Hypothesis testing in functional linear regression models with Neyman's truncation and wavelet thresholding for longitudinal data

Longitudinal data sets in biomedical research often consist of large numbers of repeated measures. In many cases, the trajectories do not look globally linear or polynomial, making it difficult to summarize the data or test hypotheses using standard longitudinal data analysis based on various linear models. An alternative approach is to apply the approaches of functional data analysis, which directly target the continuous nonlinear curves underlying discretely sampled repeated measures. For the purposes of data exploration, many functional data analysis strategies have been developed based on various schemes of smoothing, but fewer options are available for making causal inferences regarding predictor-outcome relationships, a common task seen in hypothesis-driven medical studies. To compare groups of curves, two testing strategies with good power have been proposed for high-dimensional analysis of variance: the Fourier-based adaptive Neyman test and the wavelet-based thresholding test. Using a smoking cessation clinical trial data set, this paper demonstrates how to extend the strategies for hypothesis testing into the framework of functional linear regression models (FLRMs) with continuous functional responses and categorical or continuous scalar predictors. The analysis procedure consists of three steps: first, apply the Fourier or wavelet transform to the original repeated measures; then fit a multivariate linear model in the transformed domain; and finally, test the regression coefficients using either adaptive Neyman or thresholding statistics. Since a FLRM can be viewed as a natural extension of the traditional multiple linear regression model, the development of this model and computational tools should enhance the capacity of medical statistics for longitudinal data.