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.     

Semiparametric simultaneous confidence bands for the difference of survival functions

In the analysis of censored survival data, simultaneous confidence bands are useful devices to help determine the efficacy of a treatment over a control. Semiparametric confidence bands are developed for the difference of two survival curves using empirical likelihood and compared with the nonparametric counterpart. Simulation studies are presented to show that the proposed semiparametric approach is superior, with the new confidence bands giving empirical coverage closer to the nominal level. Further comparisons reveal that the semiparametric confidence bands are tighter and, hence, more informative. For censoring rates between 10 and 40 %, the semiparametric confidence bands provide a relative reduction in enclosed area amounting to between 2 and 10 % over their nonparametric bands, with increased reduction attained for higher censoring rates. The methods are illustrated using an University of Massachusetts AIDS data set.     

IMPORTANCE BOOTSTRAP RESAMPLING FOR PROPORTIONAL HAZARDS REGRESSION

Importance resampling is an approach that uses exponential tilting to reduce the resampling necessary for the construction of nonparametric bootstrap confidence intervals. The properties of bootstrap importance confidence intervals are well established when the data is a smooth function of means and when there is no censoring. However, in the framework of survival or time-to-event data, the asymptotic properties of importance resampling have not been rigorously studied, mainly because of the unduly complicated theory incurred when data is censored. This paper uses extensive simulation to show that, for parameter estimates arising from fitting Cox proportional hazards models, importance bootstrap confidence intervals can be constructed if the importance resampling probabilities of the records for the n individuals in the study are determined by the empirical influence function for the parameter of interest. Our results show that, compared to uniform resampling, importance resampling improves the relative mean-squared-error (MSE) efficiency by a factor of nine (for n = 200). The efficiency increases significantly with sample size, is mildly associated with the amount of censoring, but decreases slightly as the number of bootstrap resamples increases. The extra CPU time requirement for calculating importance resamples is negligible when compared to the large improvement in MSE efficiency. The method is illustrated through an application to data on chronic lymphocytic leukemia, which highlights that the bootstrap confidence interval is the preferred alternative to large sample inferences when the distribution of a specific covariate deviates from normality. Our results imply that, because of its computational efficiency, importance resampling is recommended whenever bootstrap methodology is implemented in a survival framework. Its use is particularly important when complex covariates are involved or the survival problem to be solved is part of a larger problem; for instance, when determining confidence bounds for models linking survival time with clusters identified in gene expression microarray data.     

Confidence intervals for survival quantiles in the Cox regression model

Median survival times and their associated confidence intervals are often used to summarize the survival outcome of a group of patients in clinical trials with failure-time endpoints. Although there is an extensive literature on this topic for the case in which the patients come from a homogeneous population, few papers have dealt with the case in which covariates are present as in the proportional hazards model. In this paper we propose a new approach to this problem and demonstrate its advantages over existing methods, not only for the proportional hazards model but also for the widely studied cases where covariates are absent and where there is no censoring. As an illustration, we apply it to the Stanford Heart Transplant data. Asymptotic theory and simulation studies show that the proposed method indeed yields confidence intervals and bands with accurate coverage errors.     

BOOTSTRAPPED MULTI-DIMENSIONAL PRODUCT LIMIT PROCESS

We approximate the limit process for a multivariate censored survival distribution using the bootstrap. The empirical process has a complicated covariance structure depending on the survival and censoring. The bootstrapped process provides a means to develop distribution-free procedures including simultaneous confidence bands. Results extend to comparison of multivariate survival distributions. A gallstone study is examined in some detail.     

Kernel Estimation of Rate Function for Recurrent Event Data

Abstract.  Recurrent event data are largely characterized by the rate function but smoothing techniques for estimating the rate function have never been rigorously developed or studied in statistical literature. This paper considers the moment and least squares methods for estimating the rate function from recurrent event data. With an independent censoring assumption on the recurrent event process, we study statistical properties of the proposed estimators and propose bootstrap procedures for the bandwidth selection and for the approximation of confidence intervals in the estimation of the occurrence rate function. It is identified that the moment method without resmoothing via a smaller bandwidth will produce a curve with nicks occurring at the censoring times, whereas there is no such problem with the least squares method. Furthermore, the asymptotic variance of the least squares estimator is shown to be smaller under regularity conditions. However, in the implementation of the bootstrap procedures, the moment method is computationally more efficient than the least squares method because the former approach uses condensed bootstrap data. The performance of the proposed procedures is studied through Monte Carlo simulations and an epidemiological example on intravenous drug users.     

Nonparametric estimation of a survival function under progressive Type-I multistage censoring

Failure time data subject to three progressive Type-I multistage censoring schemes are studied. Product limit estimators are proposed for the estimation of the survival function. It is shown that the resulting estimators are asymptotically equivalent to the corresponding estimators where the data are subject to a random iid right censoring scheme. Many well-known results on confidence bands and tests for randomly right censored data hold for these progressive censoring schemes.     

