RSPCA - Challenging refinements meeting
A summary report is now available from the RSPCA – ‘Challenging Refinements’ meeting held in England on 4 April 2019. The main scientific session included presentations covering diverse areas of research such as neuropathic pain, rheumatoid arthritis, diabetic nephropathy, neuromodulation, haemophilia, regulatory toxicology and mitochondrial toxicology. The meeting concluded with a presentation on how the local Animal Welfare and Ethical Review Body (these are combined in the UK) can facilitate refinement, and a discussion on how sharing of refinement information between research groups, nationally and internationally, can be improved.
Literature searches for 3Rs resources
A presentation by Dr Michelle Hudson-Shore of the University of Nottingham on Searching for Information on 3Rs and 3Rs Resources has been published. This presentation provides an awareness of the need to conduct effective and in depth searches as well as highlighting the problems associated with searching. We recommend this for all information officers and researchers in order to improve basic search skills and increase their knowledge of available resources.
Research integrity in research involving animals
The UK Research Integrity Office (UKRIO) has published a primer document on research integrity in animal research. It focuses on responsible conduct, good governance and ethical oversight of animal use in research. It is intended to provide an overview of the issues that need to be considered in order to facilitate a robust approach to good practice in the context of research involving animals. This document is relevant to ethics committees and researchers involved in the use of live animals, biological materials derived from animals, or animal-derived data.
Danish 3R–Center annual symposium
The Danish 3R-Center symposium was held on the 5th and 6th of November 2018. The majority of the presentations are now available in pdf format. These include presentations on barriers and opportunities regarding Replacement, the implementation of the Directive, sharing organs and tissues, and refining mouse handling.
Codes of practice for the generation and breeding of GM animals
In August 2018, the Netherlands National Committee (NCad) issued part two of an advisory report on genetically modified (GM) animals, which sets out specific quality and efficiency criteria for creating a new GM line whilst reducing the numbers of animals used for this process. This resource consists of two appendices: Appendix I advises on how to go about creating a new line, if required, while Appendix II advises on the breeding of GM animals. These are both available in the advisory document from NCad. Please note that the contents are the opinion of NCad.
Found in Translation (FIT)
Translational barriers between species form one of the major challenges in animal research and testing. Found in Translation (FIT) is a machine-learning model that has been developed to leverage public gene expression data to extrapolate the results of a new mouse experiment to expression changes in the equivalent human condition. The results from this FIT model have been published in Nature. We recommend all researchers working in translational research read this paper.
Resources by Dr Michael Festing on experimental design
The research of Dr Michael Festing has made an enormous contribution to Laboratory Animal Science. In particular, his work has focused on genetics (the use of inbred and outbred animals in research), experimental design and statistical analysis. His work has enabled many scientists to reduce the number of animals used in research. Norecopa has created a database which includes a collection of resources authored by Dr Festing.
Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS)
The findings from the Wiggers-Bernard conference on preclinical sepsis modelling held in Vienna in May 2017 have been published. The top 260 most highly cited scientific articles on sepsis from 2002 to 2013 were reviewed by experts in the field and a set of guidelines were proposed and defined as the “Minimum Quality Threshold in Preclinical Sepsis Studies” (MQTiPSS) to enhance translational value of preclinical sepsis models. Researchers involved in preclinical sepsis modelling should only submit an application involving this model to the HPRA following a thorough review of this resource. With this in mind, we would like to again highlight the resources available on the HPRA website for researchers regarding the refinement of several severe models (sepsis, EAE, epilepsy and rheumatoid arthritis).
Non-invasive DNA sampling
Marie-Caroline Lefort and colleagues have written a review of methods for non-invasive DNA sampling. This review looks at non-invasive DNA sampling literature from 346 papers published between 2013 and 2018. It finds that 58% of reviewed papers do not comply with the original definition of non-invasive DNA sampling which refers to collection methods that do not require capture or cause disturbance to the animal, including any effects on the behaviour or fitness of the animal. This review is worth reading if you have used or are planning to use any form of genotyping in your research.
