Correlated outcomes are common in many practical problems. In some settings, one outcome is of particular interest, and others are auxiliary. To leverage information shared by all the outcomes, traditional multi-task learning (MTL) minimizes an averaged loss function over all the outcomes, which may lead to biased estimation for the target outcome, especially when the MTL model is mis-specified. In this work, based on a decomposition of estimation bias into two types, within-subspace and against-subspace, we develop a robust transfer learning approach to estimating a high-dimensional linear decision rule for the outcome of interest with the presence of auxiliary outcomes. The proposed method includes an MTL step using all outcomes to gain efficiency, and a subsequent calibration step using only the outcome of interest to correct both types of biases. We show that the final estimator can achieve a lower estimation error than the one using only the single outcome of interest. Simulations and real data analysis are conducted to justify the superiority of the proposed method.
In large epidemiologic studies, it is typical for an inexpensive, non-invasive procedure to be used to record disease status during regular follow-up visits, with less frequent assessment by a gold standard test. Inexpensive outcome measures like self-reported disease status are practical to obtain, but can be error-prone. Association analysis reliant on error-prone outcomes may lead to biased results; however, restricting analyses to only data from the less frequently observed error-free outcome could be inefficient. We have developed an augmented likelihood that incorporates data from both e…
In causal inference, principal stratification is a framework for dealing with a posttreatment intermediate variable between a treatment and an outcome, in which the principal strata are defined by the joint potential values of the intermediate variable. Because the principal strata are not fully observable, the causal effects within them, also known as the principal causal effects, are not identifiable without additional assumptions. Several previous empirical studies leveraged auxiliary variables to improve the inference of principal causal effects. We establish a general theory for identific…
It has recently become popular to define treatment effects for subsets of the target population characterized by variables not observable at the time a treatment decision is made. Characterizing and estimating such treatment effects is tricky; the most popular but naive approach inappropriately adjusts for variables affected by treatment and so is biased. We consider several appropriate ways to formalize the effects: principal stratification, stratification on a single potential auxiliary variable, stratification on an observed auxiliary variable and stratification on expected levels of auxili…
Personalized optimal decision making, finding the optimal decision rule (ODR) based on individual characteristics, has attracted increasing attention recently in many fields, such as education, economics, and medicine. Current ODR methods usually require the primary outcome of interest in samples for assessing treatment effects, namely the experimental sample. However, in many studies, treatments may have a long-term effect, and as such the primary outcome of interest cannot be observed in the experimental sample due to the limited duration of experiments, which makes the estimation of ODR imp…
Improving Mendelian Randomization Analysis by Instrument Borrowing from Auxiliary Outcome Traits
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health（约翰斯·霍普金斯彭博公共卫生学院生物统计系）；Department of Oncology, School of Medicine, Johns Hopkins University（约翰斯·霍普金斯大学医学院肿瘤系）
The problem we consider considers estimating a multivariate longitudinal panel data model whose outcomes can be a combination of discrete and continuous variables. This problem is challenging because the likelihood is usually analytically intractable. Our article makes both a methodological contribution and also a substantive contribution to the application. The methodological contribution is to introduce into the panel data literature a particle Metropolis within Gibbs method to carry out Bayesian inference, using a Hamiltonian Monte Carlo (Neal 2011} proposal for sampling the vector of unkno…
Nonparametric estimation of the conditional expectation $E(Y | U)$ of an outcome $Y$ given a covariate vector $U$ is of primary importance in many statistical applications such as prediction and personalized medicine. In some problems, there is an additional auxiliary variable $Z$ in the training dataset used to construct estimators, but $Z$ is not available for future prediction or selecting patient treatment in personalized medicine. For example, in the training dataset longitudinal outcomes are observed, but only the last outcome $Y$ is concerned in the future prediction or analysis. The lo…
In biomedical studies it is common to collect data on multiple biomarkers during study follow-up for dynamic prediction of a time-to-event clinical outcome. The biomarkers are typically intermittently measured, missing at some event times, and may be subject to high biological variations, which cannot be readily used as time-dependent covariates in a standard time-to-event model. Moreover, they can be highly correlated if they are from in the same biological pathway. To address these issues, we propose a flexible joint model framework that models the multiple biomarkers with a shared latent re…
We present a method for estimating causal effects in time series data when fine-grained information about the outcome of interest is available. Specifically, we examine what we call the split-door setting, where the outcome variable can be split into two parts: one that is potentially affected by the cause being studied and another that is independent of it, with both parts sharing the same (unobserved) confounders. We show that under these conditions, the problem of identification reduces to that of testing for independence among observed variables, and present a method that uses this approac…
