A test of the missing data mechanism for repeated measures data

The occurrence of missing data is an often unavoidable consequence of repeated measures studies. Fortunately, multivariate general linear models such as growth curve models and linear mixed models with random effects have been well developed to analyze incomplete normally-distributed repeated measures data. Most statistical methods have assumed that the missing data occur at random. This assumption may include two types of missing data mechanism: missing completely at random (MCAR) and missing at random (MAR) in the sense of Rubin (1976). In this paper, we develop a test procedure for distinguishing these two types of missing data mechanism for incomplete normally-distributed repeated measures data. The proposed test is similar in spiril to the test of Park and Davis (1992). We derive the test for incomplete normally-distribrlted repeated measures data using linear mixed models. while Park and Davis (1992) cleirved thr test for incomplete repeatctl categorical data in the framework of Grizzle Starmer. and Koch (1969). Thr proposed procedure can be applied easily to any other multivariate general linear model which allow for missing data. The test is illustrated using the hip-replacernent patient.data from Crowder and Hand (1990).     

Multivariate regression models for discrete and continuous repeated measurements

A general class of multivariate regression models is considered for repeated measurements with discrete and continuous outcome variables. The proposed model is based on the seemingly unrelated regression model (Zellner, 1962) and an extension of the model of Park and Woolson(1992). The regression parameters of the model are consistently estimated using the two-stage least squares method. When the out come variables are multivariate normal, the two-stage estimator reduces to Zellner’s two-stage estimator. As a special case, we consider the marginal distribution described by Liang and Zeger (1986). Under this this distributional assumption, we show that the two-stage estimator has similar asymptotic properties and comparable small sample properties to Liang and Zeger's estimator. Since the proposed approach is based on the least squares method, however, any distributional assumption is not required for variables outcome variables. As a result, the proposed estimator is more robust to the marginal distribution of outcomes.     

Likelihood inference for correlated binary data without any information about the joint distributions

We propose a universal robust likelihood that is able to accommodate correlated binary data without any information about the underlying joint distributions. This likelihood function is asymptotically valid for the regression parameter for any underlying correlation configurations, including varying under- or over-dispersion situations, which undermines one of the regularity conditions ensuring the validity of crucial large sample theories. This robust likelihood procedure can be easily implemented by using any statistical software that provides naïve and sandwich covariance matrices for regression parameter estimates. Simulations and real data analyses are used to demonstrate the efficacy of this parametric robust method.     

Joint analysis of longitudinal data comprising repeated measures and times to events

In biomedical and public health research, both repeated measures of biomarkers Y as well as times T to key clinical events are often collected for a subject. The scientific question is how the distribution of the responses [ T , Y | X ] changes with covariates X . [ T | X ] may be the focus of the estimation where Y can be used as a surrogate for T . Alternatively, T may be the time to drop-out in a study in which [ Y | X ] is the target for estimation. Also, the focus of a study might be on the effects of covariates X on both T and Y or on some underlying latent variable which is thought to be manifested in the observable outcomes. In this paper, we present a general model for the joint analysis of [ T , Y | X ] and apply the model to estimate [ T | X ] and other related functionals by using the relevant information in both T and Y . We adopt a latent variable formulation like that of Fawcett and Thomas and use it to estimate several quantities of clinical relevance to determine the efficacy of a treatment in a clinical trial setting. We use a Markov chain Monte Carlo algorithm to estimate the model's parameters. We illustrate the methodology with an analysis of data from a clinical trial comparing risperidone with a placebo for the treatment of schizophrenia.     

Longitudinal data analysis of mean passage time among malnutrition states: an application of Markov chains

Clinical prognosis of patients can be best described from a longitudinal study and a Markov regression model is an appropriate way of analyzing the prognosis of disease when the outcomes are serially dependent. Mean first passage time (MFPT) is a method to estimate the average number of transitions between the states of a Markov chain. The present study used the secondary data from a longitudinal study which was done during 1982–1986. This study was to illustrate the MFPT among the states of malnutrition, which were classified as Normal, Mild/Moderate and Severe among children aged 5–7 years, in South India. The 95% confidence interval (CI) for the MFPT was calculated using Monte Carlo simulation. Markov regression models were used to test for the association of state transitions across the risk factors. The average time taken for an underweight child to transit from Severe state of malnutrition to become Normal was nearly 2.73 (95% CI 2.60–2.86) years and 3.41 (95% CI 3.25–3.58) years in Rural area and 2.31(95% CI 2.20–2.42) in Urban area. The significant difference between the MFPT for some risk factors are useful to plan interventions. It will especially be useful to find the impact of duration among school-going children on their cognitive disorders.     

