title: A general approach for sample size calculation for the three-arm 'gold standard' non-inferiority design.
abstract: In the three-arm 'gold standard' non-inferiority design, an experimental treatment, an active reference, and a placebo are compared. This design is becoming increasingly popular, and it is, whenever feasible, recommended for use by regulatory guidelines. We provide a general method to calculate the required sample size for clinical trials performed in this design. As special cases, the situations of continuous, binary, and Poisson distributed outcomes are explored. Taking into account the correlation structure of the involved test statistics, the proposed approach leads to considerable savings in sample size as compared with application of ad hoc methods for all three scale levels. Furthermore, optimal sample size allocation ratios are determined that result in markedly smaller total sample sizes as compared with equal assignment. As optimal allocation makes the active treatment groups larger than the placebo group, implementation of the proposed approach is also desirable from an ethical viewpoint.
authors: Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors: Kathrin
authors: K
authors: Stucke
authors: Meinhard
authors: M
authors: Kieser
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy; D000068736:Duloxetine Hydrochloride; D006801:Humans; D016013:Likelihood Functions; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D010919:Placebos / Q000008:administration & dosage; D016012:Poisson Distribution; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D012107:Research Design; D018401:Sample Size; D013810:Therapeutic Equivalency; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D010919:Placebos; D013876:Thiophenes; D015283:Citalopram; D000068736:Duloxetine Hydrochloride