Conventional survival analysis approaches estimate risk scores or individualized time-to-event distributions conditioned on covariates. In practice, there is often great population-level phenotypic heterogeneity, resulting from (unknown) subpopulations with diverse risk profiles or survival distributions. As a result, there is an unmet need in survival analysis for identifying subpopulations with distinct risk profiles, while jointly accounting for accurate individualized time-to-event predictions. An approach that addresses this need is likely to improve characterization of individual outcomes by leveraging regularities in subpopulations, thus accounting for population-level heterogeneity. In this paper, we propose a Bayesian nonparametrics approach that represents observations (subjects) in a clustered latent space, and encourages accurate time-to-event predictions and clusters (subpopulations) with distinct risk profiles. Experiments on real-world datasets show consistent improvements in predictive performance and interpretability relative to existing state-of-the-art survival analysis models.
Survival analysis, or time-to-event modelling, is a classical statistical problem that has garnered a lot of interest for its practical use in epidemiology, demographics or actuarial sciences. Recent advances on the subject from the point of view of machine learning have been concerned with precise per-individual predictions instead of population studies, driven by the rise of individualized medicine. We introduce here a conditional normalizing flow based estimate of the time-to-event density as a way to model highly flexible and individualized conditional survival distributions. We use a nove…
Estimating individualized treatment rules is a central task for personalized medicine. [zhao2012estimating] and [zhang2012robust] proposed outcome weighted learning to estimate individualized treatment rules directly through maximizing the expected outcome without modeling the response directly. In this paper, we extend the outcome weighted learning to right censored survival data without requiring either an inverse probability of censoring weighting or a semiparametric modeling of the censoring and failure times as done in [zhao2015doubly]. To accomplish this, we take advantage of the tree ba…
Balanced representation learning methods have been applied successfully to counterfactual inference from observational data. However, approaches that account for survival outcomes are relatively limited. Survival data are frequently encountered across diverse medical applications, i.e., drug development, risk profiling, and clinical trials, and such data are also relevant in fields like manufacturing (e.g., for equipment monitoring). When the outcome of interest is a time-to-event, special precautions for handling censored events need to be taken, as ignoring censored outcomes may lead to bias…
In many important applications of precision medicine, the outcome of interest is time to an event (e.g., death, relapse of disease) and the primary goal is to identify the optimal individualized decision rule (IDR) to prolong survival time. Existing work in this area have been mostly focused on estimating the optimal IDR to maximize the We propose a new robust framework for estimating an optimal static or dynamic IDR with time-to-event outcomes based on an easy-to-interpret quantile criterion. The new method does not need to specify an outcome regression model and is robust for heavy-tailed di…
Individualized treatment rules can lead to better health outcomes when patients have heterogeneous responses to treatment. Very few individualized treatment rule estimation methods are compatible with a multi-treatment observational study with right censored survival outcomes. In this paper we extend policy evaluation methods to the right censored data setting. Existing approaches either make restrictive assumptions about the structure of the data, or use inverse weighting methods that increase the variance of the estimator resulting in decreased performance. We propose a method which uses bal…
SurvHTE-Bench: A Benchmark for Heterogeneous Treatment Effect Estimation in Survival Analysis
Machine Learning Department & Heinz College Carnegie Mellon University（机器学习系及卡内基梅隆大学海因兹学院）；Heinz College Carnegie Mellon University（卡内基梅隆大学海因兹学院）；National Library of Medicine National Institutes of Health（国家医学图书馆国立卫生研究院）
A Temporal Machine Learning-Based Time-to-Event Model for Predicting ALS Progression and Healthcare Utilization
Harrison College of Pharmacy, Auburn University（奥本大学哈里森药学院）；Fisk University（菲斯克大学）；Lewis Katz School of Medicine, Temple University（天普大学刘易斯·卡茨医学院）；Emory University（埃默里大学）；Barnett College of Public Health, Temple University（天普大学巴尼特公共卫生学院）
Counterfactual Survival Q-learning via Buckley-James Boosting, with Applications to ACTG 175 and CALGB 8923
Division of Biostatistics, The Ohio State University（俄亥俄州立大学生物统计学系）；Division of Science and Mathematics, University of Minnesota-Morris（明尼苏达州莫里斯大学科学与数学系）
School of Electrical and Computer Engineering, Purdue University（普渡大学电气与计算机工程学院）；Department of Medicine, Indiana University School of Medicine（印第安纳大学医学院医学系）；School of Electrical and Computer Engineering, Indiana University - Purdue University Indianapolis（印第安纳大学-普渡大学印第安纳波利斯分校电气与计算机工程学院）
One of the central goals in precision health is the understanding and interpretation of high-dimensional biological data to identify genes and markers associated with disease initiation, development, and outcomes. Though significant effort has been committed to harness gene expression data for multiple analyses while accounting for time-to-event modeling by including survival times, many traditional analyses have focused separately on non-negative matrix factorization (NMF) of the gene expression data matrix and survival regression with Cox proportional hazards model. In this work, Cox proport…
An individualized treatment regime (ITR) is a decision rule that assigns treatments based on patients' characteristics. The value function of an ITR is the expected outcome in a counterfactual world had this ITR been implemented. Recently, there has been increasing interest in combining heterogeneous data sources, such as leveraging the complementary features of randomized controlled trial (RCT) data and a large observational study (OS). Usually, a covariate shift exists between the source and target population, rendering the source-optimal ITR unnecessarily optimal for the target population. …
University of California, Los Angeles（加州大学洛杉矶分校）；Nuffield College, Oxford University（牛津大学纳菲尔德学院）；Oxford Man Institute, Oxford University（牛津大学牛津曼研究所）；Alan Turing Institute（艾伦·图灵研究所）
Given the limited pool of donor organs, accurate predictions of survival on the wait list and post transplantation are crucial for cardiac transplantation decisions and policy. However, current clinical risk scores do not yield accurate predictions. We develop a new methodology (ToPs, Trees of Predictors) built on the principle that specific predictors should be used for specific clusters within the target population. ToPs discovers these specific clusters of patients and the specific predictor that perform best for each cluster. In comparison with current clinical risk scoring systems, our me…
We develop methodology for a multistage decision problem with flexible number of stages in which the rewards are survival times that are subject to censoring. We present a novel Q-learning algorithm that is adjusted for censored data and allows a flexible number of stages. We provide finite sample bounds on the generalization error of the policy learned by the algorithm, and show that when the optimal Q-function belongs to the approximation space, the expected survival time for policies obtained by the algorithm converges to that of the optimal policy. We simulate a multistage clinical trial w…
An individualized risk prediction model that dynamically updates the probability of a clinical event from a specific cause is valuable for physicians to be able to optimize personalized treatment strategies in real-time by incorporating all available information collected over the follow-up. However, this is more complex and challenging when competing risks are present, because it requires simultaneously updating the overall survival and the cumulative incidence functions (CIFs) while adjusting for the time-dependent covariates and time-varying covariate effects. In this study, we developed a …
Memorial Sloan-Kettering Cancer Center（纪念斯隆-凯特琳癌症中心）；Weill Cornell Medicine（威尔康奈尔医学院）；Erasmus Medical Center-Rotterdam（伊拉斯谟医学中心-鹿特丹）
Unlike common cancers, such as those of the prostate and breast, tumor grading in rare cancers is difficult and largely undefined because of small sample sizes, the sheer volume of time needed to undertake on such a task, and the inherent difficulty of extracting human-observed patterns. One of the most challenging examples is intrahepatic cholangiocarcinoma (ICC), a primary liver cancer arising from the biliary system, for which there is well-recognized tumor heterogeneity and no grading paradigm or prognostic biomarkers. In this paper, we propose a new unsupervised deep convolutional autoenc…
