Broken adaptive ridge (BAR) is a computationally scalable surrogate to $L_0$-penalized regression, which involves iteratively performing reweighted $L_2$ penalized regressions and enjoys some appealing properties of both $L_0$ and $L_2$ penalized regressions while avoiding some of their limitations. In this paper, we extend the BAR method to the semi-parametric accelerated failure time (AFT) model for right-censored survival data. Specifically, we propose a censored BAR (CBAR) estimator by applying the BAR algorithm to the Leurgan's synthetic data and show that the resulting CBAR estimator is consistent for variable selection, possesses an oracle property for parameter estimation {and enjoys a grouping property for highly correlation covariates}. Both low and high dimensional covariates are considered. The effectiveness of our method is demonstrated and compared with some popular penalization methods using simulations. Real data illustrations are provided on a diffuse large-B-cell lymphoma data and a glioblastoma multiforme data.
Neural interval-censored survival regression with feature selection
Instituto de Ciencias Matemáticas, CSIC（数学科学研究所（西班牙高等科学研究理事会））；Universidad Autónoma de Madrid（马德里自治大学）；Harvard University（哈佛大学）；Université Paris 1 Panthéon-Sorbonne（巴黎第一大学先贤祠-索邦大学）；University of North Carolina, Chapel Hill（北卡罗来纳大学教堂山分校）
The accelerated failure time (AFT) models have proved useful in many contexts, though heavy censoring (as for example in cancer survival) and high dimensionality (as for example in microarray data) cause difficulties for model fitting and model selection. We propose new approaches to variable selection for censored data, based on AFT models optimized using regularized weighted least squares. The regularized technique uses a mixture of L1 and L2 norm penalties under two proposed elastic net type approaches. One is the the adaptive elastic net and the other is weighted elastic net. The approache…
The instability in the selection of models is a major concern with data sets containing a large number of covariates. This paper deals with variable selection methodology in the case of high-dimensional problems where the response variable can be right censored. We focuse on new stable variable selection methods based on bootstrap for two methodologies: the Cox proportional hazard model and survival trees. As far as the Cox model is concerned, we investigate the bootstrapping applied to two variable selection techniques: the stepwise algorithm based on the AIC criterion and the L1-penalization…
Tree methods (recursive partitioning) are a popular class of nonparametric methods for analyzing data. One extension of the basic tree methodology is the survival tree, which applies recursive partitioning to censored survival data. There are several existing survival tree methods in the literature, which are mainly designed for right-censored data. We propose two new survival trees for left-truncated and right-censored (LTRC) data, which can be seen as a generalization of the traditional survival tree for right-censored data. Further, we show that such trees can be used to analyze survival da…
Interval-censored data, in which the event time is only known to lie in some time interval, arise commonly in practice; for example, in a medical study in which patients visit clinics or hospitals at pre-scheduled times, and the events of interest occur between visits. Such data are appropriately analyzed using methods that account for this uncertainty in event time measurement. In this paper we propose a survival tree method for interval-censored data based on the conditional inference framework. Using Monte Carlo simulations we find that the tree is effective in uncovering underlying tree st…
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 propose a novel approach for estimating mean survival time in the presence of censored data, in which we divide the population under study into survival-ordered fractions defined by a set of proportions, and compute the mean survival time for each fraction separately. Our approach provides a detailed picture of the distribution of the time variable while preserving the appealing interpretation of the mean. Our measure proves to be of great use in applications, particularly those where we are able to detect differences in mean survival across groups for certain fractions of the population th…
A new method for the analysis of time to ankylosis complication on a dataset of replanted teeth is proposed. In this context of left-censored, interval-censored and right-censored data, a Cox model with piecewise constant baseline hazard is introduced. Estimation is carried out with the EM algorithm by treating the true event times as unobserved variables. This estimation procedure is shown to produce a block diagonal Hessian matrix of the baseline parameters. Taking advantage of this interesting feature of the estimation method a L0 penalised likelihood method is implemented in order to autom…
Methods for the evaluation of the predictive accuracy of biomarkers with respect to survival outcomes subject to right censoring have been discussed extensively in the literature. In cancer and other diseases, survival outcomes are commonly subject to interval censoring by design or due to the follow up schema. In this paper, we present an estimator for the area under the time-dependent receiver operating characteristic ROC curve for interval censored data based on a nonparametric sieve maximum likelihood approach. We establish the asymptotic properties of the proposed estimator, and illustrat…
Non-parametric maximum likelihood estimation encompasses a group of classic methods to estimate distribution-associated functions from potentially censored and truncated data, with extensive applications in survival analysis. These methods, including the Kaplan-Meier estimator and Turnbull's method, often result in overfitting, especially when the sample size is small. We propose an improvement to these methods by applying kernel smoothing to their raw estimates, based on a BIC-type loss function that balances the trade-off between optimizing model fit and controlling model complexity. In the …