This chapter covers different approaches to policy evaluation for assessing the causal effect of a treatment or intervention on an outcome of interest. As an introduction to causal inference, the discussion starts with the experimental evaluation of a randomized treatment. It then reviews evaluation methods based on selection on observables (assuming a quasi-random treatment given observed covariates), instrumental variables (inducing a quasi-random shift in the treatment), difference-in-differences and changes-in-changes (exploiting changes in outcomes over time), as well as regression discon…
In the absence of a randomized experiment, a key assumption for drawing causal inference about treatment effects is the ignorable treatment assignment. Violations of the ignorability assumption may lead to biased treatment effect estimates. Sensitivity analysis helps gauge how causal conclusions will be altered in response to the potential magnitude of departure from the ignorability assumption. However, sensitivity analysis approaches for unmeasured confounding in the context of multiple treatments and binary outcomes are scarce. We propose a flexible Monte Carlo sensitivity analysis approach…
Many estimators of the average effect of a treatment on an outcome require estimation of the propensity score, the outcome regression, or both. It is often beneficial to utilize flexible techniques such as semiparametric regression or machine learning to estimate these quantities. However, optimal estimation of these regressions does not necessarily lead to optimal estimation of the average treatment effect, particularly in settings with strong instrumental variables. A recent proposal addressed these issues via the outcome-adaptive lasso, a penalized regression technique for estimating the pr…
A flexible quantile mixed-effects model for censored outcomes
Syneos Health；Department of Mathematical Statistics and Actuarial Science, University of the Free State（自由州大学数学统计与精算科学系）；I-BioStat, KU Leuven（KU鲁汶大学生物统计研究所）；Department of Statistics and Actuarial Science, University of Stellenbosch（斯泰伦博斯大学统计与精算科学系）
When drawing causal inferences about the effects of multiple treatments on clustered survival outcomes using observational data, we need to address implications of the multilevel data structure, multiple treatments, censoring and unmeasured confounding for causal analyses. Few off-the-shelf causal inference tools are available to simultaneously tackle these issues. We develop a flexible random-intercept accelerated failure time model, in which we use Bayesian additive regression trees to capture arbitrarily complex relationships between censored survival times and pre-treatment covariates and …
Diagnostic tests are of critical importance in health care and medical research. Motivated by the impact that atypical and outlying test outcomes might have on the assessment of the discriminatory ability of a diagnostic test, we develop a flexible and robust model for conducting inference about the covariate-specific receiver operating characteristic (ROC) curve that safeguards against outlying test results while also accommodating for possible nonlinear effects of the covariates. Specifically, we postulate a location-scale additive regression model for the test outcomes in both the diseased …
Penalized spline smoothing is a popular and flexible method of obtaining estimates in nonparametric regression but the classical least-squares criterion is highly susceptible to model deviations and atypical observations. Penalized spline estimation with a resistant loss function is a natural remedy, yet to this day the asymptotic properties of M-type penalized spline estimators have not been studied. We show in this paper that M-type penalized spline estimators achieve the same rates of convergence as their least-squares counterparts, even with auxiliary scale estimation. We further find theo…
Targeted maximum likelihood estimation is a general methodology combining flexible ensemble learning and semiparametric efficiency theory in a two-step procedure for estimation of causal parameters. Proposed targeted maximum likelihood procedures for survival and competing risks analysis have so far focused on events taken values in discrete time. We here present a targeted maximum likelihood estimation procedure for event times that take values in R+. We focuson the estimation of intervention-specific mean outcomes with stochastic interventions on a time-fixed treatment. For data-adaptive est…
Interventional effects have been proposed as a solution to the unidentifiability of natural (in)direct effects under mediator-outcome confounders affected by the exposure. Such confounders are an intrinsic characteristic of studies with time-varying exposures and mediators, yet the generalization of the interventional effect framework to the time-varying case has received little attention in the literature. We present an identification result for interventional effects in a general longitudinal data structure that allows flexibility in the specification of treatment-outcome, treatment-mediator…
We propose a new, flexible model for inference of the effect of a binary treatment on a continuous outcome observed over subsequent time periods. The model allows to seperate association due to endogeneity of treatment selection from additional longitudinal association of the outcomes and hence unbiased estimation of dynamic treatment effects. We investigate the performance of the proposed method on simulated data and employ it to reanalyse data on the longitudinal effects of a long maternity leave on mothers' earnings after their return to the labour market.