Tobit regression for modeling mean survival time using data subject to multiple sources of censoring

Mean survival time is often of inherent interest in medical and epidemiologic studies. In the presence of censoring and when covariate effects are of interest, Cox regression is the strong default, but mostly due to convenience and familiarity. When survival times are uncensored, covariate effects can be estimated as differences in mean survival through linear regression. Tobit regression can validly be performed through maximum likelihood when the censoring times are fixed (ie, known for each subject, even in cases where the outcome is observed). However, Tobit regression is generally inapplicable when the response is subject to random right censoring. We propose Tobit regression methods based on weighted maximum likelihood which are applicable to survival times subject to both fixed and random censoring times. Under the proposed approach, known right censoring is handled naturally through the Tobit model, with inverse probability of censoring weighting used to overcome random censoring. Essentially, the re‐weighting data are intended to represent those that would have been observed in the absence of random censoring. We develop methods for estimating the Tobit regression parameter, then the population mean survival time. A closed form large‐sample variance estimator is proposed for the regression parameter estimator, with a semiparametric bootstrap standard error estimator derived for the population mean. The proposed methods are easily implementable using standard software. Finite‐sample properties are assessed through simulation. The methods are applied to a large cohort of patients wait‐listed for kidney transplantation.     

Bootstrapping survival times in stochastic systems by using saddlepoint approximations

The single bootstrap is implemented by using a saddlepoint approximation to determine estimates for the survival and hazard functions of first-passage times in complicated semi-Markov processes. The double bootstrap is also implemented by resampling saddlepoint inversions and provides BC_a confidence bands for these functions. Confidence intervals for the mean and variance of first-passage times are easily computed. A new characterization of the asymptotic hazard rate for survival times is presented and leads to an indirect method for constructing its bootstrap confidence interval.     

Statistical analysis of competing risks model from Marshall–Olkin extended Chen distribution under adaptive progressively interval censoring with random removals

In this paper, a new censoring scheme named by adaptive progressively interval censoring scheme is introduced. The competing risks data come from Marshall–Olkin extended Chen distribution under the new censoring scheme with random removals. We obtain the maximum likelihood estimators of the unknown parameters and the reliability function by using the EM algorithm based on the failure data. In addition, the bootstrap percentile confidence intervals and bootstrap-t confidence intervals of the unknown parameters are obtained. To test the equality of the competing risks model, the likelihood ratio tests are performed. Then, Monte Carlo simulation is conducted to evaluate the performance of the estimators under different sample sizes and removal schemes. Finally, a real data set is analyzed for illustration purpose.     

A resampling‐based test for two crossing survival curves

The area between two survival curves is an intuitive test statistic for the classical two‐sample testing problem. We propose a bootstrap version of it for assessing the overall homogeneity of these curves. Our approach allows ties in the data as well as independent right censoring, which may differ between the groups. The asymptotic distribution of the test statistic as well as of its bootstrap counterpart are derived under the null hypothesis, and their consistency is proven for general alternatives. We demonstrate the finite sample superiority of the proposed test over some existing methods in a simulation study and illustrate its application by a real‐data example.     

Random Weighted Bootstrap Method for Recurrent Events with Informative Censoring

Using the data from the AIDS Link to Intravenous Experiences cohort study as an example, an informative censoring model was used to characterize the repeated hospitalization process of a group of patients. Under the informative censoring assumption, the estimators of the baseline rate function and the regression parameters were shown to be related to a latent variable. Hence, it becomes impractical to directly estimate the unknown quantities in the moments of the estimators for the bandwidth selection of a smoothing estimator and the construction of confidence intervals, which are respectively based on the asymptotic mean squared errors and the asymptotic distributions of the estimators. To overcome these difficulties, we develop a random weighted bootstrap procedure to select appropriate bandwidths and to construct approximated confidence intervals. One can see that our method is simple and faster to implement from a practical point of view, and is at least as accurate as other bootstrap methods. In this article, it is shown that the proposed method is useful through the performance of a Monte Carlo simulation. An application of our procedure is also illustrated by a recurrent event sample of intravenous drug users for inpatient cares over time.     

Parameter estimation of Lindley step stress model with independent competing risk under type 1 censoring

Abstract

In literature, Lindley distribution is considered as an alternative to exponential distribution to fit lifetime data. In the present work, a Lindley step-stress model with independent causes of failure is proposed. An algorithm to generate random samples from the proposed model under type 1 censoring scheme is developed. Point and interval estimation of the model parameters is carried out using maximum likelihood method and percentile bootstrap approach. To understand the effectiveness of the resulting estimates, numerical illustration is provided based on simulated and real-life data sets.     

