A Baseline-free Procedure for Transformation Models Under Interval Censorship

An important property of Cox regression model is that the estimation of regression parameters using the partial likelihood procedure does not depend on its baseline survival function. We call such a procedure baseline-free. Using marginal likelihood, we show that an baseline-free procedure can be derived for a class of general transformation models under interval censoring framework. The baseline-free procedure results a simplified and stable computation algorithm for some complicated and important semiparametric models, such as frailty models and heteroscedastic hazard/rank regression models, where the estimation procedures so far available involve estimation of the infinite dimensional baseline function. A detailed computational algorithm using Markov Chain Monte Carlo stochastic approximation is presented. The proposed procedure is demonstrated through extensive simulation studies, showing the validity of asymptotic consistency and normality. We also illustrate the procedure with a real data set from a study of breast cancer. A heuristic argument showing that the score function is a mean zero martingale is provided.     

An iterative procedure for the estimation of parameters in a dose-response model

The least squares estimates of the parameters in the multistage dose-response model are unduly affected by outliers in a data set whereas the minimum sum of absolute errors, MSAE estimates are more resistant to outliers. Algorithms to compute the MSAE estimates can be tedious and computationally burdensome. We propose a linear approximation for the dose-response model that can be used to find the MSAE estimates by a simple and computationally less intensive algorithm. A few illustrative ex-amples and a Monte Carlo study show that we get comparable values of the MSAE estimates of the parameters in a dose-response model using the exact model and the linear approximation.     

On parameter estimation of software reliability models

Most software reliability models use the maximum likelihood method to estimate the parameters of the model. The maximum likelihood method assumes that the inter-failure time distributions contribute equally to the likelihood function. Since software reliability is expected to exhibit growth, a weighted likelihood function that gives higher weights to latter inter-failure times compared to earlier ones is suggested. The accuracy of the predictions obtained using the weighted likelihood method is compared with the predictions obtained when the parameters are estimated by the maximum likelihood method on three real datasets. A simulation study is also conducted.     

Bayesian gamma frailty models for survival data with semi-competing risks and treatment switching

Motivated from a colorectal cancer study, we propose a class of frailty semi-competing risks survival models to account for the dependence between disease progression time, survival time, and treatment switching. Properties of the proposed models are examined and an efficient Gibbs sampling algorithm using the collapsed Gibbs technique is developed. A Bayesian procedure for assessing the treatment effect is also proposed. The deviance information criterion (DIC) with an appropriate deviance function and Logarithm of the pseudomarginal likelihood (LPML) are constructed for model comparison. A simulation study is conducted to examine the empirical performance of DIC and LPML and as well as the posterior estimates. The proposed method is further applied to analyze data from a colorectal cancer study.     

Efficient simulated maximum likelihood with an application to online retailing

Simulated maximum likelihood estimates an analytically intractable likelihood function with an empirical average based on data simulated from a suitable importance sampling distribution. In order to use simulated maximum likelihood in an efficient way, the choice of the importance sampling distribution as well as the mechanism to generate the simulated data are crucial. In this paper we develop a new heuristic for an automated, multistage implementation of simulated maximum likelihood which, by adaptively updating the importance sampler, approximates the (locally) optimal importance sampling distribution. The proposed approach also allows for a convenient incorporation of quasi-Monte Carlo methods. Quasi-Monte Carlo methods produce simulated data which can significantly increase the accuracy of the likelihood-estimate over regular Monte Carlo methods. Several examples provide evidence for the potential efficiency gain of this new method. We apply the method to a computationally challenging geostatistical model of online retailing.     

A Class of Non-Gaussian State Space Models With Exact Likelihood Inference

The likelihood function of a general nonlinear, non-Gaussian state space model is a high-dimensional integral with no closed-form solution. In this article, I show how to calculate the likelihood function exactly for a large class of non-Gaussian state space models that include stochastic intensity, stochastic volatility, and stochastic duration models among others. The state variables in this class follow a nonnegative stochastic process that is popular in econometrics for modeling volatility and intensities. In addition to calculating the likelihood, I also show how to perform filtering and smoothing to estimate the latent variables in the model. The procedures in this article can be used for either Bayesian or frequentist estimation of the model’s unknown parameters as well as the latent state variables. Supplementary materials for this article are available online.     

SEGMENTED DOSE-RESPONSE MODELS FOR REPEATED MEASURES DATA

In a dose-response analysis, logit-transformed responses are modelled as a function of log-transformed doses. The linear trend is commonly observed. The comparison among treatment groups can be made based on the linear trend. An example in this paper came from a study to estimate the effect of aminophylline on dose-response curve of atracurium. Unlike the usual dose-response curve, this example has repeated measures and seems to have two slopes to which the usual dose-response model is not adequate to fit. We propose segmented regression models that allow two different slopes. The proposed model is an extension of the segmented regression model with a univariate response per subject. We illustrate the proposed model fits data better than the usual dose-response model.     

