A continuous-time Markov chain approach with the analytic likelihood in studies of behavioral changes

Abstract

We develop an analytic likelihood approach for a four-state CTMC by solving the backwards Kolmogorov differential equations, reducing this bias in transition rate estimates. A simulation study is performed to assess the performance of this new method and confirms that it achieves good coverage probabilities with low bias and standard errors. Finally, we analyzed data from Project SUCCESS to estimate the study each participant’s transitions among behavioral stage, consisting of risky drinking and possible ineffective using of contraception, which comprise the primary endpoint of risk of an alcohol-exposed pregnancy.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Gompertz model with time-dependent covariate in the presence of interval-, right- and left-censored data

In this paper, the Gompertz model is extended to incorporate time-dependent covariates in the presence of interval-, right-, left-censored and uncensored data. Then, its performance at different sample sizes, study periods and attendance probabilities are studied. Following that, the model is compared to a fixed covariate model. Finally, two confidence interval estimation methods, Wald and likelihood ratio (LR), are explored and conclusions are drawn based on the results of the coverage probability study. The results indicate that bias, standard error and root mean square error values of the parameter estimates decrease with the increase in study period, attendance probability and sample size. Also, LR was found to work slightly better than the Wald for parameters of the model.     

Analyzing dependence in incidence of diabetes and heart problem using generalized bivariate geometric models with covariates

For analyzing incidence data on diabetes and health problems, the bivariate geometric probability distribution is a natural choice but remained unexplored largely due to lack of models linking covariates with the probabilities of bivariate incidence of correlated outcomes. In this paper, bivariate geometric models are proposed for two correlated incidence outcomes. The extended generalized linear models are developed to take into account covariate dependence of the bivariate probabilities of correlated incidence outcomes for diabetes and heart diseases for the elderly population. The estimation and test procedures are illustrated using the Health and Retirement Study data. Two models are shown in this paper, one based on conditional-marginal approach and the other one based on the joint probability distribution with an association parameter. The joint model with association parameter appears to be a very good choice for analyzing the covariate dependence of the joint incidence of diabetes and heart diseases. Bootstrapping is performed to measure the accuracy of estimates and the results indicate very small bias.     

Bayesian Variable Selection Under Collinearity

In this article, we highlight some interesting facts about Bayesian variable selection methods for linear regression models in settings where the design matrix exhibits strong collinearity. We first demonstrate via real data analysis and simulation studies that summaries of the posterior distribution based on marginal and joint distributions may give conflicting results for assessing the importance of strongly correlated covariates. The natural question is which one should be used in practice. The simulation studies suggest that posterior inclusion probabilities and Bayes factors that evaluate the importance of correlated covariates jointly are more appropriate, and some priors may be more adversely affected in such a setting. To obtain a better understanding behind the phenomenon, we study some toy examples with Zellner’s g-prior. The results show that strong collinearity may lead to a multimodal posterior distribution over models, in which joint summaries are more appropriate than marginal summaries. Thus, we recommend a routine examination of the correlation matrix and calculation of the joint inclusion probabilities for correlated covariates, in addition to marginal inclusion probabilities, for assessing the importance of covariates in Bayesian variable selection.     

Parametric bootstrap inferences for unbalanced panel data models

This article presents parametric bootstrap (PB) approaches for hypothesis testing and interval estimation for the regression coefficients of panel data regression models with incomplete panels. Some simulation results are presented to compare the performance of the PB approaches with the approximate inferences. Our studies show that the PB approaches perform satisfactorily for various sample sizes and parameter configurations, and the performance of PB approaches is mostly better than the approximate methods with respect to the coverage probabilities and the Type I error rates. The PB inferences have almost exact coverage probabilities and Type I error rates. Furthermore, the PB procedure can be simply carried out by a few simulation steps, and the derivation is easier to understand and to be extended to the multi-way error component regression models with unbalanced panels. Finally, the proposed approaches are illustrated by using a real data example.     

Large sample properties and confidence bands for component-wise varying-coefficient regression with longitudinal dependent variable

Longitudinal studies with repeatedly measured dependent variable (out-come) and time-invariant covariates are common in biomedical and epidemi-ological studies. A useful statistical tool to evaluate the effects of covariates on the outcome variable over time is the varying-coefficient regression, which considers a linear relationship between the covariates and the outcome at a specific time point but assumes the linear coefficients to be smooth curves over time. In order to provide adequate smoothing for each coefficient curve, Wu and Chiang ( 1999 ) proposed a class of component-wise kernel estimators and determined the large sample convergence rates and some of the constant terms of the mean squared errors of their estimators. In this paper we calcu¬late the explicit large sample mean squared errors, including the convergence rates and ail the constant terms, and the asymptotic distributions of the kernel estimators of Wu and Chiang ( 1999 ). These asymptotic distributions are used to construct point-wise confidence intervals and Bonferroni-type confidence bands for the coefficient curves. Through a Monte Carlo simulation, wre show that our confidence regions have adequate coverage probabilities. Applying our procedures to a NIH fetal growth study, we show that our procedures are useful to determine the effects of maternal height, cigarette smoking and al¬cohol consumption on the growth of fetal abdominal circumference over time during pregnancy.     

