Tradition, not science, is the basis of animal model selection in translational and applied research.

ALTEX Pub Date : 2021-01-01 Epub Date: 2020-06-22 DOI:10.14573/altex.2003301
Désirée H Veening-Griffioen, Guilherme S Ferreira, Wouter P C Boon, Christine C Gispen-de Wied, Huub Schellekens, Ellen H M Moors, Peter J K Van Meer
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引用次数: 11

Abstract

National and international laws and regulations exist to protect animals used for scientific purposes in translational and applied research, which includes drug development. However, multiple animal models are available for each disease. We evaluated the argumentation behind the selection of a specific animal model using thematic content analysis in project applications issued in 2017-2019 in the Netherlands. In total, 125 animal models for translational and applied research from 110 project applications were assessed. Explanations to select a specific model included: the model’s availability (79%); the availability of expertise (62%); and the model showing similar disease pathology/symptoms (59%) to humans. Therefore, current selection of a specific animal model seems to be based on tradition rather than its potential predictive value for clinical outcome. The applicants’ explanations for the implementation of the 3R prin­ciples (replacement, reduction and refinement) as to the animal model were unspecific. Replacement was achieved by using data from prior in vitro studies, reduction by optimal experimental design and statistics, and refinement by reducing discomfort. Additionally, due to the stated need for a test model with high complexity (47%) and intactness (30%), the full replacement of animal models with alternative (non-live animal) approaches was thought unachievable. Without a clear, systematic and transparent justification for the selection of a specific animal model, the likelihood of poorly trans­latable research remains. It is not only up to the researcher to demonstrate this, as ethical committees and funding bodies can provide positive stimuli to drive this change.

在转化和应用研究中,选择动物模型的基础是传统,而不是科学。
现有的国家和国际法律法规保护在转化和应用研究(包括药物开发)中用于科学目的的动物。然而,每种疾病都有多种动物模型。我们在荷兰2017-2019年发布的项目申请中使用主题内容分析评估了选择特定动物模型背后的论证。总共评估了来自110个项目申请的125个用于转化和应用研究的动物模型。选择特定模型的解释包括:模型的可用性(79%);专业知识的可用性(62%);该模型显示出与人类相似的疾病病理/症状(59%)。因此,目前对特定动物模型的选择似乎是基于传统,而不是其对临床结果的潜在预测价值。申请人对动物模型实施3R原则(置换、还原和细化)的解释不具体。通过使用先前体外研究的数据来实现替代,通过优化实验设计和统计来减少,并通过减少不适来改进。此外,由于需要高复杂性(47%)和完整性(30%)的测试模型,用替代(非活体动物)方法完全替代动物模型被认为是不可实现的。如果没有一个明确的、系统的和透明的理由来选择特定的动物模型,研究的可翻译性很差的可能性仍然存在。这不仅取决于研究人员来证明这一点,因为伦理委员会和资助机构可以提供积极的刺激来推动这一变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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