title: Re-formulating non-inferiority trials as superiority trials: The case of binary outcomes.
abstract: Non-inferiority trials are conducted for a variety of reasons including to show that a new treatment has a negligible reduction in efficacy or safety when compared to the current standard treatment, or a more complex setting of showing that a new treatment has a negligible reduction in efficacy when compared to the current standard yet is superior in terms of other treatment characteristics. The latter reason for conducting a non-inferiority trial presents the challenge of deciding on a balance between a suitable reduction in efficacy, known as the non-inferiority margin, in return for a gain in other important treatment characteristics/findings. It would be ideal to alleviate the dilemma on the choice of margin in this setting by reverting to a traditional superiority trial design where a single p -value for superiority of both the most important endpoint (efficacy) and the most important finding (treatment characteristic) is provided. We discuss how this can be done using the information-preserving composite endpoint (IPCE) approach and consider binary outcome cases in which the combination of efficacy and treatment characteristics, but not one itself, paints a clear picture that the novel treatment is superior to the active control.
authors.affiliation: Department of Biostatistics, Bioinformatics & Epidemiology, Medical University of South Carolina, Charleston, 29425-8150, USA. durkalsv@musc.edu
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Durkalski
authors.forename: Vance W
authors.initials: VW
authors.lastname: Berger
mesh_terms: D001699:Biometry / Q000379:methods*; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination / Q000379:methods*; D015340:Epidemiologic Research Design; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods*