The generalized linear models (GLM) lately received a lot of attention in modelling the insurance data. However, the violation of assumptions about the independence of underlying data set often causes problems and misinterpretation of achieved results. The need for more exible instruments has been spoken out and consequently various proposals have been made. This thesis deals with GLM based techniques enabling to handle correlated data sets. The usage have been made of generalized linear mixed models (GLMM) and generalized estimating equations (GEE). The main aim of this thesis is to provide a solid statistical background and perform a practical application to demonstrate and compare features of various models. Powered by TCPDF (www.tcpdf.org)

在實務上，複選題分析一直處於觀察樣本情形的階段；至於進行檢定以推估母體情形的過程，則幾乎沒有人考慮到。就算曾經試圖想作類似檢定，卻也常常找不到可供參考的文獻或是使用了不適當的分析方法。 本研究的主要目的在於探討各式各樣離散型態相關資料的分析方法，其中亦包含許多複選題的分析方法。幾乎每個方法皆附上範例來說明程式撰寫及分析過程，希望對有此需求的人能有所幫助。 / Problems with multiple responses are usually analyzed by observing only the sample proportions. People don't bother to make any inferences based on the sample information mostly because they do not know how to do it. Even for those who do go beyond the stage of descriptive statistics might not work it out correctly. In the study, we review statistical methods for analyzing dependent proportions, including multiple responses. Almost every method is supplemented with an example which explains the way a related SAS program is written and the way the output is analyzed and explained. We hope that the results presented here will be helpful to those who are engaged in any analysis of multiple responses.

Longitudinal assessments are crucial in evaluating the disease state and trajectory in patients of neurodegenerative diseases. Neuropsychological outcomes measured over time often have a non-linear trajectory with autocorrelated residuals and skewed distributions. Due to these issues, statistical analysis and interpretation involving longitudinal cognitive outcomes can be a difficult and controversial task, thus hindering most convenient transformations (e.g. logarithmic) to avoid the assumption violations of common statistical modelling techniques. We propose the Adjusted Local Linear Trend (ALLT) model, an extended state space model in lieu of the commonly-used linear mixed-effects model (LMEM) 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 ALLT 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 LMEM. The ALLT model also outperforms the LMEM when data is missing completely at random (MCAR), missing at random (MAR) and, in certain cases, even in data with missing not at random (MNAR). In terms of model selection, likelihood-based inference is applicable for the ALLT model. Although a Chi-Square distribution with k degrees of freedom, where k is the number of parameter lost during estimation, was not the asymptotic distribution in the case of ALLT, we were able to derive an asymptotic distribution approximation of the likelihood ratio test statistics using the power transformation method for the utility of a Gaussian distribution to facilitate model selections for ALLT. In light of these findings, we believe that our proposed model will shed light into longitudinal data analysis not only in the neuropsychological data realm but also on a broader scale for statistical analysis of longitudinal data. / 2023-10-05T00:00:00Z

Genetic association studies have successfully identified many genetic markers associated with complex human diseases and related quantitative traits. However, for most complex diseases and quantitative traits, all associated genetic markers identified to date only explain a small proportion of heritability. Thus, exploring the unexplained heritability in these traits will help us discover novel genetic determinants for these traits and better understand disease etiology and pathophysiology. Due to limited sample size, a single cohort study may not have sufficient power to identify novel genetic association with a small effect size, and meta-analysis approaches have been proposed and applied to combine results from multiple cohorts in large consortia, increasing the sample size and statistical power. Rare genetic variants and gene by environment interaction may both play a role in genetic association studies. In this dissertation, we develop statistical methods in meta-analysis, rare genetic variants analysis and gene by environment interaction analysis, conduct extensive simulation studies, and apply these methods in real data examples. First, we develop a method of moments estimator for the between-study covariance matrix in random effects model multivariate meta-analysis. Our estimator is the first such estimator in matrix form, and holds the invariance property to linear transformations. It has similar performance with existing methods in simulation studies and real data analysis. Next, we extend the Sequence Kernel Association Test (SKAT), a rare genetic variants analysis approach for unrelated individuals, to be applicable in family samples for quantitative traits. The extension is necessary, as the original test has inflated type I error when directly applied to related individuals, and selecting an unrelated subset from family samples reduces the sample size and power. Finally, we derive methods for rare genetic variants analysis in detecting gene by environment interaction on quantitative traits, in the context of univariate test on the interaction term parameter. We develop statistical tests in the settings of both burden test and SKAT, for both unrelated and related individuals. Our methods are relevant to genetic association studies, and we hope that they can facilitate research in this field and beyond.

