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Longitudinal assessments are crucial in evaluating the disease state and trajectory in patients with neurodegenerative diseases. Neuropsychological outcomes measured over time often have a non-linear trajectory with autocorrelated residuals and a skewed distribution. We propose the adjusted local linear trend model, an extended state-space model in lieu of the commonly used linear mixed-effects model in modeling longitudinal neuropsychological outcomes. Our contributed model has the capability to utilize information from the stochasticity of the data while accounting for subject-specific trajectories with the inclusion of covariates and unequally spaced time intervals. The first step of model fitting involves a likelihood maximization step to estimate the unknown variances in the model before parsing these values into the Kalman filter and Kalman smoother recursive algorithms. Results from simulation studies showed that the adjusted local linear trend model is able to attain lower bias, lower standard errors, and high power, particularly in short longitudinal studies with equally spaced time intervals, as compared to the linear mixed-effects model. The adjusted local linear trend model also outperforms the linear mixed-effects model when data is missing completely at random, missing at random, and, in certain cases, even in data with missing not at random. [ABSTRACT FROM AUTHOR]

Generalised estimating equations with the sandwich standard-error estimator provide a promising method of analysis for stepped wedge cluster randomised trials. However, they have inflated type-one error when used with a small number of clusters, which is common for stepped wedge cluster randomised trials. We present a large simulation study of binary outcomes comparing bias-corrected standard errors from Fay and Graubard; Mancl and DeRouen; Kauermann and Carroll; Morel, Bokossa, and Neerchal; and Mackinnon and White with an independent and exchangeable working correlation matrix. We constructed 95% confidence intervals using a t -distribution with degrees of freedom including clusters minus parameters (DFC-P), cluster periods minus parameters, and estimators from Fay and Graubard (DFFG), and Pan and Wall. Fay and Graubard and an approximation to Kauermann and Carroll (with simpler matrix inversion) were unbiased in a wide range of scenarios with an independent working correlation matrix and more than 12 clusters. They gave confidence intervals with close to 95% coverage with DFFG with 12 or more clusters, and DFC-P with 18 or more clusters. Both standard errors were conservative with fewer clusters. With an exchangeable working correlation matrix, approximated Kauermann and Carroll and Fay and Graubard had a small degree of under-coverage. [ABSTRACT FROM AUTHOR]

RNA sequencing data have been abundantly generated in biomedical research for biomarker discovery and other studies. Such data at the exon level are usually heavily tailed and correlated. Conventional statistical tests based on the mean or median difference for differential expression likely suffer from low power when the between-group difference occurs mostly in the upper or lower tail of the distribution of gene expression. We propose a tail-based test to make comparisons between groups in terms of a specific distribution area rather than a single location. The proposed test, which is derived from quantile regression, adjusts for covariates and accounts for within-sample dependence among the exons through a specified correlation structure. Through Monte Carlo simulation studies, we show that the proposed test is generally more powerful and robust in detecting differential expression than commonly used tests based on the mean or a single quantile. An application to TCGA lung adenocarcinoma data demonstrates the promise of the proposed method in terms of biomarker discovery. [ABSTRACT FROM AUTHOR]

Perfusion computed tomography is an emerging functional imaging modality that uses physiological models to quantify characteristics pertaining to the passage of fluid through blood vessels. Perfusion characteristics provide physiological correlates for neovascularization induced by tumor angiogenesis and thus a quantitative basis for cancer detection, prognostication, and treatment monitoring. We consider a liver cancer study where patients underwent a dynamic computed tomography protocol to enable evaluation of multiple perfusion characteristics derived from interrogating the time-attenuation of the concentration of the intravenously administered contrast medium. The objective is to determine the effectiveness of using perfusion characteristics to identify and discriminate between regions of liver that contain malignant tissues from normal tissue. Each patient contributes multiple regions of interest which are spatially correlated due to the shared vasculature. We propose a multivariate functional data model to disclose the correlation over time and space as well as the correlation among multiple perfusion characteristics. We further propose a simultaneous classification approach that utilizes all the correlation information to predict class assignments for collections of regions. The proposed method outperforms conventional classification approaches in the presence of strong spatial correlation. The method offers maximal relative improvement in the presence of temporal sparsity wherein measurements are obtainable at only a few time points. [ABSTRACT FROM AUTHOR]

Longitudinal studies of rare events such as cervical high-grade lesions or colorectal polyps that can recur often involve correlated binary data. Risk factor for these events cannot be reliably examined using conventional statistical methods. For example, logistic regression models that incorporate generalized estimating equations often fail to converge or provide inaccurate results when analyzing data of this type. Although exact methods have been reported, they are complex and computationally difficult. The current paper proposes a mathematically straightforward and easy-to-use two-step approach involving (i) an additive model to measure associations between a rare or uncommon correlated binary event and potential risk factors and (ii) a permutation test to estimate the statistical significance of these associations. Simulation studies showed that the proposed method reliably tests and accurately estimates the associations of exposure with correlated binary rare events. This method was then applied to a longitudinal study of human leukocyte antigen (HLA) genotype and risk of cervical high grade squamous intraepithelial lesions (HSIL) among HIV-infected and HIV-uninfected women. Results showed statistically significant associations of two HLA alleles among HIV-negative but not HIV-positive women, suggesting that immune status may modify the HLA and cervical HSIL association. Overall, the proposed method avoids model nonconvergence problems and provides a computationally simple, accurate, and powerful approach for the analysis of risk factor associations with rare/uncommon correlated binary events. [ABSTRACT FROM AUTHOR]