Synthesis of Evidence in laboratory animal research
The Netherlands National Committee for the protection of animals used for scientific purposes (NCAD) has completed a review and devised an opinion on the application of Synthesis of Evidence (SoE) methods in the development of in vivo research projects. This opinion paper discusses the merits of different forms of SoE and how its application can both enhance the quality of animal research and prevent unnecessary use of animals arising from repetition of in vivo studies. It also highlights the importance of publishing negative findings and details journals which do not demonstrate publication bias.
The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines by the NC3Rs are a helpful set of guidelines created with the intention of improving the reporting of research using animals. The HPRA encourages the use of the ARRIVE Guidelines when designing animal studies.
The International Council for Laboratory Animal Science (ICLAS) has published a set of principles for better reporting called HARRP (Harmonized Animal Research Reporting Principles). The basic principles of HARRP are based on the reporting standards of the 'Gold Standard Publication Checklist', the 'ARRIVE guidelines' and the Institute for Laboratory Animal Research's (ILAR's) 'Guidance on the Description of Animal Research in Scientific Publications'. These principles aim to improve the quality of animal based research and encourage complete and accurate reporting of animal based studies.
FELASA/ECLAM/ESLAV Working Group Report on Severity
This report delivers guidance on the assignment of severity, both prospectively and at the end of a procedure. A number of animal models are used to illustrate the severity assessment process. This report is essential reading in all establishments. The report is free to download:
RSPCA: How the AWB can help with reproducibility
Dr Penny Hawkins, the Head of the RSPCA Research Animals Department, delivered an informative presentation in September 2017 at the LAVA/ESLAV/ECLAM Conference on Reproducibility of Animal Studies in Edinburgh. The presentation (which is attached to this update) provides suggestions on how AWBs and designated veterinarians can offer advice to researchers with regards reproducibility. Please share this presentation with the AWB members in your establishment.
The PREPARE (Planning Research and Experimental Procedures on Animals: Recommendations for Excellence) guidelines, written by a group of experts led by Norecopa, have been published in Laboratory Animals. These provide overarching guidance on how to plan animal studies, and cover formulation, dialogue with scientists and the animal facility, and quality control of the various components in the study. These guidelines are important reading for anyone planning a research project and are available to download free of charge. In addition, a PowerPoint presentation on the guidelines, and a simple checklist, are available from the Norecopa website.
Three-minute video on PREPARE guidelines
Norecopa have released a short film illustrating the rationale behind the development of the PREPARE guidelines for planning animal studies and why they should be used in conjunction with more commonly used reporting guidelines. This is a useful resource for all researchers.
RSPCA/LASA guidance on developing induction materials for AWB members
A useful guidance is now available online to help establishments prepare induction packs for new members of the AWERB. In the UK, the AWERB is a joint animal welfare body and ethics committee; however the guidance will still be highly relevant to animal welfare bodies in Irish establishments.
LASA guiding principles on aseptic surgery 2017
In April 2017, LASA updated its guide to aseptic technique. This is essential reading for all new and experienced researchers undertaking surgical procedures.
NC3Rs toxicology newsletter
The National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) has launched an e-newsletter (ToxNews) aimed at the toxicology community. The quarterly newsletter will provide updates on their Toxicology and Regulatory Sciences programme, including information on publications, funding opportunities and events. To subscribe, email firstname.lastname@example.org.
A report on the second Newcastle meeting on laboratory animal euthanasia has been published in Animals. The HPRA strongly advises all personnel involved in the euthanasia of mice, rats and zebrafish to review this document. It is free to download:
- Hawkins, P.; Prescott, M.J.; Carbone, L.; Dennison, N.; Johnson, C.; Makowska, I.J.; Marquardt, N.; Readman, G.; Weary, D.M.; Golledge, H.D.R. A Good Death? Report of the Second Newcastle Meeting on Laboratory Animal Euthanasia. Animals 2016, 6, 50.
AALAS-FELASA working group on harm-benefit analysis
This AALAS-FELASA working group published two documents, the first on the concepts of harm-benefit analysis, and the second outlining their recommendations for carrying out a harm-benefit analysis. These in-depth documents may be useful training documents for members of establishment ethics committees.
Publications from the European Commission
The European Commission has published a set of colour posters and guidance documents on important topics including: animal welfare bodies, education and training, inspections and enforcement, project evaluation and retrospective assessment, as well as severity assessment. These are very useful tools which should enhance understanding of the provisions of the Directive and therefore we highly recommend that you download/print these materials. All publications are available free of charge.
