Consistent model selection and data-driven smooth tests for longitudinal data in the estimating equations approach

Summary.  Model selection for marginal regression analysis of longitudinal data is challenging owing to the presence of correlation and the difficulty of specifying the full likelihood, particularly for correlated categorical data. The paper introduces a novel Bayesian information criterion type model selection procedure based on the quadratic inference function, which does not require the full likelihood or quasi-likelihood. With probability approaching 1, the criterion selects the most parsimonious correct model. Although a working correlation matrix is assumed, there is no need to estimate the nuisance parameters in the working correlation matrix; moreover, the model selection procedure is robust against the misspecification of the working correlation matrix. The criterion proposed can also be used to construct a data-driven Neyman smooth test for checking the goodness of fit of a postulated model. This test is especially useful and often yields much higher power in situations where the classical directional test behaves poorly. The finite sample performance of the model selection and model checking procedures is demonstrated through Monte Carlo studies and analysis of a clinical trial data set.     

Bayesian mixture modeling for spatial Poisson process intensities,with applications to extreme value analysis

We propose a method for the analysis of a spatial point pattern, which is assumed to arise as a set of observations from a spatial nonhomogeneous Poisson process. The spatial point pattern is observed in a bounded region, which, for most applications, is taken to be a rectangle in the space where the process is defined. The method is based on modeling a density function, defined on this bounded region, that is directly related with the intensity function of the Poisson process. We develop a flexible nonparametric mixture model for this density using a bivariate Beta distribution for the mixture kernel and a Dirichlet process prior for the mixing distribution. Using posterior simulation methods, we obtain full inference for the intensity function and any other functional of the process that might be of interest. We discuss applications to problems where inference for clustering in the spatial point pattern is of interest. Moreover, we consider applications of the methodology to extreme value analysis problems. We illustrate the modeling approach with three previously published data sets. Two of the data sets are from forestry and consist of locations of trees. The third data set consists of extremes from the Dow Jones index over a period of 1303 days.     

Criterion for the Selection of a Working Correlation Structure in the Generalized Estimating Equation Approach for Longitudinal Balanced Data

The generalized estimating equation is a popular method for analyzing correlated response data. It is important to determine a proper working correlation matrix at the time of applying the generalized estimating equation since an improper selection sometimes results in inefficient parameter estimates. We propose a criterion for the selection of an appropriate working correlation structure. The proposed criterion is based on a statistic to test the hypothesis that the covariance matrix equals a given matrix, and also measures the discrepancy between the covariance matrix estimator and the specified working covariance matrix. We evaluated the performance of the proposed criterion through simulation studies assuming that for each subject, the number of observations remains the same. The results revealed that when the proposed criterion was adopted, the proportion of selecting a true correlation structure was generally higher than that when other competing approaches were adopted. The proposed criterion was applied to longitudinal wheeze data, and it was suggested that the resultant correlation structure was the most accurate.     

Inferences on the intraclass correlation coefficients in the unbalanced two-way random effects model with interaction

In this paper, the hypothesis testing and interval estimation for the intraclass correlation coefficients are considered in a two-way random effects model with interaction. Two particular intraclass correlation coefficients are described in a reliability study. The tests and confidence intervals for the intraclass correlation coefficients are developed when the data are unbalanced. One approach is based on the generalized p-value and generalized confidence interval, the other is based on the modified large-sample idea. These two approaches simplify to the ones in Gilder et al. [2007. Confidence intervals on intraclass correlation coefficients in a balanced two-factor random design. J. Statist. Plann. Inference 137, 1199–1212] when the data are balanced. Furthermore, some statistical properties of the generalized confidence intervals are investigated. Finally, some simulation results to compare the performance of the modified large-sample approach with that of the generalized approach are reported. The simulation results indicate that the modified large-sample approach performs better than the generalized approach in the coverage probability and expected length of the confidence interval.     

A new approach: Interrelated two-way clustering of gene expression data

The paper presents a new approach to interrelated two-way clustering of gene expression data. Clustering of genes has been effected using entropy and a correlation measure, whereas the samples have been clustered using the fuzzy C-means. The efficiency of this approach has been tested on two well known data sets: the colon cancer data set and the leukemia data set. Using this approach, we were able to identify the important co-regulated genes and group the samples efficiently at the same time.     

P-value adjustment for multiple binary endpoints

The p-value-based adjustment of individual endpoints and the global test for an overall inference are the two general approaches for the analysis of multiple endpoints. Statistical procedures developed for testing multivariate outcomes often assume that the multivariate endpoints are either independent or normally distributed. This paper presents a general approach for the analysis of multivariate binary data under the framework of generalized linear models. The generalized estimating equations (GEE) approach is applied to estimate the correlation matrix of the test statistics using the identity and exchangeable working correlation matrices with the model-based as well as robust estimators. The objectives of the approaches are the adjustment of p-values of individual endpoints to identify the affected endpoints as well as the global test of an overall effect. A Monte Carlo simulation was conducted to evaluate the overall family wise error (FWE) rates of the single-step down p-value adjustment approach from two adjustment methods to three global test statistics. The p-value adjustment approach seems to control the FWE better than the global approach Applications of the proposed methods are illustrated by analyzing a carcinogenicity experiment designed to study the dose response trend for 10 tumor sites, and a developmental toxicity experiment with three malformation types: external, visceral, and skeletal.     

