Estimation with unbalanced panel data having covariate measurement error

Panel data with covariate measurement error appear frequently in various studies. Due to the sampling design and/or missing data, panel data are often unbalanced in the sense that panels have different sizes. For balanced panel data (i.e., panels having the same size), there exists a generalized method of moments (GMM) approach for adjusting covariate measurement error, which does not require additional validation data. This paper extends the GMM approach of adjusting covariate measurement error to unbalanced panel data. Two health related longitudinal surveys are used to illustrate the implementation of the proposed method.     

Analysis of longitudinal data with irregular, outcome-dependent follow-up

Summary.  A frequent problem in longitudinal studies is that subjects may miss scheduled visits or be assessed at self-selected points in time. As a result, observed outcome data may be highly unbalanced and the availability of the data may be directly related to the outcome measure and/or some auxiliary factors that are associated with the outcome. If the follow-up visit and outcome processes are correlated, then marginal regression analyses will produce biased estimates. Building on the work of Robins, Rotnitzky and Zhao, we propose a class of inverse intensity-of-visit process-weighted estimators in marginal regression models for longitudinal responses that may be observed in continuous time. This allows us to handle arbitrary patterns of missing data as embedded in a subject's visit process. We derive the large sample distribution for our inverse visit-intensity-weighted estimators and investigate their finite sample behaviour by simulation. Our approach is illustrated with a data set from a health services research study in which homeless people with mental illness were randomized to three different treatments and measures of homelessness (as percentage days homeless in the past 3 months) and other auxiliary factors were recorded at follow-up times that are not fixed by design.     

Semiparametric analysis of panel count data with correlated observation and follow-up times

This paper discusses regression analysis of panel count data that often arise in longitudinal studies concerning occurrence rates of certain recurrent events. Panel count data mean that each study subject is observed only at discrete time points rather than under continuous observation. Furthermore, both observation and follow-up times can vary from subject to subject and may be correlated with the recurrent events. For inference, we propose some shared frailty models and estimating equations are developed for estimation of regression parameters. The proposed estimates are consistent and have asymptotically a normal distribution. The finite sample properties of the proposed estimates are investigated through simulation and an illustrative example from a cancer study is provided.     

Joint modeling of multivariate longitudinal mixed measurements and time to event data using a Bayesian approach

In many longitudinal studies multiple characteristics of each individual, along with time to occurrence of an event of interest, are often collected. In such data set, some of the correlated characteristics may be discrete and some of them may be continuous. In this paper, a joint model for analysing multivariate longitudinal data comprising mixed continuous and ordinal responses and a time to event variable is proposed. We model the association structure between longitudinal mixed data and time to event data using a multivariate zero-mean Gaussian process. For modeling discrete ordinal data we assume a continuous latent variable follows the logistic distribution and for continuous data a Gaussian mixed effects model is used. For the event time variable, an accelerated failure time model is considered under different distributional assumptions. For parameter estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. The performance of the proposed methods is illustrated using some simulation studies. A real data set is also analyzed, where different model structures are used. Model comparison is performed using a variety of statistical criteria.     

The present status of confidence interval estimation on variance components in balanced and unbalanced random models

Much research has been conducted to develop confidence Intervals on linear combinations and ratios of variance components in balanced and unbalanced random models.This paper first presents confidence intervals on functions of variance components in balanced designs.These results assume that classical analysis of variance sums of squares are independent and have exact scaled chi-squared distributions.In unbalanced designs, either one or both of these assumptions are violated, and modifications to the balanced model intervals are required.We report results of some recent work that examines various modifications for some particular unbalanced designs.     

Estimating standard error of intra-class correlation coefficients up to three level unbalanced nested clinical trials

ABSTRACT

Very often researchers plan a balanced design for cluster randomization clinical trials in conducting medical research, but unavoidable circumstances lead to unbalanced data. By adopting three or more levels of nested designs, they usually ignore the higher level of nesting and consider only two levels, this situation leads to underestimation of variance at higher levels. While calculating the sample size for three-level nested designs, in order to achieve desired power, intra-class correlation coefficients (ICCs) at individual level as well as higher levels need to be considered and must be provided along with respective standard errors. In the present paper, the standard errors of analysis of variance (ANOVA) estimates of ICCs for three-level unbalanced nested design are derived. To conquer the strong appeal of distributional assumptions, balanced design, equality of variances between clusters and large sample, general expressions for standard errors of ICCs which can be deployed in unbalanced cluster randomization trials are postulated. The expressions are evaluated on real data as well as highly unbalanced simulated data.     

On the analysis of unbalanced two-level supersaturated designs via generalized linear models

Supersaturated designs (SSDs) are factorial designs in which the number of experimental runs is smaller than the number of parameters to be estimated in the model. While most of the literature on SSDs has focused on balanced designs, the construction and analysis of unbalanced designs has not been developed to a great extent. Recent studies discuss the possible advantages of relaxing the balance requirement in construction or data analysis of SSDs, and that unbalanced designs compare favorably to balanced designs for several optimality criteria and for the way in which the data are analyzed. Moreover, the effect analysis framework of unbalanced SSDs until now is restricted to the central assumption that experimental data come from a linear model. In this article, we consider unbalanced SSDs for data analysis under the assumption of generalized linear models (GLMs), revealing that unbalanced SSDs perform well despite the unbalance property. The examination of Type I and Type II error rates through an extensive simulation study indicates that the proposed method works satisfactorily.     

Quantile regression-based Bayesian semiparametric mixed-effects models for longitudinal data with non-normal,missing and mismeasured covariate

Quantile regression (QR) models have received increasing attention recently for longitudinal data analysis. When continuous responses appear non-centrality due to outliers and/or heavy-tails, commonly used mean regression models may fail to produce efficient estimators, whereas QR models may perform satisfactorily. In addition, longitudinal outcomes are often measured with non-normality, substantial errors and non-ignorable missing values. When carrying out statistical inference in such data setting, it is important to account for the simultaneous treatment of these data features; otherwise, erroneous or even misleading results may be produced. In the literature, there has been considerable interest in accommodating either one or some of these data features. However, there is relatively little work concerning all of them simultaneously. There is a need to fill up this gap as longitudinal data do often have these characteristics. Inferential procedure can be complicated dramatically when these data features arise in longitudinal response and covariate outcomes. In this article, our objective is to develop QR-based Bayesian semiparametric mixed-effects models to address the simultaneous impact of these multiple data features. The proposed models and method are applied to analyse a longitudinal data set arising from an AIDS clinical study. Simulation studies are conducted to assess the performance of the proposed method under various scenarios.     

Analysis of longitudinal data unbalanced over time

Summary.  The paper considers modelling, estimating and diagnostically verifying the response process generating longitudinal data, with emphasis on association between repeated meas-ures from unbalanced longitudinal designs. Our model is based on separate specifications of the moments for the mean, standard deviation and correlation, with different components possibly sharing common parameters. We propose a general class of correlation structures that comprise random effects, measurement errors and a serially correlated process. These three elements are combined via flexible time-varying weights, whereas the serial correlation can depend flexibly on the mean time and lag. When the measurement schedule is independent of the response process, our estimation procedure yields consistent and asymptotically normal estimates for the mean parameters even when the standard deviation and correlation are misspecified, and for the standard deviation parameters even when the correlation is misspecified. A generic diagnostic method is developed for verifying the models for the mean, standard deviation and, in particular, the correlation, which is applicable even when the data are severely unbalanced. The methodology is illustrated by an analysis of data from a longitudinal study that was designed to characterize pulmonary growth in girls.     

Accent on Teaching Materials: Notices and Reviews of Important Teaching Materials

In contrast to the analysis of variance of fully fixed or fully random component models, the analysis of variance of mixed models is fraught with potential pitfalls. It is fortunate that there are simple rules for the correct analysis of balanced data; in the case of unbalanced data there are no simple results. The potential pitfalls in the path of a correct analysis are well-known. Despite this, some computer packages still report incorrect results for the balanced model and some textbooks gloss over or ignore some of these pitfalls.     

Regression analysis of panel count data with covariate-dependent observation and censoring times

Panel count data often occur in a long-term study where the primary end point is the time to a specific event and each subject may experience multiple recurrences of this event. Furthermore, suppose that it is not feasible to keep subjects under observation continuously and the numbers of recurrences for each subject are only recorded at several distinct time points over the study period. Moreover, the set of observation times may vary from subject to subject. In this paper, regression methods, which are derived under simple semiparametric models, are proposed for the analysis of such longitudinal count data. Especially, we consider the situation when both observation and censoring times may depend on covariates. The new procedures are illustrated with data from a well-known cancer study.     

The impact of dichotomization in longitudinal data analysis: a simulation study

In this paper, a simulation study is conducted to systematically investigate the impact of dichotomizing longitudinal continuous outcome variables under various types of missing data mechanisms. Generalized linear models (GLM) with standard generalized estimating equations (GEE) are widely used for longitudinal outcome analysis, but these semi‐parametric approaches are only valid under missing data completely at random (MCAR). Alternatively, weighted GEE (WGEE) and multiple imputation GEE (MI‐GEE) were developed to ensure validity under missing at random (MAR). Using a simulation study, the performance of standard GEE, WGEE and MI‐GEE on incomplete longitudinal dichotomized outcome analysis is evaluated. For comparisons, likelihood‐based linear mixed effects models (LMM) are used for incomplete longitudinal original continuous outcome analysis. Focusing on dichotomized outcome analysis, MI‐GEE with original continuous missing data imputation procedure provides well controlled test sizes and more stable power estimates compared with any other GEE‐based approaches. It is also shown that dichotomizing longitudinal continuous outcome will result in substantial loss of power compared with LMM. Copyright © 2009 John Wiley & Sons, Ltd.     

A Comparison of Estimation Methods on the Coverage Probability of Satterthwaite Confidence Intervals for Assay Precision with Unbalanced Data

Construction of closed-form confidence intervals on linear combinations of variance components were developed generically for balanced data and studied mainly for one-way and two-way random effects analysis of variance models. The Satterthwaite approach is easily generalized to unbalanced data and modified to increase its coverage probability. They are applied on measures of assay precision in combination with (restricted) maximum likelihood and Henderson III Type 1 and 3 estimation. Simulations of interlaboratory studies with unbalanced data and with small sample sizes do not show superiority of any of the possible combinations of estimation methods and Satterthwaite approaches on three measures of assay precision. However, the modified Satterthwaite approach with Henderson III Type 3 estimation is often preferred above the other combinations.     

Performance of unit root tests in unbalanced panels: experimental evidence

This paper is about the validity of established panel unit root tests applied to panels in which the individual time series are of different lengths, a case often encountered in practice. Most of the tests considered work well under various types of cross-correlation which is true for both, their application in balanced as well as in unbalanced panels. A Monte Carlo study reveals that in unbalanced panels, procedures involving the computation of individual $p$ -values for each cross-section unit (or the combination thereof) are mostly superior to those relying on a pooled Dickey–Fuller regression framework. As the former are able to consider each unit separately, they do not require cutting back the “longer” time series so as to obtain the smallest “balanced” quadrangle which in turn means that no potentially valuable information is lost.     

Longitudinal covariate-adjusted response-adaptive randomized designs

Clinical trials often involve longitudinal data set which has two important characteristics: repeated and correlated measurements and time-varying covariates. In this paper, we propose a general framework of longitudinal covariate-adjusted response-adaptive (LCARA) randomization procedures. We study their properties under widely satisfied conditions. This design skews the allocation probabilities which depend on both patients' first observed covariates and sequentially estimated parameters based on the accrued longitudinal responses and covariates. The asymptotic properties of estimators for the unknown parameters and allocation proportions are established. The special case of binary treatment and continuous responses is studied in detail. Simulation studies and an analysis of the National Cooperative Gallstone Study (NCGS) data are carried out to illustrate the advantages of the proposed LCARA randomization procedure.     

A Bayesian model for measurement and misclassification errors alongside missing data,with an application to higher education participation in Australia

In this paper we consider the impact of both missing data and measurement errors on a longitudinal analysis of participation in higher education in Australia. We develop a general method for handling both discrete and continuous measurement errors that also allows for the incorporation of missing values and random effects in both binary and continuous response multilevel models. Measurement errors are allowed to be mutually dependent and their distribution may depend on further covariates. We show that our methodology works via two simple simulation studies. We then consider the impact of our measurement error assumptions on the analysis of the real data set.     

The random-effects proportional hazards model with grouped survival data: a comparison between the grouped continuous and continuation ratio versions

Summary.  When analysing grouped time survival data having a hierarchical structure it is often appropriate to assume a random-effects proportional hazards model for the latent continuous time and then to derive the corresponding grouped time model. There are two formally equivalent grouped time versions of the proportional hazards model obtained from different perspec-tives, known as the continuation ratio and the grouped continuous models. However, the two models require distinct estimation procedures and, more importantly, they differ substantially when extended to time-dependent covariates and/or non-proportional effects. The paper discusses these issues in the context of random-effects models, illustrating the main points with an application to a complex data set on job opportunities for a cohort of graduates.     

Semiparametric analysis of longitudinal data with informative observation times and censoring times

We focus on regression analysis of irregularly observed longitudinal data which often occur in medical follow-up studies and observational investigations. The model for such data involves two processes: a longitudinal response process of interest and an observation process controlling observation times. Restrictive models and questionable assumptions, such as Poisson assumption and independent censoring time assumption, were posed in previous works for analysing longitudinal data. In this paper, we propose a more general model together with a robust estimation approach for longitudinal data with informative observation times and censoring times, and the asymptotic normalities of the proposed estimators are established. Both simulation studies and real data application indicate that the proposed method is promising.     

Bayesian Longitudinal Data Analysis with Mixed Models and Thick-tailed Distributions using MCMC

Linear mixed effects models are frequently used to analyse longitudinal data, due to their flexibility in modelling the covariance structure between and within observations. Further, it is easy to deal with unbalanced data, either with respect to the number of observations per subject or per time period, and with varying time intervals between observations. In most applications of mixed models to biological sciences, a normal distribution is assumed both for the random effects and for the residuals. This, however, makes inferences vulnerable to the presence of outliers. Here, linear mixed models employing thick-tailed distributions for robust inferences in longitudinal data analysis are described. Specific distributions discussed include the Student-t, the slash and the contaminated normal. A Bayesian framework is adopted, and the Gibbs sampler and the Metropolis-Hastings algorithms are used to carry out the posterior analyses. An example with data on orthodontic distance growth in children is discussed to illustrate the methodology. Analyses based on either the Student-t distribution or on the usual Gaussian assumption are contrasted. The thick-tailed distributions provide an appealing robust alternative to the Gaussian process for modelling distributions of the random effects and of residuals in linear mixed models, and the MCMC implementation allows the computations to be performed in a flexible manner.     

医疗费用预测的贝叶斯多项式混合效应模型

医疗费用预测是健康保险费率厘定的前提和基础。对于多年期的医疗费用数据,通常使用线性混合效应模型对其进行拟合,但线性混合效应模型对非线性关系的纵向数据建模具有一定的局限性。本文对线性混合效应模型进行扩展,根据医疗费用数据中变量之间的非线性关系,建立了多项式混合效应模型,并将其应用于一组医疗费用数据进行实证研究。结果表明,多项式混合效应模型对住院医疗费用的拟合效果显著优于通常使用的线性混合模型,在医疗费用管理和健康保险的费率厘定中具有重要的应用价值。