title: A mixed effects model for the analysis of repeated measures cross-over studies.
abstract: A mixed effects model is developed for cross-over trials in which the response is measured repeatedly within each time period. Relative to previous work on repeated measures cross-overs, the methodology synthesizes two important features. First, our procedure eliminates preliminary testing for carry-over, defined loosely as the component of a response that is due to treatment in the preceding period. This is achieved by generalizing the methodology to cross-over designs in which preliminary testing for carry-over is unnecessary. We focus largely on 'simple' carry-over, that is, carry-over that lasts for exactly one period and is independent of the treatment administered in the period in which the carry-over occurs. However, we also illustrate a modification of the procedure for a repeated measures cross-over design which uses a more complicated model of carry-over. Second, the model allows both the between- and within-subject variance to differ among treatments. Conditions are described wherein closed-form (CF) solutions to the variance components as well as closed-form hypothesis tests of the treatment differences exist. Flexibility in the model is illustrated with an example in which inference based on the CF likelihood-based estimates of the variance, and estimates formed using an iterative routine (PROC MIXED) are compared.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, 621 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA. mputt@cceb.upenn.edu
authors.forename: M
authors.initials: M
authors.lastname: Putt
authors.forename: V M
authors.initials: VM
authors.lastname: Chinchilli
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D005260:Female; D007328:Insulin / Q000627:therapeutic use; D016013:Likelihood Functions; D008954:Models, Biological; D015233:Models, Statistical; D011479:Protamines / Q000627:therapeutic use; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011479:Protamines