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 under developed in the MPR context. The purpose of this article is to extend MPR models to handle multivariate survival data by introducing random effects in both the scale and the shape regression components. We consider a variety of possible dependence structures for these random effects (independent, shared, and correlated), and estimation proceeds using a h-likelihood approach. The performance of our estimation procedure is investigated by a way of an extensive simulation study, and the merits of our modelling approach are illustrated through applications to two real data examples, a lung cancer dataset and a bladder cancer dataset.
We develop flexible multi-parameter regression survival models for interval censored survival data arising in longitudinal prospective studies and longitudinal randomised controlled clinical trials. A multi-parameter Weibull regression survival model, which is wholly parametric, and has non-proportional hazards, is the main focus of the paper. We describe the basic model, develop the interval-censored likelihood and extend the model to include gamma frailty and a dispersion model. We evaluate the models by means of a simulation study and a detailed re-analysis of data from the Signal Tandmobie…
We introduce a general, flexible, parametric survival modelling framework which encompasses key shapes of hazard function (constant, increasing, decreasing, up-then-down, down-then-up), various common survival distributions (log-logistic, Burr type XII, Weibull, Gompertz), and includes defective distributions (i.e., cure models). This generality is achieved using four basic distributional parameters: two scale-type parameters and two shape parameters. Generalising to covariate dependence, the scale-type regression components correspond to accelerated failure time (AFT) and proportional hazards…
We discuss causal mediation analyses for survival data and propose a new approach based on the additive hazards model. The emphasis is on a dynamic point of view, that is, understanding how the direct and indirect effects develop over time. Hence, importantly, we allow for a time varying mediator. To define direct and indirect effects in such a longitudinal survival setting we take an interventional approach (Didelez (2018)) where treatment is separated into one aspect affecting the mediator and a different aspect affecting survival. In general, this leads to a version of the non-parametric g-…
We present a new backfitting algorithm estimating the complex structured non-parametric survival model of Scheike (2001) without having to use smoothing. The considered model is a non-parametric survival model with two time-scales that are equivalent up to a constant that varies over the subjects. Covariate effects are modelled linearly on each time scale by additive Aalen models. Estimators of the cumulative intensities on the two time-scales are suggested by solving local estimating equations jointly on the two time-scales. We are able to estimate the cumulative intensities solving backfitti…
Many researchers have investigated first hitting times as models for survival data. First hitting times arise naturally in many types of stochastic processes, ranging from Wiener processes to Markov chains. In a survival context, the state of the underlying process represents the strength of an item or the health of an individual. The item fails or the individual experiences a clinical endpoint when the process reaches an adverse threshold state for the first time. The time scale can be calendar time or some other operational measure of degradation or disease progression. In many applications,…
Joint modelling of longitudinal and time-to-event data is usually described by a joint model which uses shared or correlated latent effects to capture associations between the two processes. Under this framework, the joint distribution of the two processes can be derived straightforwardly by assuming conditional independence given the random effects. Alternative approaches to induce interdependency into sub-models have also been considered in the literature and one such approach is using copulas to introduce non-linear correlation between the marginal distributions of the longitudinal and time…
While there are many well-developed data science methods for classification and regression, there are relatively few methods for working with right-censored data. Here, we present "survival stacking": a method for casting survival analysis problems as classification problems, thereby allowing the use of general classification methods and software in a survival setting. Inspired by the Cox partial likelihood, survival stacking collects features and outcomes of survival data in a large data frame with a binary outcome. We show that survival stacking with logistic regression is approximately equi…
Multilevel network meta-regression for multistate models: Population-adjusted joint synthesis of progression and survival data from individual and aggregate evidence
University of California, San Francisco（旧金山加利福尼亚大学）；UCSF Helen Diller Family Comprehensive Cancer Center（UCSF海伦·迪勒家族综合癌症中心）；The Philip R. Lee Institute for Health Policy Studies（菲利普·李健康政策研究所）；Precision AQ
Truncation is a statistical phenomenon that occurs in many time to event studies. For example, autopsy-confirmed studies of neurodegenerative diseases are subject to an inherent left and right truncation, also known as double truncation. When the goal is to study the effect of risk factors on survival, the standard Cox regression model cannot be used when the data is subject to truncation. Existing methods which adjust for both left and right truncation in the Cox regression model require independence between the survival times and truncation times, which may not be a reasonable assumption in …
In survival studies it is important to record the values of key longitudinal covariates until the occurrence of event of a subject. For this reason, it is essential to study the association between longitudinal and time-to-event outcomes using the joint model. In this paper, profile likelihood approach has been used to estimate the cumulative hazard and regression parameters from the joint model of survival and longitudinal data. Moreover, we show the asymptotic normality of the profile likelihood estimator via asymptotic expansion of the profile likelihood and obtain the explicit form of the …
