title: Group-sequential three-arm noninferiority clinical trial designs.
abstract: We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum, and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its impact on the power and Type I error rate via a simulation study.
authors.affiliation: a Biostatistics Department , Shionogi & Co., Ltd. , Osaka , Japan.|b Department of Mathematical Health Science , Osaka University Graduate School of Medicine, Suita , Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: b Department of Mathematical Health Science , Osaka University Graduate School of Medicine, Suita , Japan.|c Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center , Suita , Japan.|d Department of Innovative Clinical Trials and Data Sciences , Osaka University Graduate School of Medicine, Suita , Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: e Department of Biostatistics and the Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , Massachusetts , USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Evans
authors.affiliation: c Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center , Suita , Japan.|d Department of Innovative Clinical Trials and Data Sciences , Osaka University Graduate School of Medicine, Suita , Japan.
authors.forename: Koko
authors.initials: K
authors.lastname: Asakura
authors.affiliation: b Department of Mathematical Health Science , Osaka University Graduate School of Medicine, Suita , Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohno
mesh_terms: D000074099:Equivalence Trials as Topic; D006801:Humans; D012107:Research Design; D018401:Sample Size
keywords: Assay sensitivity; Cui-Hung-Wang statistics; Type I error; average sample number; fixed margin approach; fraction approach; maximum sample size; sample size recalculation