A review of the contributions of cross-discipline collaborative European IMI/EFPIA research projects to the development of Replacement, Reduction and Refinement strategies.

The objective of this review is to report on whether, and if so, how, scientific research projects organised and managed within collaborative consortia across academia and industry are contributing to the Three Rs (i.e. reduction, replacement and refinement of the use of animals in research). A number of major technological developments have recently opened up possibilities for more direct, human-based approaches leading to a reassessment of the role and use of experimental animals in pharmacological research and biomedicine. This report reviews how projects funded by one of the research funding streams, the Innovative Medicines Initiative (IMI), are contributing to a better understanding of the challenges faced in using animal models. It also looks how the results from these various projects are impacting on the continued use of laboratory animals in research and development. From the progress identified, it is apparent that the approach of private-public partnership has demonstrated the value of multicentre studies, and how the spirit of collaboration and sharing of information can help address human health challenges. In so doing, this approach can reduce the dependence on animal use in areas where it has normally been viewed as necessary. The use of a collaborative platform enables the Three Rs to be addressed on multiple different levels, such that the selection of models to be tested, the protocols to be followed, and the interpretation of results generated, can all be optimised. This will, in turn, lead to an overall reduction in the use of laboratory animals.

How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid.

Introduction: Chronic pain can profoundly affect the wellbeing of dogs and our understanding is limited regarding the multidimensional impact it has on dog quality of life. This study aimed to assess the factors that are significant and predictive of behavior problems in dogs using the Animal Welfare Assessment Grid (AWAG) to further understand what factors influence their welfare. Methods: Seventy six AWAG assessments were undertaken across 46 dogs that clinicians diagnosed as having musculoskeletal conditions that caused chronic pain. Wilcoxon-rank sum tests were used to assess the difference in scores between dogs with behavior disorders and a cohort of healthy dogs (n = 143). Results: All physical factors besides body condition, and all psychological, environmental, and procedural factors were significantly different between healthy dogs and dogs with chronic pain, evidencing how chronic pain impacts all domains of a dog's life. Spearman Rank Correlation Coefficient (RS) revealed several significant strong positive correlations such as the association between the severity of clinical symptoms with poorer mobility and the frequency at which the dog experienced fearful stimuli. Logistic regression showed that fears and anxieties frequency, the dog's reaction to stressors, engagement with enrichment, and social interactions were significant predictors of chronic pain in dogs. Discussion: This highlights that typical signs of musculoskeletal disorders such as gait changes, stiffness, lameness might manifest after behavioral changes such as increased fearfulness, prolonged recovery from a stressful event, a reduced interested in social interactions, toys or play. Owners only seeking veterinary attention when the presence of physical signs of disease are evident may result in a delayed veterinary attention resulting in reduced welfare. Regular veterinary assessments combined with use of the AWAG can proactively identify these behavioral indicators and result in prompt treatment and improved quality of life.

Corrigendum: How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid.

[This corrects the article DOI: 10.3389/fvets.2024.1374858.].

A Multidimensional Evaluation of the Factors in the Animal Welfare Assessment Grid (AWAG) That Are Associated with, and Predictive of, Behaviour Disorders in Dogs.

Behavioural disorders in dogs are common and have severe welfare consequences for dogs. This study aimed to assess the factors that are significant and predictive of behaviour problems in dogs using the animal welfare assessment grid (AWAG) to further understand what factors influence their welfare. 177 AWAG assessments were undertaken across 129 dogs that clinicians deemed to have a behavioural disorder. Wilcoxon rank-sum tests were used to assess the difference in scores between dogs with behaviour disorders and a cohort of healthy dogs (n = 117). This analysis showed that all physical factors besides body condition, all procedural factors besides procedure pain, and all psychological, and environmental factors were significantly different between healthy dogs and dogs with behaviour disorders. Spearman rank correlation coefficient (RS) revealed several significant strong positive correlations including the procedural impact on the dog's daily routine with aggression towards unfamiliar people and procedure pain, as well as other correlations between the dog's behaviour during assessment with the frequency at which they encounter fears and anxieties, clinical assessment and procedure pain, and reaction to stressors and social interactions. These findings highlight the interdependent nature of the various influences of welfare. Logistic regression analysis identified that aggression towards the caregiver, fears and anxieties frequency, and choice, control, and predictability were all significant predictors of behaviour disorders. The findings have important implications for veterinary, behaviour, and animal welfare professionals as any changes across these factors may indicate poor welfare linked to emotional disorders in dogs.

Assessing the Welfare of Captive Group-Housed Cockroaches, Gromphadorhina oblongonota.

The welfare of invertebrates under human care is of growing concern, particularly with the increasing interest in insect farming as an environmentally sustainable means of producing food. Additionally, individual welfare monitoring systems can be time-consuming and impractical for larger groups, particularly when individual animals are difficult to identify. It is, therefore, imperative to develop a validated system for monitoring terrestrial invertebrate welfare at a group level. The Animal Welfare Assessment Grid (AWAG) is an objective welfare-monitoring tool that has been approved for use with a wide range of species. This study modified the AWAG for large group-level welfare assessments and successfully trialled it on a terrestrial invertebrate species, a group of captive male Gromphadorhina oblongonota. The modified template evaluated the group's welfare by scoring changes to 12 factors that could be tracked over time. The results highlight that the welfare of G. oblongonota is likely to be influenced by environmental and social factors, and inform practical improvements in G. oblongonota care that will result in improved welfare. The findings also demonstrate an efficient way to assess the welfare of invertebrates at the group level, and given the recent UK legislation (Animal Welfare (Sentience) Bill, 2022) plus the emerging interest in invertebrate farming, our findings hold timely significance.

Preliminary validation of a novel tool to assess dog welfare: The Animal Welfare Assessment Grid.

Animal welfare monitoring is a vital part of veterinary medicine and can be challenging due to a range of factors that contribute to the perception of welfare. Tools can be used, however; there are few validated and objective methods available for veterinary and animal welfare professionals to assess and monitor the welfare of dogs over their lifetime. This study aimed to adapt a framework previously validated for other species, The Animal Welfare Assessment Grid (AWAG), for dogs and to host the tool on an accessible, easy to use online platform. Development of the AWAG for dogs involved using the scientific literature to decide which factors were relevant to score welfare in dogs and to also write the factor descriptors. The primary tool was trialed with veterinary professionals to refine and improve the AWAG. Content validity was assessed by subject matter experts by rating the validity of the factors for assessing dog welfare using the item-level content validity index (I-CVI) and scale-level content validity index based on the average method (S-CVI/Ave). Construct validity was evaluated by users of the tool scoring healthy and sick dogs, as well as healthy dogs undergoing neutering procedures. Mann Whitney tests demonstrate that the tool can differentiate between healthy and sick dogs, and healthy and healthy dogs post elective surgery. Test re-test reliability was tested by users conducting multiple assessments on individual dogs under non-changing conditions. Inter-rater reliability was assessed by two users scoring an individual dog at the same time in veterinary referral practice. Repeated measures ANOVA for test re-test and inter-rater reliability both show no statistical difference between scores and that the scores are highly correlated. This study provides evidence that the AWAG for dogs has good content and construct validity, alongside good test re-test and inter-rater reliability.

Welfare Assessment of Invertebrates: Adapting the Animal Welfare Assessment Grid (AWAG) for Zoo Decapods and Cephalopods.

Consumer demand for invertebrates is on the rise as their numbers in the wild dwindle. However, with the growing conservation efforts of modern zoos and aquariums, and evidence from over 300 studies showing that invertebrates are capable of sentience, public interest, and moral concern for welfare of invertebrates have increased. The challenge for zoos and aquariums is in developing an objective and repeatable method for evaluating welfare that can be applied to invertebrates in zoological collections. Recently introduced into zoological collection management is the Animal Welfare Assessment Grid (AWAG). The AWAG helps to identify negative and positive welfare states, through assessing animal- and environmental-based indicators to make changes that lead to a better quality of life. Originally developed for the assessment of laboratory primates, the system has been successfully adapted to assess a variety of taxa across different environments, facilitated by the development of cloud-based software. In this study, the AWAG has been adapted to assess the cumulative lifetime experience of captive decapods and cephalopods at two different institutions, Marwell Zoo and National Marine Aquarium. This study has provided further evidence that the AWAG is adaptable and demonstrates the first time any objective scoring system has been successfully adapted for use in invertebrates. Through graphical representation, the results show that the AWAG identifies changes in welfare scores that can be attributed to specific events and can be used to predict the future vulnerability of species to welfare changes and suggest alternative management methods. This monitoring tool provides a versatile method of implementing practical welfare monitoring in zoos and aquariums.