Confidence intervals for the difference between two median survival times for clustered survival data

Clustered survival data arise often in clinical trial design, where the correlated subunits from the same cluster are randomized to different treatment groups. Under such design, we consider the problem of constructing confidence interval for the difference of two median survival time given the covariates. We use Cox gamma frailty model to account for the within-cluster correlation. Based on the conditional confidence intervals, we can identify the possible range of covariates over which the two groups would provide different median survival times. The associated coverage probability and the expected length of the proposed interval are investigated via a simulation study. The implementation of the confidence intervals is illustrated using a real data set.     

Improved orthogonal polynomial density estimates

Density estimates that are expressible as the product of a base density function and a linear combination of orthogonal polynomials are considered in this paper. More specifically, two criteria are proposed for determining the number of terms to be included in the polynomial adjustment component and guidelines are suggested for the selection of a suitable base density function. A simulation study reveals that these stopping rules produce density estimates that are generally more accurate than kernel density estimates or those resulting from the application of the Kronmal–Tarter criterion. Additionally, it is explained that the same approach can be utilized to obtain multivariate density estimates. The proposed orthogonal polynomial density estimation methodology is applied to several univariate and bivariate data sets, some of which have served as benchmarks in the statistical literature on density estimation.     

Restricted maximum likelihood estimation of joint mean‐covariance models

The class of joint mean‐covariance models uses the modified Cholesky decomposition of the within subject covariance matrix in order to arrive to an unconstrained, statistically meaningful reparameterisation. The new parameterisation of the covariance matrix has two sets of parameters that separately describe the variances and correlations. Thus, with the mean or regression parameters, these models have three sets of distinct parameters. In order to alleviate the problem of inefficient estimation and downward bias in the variance estimates, inherent in the maximum likelihood estimation procedure, the usual REML estimation procedure adjusts for the degrees of freedom lost due to the estimation of the mean parameters. Because of the parameterisation of the joint mean covariance models, it is possible to adapt the usual REML procedure in order to estimate the variance (correlation) parameters by taking into account the degrees of freedom lost by the estimation of both the mean and correlation (variance) parameters. To this end, here we propose adjustments to the estimation procedures based on the modified and adjusted profile likelihoods. The methods are illustrated by an application to a real data set and simulation studies. The Canadian Journal of Statistics 40: 225–242; 2012 © 2012 Statistical Society of Canada     

Generalized empirical likelihood inference in partial linear regression model for longitudinal data

In this paper, empirical likelihood inference for longitudinal data within the framework of partial linear regression models are investigated. The proposed procedures take into consideration the correlation within groups without involving direct estimation of nuisance parameters in the correlation matrix. The empirical likelihood method is used to estimate the regression coefficients and the baseline function, and to construct confidence intervals. A nonparametric version of Wilk's theorem for the limiting distribution of the empirical likelihood ratio is derived. Compared with methods based on normal approximations, the empirical likelihood does not require consistent estimators for the asymptotic variance and bias. The finite sample behaviour of the proposed method is evaluated with simulation and illustrated with an AIDS clinical trial data set.     

A PRESS statistic for working correlation structure selection in generalized estimating equations

Generalized estimating equations (GEE) is one of the most commonly used methods for regression analysis of longitudinal data, especially with discrete outcomes. The GEE method accounts for the association among the responses of a subject through a working correlation matrix and its correct specification ensures efficient estimation of the regression parameters in the marginal mean regression model. This study proposes a predicted residual sum of squares (PRESS) statistic as a working correlation selection criterion in GEE. A simulation study is designed to assess the performance of the proposed GEE PRESS criterion and to compare its performance with its counterpart criteria in the literature. The results show that the GEE PRESS criterion has better performance than the weighted error sum of squares SC criterion in all cases but is surpassed in performance by the Gaussian pseudo-likelihood criterion. Lastly, the working correlation selection criteria are illustrated with data from the Coronary Artery Risk Development in Young Adults study.     

A class of additive transformation models for recurrent gap times

Abstract

The gap time between recurrent events is often of primary interest in many fields such as medical studies, and in this article, we discuss regression analysis of the gap times arising from a general class of additive transformation models. For the problem, we propose two estimation procedures, the modified within-cluster resampling (MWCR) method and the weighted risk-set (WRS) method, and the proposed estimators are shown to be consistent and asymptotically follow the normal distribution. In particular, the estimators have closed forms and can be easily determined, and the methods have the advantage of leaving the correlation among gap times arbitrary. A simulation study is conducted for assessing the finite sample performance of the presented methods and suggests that they work well in practical situations. Also the methods are applied to a set of real data from a chronic granulomatous disease (CGD) clinical trial.     

