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.
Highlights
In themedical field, the development of new drugs is a journey from “bench-to-bedside”, in which effective translation of knowledge takes place from basic science into new treatment options for patients
Some information was undisclosed for reasons of employee privacy or protection of intellectual property as regulated via the Dutch Public Access to Government Information Act (“Wet openbaarheid van bestuur” or “WOB”) (Binnenlandse Zaken en Koninkrijksrelaties, 2018), which regulates the disclosure of information by the Dutch government
We investigated the consistency in argumentation within project applications by comparing the justification of the choice of the animal model to the choice of species or outcome
Summary
In the (bio)medical field, the development of new drugs is a journey from “bench-to-bedside”, in which effective translation of knowledge takes place from basic science into new treatment options for patients. These treatment options may include options to prevent the onset of diseases, or options to (improve) diagnosis, medical devices or treatment with medicinal products, i.e., pharmaceuticals (Woolf, 2008; Fontanarosa and DeAngelis, 2003). The inability of an animal model to predict clinical outcome has several reasons, which can be summarized as poor execution and poor animal model choice. Poor animal model choice concerns insufficiently taking into account a different etiology in the animal, animal-human species differences, important clinical endpoints not being available or assessed in the animal, as well as the display of different disease and pharmacodynamic markers in the animal (Denayer et al, 2014)
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