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Targeted randomization dose optimization trials enable fractional dosing of scarce drugs

Administering drug at a dose lower than that used in pivotal clinical trials, known as fractional dosing, can stretch scarce resources. Implementing fractional dosing with confidence requires understanding a drug’s dose-response relationship. Clinical trials aimed at describing dose-response in scar...

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Autores principales: Boonstra, Philip S., Tabarrok, Alex, Strohbehn, Garth W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615276/
https://www.ncbi.nlm.nih.gov/pubmed/37903093
http://dx.doi.org/10.1371/journal.pone.0287511
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author Boonstra, Philip S.
Tabarrok, Alex
Strohbehn, Garth W.
author_facet Boonstra, Philip S.
Tabarrok, Alex
Strohbehn, Garth W.
author_sort Boonstra, Philip S.
collection PubMed
description Administering drug at a dose lower than that used in pivotal clinical trials, known as fractional dosing, can stretch scarce resources. Implementing fractional dosing with confidence requires understanding a drug’s dose-response relationship. Clinical trials aimed at describing dose-response in scarce, efficacious drugs risk underdosing, leading dose-finding trials to not be pursued despite their obvious potential benefit. We developed a new set of response-adaptive randomized dose-finding trials and demonstrate, in a series of simulated trials across diverse dose-response curves, these designs’ efficiency in identifying the minimum dose that achieves satisfactory efficacy. Compared to conventional designs, these trials have higher probabilities of identifying lower doses while reducing the risks of both population- and subject-level underdosing. We strongly recommend that, upon demonstration of a drug’s efficacy, pandemic drug development swiftly proceeds with response-adaptive dose-finding trials. This unified strategy ensures that scarce effective drugs produce maximum social benefits.
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spelling pubmed-106152762023-10-31 Targeted randomization dose optimization trials enable fractional dosing of scarce drugs Boonstra, Philip S. Tabarrok, Alex Strohbehn, Garth W. PLoS One Research Article Administering drug at a dose lower than that used in pivotal clinical trials, known as fractional dosing, can stretch scarce resources. Implementing fractional dosing with confidence requires understanding a drug’s dose-response relationship. Clinical trials aimed at describing dose-response in scarce, efficacious drugs risk underdosing, leading dose-finding trials to not be pursued despite their obvious potential benefit. We developed a new set of response-adaptive randomized dose-finding trials and demonstrate, in a series of simulated trials across diverse dose-response curves, these designs’ efficiency in identifying the minimum dose that achieves satisfactory efficacy. Compared to conventional designs, these trials have higher probabilities of identifying lower doses while reducing the risks of both population- and subject-level underdosing. We strongly recommend that, upon demonstration of a drug’s efficacy, pandemic drug development swiftly proceeds with response-adaptive dose-finding trials. This unified strategy ensures that scarce effective drugs produce maximum social benefits. Public Library of Science 2023-10-30 /pmc/articles/PMC10615276/ /pubmed/37903093 http://dx.doi.org/10.1371/journal.pone.0287511 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
Boonstra, Philip S.
Tabarrok, Alex
Strohbehn, Garth W.
Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title_full Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title_fullStr Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title_full_unstemmed Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title_short Targeted randomization dose optimization trials enable fractional dosing of scarce drugs
title_sort targeted randomization dose optimization trials enable fractional dosing of scarce drugs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615276/
https://www.ncbi.nlm.nih.gov/pubmed/37903093
http://dx.doi.org/10.1371/journal.pone.0287511
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