Destructive weighted Poisson cure rate models

In this paper, we develop a flexible cure rate survival model by assuming the number of competing causes of the event of interest to follow a compound weighted Poisson distribution. This model is more flexible in terms of dispersion than the promotion time cure model. Moreover, it gives an interesting and realistic interpretation of the biological mechanism of the occurrence of event of interest as it includes a destructive process of the initial risk factors in a competitive scenario. In other words, what is recorded is only from the undamaged portion of the original number of risk factors.     

A new destructive Poisson odd log-logistic generalized half-normal cure rate model

We propose a new cure rate survival model by assuming that the initial number of competing causes of the event of interest follows a Poisson distribution and the time to event has the odd log-logistic generalized half-normal distribution. This survival model describes a realistic interpretation for the biological mechanism of the event of interest. We estimate the model parameters using maximum likelihood. For different sample sizes, various simulation scenarios are performed. We propose the diagnostics and residual analysis to verify the model assumptions. The potentiality of the new cure rate model is illustrated by means of a real data.     

Statistical methods for dependent competing risks

Many biological and medical studies have as a response of interest the time to occurrence of some event,X, such as the occurrence of cessation of smoking, conception, a particular symptom or disease, remission, relapse, death due to some specific disease, or simply death. Often it is impossible to measureX due to the occurrence of some other competing event, usually termed a competing risk. This competing event may be the withdrawal of the subject from the study (for whatever reason), death from some cause other than the one of interest, or any eventuality that precludes the main event of interest from occurring. Usually the assumption is made that all such censoring times and lifetimes are independent. In this case one uses either the Kaplan-Meier estimator or the Nelson-Aalen estimator to estimate the survival function. However, if the competing risk or censoring times are not independent ofX, then there is no generally acceptable way to estimate the survival function. There has been considerable work devoted to this problem of dependent competing risks scattered throughout the statistical literature in the past several years and this paper presents a survey of such work.     

Power and sample size considerations in clinical trials with competing risk endpoints

In clinical trials with a time-to-event endpoint, subjects are often at risk for events other than the one of interest. When the occurrence of one type of event precludes observation of any later events or alters the probably of subsequent events, the situation is one of competing risks. During the planning stage of a clinical trial with competing risks, it is important to take all possible events into account. This paper gives expressions for the power and sample size for competing risks based on a flexible parametric Weibull model. Nonuniform accrual to the study is considered and an allocation ratio other than one may be used. Results are also provided for the case where two or more of the competing risks are of primary interest.     

A New lifetime model for multivariate survival data with a surviving fraction

In this paper we propose a new lifetime model for multivariate survival data with a surviving fraction. We develop this model assuming that there are m types of unobservable competing risks, where each risk is related to a time of the occurrence of an event of interest. We explore the use of Markov chain Monte Carlo methods to develop a Bayesian analysis for the proposed model. We also perform a simulation study in order to analyse the frequentist coverage probabilities of credible interval derived from posteriors. Our modelling is illustrated through a real data set.     

Planning and analyzing clinical trials with competing risks: Recommendations for choosing appropriate statistical methodology

In the analysis of time‐to‐event data, competing risks occur when multiple event types are possible, and the occurrence of a competing event precludes the occurrence of the event of interest. In this situation, statistical methods that ignore competing risks can result in biased inference regarding the event of interest. We review the mechanisms that lead to bias and describe several statistical methods that have been proposed to avoid bias by formally accounting for competing risks in the analyses of the event of interest. Through simulation, we illustrate that Gray's test should be used in lieu of the logrank test for nonparametric hypothesis testing. We also compare the two most popular models for semiparametric modelling: the cause‐specific hazards (CSH) model and Fine‐Gray (F‐G) model. We explain how to interpret estimates obtained from each model and identify conditions under which the estimates of the hazard ratio and subhazard ratio differ numerically. Finally, we evaluate several model diagnostic methods with respect to their sensitivity to detect lack of fit when the CSH model holds, but the F‐G model is misspecified and vice versa. Our results illustrate that adequacy of model fit can strongly impact the validity of statistical inference. We recommend analysts incorporate a model diagnostic procedure and contingency to explore other appropriate models when designing trials in which competing risks are anticipated.     

The Power Series Cure Rate Model: An Application to a Cutaneous Melanoma Data

In this article we propose a new cure rate survival model. In our approach the number of competing causes of the event of interest is assumed to follow an exponential discrete power series distribution. An advantage of our model is that it is very flexible, including several particular cases, such as, Bernoulli, geometric, Poisson, etc. Moreover, we derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes and present some ways to perform global influence analysis. Distribution fitting can be tested for the best fitting in a straightforward way. Maximum likelihood estimation is discussed. Our proposed model is illustrated through cutaneous melanoma data.     

