Nonparametric Estimation of Sojourn Time Distributions for Truncated Serial Event Data—a Weight-adjusted Approach

In follow-up studies, survival data often include subjects who have had a certain event at recruitment and may potentially experience a series of subsequent events during the follow-up period. This kind of survival data collected under a cross-sectional sampling criterion is called truncated serial event data. The outcome variables of interest in this paper are serial sojourn times between successive events. To analyze the sojourn times in truncated serial event data, we need to confront two potential sampling biases arising simultaneously from a sampling criterion and induced informative censoring. In this study, nonparametric estimation of the joint probability function of serial sojourn times is developed by using inverse probabilities of the truncation and censoring times as weight functions to accommodate these two sampling biases under various situations of truncation and censoring. Relevant statistical properties of the proposed estimators are also discussed. Simulation studies and two real data are presented to illustrate the proposed methods.     

Adjusted Hazard Rate Estimator Based on a Known Censoring Probability

In most reliability studies involving censoring, one assumes that censoring probabilities are unknown. We derive a nonparametric estimator for the survival function when information regarding censoring frequency is available. The estimator is constructed by adjusting the Nelson–Aalen estimator to incorporate censoring information. Our results indicate significant improvements can be achieved if available information regarding censoring is used. We compare this model to the Koziol–Green model, which is also based on a form of proportional hazards for the lifetime and censoring distributions. Two examples of survival data help to illustrate the differences in the estimation techniques.     

General partially linear varying-coefficient transformation model with right censored data

In this paper, a unified maximum marginal likelihood estimation procedure is proposed for the analysis of right censored data using general partially linear varying-coefficient transformation models (GPLVCTM), which are flexible enough to include many survival models as its special cases. Unknown functional coefficients in the models are approximated by cubic B-spline polynomial. We estimate B-spline coefficients and regression parameters by maximizing marginal likelihood function. One advantage of this procedure is that it is free of both baseline and censoring distribution. Through simulation studies and a real data application (VA data from the Veteran's Administration Lung Cancer Study Clinical Trial), we illustrate that the proposed estimation procedure is accurate, stable and practical.     

Product-limit Estimators and Cox Regression with Missing Censoring Information

The Kaplan–Meier estimator of a survival function requires that the censoring indicator is always observed. A method of survival function estimation is developed when the censoring indicators are missing completely at random (MCAR). The resulting estimator is a smooth functional of the Nelson–Aalen estimators of certain cumulative transition intensities. The asymptotic properties of this estimator are derived. A simulation study shows that the proposed estimator has greater efficiency than competing MCAR-based estimators. The approach is extended to the Cox model setting for the estimation of a conditional survival function given a covariate.     

Semiparametric regression for restricted mean residual life under right censoring

A mean residual life function (MRLF) is the remaining life expectancy of a subject who has survived to a certain time point. In the presence of covariates, regression models are needed to study the association between the MRLFs and covariates. If the survival time tends to be too long or the tail is not observed, the restricted mean residual life must be considered. In this paper, we propose the proportional restricted mean residual life model for fitting survival data under right censoring. For inference on the model parameters, martingale estimating equations are developed, and the asymptotic properties of the proposed estimators are established. In addition, a class of goodness-of-fit test is presented to assess the adequacy of the model. The finite sample behavior of the proposed estimators is evaluated through simulation studies, and the approach is applied to a set of real life data collected from a randomized clinical trial.     

A class of nonparametric bivariate survival function estimators for randomly censored and truncated data

This paper proposes a class of nonparametric estimators for the bivariate survival function estimation under both random truncation and random censoring. In practice, the pair of random variables under consideration may have certain parametric relationship. The proposed class of nonparametric estimators uses such parametric information via a data transformation approach and thus provides more accurate estimates than existing methods without using such information. The large sample properties of the new class of estimators and a general guidance of how to find a good data transformation are given. The proposed method is also justified via a simulation study and an application on an economic data set.     

