Robust transformation mixed‐effects models for longitudinal continuous proportional data

The authors propose a robust transformation linear mixed‐effects model for longitudinal continuous proportional data when some of the subjects exhibit outlying trajectories over time. It becomes troublesome when including or excluding such subjects in the data analysis results in different statistical conclusions. To robustify the longitudinal analysis using the mixed‐effects model, they utilize the multivariate t distribution for random effects or/and error terms. Estimation and inference in the proposed model are established and illustrated by a real data example from an ophthalmology study. Simulation studies show a substantial robustness gain by the proposed model in comparison to the mixed‐effects model based on Aitchison's logit‐normal approach. As a result, the data analysis benefits from the robustness of making consistent conclusions in the presence of influential outliers. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

Likelihood analysis of joint marginal and conditional models for longitudinal categorical data

The authors develop a Markov model for the analysis of longitudinal categorical data which facilitates modelling both marginal and conditional structures. A likelihood formulation is employed for inference, so the resulting estimators enjoy the optimal properties such as efficiency and consistency, and remain consistent when data are missing at random. Simulation studies demonstrate that the proposed method performs well under a variety of situations. Application to data from a smoking prevention study illustrates the utility of the model and interpretation of covariate effects. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

An estimated‐score approach for dealing with missing covariate data in matched case–control studies

Matched case–control designs are commonly used in epidemiological studies for estimating the effect of exposure variables on the risk of a disease by controlling the effect of confounding variables. Due to retrospective nature of the study, information on a covariate could be missing for some subjects. A straightforward application of the conditional logistic likelihood for analyzing matched case–control data with the partially missing covariate may yield inefficient estimators of the parameters. A robust method has been proposed to handle this problem using an estimated conditional score approach when the missingness mechanism does not depend on the disease status. Within the conditional logistic likelihood framework, an empirical procedure is used to estimate the odds of the disease for the subjects with missing covariate values. The asymptotic distribution and the asymptotic variance of the estimator when the matching variables and the completely observed covariates are categorical. The finite sample performance of the proposed estimator is assessed through a simulation study. Finally, the proposed method has been applied to analyze two matched case–control studies. The Canadian Journal of Statistics 38: 680–697; 2010 © 2010 Statistical Society of Canada     

A linear transformation model for multivariate interval‐censored failure time data

This paper discusses multivariate interval‐censored failure time data observed when several correlated survival times of interest exist and only interval censoring is available for each survival time. Such data occur in many fields, for instance, studies of the development of physical symptoms or diseases in several organ systems. A marginal inference approach was used to create a linear transformation model and applied to bivariate interval‐censored data arising from a diabetic retinopathy study and an AIDS study. The results of simulation studies that were conducted to evaluate the performance of the presented approach suggest that it performs well. The Canadian Journal of Statistics 41: 275–290; 2013 © 2013 Statistical Society of Canada     

A class of mixed models for recurrent event data

In this article, we propose a class of mixed models for recurrent event data. The new models include the proportional rates model and Box–Cox transformation rates models as special cases, and allow the effects of covariates on the rate functions of counting processes to be proportional or convergent. For inference on the model parameters, estimating equation approaches are developed. The asymptotic properties of the resulting estimators are established and the finite sample performance of the proposed procedure is evaluated through simulation studies. A real example with data taken from a clinic study on chronic granulomatous disease (CGD) is also illustrated for the use of the proposed methodology. The Canadian Journal of Statistics 39: 578–590; 2011. © 2011 Statistical Society of Canada     

Model‐based clustering of longitudinal data

A new family of mixture models for the model‐based clustering of longitudinal data is introduced. The covariance structures of eight members of this new family of models are given and the associated maximum likelihood estimates for the parameters are derived via expectation–maximization (EM) algorithms. The Bayesian information criterion is used for model selection and a convergence criterion based on the Aitken acceleration is used to determine the convergence of these EM algorithms. This new family of models is applied to yeast sporulation time course data, where the models give good clustering performance. Further constraints are then imposed on the decomposition to allow a deeper investigation of the correlation structure of the yeast data. These constraints greatly extend this new family of models, with the addition of many parsimonious models. The Canadian Journal of Statistics 38:153–168; 2010 © 2010 Statistical Society of Canada     

Testing for generalized linear mixed models with cluster correlated data under linear inequality constraints

