Dynamic treatment regimes (DTRs) are used in medicine to tailor sequential treatment decisions to patients by considering patient heterogeneity. Common methods for learning optimal DTRs, however, have shortcomings: they are typically based on outcome prediction and not treatment effect estimation, or they use linear models that are restrictive for patient data from modern electronic health records. To address these shortcomings, we develop two novel methods for learning optimal DTRs that effectively handle complex patient data. We call our methods DTR-CT and DTR-CF. Our methods are based on a data-driven estimation of heterogeneous treatment effects using causal tree methods, specifically causal trees and causal forests, that learn non-linear relationships, control for time-varying confounding, are doubly robust, and explainable. To the best of our knowledge, our paper is the first that adapts causal tree methods for learning optimal DTRs. We evaluate our proposed methods using synthetic data and then apply them to real-world data from intensive care units. Our methods outperform state-of-the-art baselines in terms of cumulative regret and percentage of optimal decisions by a considerable margin. Our work improves treatment recommendations from electronic health record and is thus of direct relevance for personalized medicine.
The development of high-throughput sequencing and targeted therapies has led to the emergence of personalized medicine: a patient's molecular profile or the presence of a specific biomarker of drug response will correspond to a treatment recommendation made either by a physician or by a treatment assignment algorithm. The growing number of such algorithms raises the question of how to quantify their clinical impact knowing that a personalized medicine strategy will inherently include different versions of treatment. We thus specify an appropriate causal framework with multiple versions of trea…
Didi Chuxing（滴滴出行）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）
Uplift modeling is a rapidly growing approach that utilizes causal inference and machine learning methods to directly estimate the heterogeneous treatment effects, which has been widely applied to various online marketplaces to assist large-scale decision-making in recent years. The existing popular models, like causal forest (CF), are limited to either discrete treatments or posing parametric assumptions on the outcome-treatment relationship that may suffer model misspecification. However, continuous treatments (e.g., price, duration) often arise in marketplaces. To alleviate these restrictio…
Amazon.com, Inc.（亚马逊公司）；Wharton School of the University of Pennsylvania（宾夕法尼亚大学沃顿商学院）
We study the problem of observational causal inference with continuous treatments in the framework of inverse propensity-score weighting. To obtain stable weights, we design a new algorithm based on entropy balancing that learns weights to directly maximize causal inference accuracy using end-to-end optimization. In the process of optimization, these weights are automatically tuned to the specific dataset and causal inference algorithm being used. We provide a theoretical analysis demonstrating consistency of our approach. Using synthetic and real-world data, we show that our algorithm estimat…
Amazon（亚马逊）；Massachusetts Institute of Technology（麻省理工学院）
We extend the definition of the marginal causal effect to the continuous treatment setting and develop a novel characterization of causal bias in the framework of structural causal models. We prove that our derived bias expression is zero if, and only if, the causal effect is identifiable via covariate adjustment. We show that under some restrictions on the structural equations, the causal bias can be estimated efficiently and allows for causal regularization of predictive probabilistic models. We demonstrate the effectiveness of our method for causal bias quantification in various settings wh…
A lack of understanding of human biology creates a hurdle for the development of precision medicines. To overcome this hurdle we need to better understand the potential synergy between a given investigational treatment (vs. placebo or active control) and various demographic or genetic factors, disease history and severity, etc., with the goal of identifying those patients at increased risk of exhibiting clinically meaningful treatment benefit. For this reason, we propose the VG method, which combines the idea of an individual treatment effect (ITE) from Virtual Twins (Foster, et al., 2011) wit…
Forest-based methods have recently gained in popularity for non-parametric treatment effect estimation. Building on this line of work, we introduce causal survival forests, which can be used to estimate heterogeneous treatment effects in a survival and observational setting where outcomes may be right-censored. Our approach relies on orthogonal estimating equations to robustly adjust for both censoring and selection effects under unconfoundedness. In our experiments, we find our approach to perform well relative to a number of baselines.
