PREPARE before you ARRIVE: planning and reporting animal experiments - norecopa.no/Oulu
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Oulu, 31 January 2019
PREPARE before you ARRIVE:
planning and reporting animal experiments
norecopa.no/Oulu
Adrian Smith, Eddie Clutton, Elliot Lilley, Kristine Hansen & Trond Brattelid
adrian.smith@norecopa.no
norecopa.no
Norecopa
Norway’s 3R Centre and National Consensus
Platform for the Replacement, Reduction and
Refinement of Animal Experiments
European Consensus-Platform for Alternatives
www.ecopa.eu
Recognises National Consensus Platforms (NCPs) with all 4 stakeholders
equally represented in their governing bodies:
Government
Research
Industry Animal
welfare
International consensus meetings Harmonisation of the Care and Use of: Fish (2005) Wildlife (2008) Fish (2009) Agricultural animals (2012) Wildlife (2017) https://norecopa.no/meetings All presentations and consensus statements are on the internet: a lasting resource
More species- and situation- specific guidance
is needed
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: 219-224, 2011
norecopa.no/categories
norecopa.no
7,600 webpages
Video presentation of contents: 80,000 links
norecopa.no/info 175,000 pageviews /year
The search engine
Guidelines bleeding mice
Auto-complete function:
Categories, types, 3R
relevance and many more
Synonym list:
Bleeding, bloodsampling, blood sampling, venepuncture,
blood collection, phlebotomy
• An index of all the words on all the approx. 7,600 pages
• Fuzzy logic
• Boolean logic
• Wildcards
• Proximity searches
• Truncation
A help file available
Search for ‘bleeding mice’ on Google and Norecopa
‘Bleeding’ not mentioned, but identified by the synonym list
English-language newsletters
Averaging approx. 175,000 page views a year at present (2018)
Internal validity Scientific robustness of design, conduct, analysis and reporting External validity The extent to which scientific findings can be applied to another setting, population or species: Essential for lab animal science’s credibility and translatability
Design
Reporting Conduct
Analysis
Identify and ensure the quality of (at least)
the critical points in the experiment: Space Shuttle, NASA
critical for scientific validity and animal
welfare1) Columbia
First shuttle flight, Columbia, in April 1981.
Some tiles fell off at take-off, but these were not on
a critical part of the vehicle.
Photo: nasaspaceflight.com
Photo: gettyimages.no
White insulating tiles were glued to the shuttle to prevent
it from burning up on re-entry (the black areas on this
photo are areas where tiles have not yet been installed). Columbia burnt up in 2003, killing all 7 crew
members, because tiles on a critical area (the
leading edge of the wing) fell off.
Photo: cbsnews.com2) Challenger
Challenger was launched in cold weather in January
1986. The O-rings on one booster rocket
malfunctioned, allowing hot gases to ignite the
contents of the liquid fuel tank. The vehicle
subsequently disintegrated, killing all 7 crew
members.
www.mahal.org Photo: no.wikipedia.org
Flexible rubber O-rings (seen in cross-section as
black dots) prevent hot gases from escaping
between the joints of the solid rocket boosters. Details are important!!
These rings lose some of their flexibility at low
temperatures.Good planning is critical!
• Complex machines (animals) create known or unknown unknowns (interactions
between parts that are impossible to foresee until you “fly”)
• Possible design weaknesses must be discussed (damage from foam, and
susceptibility to low temperature, which the engineers knew about!)
• Avoid “pressure to launch” (political, media). = Publish or perish.
• Don’t make bad management decisions (pushing the safety envelope):
“We’ve got away with it before”
= ”We’ve managed to publish the experiments before”
• Often a combination of many factors, each of which may be harmless until they
occur simultaneously
Don’t ignore “insignificant” issues!