O objetivo principal deste trabalho é introduzir os modelos log-Birnbaum-Saunders mistos (log-BS mistos) e estender os resultados para os modelos log-Birnbaum-Saunders t-Student mistos (log-BS-t mistos). Os modelos log-BS são bastante conhecidos desde o trabalho de Rieck e Nedelman (1991) e particularmente receberam uma grande atenção nos últimos 10 anos com vários trabalhos publicados em periódicos internacionais. Contudo, o enfoque desses trabalhos tem sido em modelos log-BS ou log-BS generalizados com efeitos fixos, não havendo muita atenção para modelos com efeitos aleatórios. Inicialmente, apresentamos no trabalho uma revisão das distribuições Birnbaum-Saunders e Birnbaum-Saunders generalizada (BSG) e em seguida discutimos os modelos log-BS e log-BS-t com efeitos fixos, para os quais revisamos alguns resultados de estimação e diagnóstico. Os modelos log-BS mistos são então apresentados precedidos de uma revisão dos métodos de quadratura de Gauss Hermite (QGH). Embora a estimação dos parâmetros nos modelos log-BS mistos seja efetuada através do procedimento Proc NLMIXED do SAS (Littell et al, 1996), aplicamos o método de quadratura não adaptativa a fim de obtermos aproximações para o logaritmo da função de verossimilhança do modelo log-BS de intercepto aleatório. Com essas aproximações derivamos as funções escore e a matriz hessiana, além das curvaturas normais de influência local (Cook, 1986) para alguns esquemas de perturbação usuais. Os mesmos procedimentos são aplicados para os modelos log-BS-t de intercepto aleatório. Discussões sobre a predição dos efeitos aleatórios, teste para o componente de variância dos modelos com intercepto aleatório e análises de resíduos são também apresentados. Finalmente, comparamos os ajustes de modelos log-BS e log-BS mistos a um conjunto de dados reais. Métodos de diagnóstico são utilizados na comparação dos modelos ajustados. / The aim of this work is to introduce the log-Birnbaum-Saunders mixed models (log-BS mixed models) and to extend the results to log-Birnbaum-Saunders Student-t mixed models (log-BS-t mixed models). The log-BS models are well-known since the work by Rieck and Nedelman (1991) and particularly have received great attention in the last 10 years with various published papers in international journals. However, the emphasis given in such works has been in fixed-effects models with few attention given to random-effects models. Firstly, we present in this work a review on Birnbaum-Saunders and generalized Birnbaum-Saunders distributions and so we discuss log-BS and log-BS-t fixed-effects models for which some results on estimation and diagnostic are presented. Then, we introduce the log-BS mixed models preceded by a review on Gauss-Hermite quadrature. Although the parameter estimation of the marginal log-BS and log-BS-t mixed models are performed in the procedure NLMIXED of SAS (Littell et al., 1996), we apply the quadrature methods in order to obtain approximations for the likelihood function of the log-BS and log-BS-t random intercept models. These approximations are used to derive the respective score functions, observed information matrices as well as the normal curvature of local influence (Cook, 1986) under some usual perturbation schemes. Discussions on the prediction of the random effects, variance component tests and residual analysis are also given. Finally, we compare the fits of log-BS and log-BS-t mixed models to a real data set. Diagnostic methods are used in the comparisons.

