title: Validity issues in split-mouth trials.
abstract: The main purpose of the split-mouth design is to remove all components related to differences between subjects from the treatment comparisons. By making within-patient comparisons, rather than between-patient comparisons, the error variance (noise) of the experiment can be reduced, thereby obtaining a more powerful statistical test. Unfortunately, comparisons made on a within-patient basis have potential disadvantages. Treatments may have effects on experimental units other than those which they were assigned to (carry-across effects). Such effects cannot be estimated from split-mouth data. Neither can treatment effects be estimated. The estimable parameter in a split-mouth design is the treatment effect plus the sum of all carry-across effects. Unless a priori knowledge indicates that no carry-across effects exist, reported estimates of treatment efficacy are potentially biased. In the design of split-mouth clinical trials, potential gain in precision should be carefully weighed against a potential decrease in validity.
authors.affiliation: Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle 98195.
authors.forename: P P
authors.initials: PP
authors.lastname: Hujoel
authors.forename: T A
authors.initials: TA
authors.lastname: DeRouen
mesh_terms: D006801:Humans; D015233:Models, Statistical; D010510:Periodontal Diseases / Q000628:therapy*; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome