title: Application of semiparametric mixed models and simultaneous confidence bands in a cardiovascular safety experiment with longitudinal data.
abstract: Several pharmacological studies involve experiments aimed at testing for a difference between experimental groups wherein the data are longitudinal in nature, frequently with long sequences per subject. Oftentimes, treatment effect, if present, is not constant over time. In such situations, imposing a parametric mean structure can be too complicated and/or restrictive. A more flexible approach is to model the mean using a semiparametric smooth function, estimated using, for example, penalized smoothing splines. We formulate a series of models exhibiting how the group-specific mean profiles could possibly differ. Once an appropriate model is chosen, interest lies in identifying specific time points where the groups differ. For this purpose, we propose the use of simultaneous confidence bands around the fitted models wherein the bands take into account within and between-subject variability, as well as variability arising from smoothing.
authors.affiliation: Center for Statistics, Universiteit Hasselt, Diepenbeek, Belgium. john.maringwa@uhasselt.be
authors.forename: John T
authors.initials: JT
authors.lastname: Maringwa
authors.forename: Helena
authors.initials: H
authors.lastname: Geys
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shkedy
authors.forename: Christel
authors.initials: C
authors.lastname: Faes
authors.forename: Geert
authors.initials: G
authors.lastname: Molenberghs
authors.forename: Marc
authors.initials: M
authors.lastname: Aerts
authors.forename: Karel Van
authors.initials: KV
authors.lastname: Ammel
authors.forename: Ard
authors.initials: A
authors.lastname: Teisman
authors.forename: Luc
authors.initials: L
authors.lastname: Bijnens
mesh_terms: D000818:Animals; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D006339:Heart Rate / Q000187:drug effects*; D016014:Linear Models; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008137:Longitudinal Studies; D023421:Models, Animal; D015233:Models, Statistical; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome