Censored Survival Data Research Articles

Few-Shot Learning for Handling Highly Censored Survival Data

Few-Shot Learning for Handling Highly Censored Survival Data

Confidence bands for hazard rate function based on a debiased estimation

The hazard rate function plays an important role in survival analysis. Extensive work has been carried out for building the point estimation of hazard rate function but limited work has been done for constructing its confidence bands, which is a fundamental issue in statistical inference. To fill in this gap, we focus on investigating this problem for right censored survival data in this paper. We first propose a debiased estimation for hazard rate function, based on which, we further construct the pointwise and simultaneous confidence bands for hazard rate function. We establish some theoretical properties of the proposed method, including the convergence rate and asymptotic distributions. The finite-sample performance of the proposed procedure is evaluated via both simulation studies and an application to a real data from the breast cancer study.

Interval Censored Recursive Forests

We propose interval censored recursive forests (ICRF), an iterative tree ensemble method for interval censored survival data. This nonparametric regression estimator addresses the splitting bias problem of existing tree-based methods and iteratively updates survival estimates in a self-consistent manner. Consistent splitting rules are developed for interval censored data, convergence is monitored using out-of-bag samples, and kernel-smoothing is applied. The ICRF is uniformly consistent and displays high prediction accuracy in both simulations and applications to avalanche and national mortality data. An R package icrf is available on CRAN. Supplementary files for this article are available online.

Competing risks survival data under middle censoring—An application to COVID-19 pandemic

Survival data is being analysed here under the middle censoring scheme, using specifically quantile function modelling under competing risks. The use of middle censoring scheme has been shown to be very appropriate under the COVID-19 pandemic scenario. Cause-specific quantile inference under middle censoring is employed. Such quantile inferences are obtained through cumulative incidence function based on cause-specific proportional hazards model. The baseline lifetime is assumed to follow a very general parametric model namely the Weibull distribution, and is independent of the censoring mechanism. We obtain estimates of the unknown parameters and cause specific quantile functions under classical as well as a Bayesian set-up. A Monte Carlo simulation study assesses the relative performance of the different estimators. Finally, a real life data analysis is given for illustration of the proposed methods.

SMIM: A unified framework of survival sensitivity analysis using multiple imputation and martingale.

Censored survival data are common in clinical trial studies. We propose a unified framework for sensitivity analysis to censoring at random in survival data using multiple imputation and martingale, called SMIM. The proposed framework adopts the δ-adjusted and control-based models, indexed by the sensitivity parameter, entailing censoring at random and a wide collection of censoring not at random assumptions. Also, it targets a broad class of treatment effect estimands defined as functionals of treatment-specific survival functions, taking into account missing data due to censoring. Multiple imputation facilitates the use of simple full-sample estimation; however, the standard Rubin's combining rule may overestimate the variance for inference in the sensitivity analysis framework. We decompose the multiple imputation estimator into a martingale series based on the sequential construction of the estimator and propose the wild bootstrap inference by resampling the martingale series. The new bootstrap inference has a theoretical guarantee for consistency and is computationally efficient compared to the nonparametric bootstrap counterpart. We evaluate the finite-sample performance of the proposed SMIM through simulation and an application on an HIV clinicaltrial.

Generalized Topp-Leone-Weibull AFT Modelling: A Bayesian Analysis with MCMC Tools using R and Stan

The generalized Topp-Leone-Weibull (GTL-W) distribution is a generalization of Weibull distribution which is obtained by using generalized Topp-Leone (GTL) distribution as a generator and considering Weibull distribution as a baseline distribution. Weibull distribution is a widely used survival model that has monotone- increasing or decreasing hazard. But it cannot accommodate bathtub shaped and unimodal shaped hazards. As a survival model, GTL-W distribution is more flexible than the Weibull distribution to accommodate different types of hazards. The present study aims at fitting GTL-W model as an accelerated failure time (AFT) model to censored survival data under Bayesian setting using R and Stan languages. The GTL-W AFT model is compared with its sub-model and the baseline model. The Bayesian model selection criteria LOOIC and WAIC are applied to select the best model.