In this article, I present the user written stmixed command for the fitting of multilevel survival models, which serves as both an alternative to Stata's official mestreg, and a complimentary program with substantial extensions. stmixed can fit multilevel survival models with any number of levels and random effects at each level, including flexible spline-based approaches (such as Royston-Parmar and the log hazard equivalent) or user-defined hazard models. Simple or complex time-dependent effects can be included, as well as the addition of expected mortality for a relative survival model. Left…
Understanding the factors that explain differences in survival times is an important issue for establishing policies to improve national health systems. Motivated by breast cancer data arising from the Surveillance Epidemiology and End Results program, we propose a covariate-adjusted proportional hazards frailty model for the analysis of clustered right-censored data. Rather than incorporating exchangeable frailties in the linear predictor of commonly-used survival models, we allow the frailty distribution to flexibly change with both continuous and categorical cluster-level covariates and mod…
Survival models incorporating random effects to account for unmeasured heterogeneity are being increasingly used in biostatistical and applied research. Specifically, unmeasured covariates whose lack of inclusion in the model would lead to biased, inefficient results are commonly modelled by including a subject-specific (or cluster-specific) frailty term that follows a given distribution (e.g. Gamma or log-Normal). Despite that, in the context of parametric frailty models little is known about the impact of misspecifying the baseline hazard, the frailty distribution, or both. Therefore, our ai…
ETH Zürich（苏黎世联邦理工学院）；Human Technopole（人类技术园）；University Hospital Basel（巴塞尔大学医院）；University Children’s Hospital Basel（巴塞尔大学儿童医院）；University of Zürich（苏黎世大学）；Politecnico di Milano（米兰理工大学）；St. Gallen Cantonal Hospital（圣加仑州立医院）
In this work, we study the problem of clustering survival data $-$ a challenging and so far under-explored task. We introduce a novel semi-supervised probabilistic approach to cluster survival data by leveraging recent advances in stochastic gradient variational inference. In contrast to previous work, our proposed method employs a deep generative model to uncover the underlying distribution of both the explanatory variables and censored survival times. We compare our model to the related work on clustering and mixture models for survival data in comprehensive experiments on a wide range of sy…
We consider a parametric modelling approach for survival data where covariates are allowed to enter the model through multiple distributional parameters, i.e., scale and shape. This is in contrast with the standard convention of having a single covariate-dependent parameter, typically the scale. Taking what is referred to as a multi-parameter regression (MPR) approach to modelling has been shown to produce flexible and robust models with relatively low model complexity cost. However, it is very common to have clustered data arising from survival analysis studies, and this is something that is …
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 …
CAST: Time-Varying Treatment Effects with Application to Chemotherapy and Radiotherapy on Head and Neck Squamous Cell Carcinoma
Center for Radiological Research, Columbia University Irving Medical Center（放射医学研究中心，哥伦比亚大学伊文思医疗中心）；Department of Computer Science, Brown University（计算机科学系，布朗大学）；Department of Applied Mathematics, Columbia University（应用数学系，哥伦比亚大学）；Department of Radiation Oncology, Columbia University Irving Medical Center（放射肿瘤学系，哥伦比亚大学伊文思医疗中心）；Department of Radiation Oncology, Princess Margaret Cancer Centre（放射肿瘤学系，普里兹姆癌症中心）；Department of Biostatistics, Columbia University Irving Medical Center（生物统计学系，哥伦比亚大学伊文思医疗中心）；Data Science Institute, Columbia University（数据科学研究所，哥伦比亚大学）
Joint model for longitudinal and spatio-temporal survival data
Research Center Trustworthy Data Science and Security, UA Ruhr（鲁尔大学联盟可信数据科学与安全研究中心）；Department of Statistics, TU Dortmund（多特蒙德工业大学统计系）；School of Mathematics, University of Edinburgh（爱丁堡大学数学学院）；Business School, University of Edinburgh（爱丁堡大学商学院）