Semiparametric Proportional Mean Residual Life Model With Censoring Indicators Missing at Random

For right-censored survival data, the information that whether the observed time is survival or censoring time is frequently lost. This is the case for the competing risk data. In this article, we consider statistical inference for the right-censored survival data with censoring indicators missing at random under the proportional mean residual life model. Simple and augmented inverse probability weighted estimating equation approaches are developed, in which the nonmissingness probability and some unknown conditional expectations are estimated by the kernel smoothing technique. The asymptotic properties of all the proposed estimators are established, while extensive simulation studies demonstrate that our proposed methods perform well under the moderate sample size. At last, the proposed method is applied to a data set from a stage II breast cancer trial.     

Bayesian estimation of log odds ratios over two-way contingency tables with intraclass correlated cells

In this article, a Bayesian approach is proposed for the estimation of log odds ratios and intraclass correlations over a two-way contingency table, including intraclass correlated cells. Required likelihood functions of log odds ratios are obtained, and determination of prior structures is discussed. Hypothesis testing for log odds ratios and intraclass correlations by using the posterior simulations is outlined. Because the proposed approach includes no asymptotic theory, it is useful for the estimation and hypothesis testing of log odds ratios in the presence of certain intraclass correlation patterns. A family health status and limitations data set is analyzed by using the proposed approach in order to figure out the impact of intraclass correlations on the estimates and hypothesis tests of log odds ratios. Although intraclass correlations are small in the data set, we obtain that even small intraclass correlations can significantly affect the estimates and test results, and our approach is useful for the estimation and testing of log odds ratios in the presence of intraclass correlations.     

Subgroup Analysis with Time‐to‐Event Data Under a Logistic‐Cox Mixture Model

Subgroup detection has received increasing attention recently in different fields such as clinical trials, public management and market segmentation analysis. In these fields, people often face time‐to‐event data, which are commonly subject to right censoring. This paper proposes a semiparametric Logistic‐Cox mixture model for subgroup analysis when the interested outcome is event time with right censoring. The proposed method mainly consists of a likelihood ratio‐based testing procedure for testing the existence of subgroups. The expectation–maximization iteration is applied to improve the testing power, and a model‐based bootstrap approach is developed to implement the testing procedure. When there exist subgroups, one can also use the proposed model to estimate the subgroup effect and construct predictive scores for the subgroup membership. The large sample properties of the proposed method are studied. The finite sample performance of the proposed method is assessed by simulation studies. A real data example is also provided for illustration.     

An additive–multiplicative mean model for panel count data with dependent observation and dropout processes

This paper discusses regression analysis of panel count data with dependent observation and dropout processes. For the problem, a general mean model is presented that can allow both additive and multiplicative effects of covariates on the underlying point process. In addition, the proportional rates model and the accelerated failure time model are employed to describe possible covariate effects on the observation process and the dropout or follow‐up process, respectively. For estimation of regression parameters, some estimating equation‐based procedures are developed and the asymptotic properties of the proposed estimators are established. In addition, a resampling approach is proposed for estimating a covariance matrix of the proposed estimator and a model checking procedure is also provided. Results from an extensive simulation study indicate that the proposed methodology works well for practical situations, and it is applied to a motivating set of real data.     

Nonparametric tests for stratified additive hazards model based on current status data

Stratified regression models are commonly employed when study subjects may come from possibly different strata such as different medical centers, and for the situation, one common question of interest is to test the existence of the stratum effect. To address this, there exists some literature on the testing of the stratum effects under the framework of the proportional hazards model when one observes right-censored data or interval-censored data. In this paper, we consider the situation under the additive hazards model when one faces current status data, for which there does not seem to exist an established test procedure. The asymptotic distributions of the proposed test procedure are provided. Also a simulation study is performed to evaluate the performance of the proposed method and indicates that it works well for practical situations. The approach is applied to a set of real current status data from a tumorigenicity study.     

Selection Strategy for Covariance Structure of Random Effects in Linear Mixed‐effects Models

Linear mixed‐effects models are a powerful tool for modelling longitudinal data and are widely used in practice. For a given set of covariates in a linear mixed‐effects model, selecting the covariance structure of random effects is an important problem. In this paper, we develop a joint likelihood‐based selection criterion. Our criterion is the approximately unbiased estimator of the expected Kullback–Leibler information. This criterion is also asymptotically optimal in the sense that for large samples, estimates based on the covariance matrix selected by the criterion minimize the approximate Kullback–Leibler information. Finite sample performance of the proposed method is assessed by simulation experiments. As an illustration, the criterion is applied to a data set from an AIDS clinical trial.     

Testing of mean interval for interval-valued data

Abstract

A new parametric hypothesis test of mean interval for interval-valued data set, which can deal with massive information contained in nowadays massive data “Big data” sets, is proposed. An approach using an orthogonal transformation is introduced to obtain an equivalent hypothesis test of mean interval in terms of the mid-point and mid-range of the interval-valued variable. The new test is very efficient in small interval-valued sample scenarios. Some simulation studies are conducted for the investigation of the sample size and the power of test. The performance of the proposed test is illustrated with two real-life examples.