Mean-Squared errors of small area estimators under a multivariate linear model for repeated measures data

In this paper, we discuss the derivation of the first and second moments for the proposed small area estimators under a multivariate linear model for repeated measures data. The aim is to use these moments to estimate the mean-squared errors (MSE) for the predicted small area means as a measure of precision. At the first stage, we derive the MSE when the covariance matrices are known. At the second stage, a method based on parametric bootstrap is proposed for bias correction and for prediction error that reflects the uncertainty when the unknown covariance is replaced by its suitable estimator.     

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.     

On implementation of a test for Kronecker product covariance structure for multivariate repeated measures data

Under the assumption of multivariate normality the likelihood ratio test is derived to test a hypothesis for Kronecker product structure on a covariance matrix in the context of multivariate repeated measures data. Although the proposed hypothesis testing can be computationally performed by indirect use of Proc Mixed of SAS, the Proc Mixed algorithm often fails to converge. We provide an alternative algorithm. The algorithm is illustrated with two real data sets. A simulation study is also conducted for the purpose of sample size consideration.     

Latent class logistic regression: application to marijuana use and attitudes among high school seniors

Summary.  Analysing the use of marijuana is challenging in part because there is no widely accepted single measure of individual use. Similarly, there is no single response variable that effectively captures attitudes toward its social and moral acceptability. One approach is to view the joint distribution of multiple use and attitude indicators as a mixture of latent classes. Pooling items from the annual 'Monitoring the future' surveys of American high school seniors from 1977 to 2001, we find that marijuana use and attitudes are well summarized by a four-class model. Secular trends in class prevalences over this period reveal major shifts in use and attitudes. Applying a multinomial logistic model to the latent response, we investigate how class membership relates to demographic and life style factors, political beliefs and religiosity over time. Inferences about the parameters of the latent class logistic model are obtained by a combination of maximum likelihood and Bayesian techniques.     

Separability tests for high-dimensional,low-sample size multivariate repeated measures data

Longitudinal imaging studies have moved to the forefront of medical research due to their ability to characterize spatio-temporal features of biological structures across the lifespan. Valid inference in longitudinal imaging requires enough flexibility of the covariance model to allow reasonable fidelity to the true pattern. On the other hand, the existence of computable estimates demands a parsimonious parameterization of the covariance structure. Separable (Kronecker product) covariance models provide one such parameterization in which the spatial and temporal covariances are modeled separately. However, evaluating the validity of this parameterization in high dimensions remains a challenge. Here we provide a scientifically informed approach to assessing the adequacy of separable (Kronecker product) covariance models when the number of observations is large relative to the number of independent sampling units (sample size). We address both the general case, in which unstructured matrices are considered for each covariance model, and the structured case, which assumes a particular structure for each model. For the structured case, we focus on the situation where the within-subject correlation is believed to decrease exponentially in time and space as is common in longitudinal imaging studies. However, the provided framework equally applies to all covariance patterns used within the more general multivariate repeated measures context. Our approach provides useful guidance for high dimension, low-sample size data that preclude using standard likelihood-based tests. Longitudinal medical imaging data of caudate morphology in schizophrenia illustrate the approaches appeal.     

Bayesian semi-parametric analysis of Poisson change-point regression models: application to policy-making in Cali,Colombia

A Poisson regression model with an offset assumes a constant baseline rate after accounting for measured covariates, which may lead to biased estimates of coefficients in an inhomogeneous Poisson process. To correctly estimate the effect of time-dependent covariates, we propose a Poisson change-point regression model with an offset that allows a time-varying baseline rate. When the non-constant pattern of a log baseline rate is modeled with a non-parametric step function, the resulting semi-parametric model involves a model component of varying dimensions and thus requires a sophisticated varying-dimensional inference to obtain the correct estimates of model parameters of a fixed dimension. To fit the proposed varying-dimensional model, we devise a state-of-the-art Markov chain Monte Carlo-type algorithm based on partial collapse. The proposed model and methods are used to investigate the association between the daily homicide rates in Cali, Colombia, and the policies that restrict the hours during which the legal sale of alcoholic beverages is permitted. While simultaneously identifying the latent changes in the baseline homicide rate which correspond to the incidence of sociopolitical events, we explore the effect of policies governing the sale of alcohol on homicide rates and seek a policy that balances the economic and cultural dependencies on alcohol sales to the health of the public.     