Deep learning for quantile regression under right censoring: DeepQuantreg

The computational prediction algorithm of neural network, or deep learning, has drawn much attention recently in statistics as well as in image recognition and natural language processing. Particularly in statistical application for censored survival data, the loss function used for optimization has been mainly based on the partial likelihood from Cox's model and its variations to utilize existing neural network library such as Keras, which was built upon the open source library of TensorFlow. As a novel contribution to the literature, an extension of the neural network to the quantile regression is proposed for survival data with right censoring, which is adjusted by the inverse of the estimated censoring distribution in the check function. The main purpose is to show that the deep learning method could be flexible enough to predict nonlinear patterns more accurately compared to existing quantile regression methods such as traditional linear quantile regression and nonparametric quantile regression with total variation regularization, emphasizing practicality of the method for censored survival data. Simulation studies were performed to generate nonlinear censored survival data and compare the deep learning method with existing quantile regression methods in terms of prediction accuracy. The proposed method is illustrated with two publicly available breast cancer data sets with gene signatures. The method has been built into a package and is freely available at https://github.com/yicjia/DeepQuantreg.

Principal Component Analysis in Linear Regression Survival Model with Microarray Data

As a useful alternative to the Cox proportional hazards model, the linear regression survival model assumes a linear relationship between the covariates and a known monotone transformation, for example logarithm, of an event time of interest. In this article, we study the linear regression survival model with right censored survival data, when high-dimensional microarray measurements are present. Such data may arise in studies in vestigating the statistical influence of molecular features on survival risk. We propose using the principal component regression (PCR) technique for model reduction based on the weight least squared Stute estimate. Com pared with other model reduction techniques, the PCR approach is relatively insensitive to the number of covariates and hence suitable for high dimen sional microarray data. Component selection based on the nonparametric bootstrap, and model evaluation using the time-dependent ROC (receiver operating characteristic) technique are investigated. We demonstrate the proposed approach with datasets from two microarray gene expression pro filing studies of lymphoma cancers

Nonparametric Multiple Imputation of Left Censored Event Times in Analysis of Follow-up Data

In this paper, we consider analysis of follow-up data where each event time is either right censored, observed, left censored or left truncated. In the case of left censoring, the covariates measured at baseline are considered as missing. The work is motivated by data from the MORGAM Project, which explores the association between cardiovascular diseases and their classic and genetic risk factors. We propose a nonparametric multiple imputation (NPMI) approach where the left censored event times and the missing covariates are imputed in hot deck manner. The left truncation due to deaths prior to baseline is compensated by Lexis diagram imputation introduced in the paper. After imputation, the standard estimation methods for right censored survival data can be directly applied. The performance of the proposed imputation approach is studied with simulated and real world data. The results suggest that the NPMI is a flexible and reliable approach to the analysis of left and right censored data.

Estimating heterogeneous survival treatment effects of lung cancer screening approaches: A causal machine learning analysis

The National Lung Screening Trial (NLST) found that low-dose computed tomography (LDCT) screening provided lung cancer (LC) mortality benefit compared to chest radiography (CXR). Considerable research concerns identifying the differential treatment effects that may exist in certain subpopulations. We shed light on several important issues in existing research and highlight the need for further investigation of the heterogeneous comparative effect of LDCT versus CXR, using more flexible and rigorous statistical approaches. We used a high-performance Bayesian machine learning approach designed for censored survival data, accelerated failure time Bayesian additive regression trees model (AFT-BART), to flexibly capture the relationships between the failure time and predictors. We then used the counterfactual framework to draw Markov chain Monte Carlo samples of the individual treatment effect for each participant. Using these posterior samples, we explored the possible treatment effect heterogeneity via a stepwise binary tree approach. When re-analyzed with AFT-BART, LDCT did not have a statistically significant LC or overall mortality benefit compared to CXR. The Asian and Black (particularly those with pack-year ≥ 37 years and without emphysema) NLST population were shown to have enhanced overall mortality benefit from LDCT than the population average. Although inconclusive for LC mortality benefit, Asians, Blacks and Whites with history of chronic obstructive pulmonary disease showed a small trend towards benefit from LDCT. Causal inference with flexible machine learning modeling can provide valuable knowledge for informing treatment decision and planning targeted clinical trials emphasizing personalized medicine approaches.

Regression analysis of arbitrarily censored survival data under the proportional odds model.

Arbitrarily censored data are referred to as the survival data that contain a mixture of exactly observed, left-censored, interval-censored, and right-censored observations. Existing research work on regression analysis on arbitrarily censored data is relatively sparse and mainly focused on the proportional hazards model and the accelerated failure time model. This article studies the proportional odds (PO) model and proposes a novel estimation approach through an expectation-maximization (EM) algorithm for analyzing such data. The proposed EM algorithm has many appealing properties such as being robust to initial values, easy to implement, converging fast, and providing the variance estimate of the regression parameter estimate in closed form. An informal diagnosis plot is developed for checking the PO model assumption. Our method has shown excellent performance in estimating the regression parameters as well as the baseline survival function in a simulation study. A real-life dataset about metastatic colorectal cancer is analyzed for illustration. An R package regPO has been created for practitioners to implement our method.

Comparison of parametric and semiparametric survival regression models with kernel estimation

The modelling of censored survival data is based on different estimations of the conditional hazard function. When survival time follows a known distribution, parametric models are useful. This strong assumption is replaced by a weaker in the case of semiparametric models. For instance, the frequently used model suggested by Cox is based on the proportionality of hazards. These models use non-parametric methods to estimate some baseline hazard and parametric methods to estimate the influence of a covariate. An alternative approach is to use smoothing that is more flexible. In this paper, two types of kernel smoothing and some bandwidth selection techniques are introduced. Application to real data shows different interpretations for each approach. The extensive simulation study is aimed at comparing different approaches and assessing their benefits. Kernel estimation is demonstrated to be very helpful for verifying assumptions of parametric or semiparametric models and is able to capture changes in the hazard function in both time and covariate directions.

Cox regression analysis for distorted covariates with an unknown distortion function.

We study inference for censored survival data where some covariates are distorted by some unknown functions of an observable confounding variable in a multiplicative form. An example of this kind of data in medical studies is normalizing some important observed exposure variables by patients' body mass index , weight, or age. Such a phenomenon also appears frequently in environmental studies where an ambient measure is used for normalization and in genomic studies where the library size needs to be normalized for the next generation sequencing of data. We propose a new covariate-adjusted Cox proportional hazards regression model and utilize the kernel smoothing method to estimate the distorting function, then employ an estimated maximum likelihood method to derive the estimator for the regression parameters. We establish the large sample properties of the proposed estimator. Extensive simulation studies demonstrate that the proposed estimator performs well in correcting the bias arising from distortion. A real dataset from the National Wilms' Tumor Study is used to illustrate the proposedapproach.

Bi-selection in the high-dimensional additive hazards regression model

In this article, we consider a class of regularized regression under the additive hazards model with censored survival data and propose a novel approach to achieve simultaneous group selection, variable selection, and parameter estimation for high-dimensional censored data, by combining the composite penalty and the pseudoscore. We develop a local coordinate descent (LCD) algorithm for efficient computation and subsequently establish the theoretical properties for the proposed selection methods. As a result, the selectors possess both group selection oracle property and variable selection oracle property, and thus enable us to simultaneously identify important groups and important variables within selected groups with high probability. Simulation studies demonstrate that the proposed method and LCD algorithm perform well. A real data example is provided for illustration.

Robust Wald-type tests under random censoring.

Randomly censored survival data are frequently encountered in biomedical or reliability applications and clinical trial analyses. Testing the significance of statistical hypotheses is crucial in such analyses to get conclusive inference but the existing likelihood-based tests, under a fully parametric model, are extremely nonrobust against outliers in the data. Although there exists a few robust estimators given randomly censored data, there is hardly any robust testing procedure available in the literature in this context. One of the major difficulties here is the construction of a suitable consistent estimator of the asymptotic variance of robust estimators, since the latter is a function of the unknown censoring distribution. In this article, we take the first step in this direction by proposing a consistent estimator of asymptotic variance of the M-estimators based on randomly censored data without any assumption on the censoring scheme. We then describe and study a class of robust Wald-type tests for parametric statistical hypothesis, both simple as well as composite, under such a set-up. Robust tests for comparing two independent randomly censored samples and robust tests against one sided alternatives are also discussed. Their advantages and usefulness are demonstrated for the tests based on the minimum density power divergence estimators and illustrated with clinical trials and other medical data.

