Generalized Additive Models for Current Status Data

Current status data arise in studies where the target measurement is the time of occurrence of some event, but observations are limited to indicators of whether or not the event has occurred at the time the sample is collected - only the current status of each individual with respect to event occurrence is observed. Examples of such data arise in several fields, including demography, epidemiology, econometrics and bioassay. Although estimation of the marginal distribution of times of event occurrence is well understood, techniques for incorporating covariate information are not well developed. This paper proposes a semiparametric approach to estimation for regression models of current status data, using techniques from generalized additive modeling and isotonic regression. This procedure provides simultaneous estimates of the baseline distribution of event times and covariate effects. No parametric assumptions about the form of the baseline distribution are required. The results are illustrated using data from a demographic survey of breastfeeding practices in developing countries, and from an epidemiological study of heterosexual Human Immunodeficiency Virus (HIV) transmission. This revised version was published online in July 2006 with corrections to the Cover Date.     

Nonparametric Test for Doubly Interval-Censored Failure Time Data

This paper considers comparison of discrete failure time distributions when the survival time of interest measures elapsed time between two related events and observations on the occurrences of both events could be interval-censored. This kind of data is often referred to as doubly interval-censored failure time data. If the occurrence of the first event defining the survival time can be exactly observed, the data are usually referred to as interval-censored data. For the comparison problem based on interval-censored failure time data, Sun (1996) proposed a nonparametric test procedure. In this paper we generalize the procedure given in Sun (1996) to doubly interval-censored data case and the generalized test is evaluated by simulations.     

Regression Parameter Estimation from Panel Counts

This paper considers a study where each subject may experience multiple occurrences of an event and the rate of the event occurrences is of primary interest. Specifically, we are concerned with the situations where, for each subject, there are only records of the accumulated counts for the event occurrences at a finite number of time points over the study period. Sets of observation times may vary from subject to subject and differ between groups. We model the mean of the event occurrence number over time semiparametrically, and estimate the regression parameter. The proposed estimation procedures are illustrated with data from a bladder cancer study ( Byar, 1980 ). Both asymptotics and simulation studies on the estimators are presented.     

Joint modeling of multivariate longitudinal mixed measurements and time to event data using a Bayesian approach

In many longitudinal studies multiple characteristics of each individual, along with time to occurrence of an event of interest, are often collected. In such data set, some of the correlated characteristics may be discrete and some of them may be continuous. In this paper, a joint model for analysing multivariate longitudinal data comprising mixed continuous and ordinal responses and a time to event variable is proposed. We model the association structure between longitudinal mixed data and time to event data using a multivariate zero-mean Gaussian process. For modeling discrete ordinal data we assume a continuous latent variable follows the logistic distribution and for continuous data a Gaussian mixed effects model is used. For the event time variable, an accelerated failure time model is considered under different distributional assumptions. For parameter estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. The performance of the proposed methods is illustrated using some simulation studies. A real data set is also analyzed, where different model structures are used. Model comparison is performed using a variety of statistical criteria.     

Statistical Analysis of Linear Degradation and Failure Time Data with Multiple Failure Modes

The paper considers linear degradation and failure time models with multiple failure modes. Dependence of traumatic failure intensities on the degradation level are included into the models. Estimators of traumatic event cumulative intensities, and of various reliability characteristics are proposed. Prediction of residual reliability characteristics given a degradation value at a given moment is discussed. Non-parametric, semiparametric and parametric estimation methods are given. Theorems on simultaneous asymptotic distribution of random functions characterising degradation and intensities of traumatic events are proposed. Asymptotic properties of unconditional and residual reliability characteristics estimators are given. Real tire wear and failure time data are analysed.     

Identification of longitudinal biomarkers for survival by a score test derived from a joint model of longitudinal and competing risks data

In this paper, we consider joint modelling of repeated measurements and competing risks failure time data. For competing risks time data, a semiparametric mixture model in which proportional hazards model are specified for failure time models conditional on cause and a multinomial model for the marginal distribution of cause conditional on covariates. We also derive a score test based on joint modelling of repeated measurements and competing risks failure time data to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data.     

Methods for the estimation of failure distributions and rates from automobile warranty data

We consider the occurrence of warranty claims for automobiles when both age and mileage accumulation may affect failure. The presence of both age and mileage limits on warranties creates interesting problems for the analysis of failures. We propose a family of models that relates failure to time and mileage accumulation. Methods for fitting the models based on warranty data and supplementary information about mileage accumulation are presented and illustrated on some real data. The general problem of modelling failures in equipment when both time and usage are factors is discussed.     

Modelling and analysis of recall-based competing risks data

In this paper we consider the analysis of recall-based competing risks data. The chance of an individual recalling the exact time to event depends on the time of occurrence of the event and time of observation of the individual. In particular, it is assumed that the probability of recall depends on the time elapsed since the occurrence of an event. In this study we consider the likelihood-based inference for the analysis of recall-based competing risks data. The likelihood function is constructed by incorporating the information about the probability of recall. We consider the maximum likelihood estimation of parameters. Simulation studies are carried out to examine the performance of the estimators. The proposed estimation procedure is applied to a real life data set.     

On the Bayesian estimation and influence diagnostics for the Weibull-Negative-Binomial regression model with cure rate under latent failure causes

The purpose of this paper is to develop a Bayesian approach for the Weibull-Negative-Binomial regression model with cure rate under latent failure causes and presence of randomized activation mechanisms. We assume the number of competing causes of the event of interest follows a Negative Binomial (NB) distribution while the latent lifetimes are assumed to follow a Weibull distribution. Markov chain Monte Carlos (MCMC) methods are used to develop the Bayesian procedure. Model selection to compare the fitted models is discussed. Moreover, we develop case deletion influence diagnostics for the joint posterior distribution based on the ψ-divergence, which has several divergence measures as particular cases. The developed procedures are illustrated with a real data set.     

The Poisson Generalized Linear Failure Rate Model

We formulate a new cure rate survival model by assuming that the number of competing causes of the event of interest has the Poisson distribution, and the time to this event has the generalized linear failure rate distribution. A new distribution to analyze lifetime data is defined from the proposed cure rate model, and its quantile function as well as a general expansion for the moments is derived. We estimate the parameters of the model with cure rate in the presence of covariates for censored observations using maximum likelihood and derive the observed information matrix. We obtain the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes and present some ways to perform global influence analysis. The usefulness of the proposed cure rate survival model is illustrated in an application to real data.     

Estimation in the Cox cure model with covariates missing not at random,with application to disease screening/prediction

In an attempt to provide a statistical tool for disease screening and prediction, we propose a semiparametric approach to analysis of the Cox proportional hazards cure model in situations where the observations on the event time are subject to right censoring and some covariates are missing not at random. To facilitate the methodological development, we begin with semiparametric maximum likelihood estimation (SPMLE) assuming that the (conditional) distribution of the missing covariates is known. A variant of the EM algorithm is used to compute the estimator. We then adapt the SPMLE to a more practical situation where the distribution is unknown and there is a consistent estimator based on available information. We establish the consistency and weak convergence of the resulting pseudo-SPMLE, and identify a suitable variance estimator. The application of our inference procedure to disease screening and prediction is illustrated via empirical studies. The proposed approach is used to analyze the tuberculosis screening study data that motivated this research. Its finite-sample performance is examined by simulation.     

