On the three-arm non-inferiority trial including a placebo with a prespecified margin.

Abstract:

:Three-arm trials including the experimental treatment, an active reference treatment and a placebo are recommended in the guidelines of the ICH and EMEA/CPMP as a useful approach to the assessment of assay sensitivity. Generally, the acceptable non-inferiority margin Δ has been defined as the maximum clinically irrelevant difference between treatments in many two-arm non-inferiority trials. However, many recent articles discussing three-arm trials have considered a design with unknown Δ which is the prespecified fraction f of unknown effect size of the reference drug, where the prespecified fraction f is treated as if it were a revised margin. Therefore, these methods cannot be applied to the case where the acceptable non-inferiority margin must be a prespecified difference between treatments. In this paper, we propose a statistical test procedure for three-arm non-inferiority trials with the margin Δ defined as a prespecified difference between treatments under the situation that the primary endpoints are normally distributed with a common, but unknown, variance. In addition, we derive the optimal allocation that minimizes the total sample size. The proposed method is illustrated with data on a randomized controlled trial on major depressive disorder.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Hida E,Tango T

doi

10.1002/sim.4099

subject

Has Abstract

pub_date

2011-02-10 00:00:00

pages

224-31

issue

3

eissn

0277-6715

issn

1097-0258

journal_volume

30

pub_type

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