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Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package

Bridging studies are designed to fill the gap between two populations in terms of clinical trial data, such as toxicity, efficacy, comorbidities and doses. According to ICH-E5 guidelines, clinical data can be extrapolated from one region to another if dose–reponse curves are similar between two popu...

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Detalles Bibliográficos
Autores principales: Ollier, Adrien, Zohar, Sarah, Morita, Satoshi, Ursino, Moreno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916097/
https://www.ncbi.nlm.nih.gov/pubmed/33572323
http://dx.doi.org/10.3390/ijerph18041639
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author Ollier, Adrien
Zohar, Sarah
Morita, Satoshi
Ursino, Moreno
author_facet Ollier, Adrien
Zohar, Sarah
Morita, Satoshi
Ursino, Moreno
author_sort Ollier, Adrien
collection PubMed
description Bridging studies are designed to fill the gap between two populations in terms of clinical trial data, such as toxicity, efficacy, comorbidities and doses. According to ICH-E5 guidelines, clinical data can be extrapolated from one region to another if dose–reponse curves are similar between two populations. For instance, in Japan, Phase I clinical trials are often repeated due to this physiological/metabolic paradigm: the maximum tolerated dose (MTD) for Japanese patients is assumed to be lower than that for Caucasian patients, but not necessarily for all molecules. Therefore, proposing a statistical tool evaluating the similarity between two populations dose–response curves is of most interest. The aim of our work is to propose several indicators to evaluate the distance and the similarity of dose–toxicity curves and MTD distributions at the end of some of the Phase I trials, conducted on two populations or regions. For this purpose, we extended and adapted the commensurability criterion, initially proposed by Ollier et al. (2019), in the setting of completed phase I clinical trials. We evaluated their performance using three synthetic sets, built as examples, and six case studies found in the literature. Visualization plots and guidelines on the way to interpret the results are proposed.
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spelling pubmed-79160972021-03-01 Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package Ollier, Adrien Zohar, Sarah Morita, Satoshi Ursino, Moreno Int J Environ Res Public Health Article Bridging studies are designed to fill the gap between two populations in terms of clinical trial data, such as toxicity, efficacy, comorbidities and doses. According to ICH-E5 guidelines, clinical data can be extrapolated from one region to another if dose–reponse curves are similar between two populations. For instance, in Japan, Phase I clinical trials are often repeated due to this physiological/metabolic paradigm: the maximum tolerated dose (MTD) for Japanese patients is assumed to be lower than that for Caucasian patients, but not necessarily for all molecules. Therefore, proposing a statistical tool evaluating the similarity between two populations dose–response curves is of most interest. The aim of our work is to propose several indicators to evaluate the distance and the similarity of dose–toxicity curves and MTD distributions at the end of some of the Phase I trials, conducted on two populations or regions. For this purpose, we extended and adapted the commensurability criterion, initially proposed by Ollier et al. (2019), in the setting of completed phase I clinical trials. We evaluated their performance using three synthetic sets, built as examples, and six case studies found in the literature. Visualization plots and guidelines on the way to interpret the results are proposed. MDPI 2021-02-09 2021-02 /pmc/articles/PMC7916097/ /pubmed/33572323 http://dx.doi.org/10.3390/ijerph18041639 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ollier, Adrien
Zohar, Sarah
Morita, Satoshi
Ursino, Moreno
Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title_full Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title_fullStr Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title_full_unstemmed Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title_short Estimating Similarity of Dose–Response Relationships in Phase I Clinical Trials—Case Study in Bridging Data Package
title_sort estimating similarity of dose–response relationships in phase i clinical trials—case study in bridging data package
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916097/
https://www.ncbi.nlm.nih.gov/pubmed/33572323
http://dx.doi.org/10.3390/ijerph18041639
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