Dynamic prediction of causal effects under different treatment regimes conditional on an individual's characteristics and longitudinal history is an essential problem in precision medicine. This is challenging in practice because outcomes and treatment assignment mechanisms are unknown in observational studies, an individual's treatment efficacy is a counterfactual, and the existence of selection bias is often unavoidable.
We propose a Bayesian framework for identifying subgroup counterfactual benefits of dynamic treatment regimes by adapting Bayesian g-computation algorithm (J. Robins, 1986; Zhou, Elliott, & Little, 2019) to incorporate multivariate generalized linear mixed-effects models. Unmeasured time-invariant factors are identified as subject-specific random effects in the assumed joint distribution of outcomes, time-varying confounders, and treatment assignments. Existing methods mostly assume no unmeasured confounding and focus on balancing the observed confounder distributions between different treatments, while our method allows the presence of time-invariant unmeasured confounding. We propose a sequential ignorability assumption based on treatment assignment heterogeneity, which is analogous to balancing the latent tendency toward each treatment due to unmeasured time-invariant factors beyond the observables. We use simulation studies to assess the sensitivity of the proposed method's performance to various model assumptions. The method is applied to observational clinical data to investigate the efficacy of continuously using mycophenolate in different subgroups of scleroderma patients who were treated with the drug.
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…
An efficient monotone data augmentation (MDA) algorithm is proposed for missing data imputation for incomplete multivariate nonnormal data that may contain variables of different types, and are modeled by a sequence of regression models including the linear, binary logistic, multinomial logistic, proportional odds, Poisson, negative binomial, skew-normal, skew-t regressions or a mixture of these models. The MDA algorithm is applied to the sensitivity analyses of longitudinal trials with nonignorable dropout using the controlled pattern imputations that assume the treatment effect reduces or di…
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 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…
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…
Selection of covariates is crucial in the estimation of average treatment effects given observational data with high or even ultra-high dimensional pretreatment variables. Existing methods for this problem typically assume sparse linear models for both outcome and univariate treatment, and cannot handle situations with ultra-high dimensional covariates. In this paper, we propose a new covariate selection strategy called double screening prior adaptive lasso (DSPAL) to select confounders and predictors of the outcome for multivariate treatments, which combines the adaptive lasso method with the…
Causal inference is widely used in various fields, such as biology, psychology and economics, etc. In observational studies, we need to balance the covariates before estimating causal effect. This study extends the one-dimensional entropy balancing method to multiple dimensions to balance the covariates. Both parametric and nonparametric methods are proposed to estimate the causal effect of multivariate continuous treatments and theoretical properties of the two estimations are provided. Furthermore, the simulation results show that the proposed method is better than other methods in various c…
Measuring the causal impact of an advertising campaign on sales is an essential task for advertising companies. Challenges arise when companies run advertising campaigns in multiple stores which are spatially correlated, and when the sales data have a low signal-to-noise ratio which makes the advertising effects hard to detect. This paper proposes a solution to address both of these challenges. A novel Bayesian method is proposed to detect weaker impacts and a multivariate structural time series model is used to capture the spatial correlation between stores through placing a $\mathcal{G}$-Wis…
Our goal is to estimate causal interactions in multivariate time series. Using vector autoregressive (VAR) models, these can be defined based on non-vanishing coefficients belonging to respective time-lagged instances. As in most cases a parsimonious causality structure is assumed, a promising approach to causal discovery consists in fitting VAR models with an additional sparsity-promoting regularization. Along this line we here propose that sparsity should be enforced for the subgroups of coefficients that belong to each pair of time series, as the absence of a causal relation requires the co…
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…
A Bayesian semi-parametric approach to causal mediation for longitudinal mediators and time-to-event outcomes with application to a cardiovascular disease cohort study
The use of observational time series data to assess the impact of multi-time point interventions is becoming increasingly common as more health and activity data are collected and digitized via wearables, social media, and electronic health records. Such time series may involve hundreds or thousands of irregularly sampled observations. One common analysis approach is to simplify such time series by first discretizing them into sequences before applying a discrete-time estimation method that adjusts for time-dependent confounding. In certain settings, this discretization results in sequences wi…
Single-subject health data are becoming increasingly available thanks to advances in self-tracking technology (e.g., wearable devices, mobile apps, sensors, implants). Many users and health caregivers seek to use such observational time series data to recommend changing health practices in order to achieve desired health outcomes. However, there are few available causal inference approaches that are flexible enough to analyze such idiographic data. We develop a recently introduced causal-analysis framework based on n-of-1 randomized trials, and implement a flexible random-forests g-formula app…
Participant noncompliance, in which participants do not follow their assigned treatment protocol, often obscures the causal relationship between treatment and treatment effect in randomized trials. In the longitudinal setting, the G-computation algorithm can adjust for confounding to estimate causal effects. Typically, G-computation assumes that both 1) compliance is observed; and 2) the densities of the confounders can be correctly specified. We aim to develop a G-computation estimator in the setting where both assumptions are violated. For 1), in place of unobserved compliance, we substitute…
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 fo…
Causal mediation analysis for zero-inflated longitudinal data in the presence of treatment non-compliance and multiple mediators
University of Chicago（芝加哥大学）；Smeal College of Business, The Pennsylvania State University（宾夕法尼亚州立大学斯米尔商学院）；University of Florida（佛罗里达大学）；University of Wisconsin–Madison（威斯康星大学麦迪逊分校）
A new class of Marginal Structural Models (MSMs), History-Restricted MSMs (HRMSMs), was recently introduced for longitudinal data for the purpose of defining causal parameters which may often be better suited for public health research or at least more practicable than MSMs \citejoffe,feldman. HRMSMs allow investigators to analyze the causal effect of a treatment on an outcome based on a fixed, shorter and user-specified history of exposure compared to MSMs. By default, the latter represent the treatment causal effect of interest based on a treatment history defined by the treatments assigned …
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…
Operationalizing Longitudinal Causal Discovery Under Real-World Workflow Constraints
Kyoto University Graduate School of Medicine（京都大学医学研究科）；SANKEN The University of Osaka（SANKEN 大阪大学）；Faculty of Data Science Shiga University（Shiga大学数据科学学部）；AIP RIKEN；Faculty of Medicine, University of Miyazaki（Miyazaki大学医学部）；Hiroshima University Graduate School of Biomedical and Health Sciences（广岛大学生物医学和健康科学研究生院）
Max Planck Institute for Informatics（马克斯·普朗克信息学研究所）；Saarland University（萨尔大学）
Given data over the joint distribution of two random variables $X$ and $Y$, we consider the problem of inferring the most likely causal direction between $X$ and $Y$. In particular, we consider the general case where both $X$ and $Y$ may be univariate or multivariate, and of the same or mixed data types. We take an information theoretic approach, based on Kolmogorov complexity, from which it follows that first describing the data over cause and then that of effect given cause is shorter than the reverse direction. The ideal score is not computable, but can be approximated through the Minimum D…
Hamilton Institute（汉密尔顿研究所）；Maynooth University（梅努斯大学）；Department of Mathematics and Statistics, Maynooth University（梅努斯大学数学与统计系）
Bayesian Causal Forests (BCF) is a causal inference machine learning model based on a highly flexible non-parametric regression and classification tool called Bayesian Additive Regression Trees (BART). Motivated by data from the Trends in International Mathematics and Science Study (TIMSS), which includes data on student achievement in both mathematics and science, we present a multivariate extension of the BCF algorithm. With the help of simulation studies we show that our approach can accurately estimate causal effects for multiple outcomes subject to the same treatment. We also apply our mo…