Subgroup analysis in the heterogeneous Cox model.

In the analysis of censored survival data, to avoid a biased inference of treatment effects on the hazard function of the survival time, it is important to consider the treatment heterogeneity. Without requiring any prior knowledge about the subgroup structure, we propose a data driven subgroup analysis procedure for the heterogeneous Cox model by constructing a pairwise fusion penalized partial likelihood-based objective function. The proposed method can determine the number of subgroups, identify the group structure, and estimate the treatment effect simultaneously and automatically. A majorized alternating direction method of multipliers algorithm is then developed to deal with the numerically challenging high-dimensional problems. We also establish the oracle properties and the model selection consistency for the proposed penalized estimator. Our proposed method is evaluated by simulation studies and further illustrated by the analysis of the breast cancer data.

Deep Neural Networks for Survival Analysis Using Pseudo Values.

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 simple 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 problem, which greatly simplifies the neural network construction. Our two-step approach is simple, yet very flexible in making risk predictions for survival data, which is very appealing from the practice point of view. The source code is freely available at http://github.com/lilizhaoUM/DNNSurv.

Model-free feature screening via distance correlation for ultrahigh dimensional survival data

With the explosion of ultrahigh dimensional data in various fields, many sure independent screening methods have been proposed to reduce the dimensionality of data from a large scale to a relatively moderate scale. For censored survival data, the existing screening methods mainly adopt the Kaplan–Meier estimator to handle censoring, which may not perform well for heavy censoring cases. In this article, we propose a novel sure independent screening procedure based on distance correlation after standardizing marginal variables for ultrahigh dimensional survival data. It is a model-free approach and does not involve the Kaplan–Meier estimator, thus its performance is much more robust than the existing methods. Furthermore, our proposed method enjoys other advantages: it avoids the complication to specify an actual model from large number of covariates; it enjoys the sure screening property and the ranking consistency under some mild regularity conditions; it does not require any complicated numerical optimization, so the corresponding calculation is very simple and fast. Extensive numerical studies demonstrate that the proposed method has favorable exhibition over the existing methods. As an illustration, we apply the proposed method to a gene expression data set.

Sure joint feature screening in nonparametric transformation model for right censored data

AbstractExisting screening procedures for right censored data either posit a specific model or adopt a marginal approach; hence, they are prone to model misspecification or erroneous screening. To address these problems, we develop a joint feature screening method in nonparametric transformation models for censored survival data. A sparsity‐restricted estimator is proposed using a smoothed partial rank objective function and an iterative hard thresholding algorithm. We rigorously show that with probability tending to 1, the proposed method is capable of retaining all relevant features in the model and is more desirable than marginal screening. Furthermore, because the transformation model encompasses many popular models, such as the Cox model, as special cases, the developed joint screening method is more robust than its competitors. Its finite sample performance is illustrated using both simulation studies and a real data example. We have implemented our method using Matlab and made it available through Github https://github.com/yiucla/SPR-SJS.

Local asymptotic inference for nonparametric regression with censored survival data

We consider a penalised nonparametric estimation of the relative risk function in the Cox proportional hazards model for survival data with right censoring. We derive the convergence rate, functional Bahadur representation (FBR) and local asymptotic normality of the nonparametric estimator by using reproducing kernel Hilbert space, counting process and empirical process theory. The new theoretical results fill the gap in the smoothing splines literature for nonparametric estimation in survival models. Furthermore, we construct the corresponding local confidence intervals by the bootstrap method. Extensive simulation studies are conducted to validate the proposed method and compare with the Bayesian confidence intervals, and a data example from the Stanford heart transplant study is provided for illustration.