Additive hazards model with truncated and doubly censored data

In longitudinal studies, the additive hazard model is often used to analyze covariate effects on the duration time, defined as the elapsed time between the first and the second event. In this article, we consider the situation when the first event suffers partly interval censoring and the second event suffers left truncation and right-censoring. We proposed a two-step estimation procedure for estimating the regression coefficients of the additive hazards model. A simulation study is conducted to investigate the performance of the proposed estimator. The proposed method is applied to the Centers for Disease Control acquired immune deficiency syndrome blood transfusion data.     

A proportional hazards model for the analysis of doubly censored competing risks data

ABSTRACT

Competing risks data are common in medical research in which lifetime of individuals can be classified in terms of causes of failure. In survival or reliability studies, it is common that the patients (objects) are subjected to both left censoring and right censoring, which is refereed as double censoring. The analysis of doubly censored competing risks data in presence of covariates is the objective of this study. We propose a proportional hazards model for the analysis of doubly censored competing risks data, using the hazard rate functions of Gray (1988 Gray, R.J. (1988). A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann. Statist. 16:1141–1154.[Crossref], [Web of Science ®] , [Google Scholar]), while focusing upon one major cause of failure. We derive estimators for regression parameter vector and cumulative baseline cause specific hazard rate function. Asymptotic properties of the estimators are discussed. A simulation study is conducted to assess the finite sample behavior of the proposed estimators. We illustrate the method using a real life doubly censored competing risks data.     

A note on variance estimation in the Cox proportional hazards model

The Cox proportional hazards model is widely used in clinical trials with time-to-event outcomes to compare an experimental treatment with the standard of care. At the design stage of a trial the number of events required to achieve a desired power needs to be determined, which is frequently based on estimating the variance of the maximum partial likelihood estimate of the regression parameter with a function of the number of events. Underestimating the variance at the design stage will lead to insufficiently powered studies, and overestimating the variance will lead to unnecessarily large trials. A simple approach to estimating the variance is introduced, which is compared with two widely adopted approaches in practice. Simulation results show that the proposed approach outperforms the standard ones and gives nearly unbiased estimates of the variance.     

Assessing the prediction accuracy of cure in the Cox proportional hazards cure model: an application to breast cancer data

A cure rate model is a survival model incorporating the cure rate with the assumption that the population contains both uncured and cured individuals. It is a powerful statistical tool for prognostic studies, especially in cancer. The cure rate is important for making treatment decisions in clinical practice. The proportional hazards (PH) cure model can predict the cure rate for each patient. This contains a logistic regression component for the cure rate and a Cox regression component to estimate the hazard for uncured patients. A measure for quantifying the predictive accuracy of the cure rate estimated by the Cox PH cure model is required, as there has been a lack of previous research in this area. We used the Cox PH cure model for the breast cancer data; however, the area under the receiver operating characteristic curve (AUC) could not be estimated because many patients were censored. In this study, we used imputation‐based AUCs to assess the predictive accuracy of the cure rate from the PH cure model. We examined the precision of these AUCs using simulation studies. The results demonstrated that the imputation‐based AUCs were estimable and their biases were negligibly small in many cases, although ordinary AUC could not be estimated. Additionally, we introduced the bias‐correction method of imputation‐based AUCs and found that the bias‐corrected estimate successfully compensated the overestimation in the simulation studies. We also illustrated the estimation of the imputation‐based AUCs using breast cancer data. Copyright © 2014 John Wiley & Sons, Ltd.     

Survival analysis based on the proportional hazards model and survey data

The authors propose methods based on the stratified Cox proportional hazards model that account for the fact that the data have been collected according to a complex survey design. The methods they propose are based on the theory of estimating equations in conjunction with empirical process theory. The authors also discuss issues concerning ignorable sampling design, and the use of weighted and unweighted procedures. They illustrate their methodology by an analysis of jobless spells in Statistics Canada's Survey of Labour and Income Dynamics. They discuss briefly problems concerning weighting, model checking, and missing or mismeasured data. They also identify areas for further research.     

Statistical power to detect violation of the proportional hazards assumption when using the Cox regression model

The use of the Cox proportional hazards regression model is wide-spread. A key assumption of the model is that of proportional hazards. Analysts frequently test the validity of this assumption using statistical significance testing. However, the statistical power of such assessments is frequently unknown. We used Monte Carlo simulations to estimate the statistical power of two different methods for detecting violations of this assumption. When the covariate was binary, we found that a model-based method had greater power than a method based on cumulative sums of martingale residuals. Furthermore, the parametric nature of the distribution of event times had an impact on power when the covariate was binary. Statistical power to detect a strong violation of the proportional hazards assumption was low to moderate even when the number of observed events was high. In many data sets, power to detect a violation of this assumption is likely to be low to modest.     

