title: Design and analysis of intra-subject variability in cross-over experiments.
abstract: Recently, interest has grown in the development of inferential techniques to compare treatment variabilities in the setting of a cross-over experiment. In particular, comparison of treatments with respect to intra-subject variability has greater interest than has inter-subject variability. We begin with a presentation of a general approach for statistical inference within a cross-over design. We discuss three different statistical models where model choice depends on the design and assumptions about carry-over effects. Each model incorporates t-variate random subject effects, where t is the number of treatments. We develop maximum likelihood (ML) and restricted maximum likelihood (REML) approaches to derive parameter estimators and we consider a special case in which closed-form expressions for the variance component estimators are available. Finally, we illustrate the methodologies with the analysis of data from three examples.
authors.affiliation: Center for Biostatistics & Epidemiology, College of Medicine, Pennsylvania State University, Hershey 17033-0850, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: J D
authors.initials: JD
authors.lastname: Esinhart
mesh_terms: D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002986:Clinical Trials as Topic / Q000379:methods*; D018592:Cross-Over Studies; D004983:Ethanolamines / Q000008:administration & dosage; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012016:Reference Values; D015203:Reproducibility of Results; D012107:Research Design; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D014700:Verapamil; D008787:Metoclopramide; D000068759:Formoterol Fumarate