We present Causal Generative Neural Networks (CGNNs) to learn functional causal models from observational data. CGNNs leverage conditional independencies and distributional asymmetries to discover bivariate and multivariate causal structures. CGNNs make no assumption regarding the lack of confounders, and learn a differentiable generative model of the data by using backpropagation. Extensive experiments show their good performances comparatively to the state of the art in observational causal discovery on both simulated and real data, with respect to cause-effect inference, v-structure identif…
Causal mediation analysis seeks to investigate how the treatment effect of an exposure on outcomes is mediated through intermediate variables. Although many applications involve longitudinal data, the existing methods are not directly applicable to settings where the mediator and outcome are measured on sparse and irregular time grids. We extend the existing causal mediation framework from a functional data analysis perspective, viewing the sparse and irregular longitudinal data as realizations of underlying smooth stochastic processes. We define causal estimands of direct and indirect effects…
M-CaStLe: Uncovering Local Causal Structures in Multivariate Space-Time Gridded Data
Scientific Machine Learning, Center for Computing Research（科学机器学习，计算研究中心）；Sandia National Laboratories（沙伊达国家实验室）；Zicklin School of Business Baruch College, CUNY（巴鲁克学院Zicklin商学院，纽约大学）；Department of Computer Science University of New Mexico（新墨西哥大学计算机科学系）；Department of Atmospheric & Oceanic Science University of Maryland（马里兰大学大气与海洋科学系）；Santa Fe Institute（圣菲研究所）
Centre for Big Data Research in Health (CBDRH)（健康大数据研究中心）
Causal inference for observational longitudinal studies often requires the accurate estimation of treatment effects on time-to-event outcomes in the presence of time-dependent patient history and time-dependent covariates. To tackle this longitudinal treatment effect estimation problem, we have developed a time-variant causal survival (TCS) model that uses the potential outcomes framework with an ensemble of recurrent subnetworks to estimate the difference in survival probabilities and its confidence interval over time as a function of time-dependent covariates and treatments. Using simulated …
Most of the available multivariate statistical models dictate on fitting different parameters for the covariate effects on each multiple responses. This might be unnecessary and inefficient for some cases. In this article, we propose a modeling framework for multivariate marginal models to analyze multivariate longitudinal data which provides flexible model building strategies. We show that the model handles several response families such as binomial, count and continuous. We illustrate the model on the Mother's Stress and Children's Morbidity data set. A simulation study is conducted to exami…
We propose a statistical method for clustering of multivariate longitudinal data into homogeneous groups. This method relies on a time-varying extension on the classical K-means algorithm, where a multivariate vector autoregressive model is additionally assumed for modeling the evolution of clusters' centroids over time. We base the inference on a least squares specification of the model and coordinate descent algorithm. To illustrate our work, we consider a longitudinal dataset on human development. Three variables are modeled, namely life expectancy, education and gross domestic product.
Causal Diffusion Models for Counterfactual Outcome Distributions in Longitudinal Data
Department of Economics, Northeastern University（东北大学经济学系）；Center for Health Policy and Healthcare Research, Northeastern University（东北大学健康政策与医疗研究中心）；Department of Public Health and Health Sciences, Bouvé College of Health Sciences, Northeastern University（东北大学布维健康科学学院公共卫生与健康科学系）
Extreme hydrological events in the Danube river basin may severely impact human populations, aquatic organisms, and economic activity. One often characterizes the joint structure of the extreme events using the theory of multivariate and spatial extremes and its asymptotically justified models. There is interest however in cascading extreme events and whether one event causes another. In this paper, we argue that an improved understanding of the mechanism underlying severe events is achieved by combining extreme value modelling and causal discovery. We construct a causal inference method relyi…
RE-EM tree is a tree-based method that combines the regression tree and the linear mixed effects model for modeling univariate response longitudinal or clustered data. In this paper, we generalize the RE-EM tree method to multivariate response data, by adopting the Multivariate Regression Tree method proposed by De'Ath [2002]. The Multivariate RE-EM tree method estimates a population-level single tree structure that is driven by the multiple responses simultaneously and object-level random effects for each response variable, where correlation between the response variables and between the asso…