Pay Attention to Detailhttps://norecopa.no/alternatives/culture-of-care https://www.nc3rs.org.uk/news/creating-culture-care http://ilarjournal.oxfordjournals.org/content/48/1/3.full
Why is it taking so long to improve internal validity? Berti & Cima 1955, quoted in Öbrink and Rehbinder
Hurni 1969, quoted in Öbrink and Rehbinder
There are many guidelines for reporting animal studies
• Öbrink & Waller, 1996
• Jane Smith et al., 1997
• Adrian Smith & Trond Brattelid, 2000 (fish)
• 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 ChecklistIdentify and eliminate causes of
contingent suffering
(not just direct suffering caused by the
procedure)
e.g. fear, boredom, discomfort
which may caused by
e.g. transport, housing, husbandry, social
photo: NMBU
hierarchy
Single-housed male mice show symptoms of what in humans would be
characterised as depression
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111065
photo: colourbox.comhttps://www.nc3rs.org.uk/how-to-pick-up-a-mouse
http://bitly.com/scruff-technique
http://bitly.com/scruff-technique
”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‘Simple’ blood sampling techniques?
At the doctor:
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.An useful additional (but largely unknown) tool…
Carol M. Newton (1925-2014)
The three S’s
• Good Science
• Good Sense*
• Good Sensibilities*
National Library of Medicine *We can do this ourselves without scientific
literature!
Carol M Newton, quoted in Rowsell HC (1977): The Ethics of Biomedical Experimentation in The Future
of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing pp. 267-
281, National Academy of Sciences, Washington, D.C., ISBN 0-309-02603-2.norecopa.no/education-training/homemade-educational-materials
We may need the animals, as it were, on the
night; but the machines will do very well at
rehearsals
”Alternatives” may be too poor to replace animals totally, but may be excellent as
briefing or debriefing aids.Encourage scientists to publish 3R-improvements
somewhere where they are visible!
http://www.theodora.com/rodent_laboratory/blood_collection.html photo: NMBU
SCID-Hu mice immunized with a pneumococcal vaccine produce specific
human antibodies and show increased resistance to infection.
Saphenous vein puncture for blood sampling of the mouse, rat, hamster,
gerbil, guinea-pig, ferret and minkHealth 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
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.
Photo: NMBU
norecopa.no/farm-animals
So 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.
*
http://www.nc3rs.org.uk/sites/default/files/documents/Guidelines/ARRIVE%20Guidelines%20Speaker%20Notes.pdfARRIVE
PREPARE
Reporting guidelines like ARRIVE describe the experiment.
Guidelines like PREPARE are used to plan the experiment (choose
the «ingredients» and «baking time»)
marksandspencer.comPREPARE
ARRIVE
https://www.bls.gov/ooh/images/3077.jpg
https://www.dreamstime.comPre-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
http://journals.sagepub.com/doi/full/10.1177/0023677217724823PREPARE
The PREPARE Guidelines Checklist
Planning Research and Experimental Procedures on Animals: Recommendations for Excellence The ARRIVE Guidelines Checklist
Adrian J. Smitha, R. Eddie Cluttonb, Elliot Lilleyc, Kristine E. Aa. Hansend & Trond Brattelide
Animal Research: Reporting In Vivo Experiments
a
Norecopa, c/o Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, Norway; bRoyal (Dick) School of Veterinary Studies, Easter Bush, 1 2 3 4 5
Midlothian, EH25 9RG, U.K.; cResearch Animals Department, Science Group, RSPCA, Wilberforce Way, Southwater, Horsham, West Sussex, RH13 9RS, U.K.; Carol Kilkenny , William J Browne , Innes C Cuthill , Michael Emerson and Douglas G Altman
1
d
Section of Experimental Biomedicine, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, UK, 2School of Veterinary
Sciences, P.O. Box 8146 Dep., 0033 Oslo, Norway; eDivision for Research Management and External Funding, Western Norway University of Applied Science, University of Bristol, Bristol, UK, 3School of Biological Sciences, University of Bristol, Bristol, UK, 4National Heart and Lung
Sciences, 5020 Bergen, Norway. Institute, Imperial College London, UK, 5Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
PREPARE1 consists of planning guidelines which are complementary to reporting guidelines such as ARRIVE2. Section/
ITEM RECOMMENDATION Paragraph
PREPARE covers the three broad areas which determine the quality of the preparation for animal studies:
1. Formulation of the study Title 1 Provide as accurate and concise a description of the content of the article
2. Dialogue between scientists and the animal facility as possible.
3. Quality control of the components in the study
Abstract 2 Provide an accurate summary of the background, research objectives,
The topics will not always be addressed in the order in which they are presented here, and some topics overlap. The PREPARE including details of the species or strain of animal used, key methods,
checklist can be adapted to meet special needs, such as field studies. PREPARE includes guidance on the management of animal principal findings and conclusions of the study.
facilities, since in-house experiments are dependent upon their quality. The full version of the guidelines is available on the Norecopa
website, with links to global resources, at https://norecopa.no/PREPARE. INTRODUCTION
The PREPARE guidelines are a dynamic set which will evolve as more species- and situation-specific guidelines are produced, Background 3 a. Include sufficient scientific background (including relevant references to
and as best practice within Laboratory Animal Science progresses. previous work) to understand the motivation and context for the study,
and explain the experimental approach and rationale.
Topic Recommendation b. Explain how and why the animal species and model being used can
address the scientific objectives and, where appropriate, the study’s
(A) Formulation of the study relevance to human biology.
Objectives 4 Clearly describe the primary and any secondary objectives of the study, or
1. Literature Form a clear hypothesis, with primary and secondary outcomes. specific hypotheses being tested.
searches Consider the use of systematic reviews.
METHODS
Decide upon databases and information specialists to be consulted, and construct search terms.
Ethical statement 5 Indicate the nature of the ethical review permissions, relevant licences (e.g.
Assess the relevance of the species to be used, its biology and suitability to answer the experimental Animal [Scientific Procedures] Act 1986), and national or institutional
questions with the least suffering, and its welfare needs. guidelines for the care and use of animals, that cover the research.
Assess the reproducibility and translatability of the project. Study design 6 For each experiment, give brief details of the study design including:
a. The number of experimental and control groups.
2. Legal issues Consider how the research is affected by relevant legislation for animal research and other areas, e.g.
b. Any steps taken to minimise the effects of subjective bias when
animal transport, occupational health and safety. allocating animals to treatment (e.g. randomisation procedure) and when
Locate relevant guidance documents (e.g. EU guidance on project evaluation). assessing results (e.g. if done, describe who was blinded and when).
c. The experimental unit (e.g. a single animal, group or cage of animals).
3. Ethical issues, Construct a lay summary. A time-line diagram or flow chart can be useful to illustrate how complex
Harm-Benefit In dialogue with ethics committees, consider whether statements about this type of research have study designs were carried out.
Assessment and already been produced. Experimental 7 For each experiment and each experimental group, including controls,
procedures provide precise details of all procedures carried out. For example:
humane endpoints Address the 3Rs (Replacement, Reduction, Refinement) and the 3Ss (Good Science, Good Sense,
a. How (e.g. drug formulation and dose, site and route of administration,
Good Sensibilities). anaesthesia and analgesia used [including monitoring], surgical
Consider pre-registration and the publication of negative results. procedure, method of euthanasia). Provide details of any specialist
equipment used, including supplier(s).
Perform a Harm-Benefit Assessment and justify any likely animal harm. b. When (e.g. time of day).
Discuss the learning objectives, if the animal use is for educational or training purposes. c. Where (e.g. home cage, laboratory, water maze).
Allocate a severity classification to the project. d. Why (e.g. rationale for choice of specific anaesthetic, route of
administration, drug dose used).
Define objective, easily measurable and unequivocal humane endpoints.
Discuss the justification, if any, for death as an end-point. Experimental 8 a. Provide details of the animals used, including species, strain, sex,
animals developmental stage (e.g. mean or median age plus age range) and
weight (e.g. mean or median weight plus weight range).
4. Experimental Consider pilot studies, statistical power and significance levels.
b. Provide further relevant information such as the source of animals,
design and Define the experimental unit and decide upon animal numbers. international strain nomenclature, genetic modification status (e.g.
statistical analysis Choose methods of randomisation, prevent observer bias, and decide upon inclusion knock-out or transgenic), genotype, health/immune status, drug or test
naïve, previous procedures, etc.
and exclusion criteria.
The ARRIVE guidelines. Originally published in PLoS Biology, June 20101
Two pages, translated into 17 languages so farPREPARE:
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 Items in pink are not
7. Education and training
8. Health risks, waste disposal and decontamination
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. Necropsyhttps://norecopa.no/prepare/prepare-checklist
PREPARE
Aihe Suositus
(B) Tutkijoiden ja eläinyksikön välinen dialogi
5. Päämäärät ja Järjestä kokoukset tutkimukseen osallistuvien työntekijöiden kanssa, kun projektin alustava
aikataulutus, suunnitelma on valmis.
The PREPARE Guidelines Checklist rahoitus ja työnjako
Valmistele projektille alustava aikataulu, joka määrittää tarpeen avustamiselle valmistelussa, eläinten
Planning Research and Experimental Procedures on Animals: Recommendations for Excellence hoidossa, toimenpiteiden suorittamisessa ja jätteen hävittämisessä tai puhdistamisessa.
Adrian J. Smith , R. Eddie Clutton , Elliot Lilley , Kristine E. Aa. Hansen & Trond Brattelid
a b c d e
Laske ja tuo esille kaikki oletetut ja mahdolliset kulut.
a
Norecopa, c/o Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, Norway; Royal (Dick) School of Veterinary Studies, Easter Bush,
b
Midlothian, EH25 9RG, U.K.; cResearch Animals Department, Science Group, RSPCA, Wilberforce Way, Southwater, Horsham, West Sussex, RH13 9RS, U.K.; Valmistele yksityiskohtainen suunnitelma työnjaolle ja kulujen jaolle kaikissa tutkimuksen vaiheissa.
d
Section of Experimental Biomedicine, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life
Sciences, P.O. Box 8146 Dep., 0033 Oslo, Norway; eDivision for Research Management and External Funding, Western Norway University of Applied 6.Tilojen arviointi Suorita fyysinen arviointi käytettävistä tiloista arvioidaksesi rakennuksen ja tarvikkeiden taso ja tarpeet.
Sciences, 5020 Bergen, Norway.
Ota huomioon henkilöstön taitotasot, jos mukana on ylimääräisiä riskitekijöitä.
PREPARE1 koostuu suunnitteluohjeista, jotka ovat vastaavanlaiset kuin raportoinnille annetut ohjeet, kuten ARRIVE2.
PREPARE kattaa kolme laajaa aihealuetta, jotka määrittelevät eläintutkimusten suunnittelun laadun: 7. Koulutus ja Arvioi työntekijöiden tämänhetkinen pätevyys ja tarve lisäkoulutukselle tai -harjoittelulle ennen
1. Tutkimuksen rakenteen laatiminen harjoittelu tutkimuksen alkamista.
2. Tutkijoiden ja eläinyksikön välinen dialogi
3. Tutkimuksen osatekijöiden laadunhallinta 8. Terveysriskit, Suorita yhteistyössä eläinyksikön kanssa riskienarviointi kaikille henkilöille ja eläimille, joihin tutkimus
Aihealueita ei aina käsitellä siinä järjestyksessä, kuin ne esitetään tässä ja osassa aihealueista on päällekkäisyyksiä. PREPARE jätteiden vaikuttaa suorasti tai epäsuorasti.
tarkastuslista voidaan mukauttaa vastaamaan erityistarpeita tai erityistilanteita, kuten kenttätutkimusta varten. PREPARE sisältää hävittäminen ja
ohjeistusta eläinyksikön toiminnan johtamiseen, sillä siellä tehdyt tutkimukset ovat riippuvaisia eläinyksikön toiminnan laadusta. puhdistus Varmista ja tarvittaessa luo tarkka ohjeistus kaikkiin tutkimuksen vaiheisiin.