A new two sample type-II progressive censoring scheme

In this paper we introduce a new type-II progressive censoring scheme for two samples. It is observed that the proposed censoring scheme is analytically more tractable than the existing joint progressive type-II censoring scheme proposed by Rasouli and Balakrishnan. The maximum likelihood estimators of the unknown parameters are obtained and their exact distributions are derived. Based on the exact distributions of the maximum likelihood estimators exact confidence intervals are also constructed. For comparison purposes we have used bootstrap confidence intervals also. One data analysis has been performed for illustrative purposes. Finally we propose some open problems.     

Subgroup Analysis with Time‐to‐Event Data Under a Logistic‐Cox Mixture Model

Subgroup detection has received increasing attention recently in different fields such as clinical trials, public management and market segmentation analysis. In these fields, people often face time‐to‐event data, which are commonly subject to right censoring. This paper proposes a semiparametric Logistic‐Cox mixture model for subgroup analysis when the interested outcome is event time with right censoring. The proposed method mainly consists of a likelihood ratio‐based testing procedure for testing the existence of subgroups. The expectation–maximization iteration is applied to improve the testing power, and a model‐based bootstrap approach is developed to implement the testing procedure. When there exist subgroups, one can also use the proposed model to estimate the subgroup effect and construct predictive scores for the subgroup membership. The large sample properties of the proposed method are studied. The finite sample performance of the proposed method is assessed by simulation studies. A real data example is also provided for illustration.     

Bootstrapping Regression Parameters in Multivariate Survival Analysis

Bootstrap methods are proposed for estimating sampling distributions and associated statistics for regression parameters in multivariate survival data. We use an Independence Working Model (IWM) approach, fitting margins independently, to obtain consistent estimates of the parameters in the marginal models. Resampling procedures, however, are applied to an appropriate joint distribution to estimate covariance matrices, make bias corrections, and construct confidence intervals. The proposed methods allow for fixed or random explanatory variables, the latter case using extensions of existing resampling schemes (Loughin,1995), and they permit the possibility of random censoring. An application is shown for the viral positivity time data previously analyzed by Wei, Lin, and Weissfeld (1989). A simulation study of small-sample properties shows that the proposed bootstrap procedures provide substantial improvements in variance estimation over the robust variance estimator commonly used with the IWM. This revised version was published online in July 2006 with corrections to the Cover Date.     

Adaptive Lasso Variable Selection for the Accelerated Failure Models

This article considers the adaptive lasso procedure for the accelerated failure time model with multiple covariates based on weighted least squares method, which uses Kaplan-Meier weights to account for censoring. The adaptive lasso method can complete the variable selection and model estimation simultaneously. Under some mild conditions, the estimator is shown to have sparse and oracle properties. We use Bayesian Information Criterion (BIC) for tuning parameter selection, and a bootstrap variance approach for standard error. Simulation studies and two real data examples are carried out to investigate the performance of the proposed method.     

Statistical analysis for competing risks model from a Weibull distribution under progressively hybrid censoring

This paper considers the statistical analysis for competing risks model under the Type-I progressively hybrid censoring from a Weibull distribution. We derive the maximum likelihood estimates and the approximate maximum likelihood estimates of the unknown parameters. We then use the bootstrap method to construct the confidence intervals. Based on the non informative prior, a sampling algorithm using the acceptance–rejection sampling method is presented to obtain the Bayes estimates, and Monte Carlo method is employed to construct the highest posterior density credible intervals. The simulation results are provided to show the effectiveness of all the methods discussed here and one data set is analyzed.     

Empirical likelihood confidence regions for comparison distributions and roc curves

Abstract: The authors derive empirical likelihood confidence regions for the comparison distribution of two populations whose distributions are to be tested for equality using random samples. Another application they consider is to ROC curves, which are used to compare measurements of a diagnostic test from two populations. The authors investigate the smoothed empirical likelihood method for estimation in this context, and empirical likelihood based confidence intervals are obtained by means of the Wilks theorem. A bootstrap approach allows for the construction of confidence bands. The method is illustrated with data analysis and a simulation study.     

Lower Confidence Limits on the Generalized Exponential Distribution Percentiles Under Progressive Type-I Interval Censoring

In industrial life test and survival analysis, the percentile estimation is always a practical issue with lower confidence bound required for maintenance purpose. Sampling distributions for the maximum likelihood estimators of percentiles are usually unknown. Bootstrap procedures are common ways to estimate the unknown sampling distributions. Five parametric bootstrap procedures are proposed to estimate the confidence lower bounds on maximum likelihood estimators for the generalized exponential (GE) distribution percentiles under progressive type-I interval censoring. An intensive simulation is conducted to evaluate the performances of proposed procedures. Finally, an example of 112 patients with plasma cell myeloma is given for illustration.