Semiparametric Estimation Methods for the Accelerated Failure Time Mixture Cure Model

This paper provides an overview of two semiparametric estimation methods recently proposed in the literature for the accelerated failure time mixture cure model. We prove that the two estimation methods are asymptotically equivalent. A simulation is conducted to investigate the rate of convergence of the two methods. We apply these methods to fit the accelerated failure time mixture cure model to the survival times of leukemia patients receiving bone marrow transplantation.     

Semiparametric Likelihood Estimation in the Clayton–Oakes Failure Time Model

Multivariate failure time data arise when the sample consists of clusters and each cluster contains several possibly dependent failure times. The Clayton–Oakes model (Clayton, 1978; Oakes, 1982) for multivariate failure times characterizes the intracluster dependence parametrically but allows arbitrary specification of the marginal distributions. In this paper, we discuss estimation in the Clayton–Oakes model when the marginal distributions are modeled to follow the Cox (1972) proportional hazards regression model. Parameter estimation is based on an approximate generalized maximum likelihood estimator. We illustrate the model's application with example datasets.     

Robust Smoothed Rank Estimation Methods for Accelerated Failure Time Model Allowing Clusters

Smoothed Gehan rank estimation methods are widely used in accelerated failure time (AFT) models with/without clusters. However, most methods are sensitive to outliers in the covariates. In order to solve this problem, we propose robust approaches based on the smoothed Gehan rank estimation methods for the AFT model, allowing for clusters by employing two different weight functions. Simulation studies show that the proposed methods outperform existing smoothed rank estimation methods regarding their biases and standard deviations when there are outliers in the covariates. The proposed methods are also applied to a real dataset from the “Major cardiovascular interventions” study.     

A Semiparametric Approach for Accelerated Failure Time Models with Covariates Subject to Measurement Error

There are relatively few discussions about measurement error in the accelerated failure time (AFT) model, particularly for the semiparametric AFT model. In this article, we propose an adjusted estimation procedure for the semiparametric AFT model with covariates subject to measurement error, based on the profile likelihood approach and simulation and exploration (SIMEX) method. The simulation studies show that the proposed semiparametric SIMEX approach performs well. The proposed approach is applied to a coronary heart disease dataset from the Busselton Health study for illustration.     

Maximum Likelihood Estimation in a Semiparametric Logistic/Proportional-Hazards Mixture Model

Abstract.  We consider large sample inference in a semiparametric logistic/proportional-hazards mixture model. This model has been proposed to model survival data where there exists a positive portion of subjects in the population who are not susceptible to the event under consideration. Previous studies of the logistic/proportional-hazards mixture model have focused on developing point estimation procedures for the unknown parameters. This paper studies large sample inferences based on the semiparametric maximum likelihood estimator. Specifically, we establish existence, consistency and asymptotic normality results for the semiparametric maximum likelihood estimator. We also derive consistent variance estimates for both the parametric and non-parametric components. The results provide a theoretical foundation for making large sample inference under the logistic/proportional-hazards mixture model.     

Using Frailties in the Accelerated Failure Time Model

The accelerated failuretime (AFT) model is an important alternative to the Cox proportionalhazards model (PHM) in survival analysis. For multivariate failuretime data we propose to use frailties to explicitly account forpossible correlations (and heterogeneity) among failure times.An EM-like algorithm analogous to that in the frailty model forthe Cox model is adapted. Through simulation it is shown thatits performance compares favorably with that of the marginalindependence approach. For illustration we reanalyze a real dataset.     

Finite Mixture of Generalized Semiparametric Models: Variable Selection via Penalized Estimation

Selection of the important variables is one of the most important model selection problems in statistical applications. In this article, we address variable selection in finite mixture of generalized semiparametric models. To overcome computational burden, we introduce a class of variable selection procedures for finite mixture of generalized semiparametric models using penalized approach for variable selection. Estimation of nonparametric component will be done via multivariate kernel regression. It is shown that the new method is consistent for variable selection and the performance of proposed method will be assessed via simulation.     

On Mixture Double Autoregressive Time Series Models

This article proposes a mixture double autoregressive model by introducing the flexibility of mixture models to the double autoregressive model, a novel conditional heteroscedastic model recently proposed in the literature. To make it more flexible, the mixing proportions are further assumed to be time varying, and probabilistic properties including strict stationarity and higher order moments are derived. Inference tools including the maximum likelihood estimation, an expectation–maximization (EM) algorithm for searching the estimator and an information criterion for model selection are carefully studied for the logistic mixture double autoregressive model, which has two components and is encountered more frequently in practice. Monte Carlo experiments give further support to the new models, and the analysis of an empirical example is also reported.     

