DR PENNY HAWKINS RSPCA RESEARCH ANIMALS DEPARTMENT Identifying and reducing sources of suffering during procedures, including avoiding severe suffering

Requirements of the Directive ARTICLE 13: CHOICE OF METHODS 13(2): In choosing between procedures, those which to the greatest extent meet the following requirements shall be selected: a)use the minimum number of animals; b)involve animals with the lowest capacity to experience pain, suffering, distress or lasting harm; c)cause the least pain, suffering, distress or lasting harm; and are most likely to achieve satisfactory results

Requirements of the Directive ARTICLE 38: PROJECT EVALUATION 38(1): The project evaluation shall... Verify that the project meets the following criteria: c)The project is designed so as to enable procedures to be carried out in the most humane and environmentally sensitive manner possible 38(2): The project evaluation shall consist in particular of the following: b)An assessment of the compliance of the project with the requirement of replacement, reduction and refinement

1.Consider what will happen to each animal during the procedure, from beginning to end 2.Identify potential causes of suffering 3.Research how each of these can be avoided or refined 4.Define humane endpoints 5.The end result should be a significant reduction in suffering Eliminating or reducing suffering begins at the project planning stage THE APPROACH

The ‘user’, or person applying for project authorisation Other personnel can inform or assist the user: –Person(s) “responsible for overseeing the welfare and care of the animals in the establishment” - 24(1a) (Named Animal Care and Welfare Officer, NACWO) –Person(s) who “shall ensure that the staff dealing with animals have access to information specific to the species housed in the establishment” - 24(1b) (Named Information Officer, NIO) Who should do this?

The role of the animal- welfare body ARTICLE 27: TASKS OF THE ANIMAL-WELFARE BODY 27(1): The animal-welfare body shall, as a minimum, carry out the following tasks: a)advise the staff dealing with animals on matters related to the welfare of animals, in relation to their acquisition, accommodation, care and use; b)advise the staff on the application of the requirement of replacement, reduction and refinement, and keep it informed of technical and scientific developments concerning the application of refinement

Researchers Animal technologists Veterinarians Animal-welfare body, and/or other ethics committees In the UK, the Competent Authority may also offer advice A ‘team’ approach COMBINING DIFFERENT EXPERIENCE, KNOWLEDGE AND PERSPECTIVES

EC ‘Working Document on the Availability of Information on the Three Rs’ Scientific literature on animal behaviour and welfare –Laboratory Animals, PLoS Online resources –FELASA website, UK NC3Rs, Norecopa/AWIC 3R guide, RSPCA guidelines and working group reports Meetings and discussions with colleagues Researching refinements – information sources

1.Consider what will happen to each animal during the procedure, from beginning to end 2.Identify potential causes of suffering 3.Research how each of these can be avoided or refined 4.Define humane endpoints 5.The end result should be a significant reduction in suffering Putting the 5-stage approach into practice

1.Caught and removed from the cage 2.Restrained 3.Subjected to a needle stick, e.g. to access the sublingual vein 4.Possibly a second needle stick, if rehydration is necessary 5.Returned to the cage 1. Consider everything that will happen to the animal A SIMPLE EXAMPLE – DURING BLOOD SAMPLING, A MOUSE IS...

1.Caught and removed from the cage 2.Restrained 3.Subjected to a needle stick, e.g. to access the saphenous vein 4.Possibly a second needle stick, if rehydration is necessary 5.Returned to the cage

At the doctor’s... Doctor: “I need to take a blood sample from you today...” “... I take my blood samples by sticking a knife into your neck without anaesthesia...” “... But don’t worry, I’ll inject 2 litres of fluid into your peritoneal cavity first so you don’t die from loss of blood.”

‘Critical anthropomorphism’ = empathy + objective, knowledge-based consideration of what is likely to be significant to the animal

2. Identify potential causes of suffering

3. Research how these could be avoided or refined Hurst & West (2010) Nature Methods 7, 825-6

Refinement  Explain your choice of species, model(s) and method(s). Explain why they are the most refined for the intended purpose.  How will you minimise animal suffering in order to achieve your objectives?  Provide specific justification for any protocols categorised as ‘severe’. THE 3Rs Under the Animals (Scientific Procedures) Act 1986 section 5B(3)(b), in carrying out the evaluation of the programme of work, the Secretary of State must assess the compliance of the programme of work with the principles of replacement, reduction and refinement.

Expected adverse effects Describe the expected adverse effects of the series of regulated procedures described above. For each adverse effect indicate under the headings below:  the likely incidence  how the adverse effect will be recognised  the refinement measures and other controls you will adopt to prevent occurrence or minimise severity  practicable and realistic humane end-points. Expected adverse effects and likely incidence How the adverse effect will be recognised Refinement control measures Humane end-points and limits of severity List each of the steps in this protocol. Note: It is accepted that the order of steps may be varied according to scientific need. Indicate which steps are optional and for each give the anaesthetic code. If appropriate indicate the method of killing, Schedule 1 or non-Schedule 1. Give brief details of non- Schedule 1 methods e.g. perfusion fixation (AC). Protocol title: Species of animals (state if genetically altered): Severity category:

Severe suffering – rheumatoid arthritis research 1. ADMINISTRATION OF RA INDUCER

Severe suffering – rheumatoid arthritis research 2. EFFECTS OF ARTHRITIS

Severe suffering – rheumatoid arthritis research 3. OTHER WELFARE ISSUES

Ulcer(s) with no signs of healing after 3 days Weight bearing on tail Severe paw swelling Spontaneous, audible vocalisation Weight loss of 20 % Humane endpoints FOR RHEUMATOID ARTHRITIS RESEARCH M Seed, University of East London

Two points to note about reducing suffering: 1 EFFECTS OF PROCEDURES SHOULD BE CONSIDERED IN THE CONTEXT OF THE ANIMAL’S WHOLE LIFE EXPERIENCE Separation from the dam – all mammals Transport Capture, handling, restraint Housing and husbandry, e.g. cage change Identification Scientific procedures Effects of procedures Euthanasia

It can be obvious when a refinement will reduce suffering – but this is not always the case There has to be a system in place for evaluating refinements so that an informed decision can be made about their value, or they can be further developed This can be done as part of severity assessment REFINEMENTS NEED TO BE EVALUATED Two points to note about reducing suffering: 2

Reducing suffering starts at the project planning stage Think about every aspect of every procedure Take the animal’s whole life experience into account Use a team approach – no one person can have all the necessary knowledge and expertise Ensure a good information flow, from the literature and colleagues Regularly review and evaluate how effectively suffering is being reduced Conclusions

Thank you