The first chapter proposes multifractal analysis to measure inhomogeneity of regularity of 1H-NMR spectrum using wavelet-based multifractal tools. The geometric summaries of multifractal spectrum are informative summaries, and as such employed to discriminate 1H-NMR spectra associated with different treatments. The methodology is applied to evaluate the effect of sulfur amino acids. The second part of this thesis provides essential materials for understanding engineering background of a nano-particle fabrication process. The third chapter introduces a constrained random effect model. Since there are certain combinations of process variables resulting to unproductive process outcomes, a logistic model is used to characterize such a process behavior. For the cases with productive outcomes a normal regression serves the second part of the model. Additionally, random-effects are included in both logistics and normal regression models to describe the potential spatial correlation among data. This chapter researches a way to approximate the likelihood function and to find estimates for maximizing the approximated likelihood. The last chapter presents a method to decide the sample size under multi-layer system. The multi-layer is a series of layers, which become smaller and smaller. Our focus is to decide the sample size in each layer. The sample size decision has several objectives, and the most important purpose is the sample size should be enough to give a right direction to the next layer. Specifically, the bottom layer, which is the smallest neighborhood around the optimum, should meet the tolerance requirement. Performing the hypothesis test of whether the next layer includes the optimum gives the required sample size.

<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)

本文主要在探討自變數存在有測量誤差時，邏輯式迴歸模型的估計問題，並設計實驗使得測量誤差能滿足遞減假設，進一步應用序貫分析方法，在給定水準下，建立一個信賴範圍。 當自變數存在有測量誤差時，通常會得到有偏誤的估計量，進而在做決策時會得到與無測量誤差所做出的決策不同。在本文中提出了一個遞減的測量誤差，使得滿足這樣的假設，可以證明估計量的強收斂，並證明與無測量誤差所得到的估計量相同的近似分配。相較於先前的假設，特別是證明大樣本的性質，新增加的樣本會有更小的測量誤差是更加合理的假設。我們同時設計了一個實驗來滿足所提出遞減誤差的條件，並利用序貫設計得到一個更省時也節省成本的處理方法。 一般的case-control實驗，自變數也會出現測量誤差，我們也證明了斜率估計量的強收斂與近似分配的性質，並提出一個二階段抽樣方法，計算出所需的樣本數及建立信賴區間。 / In this thesis, we focus on the estimate of unknown parameters, experimental designs and sequential methods in both prospective and retrospective logistic regression models when there are covariates measured with errors. The imprecise measurement of exposure happens very often in practice, for example, in retrospective epidemiology studies, that may due to either the difficulty or the cost of measuring. It is known that the imprecisely measured variables can result in biased coefficients estimation in a regression model and therefore, it may lead to an incorrect inference. Thus, it is an important issue if the effects of the variables are of primary interest. When considering a prospective logistic regression model, we derive asymptotic results for the estimators of the regression parameters when there are mismeasured covariates. If the measurement error satisfies certain assumptions, we show that the estimators follow the normal distribution with zero mean, asymptotically unbiased and asymptotically normally distributed. Contrary to the traditional assumption on measurement error, which is mainly used for proving large sample properties, we assume that the measurement error decays gradually at a certain rate as there is a new observation added to the model. This kind of assumption can be fulfilled when the usual replicate observation method is used to dilute the magnitude of measurement errors, and therefore, is also more useful in practical viewpoint. Moreover, the independence of measurement error and covariate is not required in our theorems. An experimental design with measurement error satisfying the required degenerating rate is introduced. In addition, this assumption allows us to employ sequential sampling, which is popular in clinical trials, to such a measurement error logistic regression model. It is clear that the sequential method cannot be applied based on the assumption that the measurement errors decay uniformly as sample size increasing as in the most of the literature. Therefore, a sequential estimation procedure based on MLEs and such moment conditions is proposed and can be shown to be asymptotical consistent and efficient. Case-control studies are broadly used in clinical trials and epidemiological studies. It can be showed that the odds ratio can be consistently estimated with some exposure variables based on logistic models (see Prentice and Pyke (1979)). The two-stage case-control sampling scheme is employed for a confidence region of slope coefficient beta. A necessary sample size is calculated by a given pre-determined level. Furthermore, we consider the measurement error in the covariates of a case-control retrospective logistic regression model. We also derive some asymptotic results of the maximum likelihood estimators (MLEs) of the regression coefficients under some moment conditions on measurement errors. Under such kinds of moment conditions of measurement errors, the MLEs can be shown to be strongly consistent, asymptotically unbiased and asymptotically normally distributed. Some simulation results of the proposed two-stage procedures are obtained. We also give some numerical studies and real data to verify the theoretical results in different measurement error scenarios.