The RSPCA has published a resource book for lay members of ethical review and similar bodies worldwide. This free publication is intended mainly to assist lay persons with their work in ethical committees, but we think it would also be quite useful for the training of non-lay members of ethics committees. Although it refers to UK legislation and processes, the principles are relevant to ethics committees here in Ireland.
Fighting cancer: Animal research at Cambridge
As part of their commitment to openness, the University of Cambridge has released a short film about animal research in the university. It looks inside their animal facilities and discusses how mice are used for cancer research, as well as touching on the 3Rs.
The HPRA strongly encourages scientists to work on refining their animal models. The following papers are recommended reading:
Norecopa severity classification compilation
Norecopa has compiled existing guidance on severity classification and categorised the guidance into six categories: interventions on body systems and functions; induction of diseases; pharmacology and other external causes; housing, environment and behaviour; foetuses and premature animals; and clinical signs.
In ovo model for immuno-oncology screening
According to the NC3Rs Innovation Platform, the development of efficient new drugs in immuno-oncology (IO) is limited by the availability and cost of reliable in vivo models. Thus, there is a need to develop fast, sensitive, and reliable 3Rs-compliant IO models allowing large in vivo screenings for various types of IO compounds including immune checkpoint inhibitors, vaccines or adoptive cell therapies. Inovotion has developed a new assay for IO drug screening that is sensitive and reliable, using embryonated chicken eggs with a complete immune system, to test the efficacy and toxicity of anticancer drug candidates in the same in ovo model, rather than two mouse models. Academic and/or industry partners are currently being sought to provide diverse, novel immuno-oncology compounds (with preclinical data available) to test in this new model.
Beyond the 3Rs
An article entitled Beyond the 3Rs: Expanding the Use of Human-Relevant Replacement Methods in Biomedical Research has been published in Altex. The authors suggest that it is time to update the strategic application of the 3Rs, 60 years after the 3Rs framework was originally published, by prioritising the implementation of Replacement techniques and ensuring greater human relevance of non-animal methods.
Single use needle initiative
The NC3Rs has highlighted the risks of reusing needles, which include: causing unnecessary pain and suffering as well as tissue damage; transferring tissue products between animals which could compromise the science; and spreading infections between animals. They advise that single use of needles should be standard practice, which the HPRA strongly agrees with. Free A3 posters on this topic are available from the NC3Rs.
New book on experimental design
A new book “Statistical Experiment Design for Animal Research” by C.O.S. Sorzano and M. Parkinson has been published and made freely available online. This useful resource includes chapters on why we need experimental design, sample size calculations, design of experiments and statistical pitfalls.
Two-minute video introducing Humane Endpoints
A short and simple video introducing the concept of humane endpoints has been created by laboratory animal veterinarian Aurora Brønstad from the University of Bergen. This might be a useful resource for the training of new animal care staff and researchers.
Data on formulation and administration of novel substances
A paper has been published in the International Journal of Toxicology with the results of a survey, in which the authors have collected data from over 400 formulations used in more than 1,000 animal studies by multiple routes. Formulation and administration of novel substances is often a challenge in animal studies, since, by definition, there is usually very little published data on, for example, their solubility and stability. Lack of data can lead to excessive animal use, unplanned delays in the evaluation and development of drugs, results caused by the vehicle rather than the drug, etc. The data in this paper includes maximum tolerated use levels by species, route, duration of study, dose-limiting toxicity where reported, review of the available literature on each vehicle, guidance on syringe selection, volume and pH limits by route, with basic guidance on pre-clinical formulation development.
Swedish 3Rs Centre newsletter
The Swedish 3Rs Centre has released the first issue of its newsletter entitled 'Focus on the 3Rs'. This newsletter is available in both English and Swedish and includes articles on 3Rs topics and links to upcoming 3Rs events.
European Commission posters
The European Commission has created a number of posters on various important aspects of Directive 2010/63/EU that can be downloaded, printed and placed in work areas. These are useful visual aids to the understanding of key aspects of the legislation, and two new posters have been added to the collection recently – one on animal welfare bodies and one on the authorisation and reporting of the use of genetically altered animals. The HPRA would encourage the display of these visual aids in suitable locations within establishments.