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Greenstreet, Peter ; Jaki, Thomas ; Bedding, Alun ; Harbron, Chris ; Mozgunov, Pavel

A multi‐arm multi‐stage platform design that allows preplanned addition of arms while still controlling the family‐wise error

Greenstreet, Peter, Jaki, Thomas , Bedding, Alun, Harbron, Chris and Mozgunov, Pavel (2024) A multi‐arm multi‐stage platform design that allows preplanned addition of arms while still controlling the family‐wise error. Statistics in Medicine 43 (19), pp. 3613-3632.

Date of publication of this fulltext: 22 Sep 2025 07:13
Article
DOI to cite this document: 10.5283/epub.77772


Abstract

There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In some situations, platform trials need to guarantee that error rates are controlled. This paper presents a multi-stage design, that allows additional arms to be ...

There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In some situations, platform trials need to guarantee that error rates are controlled. This paper presents a multi-stage design, that allows additional arms to be added in a platform trial in a preplanned fashion, while still controlling the family-wise error rate, under the assumption of known number and timing of treatments to be added, and no time trends. A method is given to compute the sample size required to achieve a desired level of power and we show how the distribution of the sample size and the expected sample size can be found. We focus on power under the least favorable configuration which is the power of finding the treatment with a clinically relevant effect out of a set of treatments while the rest have an uninteresting treatment effect. A motivating trial is presented which focuses on two settings, with the first being a set number of stages per active treatment arm and the second being a set total number of stages, with treatments that are added later getting fewer stages. Compared to Bonferroni, the savings in the total maximum sample size are modest in a trial with three arms, <1% of the total sample size. However, the savings are more substantial in trials with more arms.



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Details

Item typeArticle
Journal or Publication TitleStatistics in Medicine
Publisher:Wiley
Open Access Type:CC-License
Volume:43
Number of Issue or Book Chapter:19
Page Range:pp. 3613-3632
Date16 June 2024
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1002/sim.10135DOI
KeywordsMAMS, multi-arm, multi-stage, platform trials, strong control of FWER
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-777725
Item ID77772

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