Assessment of the Welfare of Experimental Cattle and Pigs Using the Animal Welfare Assessment Grid.

The Animal Welfare Assessment Grid (AWAG) is a method for assessing quality of life, originally designed for experimental primates. This study adapts the AWAG for use in cattle and pigs, by adapting the factors included for these species and including data which had been collected previously as the standard approach to monitoring these species in research. The intention is that the results presented here will allow the future data collected for experimental cattle and pigs to be optimised for inclusion in an AWAG. Data were collected from two vaccine assessment studies at the Pirbright Institute. Factors were scored for every recorded event using retrospective data and CCTV clips. There was a lack of behavioural data recorded in both studies, which limited the accuracy of assessing each animal's welfare. This paper emphasises the importance of including behavioural information when assessing welfare and not simply relying on assessment of physical condition. Scores peaked following an exponential rise as animals reached set humane end points. This demonstrated the potential of using the AWAG to aid the decision-making of when euthanasia should be performed. Our study shows the AWAG to be a useful tool for assessing welfare, which can be used in harm:benefit assessment.

The extended welfare assessment grid: a matrix for the assessment of welfare and cumulative suffering in experimental animals.

Combining a range of assessment parameters into one usable entity has been identified as an important goal in providing a practical, objective and robust assessment of welfare, particularly in laboratory animals. This paper refines and extends one such previously published method. The proposed Extended Welfare Assessment Grid provides for the incorporation of changes in the state of an animal over time, allowing for predictive, retrospective, scheduled, or event monitoring. It enables the numeric, as well as visual, representation of the animal's welfare, placing this in the context of the careful and realistic justification for experimental use of the animal. This assessment method represents a valuable tool for those tasked with ensuring ethical oversight, as well as for those planning the use, or monitoring, of animals in research. It is particularly applicable to animals used in long-term studies, especially non-human primates. It is believed that this system will draw attention to the temporal component of suffering that is often overlooked in the planning of research schedules and allow an assessment of cumulative suffering imposed by the events that occur.

Too Cute to Kill? The Need for Objective Measurements of Quality of Life.

The recognition of animal suffering is influenced by cultural and societal prejudices and the cuteness of an animal leads to bias in the way it is treated. It is important to consider the animal's behaviour and its environment-not just its physical condition-when assessing its quality of life. The Animal Welfare Assessment Grid (AWAG) is a useful tool for this purpose. The AWAG offers an evidence-based tool for continual welfare assessment, using technology where appropriate, such as digital activity recording, to facilitate decision-making and lead to improvements in the animals' quality of life. It is highly adaptable to any species by assessing the four parameters of physical health, psychological wellbeing, environmental quality, and clinical and management procedural events. The outcome of assessing welfare should be action to improve it. Societal ethics and policy-making lead to legislation balancing the values we hold for different species. Influencing policy development in such matters as animal welfare, ecological conservation, and risks to humans requires a focus on public attitudes to, and understanding of, science, as well as consideration of potential unforeseen consequences of the social/environmental/economic impacts of policies.

Animal Research beyond the Laboratory: Report from a Workshop on Places Other than Licensed Establishments (POLEs) in the UK.