Quantile regression methods for left-truncated and right-censored data

Left-truncated and right-censored (LTRC) data are encountered frequently due to a prevalent cohort sampling in follow-up studies. Because of the skewness of the distribution of survival time, quantile regression is a useful alternative to the Cox's proportional hazards model and the accelerated failure time model for survival analysis. In this paper, we apply the quantile regression model to LTRC data and develops an unbiased estimating equation for regression coefficients. The proposed estimation methods use the inverse probabilities of truncation and censoring weighting technique. The resulting estimator is uniformly consistent and asymptotically normal. The finite-sample performance of the proposed estimation methods is also evaluated using extensive simulation studies. Finally, analysis of real data is presented to illustrate our proposed estimation methods.     

An Additive–Multiplicative Restricted Mean Residual Life Model

The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive–multiplicative restricted mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline. For the suggested model, some covariate effects are allowed to be time‐varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness of fit test that is asymptotically justified. The proposed methodology is evaluated via simulation studies and further applied to a kidney cancer data set collected from a clinical trial.     

Estimating a Finite Mixed Exponential Distribution under Progressively Type-II Censored Data

The Type-II progressive censoring scheme has become very popular for analyzing lifetime data in reliability and survival analysis. However, no published papers address parameter estimation under progressive Type-II censoring for the mixed exponential distribution (MED), which is an important model for reliability and survival analysis. This is the problem that we address in this paper. It is noted that maximum likelihood estimation of unknown parameters cannot be obtained in closed form due to the complicated log-likelihood function. We solve this problem by using the EM algorithm. Finally, we obtain closed form estimates of the model. The proposed methods are illustrated by both some simulations and a case analysis.     

A Novel Method to Calculate Mean Survival Time for Time-to-Event Data

In the analysis of time-to-event data, restricted mean survival time has been well investigated in the literature and provided by many commercial software packages, while calculating mean survival time remains as a challenge due to censoring or insufficient follow-up time. Several researchers have proposed a hybrid estimator of mean survival based on the Kaplan–Meier curve with an extrapolated tail. However, this approach often leads to biased estimate due to poor estimate of the parameters in the extrapolated “tail” and the large variability associated with the tail of the Kaplan–Meier curve due to small set of patients at risk. Two key challenges in this approach are (1) where the extrapolation should start and (2) how to estimate the parameters for the extrapolated tail. The authors propose a novel approach to calculate mean survival time to address these two challenges. In the proposed approach, an algorithm is used to search if there are any time points where the hazard rates change significantly. The survival function is estimated by the Kaplan–Meier method prior to the last change point and approximated by an exponential function beyond the last change point. The parameter in the exponential function is estimated locally. Mean survival time is derived based on this survival function. The simulation and case studies demonstrated the superiority of the proposed approach.     

An inverse-probability-weighted approach to estimation of the bivariate survival function under left-truncation and right-censoring

In this note, we consider estimating the bivariate survival function when both survival times are subject to random left truncation and one of the survival times is subject to random right censoring. Motivated by Satten and Datta [2001. The Kaplan–Meier estimator as an inverse-probability-of-censoring weighted average. Amer. Statist. 55, 207–210], we propose an inverse-probability-weighted (IPW) estimator. It involves simultaneous estimation of the bivariate survival function of the truncation variables and that of the censoring variable and the truncation variable of the uncensored components. We prove that (i) when there is no censoring, the IPW estimator reduces to NPMLE of van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131] and (ii) when there is random left truncation and right censoring on only one of the components and the other component is always observed, the IPW estimator reduces to the estimator of Gijbels and Gürler [1998. Covariance function of a bivariate distribution function estimator for left truncated and right censored data. Statist. Sin. 1219–1232]. Based on Theorem 3.1 of van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131, 1996b. Efficient estimation of the bivariate censoring model and repairing NPMLE. Ann. Statist. 24, 596–627], we prove that the IPW estimator is consistent under certain conditions. Finally, we examine the finite sample performance of the IPW estimator in some simulation studies. For the special case that censoring time is independent of truncation time, a simulation study is conducted to compare the performances of the IPW estimator against that of the estimator proposed by van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131, 1996b. Efficient estimation of the bivariate censoring model and repairing NPMLE. Ann. Statist. 24, 596–627]. For the special case (i), a simulation study is conducted to compare the performances of the IPW estimator against that of the estimator proposed by Huang et al. (2001. Nonnparametric estimation of marginal distributions under bivariate truncation with application to testing for age-of-onset application. Statist. Sin. 11, 1047–1068).     

