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An enhanced three-stage design with trend analysis for allergen immunotherapy trials

We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an addi...

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Autores principales: Tang, Xinyu, Rabin, Ronald L., Yan, Lihan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501591/
https://www.ncbi.nlm.nih.gov/pubmed/37708124
http://dx.doi.org/10.1371/journal.pone.0291533
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author Tang, Xinyu
Rabin, Ronald L.
Yan, Lihan K.
author_facet Tang, Xinyu
Rabin, Ronald L.
Yan, Lihan K.
author_sort Tang, Xinyu
collection PubMed
description We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an additional trend analysis to evaluate the difference in progression curves of two groups over the entire stage. Results from such analysis are used to inform persistence of end-of-stage benefit and thus provide evidence for stagewise effects beyond the study periods. We jointly apply end-of-stage and trend analyses to support the enhanced three-stage design to determine treatment response over time and sustained response to AIT. A simulation study was performed to illustrate the statistical properties (bias and power) of trend analyses under varying statistical missing mechanisms and effect sizes. The extent of bias depended on the missing mechanism and magnitude. Powers were largely driven by effect and sample sizes as well as pre-specified success margins, particularly of relative trend. As an illustration, assuming relative treatment differences of 25–30%, stagewise dropout rate of 15%, and parallel outcome progressions, a sample size of 200 per group may achieve 97% power to demonstrate a treatment effect and 53% power to demonstrate a sustained effect post-treatment. Trend analysis supplements the end-of-stage analysis to enhance the statistical claims of stagewise effects. Inferential statistics support our proposed trend analysis for evaluating benefits of AIT over time and inform clinical understanding and decisions.
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spelling pubmed-105015912023-09-15 An enhanced three-stage design with trend analysis for allergen immunotherapy trials Tang, Xinyu Rabin, Ronald L. Yan, Lihan K. PLoS One Research Article We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an additional trend analysis to evaluate the difference in progression curves of two groups over the entire stage. Results from such analysis are used to inform persistence of end-of-stage benefit and thus provide evidence for stagewise effects beyond the study periods. We jointly apply end-of-stage and trend analyses to support the enhanced three-stage design to determine treatment response over time and sustained response to AIT. A simulation study was performed to illustrate the statistical properties (bias and power) of trend analyses under varying statistical missing mechanisms and effect sizes. The extent of bias depended on the missing mechanism and magnitude. Powers were largely driven by effect and sample sizes as well as pre-specified success margins, particularly of relative trend. As an illustration, assuming relative treatment differences of 25–30%, stagewise dropout rate of 15%, and parallel outcome progressions, a sample size of 200 per group may achieve 97% power to demonstrate a treatment effect and 53% power to demonstrate a sustained effect post-treatment. Trend analysis supplements the end-of-stage analysis to enhance the statistical claims of stagewise effects. Inferential statistics support our proposed trend analysis for evaluating benefits of AIT over time and inform clinical understanding and decisions. Public Library of Science 2023-09-14 /pmc/articles/PMC10501591/ /pubmed/37708124 http://dx.doi.org/10.1371/journal.pone.0291533 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Tang, Xinyu
Rabin, Ronald L.
Yan, Lihan K.
An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title_full An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title_fullStr An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title_full_unstemmed An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title_short An enhanced three-stage design with trend analysis for allergen immunotherapy trials
title_sort enhanced three-stage design with trend analysis for allergen immunotherapy trials
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501591/
https://www.ncbi.nlm.nih.gov/pubmed/37708124
http://dx.doi.org/10.1371/journal.pone.0291533
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