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A multiple comparison procedure for dose‐finding trials with subpopulations

Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before the start of a trial it might be beneficial to set up a testin...

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Autores principales: Thomas, Marius, Bornkamp, Björn, Posch, Martin, König, Franz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973002/
https://www.ncbi.nlm.nih.gov/pubmed/31544265
http://dx.doi.org/10.1002/bimj.201800111
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author Thomas, Marius
Bornkamp, Björn
Posch, Martin
König, Franz
author_facet Thomas, Marius
Bornkamp, Björn
Posch, Martin
König, Franz
author_sort Thomas, Marius
collection PubMed
description Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before the start of a trial it might be beneficial to set up a testing strategy, which tests for a significant treatment effect not only in the full population, but also in these prespecified subpopulations. In this paper, we present a parametric multiple testing approach for tests in multiple populations for dose‐finding trials. Our approach is based on the MCP‐Mod methodology, which uses multiple comparison procedures (MCPs) to test for a dose–response signal, while considering multiple possible candidate dose–response shapes. Our proposed methods allow for heteroscedastic error variances between populations and control the family‐wise error rate over tests in multiple populations and for multiple candidate models. We show in simulations that the proposed multipopulation testing approaches can increase the power to detect a significant dose–response signal over the standard single‐population MCP‐Mod, when the specified subpopulation has an enhanced treatment effect.
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spelling pubmed-69730022020-01-27 A multiple comparison procedure for dose‐finding trials with subpopulations Thomas, Marius Bornkamp, Björn Posch, Martin König, Franz Biom J Hypothesis Testing Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before the start of a trial it might be beneficial to set up a testing strategy, which tests for a significant treatment effect not only in the full population, but also in these prespecified subpopulations. In this paper, we present a parametric multiple testing approach for tests in multiple populations for dose‐finding trials. Our approach is based on the MCP‐Mod methodology, which uses multiple comparison procedures (MCPs) to test for a dose–response signal, while considering multiple possible candidate dose–response shapes. Our proposed methods allow for heteroscedastic error variances between populations and control the family‐wise error rate over tests in multiple populations and for multiple candidate models. We show in simulations that the proposed multipopulation testing approaches can increase the power to detect a significant dose–response signal over the standard single‐population MCP‐Mod, when the specified subpopulation has an enhanced treatment effect. John Wiley and Sons Inc. 2019-09-23 2020-01 /pmc/articles/PMC6973002/ /pubmed/31544265 http://dx.doi.org/10.1002/bimj.201800111 Text en © 2019 The Authors. Biometrical Journal Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hypothesis Testing
Thomas, Marius
Bornkamp, Björn
Posch, Martin
König, Franz
A multiple comparison procedure for dose‐finding trials with subpopulations
title A multiple comparison procedure for dose‐finding trials with subpopulations
title_full A multiple comparison procedure for dose‐finding trials with subpopulations
title_fullStr A multiple comparison procedure for dose‐finding trials with subpopulations
title_full_unstemmed A multiple comparison procedure for dose‐finding trials with subpopulations
title_short A multiple comparison procedure for dose‐finding trials with subpopulations
title_sort multiple comparison procedure for dose‐finding trials with subpopulations
topic Hypothesis Testing
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973002/
https://www.ncbi.nlm.nih.gov/pubmed/31544265
http://dx.doi.org/10.1002/bimj.201800111
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