Ludwig Maximilian University of Munich（慕尼黑大学）；Siemens CT（西门子中央研究院）
Estimating individual treatment effects from data of randomized experiments is a critical task in causal inference. The Stable Unit Treatment Value Assumption (SUTVA) is usually made in causal inference. However, interference can introduce bias when the assigned treatment on one unit affects the potential outcomes of the neighboring units. This interference phenomenon is known as spillover effect in economics or peer effect in social science. Usually, in randomized experiments or observational studies with interconnected units, one can only observe treatment responses under interference. Hence…
Pharmaceutical companies continue to seek innovative ways to explore whether a drug under development is likely to be suitable for all or only an identifiable stratum of patients in the target population. The sooner this can be done during the clinical development process, the better it is for the company, and downstream for prescribers, payers, and most importantly, for patients. To help enable this vision of stratified medicine, we describe a powerful statistical framework, Patient Response Identifiers for Stratified Medicine (PRISM), for the discovery of potential predictors of drug respons…
Causal mediation analysis is used to evaluate direct and indirect causal effects of a treatment on an outcome of interest through an intermediate variable or a mediator.It is difficult to identify the direct and indirect causal effects because the mediator cannot be randomly assigned in many real applications. In this article, we consider a causal model including latent confounders between the mediator and the outcome. We present sufficient conditions for identifying the direct and indirect effects and propose an approach for estimating them. The performance of the proposed approach is evaluat…
Randomised controlled trials in reproductive medicine are often subject to outcome truncation, where study outcomes are only defined in a subset of participants. Examples include birthweight (measurable only in the subgroup of participants who give birth) and miscarriage (which can only occur in participants who become pregnant). These are typically analysed by making a comparison between treatment arms within the subgroup (comparing birthweights in the subgroup who gave birth, or miscarriages in the subgroup who became pregnant). However, this approach does not represent a randomised comparis…
Paris-Dauphine University - PSL（巴黎多芬大学-PSL大学）；CNRS（法国国家科学研究中心）；Ai Square Connect；AdWay Groupe（AdWay集团）
Estimating the Individual Treatment Effect from observational data, defined as the difference between outcomes with and without treatment or intervention, while observing just one of both, is a challenging problems in causal learning. In this paper, we formulate this problem as an inference from hidden variables and enforce causal constraints based on a model of four exclusive causal populations. We propose a new version of the EM algorithm, coined as Expected-Causality-Maximization (ECM) algorithm and provide hints on its convergence under mild conditions. We compare our algorithm to baseline…
New York University（纽约大学）；Columbia University（哥伦比亚大学）
Causal inference from observational data requires assumptions. These assumptions range from measuring confounders to identifying instruments. Traditionally, causal inference assumptions have focused on estimation of effects for a single treatment. In this work, we construct techniques for estimation with multiple treatments in the presence of unobserved confounding. We develop two assumptions based on shared confounding between treatments and independence of treatments given the confounder. Together, these assumptions lead to a confounder estimator regularized by mutual information. For this e…
University College London（伦敦大学学院）；University of Oxford（牛津大学）
We address the estimation of conditional average treatment effects (CATEs) for structured treatments (e.g., graphs, images, texts). Given a weak condition on the effect, we propose the generalized Robinson decomposition, which (i) isolates the causal estimand (reducing regularization bias), (ii) allows one to plug in arbitrary models for learning, and (iii) possesses a quasi-oracle convergence guarantee under mild assumptions. In experiments with small-world and molecular graphs we demonstrate that our approach outperforms prior work in CATE estimation.
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 …
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…
Suppose that a sequence of treatments are assigned to influence an outcome of interest that occurs after the last treatment. Between treatments there exist time-dependent covariates that may be posttreatment variables of the earlier treatments and confounders of the subsequent treatments. In this article, we develop a parametric approach to inference of the causal effect of the treatment sequence on the outcome called the sequential causal effect. We construct a point parametrization for the conditional distribution of an outcome given all treatments and time-dependent covariates, in which the…
In semicompeting risks problems, nonterminal time-to-event outcomes such as time to hospital readmission are subject to truncation by death. These settings are often modeled with illness-death models for the hazards of the terminal and nonterminal events, but evaluating causal treatment effects with hazard models is problematic due to conditioning on survival (a post-treatment outcome) that is embedded in the definition of a hazard. Extending an existing survivor average causal effect (SACE) estimand, we frame the evaluation of treatment effects in the context of semicompeting risks with princ…
In causal mediation studies that decompose an average treatment effect into a natural indirect effect (NIE) and a natural direct effect (NDE), examples of post-treatment confounding are abundant. Past research has generally considered it infeasible to adjust for a post-treatment confounder of the mediator-outcome relationship due to incomplete information: it is observed under the actual treatment condition while missing under the counterfactual treatment condition. This study proposes a new sensitivity analysis strategy for handling post-treatment confounding and incorporates it into weightin…
CIMTx provides efficient and unified functions to implement modern methods for causal inferences with multiple treatments using observational data with a focus on binary outcomes. The methods include regression adjustment, inverse probability of treatment weighting, Bayesian additive regression trees, regression adjustment with multivariate spline of the generalized propensity score, vector matching and targeted maximum likelihood estimation. In addition, CIMTx illustrates ways in which users can simulate data adhering to the complex data structures in the multiple treatment setting. Furthermo…
The estimation of optimal treatment regimes is of considerable interest to precision medicine. In this work, we propose a causal $k$-nearest neighbor method to estimate the optimal treatment regime. The method roots in the framework of causal inference, and estimates the causal treatment effects within the nearest neighborhood. Although the method is simple, it possesses nice theoretical properties. We show that the causal $k$-nearest neighbor regime is universally consistent. That is, the causal $k$-nearest neighbor regime will eventually learn the optimal treatment regime as the sample size …
Marginal structural models (MSM) with inverse probability weighting (IPW) are used to estimate causal effects of time-varying treatments, but can result in erratic finite-sample performance when there is low overlap in covariate distributions across different treatment patterns. Modifications to IPW which target the average treatment effect (ATE) estimand either introduce bias or rely on unverifiable parametric assumptions and extrapolation. This paper extends an alternate estimand, the average treatment effect on the overlap population (ATO) which is estimated on a sub-population with a reaso…
One of the main tasks of causal inference is estimating well-defined causal parameters. One of the main causal parameters is the average causal effect (ACE) - the expected value of the individual level causal effects in the target population. For binary treatments, the individual level causal effect is defined as contrast between potential outcomes. For continuous outcomes, however, there are many such contrasts in finite samples, thus hampering their use as a useful summary of the causal relationship. Here, we proposed a generalized version of the ACE, where individual level causal effects ar…
Georgia Institute of Technology（佐治亚理工学院）；Microsoft Research India（微软印度研究院）；Microsoft（微软）；Microsoft Research AI（微软人工智能研究院）
For many kinds of interventions, such as a new advertisement, marketing intervention, or feature recommendation, it is important to target a specific subset of people for maximizing its benefits at minimum cost or potential harm. However, a key challenge is that no data is available about the effect of such a prospective intervention since it has not been deployed yet. In this work, we propose a split-treatment analysis that ranks the individuals most likely to be positively affected by a prospective intervention using past observational data. Unlike standard causal inference methods, the spli…
The average causal effect can often be best understood in the context of its variation. We demonstrate with two sets of four graphs, all of which represent the same average effect but with much different patterns of heterogeneity. As with the famous correlation quartet of Anscombe (1973), these graphs dramatize the way in which real-world variation can be more complex than simple numerical summaries. The graphs also give insight into why the average effect is often much smaller than anticipated.
