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Burnett, Thomas ; König, Franz ; Jaki, Thomas

Adding experimental treatment arms to multi‐arm multi‐stage platform trials in progress

Burnett, Thomas, König, Franz and Jaki, Thomas (2024) Adding experimental treatment arms to multi‐arm multi‐stage platform trials in progress. Statistics in Medicine 43 (18), pp. 3447-3462.

Date of publication of this fulltext: 22 Sep 2025 07:29
Article
DOI to cite this document: 10.5283/epub.77774


Abstract

Multi-arm multi-stage (MAMS) platform trials efficiently compare several treatments with a common control arm. Crucially MAMS designs allow for adjustment for multiplicity if required. If for example, the active treatment arms in a clinical trial relate to different dose levels or different routes of administration of a drug, the strict control of the family-wise error rate (FWER) is paramount. ...

Multi-arm multi-stage (MAMS) platform trials efficiently compare several treatments with a common control arm. Crucially MAMS designs allow for adjustment for multiplicity if required. If for example, the active treatment arms in a clinical trial relate to different dose levels or different routes of administration of a drug, the strict control of the family-wise error rate (FWER) is paramount. Suppose a further treatment becomes available, it is desirable to add this to the trial already in progress; to access both the practical and statistical benefits of the MAMS design. In any setting where control of the error rate is required, we must add corresponding hypotheses without compromising the validity of the testing procedure.To strongly control the FWER, MAMS designs use pre-planned decision rules that determine the recruitment of the next stage of the trial based on the available data. The addition of a treatment arm presents an unplanned change to the design that we must account for in the testing procedure. We demonstrate the use of the conditional error approach to add hypotheses to any testing procedure that strongly controls the FWER. We use this framework to add treatments to a MAMS trial in progress. Simulations illustrate the possible characteristics of such procedures.



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Details

Item typeArticle
Journal or Publication TitleStatistics in Medicine
Publisher:Wiley
Volume:43
Number of Issue or Book Chapter:18
Page Range:pp. 3447-3462
Date9 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.10090DOI
Keywordsadaptive designs, conditional error, design modification, multi-arm multi-stage
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-777749
Item ID77774

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