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Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review

The analysis of dose–response, concentration–response, and time–response relationships is a central component of toxicological research. A major decision with respect to the statistical analysis is whether to consider only the actually measured concentrations or to assume an underlying (parametric)...

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Autores principales: Kappenberg, Franziska, Duda, Julia C., Schürmeyer, Leonie, Gül, Onur, Brecklinghaus, Tim, Hengstler, Jan G., Schorning, Kirsten, Rahnenführer, Jörg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474994/
https://www.ncbi.nlm.nih.gov/pubmed/37572131
http://dx.doi.org/10.1007/s00204-023-03561-w
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author Kappenberg, Franziska
Duda, Julia C.
Schürmeyer, Leonie
Gül, Onur
Brecklinghaus, Tim
Hengstler, Jan G.
Schorning, Kirsten
Rahnenführer, Jörg
author_facet Kappenberg, Franziska
Duda, Julia C.
Schürmeyer, Leonie
Gül, Onur
Brecklinghaus, Tim
Hengstler, Jan G.
Schorning, Kirsten
Rahnenführer, Jörg
author_sort Kappenberg, Franziska
collection PubMed
description The analysis of dose–response, concentration–response, and time–response relationships is a central component of toxicological research. A major decision with respect to the statistical analysis is whether to consider only the actually measured concentrations or to assume an underlying (parametric) model that allows extrapolation. Recent research suggests the application of modelling approaches for various types of toxicological assays. However, there is a discrepancy between the state of the art in statistical methodological research and published analyses in the toxicological literature. The extent of this gap is quantified in this work using an extensive literature review that considered all dose–response analyses published in three major toxicological journals in 2021. The aspects of the review include biological considerations (type of assay and of exposure), statistical design considerations (number of measured conditions, design, and sample sizes), and statistical analysis considerations (display, analysis goal, statistical testing or modelling method, and alert concentration). Based on the results of this review and the critical assessment of three selected issues in the context of statistical research, concrete guidance for planning, execution, and analysis of dose–response studies from a statistical viewpoint is proposed.
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spelling pubmed-104749942023-09-04 Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review Kappenberg, Franziska Duda, Julia C. Schürmeyer, Leonie Gül, Onur Brecklinghaus, Tim Hengstler, Jan G. Schorning, Kirsten Rahnenführer, Jörg Arch Toxicol In Silico The analysis of dose–response, concentration–response, and time–response relationships is a central component of toxicological research. A major decision with respect to the statistical analysis is whether to consider only the actually measured concentrations or to assume an underlying (parametric) model that allows extrapolation. Recent research suggests the application of modelling approaches for various types of toxicological assays. However, there is a discrepancy between the state of the art in statistical methodological research and published analyses in the toxicological literature. The extent of this gap is quantified in this work using an extensive literature review that considered all dose–response analyses published in three major toxicological journals in 2021. The aspects of the review include biological considerations (type of assay and of exposure), statistical design considerations (number of measured conditions, design, and sample sizes), and statistical analysis considerations (display, analysis goal, statistical testing or modelling method, and alert concentration). Based on the results of this review and the critical assessment of three selected issues in the context of statistical research, concrete guidance for planning, execution, and analysis of dose–response studies from a statistical viewpoint is proposed. Springer Berlin Heidelberg 2023-08-12 2023 /pmc/articles/PMC10474994/ /pubmed/37572131 http://dx.doi.org/10.1007/s00204-023-03561-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle In Silico
Kappenberg, Franziska
Duda, Julia C.
Schürmeyer, Leonie
Gül, Onur
Brecklinghaus, Tim
Hengstler, Jan G.
Schorning, Kirsten
Rahnenführer, Jörg
Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title_full Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title_fullStr Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title_full_unstemmed Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title_short Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
title_sort guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review
topic In Silico
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474994/
https://www.ncbi.nlm.nih.gov/pubmed/37572131
http://dx.doi.org/10.1007/s00204-023-03561-w
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