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      Conceptual foundations for a clarified meaning of the 3Rs principles in animal experimentation

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          Abstract

          Russell and Burch’s 1959 original definitions of the 3Rs (replacement, reduction and refinement) are widely used today as standards for the ethical use of non-human animals in research, although they have a number of limitations. Authors and institutions around the world have addressed some of these, coming up in certain cases with more accurate, functional, and up-to-date definitions. However, not only do there still remain limitations needing to be addressed, but some that have been addressed resulted in discrepancies, contradictions, and general confusion as to how best apply the 3Rs in practice. In order to clarify the meaning of the 3Rs and enable more optimal implementation of these principles in animal experimentation, this article provides a theoretical discussion for revised definitions of the original 3Rs via examination of some of their main limitations and inconsistencies. First, we offer up the original definitions as presented in the context of Russell and Burch’s book The Principles of Humane Experimental Technique. Then, we examine the main limitations and present clear specifications and requirements for such revised definitions. After presenting our revised definitions, we conclude with various implications for animal welfare within the context of experimentation.

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          What makes clinical research ethical?

          Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.
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            PREPARE: guidelines for planning animal research and testing

            There is widespread concern about the quality, reproducibility and translatability of studies involving research animals. Although there are a number of reporting guidelines available, there is very little overarching guidance on how to plan animal experiments, despite the fact that this is the logical place to start ensuring quality. In this paper we present the PREPARE guidelines: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: formulation, dialogue between scientists and the animal facility, and quality control of the various components in the study. Some topics overlap and the PREPARE checklist should be adapted to suit specific needs, for example in field research. Advice on use of the checklist is available on the Norecopa website, with links to guidelines for animal research and testing, at https://norecopa.no/PREPARE.
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              The 2020 Five Domains Model: Including Human–Animal Interactions in Assessments of Animal Welfare

              Simple Summary This review outlines the latest in a succession of updates of the Five Domains Model, which, at each stage, incorporated contemporary verified scientific thinking of relevance to animal welfare assessment. The current update includes, within the structure of the Model, specific guidance on how to evaluate the negative and/or positive impacts of human behaviour on animal welfare. Persons whose actions may be evaluated include, but are not limited to, livestock handlers, owners of draught animals, veterinary care staff, pound/shelter staff, zoo-keepers, wildlife managers, hunters, researchers, companion animal owners, owners of sport/recreational animals, animal trainers and service animal handlers. Situations where human–animal interactions may have negative welfare impacts include: when animals have had little or no prior human contact, when human presence adds to already threatening circumstances, when human actions are directly unpleasant, threatening and/or noxious, when humans’ prior actions are remembered as being aversive or noxious and when the actions of bonded humans cause unintended harms. In contrast, situations where human–animal interactions may have positive welfare impacts include: when the companionable presence of humans provides company and feelings of safety, when humans provide preferred foods, tactile contacts and/or training reinforcements, when humans participate in enjoyable routine activities or in engaging variable activities, when the presence of familiar humans is calming in threatening circumstances and when humans act to end periods of deprivation, inhibition or harm. The explicit delineation within the Model of the potential impacts of human interactions on the welfare of animals enhances the Model’s utility. Additional updates in this latest version are also explained. Abstract Throughout its 25-year history, the Five Domains Model for animal welfare assessment has been regularly updated to include at each stage the latest authenticated developments in animal welfare science thinking. The domains of the most up-to-date Model described here are: 1 Nutrition, 2 Physical Environment, 3 Health, 4 Behavioural Interactions and 5 Mental State. The first four domains focus attention on factors that give rise to specific negative or positive subjective experiences (affects), which contribute to the animal’s mental state, as evaluated in Domain 5. More specifically, the first three domains focus mainly on factors that disturb or disrupt particular features of the body’s internal stability. Each disturbed or disrupted feature generates sensory inputs which are processed by the brain to form specific negative affects, and these affects are associated with behaviours that act to restore the body’s internal stability. As each such behaviour is essential for the survival of the animal, the affects associated with them are collectively referred to as “survival-critical affects”. In contrast, Domain 4, now named Behavioural Interactions, focusses on evidence of animals consciously seeking specific goals when interacting behaviourally with (1) the environment, (2) other non-human animals and (3) as a new feature of the Model outlined here, humans. The associated affects, evaluated via Domain 5, are mainly generated by brain processing of sensory inputs elicited by external stimuli. The success of the animals’ behavioural attempts to achieve their chosen goals is reflected in whether the associated affects are negative or positive. Collectively referred to as “situation-related affects”, these outcomes are understood to contribute to animals’ perceptions of their external circumstances. These observations reveal a key distinction between the way survival-critical and situation-related affects influence animals’ aligned behaviours. The former mainly reflect compelling motivations to engage in genetically embedded behavioural responses, whereas the latter mainly involve conscious behavioural choices which are the hallmarks of agency. Finally, numerous examples of human–animal interactions and their attendant affects are described, and the qualitative grading of interactions that generate negative or positive affect is also illustrated.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – original draftRole: Writing – review & editing
                Role: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Journal
                Anim Welf
                Anim Welf
                AWF
                Animal Welfare
                Cambridge University Press (Cambridge, UK )
                0962-7286
                2054-1538
                2024
                23 September 2024
                : 33
                : e37
                Affiliations
                [1 ]Institute for Biomedical Ethics, University of Basel , Basel, Switzerland
                [2 ]Institute for Animal Hygiene, Animal Welfare, and Farm Animal Behaviour, University of Veterinary Medicine , Hannover, Germany
                [3 ]Centre of Legal Medicine, Faculty of Medicine, University of Geneva , Geneva, Switzerland
                Author notes
                Corresponding author: Edwin Louis-Maerten; Email: edwin.louis@ 123456unibas.ch

                Author contributions: Conceptualisation: ELM; Funding acquisition: BSE; Project administration: BSE; Resources: BSE; Supervision: KP, BSE; Visualisation: ELM; Writing – Original draft: ELM, CRP, RMC; Writing – Review & Editing: ELM, CRP, RMC, KP, BSE

                Author information
                https://orcid.org/0009-0001-6554-4821
                https://orcid.org/0000-0001-8944-1504
                https://orcid.org/0000-0002-2769-4888
                https://orcid.org/0000-0001-8783-1437
                https://orcid.org/0000-0002-4249-7399
                Article
                S0962728624000393
                10.1017/awf.2024.39
                11428052
                39347486
                48b64de4-19ed-466a-8c4b-d3c71ae3a0a7
                © The Author(s) 2024

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.

                History
                : 26 January 2024
                : 06 June 2024
                : 19 July 2024
                Page count
                Tables: 1, References: 70, Pages: 11
                Funding
                Funded by: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, doi http://dx.doi.org/10.13039/501100001711;
                Award ID: 206432
                Categories
                Opinion Paper

                animal experimentation,animal research ethics,animal rights,animal welfare,policy,3rs

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