O objetivo principal deste trabalho é introduzir os modelos log-Birnbaum-Saunders mistos (log-BS mistos) e estender os resultados para os modelos log-Birnbaum-Saunders t-Student mistos (log-BS-t mistos). Os modelos log-BS são bastante conhecidos desde o trabalho de Rieck e Nedelman (1991) e particularmente receberam uma grande atenção nos últimos 10 anos com vários trabalhos publicados em periódicos internacionais. Contudo, o enfoque desses trabalhos tem sido em modelos log-BS ou log-BS generalizados com efeitos fixos, não havendo muita atenção para modelos com efeitos aleatórios. Inicialmente, apresentamos no trabalho uma revisão das distribuições Birnbaum-Saunders e Birnbaum-Saunders generalizada (BSG) e em seguida discutimos os modelos log-BS e log-BS-t com efeitos fixos, para os quais revisamos alguns resultados de estimação e diagnóstico. Os modelos log-BS mistos são então apresentados precedidos de uma revisão dos métodos de quadratura de Gauss Hermite (QGH). Embora a estimação dos parâmetros nos modelos log-BS mistos seja efetuada através do procedimento Proc NLMIXED do SAS (Littell et al, 1996), aplicamos o método de quadratura não adaptativa a fim de obtermos aproximações para o logaritmo da função de verossimilhança do modelo log-BS de intercepto aleatório. Com essas aproximações derivamos as funções escore e a matriz hessiana, além das curvaturas normais de influência local (Cook, 1986) para alguns esquemas de perturbação usuais. Os mesmos procedimentos são aplicados para os modelos log-BS-t de intercepto aleatório. Discussões sobre a predição dos efeitos aleatórios, teste para o componente de variância dos modelos com intercepto aleatório e análises de resíduos são também apresentados. Finalmente, comparamos os ajustes de modelos log-BS e log-BS mistos a um conjunto de dados reais. Métodos de diagnóstico são utilizados na comparação dos modelos ajustados. / The aim of this work is to introduce the log-Birnbaum-Saunders mixed models (log-BS mixed models) and to extend the results to log-Birnbaum-Saunders Student-t mixed models (log-BS-t mixed models). The log-BS models are well-known since the work by Rieck and Nedelman (1991) and particularly have received great attention in the last 10 years with various published papers in international journals. However, the emphasis given in such works has been in fixed-effects models with few attention given to random-effects models. Firstly, we present in this work a review on Birnbaum-Saunders and generalized Birnbaum-Saunders distributions and so we discuss log-BS and log-BS-t fixed-effects models for which some results on estimation and diagnostic are presented. Then, we introduce the log-BS mixed models preceded by a review on Gauss-Hermite quadrature. Although the parameter estimation of the marginal log-BS and log-BS-t mixed models are performed in the procedure NLMIXED of SAS (Littell et al., 1996), we apply the quadrature methods in order to obtain approximations for the likelihood function of the log-BS and log-BS-t random intercept models. These approximations are used to derive the respective score functions, observed information matrices as well as the normal curvature of local influence (Cook, 1986) under some usual perturbation schemes. Discussions on the prediction of the random effects, variance component tests and residual analysis are also given. Finally, we compare the fits of log-BS and log-BS-t mixed models to a real data set. Diagnostic methods are used in the comparisons.

In this thesis, we first go through classical results from the field of credibility theory. One of the most well-known models in the field is the Büuhlmann-Straub model. The model is relatively straightforward to apply in practice and is widely used. A major advantage of the model is its simplicity and intuitive dependency on its model parameters. From our perspective, the main drawback is the assumption regarding uncorrelated data. We show that the correlation can be used to cancel observational noise and therefore obtain more accurate estimators. This leads to an extended credibility formula that contains the Bühlmann-Straub model as a special case. This comes at the cost of introducing singularities which may cause the estimator to behave unexpectedly under certain circumstances. Further research is needed to better understand how often the circumstances are met in practice and if transforming the optimal weights could be a way forward in such cases. Finally, a simulation study based on real-world data shows that the proposed model outperforms the Bühlmann-Straub model.

<p>Correlated data with complex association structures arise from longitudinal studies and cluster randomized trials. However, some methodological challenges in the design and analysis of such studies or trials have not been overcome. In this thesis, we address three of the challenges: 1) <em>Power analysis for population based longitudinal study investigating gene-environment interaction effects on chronic disease:</em> For longitudinal studies with interest in investigating the gene-environment interaction in disease susceptibility and progression, rigorous statistical power estimation is crucial to ensure that such studies are scientifically useful and cost-effective since human genome epidemiology is expensive. However conventional sample size calculations for longitudinal study can seriously overestimate the statistical power due to overlooking the measurement error, unmeasured etiological determinants, and competing events that can impede the occurrence of the event of interest. 2) <em>Comparing the performance of different multiple imputation strategies for missing binary outcomes in cluster randomized trials</em>: Though researchers have proposed various strategies to handle missing binary outcome in cluster randomized trials (CRTs), comprehensive guidelines on the selection of the most appropriate or optimal strategy are not available in the literature. 3) <em>Comparison of population-averaged and cluster-specific models for the analysis of cluster randomized trials with missing binary outcome</em>: Both population-averaged and cluster-specific models are commonly used for analyzing binary outcomes in CRTs. However, little attention has been paid to their accuracy and efficiency when analyzing data with missing outcomes. The objective of this thesis is to provide researchers recommendations and guidance for future research in handling the above issues.</p> / Doctor of Philosophy (PhD)