Testing order restricted hypotheses with proportional hazards

Inferences for survival curves based on right censored continuous or grouped data are studied. Testing homogeneity with an ordered restricted alternative and testing the order restriction as the null hypothesis are considered. Under a proportional hazards model, the ordering on the survival curves corresponds to an ordering on the regression coefficients. Approximate likelihood methods are obtained by applying order restricted procedures to the estimates of the regression coefficients. Ordered analogues to the log rank test which are based on the score statistics are considered also. Chi-bar-squared distributions, which have been studied extensively, are shown to provide reasonable approximations to the null distributions of these tests statistics. Using Monte Carlo techniques, the powers of these two types of tests are compared with those that are available in the literature.     

Estimation in multiple linear regression model with doubly censored data

In this article, we propose three M-estimators for multiple regression model when response variable is subject to double censoring. The consistency of the proposed M-estimators is established. A simulation study is conducted to investigate the performance of the proposed estimators. Furthermore, the simple bootstrap methods are used to construct interval estimators.     

Choosing between Cox proportional hazards and logistic models for interval- censored data via bootstrap

This work develops a new methodology in order to discriminate models for interval- censored data based on bootstrap residual simulation by observing the deviance difference from one model in relation to another, according to Hinde (1992). Generally, this sort of data can generate a large number of tied observations and, in this case, survival time can be regarded as discrete. Therefore, the Cox proportional hazards model for grouped data (Prentice & Gloeckler, 1978) and the logistic model (Lawless, 1982) can be fitted by means of generalized linear models. Whitehead (1989) considered censoring to be an indicative variable with a binomial distribution and fitted the Cox proportional hazards model using complementary log-log as a link function. In addition, a logistic model can be fitted using logit as a link function. The proposed methodology arises as an alternative to the score tests developed by Colosimo et al. (2000), where such models can be obtained for discrete binary data as particular cases from the Aranda-Ordaz distribution asymmetric family. These tests are thus developed with a basis on link functions to generate such a fit. The example that motivates this study was the dataset from an experiment carried out on a flax cultivar planted on four substrata susceptible to the pathogen Fusarium oxysoprum . The response variable, which is the time until blighting, was observed in intervals during 52 days. The results were compared with the model fit and the AIC values.     

Estimation under Cox proportional hazards model with covariates missing not at random

This paper considers likelihood-based estimation under the Cox proportional hazards model in the situations where some covariate entries are missing not at random. Assuming the conditional distribution of the missing entries is known, we demonstrate the existence of the semiparametric maximum likelihood estimator of the model parameters, establish the consistency and weak convergence. By simulation, we examine the finite-sample performance of the estimation procedure, and compare the SPMLE with the one resulted from using an estimated conditional distribution of the missing entries. We analyze the data from a tuberculosis (TB) study applying the proposed approach for illustration.     

Quantile estimation in the proportional hazards model of random censorship

The asymptotic theory is given for quantile estimation in the proportional hazards model of random censorship. In this model, the tail of the censoring distribution function is some power of the tail of the survival distribution function. The quantile estimator is based on the maximum likelihood estimator for the survival time distribution, due to Abdushukurov, Cheng and Lin.     

The random-effects proportional hazards model with grouped survival data: a comparison between the grouped continuous and continuation ratio versions

Summary.  When analysing grouped time survival data having a hierarchical structure it is often appropriate to assume a random-effects proportional hazards model for the latent continuous time and then to derive the corresponding grouped time model. There are two formally equivalent grouped time versions of the proportional hazards model obtained from different perspec-tives, known as the continuation ratio and the grouped continuous models. However, the two models require distinct estimation procedures and, more importantly, they differ substantially when extended to time-dependent covariates and/or non-proportional effects. The paper discusses these issues in the context of random-effects models, illustrating the main points with an application to a complex data set on job opportunities for a cohort of graduates.     

Estimation of the bivariate cause-specific distribution function with doubly censored competing risks data

In this article, we consider estimating the bivariate cause-specific distribution function when both components are subject to double censoring. We propose two types of estimators as generalizations of the Dabrowska and Campbell and Földes estimators. The asymptotical properties of the proposed estimators are established. A simulation study is conducted to investigate the performance of the proposed estimators.     

