Abstract
Hierarchical functional data are widely seen in complex studies where subunits are nested within units, which in turn are nested within treatment groups. We propose a general framework of functional mixed effects model for such data: within-unit and within-subunit variations are modeled through two separate sets of principal components; the subunit level functions are allowed to be correlated. Penalized splines are used to model both the mean functions and the principal components functions, where roughness penalties are used to regularize the spline fit. An expectation–maximization (EM) algorithm is developed to fit the model, while the specific covariance structure of the model is utilized for computational efficiency to avoid storage and inversion of large matrices. Our dimension reduction with principal components provides an effective solution to the difficult tasks of modeling the covariance kernel of a random function and modeling the correlation between functions. The proposed methodology is illustrated using simulations and an empirical dataset from a colon carcinogenesis study. Supplemental materials are available online.