Causal effects may vary among individuals and can even be of opposite signs. When significant effect heterogeneity exists, the population average causal effect might be uninformative for an individual. Due to the fundamental problem of causality, individual causal effects (ICEs) cannot be retrieved from cross-sectional data. However, in crossover studies, it is accepted that ICEs can be estimated under the assumptions of no carryover effects and time invariance of potential outcomes. A generic potential-outcome formulation with appropriate statistical assumptions to identify ICEs is lacking for other longitudinal data with time-varying exposures. We present a general framework for causal effect heterogeneity in which individual-specific effect modification is parameterized with a latent variable, the receptiveness factor. If the exposure varies over time, then the repeated measurements contain information on an individual's level of this receptiveness factor. Therefore, we study the conditional distribution of the ICE given all an individual's factual information. This novel conditional random variable is called the cross-world causal effect (CWCE). For known causal structures and time-varying exposures, the variability of the CWCE reduces with an increasing number of repeated measurements. The CWCE becomes identifiable from observational data under the causal assumption of cross-world similarity of individual-effect modification (i.e. there exists an exposure strategy whose effect is affected by all latent causes). We illustrate the theory with examples in which the cause-effect relations can be parameterized as generalized linear mixed assignments.
Exposure mappings facilitate investigations of complex causal effects when units interact in experiments. Current methods require experimenters to use the same exposure mappings both to define the effect of interest and to impose assumptions on the interference structure. However, the two roles rarely coincide in practice, and experimenters are forced to make the often questionable assumption that their exposures are correctly specified. This paper argues that the two roles exposure mappings currently serve can, and typically should, be separated, so that exposures are used to define effects w…
Causal inference methods have been applied in various fields where researchers want to estimate treatment effects. In traditional causal inference settings, one assumes that the outcome of a unit does not depend on treatments of other units. However, as causal inference methods are extended to more applications, there is a greater need for estimators of general causal effects. We use an exposure mapping framework [Aronow and Samii, 2017] to map the relationship between the treatment allocation and the potential outcomes. Under the exposure model, we propose linear unbiased estimators (LUEs) fo…
Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a causal effect of the exposure on the outcome. Complications arise with a binary exposure that is a dichotomization of a continuous risk factor (for example, hypertension is a dichotomization of blood pressure). This can lead to violation of the exclusion restriction assumption: the genetic variant can influence the outcome via the continuous risk factor even if…
Improving Causal Inference with Measurement Errors in Exposures and Confounders: A New Method and Its Application to Air Pollution Exposure Assessment and Epidemiology
Two-stage Estimation for Causal Inference Involving a Semi-continuous Exposure
University of Waterloo（滑铁卢大学）；Ankara University（安卡拉大学）；Columbia University（哥伦比亚大学）；Wayne State University（韦恩州立大学）；University of Technology Sydney（悉尼科技大学）
In many scientific studies, it is of interest to determine whether an exposure has a causal effect on an outcome. In observational studies, this is a challenging task due to the presence of confounding variables that affect both the exposure and the outcome. Many methods have been developed to test for the presence of a causal effect when all such confounding variables are observed and when the exposure of interest is discrete. In this article, we propose a class of nonparametric tests of the null hypothesis that there is no average causal effect of an arbitrary univariate exposure on an outco…
Mediation analysis is concerned with the decomposition of the total effect of an exposure on an outcome into the indirect effect through a given mediator, and the remaining direct effect. This is ideally done using longitudinal measurements of the mediator, as these capture the mediator process more finely. However, longitudinal measurements pose challenges for mediation analysis. This is because the mediators and outcomes measured at a given time-point can act as confounders for the association between mediators and outcomes at a later time-point; these confounders are themselves affected by …
A standard assumption for causal inference about the joint effects of time-varying treatment is that one has measured sufficient covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values, also known as "sequential randomization assumption (SRA)". SRA is often criticized as it requires one to accurately measure all confounders. Realistically, measured covariates can rarely capture all confounders with certainty. Often covariate measurements are at best proxies of confounders, thus invalidating inferences under SRA. In this paper, we extend the…
Many causal models of interest in epidemiology involve longitudinal exposures, confounders and mediators. However, repeated measurements are not always available or used in practice, leading analysts to overlook the time-varying nature of exposures and work under over-simplified causal models. Our objective is to assess whether - and how - causal effects identified under such misspecified causal models relates to true causal effects of interest. We derive sufficient conditions ensuring that the quantities estimated in practice under over-simplified causal models can be expressed as weighted av…
Background: Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction. Methods: We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure. Results: Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous and the effect of the exposure on the outcome is non-linear on the …
The Clean Air Act mandates that the National Ambient Air Quality Standards (NAAQS) must be routinely assessed to protect populations based on the latest science. Therefore, researchers should continue to address whether exposure to levels of air pollution below the NAAQS is harmful to human health. The contentious nature surrounding environmental regulations urges us to cast this question within a causal inference framework. Parametric and semi-parametric regression approaches have been used to estimate the exposure-response (ER) curve between ambient air pollution and health outcomes. Most of…
The generalized propensity score (GPS) is an extension of the propensity score for use with quantitative or continuous exposures (e.g., dose of medication or years of education). Current GPS methods allow estimation of the dose-response relationship between a single continuous exposure and an outcome. However, in many real-world settings, there are multiple exposures occurring simultaneously that could be causally related to the outcome. We propose a multivariate GPS method (mvGPS) that allows estimation of a dose-response surface that relates the joint distribution of multiple continuous expo…
We propose a new approach for estimating causal effects when the exposure is measured with error and confounding adjustment is performed via a generalized propensity score (GPS). Using validation data, we propose a regression calibration (RC)-based adjustment for a continuous error-prone exposure combined with GPS to adjust for confounding (RC-GPS). The outcome analysis is conducted after transforming the corrected continuous exposure into a categorical exposure. We consider confounding adjustment in the context of GPS subclassification, inverse probability treatment weighting (IPTW) and match…
Causal Inference with Missing Exposures and Missing Outcomes
University of California Berkeley（加州大学伯克利分校）；University of California San Francisco（加州大学旧金山分校）；Infectious Diseases Research Collaboration（传染病研究协作组织）；Makerere University（马凯雷雷大学）
Missing exposure information is a very common feature of many observational studies. Here we study identifiability and efficient estimation of causal effects on vector outcomes, in such cases where treatment is unconfounded but partially missing. We consider a missing at random setting where missingness in treatment can depend not only on complex covariates, but also on post-treatment outcomes. We give a new identifying expression for average treatment effects in this setting, along with the efficient influence function for this parameter in a nonparametric model, which yields a nonparametric …
Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Towards this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the non-causal nuisance parameters. This leads to a series of difficulties in int…
The paper considers mediation analysis with longitudinal data under latent growth curve models within a counterfactual framework. Estimators and their standard errors are derived for natural direct and indirect effects when the mediator, the outcome, and possibly also the exposure can be modeled by an underlying latent variable giving rise to a growth curve. Settings are also considered in which the exposure is instead fixed at a single point in time.
In many scientific fields such as biology, psychology and sociology, there is an increasing interest in estimating the causal effect of a matrix exposure on an outcome. Covariate balancing is crucial in causal inference and both exact balancing and approximate balancing methods have been proposed in the past decades. However, due to the large number of constraints, it is difficult to achieve exact balance or to select the threshold parameters for approximate balancing methods when the treatment is a matrix. To meet these challenges, we propose the weighted Euclidean balancing method, which app…
In this paper we propose a new template for empirical studies intended to assess causal effects: the outcome-wide longitudinal design. The approach is an extension of what is often done to assess the causal effects of a treatment or exposure using confounding control, but now, over numerous outcomes. We discuss the temporal and confounding control principles for such outcome-wide studies, metrics to evaluate robustness or sensitivity to potential unmeasured confounding for each outcome, and approaches to handle multiple testing. We argue that the outcome-wide longitudinal design has numerous a…
Although review papers on causal inference methods are now available, there is a lack of introductory overviews on what they can render and on the guiding criteria for choosing one particular method. This tutorial gives an overview in situations where an exposure of interest is set at a chosen baseline (`point exposure') and the target outcome arises at a later time point. We first phrase relevant causal questions and make a case for being specific about the possible exposure levels involved and the populations for which the question is relevant. Using the potential outcomes framework, we desc…
Centre for Speckled Computing（散斑计算中心）；University of Edinburgh（爱丁堡大学）
According to the Lancet report on the global burden of disease published in October 2020, air pollution is among the five highest risk factors for global health, reducing life expectancy on average by 20 months. This paper describes a data-driven method for establishing causal relationships within and between two multivariate time series data streams derived from wearable sensors: personal exposure to airborne particulate matter of aerodynamic sizes less than 2.5um (PM2.5) gathered from the Airspeck monitor worn on the person and continuous respiratory rate (breaths per minute) measured by the…
Mediation analysis is a strategy for understanding the mechanisms by which treatments or interventions affect later outcomes. Mediation analysis is frequently applied in randomized trial settings, but typically assumes: a) that randomized assignment is the exposure of interest as opposed to actual take-up of the intervention, and b) no unobserved confounding of the mediator-outcome relationship. In contrast to the rich literature on instrumental variable (IV) methods to estimate a total effect of a non-randomized exposure, there has been almost no research into using IV as an identification st…
Most causal inference studies rely on the assumption of overlap to estimate population or sample average causal effects. When data exhibit non-overlap, estimation of these estimands requires reliance on model specifications, due to poor data support. All existing methods to address non-overlap, such as trimming or down-weighting data in regions of poor support, change the estimand. In environmental health research, where study results are often intended to influence policy, changes in the estimand can diminish the study's impact, because estimates may not be representative of effects in the po…
A recent cohort study revealed a positive correlate between major structural birth defects in infants and a certain medication taken by pregnant women. To draw valid causal inference, an outstanding problem to overcome was the missing birth defect outcomes among pregnancy losses resulting from spontaneous abortion. This led to missing not at random since, according to the theory of "terathanasia", a defected fetus is more likely to be spontaneously aborted. Other complications in the data included left truncation, right censoring, observational nature, and rare events. In addition, the previou…
Recently, the intervention calculus when the DAG is absent (IDA) method was developed to estimate lower bounds of causal effects from observational high-dimensional data. Originally it was introduced to assess the effect of baseline biomarkers which do not vary over time. However, in many clinical settings, measurements of biomarkers are repeated at fixed time points during treatment exposure and, therefore, this method need to be extended. The purpose of this paper is then to extend the first step of the IDA, the Peter Clarks (PC)-algorithm, to a time-dependent exposure in the context of a bi…
In animal behavior studies, a common goal is to investigate the causal pathways between an exposure and outcome, and a mediator that lies in between. Causal mediation analysis provides a principled approach for such studies. Although many applications involve longitudinal data, the existing causal mediation models are not directly applicable to settings where the mediators are measured on irregular time grids. In this paper, we propose a causal mediation model that accommodates longitudinal mediators on arbitrary time grids and survival outcomes simultaneously. We take a functional data analys…