Interval-censored data analysis is important in biomedical statistics for any type of time-to-event response where the time of response is not known exactly, but rather only known to occur between two assessment times. Many clinical trials and longitudinal studies generate interval-censored data; one common example occurs in medical studies that entail periodic follow-up. In this paper we propose a survival forest method for interval-censored data based on the conditional inference framework. We describe how this framework can be adapted to the situation of interval-censored data. We show that…
We propose the interval censored recursive forests (ICRF) which is an iterative tree ensemble method for interval censored survival data. This nonparametric regression estimator makes the best use of censored information by iteratively updating the survival estimate, and can be viewed as a self-consistent estimator with convergence monitored using out-of-bag samples. Splitting rules optimized for interval censored data are developed and kernel-smoothing is applied. The ICRF displays the highest prediction accuracy among competing nonparametric methods in most of the simulations and in an appli…
In this paper we utilize a survival analysis methodology incorporating Bayesian additive regression trees to account for nonlinear and additive covariate effects. We compare the performance of Bayesian additive regression trees, Cox proportional hazards and random survival forests models for censored survival data, using simulation studies and survival analysis for breast cancer with U.S. SEER database for the year 2005. In simulation studies, we compare the three models across varying sample sizes and censoring rates on the basis of bias and prediction accuracy. In survival analysis for breas…
Censored broken adaptive ridge rank regression via induced smoothing
School of Mathematics, Statistics and Data Science, Sungshin Women’s University（成均馆大学数学、统计与数据科学学院）；Sungshin Women’s University（诚信女子大学）；Department of Biostatistics, Virginia Commonwealth University（弗吉尼亚联邦大学生物统计系）；Virginia Commonwealth University（弗吉尼亚联邦大学）；Center for Data Science, Sungshin Women’s University（诚信女子大学数据科学中心）
Survival analysis of right censored data arises often in many areas of research including medical research. Effect of covariates (and their interactions) on survival distribution can be studied through existing methods which requires to pre-specify the functional form of the covariates including their interactions. Survival trees offer relatively flexible approach when the form of covariates' effects is unknown. Most of the currently available survival tree construction techniques are not based on a formal test of significance; however, recently proposed ctree algorithm (Hothorn et al., 2006) …
Nonparametric and semiparametric methods are commonly used in survival analysis to mitigate the bias due to model misspecification. However, such methods often cannot estimate upper-tail survival quantiles when a sizable proportion of the data are censored, in which case parametric likelihood-based estimators present a viable alternative. In this article, we extend a popular family of parametric survival models which make the Accelerated Failure Time (AFT) assumption to account for heteroscedasticity in the survival times. The conditional variances can depend on arbitrary covariates, thus addi…
We investigate the performance of model based bootstrap methods for constructing point-wise confidence intervals around the survival function with interval censored data. We show that bootstrapping from the nonparametric maximum likelihood estimator of the survival function is inconsistent for both the current status and case 2 interval censoring models. A model based smoothed bootstrap procedure is proposed and shown to be consistent. In addition, simulation studies are conducted to illustrate the (in)-consistency of the bootstrap methods. Our conclusions in the interval censoring model would…
In randomized clinical trials with survival outcome, there has been an increasing interest in subgroup identification based on baseline genomic, proteomic markers or clinical characteristics. Some of the existing methods identify subgroups that benefit substantially from the experimental treatment by directly modeling outcomes or treatment effect. When the goal is to find an optimal treatment for a given patient rather than finding the right patient for a given treatment, methods under the individualized treatment regime framework estimate an individualized treatment rule that would lead to th…
Doubly Robust Conformalized Survival Analysis with Right-Censored Data
Department of Data Sciences and Operations（数据科学与运营系）；Department of Computer Science, University of Southern California（计算机科学系，南加州大学）；Merck & Co., Inc.（默克公司）
A comprehensive, unified approach to modeling arbitrarily censored spatial survival data is presented for the three most commonly-used semiparametric models: proportional hazards, proportional odds, and accelerated failure time. Unlike many other approaches, all manner of censored survival times are simultaneously accommodated including uncensored, interval censored, current-status, left and right censored, and mixtures of these. Left-truncated data are also accommodated leading to models for time-dependent covariates. Both georeferenced (location exactly observed) and areally observed (locati…
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…
Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the "difference" and "product" methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two meth…
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.