Research involving animals that occurs outside the laboratory raises an array of unique challenges. With regard to UK legislation, however, it receives only limited attention in terms of official guidelines, support, and statistics, which are unsurprisingly orientated towards the laboratory environment in which the majority of animal research takes place. In September 2019, four social scientists from the Animal Research Nexus program gathered together a group of 13 experts to discuss nonlaboratory research under the Animals (Scientific Procedures) Act (A(SP)A) of 1986 (mirroring European Union (EU) Directive 2010/63/EU), which is the primary mechanism for regulating animal research in the UK. Such nonlaboratory research under the A(SP)A often occurs at Places Other than Licensed Establishments (POLEs). The primary objective of the workshop was to assemble a diverse group with experience across a variety of POLEs (e.g., wildlife field sites, farms, fisheries, veterinary clinics, zoos) to explore the practical, ethical, and regulatory challenges of conducting research at POLEs. While consensus was not sought, nor reached on every point of discussion, we collectively identified five key areas that we propose require further discussion and attention. These relate to: (1) support and training; (2) ethical review; (3) cultures of care, particularly in nonregulated research outside of the laboratory; (4) the setting of boundaries; and (5) statistics and transparency. The workshop generated robust discussion and thereby highlighted the value of focusing on the unique challenges posed by POLEs, and the need for further opportunities for exchanging experiences and sharing best practice relating to research projects outside of the laboratory in the UK and elsewhere.

Refinements in husbandry, care and common procedures for non-human primates: Ninth report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement.

Preface Whenever animals are used in research, minimizing pain and distress and promoting good welfare should be as important an objective as achieving the experimental results. This is important for humanitarian reasons, for good science, for economic reasons and in order to satisfy the broad legal principles in international legislation. It is possible to refine both husbandry and procedures to minimize suffering and improve welfare in a number of ways, and this can be greatly facilitated by ensuring that up-to-date information is readily available. The need to provide such information led the British Veterinary Association Animal Welfare Foundation (BVAAWF), the Fund for the Replacement of Animals in Medical Experiments (FRAME), the Royal Society for the Prevention of Cruelty to Animals (RSPCA) and the Universities Federation for Animal Welfare (UFAW) to establish a Joint Working Group on Refinement (JWGR) in the UK. The chair is Professor David Morton and the secretariat is provided by the RSPCA. This report is the ninth in the JWGR series. The RSPCA is opposed to the use of animals in experiments that cause pain, suffering, distress or lasting harm and together with FRAME has particular concerns about the continued use of non-human primates. The replacement of primate experiments is a primary goal for the RSPCA and FRAME. However, both organizations share with others in the Working Group, the common aim of replacing primate experiments wherever possible, reducing suffering and improving welfare while primate use continues. The reports of the refinement workshops are intended to help achieve these aims. This report produced by the British Veterinary Association Animal Welfare Foundation (BVAAWF)/Fund for the Replacement of Animals in Medical Experiments (FRAME)/Royal Society for the Prevention of Cruelty to Animals (RSPCA)/Universities Federation for Animal Welfare (UFAW) Joint Working Group on Refinement (JWGR) sets out practical guidance on refining the husbandry and care of non-human primates (hereinafter primates) and on minimizing the adverse effects of some common procedures. It provides a valuable resource to help understand the physical, social and behavioural characteristics and needs of individual primates, and is intended to develop and complement the existing literature and legislative guidelines. Topics covered include refinements in housing, husbandry and common procedures such as restraint, identification and sampling, with comprehensive advice on issues such as primate communication, assessing and facilitating primate wellbeing, establishing and maintaining social groups, environmental and nutritional enrichment and animal passports. The most commonly used species are the key focus of this resource, but its information and recommendations are generally applicable to other species, provided that relevant individual species characteristics are taken into account.

Assessment of Welfare in Zoo Animals: Towards Optimum Quality of Life.

Zoos are required to maintain a high standard of animal welfare, and this can be assessed using a combination of resource-based and animal-based indices usually divided into behavioural indicators, physiological indicators and clinical/pathological signs. Modern animal welfare assessments should aim to encompass positive affective states and the indicators that are useful in assessing these are discussed. When developing factors to be scored for each species, there is huge variability in the available information about the natural biology for some zoo species and even less information concerning those animals in captivity. Wild baselines are not always the most accurate indicator of what is right for an animal in captivity, which makes the identification of factors to include within species-specific welfare assessment even more challenging. When planning a welfare strategy for any species, it is important that the full range of their biological requirements and needs are considered, but this can be challenging for some zoo species and it is not possible to define a “one size fits all” welfare strategy. The different approaches for welfare assessment are reviewed, including the development of the Animal Welfare Assessment Grid which offers an evidence-based tool for continual welfare assessment, using technology where appropriate, to facilitate decision making and lead to improvements in the animals’ quality of life.