Parametric bootstrap inferences for the growth curve models with intraclass correlation structure

This paper presents parametric bootstrap (PB) approaches for hypothesis testing and interval estimation of the fixed effects and the variance component in the growth curve models with intraclass correlation structure. The PB pivot variables are proposed based on the sufficient statistics of the parameters. Some simulation results are presented to compare the performance of the proposed approaches with the generalized inferences. Our studies show that the PB approaches perform satisfactorily for various cell sizes and parameter configurations, and tends to outperform the generalized inferences with respect to the coverage probabilities and powers. The PB approaches not only have almost exact coverage probabilities and Type I error rates, but also have the shorter expected lengths and the higher powers. Furthermore, the PB procedure can be simply carried out by a few simulation steps. Finally, the proposed approaches are illustrated by using a real data example.     

Confidence limits for stress–strength reliability involving Weibull models

The problem of interval estimation of the stress–strength reliability involving two independent Weibull distributions is considered. An interval estimation procedure based on the generalized variable (GV) approach is given when the shape parameters are unknown and arbitrary. The coverage probabilities of the GV approach are evaluated by Monte Carlo simulation. Simulation studies show that the proposed generalized variable approach is very satisfactory even for small samples. For the case of equal shape parameter, it is shown that the generalized confidence limits are exact. Some available asymptotic methods for the case of equal shape parameter are described and their coverage probabilities are evaluated using Monte Carlo simulation. Simulation studies indicate that no asymptotic approach based on the likelihood method is satisfactory even for large samples. Applicability of the GV approach for censored samples is also discussed. The results are illustrated using an example.     

Locally efficient semiparametric estimators for a class of Poisson models with measurement error

The presence of measurement error may cause bias in parameter estimation and can lead to incorrect conclusions in data analyses. Despite a large body of literature on general measurement error problems, relatively few works exist to handle Poisson models. In this article we thoroughly study Poisson models with errors in covariates and propose consistent and locally efficient semiparametric estimators. We assess the finite sample performance of the estimators through extensive simulation studies and illustrate the proposed methodologies by analyzing data from the Stroke Recovery in Underserved Populations Study. The Canadian Journal of Statistics 47: 157–181; 2019 © 2019 Statistical Society of Canada     

Treatment design selection effects on parameter estimation in dynamic logistic models for longitudinal binary data

In a longitudinal set-up, to examine the effects of certain fixed covariates on the repeated binary responses, there exists an approach to model the binary probabilities through a dynamic logistic relationship. In some practical situations such as in longitudinal clinical studies, it may happen that some of the covariates such as treatments are selected randomly following an adaptive design, whereas the rest of the covariates may be fixed by nature. The purpose of this study is to examine the effects of the design weights selection on the parameter estimation including the treatment effects, after taking the longitudinal correlations of the repeated binary responses into account.     

Confidence intervals for ratios of AUCs in the case of serial sampling: a comparison of seven methods

Pharmacokinetic studies are commonly performed using the two-stage approach. The first stage involves estimation of pharmacokinetic parameters such as the area under the concentration versus time curve (AUC) for each analysis subject separately, and the second stage uses the individual parameter estimates for statistical inference. This two-stage approach is not applicable in sparse sampling situations where only one sample is available per analysis subject similar to that in non-clinical in vivo studies. In a serial sampling design, only one sample is taken from each analysis subject. A simulation study was carried out to assess coverage, power and type I error of seven methods to construct two-sided 90% confidence intervals for ratios of two AUCs assessed in a serial sampling design, which can be used to assess bioequivalence in this parameter.     

Markov Poisson regression models for discrete time series. Part 1: Methodology

This paper proposes and investigates a class of Markov Poisson regression models in which Poisson rate functions of covariates are conditional on unobserved states which follow a finite-state Markov chain. Features of the proposed model, estimation, inference, bootstrap confidence intervals, model selection and other implementation issues are discussed. Monte Carlo studies suggest that the proposed estimation method is accurate and reliable for single- and multiple-subject time series data; the choice of starting probabilities for the Markov process has little eff ect on the parameter estimates; and penalized likelihood criteria are reliable for determining the number of states. Part 2 provides applications of the proposed model.     

Bayesian and likelihood-based inference for the bivariate normal correlation coefficient

The paper develops some objective priors for correlation coefficient of the bivariate normal distribution. The criterion used is the asymptotic matching of coverage probabilities of Bayesian credible intervals with the corresponding frequentist coverage probabilities. The paper uses various matching criteria, namely, quantile matching, highest posterior density matching, and matching via inversion of test statistics. Each matching criterion leads to a different prior for the parameter of interest. We evaluate their performance by comparing credible intervals through simulation studies. In addition, inference through several likelihood-based methods have been discussed.     

