title: Randomized clinical trial design for assessing noninferiority when superiority is expected.
abstract: The randomized clinical trial (RCT) is the gold standard for definitive evaluation of new therapies. RCTs designed to show that the therapeutic efficacy of a new therapy is not unacceptably inferior to that of standard therapy are called noninferiority trials. Traditionally, noninferiority trials have required very large sample sizes. Sometimes, a new treatment regimen with a favorable toxicity and/or tolerability profile is also expected to have some modest improvement in efficacy. In such specialized settings we describe a hybrid trial-design approach that requires a dramatically smaller sample size than that of a standard noninferiority design. This hybrid design can naturally incorporate a formal test of superiority as well as noninferiority.
authors.affiliation: Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. freidlinb@ctep.nci.nih.gov
authors.forename: Boris
authors.initials: B
authors.lastname: Freidlin
authors.forename: Edward L
authors.initials: EL
authors.lastname: Korn
authors.forename: Stephen L
authors.initials: SL
authors.lastname: George
authors.forename: Robert
authors.initials: R
authors.lastname: Gray
mesh_terms: D006801:Humans; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size