Comparison of goodness of fit tests for the cox proportional hazards model

The proportional hazards regression model of Cox(1972) is widely used in analyzing survival data. We examine several goodness of fit tests for checking the proportionality of hazards in the Cox model with two-sample censored data, and compare the performance of these tests by a simulation study. The strengths and weaknesses of the tests are pointed out. The effects of the extent of random censoring on the size and power are also examined. Results of a simulation study demonstrate that Gill and Schumacher's test is most powerful against a broad range of monotone departures from the proportional hazards assumption, but it may not perform as well fail for alternatives of nonmonotone hazard ratio. For the latter kind of alternatives, Andersen's test may detect patterns of irregular changes in hazards.     

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.     

Maximum likelihood methods for complex sample data: logistic regression and discrete proportional hazards models

To estimate model parameters from complex sample data. we apply maximum likelihood techniques to the complex sample data from the finite population, which is treated as a sample from an i nfinite superpopulation. General asymptotic distribution theory is developed and then applied to both logistic regression and discrete proportional hazards models. Data from the Lipid Research Clinics Program areused to illustrate each model, demonstrating the effects on inference of neglecting the sampling design during parameter estimation. These empirical results also shed light on the issue of model-based vs. design-based inferences.     

Generating data from improper distributions: application to Cox proportional hazards models with cure

Cure rate models are survival models characterized by improper survivor distributions which occur when the cumulative distribution function, say F, of the survival times does not sum up to 1 (i.e. F(+∞)<1). The first objective of this paper is to provide a general approach to generate data from any improper distribution. An application to times to event data randomly drawn from improper distributions with proportional hazards is investigated using the semi-parametric proportional hazards model with cure obtained as a special case of the nonlinear transformation models in [Tsodikov, Semiparametric models: A generalized self-consistency approach, J. R. Stat. Soc. Ser. B 65 (2003), pp. 759–774]. The second objective of this paper is to show by simulations that the bias, the standard error and the mean square error of the maximum partial likelihood (PL) estimator of the hazard ratio as well as the statistical power based on the PL estimator strongly depend on the proportion of subjects in the whole population who will never experience the event of interest.     

Maximum likelihood estimation for the proportional hazards model with partly interval-censored data

Summary. The maximum likelihood estimator (MLE) for the proportional hazards model with partly interval-censored data is studied. Under appropriate regularity conditions, the MLEs of the regression parameter and the cumulative hazard function are shown to be consistent and asymptotically normal. Two methods to estimate the variance–covariance matrix of the MLE of the regression parameter are considered, based on a generalized missing information principle and on a generalized profile information procedure. Simulation studies show that both methods work well in terms of the bias and variance for samples of moderate size. An example illustrates the methods.     

Sample size calculation for a proportional hazards mixture cure model with nonbinary covariates

Sample size calculation is a critical issue in clinical trials because a small sample size leads to a biased inference and a large sample size increases the cost. With the development of advanced medical technology, some patients can be cured of certain chronic diseases, and the proportional hazards mixture cure model has been developed to handle survival data with potential cure information. Given the needs of survival trials with potential cure proportions, a corresponding sample size formula based on the log-rank test statistic for binary covariates has been proposed by Wang et al. [25]. However, a sample size formula based on continuous variables has not been developed. Herein, we presented sample size and power calculations for the mixture cure model with continuous variables based on the log-rank method and further modified it by Ewell's method. The proposed approaches were evaluated using simulation studies for synthetic data from exponential and Weibull distributions. A program for calculating necessary sample size for continuous covariates in a mixture cure model was implemented in R.     

Proportional hazards regression with interval-censored and left-truncated data

This paper considers the estimation of the regression coefficients in the Cox proportional hazards model with left-truncated and interval-censored data. Using the approaches of Pan [A multiple imputation approach to Cox regression with interval-censored data, Biometrics 56 (2000), pp. 199–203] and Heller [Proportional hazards regression with interval censored data using an inverse probability weight, Lifetime Data Anal. 17 (2011), pp. 373–385], we propose two estimates of the regression coefficients. The first estimate is based on a multiple imputation methodology. The second estimate uses an inverse probability weight to select event time pairs where the ordering is unambiguous. A simulation study is conducted to investigate the performance of the proposed estimators. The proposed methods are illustrated using the Centers for Disease Control and Prevention (CDC) acquired immunodeficiency syndrome (AIDS) Blood Transfusion Data.