Randomized experiments are the gold standard for estimating the causal effects of an intervention. In the simplest setting, each experimental unit is randomly assigned to receive treatment or control, and then the outcomes in each treatment arm are compared. In many settings, however, randomized experiments need to be executed over several time periods such that treatment assignment happens at each time period. In such temporal experiments, it has been observed that the effects of an intervention on a given unit may be large when the unit is first exposed to it, but then it often attenuates, o…
Background/aims: While randomized controlled trials are the gold standard for measuring causal effects, robust conclusions about causal relationships can be obtained using data from observational studies if proper statistical techniques are used to account for the imbalance of pretreatment confounders across groups. Propensity score (PS) and balance weighting are useful techniques that aim to reduce the observed imbalances between treatment groups by weighting the groups to be as similar as possible with respect to observed confounders. Methods: We have created CoBWeb, a free and easy-to-use w…
Estimating individual level treatment effects (ITE) from observational data is a challenging and important area in causal machine learning and is commonly considered in diverse mission-critical applications. In this paper, we propose an information theoretic approach in order to find more reliable representations for estimating ITE. We leverage the Information Bottleneck (IB) principle, which addresses the trade-off between conciseness and predictive power of representation. With the introduction of an extended graphical model for causal information bottleneck, we encourage the independence be…
The propensity score is a common tool for estimating the causal effect of a binary treatment in observational data. In this setting, matching, subclassification, imputation, or inverse probability weighting on the propensity score can reduce the initial covariate bias between the treatment and control groups. With more than two treatment options, however, estimation of causal effects requires additional assumptions and techniques, the implementations of which have varied across disciplines. This paper reviews current methods, and it identifies and contrasts the treatment effects that each one …
Benchmarking Bayesian Causal Discovery Methods for Downstream Treatment Effect Estimation
Technical University of Munich（慕尼黑工业大学）；Mila - Quebec AI Institute（米拉 - 魁北克人工智能研究所）；ServiceNow Research（ServiceNow研究院）；Université de Montréal（蒙特利尔大学）；Helmholtz AI（亥姆霍兹人工智能研究所）
Treatment switching in a randomized controlled trial is said to occur when a patient randomized to one treatment arm switches to another treatment arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously dilute the estimated effect of treatment on overall survival. In this paper, we aim to account for the potential impact of treatment switching in a re-analysis evaluating the treatment effect of NucleosideReverse Transc…
Stochastic Causal Programming for Bounding Treatment Effects
Helmholtz AI（亥姆霍兹人工智能研究所）；Helmholtz Munich（亥姆霍兹慕尼黑中心）；Technical University Munich（慕尼黑工业大学）；University College London（伦敦大学学院）；King’s College London（伦敦国王学院）
Cause-effect relationships are typically evaluated by comparing outcome responses to binary treatment values, representing two arms of a hypothetical randomized controlled trial. However, in certain applications, treatments of interest are continuous and multidimensional. For example, understanding the causal relationship between severity of radiation therapy, summarized by a multidimensional vector of radiation exposure values and post-treatment side effects is a problem of clinical interest in radiation oncology. An appropriate strategy for making interpretable causal conclusions is to reduc…
Randomized clinical trials (RCTs) are ideal for estimating causal effects, because the distributions of background covariates are similar in expectation across treatment groups. When estimating causal effects using observational data, matching is a commonly used method to replicate the covariate balance achieved in a RCT. Matching algorithms have a rich history dating back to the mid-1900s, but have been used mostly to estimate causal effects between two treatment groups. When there are more than two treatments, estimating causal effects requires additional assumptions and techniques. We propo…
Causal inference methods are widely applied in the fields of medicine, policy, and economics. Central to these applications is the estimation of treatment effects to make decisions. Current methods make binary yes-or-no decisions based on the treatment effect of a single outcome dimension. These methods are unable to capture continuous space treatment policies with a measure of intensity. They also lack the capacity to consider the complexity of treatment such as matching candidate treatments with the subject. We propose to formulate the effectiveness of treatment as a parametrizable model, ex…
Consider a situation with two treatments, the first of which is randomized but the second is not, and the multifactor version of this. Interest is in treatment effects, defined using standard factorial notation. We define estimators for the treatment effects and explore their properties when there is information about the nonrandomized treatment assignment and when there is no information on the assignment of the nonrandomized treatment. We show when and how hidden treatments can bias estimators and inflate their sampling variances.
Estimating causal effects of continuous-time dynamic treatments with unmeasured confounders
Key Laboratory of Advanced Theory and Application in Statistics and Data Science -MOE, School of Statistics, East China Normal University（华东师范大学统计学院统计学与数据科学前沿理论及应用教育部重点实验室）
We apply causal forests to a dataset derived from the National Study of Learning Mindsets, and consider resulting practical and conceptual challenges. In particular, we discuss how causal forests use estimated propensity scores to be more robust to confounding, and how they handle data with clustered errors.
We develop a Bayesian nonparametric (BNP) approach to evaluate the causal effect of treatment in a randomized trial where a nonterminal event may be censored by a terminal event, but not vice versa (i.e., semi-competing risks). Based on the idea of principal stratification, we define a novel estimand for the causal effect of treatment on the nonterminal event. We introduce identification assumptions, indexed by a sensitivity parameter, and show how to draw inference using our BNP approach. We conduct simulation studies and illustrate our methodology using data from a brain cancer trial.
