title: Assessing non-inferiority of a new treatment in a three-arm clinical trial including a placebo.
abstract: In non-inferiority trials, where non-inferiority of a new experimental drug compared to an active control has to be shown, it may be advisable to use an additional placebo group for internal validation if ethically justifiable. The focus of this paper is on such designs. Assuming normality and homogeneity of variances we will derive a statistical test procedure which turns out to be equivalent to the assessment based on Fieller's confidence interval. Based on the power function of this test, sample size calculations are carried out to achieve a given power. Additionally, the optimal allocation of the total sample size is derived. As an alternative to this parametric procedure, the bootstrap percentile interval is discussed and finally compared with Fieller's confidence interval in a study on mildly asthmatic patients.
authors.affiliation: Institute of Statistics, University of Bremen, Postfach 330440, 28334 Bremen, Germany. pigeot@bips.uni-bremen.de
authors.forename: Iris
authors.initials: I
authors.lastname: Pigeot
authors.forename: Juliane
authors.initials: J
authors.lastname: Schäfer
authors.forename: Joachim
authors.initials: J
authors.lastname: Röhmel
authors.forename: Dieter
authors.initials: D
authors.lastname: Hauschke
mesh_terms: D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D006801:Humans; D009716:Numerical Analysis, Computer-Assisted; D012107:Research Design; D018401:Sample Size; D013810:Therapeutic Equivalency; D014797:Vital Capacity
chemical_list: D018927:Anti-Asthmatic Agents