An EM type estimation procedure for the destructive exponentially weighted Poisson regression cure model under generalized gamma lifetime

In this paper, we assume the number of competing causes to follow an exponentially weighted Poisson distribution. By assuming the initial number of competing causes can undergo destruction and that the population of interest has a cure fraction, we develop the EM algorithm for the determination of the MLEs of the model parameters of such a general cure model. This model is more flexible than the promotion time cure model and also provides an interesting and realistic interpretation of the biological mechanism of the occurrence of an event of interest. Instead of assuming a particular parametric distribution for the lifetime, we assume the lifetime to belong to the wider class of generalized gamma distribution. This allows us to carry out a model discrimination to select a parsimonious lifetime distribution that provides the best fit to the data. Within the EM framework, a two-way profile likelihood approach is proposed to estimate the shape parameters. An extensive Monte Carlo simulation study is carried out to demonstrate the performance of the proposed estimation method. Model discrimination is carried out by means of the likelihood ratio test and information-based methods. Finally, a data on melanoma is analyzed for illustrative purpose.     

COM–Poisson cure rate survival models and an application to a cutaneous melanoma data

In this paper, we develop a flexible cure rate survival model by assuming the number of competing causes of the event of interest to follow the Conway–Maxwell Poisson distribution. This model includes as special cases some of the well-known cure rate models discussed in the literature. Next, we discuss the maximum likelihood estimation of the parameters of this cure rate survival model. Finally, we illustrate the usefulness of this model by applying it to a real cutaneous melanoma data.     

A model with long-term survivors: negative binomial Birnbaum-Saunders

Abstract

We propose a cure rate survival model by assuming that the number of competing causes of the event of interest follows the negative binomial distribution and the time to the event of interest has the Birnbaum-Saunders distribution. Further, the new model includes as special cases some well-known cure rate models published recently. We consider a frequentist analysis for parameter estimation of the negative binomial Birnbaum-Saunders model with cure rate. Then, we derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We illustrate the usefulness of the proposed model in the analysis of a real data set from the medical area.     

A Bayesian analysis of the Conway–Maxwell–Poisson cure rate model

The purpose of this paper is to develop a Bayesian analysis for the right-censored survival data when immune or cured individuals may be present in the population from which the data is taken. In our approach the number of competing causes of the event of interest follows the Conway–Maxwell–Poisson distribution which generalizes the Poisson distribution. Markov chain Monte Carlo (MCMC) methods are used to develop a Bayesian procedure for the proposed model. Also, some discussions on the model selection and an illustration with a real data set are considered.     

Influence diagnostics for the Weibull-Negative-Binomial regression model with cure rate under latent failure causes

In this paper, we propose a flexible cure rate survival model by assuming that the number of competing causes of the event of interest follows the Negative Binomial distribution and the time to event follows a Weibull distribution. Indeed, we introduce the Weibull-Negative-Binomial (WNB) distribution, which can be used in order to model survival data when the hazard rate function is increasing, decreasing and some non-monotonous shaped. Another advantage of the proposed model is that it has some distributions commonly used in lifetime analysis as particular cases. Moreover, the proposed model includes as special cases some of the well-know cure rate models discussed in the literature. We consider a frequentist analysis for parameter estimation of a WNB model with cure rate. Then, we derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes and present some ways to perform global influence analysis. Finally, the methodology is illustrated on a medical data.     

A general long-term aging model with different underlying activation mechanisms: Modeling,Bayesian estimation,and case influence diagnostics

In this paper we propose a general cure rate aging model. Our approach enables different underlying activation mechanisms which lead to the event of interest. The number of competing causes of the event of interest is assumed to follow a logarithmic distribution. The model is parameterized in terms of the cured fraction which is then linked to covariates. We explore the use of Markov chain Monte Carlo methods to develop a Bayesian analysis for the proposed model. Moreover, some discussions on the model selection to compare the fitted models are given, as well as case deletion influence diagnostics are developed for the joint posterior distribution based on the ψ-divergence, which has several divergence measures as particular cases, such as the Kullback–Leibler (K-L), J-distance, L₁ norm, and χ²-square divergence measures. Simulation studies are performed and experimental results are illustrated based on a real malignant melanoma data.     

