title: Is the 'simple carry-over' model useful?
abstract: It is argued that the models usually employed for carry-over effects in cross-over trials are not reasonable. The example of a non-linear dose response for a dose-finding trial arranged in a Williams square is developed to show that if carry-over is present to any appreciable degree the usual statistical models provide no guaranteed protection against its effects. It is concluded that the most reasonably defended assumption about carry-over effects is that no important carry-over has taken place and that, where this assumption cannot be defended, statistical models provide no satisfactory substitute for it.
authors.affiliation: Medical Department, CIBA-GEIGY Ltd, Basle, Switzerland.
authors.forename: S J
authors.initials: SJ
authors.lastname: Senn
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic / Q000592:standards*; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000592:standards*; D006801:Humans; D016018:Least-Squares Analysis; D010599:Pharmacokinetics; D013997:Time Factors