A semi-parametric estimation of a survival function from incomplete and doubly censored data

The purpose of this paper is to present a semi-parametric estimation of a survival function when analyzing incomplete and doubly censored data. Under the assumption that the chance of censoring is not related to the individual's survivorship, we propose a consistent estimation of survival. The derived estimator treats the uncensored observations nonparametrically and uses parametric models for both right and left censored data. Some asymptotic properties and simulation studies are also presented in order to analyze the behavior of the proposed estimator.     

Likelihood Ratio Confidence Bands in Non–parametric Regression with Censored Data

Let ( X , Y ) be a random vector, where Y denotes the variable of interest possibly subject to random right censoring, and X is a covariate. We construct confidence intervals and bands for the conditional survival and quantile function of Y given X using a non-parametric likelihood ratio approach. This approach was introduced by Thomas & Grunkemeier (1975 ), who estimated confidence intervals of survival probabilities based on right censored data. The method is appealing for several reasons: it always produces intervals inside [0, 1], it does not involve variance estimation, and can produce asymmetric intervals. Asymptotic results for the confidence intervals and bands are obtained, as well as simulation results, in which the performance of the likelihood ratio intervals and bands is compared with that of the normal approximation method. We also propose a bandwidth selection procedure based on the bootstrap and apply the technique on a real data set.     

Improved precision in the analysis of randomized trials with survival outcomes,without assuming proportional hazards

We present a new estimator of the restricted mean survival time in randomized trials where there is right censoring that may depend on treatment and baseline variables. The proposed estimator leverages prognostic baseline variables to obtain equal or better asymptotic precision compared to traditional estimators. Under regularity conditions and random censoring within strata of treatment and baseline variables, the proposed estimator has the following features: (i) it is interpretable under violations of the proportional hazards assumption; (ii) it is consistent and at least as precise as the Kaplan–Meier and inverse probability weighted estimators, under identifiability conditions; (iii) it remains consistent under violations of independent censoring (unlike the Kaplan–Meier estimator) when either the censoring or survival distributions, conditional on covariates, are estimated consistently; and (iv) it achieves the nonparametric efficiency bound when both of these distributions are consistently estimated. We illustrate the performance of our method using simulations based on resampling data from a completed, phase 3 randomized clinical trial of a new surgical treatment for stroke; the proposed estimator achieves a 12% gain in relative efficiency compared to the Kaplan–Meier estimator. The proposed estimator has potential advantages over existing approaches for randomized trials with time-to-event outcomes, since existing methods either rely on model assumptions that are untenable in many applications, or lack some of the efficiency and consistency properties (i)–(iv). We focus on estimation of the restricted mean survival time, but our methods may be adapted to estimate any treatment effect measure defined as a smooth contrast between the survival curves for each study arm. We provide R code to implement the estimator.

     

Smoothing Spline Estimation for Partially Linear Single-index Models

In this article, the partially linear single-index models are discussed based on smoothing spline and average derivative estimation method. This proposed technique consists of two stages: one is to estimate the vector parameter in the linear part using the smoothing cubic spline method, simultaneously, obtaining the estimator of unknown single-index function; the other is to estimate the single-index coefficients in the single-index part by the using average derivative estimator procedure. Some simulated and real examples are presented to illustrate the performance of this method.     