Kernel-based global MLE of partial linear random effects models for longitudinal data

Random effects models have been playing a critical role for modelling longitudinal data. However, there are little studies on the kernel-based maximum likelihood method for semiparametric random effects models. In this paper, based on kernel and likelihood methods, we propose a pooled global maximum likelihood method for the partial linear random effects models. The pooled global maximum likelihood method employs the local approximations of the nonparametric function at a group of grid points simultaneously, instead of one point. Gaussian quadrature is used to approximate the integration of likelihood with respect to random effects. The asymptotic properties of the proposed estimators are rigorously studied. Simulation studies are conducted to demonstrate the performance of the proposed approach. We also apply the proposed method to analyse correlated medical costs in the Medical Expenditure Panel Survey data set.     

A Bayesian Change-Point Analysis for Software Reliability Models

In most software reliability models which utilize the nonhomogeneous Poisson process (NHPP), the intensity function for the counting process is usually assumed to be continuous and monotone. However, on account of various practical reasons, there may exist some change points in the intensity function and thus the assumption of continuous and monotone intensity function may be unrealistic in many real situations. In this article, the Bayesian change-point approach using beta-mixtures for modeling the intensity function with possible change points is proposed. The hidden Markov model with non constant transition probabilities is applied to the beta-mixture for detecting the change points of the parameters. The estimation and interpretation of the model is illustrated using the Naval Tactical Data System (NTDS) data. The proposed change point model will be also compared with the competing models via marginal likelihood. It can be seen that the proposed model has the highest marginal likelihood and outperforms the competing models.     

Classical model selection via simulated annealing

Summary. The classical approach to statistical analysis is usually based upon finding values for model parameters that maximize the likelihood function. Model choice in this context is often also based on the likelihood function, but with the addition of a penalty term for the number of parameters. Though models may be compared pairwise by using likelihood ratio tests for example, various criteria such as the Akaike information criterion have been proposed as alternatives when multiple models need to be compared. In practical terms, the classical approach to model selection usually involves maximizing the likelihood function associated with each competing model and then calculating the corresponding criteria value(s). However, when large numbers of models are possible, this quickly becomes infeasible unless a method that simultaneously maximizes over both parameter and model space is available. We propose an extension to the traditional simulated annealing algorithm that allows for moves that not only change parameter values but also move between competing models. This transdimensional simulated annealing algorithm can therefore be used to locate models and parameters that minimize criteria such as the Akaike information criterion, but within a single algorithm, removing the need for large numbers of simulations to be run. We discuss the implementation of the transdimensional simulated annealing algorithm and use simulation studies to examine its performance in realistically complex modelling situations. We illustrate our ideas with a pedagogic example based on the analysis of an autoregressive time series and two more detailed examples: one on variable selection for logistic regression and the other on model selection for the analysis of integrated recapture–recovery data.     

Statistical evidence in contingency tables analysis

The likelihood ratio is used for measuring the strength of statistical evidence. The probability of observing strong misleading evidence along with that of observing weak evidence evaluate the performance of this measure. When the corresponding likelihood function is expressed in terms of a parametric statistical model that fails, the likelihood ratio retains its evidential value if the likelihood function is robust [Royall, R., Tsou, T.S., 2003. Interpreting statistical evidence by using imperfect models: robust adjusted likelihood functions. J. Roy. Statist. Soc. Ser. B 65, 391–404]. In this paper, we extend the theory of Royall and Tsou [2003. Interpreting statistical evidence by using imperfect models: robust adjusted likelihood functions. J. Roy. Statist. Soc., Ser. B 65, 391–404] to the case when the assumed working model is a characteristic model for two-way contingency tables (the model of independence, association and correlation models). We observe that association and correlation models are not equivalent in terms of statistical evidence. The association models are bounded by the maximum of the bump function while the correlation models are not.     

Linear regression model with new symmetric distributed errors

Regression models play a dominant role in analyzing several data sets arising from areas like agricultural experiment, space experiment, biological experiment, financial modeling, etc. One of the major strings in developing the regression models is the assumption of the distribution of the error terms. It is customary to consider that the error terms follow the Gaussian distribution. However, there are some drawbacks of Gaussian errors such as the distribution being mesokurtic having kurtosis three. In many practical situations the variables under study may not be having mesokurtic but they are platykurtic. Hence, to analyze these sorts of platykurtic variables, a two-variable regression model with new symmetric distributed errors is developed and analyzed. The maximum likelihood (ML) estimators of the model parameters are derived. The properties of the ML estimators with respect to the new symmetrically distributed errors are also discussed. A simulation study is carried out to compare the proposed model with that of Gaussian errors and found that the proposed model performs better when the variables are platykurtic. Some applications of the developed model are also pointed out.     