Addressing misclassification for binary data: probit and t-link regressions

Generalized linear models are addressed to describe the dependence of data on explanatory variables when the binary outcome is subject to misclassification. Both probit and t-link regressions for misclassified binary data under Bayesian methodology are proposed. The computational difficulties have been avoided by using data augmentation. The idea of using a data augmentation framework (with two types of latent variables) is exploited to derive efficient Gibbs sampling and expectation–maximization algorithms. Besides, this formulation has allowed to obtain the probit model as a particular case of the t-link model. Simulation examples are presented to illustrate the model performance when comparing with standard methods that do not consider misclassification. In order to show the potential of the proposed approaches, a real data problem arising when studying hearing loss caused by exposure to occupational noise is analysed.     

Bayesian inference for categorical data analysis

This article surveys Bayesian methods for categorical data analysis, with primary emphasis on contingency table analysis. Early innovations were proposed by Good (1953, 1956, 1965) for smoothing proportions in contingency tables and by Lindley (1964) for inference about odds ratios. These approaches primarily used conjugate beta and Dirichlet priors. Altham (1969, 1971) presented Bayesian analogs of small-sample frequentist tests for 2 x 2 tables using such priors. An alternative approach using normal priors for logits received considerable attention in the 1970s by Leonard and others (e.g., Leonard 1972). Adopted usually in a hierarchical form, the logit-normal approach allows greater flexibility and scope for generalization. The 1970s also saw considerable interest in loglinear modeling. The advent of modern computational methods since the mid-1980s has led to a growing literature on fully Bayesian analyses with models for categorical data, with main emphasis on generalized linear models such as logistic regression for binary and multi-category response variables.     

A segmented regression model for event history data: an application to the fertility patterns in Italy

We propose a segmented discrete-time model for the analysis of event history data in demographic research. Through a unified regression framework, the model provides estimates of the effects of explanatory variables and jointly accommodates flexibly non-proportional differences via segmented relationships. The main appeal relies on ready availability of parameters, changepoints, and slopes, which may provide meaningful and intuitive information on the topic. Furthermore, specific linear constraints on the slopes may also be set to investigate particular patterns. We investigate the intervals between cohabitation and first childbirth and from first to second childbirth using individual data for Italian women from the Second National Survey on Fertility. The model provides insights into dramatic decrease of fertility experienced in Italy, in that it detects a ‘common’ tendency in delaying the onset of childbearing for the more recent cohorts and a ‘specific’ postponement strictly depending on the educational level and age at cohabitation.     

EM algorithm-based likelihood estimation for a generalized Gompertz regression model in presence of survival data with long-term survivors: an application to uterine cervical cancer data

In this paper we develop a regression model for survival data in the presence of long-term survivors based on the generalized Gompertz distribution introduced by El-Gohary et al. [The generalized Gompertz distribution. Appl Math Model. 2013;37:13–24] in a defective version. This model includes as special case the Gompertz cure rate model proposed by Gieser et al. [Modelling cure rates using the Gompertz model with covariate information. Stat Med. 1998;17:831–839]. Next, an expectation maximization algorithm is then developed for determining the maximum likelihood estimates (MLEs) of the parameters of the model. In addition, we discuss the construction of confidence intervals for the parameters using the asymptotic distributions of the MLEs and the parametric bootstrap method, and assess their performance through a Monte Carlo simulation study. Finally, the proposed methodology was applied to a database on uterine cervical cancer.     

A spatial model for the needle losses of pine-trees in the forests of Baden-Württemberg: an application of Bayesian structured additive regression

Summary.  The data that are analysed are from a monitoring survey which was carried out in 1994 in the forests of Baden-Württemberg, a federal state in the south-western region of Germany. The survey is part of a large monitoring scheme that has been carried out since the 1980s at different spatial and temporal resolutions to observe the increase in forest damage. One indicator for tree vitality is tree defoliation, which is mainly caused by intrinsic factors, age and stand conditions, but also by biotic (e.g. insects) and abiotic stresses (e.g. industrial emissions). In the survey, needle loss of pine-trees and many potential covariates are recorded at about 580 grid points of a 4 km × 4 km grid. The aim is to identify a set of predictors for needle loss and to investigate the relationships between the needle loss and the predictors. The response variable needle loss is recorded as a percentage in 5% steps estimated by eye using binoculars and categorized into healthy trees (10% or less), intermediate trees (10–25%) and damaged trees (25% or more). We use a Bayesian cumulative threshold model with non-linear functions of continuous variables and a random effect for spatial heterogeneity. For both the non-linear functions and the spatial random effect we use Bayesian versions of P -splines as priors. Our method is novel in that it deals with several non-standard data requirements: the ordinal response variable (the categorized version of needle loss), non-linear effects of covariates, spatial heterogeneity and prediction with missing covariates. The model is a special case of models with a geoadditive or more generally structured additive predictor. Inference can be based on Markov chain Monte Carlo techniques or mixed model technology.