Nonparametric non-inferiority analyses in the three-arm design with active control and placebo

Stat Med. 2009 Dec 20;28(29):3643-56. doi: 10.1002/sim.3727.

Abstract

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.

MeSH terms

  • Clinical Trials as Topic / methods*
  • Computer Simulation
  • Diabetic Neuropathies / drug therapy
  • Humans
  • Multicenter Studies as Topic / methods*
  • Pain / prevention & control
  • Statistics, Nonparametric*
  • Therapeutic Equivalency*
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / therapeutic use

Substances

  • Thioctic Acid