Using the Five Domains Model to Assess the Adverse Impacts of Husbandry, Veterinary, and Equitation Interventions on Horse Welfare.

The aim of this study was to conduct a series of paper-based exercises in order to assess the negative (adverse) welfare impacts, if any, of common interventions on domestic horses across a broad range of different contexts of equine care and training. An international panel (with professional expertise in psychology, equitation science, veterinary science, education, welfare, equestrian coaching, advocacy, and community engagement; n = 16) met over a four-day period to define and assess these interventions, using an adaptation of the domain-based assessment model. The interventions were considered within 14 contexts: C1 Weaning; C2 Diet; C3 Housing; C4 Foundation training; C5 Ill-health and veterinary interventions (chiefly medical); C6 Ill-health and veterinary interventions (chiefly surgical); C7 Elective procedures; C8 Care procedures; C9 Restraint for management procedures; C10 Road transport; C11 Activity-competition; C12 Activity-work; C13 Activity-breeding females; and C14 Activity-breeding males. Scores on a 1-10 scale for Domain 5 (the mental domain) gathered during the workshop were compared with overall impact scores on a 1-10 scale assigned by the same panellists individually before the workshop. The most severe (median and interquartile range, IQR) impacts within each context were identified during the workshop as: C1 abrupt, individual weaning (10 IQR 1); C2 feeding 100% low-energy concentrate (8 IQR 2.5); C3 indoor tie stalls with no social contact (9 IQR 1.5); C4 both (i) dropping horse with ropes (9 IQR 0.5) and forced flexion (9 IQR 0.5); C5 long-term curative medical treatments (8 IQR 3); C6 major deep intracavity surgery (8.5 IQR 1); C7 castration without veterinary supervision (10 IQR 1); C8 both (i) tongue ties (8 IQR 2.5) and (ii) restrictive nosebands (8 IQR 2.5); C9 ear twitch (8 IQR 1); C10 both (i) individual transport (7.00 IQR 1.5) and group transport with unfamiliar companions (7 IQR 1.5); C11 both (i) jumps racing (8 IQR 2.5) and Western performance (8 IQR 1.5); C12 carriage and haulage work (6 IQR 1.5); C13 wet nurse during transition between foals (7.5 IQR 3.75); and C14 teaser horse (7 IQR 8). Associations between pre-workshop and workshop scores were high, but some rankings changed after workshop participation, particularly relating to breeding practices. Domain 1 had the weakest association with Domain 5. The current article discusses the use of the domain-based model in equine welfare assessment, and offers a series of assumptions within each context that future users of the same approach may make when assessing animal welfare under the categories reported here. It also discusses some limitations in the framework that was used to apply the model.

Developing a Collaborative Agenda for Humanities and Social Scientific Research on Laboratory Animal Science and Welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including on issues around: international harmonisation, openness and public engagement, 'cultures of care', harm-benefit analysis and the future of the 3Rs. The process outlined below underlines the value of interdisciplinary exchange for improving communication across different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy.

Alopecia scoring: the quantitative assessment of hair loss in captive macaques.

Many captive animals show forms of pelage loss that are absent in wild or free-living conspecifics, which result from grooming or plucking behaviours directed at themselves or at other individuals. For instance, dorsal hair loss in primates such as rhesus macaques (Macaca mulatta) in research facilities, results from excessive hair-pulling or over-grooming by cage-mates. This behaviour appears to be associated with stress, and is controllable to some extent with environmental enrichment. Quantifying alopecia in primates (as in many species) is therefore potentially useful for welfare assessment. A simple system for scoring alopecia was developed and its reliability was tested. Study 1 showed high interobserver reliability between two independent scorers in assessing the state of monkeys coats from photographs. Study 2 showed that there were no significant differences between the scores derived from photographs and from direct observations. Thus, where hair loss due to hair pulling exists in captive primates, this scoring system provides an easy, rapid, and validated quantitative method, for use in assessing the success of attempts to reduce it via improved husbandry. In the future, such scoring systems might also prove useful for quantifying barbering in laboratory rodents.