Smooth Semi‐nonparametric Analysis for Mixture Cure Models and Its Application to Breast Cancer

Mixture cure models are widely used when a proportion of patients are cured. The proportional hazards mixture cure model and the accelerated failure time mixture cure model are the most popular models in practice. Usually the expectation–maximisation (EM) algorithm is applied to both models for parameter estimation. Bootstrap methods are used for variance estimation. In this paper we propose a smooth semi‐nonparametric (SNP) approach in which maximum likelihood is applied directly to mixture cure models for parameter estimation. The variance can be estimated by the inverse of the second derivative of the SNP likelihood. A comprehensive simulation study indicates good performance of the proposed method. We investigate stage effects in breast cancer by applying the proposed method to breast cancer data from the South Carolina Cancer Registry.     

Likelihood-free stochastic approximation EM for inference in complex models

A maximum likelihood methodology for the parameters of models with an intractable likelihood is introduced. We produce a likelihood-free version of the stochastic approximation expectation-maximization (SAEM) algorithm to maximize the likelihood function of model parameters. While SAEM is best suited for models having a tractable “complete likelihood” function, its application to moderately complex models is a difficult or even impossible task. We show how to construct a likelihood-free version of SAEM by using the “synthetic likelihood” paradigm. Our method is completely plug-and-play, requires almost no tuning and can be applied to both static and dynamic models.     

Analysis of dose-response in flexible dose titration clinical studies

Assessing dose-response from flexible-dose clinical trials (e.g., titration or dose escalation studies) is challenging and often problematic due to the selection bias caused by 'titration-to-response'. We investigate the performance of a dynamic linear mixed-effects (DLME) model and marginal structural model (MSM) in evaluating dose-response from flexible-dose titration clinical trials via simulations. The simulation results demonstrated that DLME models with previous exposure as a time-varying covariate may provide an unbiased and efficient estimator to recover exposure-response relationship from flexible-dose clinical trials. Although the MSM models with independent and exchangeable working correlations appeared to be able to recover the right direction of the dose-response relationship, it tended to over-correct selection bias and overestimated the underlying true dose-response. The MSM estimators were also associated with large variability in the parameter estimates. Therefore, DLME may be an appropriate modeling option in identifying dose-response when data from fixed-dose studies are absent or a fixed-dose design is unethical to be implemented.     

Empirical likelihood based variable selection

Information criteria form an important class of model/variable selection methods in statistical analysis. Parametric likelihood is a crucial part of these methods. In some applications such as the generalized linear models, the models are only specified by a set of estimating functions. To overcome the non-availability of well defined likelihood function, the information criteria under empirical likelihood are introduced. Under this setup, we successfully solve the existence problem of the profile empirical likelihood due to the over constraint in variable selection problems. The asymptotic properties of the new method are investigated. The new method is shown to be consistent at selecting the variables under mild conditions. Simulation studies find that the proposed method has comparable performance to the parametric information criteria when a suitable parametric model is available, and is superior when the parametric model assumption is violated. A real data set is also used to illustrate the usefulness of the new method.     

Direct parametric inference for the cumulative incidence function

Summary.  In survival data that are collected from phase III clinical trials on breast cancer, a patient may experience more than one event, including recurrence of the original cancer, new primary cancer and death. Radiation oncologists are often interested in comparing patterns of local or regional recurrences alone as first events to identify a subgroup of patients who need to be treated by radiation therapy after surgery. The cumulative incidence function provides estimates of the cumulative probability of locoregional recurrences in the presence of other competing events. A simple version of the Gompertz distribution is proposed to parameterize the cumulative incidence function directly. The model interpretation for the cumulative incidence function is more natural than it is with the usual cause-specific hazard parameterization. Maximum likelihood analysis is used to estimate simultaneously parametric models for cumulative incidence functions of all causes. The parametric cumulative incidence approach is applied to a data set from the National Surgical Adjuvant Breast and Bowel Project and compared with analyses that are based on parametric cause-specific hazard models and nonparametric cumulative incidence estimation.     

Estimating the turning point of the log-logistic hazard function in the presence of long-term survivors with an application for uterine cervical cancer data

The hazard function plays an important role in cancer patient survival studies, as it quantifies the instantaneous risk of death of a patient at any given time. Often in cancer clinical trials, unimodal hazard functions are observed, and it is of interest to detect (estimate) the turning point (mode) of hazard function, as this may be an important measure in patient treatment strategies with cancer. Moreover, when patient cure is a possibility, estimating cure rates at different stages of cancer, in addition to their proportions, may provide a better summary of the effects of stages on survival rates. Therefore, the main objective of this paper is to consider the problem of estimating the mode of hazard function of patients at different stages of cervical cancer in the presence of long-term survivors. To this end, a mixture cure rate model is proposed using the log-logistic distribution. The model is conveniently parameterized through the mode of the hazard function, in which cancer stages can affect both the cured fraction and the mode. In addition, we discuss aspects of model inference through the maximum likelihood estimation method. A Monte Carlo simulation study assesses the coverage probability of asymptotic confidence intervals.     

Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.