Applying competing risks regression models: an overview

In many clinical research applications the time to occurrence of one event of interest, that may be obscured by another??so called competing??event, is investigated. Specific interventions can only have an effect on the endpoint they address or research questions might focus on risk factors for a certain outcome. Different approaches for the analysis of time-to-event data in the presence of competing risks were introduced in the last decades including some new methodologies, which are not yet frequently used in the analysis of competing risks data. Cause-specific hazard regression, subdistribution hazard regression, mixture models, vertical modelling and the analysis of time-to-event data based on pseudo-observations are described in this article and are applied to a dataset of a cohort study intended to establish risk stratification for cardiac death after myocardial infarction. Data analysts are encouraged to use the appropriate methods for their specific research questions by comparing different regression approaches in the competing risks setting regarding assumptions, methodology and interpretation of the results. Notes on application of the mentioned methods using the statistical software R are presented and extensions to the presented standard methods proposed in statistical literature are mentioned.     

The Geometric Birnbaum-Saunders regression model with cure rate

In this paper, we propose a cure rate survival model by assuming the number of competing causes of the event of interest follows the Geometric distribution and the time to event follow a Birnbaum Saunders distribution. We consider a frequentist analysis for parameter estimation of a Geometric Birnbaum Saunders model with cure rate. Finally, to analyze a data set from the medical area.     

Marginal Means/Rates Models for Multiple Type Recurrent Event Data

Recurrent events are frequently observed in biomedical studies, and often more than one type of event is of interest. Follow-up time may be censored due to loss to follow-up or administrative censoring. We propose a class of semi-parametric marginal means/rates models, with a general relative risk form, for assessing the effect of covariates on the censored event processes of interest. We formulate estimating equations for the model parameters, and examine asymptotic properties of the parameter estimators. Finite sample properties of the regression coefficients are examined through simulations. The proposed methods are applied to a retrospective cohort study of risk factors for preschool asthma.     

Applying a marginalized frailty model to competing risks

The marginalized frailty model is often used for the analysis of correlated times in survival data. When only two correlated times are analyzed, this model is often referred to as the Clayton–Oakes model [7,22]. With time-to-event data, there may exist multiple end points (competing risks) suggesting that an analysis focusing on all available outcomes is of interest. The purpose of this work is to extend the single risk marginalized frailty model to the multiple risk setting via cause-specific hazards (CSH). The methods herein make use of the marginalized frailty model described by Pipper and Martinussen [24]. As such, this work uses the martingale theory to develop a likelihood based on estimating equations and observed histories. The proposed multivariate CSH model yields marginal regression parameter estimates while accommodating the clustering of outcomes. The multivariate CSH model can be fitted using a data augmentation algorithm described by Lunn and McNeil [21] or by fitting a series of single risk models for each of the competing risks. An example of the application of the multivariate CSH model is provided through the analysis of a family-based follow-up study of breast cancer with death in absence of breast cancer as a competing risk.     

A competing risks approach for nonparametric estimation of transition probabilities in a non-Markov illness-death model

Competing risks model time to first event and type of first event. An example from hospital epidemiology is the incidence of hospital-acquired infection, which has to account for hospital discharge of non-infected patients as a competing risk. An illness-death model would allow to further study hospital outcomes of infected patients. Such a model typically relies on a Markov assumption. However, it is conceivable that the future course of an infected patient does not only depend on the time since hospital admission and current infection status but also on the time since infection. We demonstrate how a modified competing risks model can be used for nonparametric estimation of transition probabilities when the Markov assumption is violated.     

Modeling marginal features in studies of recurrent events in the presence of a terminal event

We study models for recurrent events with special emphasis on the situation where a terminal event acts as a competing risk for the recurrent events process and where there may be gaps between periods during which subjects are at risk for the recurrent event. We focus on marginal analysis of the expected number of events and show that an Aalen–Johansen type estimator proposed by Cook and Lawless is applicable in this situation. A motivating example deals with psychiatric hospital admissions where we supplement with analyses of the marginal distribution of time to the competing event and the marginal distribution of the time spent in hospital. Pseudo-observations are used for the latter purpose.

     

The odd log-logistic Lindley Poisson model for lifetime data

We define two new lifetime models called the odd log-logistic Lindley (OLL-L) and odd log-logistic Lindley Poisson (OLL-LP) distributions with various hazard rate shapes such as increasing, decreasing, upside-down bathtub, and bathtub. Various structural properties are derived. Certain characterizations of OLL-L distribution are presented. The maximum likelihood estimators of the unknown parameters are obtained. We propose a flexible cure rate survival model by assuming that the number of competing causes of the event of interest has a Poisson distribution and the time to event has an OLL-L distribution. The applicability of the new models is illustrated by means real datasets.