In this paper, we explore a method for treating survival analysis as a classification problem. The method uses a "stacking" idea that collects the features and outcomes of the survival data in a large data frame, and then treats it as a classification problem. In this framework, various statistical learning algorithms (including logistic regression, random forests, gradient boosting machines and neural networks) can be applied to estimate the parameters and make predictions. For stacking with logistic regression, we show that this approach is approximately equivalent to the Cox proportional ha…
Proportional hazards (PH), proportional odds (PO) and accelerated failure time (AFT) models have been widely used to deal with survival data in different fields of knowledge. Despite their popularity, such models are not suitable to handle survival data with crossing survival curves. Yang and Prentice (2005) proposed a semiparametric two-sample approach, denoted here as the YP model, allowing the analysis of crossing survival curves and including the PH and PO configurations as particular cases. In a general regression setting, the present work proposes a fully likelihood-based approach to fit…
Google Research（谷歌研究院）；Carnegie Mellon University（卡内基梅隆大学）
Survival analysis is a challenging variation of regression modeling because of the presence of censoring, where the outcome measurement is only partially known, due to, for example, loss to follow up. Such problems come up frequently in medical applications, making survival analysis a key endeavor in biostatistics and machine learning for healthcare, with Cox regression models being amongst the most commonly employed models. We describe a new approach for survival analysis regression models, based on learning mixtures of Cox regressions to model individual survival distributions. We propose an…
Medical investigations focusing on patient survival often generate not only a failure time for each patient but also a sequence of measurements on patient health at annual or semi-annual check-ups while the patient remains alive. Such a sequence of random length accompanied by a survival time is called a survival process. Ordinarily robust health is associated with longer survival, so the two parts of a survival process cannot be assumed independent. This paper is concerned with a general technique---time reversal---for constructing statistical models for survival processes. A revival model is…
Recently Goswami et al. \cite{goswami2022concordance} introduced two novel implementations of combined regression strategy to find the conditional survival function. The paper uses regression-based weak learners and provides an alternative version of the combined regression strategy (COBRA) ensemble using the Integrated Brier Score to predict conditional survival function. We create a novel predictor based on a weighted version of all machine predictions taking weights as a specific function of normalized Integrated Brier Score. We use two different norms (Frobenius and Sup norm) to extract th…
IMPORTANCE: Time-to-event outcomes are commonly used in clinical trials and biomarker discovery studies and have been primarily analyzed using Cox proportional hazards models. But it's unclear which statistical models should be recommended for feature selection tasks when time-to-event outcomes are of the primary interest. OBJECTIVE: To explore if Gaussian regression of log-transformed survival time could outperform Cox proportional hazards models in feature selection. DESIGN: In this simulation study, the true models are multivariate Cox proportional hazards models with 10 covariates. For all…
Applications of machine learning in healthcare often require working with time-to-event prediction tasks including prognostication of an adverse event, re-hospitalization or death. Such outcomes are typically subject to censoring due to loss of follow up. Standard machine learning methods cannot be applied in a straightforward manner to datasets with censored outcomes. In this paper, we present auton-survival, an open-source repository of tools to streamline working with censored time-to-event or survival data. auton-survival includes tools for survival regression, adjustment in the presence o…
We describe a new approach to estimating relative risks in time-to-event prediction problems with censored data in a fully parametric manner. Our approach does not require making strong assumptions of constant proportional hazard of the underlying survival distribution, as required by the Cox-proportional hazard model. By jointly learning deep nonlinear representations of the input covariates, we demonstrate the benefits of our approach when used to estimate survival risks through extensive experimentation on multiple real world datasets with different levels of censoring. We further demonstra…
In this paper, we expand the methodology presented in Mertens et. al (2020, Biometrical Journal) to the study of life-time (survival) outcome which is subject to censoring and when imputation is used to account for missing values. We consider the problem where missing values can occur in both the calibration data as well as newly - to-be-predicted - observations (validation). We focus on the Cox model. Methods are described to combine imputation with predictive calibration in survival modeling subject to censoring. Application to cross-validation is discussed. We demonstrate how conclusions br…
Bias - variance decomposition of the expected error defined for regression and classification problems is an important tool to study and compare different algorithms, to find the best areas for their application. Here the decomposition is introduced for the survival analysis problem. In our experiments, we study bias -variance parts of the expected error for two algorithms: original Cox proportional hazard regression and CoxPath, path algorithm for L1-regularized Cox regression, on the series of increased training sets. The experiments demonstrate that, contrary expectations, CoxPath does not …
Estimating equations for causal survival analysis with pooled logistic regression
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校吉林斯全球公共卫生学院流行病学系）；Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校吉林斯全球公共卫生学院生物统计系）；Nuffield Department of Population Health, University of Oxford（牛津大学纽菲尔德人口健康系）
merlin can do a lot of things. From simple stuff, like fitting a linear regression or a Weibull survival model, to a three-level logistic mixed effects model, or a multivariate joint model of multiple longitudinal outcomes (of different types) and a recurrent event and survival with non-linear effects...the list is rather endless. merlin can do things I haven't even thought of yet. I'll take a single dataset, and attempt to show you the full range of capabilities of merlin, and discuss some future directions for the implementation in Stata.