Semiparametric modeling is a hybrid of the parametric and nonparametric modelings where some function forms are known and others are unknown. In this dissertation, we have made several contributions to semiparametric modeling based on the single index model related to the following three topics: the first is to propose a model for detecting change points simultaneously with estimating the unknown function; the second is to develop two models for spatially correlated data; and the third is to further develop two models for spatially-temporally correlated data. To address the first topic, we propose a unified approach in its ability to simultaneously estimate the nonlinear relationship and change points. We propose a single index change point model as our unified approach by adjusting for several other covariates. We nonparametrically estimate the unknown function using kernel smoothing and also provide a permutation based testing procedure to detect multiple change points. We show the asymptotic properties of the permutation testing based procedure. The advantage of our approach is demonstrated using the mortality data of Seoul, Korea from January, 2000 to December, 2007. On the second topic, we propose two semiparametric single index models for spatially correlated data. One additively separates the nonparametric function and spatially correlated random effects, while the other does not separate the nonparametric function and spatially correlated random effects. We estimate these two models using two algorithms based on Markov Chain Expectation Maximization algorithm. Our approaches are compared using simulations, suggesting that the semiparametric single index nonadditive model provides more accurate estimates of spatial correlation. The advantage of our approach is demonstrated using the mortality data of six cities, Korea from January, 2000 to December, 2007. The third topic involves proposing two semiparametric single index models for spatially and temporally correlated data. Our first model has the nonparametric function which can separate from spatially and temporally correlated random effects. We refer it to "semiparametric spatio-temporal separable single index model (SSTS-SIM)", while the second model does not separate the nonparametric function from spatially correlated random effects but separates the time random effects. We refer our second model to "semiparametric nonseparable single index model (SSTN-SIM)". Two algorithms based on Markov Chain Expectation Maximization algorithm are introduced to simultaneously estimate parameters, spatial effects, and times effects. The proposed models are then applied to the mortality data of six major cities in Korea. Our results suggest that SSTN-SIM is more flexible than SSTS-SIM because it can estimate various nonparametric functions while SSTS-SIM enforces the similar nonparametric curves. SSTN-SIM also provides better estimation and prediction. / Ph. D.

In today's competitive business and industrial environment, it is becoming more crucial than ever to assess precisely process losses due to non-compliance to customer specifications. To assess these losses, industry is extensively using Process Capability Indices for performance evaluation of their processes. Determination of the performance capability of a stable process using the standard process capability indices such as and requires that the underlying quality characteristics data follow a normal distribution. However it is an undisputed fact that real processes very often produce non-normal quality characteristics data and also these quality characteristics are very often correlated with each other. For such non-normal and correlated multivariate quality characteristics, application of standard capability measures using conventional methods can lead to erroneous results. The research undertaken in this PhD thesis presents several capability assessment methods to estimate more precisely and accurately process performances based on univariate as well as multivariate quality characteristics. The proposed capability assessment methods also take into account the correlation, variance and covariance as well as non-normality issues of the quality characteristics data. A comprehensive review of the existing univariate and multivariate PCI estimations have been provided. We have proposed fitting Burr XII distributions to continuous positively skewed data. The proportion of nonconformance (PNC) for process measurements is then obtained by using Burr XII distribution, rather than through the traditional practice of fitting different distributions to real data. Maximum likelihood method is deployed to improve the accuracy of PCI based on Burr XII distribution. Different numerical methods such as Evolutionary and Simulated Annealing algorithms are deployed to estimate parameters of the fitted Burr XII distribution. We have also introduced new transformation method called Best Root Transformation approach to transform non-normal data to normal data and then apply the traditional PCI method to estimate the proportion of non-conforming data. Another approach which has been introduced in this thesis is to deploy Burr XII cumulative density function for PCI estimation using Cumulative Density Function technique. The proposed approach is in contrast to the approach adopted in the research literature i.e. use of best-fitting density function from known distributions to non-normal data for PCI estimation. The proposed CDF technique has also been extended to estimate process capability for bivariate non-normal quality characteristics data. A new multivariate capability index based on the Generalized Covariance Distance (GCD) is proposed. This novel approach reduces the dimension of multivariate data by transforming correlated variables into univariate ones through a metric function. This approach evaluates process capability for correlated non-normal multivariate quality characteristics. Unlike the Geometric Distance approach, GCD approach takes into account the scaling effect of the variance-covariance matrix and produces a Covariance Distance variable that is based on the Mahanalobis distance. Another novelty introduced in this research is to approximate the distribution of these distances by a Burr XII distribution and then estimate its parameters using numerical search algorithm. It is demonstrates that the proportion of nonconformance (PNC) using proposed method is very close to the actual PNC value.