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

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 st...

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Autores principales: Serra, Alessandra, Mozgunov, Pavel, Jaki, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612618/
https://www.ncbi.nlm.nih.gov/pubmed/35048391
http://dx.doi.org/10.1002/sim.9314
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author Serra, Alessandra
Mozgunov, Pavel
Jaki, Thomas
author_facet Serra, Alessandra
Mozgunov, Pavel
Jaki, Thomas
author_sort Serra, Alessandra
collection PubMed
description 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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spelling pubmed-76126182022-04-30 An order restricted multi‐arm multi‐stage clinical trial design Serra, Alessandra Mozgunov, Pavel Jaki, Thomas Stat Med Research Articles 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. John Wiley and Sons Inc. 2022-01-19 2022-04-30 /pmc/articles/PMC7612618/ /pubmed/35048391 http://dx.doi.org/10.1002/sim.9314 Text en © 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Serra, Alessandra
Mozgunov, Pavel
Jaki, Thomas
An order restricted multi‐arm multi‐stage clinical trial design
title An order restricted multi‐arm multi‐stage clinical trial design
title_full An order restricted multi‐arm multi‐stage clinical trial design
title_fullStr An order restricted multi‐arm multi‐stage clinical trial design
title_full_unstemmed An order restricted multi‐arm multi‐stage clinical trial design
title_short An order restricted multi‐arm multi‐stage clinical trial design
title_sort order restricted multi‐arm multi‐stage clinical trial design
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612618/
https://www.ncbi.nlm.nih.gov/pubmed/35048391
http://dx.doi.org/10.1002/sim.9314
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