Health economic evaluations often require predictions of survival rates beyond the follow-up period. Parametric survival models can be more convenient for economic modelling than the Cox model. The generalized gamma (GG) and generalized F (GF) distributions are extensive families that contain almost all commonly used distributions with various hazard shapes and arbitrary complexity. In this study, we present a new SAS macro for implementing a wide variety of flexible parametric models including the GG and GF distributions and their special cases, as well as the Gompertz distribution. Proper cu…
Silesian University of Technology（西里西亚工业大学）；Institute of Innovative Technologies, EMAG（EMAG创新技术研究所）
This article presents GuideR, a user-guided rule induction algorithm, which overcomes the largest limitation of the existing methods-the lack of the possibility to introduce user's preferences or domain knowledge to the rule learning process. Automatic selection of attributes and attribute ranges often leads to the situation in which resulting rules do not contain interesting information. We propose an induction algorithm which takes into account user's requirements. Our method uses the sequential covering approach and is suitable for classification, regression, and survival analysis problems.…
Survival analysis concerns the study of timeline data where the event of interest may remain unobserved (i.e., censored). Studies commonly record more than one type of event, but conventional survival techniques focus on a single event type. We set out to integrate both multiple independently censored time-to-event variables as well as missing observations. An energy-based approach is taken with a bi-partite structure between latent and visible states, known as harmoniums (or restricted Boltzmann machines). The present harmonium is shown, both theoretically and experimentally, to capture non-l…
Longitudinal and high-dimensional measurements have become increasingly common in biomedical research. However, methods to predict survival outcomes using covariates that are both longitudinal and high-dimensional are currently missing. In this article, we propose penalized regression calibration (PRC), a method that can be employed to predict survival in such situations. PRC comprises three modeling steps: First, the trajectories described by the longitudinal predictors are flexibly modeled through the specification of multivariate mixed effects models. Second, subject-specific summaries of t…
This paper studies Cox's regression hazard model with an unobservable random frailty where no specific distribution is postulated for the frailty variable, and the marginal lifetime distribution allows both parametric and non-parametric models. Laplace's approximation method and gradient search on smooth manifolds embedded in Euclidean space are applied, and a non-iterative profile likelihood optimization method is proposed for estimating the regression coefficients. The proposed method is compared with the Expected-Maximization method developed based on a gamma frailty assumption, and also in…
Survival regression is used to estimate the relation between time-to-event and feature variables, and is important in application domains such as medicine, marketing, risk management and sales management. Nonlinear tree based machine learning algorithms as implemented in libraries such as XGBoost, scikit-learn, LightGBM, and CatBoost are often more accurate in practice than linear models. However, existing state-of-the-art implementations of tree-based models have offered limited support for survival regression. In this work, we implement loss functions for learning accelerated failure time (A…
Survival data is encountered in a range of disciplines, most notably health and medical research. Although Bayesian approaches to the analysis of survival data can provide a number of benefits, they are less widely used than classical (e.g. likelihood-based) approaches. This may be in part due to a relative absence of user-friendly implementations of Bayesian survival models. In this article we describe how the rstanarm R package can be used to fit a wide range of Bayesian survival models. The rstanarm package facilitates Bayesian regression modelling by providing a user-friendly interface (us…
The Cox proportional hazard model is one of the most popular tools in analyzing time-to-event data in public health studies. When outcomes observed in clinical data from different regions yield a varying pattern correlated with location, it is often of great interest to investigate spatially varying effects of covariates. In this paper, we propose a geographically weighted Cox regression model for sparse spatial survival data. In addition, a stochastic neighborhood weighting scheme is introduced at the county level. Theoretical properties of the proposed geographically weighted estimators are …
Gene/pathway-based methods are drawing significant attention due to their usefulness in detecting rare and common variants that affect disease susceptibility. The biological mechanism of drug responses indicates that a gene-based analysis has even greater potential in pharmacogenetics. Motivated by a study from the Vitamin Intervention for Stroke Prevention (VISP) trial, we develop a gene-trait similarity regression for survival analysis to assess the effect of a gene or pathway on time-to-event outcomes. The similarity regression has a general framework that covers a range of survival models,…
