PREPARE before you ARRIVE: advice on how to plan animal studies from day one
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1 IAT Dublin, 23 May 2018 PREPARE before you ARRIVE: advice on how to plan animal studies from day one norecopa.no/prepare Adrian Smith, Eddie Clutton, Elliot Lilley, Kristine Hansen & Trond Brattelid norecopa.no
2 Norecopa National Consensus Platform for the Replacement, Reduction and Refinement of Animal Experiments
3 European Consensus-Platform for Alternatives ecopa.eu Established in 2000 Recognises National Consensus Platforms (NCPs) with 4 stakeholders equally represented: Research Government Industry Animal welfare
4 norecopa.no 7,600 webpages 80,000 links 22,000 unique links <3.5% dead links
5 Averaging 150,000 page views a year at present
6 English-language newsletters
7 International consensus meetings Harmonisation of the Care and Use of: Fish (2005) Wildlife (2008) Fish (2009) Agricultural animals (2012) Wildlife October 2017 All presentations and consensus statements are on the internet: a lasting resource International Meetings Calendar:
8 Pre-published under Open Access on 3 August 2017, sponsored by the Universities Federation for Animal Welfare (UFAW), UK Published in the April 2018 issue of Laboratory Animals
9 Berti & Cima 1955, quoted in Öbrink and Rehbinder
10 Hurni 1969, quoted in Öbrink and Rehbinder
11 There are many guidelines for reporting animal studies GV-SOLAS committee, chaired by AW Ellery (1985) Öbrink & Waller, 1996 Jane Smith et al., 1997 Öbrink & Rehbinder: Animal definition: a necessity for the validity of animal experiments? Laboratory Animals, 2000 ARRIVE Guidelines, 2010 (Kilkenny et al., NC3Rs) Gold Standard Publication Checklist, 2010 (SYRCLE) Institute for Laboratory Animal Research, NRC, 2011 Instructions to authors, in many journals e.g. Nature s Reporting Checklist More species- and situation- specific guidance is needed
12 Laboratory Animals, 2000
13 Guidance on the severity classification of procedures involving fish Report from a Working Group convened by Norecopa P Hawkins, N Dennison, G Goodman, S Hetherington, S Llywelyn-Jones, K Ryder and AJ Smith Laboratory Animals, 45: , 2011 norecopa.no/categories
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15 Why do we need PREPARE when we have ARRIVE? The ARRIVE guidelines claim that they provide a logical checklist with all the things that need to be considered when designing an experiment * In our experience when planning animal research, a number of additional points need to be addressed at the planning stage. These items not only improve study quality and animal welfare (and therefore reproducibility), but also the safety of humans and animals affected directly or indirectly by the work. *
16 The elephants in the room... reddit.com...the largest of them all is the lack of focus on planning animal experiments
17 Rory Wilson, Swansea University ohiobirdsanctuary.com The stress of capture and restraint!
18 Simple identification methods? Flipper bands can reduce the penguin s ability to swim efficiently Photo: T. Poppe, NMBU Tags can collect seaweed and shellfish, which dramatically reduce the fish s ability to swim efficiently Photo: colourbox.com Many animals can be identified by non-invasive biometric methods, like photographing the pattern of stripes on the zebra
19 Contingent suffering (not just direct suffering caused by the procedure) e.g. fear, boredom, discomfort which maycaused by e.g. transport, housing, husbandry, social hierarchy photo: NMBU Single-housed male mice show symptoms of what in humans would be characterised as depression photo: colourbox.com
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21 Simple techniques? Photo: NMBU Are you sure that your injection ends up in the same place each time? Are the injections painful? Are they feasible? e.g. intramuscular injections in small animals
22 Disposable needles are designed to be used only once! Lucy Whitfield, RVC and Sally Robinson, AstraZeneca Photo: AstraZeneca
23 the drug was administered by gavage in 3 daily doses photo: NMBU How much ethanol do I need to give a mouse to be the equivalent of 2 glasses of red wine in the evening? Carefully consider the dose, use of allometric scaling, and the method of administration
24 Simple blood sampling techniques? At thedoctor: I think I ll take a blood sample from you tomorrow. I take my blood samples by sticking a knife into your neck, without anaesthesia. But don t worry, I ll inject 2 litres of liquid into your abdomen first so you don t die from fluid loss. medipoint.com/html/for_use_on_mice.html The best blood sampling techniques are those where you can (1) see the blood vessel, (2) control the amount of blood you remove, (3) stop the bleeding easily and (4) not damage surrounding tissue.
