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J Biopharm Stat. 2017;27(1):1-24. doi: 10.1080/10543406.2016.1148710. Epub 2016 Feb 18.

Group-sequential three-arm noninferiority clinical trial designs.

Author information

1
a Biostatistics Department , Shionogi & Co., Ltd. , Osaka , Japan.
2
b Department of Mathematical Health Science , Osaka University Graduate School of Medicine, Suita , Japan.
3
c Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center , Suita , Japan.
4
d Department of Innovative Clinical Trials and Data Sciences , Osaka University Graduate School of Medicine, Suita , Japan.
5
e Department of Biostatistics and the Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , Massachusetts , USA.

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.

KEYWORDS:

Assay sensitivity; Cui-Hung-Wang statistics; Type I error; average sample number; fixed margin approach; fraction approach; maximum sample size; sample size recalculation

PMID:
26892481
PMCID:
PMC4990829
DOI:
10.1080/10543406.2016.1148710
[Indexed for MEDLINE]
Free PMC Article

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