Longitudinal studies contain correlated data due to the repeated measurements on the same subject. The changing values of the time-dependent covariates and their association with the outcomes presents another source of correlation. Most methods used to analyze longitudinal data average the effects of time-dependent covariates on outcomes over time and provide a single regression coefficient per time-dependent covariate. This denies researchers the opportunity to follow the changing impact of time-dependent covariates on the outcomes. This dissertation addresses such issue through the use of partitioned regression coefficients in three different papers.

In the first paper, an alternative approach to the partitioned Generalized Method of Moments logistic regression model for longitudinal binary outcomes is presented. This method relies on Bayes estimators and is utilized when the partitioned Generalized Method of Moments model provides numerically unstable estimates of the regression coefficients. It is used to model obesity status in the Add Health study and cognitive impairment diagnosis in the National Alzheimer’s Coordination Center database.

The second paper develops a model that allows the joint modeling of two or more binary outcomes that provide an overall measure of a subject’s trait over time. The simultaneous modelling of all outcomes provides a complete picture of the overall measure of interest. This approach accounts for the correlation among and between the outcomes across time and the changing effects of time-dependent covariates on the outcomes. The model is used to analyze four outcomes measuring overall the quality of life in the Chinese Longitudinal Healthy Longevity Study.

The third paper presents an approach that allows for estimation of cross-sectional and lagged effects of the covariates on the outcome as well as the feedback of the response on future covariates. This is done in two-parts, in part-1, the effects of time-dependent covariates on the outcomes are estimated, then, in part-2, the outcome influences on future values of the covariates are measured. These model parameters are obtained through a Generalized Method of Moments procedure that uses valid moment conditions between the outcome and the covariates. Child morbidity in the Philippines and obesity status in the Add Health data are analyzed.

In the presence of correlation, generalized linear models cannot be employed to obtain regression parameter estimates. To appropriately address the extravariation due to correlation, methods to estimate and model the additional variation are investigated. A general form of the mean-variance relationship is proposed which incorporates the canonical parameter. The two variance parameters are estimated using generalized method of moments, negating the need for a distributional assumption. The mean-variance relation estimates are applied to clustered data and implemented in an adjusted generalized quasi-likelihood approach through an adjustment to the covariance matrix. In the presence of significant correlation in hierarchical structured data, the adjusted generalized quasi-likelihood model shows improved performance for random effect estimates. In addition, submodels to address deviation in skewness and kurtosis are provided to jointly model the mean, variance, skewness, and kurtosis. The additional models identify covariates influencing the third and fourth moments. A cutoff to trim the data is provided which improves parameter estimation and model fit. For each topic, findings are demonstrated through comprehensive simulation studies and numerical examples. Examples evaluated include data on children’s morbidity in the Philippines, adolescent health from the National Longitudinal Study of Adolescent to Adult Health, as well as proteomic assays for breast cancer screening.

Correlation is common in many types of data, including those collected through longitudinal studies or in a hierarchical structure. In the case of clustering, or repeated measurements, there is inherent correlation between observations within the same group, or between observations obtained on the same subject. Longitudinal studies also introduce association between the covariates and the outcomes across time. When multiple outcomes are of interest, association may exist between the various models. These correlations can lead to issues in model fitting and inference if not properly accounted for. This dissertation presents three papers discussing appropriate methods to properly consider different types of association. The first paper introduces an ANOVA based measure of intraclass correlation for three level hierarchical data with binary outcomes, and corresponding properties. This measure is useful for evaluating when the correlation due to clustering warrants a more complex model. This measure is used to investigate AIDS knowledge in a clustered study conducted in Bangladesh. The second paper develops the Partitioned generalized method of moments (Partitioned GMM) model for longitudinal studies. This model utilizes valid moment conditions to separately estimate the varying effects of each time-dependent covariate on the outcome over time using multiple coefficients. The model is fit to data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to investigate risk factors of childhood obesity. In the third paper, the Partitioned GMM model is extended to jointly estimate regression models for multiple outcomes of interest. Thus, this approach takes into account both the correlation between the multivariate outcomes, as well as the correlation due to time-dependency in longitudinal studies. The model utilizes an expanded weight matrix and objective function composed of valid moment conditions to simultaneously estimate optimal regression coefficients. This approach is applied to Add Health data to simultaneously study drivers of outcomes including smoking, social alcohol usage, and obesity in children.

Though the likelihood is a useful tool for obtaining estimates of regression parameters, it is not readily available in the fit of hierarchical binary data models. The correlated observations negate the opportunity to have a joint likelihood when fitting hierarchical logistic regression models. Through conditional likelihood, inferences for the regression and covariance parameters as well as the intraclass correlation coefficients are usually obtained. In those cases, I have resorted to use of Laplace approximation and large sample theory approach for point and interval estimates such as Wald-type confidence intervals and profile likelihood confidence intervals. These methods rely on distributional assumptions and large sample theory. However, when dealing with small hierarchical datasets they often result in severe bias or non-convergence. I present a generalized quasi-likelihood approach and a generalized method of moments approach; both do not rely on any distributional assumptions but only moments of response. As an alternative to the typical large sample theory approach, I present bootstrapping hierarchical logistic regression models which provides more accurate interval estimates for small binary hierarchical data. These models substitute computations as an alternative to the traditional Wald-type and profile likelihood confidence intervals. I use a latent variable approach with a new split bootstrap method for estimating intraclass correlation coefficients when analyzing binary data obtained from a three-level hierarchical structure. It is especially useful with small sample size and easily expanded to multilevel. Comparisons are made to existing approaches through both theoretical justification and simulation studies. Further, I demonstrate my findings through an analysis of three numerical examples, one based on cancer in remission data, one related to the China’s antibiotic abuse study, and a third related to teacher effectiveness in schools from a state of southwest US.

Value-added models (VAMs) are used by many states to assess contributions of individual teachers and schools to students' academic growth. The generalized persistence VAM, one of the most flexible in the literature, estimates the ``value added'' by individual teachers to their students' current and future test scores by employing a mixed model with a longitudinal database of test scores. There is concern, however, that missing values that are common in the longitudinal student scores can bias value-added assessments, especially when the models serve as a basis for personnel decisions -- such as promoting or dismissing teachers -- as they are being used in some states. Certain types of missing data require that the VAM be modeled jointly with the missingness process in order to obtain unbiased parameter estimates. This dissertation studies two problems. First, the flexibility and multimembership random effects structure of the generalized persistence model lead to computational challenges that have limited the model's availability. To this point, no methods have been developed for scalable maximum likelihood estimation of the model. An EM algorithm to compute maximum likelihood estimates efficiently is developed, making use of the sparse structure of the random effects and error covariance matrices. The algorithm is implemented in the package GPvam in R statistical software. Illustrations of the gains in computational efficiency achieved by the estimation procedure are given. Furthermore, to address the presence of potentially nonignorable missing data, a flexible correlated random effects model is developed that extends the generalized persistence model to jointly model the test scores and the missingness process, allowing the process to depend on both students and teachers. The joint model gives the ability to test the sensitivity of the VAM to the presence of nonignorable missing data. Estimation of the model is challenging due to the non-hierarchical dependence structure and the resulting intractable high-dimensional integrals. Maximum likelihood estimation of the model is performed using an EM algorithm with fully exponential Laplace approximations for the E step. The methods are illustrated with data from university calculus classes and with data from standardized test scores from an urban school district.