Zero-inflated beta distribution for modeling the proportions in quantitative fatty acid signature analysis

Quantitative fatty acid signature analysis (QFASA) produces diet estimates containing the proportion of each species of prey in a predator's diet. Since the diet estimates are compositional, often contain an abundance of zeros (signifying the absence of a species in the diet), and samples sizes are generally small, inference problems require the use of nonstandard statistical methodology. Recently, a mixture distribution involving the multiplicative logistic normal distribution (and its skew-normal extension) was introduced in relation to QFASA to manage the problematic zeros. In this paper, we examine an alternative mixture distribution, namely, the recently proposed zero-inflated beta (ZIB) distribution. A potential advantage of using the ZIB distribution over the previously considered mixture models is that it does not require transformation of the data. To assess the usefulness of the ZIB distribution in QFASA inference problems, a simulation study is first carried out which compares the small sample properties of the maximum likelihood estimators of the means. The fit of the distributions is then examined using ‘pseudo-predators’ generated from a large real-life prey base. Finally, confidence intervals for the true diet based on the ZIB distribution are compared with earlier results through a simulation study and harbor seal data.     

Semiparametric model for recurrent event data with excess zeros and informative censoring

Recurrent event data are often encountered in longitudinal follow-up studies in many important areas such as biomedical science, econometrics, reliability, criminology and demography. Multiplicative marginal rates models have been used extensively to analyze recurrent event data, but often fail to fit the data adequately. In addition, the analysis is complicated by excess zeros in the data as well as the presence of a terminal event that precludes further recurrence. To address these problems, we propose a semiparametric model with an additive rate function and an unspecified baseline to analyze recurrent event data, which includes a parameter to accommodate excess zeros and a frailty term to account for a terminal event. Local likelihood procedure is applied to estimate the parameters, and the asymptotic properties of the estimators are established. A simulation study is conducted to evaluate the performance of the proposed methods, and an example of their application is presented on a set of tumor recurrent data for bladder cancer.     

Nonparametric estimation of transition probabilities in a non-Markov illness–death model

In this paper we consider nonparametric estimation of transition probabilities for multi-state models. Specifically, we focus on the illness-death or disability model. The main novelty of the proposed estimators is that they do not rely on the Markov assumption, typically assumed to hold in a multi-state model. We investigate the asymptotic properties of the introduced estimators, such as their consistency and their convergence to a normal law. Simulations demonstrate that the new estimators may outperform Aalen–Johansen estimators (the classical nonparametric tool for estimating the transition probabilities) in non-Markov situation. An illustration through real data analysis is included.     

Asymptotic properties of the maximum-likelihood estimator in zero-inflated binomial regression

The zero-inflated binomial (ZIB) regression model was proposed to account for excess zeros in binomial regression. Since then, the model has been applied in various fields, such as ecology and epidemiology. In these applications, maximum-likelihood estimation (MLE) is used to derive parameter estimates. However, theoretical properties of the MLE in ZIB regression have not yet been rigorously established. The current paper fills this gap and thus provides a rigorous basis for applying the model. Consistency and asymptotic normality of the MLE in ZIB regression are proved. A consistent estimator of the asymptotic variance–covariance matrix of the MLE is also provided. Finite-sample behavior of the estimator is assessed via simulations. Finally, an analysis of a data set in the field of health economics illustrates the paper.     

A unified approach to estimating association measures via a joint generalized linear model for paired binary data

Paired binary data arise frequently in biomedical studies with unique features of their own. For instance, in clinical studies involving pairs such as ears, eyes etc., often both the intrapair association parameter and the event probability are of interest. In addition, we may be interested in the dependence of the association parameter on certain covariates as well. Although various methods have been proposed to model paired binary data, this paper proposes a unified approach for estimating various intrapair measures under a generalized linear model with simultaneous maximum likelihood estimates of the marginal probabilities and the intrapair association. The methods are illustrated with a twin morbidity study.     

Additive Transformation Models for Recurrent Events

In this article, we propose a class of additive transformation models for recurrent event data, which includes the additive rates model as a special case. The new models offer great flexibility in formulating the effects of covariates on the mean function of recurrent events. Estimating equation approaches are developed for the model parameters, and asymptotic properties of the resulting estimators are established. In addition, a model checking procedure is presented to assess the adequacy of the model. The finite sample performance of the proposed estimators is examined through simulation studies, and an application to a bladder cancer study is presented.     

The analysis of multivariate recurrent events with partially missing event types

In many clinical studies, subjects are at risk of experiencing more than one type of potentially recurrent event. In some situations, however, the occurrence of an event is observed, but the specific type is not determined. We consider the analysis of this type of incomplete data when the objectives are to summarize features of conditional intensity functions and associated treatment effects, and to study the association between different types of event. Here we describe a likelihood approach based on joint models for the multi-type recurrent events where parameter estimation is obtained from a Monte-Carlo EM algorithm. Simulation studies show that the proposed method gives unbiased estimators for regression coefficients and variance–covariance parameters, and the coverage probabilities of confidence intervals for regression coefficients are close to the nominal level. When the distribution of the frailty variable is misspecified, the method still provides estimators of the regression coefficients with good properties. The proposed method is applied to a motivating data set from an asthma study in which exacerbations were to be sub-typed by cellular analysis of sputum samples as eosinophilic or non-eosinophilic.     

Weighting for unequal selection probabilities in multilevel models

When multilevel models are estimated from survey data derived using multistage sampling, unequal selection probabilities at any stage of sampling may induce bias in standard estimators, unless the sources of the unequal probabilities are fully controlled for in the covariates. This paper proposes alternative ways of weighting the estimation of a two-level model by using the reciprocals of the selection probabilities at each stage of sampling. Consistent estimators are obtained when both the sample number of level 2 units and the sample number of level 1 units within sampled level 2 units increase. Scaling of the weights is proposed to improve the properties of the estimators and to simplify computation. Variance estimators are also proposed. In a limited simulation study the scaled weighted estimators are found to perform well, although non-negligible bias starts to arise for informative designs when the sample number of level 1 units becomes small. The variance estimators perform extremely well. The procedures are illustrated using data from the survey of psychiatric morbidity.     

General purpose multiply robust data integration procedures for handling nonprobability samples

In recent years, there has been an increased interest in combining probability and nonprobability samples. Nonprobability sample are cheaper and quicker to conduct but the resulting estimators are vulnerable to bias as the participation probabilities are unknown. To adjust for the potential bias, estimation procedures based on parametric or nonparametric models have been discussed in the literature. However, the validity of the resulting estimators relies heavily on the validity of the underlying models. Also, nonparametric approaches may suffer from the curse of dimensionality and poor efficiency. We propose a data integration approach by combining multiple outcome regression models and propensity score models. The proposed approach can be used for estimating general parameters including totals, means, distribution functions, and percentiles. The resulting estimators are multiply robust in the sense that they remain consistent if all but one model are misspecified. The asymptotic properties of point and variance estimators are established. The results from a simulation study show the benefits of the proposed method in terms of bias and efficiency. Finally, we apply the proposed method using data from the Korea National Health and Nutrition Examination Survey and data from the National Health Insurance Sharing Services.     

Using ranked set sampling with binary outcomes in cluster randomized designs

We study the use of ranked set sampling (RSS) with binary outcomes in cluster-randomized designs (CRDs), where a generalized linear mixed model (GLMM) is used to model the hierarchical data structure involved. Under the GLMM-based framework, we propose three different approaches to estimate the treatment effect, including the nonparametric (NP), maximum likelihood (ML) and pseudo likelihood (PL) estimators. We investigate their asymptotic properties and examine their finite-sample performance via simulation. Based on these three RSS estimators, we further develop procedures for testing the existence of the treatment effect. We examine the power and size of our proposed RSS tests and compare them with existing tests based on simple random sampling (SRS). All the proposed RSS estimation and test methods are illustrated with two data examples, one for rare events and the other for non-extreme events. Throughout our investigations, we also consider the possible effect of imperfect ranking. Among the proposed methods, we provide recommendations on whether to use RSS rather than SRS with binary outcomes in CRDs and, if yes, when to use which RSS method. The Canadian Journal of Statistics 48: 342–365; 2020 © 2019 Statistical Society of Canada     

Model averaging for multivariate multiple regression models

The theories and applications of model averaging have been developed comprehensively in the past two decades. In this paper, we consider model averaging for multivariate multiple regression models. In order to make use of the correlation information of the dependent variables sufficiently, we propose a model averaging method based on Mahalanobis distance which is related to the correlation of the dependent variables. We prove the asymptotic optimality of the resulting Mahalanobis Mallows model averaging (MMMA) estimators under certain assumptions. In the simulation study, we show that the proposed MMMA estimators compare favourably with model averaging estimators based on AIC and BIC weights and the Mallows model averaging estimators from the single dependent variable regression models. We further apply our method to the real data on urbanization rate and the proportion of non-agricultural population in ethnic minority areas of China.     

Nonparametric Estimation of Sojourn Time Distributions for Truncated Serial Event Data—a Weight-adjusted Approach

In follow-up studies, survival data often include subjects who have had a certain event at recruitment and may potentially experience a series of subsequent events during the follow-up period. This kind of survival data collected under a cross-sectional sampling criterion is called truncated serial event data. The outcome variables of interest in this paper are serial sojourn times between successive events. To analyze the sojourn times in truncated serial event data, we need to confront two potential sampling biases arising simultaneously from a sampling criterion and induced informative censoring. In this study, nonparametric estimation of the joint probability function of serial sojourn times is developed by using inverse probabilities of the truncation and censoring times as weight functions to accommodate these two sampling biases under various situations of truncation and censoring. Relevant statistical properties of the proposed estimators are also discussed. Simulation studies and two real data are presented to illustrate the proposed methods.     

A Marginal Additive Rates Model for Recurrent Event Data with a Terminal Event

Recurrent events data with a terminal event often arise in many longitudinal studies. Most of existing models assume multiplicative covariate effects and model the conditional recurrent event rate given survival. In this article, we propose a marginal additive rates model for recurrent events with a terminal event, and develop two procedures for estimating the model parameters. The asymptotic properties of the resulting estimators are established. In addition, some numerical procedures are presented for model checking. The finite-sample behavior of the proposed methods is examined through simulation studies, and an application to a bladder cancer study is also illustrated.     

Evaluating bias correction in weighted proportional hazards regression

Often in observational studies of time to an event, the study population is a biased (i.e., unrepresentative) sample of the target population. In the presence of biased samples, it is common to weight subjects by the inverse of their respective selection probabilities. Pan and Schaubel (Can J Stat 36:111–127, 2008) recently proposed inference procedures for an inverse selection probability weighted (ISPW) Cox model, applicable when selection probabilities are not treated as fixed but estimated empirically. The proposed weighting procedure requires auxiliary data to estimate the weights and is computationally more intense than unweighted estimation. The ignorability of sample selection process in terms of parameter estimators and predictions is often of interest, from several perspectives: e.g., to determine if weighting makes a significant difference to the analysis at hand, which would in turn address whether the collection of auxiliary data is required in future studies; to evaluate previous studies which did not correct for selection bias. In this article, we propose methods to quantify the degree of bias corrected by the weighting procedure in the partial likelihood and Breslow-Aalen estimators. Asymptotic properties of the proposed test statistics are derived. The finite-sample significance level and power are evaluated through simulation. The proposed methods are then applied to data from a national organ failure registry to evaluate the bias in a post-kidney transplant survival model.     

On the small sample properties of norm-restricted maximum likelihood estimators for logistic regression models

This paper develops alternatives to maximum likelihood estimators (MLE) for logistic regression models and compares the mean squared error (MSE) of the estimators. The MLE for the vector of underlying success probabilities has low MSE only when the true probabilities are extreme (i.e., near 0 or 1). Extreme probabilities correspond to logistic regression parameter vectors which are large in norm. A competing “restricted” MLE and an empirical version of it are suggested as estimators with better performance than the MLE for central probabilities. An approximate EM-algorithm for estimating the restriction is described. As in the case of normal theory ridge estimators, the proposed estimators are shown to be formally derivable by Bayes and empirical Bayes arguments. The small sample operating characteristics of the proposed estimators are compared to the MLE via a simulation study; both the estimation of individual probabilities and of logistic parameters are considered.     

Additive–multiplicative rates model for recurrent events

Recurrent events are frequently encountered in biomedical studies. Evaluating the covariates effects on the marginal recurrent event rate is of practical interest. There are mainly two types of rate models for the recurrent event data: the multiplicative rates model and the additive rates model. We consider a more flexible additive–multiplicative rates model for analysis of recurrent event data, wherein some covariate effects are additive while others are multiplicative. We formulate estimating equations for estimating the regression parameters. The estimators for these regression parameters are shown to be consistent and asymptotically normally distributed under appropriate regularity conditions. Moreover, the estimator of the baseline mean function is proposed and its large sample properties are investigated. We also conduct simulation studies to evaluate the finite sample behavior of the proposed estimators. A medical study of patients with cystic fibrosis suffered from recurrent pulmonary exacerbations is provided for illustration of the proposed method.     

Joint analysis of nonlinear heterogeneous longitudinal data and binary outcome: an application to AIDS clinical studies

Finite mixture models are currently used to analyze heterogeneous longitudinal data. By releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, finite mixture models not only can estimate model parameters but also cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, which might be associated with a clinically important binary outcome. This article develops a joint modeling of a finite mixture of NLME models for longitudinal data in the presence of covariate measurement errors and a logistic regression for a binary outcome, linked by individual latent class indicators, under a Bayesian framework. Simulation studies are conducted to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and logistic regression are fitted separately, followed by an application to a real data set from an AIDS clinical trial, in which the viral dynamics and dichotomized time to the first decline of CD4/CD8 ratio are analyzed jointly.     

Semiparametric transformation models with random effects for clustered doubly censored data

For right-censored data, Zeng et al. [Semiparametirc transformation modes with random effects for clustered data. Statist Sin. 2008;18:355–377] proposed a class of semiparametric transformation models with random effects to formulate the effects of possibly time-dependent covariates on clustered failure times. In this article, we demonstrate that the approach of Zeng et al. can be extended to analyse clustered doubly censored data. The asymptotic properties of the nonparametric maximum likelihood estimators of the model parameters are derived. A simulation study is conducted to investigate the performance of the proposed estimators.     

Two-parameter ridge estimator in the binary logistic regression

The binary logistic regression is a commonly used statistical method when the outcome variable is dichotomous or binary. The explanatory variables are correlated in some situations of the logit model. This problem is called multicollinearity. It is known that the variance of the maximum likelihood estimator (MLE) is inflated in the presence of multicollinearity. Therefore, in this study, we define a new two-parameter ridge estimator for the logistic regression model to decrease the variance and overcome multicollinearity problem. We compare the new estimator to the other well-known estimators by studying their mean squared error (MSE) properties. Moreover, a Monte Carlo simulation is designed to evaluate the performances of the estimators. Finally, a real data application is illustrated to show the applicability of the new method. According to the results of the simulation and real application, the new estimator outperforms the other estimators for all of the situations considered.     

Semiparametric proportional means model for marker data contingent on recurrent event

In many biomedical studies with recurrent events, some markers can only be measured when events happen. For example, medical cost attributed to hospitalization can only incur when patients are hospitalized. Such marker data are contingent on recurrent events. In this paper, we present a proportional means model for modelling the markers using the observed covariates contingent on the recurrent event. We also model the recurrent event via a marginal rate model. Estimating equations are constructed to derive the point estimators for the parameters in the proposed models. The estimators are shown to be asymptotically normal. Simulation studies are conducted to examine the finite-sample properties of the proposed estimators and the proposed method is applied to a data set from the Vitamin A Community Trial.