In some biomedical studies, biomarkers are measured repeatedly along some spatial structure or over time and are subject to measurement error. In these studies, it is often of interest to evaluate associations between a clinical endpoint and these biomarkers (also known as functional biomarkers). There are potentially two levels of correlation in such data, namely, between repeated measurements of a biomarker from the same subject and between multiple biomarkers from the same subject; none of the existing methods accounts for correlation between multiple functional biomarkers. We propose a Bayesian approach to model a clinical outcome of interest (e.g. risk for colorectal cancer) in the presence of multiple functional biomarkers while accounting for potential correlation. Our simulations show that the proposed approach achieves good performance in finite samples under various settings. In the presence of substantial or moderate correlation, the proposed approach outperforms an existing approach that does not account for correlation. The proposed approach is applied to a study of biomarkers of risk for colorectal neoplasms and our results show that the risk for colorectal cancer is associated with two functional biomarkers, APC and TGF-α, in particular, with their values in the region between the proliferating and differentiating zones of colorectal crypts. [ABSTRACT FROM AUTHOR]

This article reviews the challenges and opportunities that oral health research may offer to a statistician. To illustrate this, we focus on the Signal Tandmobiel® study, a longitudinal oral health survey that triggered many statistical explorations and developments over the last two decades. For example, non-standard distributions are more the rule than the exception in oral health research. In addition, often measurement error problems need to be addressed. The hierarchical structure of the oral health data also poses non-standard challenges. For instance, caries experience in the mouth is spatially correlated with, however, a specific metric defining the distance between two occurrences. In addition, since caries experience in the context of an epidemiological study is only measured at intervals, analysis of survival involves interval-censoring. Finally, when analyzing a realistic data set in oral health, all the above issues may have to be dealt with simultaneously. [ABSTRACT FROM AUTHOR]

Several statistical methods are nowadays available for the analysis of gene expression data recorded through microarray technology. In this article, we take a closer look at several Gaussian mixture models which have recently been proposed to model gene expression data. It can be shown that these are special cases of a more general model, called the mixture of structural equation models (mixture of SEMs), which has been developed in psychometrics. This model combines mixture modelling and SEMs by assuming that component-specific means and variances are subject to a SEM. The connection with SEM is useful for at least two reasons: (1) it shows the basic assumptions of existing methods more explicitly and (2) it helps in straightforward development of alternative mixture models for gene expression data with alternative mean/covariance structures. Different specifications of mixture of SEMs for clustering gene expression data are illustrated using two benchmark datasets. [ABSTRACT FROM AUTHOR]

We propose a method for reducing the error of the prediction of a quantity of interest when the outcome has missing values that are suspected to be nonignorable and the data are correlated in space. We develop a maximum likelihood approach for the parameter estimation of semi-parametric regressions in a mixed model framework. We apply the proposed method to phytoplankton data collected at fixed stations in the Chesapeake Bay, for which chlorophyll data coming from remote sensing are available. A simulation study is also performed. The availability of a variable correlated to the response allows us to achieve a substantial reduction of the prediction error of the expected value of the smoother, without having to specify a nonignorable model. [ABSTRACT FROM AUTHOR]

Although repeated tooth-surface-specific information is commonly collected during a longitudinal caries clinical trial, traditional methods often make limited use of the repeated measures. Newer methods of analysis, such as methods based on time-to-event and methods for longitudinal or clustered data, have the potential to increase the efficiency of the statistical analysis. We compare a range of analytical methods from the traditional analysis based only on the number of caries onsets to newer methods that incorporate time at risk and surface-specific information, such as Poisson regression methods for clustered data, with respect to the efficiency of treatment comparisons. Under most circumstances, the greatest gain in efficiency associated with time-to-event methods will be due to the ability of subjects to contribute caries onsets to the analysis until they are lost from the study. Incorporating the number of surfaces at risk, the surface time at risk, and surface-specific characteristics will typically produce only a modest gain in efficiency. [ABSTRACT FROM AUTHOR]

In the past 10 to 12 years, there have been several statistical issues identified in periodontal research which require and have generated non-standard or new statistical approaches. The purpose of this paper is to give an overview of these issues and approaches. Three general categories of issues are described: (i) statistical methods for detecting when disease progression occurs, and biological theories and corresponding statistical models which attempt to describe how the disease progresses; (ii) design issues in studies of therapeutic efficacy; and (iii) analytic issues arising from periodontal data analysis. [ABSTRACT FROM AUTHOR]