abstract: Researchers who conduct longitudinal studies are inherently interested in studying individual and population changes over time (e.g., mathematics achievement, subjective well-being). To answer such research questions, models of change (e.g., growth models) make the assumption of longitudinal measurement invariance. In many applied situations, key constructs are measured by a collection of ordered-categorical indicators (e.g., Likert scale items). To evaluate longitudinal measurement invariance with ordered-categorical indicators, a set of hierarchical models can be sequentially tested and compared. If the statistical tests of measurement invariance fail to be supported for one of the models, it is useful to have a method with which to gauge the practical significance of the differences in measurement model parameters over time. Drawing on studies of latent growth models and second-order latent growth models with continuous indicators (e.g., Kim & Willson, 2014a; 2014b; Leite, 2007; Wirth, 2008), this study examined the performance of a potential sensitivity analysis to gauge the practical significance of violations of longitudinal measurement invariance for ordered-categorical indicators using second-order latent growth models. The change in the estimate of the second-order growth parameters following the addition of an incorrect level of measurement invariance constraints at the first-order level was used as an effect size for measurement non-invariance. This study investigated how sensitive the proposed sensitivity analysis was to different locations of non-invariance (i.e., non-invariance in the factor loadings, the thresholds, and the unique factor variances) given a sufficient sample size. This study also examined whether the sensitivity of the proposed sensitivity analysis depended on a number of other factors including the magnitude of non-invariance, the number of non-invariant indicators, the number of non-invariant occasions, and the number of response categories in the indicators. / Dissertation/Thesis / Doctoral Dissertation Psychology 2016

Pharmacodynamic processes and disease progression are increasingly characterized with pharmacometric models. However, modelling options for discrete-type responses remain limited, although these response variables are commonly encountered clinical endpoints. Types of data defined as discrete data are generally ordinal, e.g. symptom severity, count, i.e. event frequency, and time-to-event, i.e. event occurrence. Underlying assumptions accompanying discrete data models need investigation and possibly adaptations in order to expand their use. Moreover, because these models are highly non-linear, estimation with linearization-based maximum likelihood methods may be biased. The aim of this thesis was to explore pharmacometric methods and novel models for discrete data through (i) the investigation of benefits of treating discrete data with different modelling approaches, (ii) evaluations of the performance of several estimation methods for discrete models, and (iii) the development of novel models for the handling of complex discrete data recorded during (pre-)clinical studies. A simulation study indicated that approaches such as a truncated Poisson model and a logit-transformed continuous model were adequate for treating ordinal data ranked on a 0-10 scale. Features that handled serial correlation and underdispersion were developed for the models to subsequently fit real pain scores. The performance of nine estimation methods was studied for dose-response continuous models. Other types of serially correlated count models were studied for the analysis of overdispersed data represented by the number of epilepsy seizures per day. For these types of models, the commonly used Laplace estimation method presented a bias, whereas the adaptive Gaussian quadrature method did not. Count models were also compared to repeated time-to-event models when the exact time of gastroesophageal symptom occurrence was known. Two new model structures handling repeated time-to-categorical events, i.e. events with an ordinal severity aspect, were introduced. Laplace and two expectation-maximisation estimation methods were found to be performing well for frequent repeated time-to-event models. In conclusion, this thesis presents approaches, estimation methods, and diagnostics adapted for treating discrete data. Novel models and diagnostics were developed when lacking and applied to biological observations.

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