Exponentiated Weibull regression for time-to-event data

The Weibull, log-logistic and log-normal distributions are extensively used to model time-to-event data. The Weibull family accommodates only monotone hazard rates, whereas the log-logistic and log-normal are widely used to model unimodal hazard functions. The increasing availability of lifetime data with a wide range of characteristics motivate us to develop more flexible models that accommodate both monotone and nonmonotone hazard functions. One such model is the exponentiated Weibull distribution which not only accommodates monotone hazard functions but also allows for unimodal and bathtub shape hazard rates. This distribution has demonstrated considerable potential in univariate analysis of time-to-event data. However, the primary focus of many studies is rather on understanding the relationship between the time to the occurrence of an event and one or more covariates. This leads to a consideration of regression models that can be formulated in different ways in survival analysis. One such strategy involves formulating models for the accelerated failure time family of distributions. The most commonly used distributions serving this purpose are the Weibull, log-logistic and log-normal distributions. In this study, we show that the exponentiated Weibull distribution is closed under the accelerated failure time family. We then formulate a regression model based on the exponentiated Weibull distribution, and develop large sample theory for statistical inference. We also describe a Bayesian approach for inference. Two comparative studies based on real and simulated data sets reveal that the exponentiated Weibull regression can be valuable in adequately describing different types of time-to-event data.     

A new three-parameter ageing distribution

We propose a new three-parameter ageing distribution called the Weibull-Poisson (WP) distribution, which generalizes the exponential-Poisson (EP) distribution introduced by Kus (2007). This new distribution has a more general form of failure rate (hazard rate) function. With appropriate choice of parameter values, it is able to model three ageing classes of life distributions including decreasing failure rate (DFR), increasing failure rate (IFR), and modified upside-down-bathtub (MUBT)-shaped failure rate. It thus provides an alternative to many existing life distributions. Various properties of this distribution are discussed and the estimation of the parameters is considered by the expectation maximization (EM) algorithm. Also, the asymptotic variance-covariance matrices of these estimates are obtained. Furthermore, some expressions for the Rènyi and Shannon entropies are given. Simulation studies are performed and experimental results are illustrated based on a real data set.     

Variance estimation of the risk difference when using propensity-score matching and weighting with time-to-event outcomes

Observational studies are increasingly being used in medicine to estimate the effects of treatments or exposures on outcomes. To minimize the potential for confounding when estimating treatment effects, propensity score methods are frequently implemented. Often outcomes are the time to event. While it is common to report the treatment effect as a relative effect, such as the hazard ratio, reporting the effect using an absolute measure of effect is also important. One commonly used absolute measure of effect is the risk difference or difference in probability of the occurrence of an event within a specified duration of follow-up between a treatment and comparison group. We first describe methods for point and variance estimation of the risk difference when using weighting or matching based on the propensity score when outcomes are time-to-event. Next, we conducted Monte Carlo simulations to compare the relative performance of these methods with respect to bias of the point estimate, accuracy of variance estimates, and coverage of estimated confidence intervals. The results of the simulation generally support the use of weighting methods (untrimmed ATT weights and IPTW) or caliper matching when the prevalence of treatment is low for point estimation. For standard error estimation the simulation results support the use of weighted robust standard errors, bootstrap methods, or matching with a naïve standard error (i.e., Greenwood method). The methods considered in the article are illustrated using a real-world example in which we estimate the effect of discharge prescribing of statins on patients hospitalized for acute myocardial infarction.     

A pool-adjacent-violators type algorithm for non-parametric estimation of current status data with dependent censoring

A likelihood based approach to obtaining non-parametric estimates of the failure time distribution is developed for the copula based model of Wang et al. (Lifetime Data Anal 18:434–445, 2012) for current status data under dependent observation. Maximization of the likelihood involves a generalized pool-adjacent violators algorithm. The estimator coincides with the standard non-parametric maximum likelihood estimate under an independence model. Confidence intervals for the estimator are constructed based on a smoothed bootstrap. It is also shown that the non-parametric failure distribution is only identifiable if the copula linking the observation and failure time distributions is fully-specified. The method is illustrated on a previously analyzed tumorigenicity dataset.     

