments by defining discrete analogues of the cumulative effects over ordered treatment levels that preserve these structural properties. We establish decomposition and identification results for the proposed measures under standard causal assumptions. We illustrate their behavior, in comparison with NDE and NIE, using canonical linear mediation models with interaction and a real-world dataset.
Mendelian randomization (MR) infers causal effects of exposures on outcomes using genetic variants as instrumental variables, but existing methods remain vulnerable to bias and loss of power when instruments are invalid. We hypothesize that closely related outcome traits share a large overlap in their valid instruments for a given exposure, so that borrowing instruments across such traits can yield more robust MR inference. To operationalize this, we introduce a novel…
Principal stratification (PS) is a commonly used approach for understanding the mechanisms through which a treatment affects an outcome. The goal of this work is to extend the PS framework to studies with continuous treatments, which introduces a number of both challenges and opportunities in terms of defining causal effects and performing inference. This manuscript provides multiple key methodological contributions: 1) we introduce principal causal estimands for continuous…
Background: Generalized Odds (Gen Odds) provide summaries for ordinal outcomes without requiring the proportional odds assumption. However, conventional Gen Odds compares independently drawn treatment and control outcomes and targets a population-level contrast rather than an individual-level contrast. We developed an individual-level causal formulation of Gen Odds and examined its identification. Methods: We defined the Causal Gen Odds using the joint distribution of…
We develop a semiparametric continuous time inferential framework for testing cumulative treatment effects, including both immediate and carryover effects. The latent state process is modeled by an ordinary differential equation (ODE) whose drift depends on state and treatment, while the observed data are noisy measurements of this latent state at irregular, multi resolution time points. We define the average treatment effect (ATE) as the difference of expected cumulative…
We study inference for continuous linear functionals of solutions to ill-posed inverse problems, including Euclidean parameters arising in nonparametric instrumental variables, proximal causal inference, and shadow-variable models. Although pointwise root-$n$ inference is possible under standard conditions, we show that this need not translate into locally reliable inference. Under a model imposing only minimal regularity conditions, the target is Hellinger discontinuous…
Motivation: Mediation analysis is an important tool for elucidating causal mechanisms in biomedical research and has recently gained increasing attention in microbiome studies. Motivated by a microbiome study of acute myeloid leukemia (AML) patients, we investigate whether the effect of induction chemotherapy intensity on infection status is mediated through gut microbial taxa. This problem poses substantial methodological challenges due to the high dimensionality, zero…