On the estimators and tests for the semiparametric hazards regression model

In the accelerated hazards regression model with censored data, estimation of the covariance matrices of the regression parameters is difficult, since it involves the unknown baseline hazard function and its derivative. This paper provides simple but reliable procedures that yield asymptotically normal estimators whose covariance matrices can be easily estimated. A class of weight functions are introduced to result in the estimators whose asymptotic covariance matrices do not involve the derivative of the unknown hazard function. Based on the estimators obtained from different weight functions, some goodness-of-fit tests are constructed to check the adequacy of the accelerated hazards regression model. Numerical simulations show that the estimators and tests perform well. The procedures are illustrated in the real world example of leukemia cancer. For the leukemia cancer data, the issue of interest is a comparison of two groups of patients that had two different kinds of bone marrow transplants. It is found that the difference of the two groups are well described by a time-scale change in hazard functions, i.e., the accelerated hazards model.     

Quantile regression for competing risks analysis under case-cohort design

The case-cohort design brings cost reduction in large cohort studies. In this paper, we consider a nonlinear quantile regression model for censored competing risks under the case-cohort design. Two different estimation equations are constructed with or without the covariates information of other risks included, respectively. The large sample properties of the estimators are obtained. The asymptotic covariances are estimated by using a fast resampling method, which is useful to consider further inferences. The finite sample performance of the proposed estimators is assessed by simulation studies. Also a real example is used to demonstrate the application of the proposed methods.     

Maximum of the weighted Kaplan–Meier tests for the two-sample censored data

In this paper, some versatile test procedures are considered, which are useful for the case where the association of survival functions is unclear. These procedures are based on a maximum of a class of the weighted Kaplan–Meier statistics. The weight functions used in the procedures account for both the censored and non-censored data points. Numerical simulations with these weight functions show that, under various levels of censoring, the proposed procedures perform well across a wide range of alternative configurations. Implementation of the proposed procedures is illustrated in a real data example.     

The Use of Resampling Methods to Simplify Regression Models in Medical Statistics

The number of variables in a regression model is often too large and a more parsimonious model may be preferred. Selection strategies (e.g. all-subset selection with various penalties for model complexity, or stepwise procedures) are widely used, but there are few analytical results about their properties. The problems of replication stability, model complexity, selection bias and an over-optimistic estimate of the predictive value of a model are discussed together with several proposals based on resampling methods. The methods are applied to data from a case–control study on atopic dermatitis and a clinical trial to compare two chemotherapy regimes by using a logistic regression and a Cox model. A recent proposal to use shrinkage factors to reduce the bias of parameter estimates caused by model building is extended to parameterwise shrinkage factors and is discussed as a further possibility to illustrate problems of models which are too complex. The results from the resampling approaches favour greater simplicity of the final regression model.     

Marginal semiparametric multivariate accelerated failure time model with generalized estimating equations

The semiparametric accelerated failure time (AFT) model is not as widely used as the Cox relative risk model due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations for censored data provide promising tools to make the AFT models more attractive in practice. For multivariate AFT models, we propose a generalized estimating equations (GEE) approach, extending the GEE to censored data. The consistency of the regression coefficient estimator is robust to misspecification of working covariance, and the efficiency is higher when the working covariance structure is closer to the truth. The marginal error distributions and regression coefficients are allowed to be unique for each margin or partially shared across margins as needed. The initial estimator is a rank-based estimator with Gehan’s weight, but obtained from an induced smoothing approach with computational ease. The resulting estimator is consistent and asymptotically normal, with variance estimated through a multiplier resampling method. In a large scale simulation study, our estimator was up to three times as efficient as the estimateor that ignores the within-cluster dependence, especially when the within-cluster dependence was strong. The methods were applied to the bivariate failure times data from a diabetic retinopathy study.     

Fast accelerated failure time modeling for case-cohort data

Semiparametric accelerated failure time (AFT) models directly relate the expected failure times to covariates and are a useful alternative to models that work on the hazard function or the survival function. For case-cohort data, much less development has been done with AFT models. In addition to the missing covariates outside of the sub-cohort in controls, challenges from AFT model inferences with full cohort are retained. The regression parameter estimator is hard to compute because the most widely used rank-based estimating equations are not smooth. Further, its variance depends on the unspecified error distribution, and most methods rely on computationally intensive bootstrap to estimate it. We propose fast rank-based inference procedures for AFT models, applying recent methodological advances to the context of case-cohort data. Parameters are estimated with an induced smoothing approach that smooths the estimating functions and facilitates the numerical solution. Variance estimators are obtained through efficient resampling methods for nonsmooth estimating functions that avoids full blown bootstrap. Simulation studies suggest that the recommended procedure provides fast and valid inferences among several competing procedures. Application to a tumor study demonstrates the utility of the proposed method in routine data analysis.     

M-estimation of the accelerated failure time model under a convex discrepancy function

Based on the Kaplan–Meier weight functions, we introduce a class of M-estimators of regression parameters for the accelerated failure time (AFT) model with right censored data. The proposed M-estimator is root-n consistent and asymptotically normal under appropriate assumptions. For robustness analysis, we also derive the corresponding influence functions. Appropriate criteria are developed for tests of hypotheses concerning regression parameters. The results are applied to several particular cases. We evaluate the finite-sample performance of the proposed methods through extensive simulation studies.     

Checking the censored two-sample accelerated life model using integrated cumulative hazard difference

In this paper, new statistical tests for the censored two-sample accelerated life model are discussed. From the estimating functions using integrated cumulative hazard difference, stochastic processes are constructed. They can be described by martingale residuals, and, given the data, conditional distributions can be approximated by zero mean Gaussian processes. The new methods, based on these processes, provide asymptotically consistent tests against a general departure from the model. A graphical method is also discussed. In various numerical studies, the new tests performed better than the existing method, especially when the hazard curves cross. The proposed procedures are illustrated with two real data sets.     

Weighted transformed hazard anova for censored and truncated data

In this paper ANOVA test procedures based on weighted transformations of the cumulative hazard are discussed. These procedures may be applied in situations where the observations are censored and/or truncated. Besides, the techniques examined are flexible thanks to the choice of different transformations and weight functions. The popular logrank test is used as a yardstick in the performance evaluation.     

Nonparametric bayes estimation of the survival function from a record of failures and follow-ups

In some observational studies, we have random censoring model. However, the data available may be partially observable censored data consisting of the observed failure times and only those nonfailure times which are subject to follow-up. Suzuki (1985) discussed the problem of nonparametric estimation of the survival function from such partially observable censored data. In this article, we derive a nonparametric Bayes estimator of the survival function for such data of failures and follow-ups under a Dirichlet process prior and squared error loss. The limiting properties such as the mean square consistency, weak convergence and strong consistency of the Bayes estimator are studied. Finally, the procedures developed are illustrated by means of an example.     

On Nonsmooth Estimating Functions via Jackknife Empirical Likelihood

In many applications, the parameters of interest are estimated by solving non‐smooth estimating functions with U‐statistic structure. Because the asymptotic covariances matrix of the estimator generally involves the underlying density function, resampling methods are often used to bypass the difficulty of non‐parametric density estimation. Despite its simplicity, the resultant‐covariance matrix estimator depends on the nature of resampling, and the method can be time‐consuming when the number of replications is large. Furthermore, the inferences are based on the normal approximation that may not be accurate for practical sample sizes. In this paper, we propose a jackknife empirical likelihood‐based inferential procedure for non‐smooth estimating functions. Standard chi‐square distributions are used to calculate the p‐value and to construct confidence intervals. Extensive simulation studies and two real examples are provided to illustrate its practical utilities.     

Nonparametric analysis of aggregate loss models

This paper describes a nonparametric approach to make inferences for aggregate loss models in the insurance framework. We assume that an insurance company provides a historical sample of claims given by claim occurrence times and claim sizes. Furthermore, information may be incomplete as claims may be censored and/or truncated. In this context, the main goal of this work consists of fitting a probability model for the total amount that will be paid on all claims during a fixed future time period. In order to solve this prediction problem, we propose a new methodology based on nonparametric estimators for the density functions with censored and truncated data, the use of Monte Carlo simulation methods and bootstrap resampling. The developed methodology is useful to compare alternative pricing strategies in different insurance decision problems. The proposed procedure is illustrated with a real dataset provided by the insurance department of an international commercial company.     

The log-odd log-logistic Weibull regression model: modelling,estimation, influence diagnostics and residual analysis

In applications of survival analysis, the failure rate function may frequently present a unimodal shape. In such cases, the log-normal and log-logistic distributions are used. In this paper, we shall be concerned only with parametric forms, so a location-scale regression model based on the odd log-logistic Weibull distribution is proposed for modelling data with a decreasing, increasing, unimodal and bathtub failure rate function as an alternative to the log-Weibull regression model. For censored data, we consider a classic method to estimate the parameters of the proposed model. We derive the appropriate matrices for assessing local influences on the parameter estimates under different perturbation schemes and present some ways to assess global influences. Further, for different parameter settings, sample sizes and censoring percentages, various simulations are performed. In addition, the empirical distribution of some modified residuals is determined and compared with the standard normal distribution. These studies suggest that the residual analysis usually performed in normal linear regression models can be extended to a modified deviance residual in the new regression model applied to censored data. We analyse a real data set using the log-odd log-logistic Weibull regression model.     

Goodness of fit tests with interval censored data

Cramér–von Mises type goodness of fit tests for interval censored data case 2 are proposed based on a resampling method called the leveraged bootstrap, and their asymptotic consistency is shown. The proposed tests are computationally efficient, and in fact can be applied to other types of censored data, including right censored data, doubly censored data and (mixture of) case k interval censored data. Some simulation results and an example from AIDS research are presented.     

Estimation and goodness-of-fit for the Cox model with various types of censored data

The currently existing estimation methods and goodness-of-fit tests for the Cox model mainly deal with right censored data, but they do not have direct extension to other complicated types of censored data, such as doubly censored data, interval censored data, partly interval-censored data, bivariate right censored data, etc. In this article, we apply the empirical likelihood approach to the Cox model with complete sample, derive the semiparametric maximum likelihood estimators (SPMLE) for the Cox regression parameter and the baseline distribution function, and establish the asymptotic consistency of the SPMLE. Via the functional plug-in method, these results are extended in a unified approach to doubly censored data, partly interval-censored data, and bivariate data under univariate or bivariate right censoring. For these types of censored data mentioned, the estimation procedures developed here naturally lead to Kolmogorov-Smirnov goodness-of-fit tests for the Cox model. Some simulation results are presented.     

Confidence Intervals on Regression Models with Censored Data

Stute (1993, Consistent estimation under random censorship when covariables are present. Journal of Multivariate Analysis 45, 89–103) proposed a new method to estimate regression models with a censored response variable using least squares and showed the consistency and asymptotic normality for his estimator. This article proposes a new bootstrap-based methodology that improves the performance of the asymptotic interval estimation for the small sample size case. Therefore, we compare the behavior of Stute's asymptotic confidence interval with that of several confidence intervals that are based on resampling bootstrap techniques. In order to build these confidence intervals, we propose a new bootstrap resampling method that has been adapted for the case of censored regression models. We use simulations to study the improvement the performance of the proposed bootstrap-based confidence intervals show when compared to the asymptotic proposal. Simulation results indicate that, for the new proposals, coverage percentages are closer to the nominal values and, in addition, intervals are narrower.     

Weighted Mean Survival Test Statistics: a Class of Distance Tests for Censored Survival Data

A class of test statistics is introduced which is sensitive against the alternative of stochastic ordering in the two-sample censored data problem. The test statistics for evaluating a cumulative weighted difference in survival distributions are developed while taking into account the imbalances in base-line covariates between two groups. This procedure can be used to test the null hypothesis of no treatment effect, especially when base-line hazards cross and prognostic covariates need to be adjusted. The statistics are semiparametric, not rank based, and can be written as integrated weighted differences in estimated survival functions, where these survival estimates are adjusted for covariate imbalances. The asymptotic distribution theory of the tests is developed, yielding test procedures that are shown to be consistent under a fixed alternative. The choice of weight function is discussed and relies on stability and interpretability considerations. An example taken from a clinical trial for acquired immune deficiency syndrome is presented.     

The generalized log-gamma mixture model with covariates: local influence and residual analysis

In a sample of censored survival times, the presence of an immune proportion of individuals who are not subject to death, failure or relapse, may be indicated by a relatively high number of individuals with large censored survival times. In this paper the generalized log-gamma model is modified for the possibility that long-term survivors may be present in the data. The model attempts to separately estimate the effects of covariates on the surviving fraction, that is, the proportion of the population for which the event never occurs. The logistic function is used for the regression model of the surviving fraction. Inference for the model parameters is considered via maximum likelihood. Some influence methods, such as the local influence and total local influence of an individual are derived, analyzed and discussed. Finally, a data set from the medical area is analyzed under the log-gamma generalized mixture model. A residual analysis is performed in order to select an appropriate model. The authors would like to thank the editor and referees for their helpful comments. This work was supported by CNPq, Brazil.     

Estimation for the three-parameter inverse Gaussian distribution under progressive Type-II censoring

Inverse Gaussian distribution has been used widely as a model in analysing lifetime data. In this regard, estimation of parameters of two-parameter (IG2) and three-parameter inverse Gaussian (IG3) distributions based on complete and censored samples has been discussed in the literature. In this paper, we develop estimation methods based on progressively Type-II censored samples from IG3 distribution. In particular, we use the EM-algorithm, as well as some other numerical methods for determining the maximum-likelihood estimates (MLEs) of the parameters. The asymptotic variances and covariances of the MLEs from the EM-algorithm are derived by using the missing information principle. We also consider some simplified alternative estimators. The inferential methods developed are then illustrated with some numerical examples. We also discuss the interval estimation of the parameters based on the large-sample theory and examine the true coverage probabilities of these confidence intervals in case of small samples by means of Monte Carlo simulations.     

Estimation in Maxwell distribution with randomly censored data

In many practical situations, complete data are not available in lifetime studies. Many of the available observations are right censored giving survival information up to a noted time and not the exact failure times. This constitutes randomly censored data. In this paper, we consider Maxwell distribution as a survival time model. The censoring time is also assumed to follow a Maxwell distribution with a different parameter. Maximum likelihood estimators and confidence intervals for the parameters are derived with randomly censored data. Bayes estimators are also developed with inverted gamma priors and generalized entropy loss function. A Monte Carlo simulation study is performed to compare the developed estimation procedures. A real data example is given at the end of the study.