Nonparametric causal effects based on marginal structural models

A parametric marginal structural model (PMSM) approach to Causal Inference has been favored since the introduction of MSMs by Robins [1998a. Marginal structural models. In: 1997 Proceedings of the American Statistical Association. American Statistical Association, Alexandria, VA, pp. 1–10]. We propose an alternative, nonparametric MSM (NPMSM) approach that extends the definition of causal parameters of interest and causal effects. This approach is appealing in practice as it does not require correct specification of a parametric model but instead relies on a working model which can be willingly misspecified. We propose a methodology for longitudinal data to generate and estimate so-called NPMSM parameters describing so-called nonparametric causal effects and provide insight on how to interpret these parameters causally in practice. Results are illustrated with a point treatment simulation study. The proposed NPMSM approach to Causal Inference is compared to the more typical PMSM approach and we contribute to the general understanding of PMSM estimation by addressing the issue of PMSM misspecification.     

Estimating the causal effects in randomized trials for survival data with a cure fraction and non compliance

We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.     

Identification of Longitudinal Biomarkers in Survival Analysis for Competing Risks Data

In recent years, joint analysis of longitudinal measurements and survival data has received much attention. However, previous work has primarily focused on a single failure type for the event time. In this article, we consider joint modeling of repeated measurements and competing risks failure time data to allow for more than one distinct failure type in the survival endpoint so we fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure. Besides, previous work does not focus on the hypothesis to test a separate latent association between longitudinal measurements and each cause of failure. In this article, we derive a score test to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data. With a carefully chosen definition of complete data, the maximum likelihood estimation of the cause-specific hazard functions is performed via an EM algorithm. We extend this work and allow random effects to be present in both the longitudinal biomarker and underlying survival function. The random effects in the biomarker are introduced via an explicit term while the random effect in the underlying survival function is introduced by the inclusion of frailty into the model.

We use simulations to explore how the number of individuals, the number of time points per individual and the functional form of the random effects from the longitudinal biomarkers considering heterogeneous baseline hazards in individuals influence the power to detect the association of a longitudinal biomarker and the survival time.     

Joint modeling of multivariate longitudinal mixed measurements and time to event data using a Bayesian approach

In many longitudinal studies multiple characteristics of each individual, along with time to occurrence of an event of interest, are often collected. In such data set, some of the correlated characteristics may be discrete and some of them may be continuous. In this paper, a joint model for analysing multivariate longitudinal data comprising mixed continuous and ordinal responses and a time to event variable is proposed. We model the association structure between longitudinal mixed data and time to event data using a multivariate zero-mean Gaussian process. For modeling discrete ordinal data we assume a continuous latent variable follows the logistic distribution and for continuous data a Gaussian mixed effects model is used. For the event time variable, an accelerated failure time model is considered under different distributional assumptions. For parameter estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. The performance of the proposed methods is illustrated using some simulation studies. A real data set is also analyzed, where different model structures are used. Model comparison is performed using a variety of statistical criteria.     

A general joint model for longitudinal measurements and competing risks survival data with heterogeneous random effects

This article studies a general joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the competing risks survival data, and a regression sub-model for the variance–covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. The model provides a useful approach to adjust for non-ignorable missing data due to dropout for the longitudinal outcome, enables analysis of the survival outcome with informative censoring and intermittently measured time-dependent covariates, as well as joint analysis of the longitudinal and survival outcomes. Unlike previously studied joint models, our model allows for heterogeneous random covariance matrices. It also offers a framework to assess the homogeneous covariance assumption of existing joint models. A Bayesian MCMC procedure is developed for parameter estimation and inference. Its performances and frequentist properties are investigated using simulations. A real data example is used to illustrate the usefulness of the approach.     

Using information on realized effects to determine prospective causal effects

The potential outcomes approach to causal inference postulates that each individual has a number of possibly latent outcomes, each of which would be observed under a different treatment. For any individual, some of these outcomes will be unobservable or counterfactual. Information about post-treatment characteristics sometimes allows statements about what would have happened if an individual or group with these characteristics had received a different treatment. These are statements about the realized effects of the treatment. Determining the likely effect of an intervention before making a decision involves inference about effects in populations defined only by characteristics observed before decisions about treatment are made. Information on realized effects can tighten bounds on these prospectively defined measures of the intervention effect. We derive formulae for the bounds and their sampling variances and illustrate these points with data from a hypothetical study of the efficacy of screening mammography.     

Likelihood-based approach for analysis of longitudinal nominal data using marginalized random effects models

Likelihood-based marginalized models using random effects have become popular for analyzing longitudinal categorical data. These models permit direct interpretation of marginal mean parameters and characterize the serial dependence of longitudinal outcomes using random effects [12,22]. In this paper, we propose model that expands the use of previous models to accommodate longitudinal nominal data. Random effects using a new covariance matrix with a Kronecker product composition are used to explain serial and categorical dependence. The Quasi-Newton algorithm is developed for estimation. These proposed methods are illustrated with a real data set and compared with other standard methods.     

Formative Indicators and Effects of a Causal Model for Household Human Capital with Application

Dagum and Slottje (2000) estimated household human capital (HC) as a latent variable (LV) and proposed its monetary estimation by means of an actuarial approach. This paper introduces an improved method for the estimation of household HC as an LV by means of formative and reflective indicators in agreement with the accepted economic definition of HC. The monetary value of HC is used in a recursive causal model to obtain short- and long-term multipliers that measure the direct and total effects of the variables that determine household HC. The new method is applied to estimate US household HC for year 2004.     

Minque of variance components in generalized linear model with random effects

We consider the estimation of thc variance components in generalized Linear model with random effects. The Method of Minimum Norm Quadratic Unbiased Estimators extending the Rao's argument is outlined. The method is illustrated with an analysis of cell irradiation data and compared to the methods of estimation proposed by Schall (1991).     

Random effects models for operational patient pathways

Patient flow modeling is a growing field of interest in health services research. Several techniques have been applied to model movement of patients within and between health-care facilities. However, individual patient experience during the delivery of care has always been overlooked. In this work, a random effects model is introduced to patient flow modeling and applied to a London Hospital Neonatal unit data. In particular, a random effects multinomial logit model is used to capture individual patient trajectories in the process of care with patient frailties modeled as random effects. Intuitively, both operational and clinical patient flow are modeled, the former being physical and the latter latent. Two variants of the model are proposed, one based on mere patient pathways and the other based on patient characteristics. Our technique could identify interesting pathways such as those that result in high probability of death (survival), pathways incurring the least (highest) cost of care or pathways with the least (highest) length of stay. Patient-specific discharge probabilities from the health care system could also be predicted. These are of interest to health-care managers in planning the scarce resources needed to run health-care institutions.     

计量经济学中的潜变量模型：一个方法论角度的考察

上世纪中叶,因子分析和典型相关分析方法的发展完善,解决了潜变量的测度及其相关关系衡量问题,奠定了潜变量因果模型的方法论基础。此后,潜变量模型被引入到计量经济学研究领域,依次经历了共同结构范式模型、经典潜变量模型和非经典潜变量模型三个阶段,逐步成为现代计量经济模型的重要组成部分。本文从方法论角度对计量经济学中的潜变量模型发展过程进行了全面考察,比较了各个阶段建模方法论的特征,归纳总结了其发展演化规律,并对下一步研究的重点领域进行了展望。     

Estimation of Causal Effects in Latent Strata with an Encouragement for Response

We consider a new approach to deal with non ignorable non response on an outcome variable, in a causal inference framework. Assuming that a binary instrumental variable for non response is available, we provide a likelihood-based approach to identify and estimate heterogeneous causal effects of a binary treatment on specific latent subgroups of units, named principal strata, defined by the non response behavior under each level of the treatment and of the instrument. We show that, within each stratum, non response is ignorable and respondents can be properly compared by treatment status. In order to assess our method and its robustness when the usually invoked assumptions are relaxed or misspecified, we simulate data to resemble a real experiment conducted on a panel survey which compares different methods of reducing panel attrition.     

Joint modeling of longitudinal data with a dependent terminal event

ABSTRACT

Longitudinal data often arise in longitudinal follow-up studies, and there may exist a dependent terminal event such as death that stops the follow-up. In this article, we propose a new joint modeling for the analysis of longitudinal data with informative observation times via a dependent terminal event and two latent variables. Estimating equations are developed for parameter estimation, and asymptotic properties of the resulting estimators are established. In addition, a generalization of the joint model with time-varying coefficients for the longitudinal response variable is considered, and goodness-of-fit methods for assessing the adequacy of the model are also provided. The proposed method works well in our simulation studies, and is applied to a data set from a bladder cancer study.     

含非随机缺失数据的面板数据参数估计方法

抽样调查领域常采用对多个受访者进行跟踪调查得到面板数据,进而对总体特性进行统计推断,在面板数据中常含缺失数据,大多数处理面板缺失数据的软件都是直接删去含缺失值的受访者以得到完全数据集,当数据缺失机制为非随机缺失时会导致总体参数估计结果有偏。本文针对数据缺失机制为非随机缺失情形下,如何对面板数据进行统计分析进行了阐述,主要采用的是基于模型的似然推断法,对目标变量、缺失指示变量和随机效应向量的联合分布建模,在已有选择模型和模式混合模型的基础上,引入随机效应,研究目标变量期望的计算方法,并研究随机效应杂合模型下参数的估计方法,在变量分布相对简单的情形下给出了用极大似然法推断总体参数的估计步骤,最后通过模拟分析比较方法的优劣。     

Causal Reasoning from Longitudinal Data*

Abstract. This paper reviews some of the key statistical ideas that are encountered when trying to find empirical support to causal interpretations and conclusions, by applying statistical methods on experimental or observational longitudinal data. In such data, typically a collection of individuals are followed over time, then each one has registered a sequence of covariate measurements along with values of control variables that in the analysis are to be interpreted as causes, and finally the individual outcomes or responses are reported. Particular attention is given to the potentially important problem of confounding. We provide conditions under which, at least in principle, unconfounded estimation of the causal effects can be accomplished. Our approach for dealing with causal problems is entirely probabilistic, and we apply Bayesian ideas and techniques to deal with the corresponding statistical inference. In particular, we use the general framework of marked point processes for setting up the probability models, and consider posterior predictive distributions as providing the natural summary measures for assessing the causal effects. We also draw connections to relevant recent work in this area, notably to Judea Pearl's formulations based on graphical models and his calculus of so‐called do‐probabilities. Two examples illustrating different aspects of causal reasoning are discussed in detail.     