25 Carol M. Newton ( ) The three S s Good Science Good Sense Good Sensibilities National Library of Medicine Rowsell HC (1977): The Ethics of Biomedical Experimentation, in The Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing pp , National Academy of Sciences, Washington, D.C., ISBN
26 The use of animals in education and training frame.org.uk We may need the animals, as it were, on the night; but the machines will do very well at rehearsals
27 norecopa.no/education-training/homemade-educational-materials Workshop 11 April in Oslo norecopa.no/education-training/homemade-educational-materials
28 PREPARE ARRIVE
29 ARRIVE PREPARE Reporting guidelines like ARRIVE describe the experiment. Guidelines like PREPARE are used to plan the experiment (choose the «ingredients» and «baking time») marksandspencer.com
30 PREPARE: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence PREPARE covers 15 topics: Formulation of the study 1. Literature searches 2. Legal issues 3. Ethical issues, harm-benefit assessment and humane endpoints 4. Experimental design and statistical analysis Dialogue between scientists and the animal facility 5. Objectives and timescale, funding and division of labour 6. Facility evaluation 7. Education and training 8. Health risks, waste disposal and decontamination Items in pink are not highlighted in ARRIVE Methods 9. Test substances and procedures 10. Experimental animals 11. Quarantine and health monitoring 12. Housing and husbandry 13. Experimental procedures 14. Humane killing, release, reuse or rehoming 15. Necropsy
31 Two pages, translated into 13 languages so far
32 In addition to the checklist, much more information is available on: norecopa.no/prepare
33 norecopa.no/prepare Links to quality guidelines worldwide on e.g. blood sampling, injection volumes, housing and husbandry, analgesia, humane endpoints, experimental design
34 Health risks: there are many people to think about People engaged in animal capture, transport and breeding Animal carers and technologists Security personnel Administrative personnel with occasional access to the animal facility Students Sales representatives and those delivering supplies or equipment Craftsmen carrying out facility repairs Other visitors, including inspectors, journalists and students Cleaning staff Waste disposal personnel Those who re-home research animals
35 Many of these people often possess a number of features which increase their health risks They may: enter the facility outside normal working hours, when advice on hazards may not be readily available not understand messages left in the facility, especially if scientific jargon is used. Special consideration should be paid to employees with other native languages. have little knowledge of animal research, scientific method and the need for controlled experiments have no intrinsic concern of potential health hazards unless these are pointed out to them. Ironically, the cleaner and tidier an animal facility appears to be, the less likely they are to be fearful of such hazards. have not been health-screened before entering the facility. Those predisposed for allergy or asthma are particularly at risk when working with animals. be planning a family. Early embryonic development and spermatogenesis are known to be at risk upon exposure to ionising radiation and chemicals, including volatile anaesthetics.
36 Are we prepared for equipment failure? Anything that can go wrong, will go wrong (Murphy s Law) Photo: NMBU
37 Are the animals ready for the experiment? Photo: NMBU
38 norecopa.no/farm-animals
39 Contract between the animal facility and the research group Animal Researcher Not The division of labour, responsibilities and costs between the two parties, with the aim of clarifying all stages of the experiment and ensuring that all necessary parameters are recorded. Animal: Arrival date Species Strain/stock and substrain Supplier (full name and address) or bred on the premises Number and sex Age, weight, stage of life cycle on arrival facility applicable Pre-treatment (surgical or medical) from supplier Quality (e.g. SPF, germ-free, gnotobiotic, conventional) Acclimation time before the start of the experiment Time and duration of fasting (with/without water and bedding) Environment: Type of housing: barrier/conventional Temperature (mean ± variation) Light schedule Relative humidity (mean ± variation) Number of air changes in the animal room/cabinet per hour Environmental enrichment Housing: Free-range, shelf, cabinet, isolator Cage type and size Number and method of distribution of animals per cage
40 Quality assurance and a culture of care at all levels of the animal facility SOPs describing good techniques, carried out by competent operators Checklist ( contract ) between researcher and the facility The AAALAC Program Description template* as an overall performance checklist Institutional policies on animal care and use Animal environment, housing and management Veterinary care Physical plant A Master Plan as a weekly checklist for the whole facility during the year *
41 A simple but effective Master Plan
42 Think 3R-Alternatives at all stages Breeding Transport Acclimation Procedures, e.g. choice of dose method of administration methods of data collection (blood sampling, body temperature, heart rate, blood pressure etc.) Pilot studies Consult the technicians from Day 1: they have a right to know and will be more motivated they know the possibilities (and limitations) in the animal facility they often possess a large range of practical skills and are good at lateral thinking they know the animals best the animals know them best
43 Even experienced pilots use checklists as an aide memoire...
44 Søren Kirkegaard ( ) It is perfectly true, as philosophers say, that life must be understood backwards. Reporting! wikipedia.org But they forget the other proposition, that it must be lived forwards. PREPARE!
45 Thanks to our main sponsors: Standing Committee on Business Affairs, Norwegian Parliament Norwegian Ministries of Agriculture and Fisheries Research Council of Norway Laboratory Animals Ltd. Nordic Society Against Painful Experiments (NSMSD) Novo Nordisk Scottish Accreditation Board Stiansen Foundation Universities Federation for Animal Welfare (UFAW) US Department of Agriculture, Animal Welfare Information Center (AWIC) Graphics: colourbox.com Established 1926
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