A comparison of semi-parametric statistical modeling approaches to dynamic classification of irregularly and sparsely sampled curves

This study describes and compares the performance of several semi-parametric statistical modeling approaches to dynamically classify subjects into two groups, based on an irregularly and sparsely sampled curve. The motivating example of this study is the diagnosis of a complication following cardiac surgery, based on repeated measures of a single cardiac biomarker where early detection enables prompt intervention by clinicians. We first simulate data to compare the dynamic predictive performance over time for growth charts, conditional growth charts, a varying-coefficient model, a generalized functional linear model and longitudinal discriminant analysis. Our results demonstrate that functional regression approaches that implicitly incorporate historic information through random effects, provide superior discriminative ability compared to approaches that do not take historic information into account or explicitly model historic information through autoregressive terms. Semi-parametric modeling approaches show a benefit in terms of dynamic discriminative ability compared to the clinical practice of using a fixed threshold on the raw measured value. Under high degrees of sparsity the functional regression approaches are less advantageous compared to varying-coefficient models or quantile regression. The class imbalance of the outcome affects the historic and non-historic approaches in equal measure, with lower event rates reducing performance. Finally, the functional regression and varying-coefficient model were applied to a real-world clinical dataset to demonstrate their performance and application.