Engaging Industry to develop best practice for laboratory-housed dogs, improving welfare and quality of scientific output

Over 3,500 dogs were used in UK laboratories in 2013 in the safety testing of new medicines, with many more used
globally and use set to rise given changes in legislation on testing chemicals and safety assessment. Despite this, we do not have a sound evidence-base to determine the best practice for housing or scientific procedures in the dog. Our BBSRC Industrial CASE studentship project sought to identify the link between dog welfare and quality of data output, as well as developing Refinement strategies to improve and harmonise welfare and data quality. The results of the study showed an effect of welfare particularly on heart rate and blood pressure data, but also on behaviour, psychological state, and sensitivity to mechanical pressure. Our findings also showed significant benefits to welfare of implementing a short training protocol in the pre-study acclimatisation phase of a study where a compound was delivered directly to the dog's stomach through a tube (oral gavage). There are many more aspects of the laboratory dog's life cycle which remain to be Refined and data are still lacking on the best methods for doing so.

We have hosted an Impact Workshop with our existing and other potential partners, as well as a member of the Home Office's Animals in Science Regulation Unit (ASRU), to identify procedures most suitable for Refinement and to develop practical strategies which can be integrated into existing protocols.

We have three main objectives:

(1) Despite new European legislation there is still a need to harmonise practices across multinational Industry to ensure that data are comparable. Our first objective is to for LH to acquire a broad understanding of the range of housing, husbandry, and procedure practice, together with the rationale for the existing practices, and provide a centralised resource, in the form of a website to share across all users. Much of this will be open access, providing details of welfare assessment in the dog. It will include photographs, videos and recent publications. A closed registration-only section will provide information on how to conduct procedures, such as oral gavage and inhalation, as humanely as possible.
(2) Our Partners have highlighted four procedures, oral gavage, inhalation studies, jacketed telemetry and single housing, that could be modified to improve welfare. Data will be collected on the dogs' welfare and the quality of data output. We shall also collect data on the time investment as any changes must be feasible to implement.
(3) Building up on the knowledge and experience gained from both the PhD and from the second objective, we shall deliver training and engagement activities that will be accredited by LASA for relevant staff to gain recognised qualifications. These will include training courses, talks and other activities, and will be delivered free of charge to all major companies using dogs in the UK (one Partner company will no longer be housing dogs, but is instrumental in the development of the engagement activities). Increasing understanding of welfare and learning theory would also allow responsible staff such as technicians and welfare officers to promote better welfare and understand the need for Refinement and its benefits to the quality of scientific data.

The outcome of this project will be for LH to gain skills and experience, and to provide evidence-based recommendations to disseminated across a network of highly-experienced colleagues working with dogs to improve their welfare and scientific output, with the potential to reduce the number of dogs used in laboratory research and testing and impact on guidelines and policy.

In the UK, around 85% of the >3,500 dogs used in scientific research are used for safety assessment of new medicines. Our objectives are to:
(1) Develop a centralised web resource for those working in dog facilities
LH will learn about existing practices and welfare implications for dogs, and bring together the information (written materials, guides, publications, videos and photographs) to share with the dog-using community to allow them to make planned Refinements. The website will be available to those employed in dog facilities.
(2) Quantify the Refinements of scientific procedures with Partners
In association with our Partners and using the Welfare Assessment Framework which has validated indicators of positive and negative welfare (eg behaviour, nociception, cardiac, affect), we have identified four potential regulated procedures for Refinement. These will be rolled out where appropriate utilising desensitisation, positive reinforcement training and increased predictability. Changes to key parameters will be monitored (eg clinical pathology) to determine whether the quality of the scientific output is also improved.
(3) Deliver engagement activities to Industry
Using existing data and that developed, we will deliver targeted, and accredited, training to staff in dog facilities, specifically using positive reinforcement training and desensitisation. Staff will be trained in principles of welfare monitoring and learning theory, undertaking practical experience of training with on-going support available via (1). The experience and skills gained in objectives 1 and 2, as well as our Partners' input are critical to the success of 3.
The project should provide LH with the knowledge, skills and expertise to be uniquely placed to provide a network for the dissemination, sharing and harmonisation of best practice nationally and internationally. Our Partners will provide the opportunity to acquire the skills and knowledge and share their expertise

Interchanger (Researcher Co-I)

The primary impact will be upon the Interchanger (LH). While LH is well-placed to conduct this research, and has considerable experience in working with laboratory-housed dogs, experience of different facilities and operating procedures will increase her understanding of global dog use. While LH holds a PIL, she is not experienced in conducting regulated procedures. Designing Refinements in conjunction with experienced staff will allow LH a greater understanding of each regulated procedure. While LH has experience collecting and analyzing behavioural and cardiovascular data, she is not experienced in collecting and analyzing physiological data. Staff at our Partner companies are experienced in these techniques and time spent on site will allow LH to learn these techniques (e.g. clinical pathology, pathology).

Industry

The beneficiaries will be those working in industry using dogs in (especially safety assessment) research. There are seven multinational companies with dog facilities in the UK, three of whom are partners, and another three are supporting our project (see letters). Breeders of dogs for scientific purposes also have a vested interest in increasing the fidelity of the dog models they supply to Industry. The material on offer in the engagement activities, training and website will be of value to care, technical and scientific staff.


Harmonisation of welfare and data output between sites within companies has proven to be difficult, even under considerable standardisation, with improved welfare often leading to greater harmonisation in data output. Dog use most likely exceeds 100,000 dogs per year, much of which is conducted outwith the UK by companies with a UK presence. The potential impact of this research is considerable. We describe stakeholders in the project in broad categories. Two Impact Workshops are planned for the beginning and end of the project to bring key stakeholders together to engage in and then monitor the impact of the project.

Regulators

The Home Office Animals in Science Regulation Unit (ASRU) was represented at our Impact Workshop suggesting that the information gained by Refinements, and the materials for training, could be incorporated into the Home Office dog module which prospective new licensees must undertake. Refinements may lead to a downgrade in severity limits.

Information which changes the interpretation of findings or increases confidence in its interpretation is of interest to medical regulatory bodies such as MHRA and FDA. Increasing certainty in the cause of observed changes is critical in improving the predictability of animal models.

The public

The public continue to show a vested interest in the welfare of animals used in science and the success of research. Recently, patient groups have become more involved in LAS. The general public have particular concerns about the use of dogs, hence their special protection. There is little in the public domain supporting good practices in the dog or disseminating progress in the 3Rs. Our prospective Partners have committed to providing information for a website to support those working with dogs, with an open access area showcasing best practice.

The Government and NC3Rs

The Government has a commitment to Reducing the numbers of animals used in scientific procedures, while also supporting scientific progress. Refinement of procedures and improvement of data quality can increase statistical power and Reduce animal numbers. The Government set up and contributes to funding the NC3Rs with the remit of promoting the 3Rs in UK-based research. Hall has already provided information for the NC3Rs webpage promoting best practice in the dog.

Organisations supporting the Laboratory Animal Sciences (LAS)

Within the UK there are several organisations, such as LASA, LAVA and IAT which support those working in LAS and provide information on best practice and technical training.