Mixture cure rate models with accelerated failures and nonparametric form of covariate effects

Two-component mixture cure rate model is popular in cure rate data analysis with the proportional hazards and accelerated failure time (AFT) models being the major competitors for modelling the latency component. [Wang, L., Du, P., and Liang, H. (2012), ‘Two-Component Mixture Cure Rate Model with Spline Estimated Nonparametric Components’, Biometrics, 68, 726–735] first proposed a nonparametric mixture cure rate model where the latency component assumes proportional hazards with nonparametric covariate effects in the relative risk. Here we consider a mixture cure rate model where the latency component assumes AFTs with nonparametric covariate effects in the acceleration factor. Besides the more direct physical interpretation than the proportional hazards, our model has an additional scalar parameter which adds more complication to the computational algorithm as well as the asymptotic theory. We develop a penalised EM algorithm for estimation together with confidence intervals derived from the Louis formula. Asymptotic convergence rates of the parameter estimates are established. Simulations and the application to a melanoma study shows the advantages of our new method.     

A profile likelihood method for normal mixture with unequal variance

It is well known that the normal mixture with unequal variance has unbounded likelihood and thus the corresponding global maximum likelihood estimator (MLE) is undefined. One of the commonly used solutions is to put a constraint on the parameter space so that the likelihood is bounded and then one can run the EM algorithm on this constrained parameter space to find the constrained global MLE. However, choosing the constraint parameter is a difficult issue and in many cases different choices may give different constrained global MLE. In this article, we propose a profile log likelihood method and a graphical way to find the maximum interior mode. Based on our proposed method, we can also see how the constraint parameter, used in the constrained EM algorithm, affects the constrained global MLE. Using two simulation examples and a real data application, we demonstrate the success of our new method in solving the unboundness of the mixture likelihood and locating the maximum interior mode.     

Two-Sample Statistics for Testing the Equality of Survival Functions Against Improper Semi-parametric Accelerated Failure Time Alternatives: An Application to the Analysis of a Breast Cancer Clinical Trial

This paper presents two-sample statistics suited for testing equality of survival functions against improper semi-parametric accelerated failure time alternatives. These tests are designed for comparing either the short- or the long-term effect of a prognostic factor, or both. These statistics are obtained as partial likelihood score statistics from a time-dependent Cox model. As a consequence, the proposed tests can be very easily implemented using widely available software. A breast cancer clinical trial is presented as an example to demonstrate the utility of the proposed tests.     

An Alternative Estimation Approach for the Heterogeneity Linear Mixed Model

In this article, an alternative estimation approach is proposed to fit linear mixed effects models where the random effects follow a finite mixture of normal distributions. This heterogeneity linear mixed model is an interesting tool since it relaxes the classical normality assumption and is also perfectly suitable for classification purposes, based on longitudinal profiles. Instead of fitting directly the heterogeneity linear mixed model, we propose to fit an equivalent mixture of linear mixed models under some restrictions which is computationally simpler. Unlike the former model, the latter can be maximized analytically using an EM-algorithm and the obtained parameter estimates can be easily used to compute the parameter estimates of interest.     

A Kernel Smooth Approach for Joint Modeling of Accelerated Failure Time and Longitudinal Data

Joint likelihood approaches have been widely used to handle survival data with time-dependent covariates. In construction of the joint likelihood function for the accelerated failure time (AFT) model, the unspecified baseline hazard function is assumed to be a piecewise constant function in the literature. However, there are usually no close form formulas for the regression parameters, which require numerical methods in the EM iterations. The nonsmooth step function assumption leads to very spiky likelihood function which is very hard to find the globe maximum. Besides, due to nonsmoothness of the likelihood function, direct search methods are conducted for the maximization which are very inefficient and time consuming. To overcome the two disadvantages, we propose a kernel smooth pseudo-likelihood function to replace the nonsmooth step function assumption. The performance of the proposed method is evaluated by simulation studies. A case study of reproductive egg-laying data is provided to demonstrate the usefulness of the new approach.     

An Exponential-Family Multidimensional Scaling Mixture Methodology

A multidimensional scaling methodology (STUNMIX) for the analysis of subjects' preference/choice of stimuli that sets out to integrate the previous work in this area into a single framework, as well as to provide a variety of new options and models, is presented. Locations of the stimuli and the ideal points of derived segments of subjects on latent dimensions are estimated simultaneously. The methodology is formulated in the framework of the exponential family of distributions, whereby a wide range of different data types can be analyzed. Possible reparameterizations of stimulus coordinates by stimulus characteristics, as well as of probabilities of segment membership by subject background variables, are permitted. The models are estimated in a maximum likelihood framework. The performance of the models is demonstrated on synthetic data, and robustness is investigated. An empirical application is provided, concerning intentions to buy portable telephones.     

Composite Estimating Equation Method for the Accelerated Failure Time Model with Length‐biased Sampling Data

Length‐biased sampling data are often encountered in the studies of economics, industrial reliability, epidemiology, genetics and cancer screening. The complication of this type of data is due to the fact that the observed lifetimes suffer from left truncation and right censoring, where the left truncation variable has a uniform distribution. In the Cox proportional hazards model, Huang & Qin (Journal of the American Statistical Association, 107, 2012, p. 107) proposed a composite partial likelihood method which not only has the simplicity of the popular partial likelihood estimator, but also can be easily performed by the standard statistical software. The accelerated failure time model has become a useful alternative to the Cox proportional hazards model. In this paper, by using the composite partial likelihood technique, we study this model with length‐biased sampling data. The proposed method has a very simple form and is robust when the assumption that the censoring time is independent of the covariate is violated. To ease the difficulty of calculations when solving the non‐smooth estimating equation, we use a kernel smoothed estimation method (Heller; Journal of the American Statistical Association, 102, 2007, p. 552). Large sample results and a re‐sampling method for the variance estimation are discussed. Some simulation studies are conducted to compare the performance of the proposed method with other existing methods. A real data set is used for illustration.     

Chi-Squared Goodness-of-Fit Tests for Parametric Accelerated Failure Time Models

We give chi-squared goodness-of fit tests for parametric regression models such as accelerated failure time, proportional hazards, generalized proportional hazards, frailty models, transformation models, and models with cross-effects of survival functions. Random right censored data are used. Choice of random grouping intervals as data functions is considered.     

Calibration of Proportional Hazards and Accelerated Failure Time Models

Given a prognostic model based on one population, one may ask: Can this model be used to accurately predict disease in a different population? When the underlying rate of disease differs in the new population, the model must be calibrated. van Houwelingen (2000 van Houwelingen , H. ( 2000 ). Validation, calibration, revision and combination of prognostic survival models . Statistics in Medicine 19 : 3401 – 3415 .[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) considered this calibration problem focusing on proportional hazards models. We extend the validation by calibration to the log-logistic accelerated failure time model. We use calibration of proportional hazards models and log-logistic accelerated failure time models to examine whether a survival model based on the Framingham Heart Study can be applied to diverse studies around the world.     

Clustering Discrete Data Through the Multinomial Mixture Model

In this work, the multinomial mixture model is studied, through a maximum likelihood approach. The convergence of the maximum likelihood estimator to a set with characteristics of interest is shown. A method to select the number of mixture components is developed based on the form of the maximum likelihood estimator. A simulation study is then carried out to verify its behavior. Finally, two applications on real data of multinomial mixtures are presented.     

Model Selection For A Family Of Discrete Failure Time Distributions

In recent years, a large number of new discrete distributions have appeared in the literature. However, flexible discrete models which, at the same time, allow for easy statistical inference, are still an exception. This paper makes a detailed analysis of a family of discrete failure time distributions which meets both requirements. It examines the maximum likelihood estimation of the unknown parameters and presents a goodness-of-fit test for this model. The test is used for the selection of an appropriate model for datasets of frequencies of the duration of atmospheric circulation patterns.     

Promotion Time Cure Rate Model with Bivariate Random Effects

In this article, we consider the inclusion of random effects in both the survival function for at-risk subjects and the cure probability assuming a bivariate normal distribution for those effects in each cluster. For parameter estimation, we implemented the restricted maximum likelihood (REML) approach. We consider Weibull and Piecewise Exponential distributions to model the survival function for non-cured individuals. Simulation studies are performed, and based on a real database we evaluate the performance of our proposed model. Effect of different follow-up times and the effect of considering independent random effects instead of bivariate random effects are also studied.