دورية أكاديمية
Retrospective analysis of the potential use of virtual control groups in preclinical toxicity assessment using the eTOX database.
| العنوان: | Retrospective analysis of the potential use of virtual control groups in preclinical toxicity assessment using the eTOX database. |
|---|---|
| المؤلفون: | Wright PSR; University of Cambridge, Chemistry, Cambridge, United Kingdom. Electronic address: psrw2@cam.ac.uk., Smith GF; AstraZeneca, Data Science and AI, Clinical Pharmacology and Safety Sciences, R&D, Cambridge, United Kingdom., Briggs KA; Lhasa Limited, Leeds, United Kingdom., Thomas R; Lhasa Limited, Leeds, United Kingdom., Maglennon G; AstraZeneca, Oncology Pathology, Clinical Pharmacology and Safety Sciences, R&D, Melbourn, United Kingdom., Mikulskis P; AstraZeneca, Imaging and Data Analytics, Clinical Pharmacology & Safety Sciences, R&D, Gothenburg, Sweden., Chapman M; AstraZeneca, Toxicology, Clinical Pharmacology and Safety Sciences, R&D, Melbourn, United Kingdom., Greene N; AstraZeneca, Imaging and Data Analytics, Clinical Pharmacology & Safety Sciences, R&D, Waltham, MA, USA., Phillips BU; AstraZeneca, Data Sciences and Quantitative Biology, Discovery Sciences, Cambridge Biomedical Campus, Cambridge, United Kingdom., Bender A; University of Cambridge, Chemistry, Cambridge, United Kingdom. Electronic address: andreas.bender@cantab.net. |
| المصدر: | Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2023 Feb; Vol. 138, pp. 105309. Date of Electronic Publication: 2022 Dec 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8214983 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0295 (Electronic) Linking ISSN: 02732300 NLM ISO Abbreviation: Regul Toxicol Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2003>- : Amsterdam : Elsevier Original Publication: New York : Academic Press, [c1981- |
| مواضيع طبية MeSH: | Toxicity Tests*, Rats ; Animals ; Dogs ; Retrospective Studies ; Control Groups ; Databases, Factual |
| مستخلص: | Virtual Control Groups (VCGs) based on Historical Control Data (HCD) in preclinical toxicity testing have the potential to reduce animal usage. As a case study we retrospectively analyzed the impact of replacing Concurrent Control Groups (CCGs) with VCGs on the treatment-relatedness of 28 selected histopathological findings reported in either rat or dog in the eTOX database. We developed a novel methodology whereby statistical predictions of treatment-relatedness using either CCGs or VCGs of varying covariate similarity to CCGs were compared to designations from original toxicologist reports; and changes in agreement were used to quantify changes in study outcomes. Generally, the best agreement was achieved when CCGs were replaced with VCGs with the highest level of similarity; the same species, strain, sex, administration route, and vehicle. For example, balanced accuracies for rat findings were 0.704 (predictions based on CCGs) vs. 0.702 (predictions based on VCGs). Moreover, we identified covariates which resulted in poorer identification of treatment-relatedness. This was related to an increasing incidence rate divergence in HCD relative to CCGs. Future databases which collect data at the individual animal level including study details such as animal age and testing facility are required to build adequate VCGs to accurately identify treatment-related effects. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PW is funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) under grant ID NC/R001952/1. KB, and RT are employees of Lhasa Limited. GF, GM, PM, MC, NG, and BP are employees of AstraZeneca. AB is a co-founder of Healx Ltd., PharmEnable Ltd., and Terra Lumina, and a consultant for various pharmaceutical and consumer goods companies. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | NC/R001952/1 United Kingdom NC3RS_ National Centre for the Replacement, Refinement and Reduction of Animals in Research |
| فهرسة مساهمة: | Keywords: Control incidence rates; Histopathology; Preclinical studies; Statistical modeling; Toxicology; Treatment related; Virtual control group |
| تواريخ الأحداث: | Date Created: 20221208 Date Completed: 20230208 Latest Revision: 20230215 |
| رمز التحديث: | 20230215 |
| DOI: | 10.1016/j.yrtph.2022.105309 |
| PMID: | 36481280 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0295 |
|---|---|
| DOI: | 10.1016/j.yrtph.2022.105309 |