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Online control of the False Discovery Rate in group-sequential platform trials
When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate assume that all p-values are available at the time point of test decision. In platform trials, however, treatment arms enter and leave the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130539/ https://www.ncbi.nlm.nih.gov/pubmed/36189481 http://dx.doi.org/10.1177/09622802221129051 |
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author | Zehetmayer, Sonja Posch, Martin Koenig, Franz |
author_facet | Zehetmayer, Sonja Posch, Martin Koenig, Franz |
author_sort | Zehetmayer, Sonja |
collection | PubMed |
description | When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate assume that all p-values are available at the time point of test decision. In platform trials, however, treatment arms enter and leave the trial at different times during its conduct. Therefore, the actual number of treatments and hypothesis tests is not fixed in advance and hypotheses are not tested at once, but sequentially. Recently, for such a setting the concept of online control of the False Discovery Rate was introduced. We propose several heuristic variations of the LOND procedure (significance Levels based On Number of Discoveries) that incorporate interim analyses for platform trials, and study their online False Discovery Rate via simulations. To adjust for the interim looks spending functions are applied with O’Brien-Fleming or Pocock type group-sequential boundaries. The power depends on the prior distribution of effect sizes, for example, whether true alternatives are uniformly distributed over time or not. We consider the choice of design parameters for the LOND procedure to maximize the overall power and investigate the impact on the False Discovery Rate by including both concurrent and non-concurrent control data. |
format | Online Article Text |
id | pubmed-10130539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-101305392023-04-27 Online control of the False Discovery Rate in group-sequential platform trials Zehetmayer, Sonja Posch, Martin Koenig, Franz Stat Methods Med Res Original Research Articles When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate assume that all p-values are available at the time point of test decision. In platform trials, however, treatment arms enter and leave the trial at different times during its conduct. Therefore, the actual number of treatments and hypothesis tests is not fixed in advance and hypotheses are not tested at once, but sequentially. Recently, for such a setting the concept of online control of the False Discovery Rate was introduced. We propose several heuristic variations of the LOND procedure (significance Levels based On Number of Discoveries) that incorporate interim analyses for platform trials, and study their online False Discovery Rate via simulations. To adjust for the interim looks spending functions are applied with O’Brien-Fleming or Pocock type group-sequential boundaries. The power depends on the prior distribution of effect sizes, for example, whether true alternatives are uniformly distributed over time or not. We consider the choice of design parameters for the LOND procedure to maximize the overall power and investigate the impact on the False Discovery Rate by including both concurrent and non-concurrent control data. SAGE Publications 2022-10-03 2022-12 /pmc/articles/PMC10130539/ /pubmed/36189481 http://dx.doi.org/10.1177/09622802221129051 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Articles Zehetmayer, Sonja Posch, Martin Koenig, Franz Online control of the False Discovery Rate in group-sequential platform trials |
title | Online control of the False Discovery Rate in group-sequential platform trials |
title_full | Online control of the False Discovery Rate in group-sequential platform trials |
title_fullStr | Online control of the False Discovery Rate in group-sequential platform trials |
title_full_unstemmed | Online control of the False Discovery Rate in group-sequential platform trials |
title_short | Online control of the False Discovery Rate in group-sequential platform trials |
title_sort | online control of the false discovery rate in group-sequential platform trials |
topic | Original Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130539/ https://www.ncbi.nlm.nih.gov/pubmed/36189481 http://dx.doi.org/10.1177/09622802221129051 |
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