Generalized linear mixed models (GLMMs) are often used for analyzing cluster correlated data, including longitudinal data and repeated measurements. Full unrestricted maximum likelihood (ML) approaches for inference on both fixed‐and random‐effects parameters in GLMMs have been extensively studied in the literature. However, parameter orderings or constraints may occur naturally in practice, and in such cases, the efficiency of a statistical method is improved by incorporating the parameter constraints into the ML estimation and hypothesis testing. In this paper, inference for GLMMs under linear inequality constraints is considered. The asymptotic properties of the constrained ML estimators and constrained likelihood ratio tests for GLMMs have been studied. Simulations investigated the empirical properties of the constrained ML estimators, compared to their unrestricted counterparts. An application to a recent survey on Canadian youth smoking patterns is also presented. As these survey data exhibit natural parameter orderings, a constrained GLMM has been considered for data analysis. The Canadian Journal of Statistics 40: 243–258; 2012 © 2012 Crown in the right of Canada     

Regression analysis for a summed missing data problem under an outcome‐dependent sampling scheme

In this paper, we consider a regression analysis for a missing data problem in which the variables of primary interest are unobserved under a general biased sampling scheme, an outcome‐dependent sampling (ODS) design. We propose a semiparametric empirical likelihood method for accessing the association between a continuous outcome response and unobservable interesting factors. Simulation study results show that ODS design can produce more efficient estimators than the simple random design of the same sample size. We demonstrate the proposed approach with a data set from an environmental study for the genetic effects on human lung function in COPD smokers. The Canadian Journal of Statistics 40: 282–303; 2012 © 2012 Statistical Society of Canada     

New estimation and feature selection methods in mixture‐of‐experts models

We study estimation and feature selection problems in mixture‐of‐experts models. An $l_2$ ‐penalized maximum likelihood estimator is proposed as an alternative to the ordinary maximum likelihood estimator. The estimator is particularly advantageous when fitting a mixture‐of‐experts model to data with many correlated features. It is shown that the proposed estimator is root‐$n$ consistent, and simulations show its superior finite sample behaviour compared to that of the maximum likelihood estimator. For feature selection, two extra penalty functions are applied to the $l_2$ ‐penalized log‐likelihood function. The proposed feature selection method is computationally much more efficient than the popular all‐subset selection methods. Theoretically it is shown that the method is consistent in feature selection, and simulations support our theoretical results. A real‐data example is presented to demonstrate the method. The Canadian Journal of Statistics 38: 519–539; 2010 © 2010 Statistical Society of Canada     

Model‐based linear clustering

The authors propose a profile likelihood approach to linear clustering which explores potential linear clusters in a data set. For each linear cluster, an errors‐in‐variables model is assumed. The optimization of the derived profile likelihood can be achieved by an EM algorithm. Its asymptotic properties and its relationships with several existing clustering methods are discussed. Methods to determine the number of components in a data set are adapted to this linear clustering setting. Several simulated and real data sets are analyzed for comparison and illustration purposes. The Canadian Journal of Statistics 38: 716–737; 2010 © 2010 Statistical Society of Canada     

Change detection in linear regression with time series errors

A new test for detecting a change in linear regression parameters assuming a general weakly dependent error structure is given. It extends earlier methods based on cumulative sums assuming independent errors. The novelty is in the new standardization method and in smoothing when the time series is dominated by high frequencies. Simulations show the excellent performance of the test. Examples are taken from environmental applications. The algorithm is easy to implement. Testing for multiple changes can be done by segmentation. The Canadian Journal of Statistics 38:65–79; 2010 © 2009 Statistical Society of Canada     

State-space models for multivariate longitudinal data of mixed types

We propose a class of state-space models for multivariate longitudinal data where the components of the response vector may have different distributions. The approach is based on the class of Tweedie exponential dispersion models, which accommodates a wide variety of discrete, continuous and mixed data. The latent process is assumed to be a Markov process, and the observations are conditionally independent given the latent process, over time as well as over the components of the response vector. This provides a fully parametric alternative to the quasilikelihood approach of Liang and Zeger. We estimate the regression parameters for time-varying covariates entering either via the observation model or via the latent process, based on an estimating equation derived from the Kalman smoother. We also consider analysis of residuals from both the observation model and the latent process.     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Bootstrap tests for variance components in generalized linear mixed models

In many applications of generalized linear mixed models to clustered correlated or longitudinal data, often we are interested in testing whether a random effects variance component is zero. The usual asymptotic mixture of chi‐square distributions of the score statistic for testing constrained variance components does not necessarily hold. In this article, the author proposes and explores a parametric bootstrap test that appears to be valid based on its estimated level of significance under the null hypothesis. Results from a simulation study indicate that the bootstrap test has a level much closer to the nominal one while the asymptotic test is conservative, and is more powerful than the usual asymptotic score test based on a mixture of chi‐squares. The proposed bootstrap test is illustrated using two sets of real‐life data obtained from clinical trials. The Canadian Journal of Statistics © 2009 Statistical Society of Canada