Internal consistency and compatibility of the 3Rs and 3Vs principles for project evaluation of animal research

Abstract

Using animals for research raises ethical concerns that are addressed in project evaluation by weighing expected harm to animals against expected benefit to society. A harm–benefit analysis (HBA) relies on two preconditions: (a) the study protocol is scientifically suitable and (b) the use of (sentient) animals and harm imposed on them are necessary for achieving the study’s aims. The 3Rs (Replace, Reduce and Refine) provide a guiding principle for evaluating whether the use of animals, their number and the harm imposed on them are necessary. A similar guiding principle for evaluating whether a study protocol is scientifically suitable has recently been proposed: the 3Vs principle referring to the three main aspects of scientific validity in animal research (construct, internal and external validity). Here, we analyse the internal consistency and compatibility of these two principles, address conflicts within and between the 3Rs and 3Vs principles and discuss their implications for project evaluation. We show that a few conflicts and trade-offs exist, but that these can be resolved either by appropriate study designs or by ethical deliberation in the HBA. In combination, the 3Vs, 3Rs and the HBA thus offer a coherent framework for a logically structured evaluation procedure to decide about the legitimacy of animal research projects.

Role of Environment and Experimenter in Reproducibility of Behavioral Studies With Laboratory Mice

“…In order to investigate the experimenter and the environment contribution separately, our study deeply explored their relative impact on the detection of behavioral traits in C57BL/6J and DBA/2J female mice. Overall, this approach is in line with the concept of systematic heterogenization (Richter, 2017(Richter, , 2020Voelkl et al, 2020) recommended for enhancing external validity and generalization (Karp, 2018;Eggel and Wurbel, 2021).…”

A nonhuman primate model of vertical sleeve gastrectomy facilitates mechanistic and translational research in human obesity

“…In this study, we report a model of laparoscopic VSG performed in an NHP as an innovative translational approach to the understanding of obesity and its treatment. This model demonstrates strong preclinical validity in the three major categories of construct, face, and predictive validity ( Eggel and Würbel, 2020 ; Willner, 1984 ), closely mimicking both the surgical approach and patient outcomes are seen clinically, including weight loss with reduction of adiposity, metabolic improvements, increased postprandial incretin secretion, gut microbiome changes, and increased BA levels. We also report weight-independent metabolic control and long-term reduction of inflammation in the VAT in NHPs after VSG.…”

“…Conversely, the immune system differences between rodents and humans are well-documented, with notable variations in immune education, leukocyte subsets, B and T cell signaling pathways, and cytokines and receptors ( Mestas and Hughes, 2004 ). Selecting an animal model fit for the outcome measure of interest is fundamental to translating findings from our animal models into patient therapies and ensuring appropriate use of animal subjects as outlined by the 3Rs ( Eggel and Würbel, 2020 ; Kirk, 2018 ). Our reported NHP model provides a translational method for probing the cross-talk between the microbiome, metabolome, and immune system.…”

Alternative to animal experimentation in pharmacology teaching: Development and validation of an equivalent digital learning tool

“…The two groups studied during a practical class, the effect of furosemide on diuresis in rats. The learning objectives, which outlines the knowledge, skills, and/or attitudes the learners will gain from the educational activity, 11 were the same for both groups: (1) To know the steps involved in an experiment carried out in an experimental animal to answer a scientific question; (2) to know how to use experimental data and present it in the form of a graph; (3) to identify the different parameters or groups to compare to answer a scientific question; (4) to compare parameters or groups using appropriate statistical tests; (5) to calculate concentrations or volumes of solutions of diuretic agent to administer starting from powder form or dosage form; and (6) to acquire critical thinking and writing skills in order to discuss the results in relation to the published data.…”

“…In the same perspective, the teaching department of pharmacology at the Faculty of Pharmacy undertook an ethical review on the necessity of animal use in the setting of undergraduate teaching. Therefore, taking into consideration the three R’s rule (i.e., reduction, refinement, replacement), 2 parties involved in animal experimentation sought to reduce the number of animals in teaching notably by implementing digital tools 3 . Digital tools allow a diversity of resources provided to students and the development of new interactive forms of delivery.…”