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Nonparametric non‐inferiority analyses in the three‐arm design with active control and placebo
Author(s) -
Munzel Ullrich
Publication year - 2009
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3727
Subject(s) - nonparametric statistics , confidence interval , statistics , placebo , mathematics , rank (graph theory) , asymptotic analysis , econometrics , computer science , medicine , combinatorics , alternative medicine , pathology
The three‐arm design with test treatment, reference treatment and placebo offers internal assay sensitivity for a proof of non‐inferiority. In this design the relative effects known from nonparametric theory are robust tools allowing the assessment of non‐inferiority in a range of situations. An asymptotic nonparametric theory is established in the three‐arm design based on the asymptotic distribution of rank means under alternative. A rank test for non‐inferiority is derived. Fieller's formula is used to calculate a respective confidence interval. The approach is expanded to multicentre studies. The simulation studies are conducted demonstrating the accuracy of the methods and an example is discussed. Copyright © 2009 John Wiley & Sons, Ltd.