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 treatment to define the causal effects of interest for precision medicine strategies and estimate them emulating clinical trials with observational data. Therefore, we determine whether the treatment assignment algorithm is more efficient than different control arms: gold standard treatment, observed treatments or random assignment of targeted treatments.
Causal estimates of the precision medicine effects are first evaluated on simulated data and they demonstrate a lower biases and variances compared with naive estimation of the difference in expected outcome between treatment arms. The various simulations scenarios also point out the different bias sources depending on the clinical situation (heterogeneity of response, assignment of observed treatments etc.). A RShiny interactive application is also provided to further explore other user-defined scenarios. The method is then applied to data from patient-derived xenografts (PDX): each patient tumour is implanted in several immunodeficient cloned mice later treated with different drugs, thus providing access to all corresponding drug sensitivities for all patients. Access to these unique pre-clinical data emulating counterfactual outcomes allows to validate the reliability of causal estimates obtained with the proposed method.
Causal Meta-Analysis: Rethinking the Foundations of Evidence-Based Medicine
PreMeDICaL, Inria, Univ Montpellier, France（法国蒙彼利埃大学 PreMeDICaL 团队）；University Medical Center Utrecht, Netherlands（荷兰乌得勒支大学医学中心）；Sorbonne Université and Université Paris Cité, CNRS（索邦大学与巴黎西岱大学，法国国家科学研究中心）
Mobile health studies can leverage longitudinal sensor data from smartphones to guide the application of personalized medical interventions. In this paper, we propose that adoption of an instrumental variable approach for randomized trials with imperfect compliance provides a natural framework for personalized causal inference of medication response in mobile health studies. Randomized treatment suggestions can be easily delivered to the study participants via electronic messages popping up on the smart-phone screen. Under quite general assumptions we can identify the causal effect of the actu…
Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the ability to design clinical trials that investigate the role of patient covariates on treatment effects. In this work, we study the optimal design of two-armed clinical trials to maximize accuracy of statistical models where the interaction between patient covariates and treatment effect are incorporated to enable precision medication. Such a modeling extensio…
Randomized experimentation (also known as A/B testing or bucket testing) is widely used in the internet industry to measure the metric impact obtained by different treatment variants. A/B tests identify the treatment variant showing the best performance, which then becomes the chosen or selected treatment for the entire population. However, the effect of a given treatment can differ across experimental units and a personalized approach for treatment selection can greatly improve upon the usual global selection strategy. In this work, we develop a framework for personalization through (i) estim…
Causal inference has received great attention across different fields from economics, statistics, education, medicine, to machine learning. Within this area, inferring causal effects at individual level in observational studies has become an important task, especially in high dimensional settings. In this paper, we propose a framework for estimating Individualized Treatment Effects in high-dimensional non-experimental data. We provide both theoretical and empirical justifications, the latter by comparing our framework with current best-performing methods. Our proposed framework rivals the stat…
Personalized medicine has become an important part of medicine, for instance predicting individual drug responses based on genomic information. However, many current statistical methods are not tailored to this task, because they overlook the individual heterogeneity of patients. In this paper, we look at personalized medicine from a linear regression standpoint. We introduce an alternative version of the ridge estimator and target individuals by establishing a tuning parameter calibration scheme that minimizes prediction errors of individual patients. In stark contrast, classical schemes such…
Johns Hopkins University（约翰斯·霍普金斯大学）；Harvard T. H. Chan School of Public Health（哈佛陈曾熙公共卫生学院）
The goal of personalized decision making is to map a unit's characteristics to an action tailored to maximize the expected outcome for that unit. Obtaining high-quality mappings of this type is the goal of the dynamic regime literature. In healthcare settings, optimizing policies with respect to a particular causal pathway may be of interest as well. For example, we may wish to maximize the chemical effect of a drug given data from an observational study where the chemical effect of the drug on the outcome is entangled with the indirect effect mediated by differential adherence. In such cases,…
In medicine, researchers often seek to infer the effects of a given treatment on patients' outcomes. However, the standard methods for causal survival analysis make simplistic assumptions about the data-generating process and cannot capture complex interactions among patient covariates. We introduce the Dynamic Survival Transformer (DynST), a deep survival model that trains on electronic health records (EHRs). Unlike previous transformers used in survival analysis, DynST can make use of time-varying information to predict evolving survival probabilities. We derive a semi-synthetic EHR dataset …
A Causal Inference Approach for Evaluating Diagnostic Tests and AI-Enabled Medical Devices: From Effect Modification to Information-Augmented Decision-Making
Division of Biostatistics, University of California, Berkeley（加州大学伯克利分校生物统计系）
Personalized Binomial DAGs Learning with Network Structured Covariates
Booth School of Business, University of Chicago（芝加哥大学布斯商学院）；University of Michigan（密歇根大学）；Ant Financial Group（蚂蚁集团）；Marshall School of Business, University of Southern California（南加州大学马歇尔商学院）
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…
Precision medicine involves answering counterfactual questions such as "Would this patient respond better to treatment A or treatment B?" These types of questions are causal in nature and require the tools of causal inference to be answered, e.g., with a structural causal model (SCM). In this work, we develop an SCM that models the interaction between demographic information, disease covariates, and magnetic resonance (MR) images of the brain for people with multiple sclerosis. Inference in the SCM generates counterfactual images that show what an MR image of the brain would look like if demog…
With the increasing need of personalised decision making, such as personalised medicine and online recommendations, a growing attention has been paid to the discovery of the context and heterogeneity of causal relationships. Most existing methods, however, assume a known cause (e.g. a new drug) and focus on identifying from data the contexts of heterogeneous effects of the cause (e.g. patient groups with different responses to the new drug). There is no approach to efficiently detecting directly from observational data context specific causal relationships, i.e. discovering the causes and thei…
Estimating the causal effects of an intervention in the presence of confounding is a frequently occurring problem in applications such as medicine. The task is challenging since there may be multiple confounding factors, some of which may be missing, and inferences must be made from high-dimensional, noisy measurements. In this paper, we propose a decision-theoretic approach to estimate the causal effects of interventions where a subset of the covariates is unavailable for some patients during testing. Our approach uses the information bottleneck principle to perform a discrete, low-dimensiona…
Department of Computer Science and Engineering, Hanyang University（韩阳大学计算机科学与工程系）；Department of Applied Artificial Intelligence, Hanyang University（韩阳大学应用人工智能系）
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…
We study the problem of learning conditional average treatment effects (CATE) from observational data with unobserved confounders. The CATE function maps baseline covariates to individual causal effect predictions and is key for personalized assessments. Recent work has focused on how to learn CATE under unconfoundedness, i.e., when there are no unobserved confounders. Since CATE may not be identified when unconfoundedness is violated, we develop a functional interval estimator that predicts bounds on the individual causal effects under realistic violations of unconfoundedness. Our estimator t…
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 …
Max Planck Institute for Intelligent Systems（马克斯·普朗克智能系统研究所）；Max Planck Institute for Biological Cybernetics（马克斯·普朗克生物控制论研究所）；University of Tübingen（图宾根大学）
The use of inverse probability weighting (IPW) methods to estimate the causal effect of treatments from observational studies is widespread in econometrics, medicine and social sciences. Although these studies often involve sensitive information, thus far there has been no work on privacy-preserving IPW methods. We address this by providing a novel framework for privacy-preserving IPW (PP-IPW) methods. We include a theoretical analysis of the effects of our proposed privatisation procedure on the estimated average treatment effect, and evaluate our PP-IPW framework on synthetic, semi-synthetic…
OATML（牛津大学机器学习与应用实验室）；University of Oxford（牛津大学）；Machine Learning and Causal Inference in Healthcare Lab（医疗保健机器学习与因果推理实验室）；Technion（以色列理工学院）
Estimating personalized treatment effects from high-dimensional observational data is essential in situations where experimental designs are infeasible, unethical, or expensive. Existing approaches rely on fitting deep models on outcomes observed for treated and control populations. However, when measuring individual outcomes is costly, as is the case of a tumor biopsy, a sample-efficient strategy for acquiring each result is required. Deep Bayesian active learning provides a framework for efficient data acquisition by selecting points with high uncertainty. However, existing methods bias trai…
Spotify（声田）；University College London（伦敦大学学院）；Babylon Health（巴比伦健康）
The discovery of causal relationships is a fundamental problem in science and medicine. In recent years, many elegant approaches to discovering causal relationships between two variables from observational data have been proposed. However, most of these deal only with purely directed causal relationships and cannot detect latent common causes. Here, we devise a general heuristic which takes a causal discovery algorithm that can only distinguish purely directed causal relations and modifies it to also detect latent common causes. We apply our method to two directed causal discovery algorithms, …
University of California Irvine（加州大学欧文分校）；North Carolina State University（北卡罗来纳州立大学）；Merck & Co., Inc.（默沙东公司）
Personalized medicine, a paradigm of medicine tailored to a patient's characteristics, is an increasingly attractive field in health care. An important goal of personalized medicine is to identify a subgroup of patients, based on baseline covariates, that benefits more from the targeted treatment than other comparative treatments. Most of the current subgroup identification methods only focus on obtaining a subgroup with an enhanced treatment effect without paying attention to subgroup size. Yet, a clinically meaningful subgroup learning approach should identify the maximum number of patients …
University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）；North Carolina State University（北卡罗来纳州立大学）
The complexity of human cancer often results in significant heterogeneity in response to treatment. Precision medicine offers potential to improve patient outcomes by leveraging this heterogeneity. Individualized treatment rules (ITRs) formalize precision medicine as maps from the patient covariate space into the space of allowable treatments. The optimal ITR is that which maximizes the mean of a clinical outcome in a population of interest. Patient-derived xenograft (PDX) studies permit the evaluation of multiple treatments within a single tumor and thus are ideally suited for estimating opti…
Deconfounded Warm-Start Thompson Sampling with Applications to Precision Medicine
Daniels School of Business, Purdue University（普渡大学 Daniels 商学院）；Mays Business School, Texas A&M University（德克萨斯农工大学 Mays 商学院）；McCombs School of Business, University of Texas at Austin（德克萨斯大学奥斯汀分校 McCombs 商学院）