Flexible semi-parametric regression of state occupational probabilities in a multistate model with right-censored data

Inference for the state occupation probabilities, given a set of baseline covariates, is an important problem in survival analysis and time to event multistate data. We introduce an inverse censoring probability re-weighted semi-parametric single index model based approach to estimate conditional state occupation probabilities of a given individual in a multistate model under right-censoring. Besides obtaining a temporal regression function, we also test the potential time varying effect of a baseline covariate on future state occupation. We show that the proposed technique has desirable finite sample performances and its performance is competitive when compared with three other existing approaches. We illustrate the proposed methodology using two different data sets. First, we re-examine a well-known data set dealing with leukemia patients undergoing bone marrow transplant with various state transitions. Our second illustration is based on data from a study involving functional status of a set of spinal cord injured patients undergoing a rehabilitation program.     

Semiparametric analysis of recurrent events: artificial censoring,truncation, pairwise estimation and inference

The analysis of recurrent failure time data from longitudinal studies can be complicated by the presence of dependent censoring. There has been a substantive literature that has developed based on an artificial censoring device. We explore in this article the connection between this class of methods with truncated data structures. In addition, a new procedure is developed for estimation and inference in a joint model for recurrent events and dependent censoring. Estimation proceeds using a mixed U-statistic based estimating function approach. New resampling-based methods for variance estimation and model checking are also described. The methods are illustrated by application to data from an HIV clinical trial as with a limited simulation study.     

A Bayesian approach to non-parametric monotone function estimation

Summary.  The paper proposes two Bayesian approaches to non-parametric monotone function estimation. The first approach uses a hierarchical Bayes framework and a characterization of smooth monotone functions given by Ramsay that allows unconstrained estimation. The second approach uses a Bayesian regression spline model of Smith and Kohn with a mixture distribution of constrained normal distributions as the prior for the regression coefficients to ensure the monotonicity of the resulting function estimate. The small sample properties of the two function estimators across a range of functions are provided via simulation and compared with existing methods. Asymptotic results are also given that show that Bayesian methods provide consistent function estimators for a large class of smooth functions. An example is provided involving economic demand functions that illustrates the application of the constrained regression spline estimator in the context of a multiple-regression model where two functions are constrained to be monotone.     

Spatially-adaptive Penalties for Spline Fitting

The paper studies spline fitting with a roughness penalty that adapts to spatial heterogeneity in the regression function. The estimates are p th degree piecewise polynomials with p − 1 continuous derivatives. A large and fixed number of knots is used and smoothing is achieved by putting a quadratic penalty on the jumps of the p th derivative at the knots. To be spatially adaptive, the logarithm of the penalty is itself a linear spline but with relatively few knots and with values at the knots chosen to minimize the generalized cross validation (GCV) criterion. This locally-adaptive spline estimator is compared with other spline estimators in the literature such as cubic smoothing splines and knot-selection techniques for least squares regression. Our estimator can be interpreted as an empirical Bayes estimate for a prior allowing spatial heterogeneity. In cases of spatially heterogeneous regression functions, empirical Bayes confidence intervals using this prior achieve better pointwise coverage probabilities than confidence intervals based on a global-penalty parameter. The method is developed first for univariate models and then extended to additive models.     

Variable kernel density estimation

This paper considers the problem of selecting optimal bandwidths for variable (sample‐point adaptive) kernel density estimation. A data‐driven variable bandwidth selector is proposed, based on the idea of approximating the log‐bandwidth function by a cubic spline. This cubic spline is optimized with respect to a cross‐validation criterion. The proposed method can be interpreted as a selector for either integrated squared error (ISE) or mean integrated squared error (MISE) optimal bandwidths. This leads to reflection upon some of the differences between ISE and MISE as error criteria for variable kernel estimation. Results from simulation studies indicate that the proposed method outperforms a fixed kernel estimator (in terms of ISE) when the target density has a combination of sharp modes and regions of smooth undulation. Moreover, some detailed data analyses suggest that the gains in ISE may understate the improvements in visual appeal obtained using the proposed variable kernel estimator. These numerical studies also show that the proposed estimator outperforms existing variable kernel density estimators implemented using piecewise constant bandwidth functions.