Assessing non-inferiority of a new treatment in a three-arm trial in the presence of heteroscedasticity.
In this paper, we describe an adjusted method to facilitate non-inferiority tests in a three-arm design. While the methodology is readily available in the situation of homogeneous group variances, the adjusted method will also maintain the alpha-level in the presence of heteroscedasticity. We propose explicit criteria for an optimal allocation. Depending on the pattern of heterogeneity, remarkably unbalanced designs are power optimal. We will apply the method to a randomized clinical trial and a toxicological experiment.
Hasler
Mario
M
Institute of Biostatistics, Leibniz Universität Hannover, Hannover, Germany. hasler@biostat.uni-hannover.de
Vonk
Richardus
R
Hothorn
Ludwig A
LA
D000818:Animals; D003627:Data Interpretation, Statistical; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D015162:Micronucleus Tests / Q000706:statistics & numerical data; D015233:Models, Statistical; D010919:Placebos; D011897:Random Allocation; D014116:Toxicology / Q000706:statistics & numerical data; D016896:Treatment Outcome
D006873:Hydroquinones; D010919:Placebos; C031927:hydroquinone