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Identifying combined design and analysis procedures in two-stage trials with a binary end point

Two-stage trial designs provide the flexibility to stop early for efficacy or futility and are popular because they have a smaller sample size on average than a traditional trial has with the same type I and II error rates. This makes them financially attractive but also has the ethical benefit of r...

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Detalles Bibliográficos
Autores principales: Bowden, Jack, Wason, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546375/
https://www.ncbi.nlm.nih.gov/pubmed/22786815
http://dx.doi.org/10.1002/sim.5468
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author Bowden, Jack
Wason, James
author_facet Bowden, Jack
Wason, James
author_sort Bowden, Jack
collection PubMed
description Two-stage trial designs provide the flexibility to stop early for efficacy or futility and are popular because they have a smaller sample size on average than a traditional trial has with the same type I and II error rates. This makes them financially attractive but also has the ethical benefit of reducing, in the long run, the number of patients who are given ineffective treatments. Designs that minimise the expected sample size are often referred to as ‘optimal’. However, two-stage designs can impart a substantial bias into the parameter estimate at the end of the trial. In this paper, we argue that the expected performance of one's chosen estimation method should also be considered when deciding on a two-stage trial design. We review the properties of standard and bias-adjusted maximum likelihood estimators as well as mean and median unbiased estimators. We then identify optimal two-stage design and analysis procedures that balance projected sample size considerations with those of estimator performance. We make available software to implement this new methodology. Copyright © 2012 John Wiley & Sons, Ltd.
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spelling pubmed-35463752013-01-16 Identifying combined design and analysis procedures in two-stage trials with a binary end point Bowden, Jack Wason, James Stat Med Research Articles Two-stage trial designs provide the flexibility to stop early for efficacy or futility and are popular because they have a smaller sample size on average than a traditional trial has with the same type I and II error rates. This makes them financially attractive but also has the ethical benefit of reducing, in the long run, the number of patients who are given ineffective treatments. Designs that minimise the expected sample size are often referred to as ‘optimal’. However, two-stage designs can impart a substantial bias into the parameter estimate at the end of the trial. In this paper, we argue that the expected performance of one's chosen estimation method should also be considered when deciding on a two-stage trial design. We review the properties of standard and bias-adjusted maximum likelihood estimators as well as mean and median unbiased estimators. We then identify optimal two-stage design and analysis procedures that balance projected sample size considerations with those of estimator performance. We make available software to implement this new methodology. Copyright © 2012 John Wiley & Sons, Ltd. Blackwell Publishing Ltd 2012-12-20 2012-07-11 /pmc/articles/PMC3546375/ /pubmed/22786815 http://dx.doi.org/10.1002/sim.5468 Text en Copyright © 2012 John Wiley & Sons, Ltd. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Bowden, Jack
Wason, James
Identifying combined design and analysis procedures in two-stage trials with a binary end point
title Identifying combined design and analysis procedures in two-stage trials with a binary end point
title_full Identifying combined design and analysis procedures in two-stage trials with a binary end point
title_fullStr Identifying combined design and analysis procedures in two-stage trials with a binary end point
title_full_unstemmed Identifying combined design and analysis procedures in two-stage trials with a binary end point
title_short Identifying combined design and analysis procedures in two-stage trials with a binary end point
title_sort identifying combined design and analysis procedures in two-stage trials with a binary end point
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546375/
https://www.ncbi.nlm.nih.gov/pubmed/22786815
http://dx.doi.org/10.1002/sim.5468
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