Refinement
Refinement refers to the reduction or avoidance of pain, suffering, and distress in laboratory animals that occur or could occur either in husbandry, breeding of genetically altered strains with reduced wellbeing, or over the course of the experiment being conducted. Approaches that improve the basic level of animal-well-being, for example, through newly developed more species-specific husbandry standards, are also among possible refinement-methods.
Potential refinement approaches include:
- Improving existing experimental methods that result in maintained information gain with less distress for animals, e.g. by the use of tailored anesthesia and analgesia protocols, or alternative application techniques
- Regular training of staff and adaptation of common working routines (e.g.: blood sampling)
- Improving husbandry standards to allow for more species-specific behavior
- Conditioning of animals for parts of the experimental procedure, for example through positive reinforcement
- Improved termination criteria for experimental procedures
Refinement provides a valuable tool to address the reproducibility and translatability crisis that is currently often discussed, as the presence of pain, suffering, or distress can affect the physiology of the animal and thus the variability of results (1, 2, 3).
Due to the implementation of the 3Rs principle in the Austrian Animal Experiments Act, as well as the EU Directive, project applications must describe how potential refinements will be considered during the course of the project.
Additionally, because of the steadily increasing international relevance of the 3Rs principle in preclinical research with animals, a large number of organizations have focussed on providing relevant information material to facilitate the search for resources for researchers in the preclinical field. These sources of information have been collected as part of a work of the Joint Research Center of the European Commission and are available on the official site of the JRC4 as well as in form of an application provided by Douglas Connect5, which was specifically made to ease the use of the dataset.
Here you will find a list of various refinement-focussed platforms and websites that offer online collections of relevant scientific publications or methods already in use with regard to the focus of refinement:
Refinement Database - Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research6:
The Refinement Database of the Animal Welfare Institute in Washington was created in 2000 and since then offers a list of publications on the topic of refinement that is updated once a quarter. The focus of interest can be filtered by animal species and subject area (e.g. anesthesia, husbandry, animal experimentation, etc.).
Link to the database: AWI-Online: Refinement Database
Norecopa: Refinement-Wiki 7:
The Norwegian organization for the promotion of the 3Rs Norecopa has established a discussion platform focused on refinement, with the following goals:
- To rapidly disseminate developed refinement strategies where there are limited resources for publishing
- To make it easier to find collaborative partners for the development of refinement strategies in multicenter studies
- Researchers should be encouraged to share their experiences or to present new strategies
Further information on the platform and how to register as author can be found here: Norecopa - Refinement Wiki
Special issue of the journal Animals: "Refinement to Animal Models for Biomedical Research" 8:
The journal Animals addressed the question of how to consistently push evidence-based strategies for implementing refinement in preclinical research, as well as how to more easily identify areas for improvement. To this end, authors were invited to submit relevant papers, which have been collected and presented in this special issue.
Link to the special issue: Animals - Refinement to Animal Models for Biomedical Research
LAREF - Laboratory Animal Refinement Forum 9:
LAREF provides an online discussion platform for animal caretakers, students, veterinarians and researchers who are, or have been in the past, confronted with the care of laboratory animals. Through an intensive exchange of information, common problems in husbandry or experimental procedures should be more easily identified, and refinement concepts that have already been shown by experience to work well should be more easily disseminated. Here you can find a list of already published discussions.
Under the following link you will find a detailed description, as well as the possibility to subscribe to LAREF by e-mail: LAREF - Laboratory Animal Refinement Forum
NC3Rs - Grimace scales 10:
Standardized guidelines are needed to better identify pain, distress, and suffering in order to be able to implement adequate refinement-strategies, since species-specific behavioral patterns are often only visible as very subtle differences. Researchers, in cooperation with and funded by the UK NC3Rs, have developed appropriate scales to better classify these differences in various animal species. The scales are intended to be used to sensitize personnel to the important signs of suffering in order to prevent animal suffering at an early stage, but also to make it easier to make decisions regarding possible humane endpoints.
Here you will find a link with detailed explanations, as well as the possibility to download the Grimace scales for the respective animal species in PDF form: Grimace scales | NC3Rs
Education and Training Platform for Laboratory Animal Science - ETPLAS 11:
While education and training are the responsibility of the Member States according to Directive 2010/63/EU, harmonization and mutual recognition of training programs are important prerequisites for Europe-wide scientific exchange and mobility of personnel.
For this reason, the EU Education and Training Framework recommended establishing an Education and Training Platform for Laboratory Animal Science (ETPLAS). ETPLAS was established in 2014, and set up as an information portal to enable information exchange and communication between training providers, accreditation bodies, employers and Member State authorities.
The platform offers, among other things, a series of eLearning modules on education and training in laboratory animal science and alternatives to animal testing.
For the latest news on the 3Rs, click here.
References
1 Carbone L. Pain in laboratory animals: the ethical and regulatory imperatives. PLoS One. 2011;6(9):e21578. Epub 2011/09/15. pmid:21915253; PubMed Central PMCID: PMC3168441.
2 Carbone L, Austin J (2016) Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare. PLoS ONE 11(5): e0155001. https://doi.org/10.1371/journal.pone.0155001
3 Committee on Recognition and Alleviation of Pain in Laboratory Animals NRC. Recognition and Alleviation of Pain in Laboratory Animals. Washington, D.C.: The National Academies Press 2009. 270 p.
4 Holley, T., Bowe, G., Campia, I., Belz, S., Berggren, E., Janusch Roi, A., Wittwehr, C. and Whelan, M., Accelerating progress in the Replacement, Reduction and Refinement of animal testing through better knowledge sharing, EUR 28234 EN, Publications Office of the European Union, Luxembourg, 2016, ISBN 978-92-79-63892-3 (online),978-92-79-63893-0 (print); 978-92-79-75214-8 (ePub), doi:10.2788/934083 (online),10.2788/243531 (print), 10.2788/35428 (ePub), JRC103906
5 Edelweiss Connect (3. Mai 2018): App pulls 3Rs knowledge together. Retrieved on 14th April 2021, from https://www.edelweissconnect.com/blog/app-pulls-3rs-knowledge-together
6 Animal Welfare Institute: Refinement Database. Retrieved on 14th April 2021, from https://awionline.org/content/refinement-database
7 Norecopa (Januar 2021): Grimace scales. Retrieved on 14th April 2021, from https://norecopa.no/wiki
8 Musk GC. Refinements to Animal Models for Biomedical Research. Animals. 2020; 10(12):2425. https://doi.org/10.3390/ani10122425
9 Animal Welfare Institute: Refinement Forum (LAREF). Retrieved on 14th April 2021, from https://awionline.org/content/refinement-forum-laref
10 NC3Rs: Wiki. Retrieved on 14th April 2021, from https://nc3rs.org.uk/grimacescales
11 ETPLAS: Education and Training Platform for Laboratory Animal Science. Retrieved 14th July 2022, von https://etplas.eu
Biomodellen (The 3R Society)
Postfach 0014
A-8036 Graz