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Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment

BACKGROUND: Planning the design of a new trial comparing two treatments already in a network of trials with an a-priori plan to estimate the effect size using a network meta-analysis increases power or reduces the sample size requirements. However, when the comparison of interest is between a treatm...

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Autores principales: Ye, Fangshu, Wang, Chong, O’Connor, Annette M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638718/
https://www.ncbi.nlm.nih.gov/pubmed/37951877
http://dx.doi.org/10.1186/s12874-023-02089-y
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author Ye, Fangshu
Wang, Chong
O’Connor, Annette M.
author_facet Ye, Fangshu
Wang, Chong
O’Connor, Annette M.
author_sort Ye, Fangshu
collection PubMed
description BACKGROUND: Planning the design of a new trial comparing two treatments already in a network of trials with an a-priori plan to estimate the effect size using a network meta-analysis increases power or reduces the sample size requirements. However, when the comparison of interest is between a treatment already in the existing network (old treatment) and a treatment that hasn’t been studied previously (new treatment), the impact of leveraging information from the existing network to inform trial design has not been extensively investigated. We aim to identify the most powerful trial design for a comparison of interest between an old treatment A and a new treatment Z, given a fixed total sample size. We consider three possible designs: a two-arm trial between A and Z (’direct two-arm’), a two-arm trial between another old treatment B and Z (’indirect two-arm’), and a three-arm trial among A, B, and Z. METHODS: We compare the standard error of the estimated effect size between treatments A and Z for each of the three trial designs using formulas. For continuous outcomes, the direct two-arm trial always has the largest power, while for a binary outcome, the minimum variances among the three trial designs are conclusive only when [Formula: see text] . Simulation studies are conducted to demonstrate the potential for the indirect two-arm and three-arm trials to outperform the direct two-arm trial in terms of power under the condition of [Formula: see text] . RESULTS: Based on the simulation results, we observe that the indirect two-arm and three-arm trials have the potential to be more powerful than a direct two-arm trial only when [Formula: see text] . This power advantage is influenced by various factors, including the risk of the three treatments, the total sample size, and the standard error of the estimated effect size from the existing network meta-analysis. CONCLUSIONS: The standard two-arm trial design between two treatments in the comparison of interest may not always be the most powerful design. Utilizing information from the existing network meta-analysis, incorporating an additional old treatment into the trial design through an indirect two-arm trial or a three-arm trial can increase power.
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spelling pubmed-106387182023-11-11 Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment Ye, Fangshu Wang, Chong O’Connor, Annette M. BMC Med Res Methodol Research BACKGROUND: Planning the design of a new trial comparing two treatments already in a network of trials with an a-priori plan to estimate the effect size using a network meta-analysis increases power or reduces the sample size requirements. However, when the comparison of interest is between a treatment already in the existing network (old treatment) and a treatment that hasn’t been studied previously (new treatment), the impact of leveraging information from the existing network to inform trial design has not been extensively investigated. We aim to identify the most powerful trial design for a comparison of interest between an old treatment A and a new treatment Z, given a fixed total sample size. We consider three possible designs: a two-arm trial between A and Z (’direct two-arm’), a two-arm trial between another old treatment B and Z (’indirect two-arm’), and a three-arm trial among A, B, and Z. METHODS: We compare the standard error of the estimated effect size between treatments A and Z for each of the three trial designs using formulas. For continuous outcomes, the direct two-arm trial always has the largest power, while for a binary outcome, the minimum variances among the three trial designs are conclusive only when [Formula: see text] . Simulation studies are conducted to demonstrate the potential for the indirect two-arm and three-arm trials to outperform the direct two-arm trial in terms of power under the condition of [Formula: see text] . RESULTS: Based on the simulation results, we observe that the indirect two-arm and three-arm trials have the potential to be more powerful than a direct two-arm trial only when [Formula: see text] . This power advantage is influenced by various factors, including the risk of the three treatments, the total sample size, and the standard error of the estimated effect size from the existing network meta-analysis. CONCLUSIONS: The standard two-arm trial design between two treatments in the comparison of interest may not always be the most powerful design. Utilizing information from the existing network meta-analysis, incorporating an additional old treatment into the trial design through an indirect two-arm trial or a three-arm trial can increase power. BioMed Central 2023-11-11 /pmc/articles/PMC10638718/ /pubmed/37951877 http://dx.doi.org/10.1186/s12874-023-02089-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ye, Fangshu
Wang, Chong
O’Connor, Annette M.
Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title_full Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title_fullStr Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title_full_unstemmed Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title_short Optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
title_sort optimal trial design selection: a comparative analysis between two-arm and three-arm trials incorporating network meta-analysis for evaluating a new treatment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638718/
https://www.ncbi.nlm.nih.gov/pubmed/37951877
http://dx.doi.org/10.1186/s12874-023-02089-y
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