Several gene-based association tests for time-to-event traits have been proposed recently, to detect whether a gene region (containing multiple variants), as a set, is associated with the survival outcome. However, for bivariate survival outcomes, to the best of our knowledge, there is no statistical method that can be directly applied for gene-based association analysis. Motivated by a genetic study to discover gene regions associated with the progression of a bilateral eye disease, Age-related Macular Degeneration (AMD), we implement a novel functional regression method under the copula fram…
Dana–Farber Cancer Institute（达纳-法伯癌症研究所）；Harvard Medical School（哈佛医学院）；University of Oxford（牛津大学）；Improbable（Improbable公司）
Survival models are a popular tool for the analysis of time to event data with applications in medicine, engineering, economics, and many more. Advances like the Cox proportional hazard model have enabled researchers to better describe hazard rates for the occurrence of single fatal events, but are unable to accurately model competing events and transitions. Common phenomena are often better described through multiple states, for example: the progress of a disease modeled as healthy, sick and dead instead of healthy and dead, where the competing nature of death and disease has to be taken into…
The Cox regression model is a popular model for analyzing the relationship between a covariate and a survival endpoint. The standard Cox model assumes a constant covariate effect across the entire covariate domain. However, in many epidemiological and other applications, the covariate of main interest is subject to a threshold effect: a change in the slope at a certain point within the covariate domain. Often, the covariate of interest is subject to some degree of measurement error. In this paper, we study measurement error correction in the case where the threshold is known. Several bias corr…
We consider a non-proportional hazards model where the regression coefficient is not constant but piecewise constant. Following Andersen and Gill (1982), we know that a knowledge of the changepoint leads to a relatively straightforward estimation of the regression coefficients on either side of the changepoint. Between adjacent changepoints, we place ourselves under the proportional hazards model. We can then maximize the partial likelihood to obtain a consistent estimation of the regression coefficients. Difficulties occur when we want to estimate these changepoints. We obtain a confidence re…
Modelling customer churn for the retail industry in a deep learning based sequential framework
University of Essex（埃塞克斯大学）；Profusion Media Ltd.（Profusion传媒有限公司）；Essex Business School（埃塞克斯商学院）；Friedrich-Alexander University Erlangen-Nuremberg（埃尔朗根-纽伦堡弗里德里希-亚历山大大学）
We consider a log-linear model for survival data, where both the location and scale parameters depend on covariates and the baseline hazard function is completely unspecified. This model provides the flexibility needed to capture many interesting features of survival data at a relatively low cost in model complexity. Estimation procedures are developed and asymptotic properties of the resulting estimators are derived using empirical process theory. Finally, a resampling procedure is developed to estimate the limiting variances of the estimators. The finite sample properties of the estimators a…
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…
Patient-level health economic data collected alongside clinical trials are an important component of the process of technology appraisal, with a view to informing resource allocation decisions. For end of life treatments, such as cancer treatments, modelling of cost-effectiveness/utility data may involve some form of partitioned survival analysis, where measures of health-related quality of life and survival time for both pre- and post-progression periods are combined to generate some aggregate measure of clinical benefits (e.g. quality-adjusted survival). In addition, resource use data are of…
University of Michigan（密歇根大学）；Merck Research Laboratories（默克研究实验室）
There has been increasing interest in modelling survival data using deep learning methods in medical research. Current approaches have focused on designing special cost functions to handle censored survival data. We propose a very different method with two steps. In the first step, we transform each subject's survival time into a series of jackknife pseudo conditional survival probabilities and then use these pseudo probabilities as a quantitative response variable in the deep neural network model. By using the pseudo values, we reduce a complex survival analysis to a standard regression probl…
In this paper, we derive the joint distribution of progression-free and overall survival as a function of transition probabilities in a multistate model. No assumptions on copulae or latent event times are needed and the model is allowed to be non-Markov. From the joint distribution, statistics of interest can then be computed. As an example, we provide closed formulas and statistical inference for Pearson's correlation coefficient between progression-free and overall survival in a parametric framework. The example is inspired by recent approaches to quantify the dependence between progression…