The analysis of incomplete data using stochastic covariates

In the development of many diseases there are often associated random variables which continuously reflect the progress of a subject towards the final expression of the disease (failure). At any given time these processes, which we call stochastic covariates, may provide information about the current hazard and the remaining time to failure. Likewise, in situations when the specific times of key prior events are not known, such as the time of onset of an occult tumour or the time of infection with HIV-1, it may be possible to identify a stochastic covariate which reveals, indirectly, when the event of interest occurred. The analysis of carcinogenicity trials which involve occult tumours is usually based on the time of death or sacrifice and an indicator of tumour presence for each animal in the experiment. However, the size of an occult tumour observed at the endpoint represents data concerning tumour development which may convey additional information concerning both the tumour incidence rate and the rate of death to which tumour-bearing animals are subject. We develop a stochastic model for tumour growth and suggest different ways in which the effect of this growth on the hazard of failure might be modelled. Using a combined model for tumour growth and additive competing risks of death, we show that if this tumour size information is used, assumptions concerning tumour lethality, the context of observation or multiple sacrifice times are no longer necessary in order to estimate the tumour incidence rate. Parametric estimation based on the method of maximum likelihood is outlined and is applied to simulated data from the combined model. The results of this limited study confirm that use of the stochastic covariate tumour size results in more precise estimation of the incidence rate for occult tumours.     

A parametric model fitting time to first event for overdispersed data: application to time to relapse in multiple sclerosis

In this article, we propose a parametric model for the distribution of time to first event when events are overdispersed and can be properly fitted by a Negative Binomial distribution. This is a very common situation in medical statistics, when the occurrence of events is summarized as a count for each patient and the simple Poisson model is not adequate to account for overdispersion of data. In this situation, studying the time of occurrence of the first event can be of interest. From the Negative Binomial distribution of counts, we derive a new parametric model for time to first event and apply it to fit the distribution of time to first relapse in multiple sclerosis (MS). We develop the regression model with methods for covariate estimation. We show that, as the Negative Binomial model properly fits relapse counts data, this new model matches quite perfectly the distribution of time to first relapse, as tested in two large datasets of MS patients. Finally we compare its performance, when fitting time to first relapse in MS, with other models widely used in survival analysis (the semiparametric Cox model and the parametric exponential, Weibull, log-logistic and log-normal models).     

An estimator for the scale parameter of the two parameter weibull distribution for type i singly right-censored data

For type I censoring, in addition to the failure times, the number failures is also observed as part of the data. Using this feature of type I singly right-censored data a simple estimator is obtained for the scale parameter of the two parameter Weibull distribution. The exact mean and variance of the estimator are derived and computed for finite sample sizes. Its limiting properties such as asymptotic normality and asymptotic relative efficiency are obtained. The estimator has high efficiency for moderate and heavy censoring. Its use is illustrated by means of an example.     

Empirical likelihood method for the multivariate accelerated failure time models

In applications, multivariate failure time data appears when each study subject may potentially experience several types of failures or recurrences of a certain phenomenon, or failure times may be clustered. Three types of marginal accelerated failure time models dealing with multiple events data, recurrent events data and clustered events data are considered. We propose a unified empirical likelihood inferential procedure for the three types of models based on rank estimation method. The resulting log-empirical likelihood ratios are shown to possess chi-squared limiting distributions. The properties can be applied to do tests and construct confidence regions without the need to solve the rank estimating equations nor to estimate the limiting variance-covariance matrices. The related computation is easy to implement. The proposed method is illustrated by extensive simulation studies and a real example.     

Covariate selection for accelerated failure time data

Selection of appropriate predictors for right censored time to event data is very often encountered by the practitioners. We consider the ?₁ penalized regression or “least absolute shrinkage and selection operator” as a tool for predictor selection in association with accelerated failure time model. The choice of the penalizing parameter λ is crucial to identify the correct set of covariates. In this paper, we propose an information theory-based method to choose λ under log-normal distribution. Furthermore, an efficient algorithm is discussed in the same context. The performance of the proposed λ and the algorithm is illustrated through simulation studies and a real data analysis. The convergence of the algorithm is also discussed.