3Rs Information - General

Focus on Severe Suffering

While any level of animal suffering is a concern, tackling severe suffering should be a focus for all those involved in the use of animals for research or regulatory purposes. The RSPCA have a web resource focusonseveresuffering.co.uk, as part of their ‘Focus on Severe Suffering’ initiative. This resource provides information on what can cause ‘severe’ suffering in laboratory animals, along with practical approaches that can be adopted to reduce, or ideally eliminate, severe suffering experienced by animals.

3Rs Self-Assessment Tools

The NC3Rs has two online self-assessment tools that research groups and establishments can use to collate and track their 3Rs activities. These free-to-use, secure interactive tools help researchers, ethics committee members and others to identify and implement 3Rs opportunities.

 

Environmental Enrichment

The NC3Rs have developed a web resource to assist technicians and researchers make informed decisions about the suitability of environmental enrichment items for animals within their facility. Example enrichment protocols are available, focusing on rat, mouse and zebrafish husbandry, however, the general advice is applicable to all species.
 

RSPCA - Challenging refinements meeting

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)

A series of three articles published in the journal Shock in 2019 stipulate the minimum quality thresholds in preclinical sepsis studies. Part 1 discusses study design and humane endpoints; Part 2 discusses types of infection and organ dysfunction; and Part 3 discusses fluid resuscitation and anti-microbial therapy. An editorial published in Clinical Science in July 2020, explores further the clinical translatability and incorporation of the 3Rs into sepsis research. These reports should be consulted when preparing project applications that use these models, in order to demonstrate that appropriate consideration has been given to the principles of the 3Rs. Due to the potential for severe suffering in models of sepsis, it is of particular importance that all opportunities to incorporate the principles of the 3Rs are adopted.

 

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. 

 

ARRIVE Guidelines

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.

 

HARRP guidelines

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: 

 

 

PREPARE guidelines

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.

 

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 enquiries@nc3rs.org.uk.

 

Euthanasia

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:

 

The American Veterinary Medical Association (AVMA) have released a 2020 edition of their guidelines for the euthanasia of animals. Although these comprehensive guidelines are intended for veterinarians who carry out or oversee the euthanasia of animals, they would also be of relevance to researchers and technicians who carry out euthanasia. The guidelines cover a wide range of species with a section dedicated to laboratory animals including farm animals, rodents, dogs, cats, rabbits, ferrets, amphibians, reptiles and fish. 

 

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.

 

Ethical Review

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.

AWB resources


The RSCPA have a collection of resources for animal welfare ethical review bodies (AWERBs) including a Scientist – AWERB engagement pack and a useful guidance 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.
 

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. 

Refinement of severe animal models

 The following papers are essential reading for these specific models:

 

 

 

 

 

 

 

 

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.

 

Book on experimental design

A 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.

 

Sex differences in animal studies

 A perspective article in the journal Science highlights the importance of examining sex differences in biological research. A significant sex bias persists in preclinical animal research, with a majority of studies investigating male subjects only. This is true even in the case of conditions that show a marked female predominance. 

European Commission inventory of 3Rs knowledge sources

 An inventory of knowledge sources potentially relevant to the 3Rs has been compiled by the EC's Joint Research Centre (JRC) based on data from its survey in 2016 of 800 knowledge sources relevant to the 3Rs. The inventory should be viewed as a snapshot of the current status of knowledge sources available, and as a starting point for further analysis of knowledge sharing strategies.

Culture of care

The European Federation of the Pharmaceutical Industry and Associations (EFPIA) Research and Animal Welfare Group’s paper entitled ‘Assessing and benchmarking ‘Culture of Care’ in the context of using animals for scientific purpose’ is a framework document that has been developed with the aim of helping organisations performing animal research and testing to identify gaps or potential areas for improvement in support of a positive culture of care.

A second useful document on culture of care, published by the RSPCA, is an information sheet on promoting a culture of care.

Animal study registries

Study registries ask researchers to detail their hypothesis, experimental strategy and analytical plans before the studies begin, in order to prevent cherry-picking of findings. The aim of study registries is to counter publication bias, improve investigations and increase transparency, and registries can actually boost a study’s credibility. This approach is common in clinical trials, with the largest registry, ClinicalTrials.gov, having over 330,000 registered studies. There are now two animal specific study registries available and researchers are strongly encouraged to participate: Preclinicaltrials.eu was set up in 2018 in the Netherlands, and Animalstudyregistry.org was set up in early 2019 by Germany’s 3Rs Centre.

Systematic reviews

A review paper was published in Animals entitled ‘How can systematic reviews teach us more about the implementation of the 3Rs and animal welfare?’. The authors introduce the systematic review methodology and value of this methodology in relation to the 3Rs and beyond, with examples included on how this can lead to more responsible and sustainable research.

Research integrity in universities

The League of European Research Universities (LERU) has issued a comprehensive advice paper identifying ways in which universities can develop a research integrity culture within their institution. This includes advice on how universities can improve research design, conduct and reporting, and how to educate researchers about research integrity. It also highlights the benefits of transparency and accountability at universities, and what universities can do to instil a culture of research integrity.

Experimental replications in animal trials

An article in Laboratory Animals addresses the problem of experimental replication, where researchers claim they have to replicate each experiment at least twice in order to have their research accepted for publication. The authors believe that how such replications are summarised to prove reproducibility in practice appears to be quite problematic from a statistical point of view. This article aims to fill this gap in the literature and to provide a reference for preclinical researchers which allows them to choose a powerful study design that fully adheres to replicability demands.
 


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