Mediation analysis (Robins & Greenland 1992, Pearl 2001, Imai, Keele & Tingley 2010, Tchetgen Tchetgen & Shpitser 2012) provides a principled framework for investigating causal mechanisms by decomposing the effect of a treatment A on an outcome Y into pathways operating through a mediator of interest M. Classical mediation analysis focuses on the natural indirect effect, corresponding to the pathway from Ato Y through M, and the natural direct effect, corresponding to pathways not through M. These estimands are well understood when a single mediator is present and strong identification assumptions hold. However, in many applications, there exist multiple intermediate variables between treatment and outcome. In such settings, conventional mediation analysis typically requires the absence of treatment-induced mediator-outcome confounders--often referred to as recanting witnesses--as well as the absence of unmeasured confounding. Under these circumstances, commonly used identification assumptions such as sequential ignorability (Imai, Keele & Yamamoto 2010) or nonparametric structural equation models with independent errors (NPSEM-IE) (Pearl 2009) no longer suffice to identify natural indirect effects (Avin et al. 2005, Tchetgen Tchetgen & VanderWeele 2014). Figure 1 illustrates this issue: the recanting witness D is directly affected by A and simultaneously confounds the relationship between M and Y. Such treatment-induced confounding is common in epidemiologic studies, particularly when the mediator of interest occurs long after the treatment initiation (Robins 1999). A motivating example arises in studies of preterm birth. Mediation analysis has been widely used to explore whether adequate prenatal care (A) reduces the risk of preterm birth (Y) through preeclampsia (M) (Vansteelandt & VanderWeele 2012, VanderWeele et al. 2014, Xia & Chan 2023).

In various domains, different subjects may exhibit different responses to the same set of treatments. The exploration of this heterogeneity in the effects resulting from exposure has gained substantial interest in recent years. For instance, inferring the heterogeneous effect of a medical treatment on clinical outcome can contribute to the development of personalized treatment (Cai et al., 2011). A similar concept has found application in personalized marketing as well (Chandra et al., 2022).

Estimating causal effects of continuous treatments is a common problem in practice, for example, in studying dose-response functions. Classical analyses typically assume that all confounders are fully observed, whereas in real-world applications, unmeasured confounding often persists. In this article, we propose a novel framework for local identification of dose-response functions using instrumental variables, thereby mitigating bias induced by unobserved confounders. We introduce the concept of a uniform regular weighting function and consider covering the treatment space with a finite collection of open sets. On each of these sets, such a weighting function exists, allowing us to identify the dose-response function locally within the corresponding region. For estimation, we develop an augmented inverse probability weighting score for continuous treatments under a debiased machine learning framework with instrumental variables. We further establish the asymptotic properties when the dose-response function is estimated via kernel regression or empirical risk minimization. Finally, we conduct both simulation and empirical studies to assess the finite-sample performance of the proposed methods.

Dynamic treatment regimes are sequential decision rules that adapt treatment according to individual time-varying characteristics and outcomes to achieve optimal effects, with applications in precision medicine, personalized recommendations, and dynamic marketing. Estimating optimal dynamic treatment regimes via sequential randomized trials might face costly and ethical hurdles, often necessitating the use of historical observational data. In this work, we utilize proximal causal inference framework for learning optimal dynamic treatment regimes when the unconfoundedness assumption fails. Our contributions are four-fold: (i) we propose three nonparametric identification methods for optimal dynamic treatment regimes; (ii) we establish the semiparametric efficiency bound for the value function of a given regime; (iii) we propose a (K+1)-robust method for learning optimal dynamic treatment regimes, where K is the number of stages; (iv) as a by-product for marginal structural models, we establish identification and estimation of counterfactual means under a static regime. Numerical experiments validate the efficiency and multiple robustness of our proposed methods.

Instrumental variable methods are fundamental to causal inference when treatment assignment is confounded by unobserved variables. In this article, we develop a general nonparametric framework for identification and learning with multi-categorical or continuous instrumental variables. Specifically, we propose an additive instrumental variable framework to identify mean potential outcomes and the average treatment effect with a weighting function. Leveraging semiparametric theory, we derive efficient influence functions and construct consistent, asymptotically normal estimators via debiased machine learning. Extensions to longitudinal data, dynamic treatment regimes, and multiplicative instrumental variables are further developed. We demonstrate the proposed method by employing simulation studies and analyzing real data from the Job Training Partnership Act program.

Causal inference is no exception.