Hybrid regions for post-change mean in a sequence of normal variables

The hybrid bootstrap uses resampling ideas to extend the duality approach to the interval estimation for a parameter of interest when there are nuisance parameters. The confidence region constructed by the hybrid bootstrap may perform much better than the ordinary bootstrap region in a situation where the data provide substantial information about the nuisance parameter, but limited information about the parameter of interest. We apply this method to estimate the post-change mean after a change is detected by a stopping procedure in a sequence of independent normal variables. Since distribution theory in change point problems is generally a challenge, we use bootstrap simulation to find empirical distributions of test statistics and calculate critical thresholds. Both likelihood ratio and Bayesian test statistics are considered to set confidence regions for post-change means in the normal model. In the simulation studies, the performance of hybrid regions are compared with that of ordinary bootstrap regions in terms of the widths and coverage probabilities of confidence intervals.     

Time-varying coefficients in a multivariate frailty model: Application to breast cancer recurrences of several types and death

During their follow-up, patients with cancer can experience several types of recurrent events and can also die. Over the last decades, several joint models have been proposed to deal with recurrent events with dependent terminal event. Most of them require the proportional hazard assumption. In the case of long follow-up, this assumption could be violated. We propose a joint frailty model for two types of recurrent events and a dependent terminal event to account for potential dependencies between events with potentially time-varying coefficients. For that, regression splines are used to model the time-varying coefficients. Baseline hazard functions (BHF) are estimated with piecewise constant functions or with cubic M-Splines functions. The maximum likelihood estimation method provides parameter estimates. Likelihood ratio tests are performed to test the time dependency and the statistical association of the covariates. This model was driven by breast cancer data where the maximum follow-up was close to 20 years.     

Inferences in dynamic logit models in semi-parametric setup for repeated binary data

Binary dynamic fixed and mixed logit models are extensively studied in the literature. These models are developed to examine the effects of certain fixed covariates through a parametric regression function as a part of the models. However, there are situations where one may like to consider more covariates in the model but their direct effect is not of interest. In this paper we propose a generalization of the existing binary dynamic logit (BDL) models to the semi-parametric longitudinal setup to address this issue of additional covariates. The regression function involved in such a semi-parametric BDL model contains (i) a parametric linear regression function in some primary covariates, and (ii) a non-parametric function in certain secondary covariates. We use a simple semi-parametric conditional quasi-likelihood approach for consistent estimation of the non-parametric function, and a semi-parametric likelihood approach for the joint estimation of the main regression and dynamic dependence parameters of the model. The finite sample performance of the estimation approaches is examined through a simulation study. The asymptotic properties of the estimators are also discussed. The proposed model and the estimation approaches are illustrated by reanalysing a longitudinal infectious disease data.     

Statistical inference for Cox proportional hazards models with a diverging number of covariates

For statistical inference on regression models with a diverging number of covariates, the existing literature typically makes sparsity assumptions on the inverse of the Fisher information matrix. Such assumptions, however, are often violated under Cox proportion hazards models, leading to biased estimates with under-coverage confidence intervals. We propose a modified debiased lasso method, which solves a series of quadratic programming problems to approximate the inverse information matrix without posing sparse matrix assumptions. We establish asymptotic results for the estimated regression coefficients when the dimension of covariates diverges with the sample size. As demonstrated by extensive simulations, our proposed method provides consistent estimates and confidence intervals with nominal coverage probabilities. The utility of the method is further demonstrated by assessing the effects of genetic markers on patients' overall survival with the Boston Lung Cancer Survival Cohort, a large-scale epidemiology study investigating mechanisms underlying the lung cancer.     

Regression analysis of longitudinal data with correlated censoring and observation times

Longitudinal data occur in many fields such as the medical follow-up studies that involve repeated measurements. For their analysis, most existing approaches assume that the observation or follow-up times are independent of the response process either completely or given some covariates. In practice, it is apparent that this may not be true. In this paper, we present a joint analysis approach that allows the possible mutual correlations that can be characterized by time-dependent random effects. Estimating equations are developed for the parameter estimation and the resulted estimators are shown to be consistent and asymptotically normal. The finite sample performance of the proposed estimators is assessed through a simulation study and an illustrative example from a skin cancer study is provided.     

A new compounding life distribution: the Weibull–Poisson distribution

In this paper, a new compounding distribution, named the Weibull–Poisson distribution is introduced. The shape of failure rate function of the new compounding distribution is flexible, it can be decreasing, increasing, upside-down bathtub-shaped or unimodal. A comprehensive mathematical treatment of the proposed distribution and expressions of its density, cumulative distribution function, survival function, failure rate function, the kth raw moment and quantiles are provided. Maximum likelihood method using EM algorithm is developed for parameter estimation. Asymptotic properties of the maximum likelihood estimates are discussed, and intensive simulation studies are conducted for evaluating the performance of parameter estimation. The use of the proposed distribution is illustrated with examples.