Regression analysis of longitudinal data with time-dependent covariates in the presence of informative observation and censoring times

In longitudinal observational studies, repeated measures are often correlated with observation times as well as censoring time. This article proposes joint modeling and analysis of longitudinal data with time-dependent covariates in the presence of informative observation and censoring times via a latent variable. Estimating equation approaches are developed for parameter estimation and asymptotic properties of the proposed estimators are established. In addition, a generalization of the semiparametric model with time-varying coefficients for the longitudinal response is considered. Furthermore, a lack-of-fit test is provided for assessing the adequacy of the model, and some tests are presented for investigating whether or not covariate effects vary with time. The finite-sample behavior of the proposed methods is examined in simulation studies, and an application to a bladder cancer study is illustrated.     

Bayesian response adaptive randomization using longitudinal outcomes

The response adaptive randomization (RAR) method is used to increase the number of patients assigned to more efficacious treatment arms in clinical trials. In many trials evaluating longitudinal patient outcomes, RAR methods based only on the final measurement may not benefit significantly from RAR because of its delayed initiation. We propose a Bayesian RAR method to improve RAR performance by accounting for longitudinal patient outcomes (longitudinal RAR). We use a Bayesian linear mixed effects model to analyze longitudinal continuous patient outcomes for calculating a patient allocation probability. In addition, we aim to mitigate the loss of statistical power because of large patient allocation imbalances by embedding adjusters into the patient allocation probability calculation. Using extensive simulation we compared the operating characteristics of our proposed longitudinal RAR method with those of the RAR method based only on the final measurement and with an equal randomization method. Simulation results showed that our proposed longitudinal RAR method assigned more patients to the presumably superior treatment arm compared with the other two methods. In addition, the embedded adjuster effectively worked to prevent extreme patient allocation imbalances. However, our proposed method may not function adequately when the treatment effect difference is moderate or less, and still needs to be modified to deal with unexpectedly large departures from the presumed longitudinal data model. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantile regression for longitudinal data based on latent Markov subject-specific parameters

We propose a latent Markov quantile regression model for longitudinal data with non-informative drop-out. The observations, conditionally on covariates, are modeled through an asymmetric Laplace distribution. Random effects are assumed to be time-varying and to follow a first order latent Markov chain. This latter assumption is easily interpretable and allows exact inference through an ad hoc EM-type algorithm based on appropriate recursions. Finally, we illustrate the model on a benchmark data set.     

Modelling Survival Events with Longitudinal Covariates Measured with Error

In survival analysis, time-dependent covariates are usually present as longitudinal data collected periodically and measured with error. The longitudinal data can be assumed to follow a linear mixed effect model and Cox regression models may be used for modelling of survival events. The hazard rate of survival times depends on the underlying time-dependent covariate measured with error, which may be described by random effects. Most existing methods proposed for such models assume a parametric distribution assumption on the random effects and specify a normally distributed error term for the linear mixed effect model. These assumptions may not be always valid in practice. In this article, we propose a new likelihood method for Cox regression models with error-contaminated time-dependent covariates. The proposed method does not require any parametric distribution assumption on random effects and random errors. Asymptotic properties for parameter estimators are provided. Simulation results show that under certain situations the proposed methods are more efficient than the existing methods.     

Gene Pathways Discovery in Asbestos-Related Diseases using Local Causal Discovery Algorithm

To learn about the progression of a complex disease, it is necessary to understand the physiology and function of many genes operating together in distinct interactions as a system. In order to significantly advance our understanding of the function of a system, we need to learn the causal relationships among its modeled genes. To this end, it is desirable to compare experiments of the system under complete interventions of some genes, e.g., knock-out of some genes, with experiments of the system without interventions. However, it is expensive and difficult (if not impossible) to conduct wet lab experiments of complete interventions of genes in animal models, e.g., a mouse model. Thus, it will be helpful if we can discover promising causal relationships among genes with observational data alone in order to identify promising genes to perturb in the system that can later be verified in wet laboratories. While causal Bayesian networks have been actively used in discovering gene pathways, most of the algorithms that discover pairwise causal relationships from observational data alone identify only a small number of significant pairwise causal relationships, even with a large dataset. In this article, we introduce new causal discovery algorithms—the Equivalence Local Implicit latent variable scoring Method (EquLIM) and EquLIM with Markov chain Monte Carlo search algorithm (EquLIM-MCMC)—that identify promising causal relationships even with a small observational dataset.