title: A mixed approach for proving non-inferiority in clinical trials with binary endpoints.
abstract: When a new treatment is compared to an established one in a randomized clinical trial, it is standard practice to statistically test for non-inferiority rather than for superiority. When the endpoint is binary, one usually compares two treatments using either an odds-ratio or a difference of proportions. In this paper, we propose a mixed approach which uses both concepts. One first defines the non-inferiority margin using an odds-ratio and one ultimately proves non-inferiority statistically using a difference of proportions. The mixed approach is shown to be more powerful than the conventional odds-ratio approach when the efficacy of the established treatment is known (with good precision) and high (e.g. with more than 56% of success). The gain of power achieved may lead in turn to a substantial reduction in the sample size needed to prove non-inferiority. The mixed approach can be generalized to ordinal endpoints.
authors.affiliation: Statistical Unit, Institute for Social and Preventive Medicine, University of Lausanne, Rue du Bugnon 17, 1005 Lausanne, Switzerland. Valentin.Rousson@chuv.ch
authors.forename: Valentin
authors.initials: V
authors.lastname: Rousson
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002981:Clindamycin / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D018401:Sample Size; D013810:Therapeutic Equivalency; D016585:Vaginosis, Bacterial / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin