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Serra, Alessandra ; Mozgunov, Pavel ; Jaki, Thomas

An order restricted multi‐arm multi‐stage clinical trial design

Article

Serra, Alessandra, Mozgunov, Pavel and Jaki, Thomas (2022) An order restricted multi‐arm multi‐stage clinical trial design. Statistics in Medicine 41 (9), pp. 1613-1626.

DOI to cite this document: 10.5283/epub.77855


Abstract

One family of designs that can noticeably improve efficiency in later stages of drug development are multi-arm multi-stage (MAMS) designs. They allow several arms to be studied concurrently and gain efficiency by dropping poorly performing treatment arms during the trial as well as by allowing to stop early for benefit. Conventional MAMS designs were developed for the setting, in which treatment ...

One family of designs that can noticeably improve efficiency in later stages of drug development are multi-arm multi-stage (MAMS) designs. They allow several arms to be studied concurrently and gain efficiency by dropping poorly performing treatment arms during the trial as well as by allowing to stop early for benefit. Conventional MAMS designs were developed for the setting, in which treatment arms are independent and hence can be inefficient when an order in the effects of the arms can be assumed (eg, when considering different treatment durations or different doses). In this work, we extend the MAMS framework to incorporate the order of treatment effects when no parametric dose-response or duration-response model is assumed. The design can identify all promising treatments with high probability. We show that the design provides strong control of the family-wise error rate and illustrate the design in a study of symptomatic asthma. Via simulations we show that the inclusion of the ordering information leads to better decision-making compared to a fixed sample and a MAMS design. Specifically, in the considered settings, reductions in sample size of around 15% were achieved in comparison to a conventional MAMS design.



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Details

Item typeArticle
Journal or Publication TitleStatistics in Medicine
PublisherWiley
Open Access TypeCC-License
Volume41
Number of Issue or Book Chapter9
Page Rangepp. 1613-1626
Date19 January 2022
Date of publication29 Sep 2025 11:59
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1002/sim.9314DOI
Keywordsadaptive designs infectious diseases multi-arm multi-stage order restriction
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgNo
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-778559
Item ID77855

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