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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 type | Article | ||||
| Journal or Publication Title | Statistics in Medicine | ||||
| Publisher | Wiley | ||||
| Open Access Type | CC-License | ||||
| Volume | 41 | ||||
| Number of Issue or Book Chapter | 9 | ||||
| Page Range | pp. 1613-1626 | ||||
| Date | 19 January 2022 | ||||
| Date of publication | 29 Sep 2025 11:59 | ||||
| Institutions | Informatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki) | ||||
| Identification Number |
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| Keywords | adaptive designs infectious diseases multi-arm multi-stage order restriction | ||||
| Dewey Decimal Classification | 000 Computer science, information & general works > 004 Computer science | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | No | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-778559 | ||||
| Item ID | 77855 |
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