In medical and biological research, longitudinal data and survival data types are commonly seen. Traditional statistical models mostly consider to deal with either of the data types, such as linear mixed models for longitudinal data, and the Cox models for survival data, while they do not adjust the association between these two different data types. It is desirable to have a joint modeling approach which accomadates both data types and the dependency between them. In this paper, we extend traditional single-index models to a new joint modeling approach, by replacing the single-index component…
Residuals in normal regression are used to assess a model's goodness-of-fit (GOF) and discover directions for improving the model. However, there is a lack of residuals with a characterized reference distribution for censored regression. In this paper, we propose to diagnose censored regression with normalized randomized survival probabilities (RSP). The key idea of RSP is to replace the survival probability of a censored failure time with a uniform random number between 0 and the survival probability of the censored time. We prove that RSPs always have the uniform distribution on $(0,1)$ unde…
In this paper the regression discontinuity design is adapted to the survival analysis setting with right-censored data, studied in an intensity based counting process framework. In particular, a local polynomial regression version of the Aalen additive hazards estimator is introduced as an estimator of the difference between two covariate dependent cumulative hazard rate functions. Large-sample theory for this estimator is developed, including confidence intervals that take into account the uncertainty associated with bias correction. As is standard in the causality literature, the models and …
Quantifying uncertainty of individualized treatment effects in right-censored survival data: A comparison of Bayesian additive regression trees and causal survival forest
We propose a novel personalized concept for the optimal treatment selection for a situation where the response is a multivariate vector, that could contain right-censored variables such as survival time. The proposed method can be applied with any number of treatments and outcome variables, under a broad set of models. Following a working semiparametric Single Index Model that relates covariates and responses, we first define a patient-specific composite score, constructed from individual covariates. We then estimate conditional means of each response, given the patient score, correspond to ea…
Maximum approximate Bernstein likelihood estimates of the baseline density function and the regression coefficients in the proportional hazard regression models based on interval-censored event time data are proposed. This results in not only a smooth estimate of the survival function which enjoys faster convergence rate but also improved estimates of the regression coefficients. Simulation shows that the finite sample performance of the proposed method is better than the existing ones. The proposed method is illustrated by real data applications.
We propose a general index model for survival data, which generalizes many commonly used semiparametric survival models and belongs to the framework of dimension reduction. Using a combination of geometric approach in semiparametrics and martingale treatment in survival data analysis, we devise estimation procedures that are feasible and do not require covariate-independent censoring as assumed in many dimension reduction methods for censored survival data. We establish the root-$n$ consistency and asymptotic normality of the proposed estimators and derive the most efficient estimator in this …
We introduce a novel procedure to perform Bayesian non-parametric inference with right-censored data, the \emph{beta-Stacy bootstrap}. This approximates the posterior law of summaries of the survival distribution (e.g. the mean survival time). More precisely, our procedure approximates the joint posterior law of functionals of the beta-Stacy process, a non-parametric process prior that generalizes the Dirichlet process and that is widely used in survival analysis. The beta-Stacy bootstrap generalizes and unifies other common Bayesian bootstraps for complete or censored data based on non-parame…
With the availability of high dimensional genetic biomarkers, it is of interest to identify heterogeneous effects of these predictors on patients' survival, along with proper statistical inference. Censored quantile regression has emerged as a powerful tool for detecting heterogeneous effects of covariates on survival outcomes. To our knowledge, there is little work available to draw inference on the effects of high dimensional predictors for censored quantile regression. This paper proposes a novel procedure to draw inference on all predictors within the framework of global censored quantile …