In the absence of unobserved confounders, matching and weighting methods are widely used to estimate causal quantities including the Average Treatment Effect on the Treated (ATT). Unfortunately, these methods do not necessarily achieve their goal of making the multivariate distribution of covariates for the control group identical to that of the treated, leaving some (potentially multivariate) functions of the covariates with different means between the two groups. When these "imbalanced" functions influence the non-treatment potential outcome, the conditioning on observed covariates fails, an…
Expanding a lower-dimensional problem to a higher-dimensional space and then projecting back is often beneficial. This article rigorously investigates this perspective in the context of finite mixture models, namely how to improve inference for mixture models by using auxiliary variables. Despite the large literature in mixture models and several empirical examples, there is no previous work that gives general theoretical justification for including auxiliary variables in mixture models, even for special cases. We provide a theoretical basis for comparing inference for mixture multivariate mod…
Patient-reported outcome (PRO) measures are increasingly collected as a means of measuring healthcare quality and value. The capability to predict such measures enables patient-provider shared decision making and the delivery of patient-centered care. However, due to their voluntary nature, PRO measures often suffer from a high missing rate, and the missingness may depend on many patient factors. Under such a complex missing mechanism, statistical inference of the parameters in prediction models for PRO measures is challenging, especially when flexible imputation models such as machine learnin…
Prior work has shown that combining bootstrap imputation with tree-based machine learning variable selection methods can provide good performances achievable on fully observed data when covariate and outcome data are missing at random (MAR). This approach however is computationally expensive, especially on large-scale datasets. We propose an inference-based method, called RR-BART, which leverages the likelihood-based Bayesian machine learning technique, Bayesian additive regression trees, and uses Rubin's rule to combine the estimates and variances of the variable importance measures on multip…
We are interested in the estimation of average treatment effects based on right-censored data of an observational study. We focus on causal inference of differences between t-year absolute event risks in a situation with competing risks. We derive doubly robust estimation equations and implement estimators for the nuisance parameters based on working regression models for the outcome, the censoring and the treatment distribution conditional on auxiliary baseline covariates. We use the functional delta method to show that our estimators are regular asymptotically linear estimators and estimate …
Time-smoothed inverse probability weighted estimation of effects of generalized time-varying treatment strategies on repeated outcomes truncated by death
Small area estimation (SAE) entails estimating characteristics of interest for domains, often geographical areas, in which there may be few or no samples available. SAE has a long history and a wide variety of methods have been suggested, from a bewildering range of philosophical standpoints. We describe design-based and model-based approaches and models that are specified at the area-level and at the unit-level, focusing on health applications and fully Bayesian spatial models. The use of auxiliary information is a key ingredient for successful inference when response data are sparse and we d…
Scalable and accurate identification of specific clinical outcomes has been enabled by machine-learning applied to electronic medical record (EMR) systems. The development of classification models requires the collection of a complete labeled data set, where true clinical outcomes are obtained by human expert manual review. For example, the development of natural language processing algorithms requires the abstraction of clinical text data to obtain outcome information necessary for training models. However, if the outcome is rare then simple random sampling results in very few cases and insuf…
A framework for causal inference from two-level factorial designs is proposed. The framework utilizes the concept of potential outcomes that lies at the center stage of causal inference and extends Neyman's repeated sampling approach for estimation of causal effects and randomization tests based on Fisher's sharp null hypothesis to the case of 2-level factorial experiments. The framework allows for statistical inference from a finite population, permits definition and estimation of estimands other than "average factorial effects" and leads to more flexible inference procedures than those based…