Ohjeiden kokonainen versio löytyy Norecopa:n nettisivuilta, https://norecopa.no/PREPARE, jossa on myös linkit kansainvälisiin (dekontaminaatio) Määrittele kaikelle välineistölle eristys-, puhdistus- ja hävitysmenetelmät.
lähteisiin.PREPARE -ohjeistus on dynaaminen paketti, joka kehittyy sitä mukaa, kun laji- ja tilannekohtaisia ohjeita tuotetaan ja
koe-eläintieteen hyvät käytänteet edistyvät.
(C) Tutkimuksen osatekijöiden laadunhallinta
Aihe Suositus
9. Testiaineet ja Tarjoa testiaineista niin paljon tietoa kuin mahdollista.
(A) Tutkimuksen rakenteen laatiminen toimenpiteet Varmista toimenpiteiden soveltuvuus ja kelpoisuus sekä tarvittavat taidot niiden suorittamiseen.
1. Kirjallisuushaut Mudosta selvä hypoteesi, josta ilmenee ensi- ja toissijaiset lopputulokset.
Harkitse systemaattisten selostusten (systematic reviews) käyttämistä. 10. Koe-eläimet Päätä mitkä tiedot eläimistä ovat olennaisia tutkimukselle ja raportoitavaksi.
Valitse käytettävät tietokannat ja konsultoitavat tietoasiantuntijat, ja määrittele hakutermit.
Vältä ylijäämäeläinten muodostuminen.
Arvioi käytettävän lajin sopivuus, sen biologia ja soveltuvuus vastaamaan tutkimuskysymyksiin aiheuttaen
11. Karanteeni ja Ota huomioon eläinten mahdollinen terveystaso, kaikki tarpeet kuljetukselle, karanteenille ja eristykselle,
mahdollisimman vähän kärsimystä, ja ottaen huomioon eläinten hyvinvointiin liittyvät tarpeet.
terveyden tarkkailu
Arvioi projektin toistettavuus ja soveltuvuus (translatability). terveysterveystarkkailulle, sekä seuraukset henkilökunnalle.
2. Juridiset asiat Ota huomioon, kuinka koe-eläintoimintaa tai muuta olennaista osaa koskeva lainsäädäntö vaikuttaa 12. Kasvatus ja Kiinnitä huomiota eläinten lajikohtaisiin vaistoihin ja tarpeisiin, yhteistyössä asiantuntevan henkilökunnan kanssa.
tutkimukseen, kuten esim. eläinten kuljetukset ja työturvallisuus. hoito Keskustele akklimatisoinnista, optimaalisista kasvatusolosuhteista, ympäristötekijöistä ja kaikista näihin
Etsi olennaiset ohjeasiakirjat (esim. EU:n ohjeistus hankearvioinnista). liittyvistä tutkimuksellisista rajoituksista (esim. ruokinnan rajoittaminen tai yksin pitämisestä)
13. Kokeelliset Kehitä parannellut toimenpiteet kiinniottamiseen, kiinnipitämiseen, merkitsemiseen ja vapauttamiseen
3. Eettiset Valmistele yleistajuinen tiivistelmä. toimenpiteet tai uudelleensijoittamiseen/kotiuttamiseen.
asiat, Hyöty-Haitta Keskusteltaessa eettisten toimikuntien kanssa, ota huomioon, onko tämän tyyppisestä tutkimuksesta Kehitä parannellut toimenpiteet aineiden annosteluun, näytteiden ottoon, rauhoittamiseen ja
arviointi sekä jo olemassa kannanottoa. anestesiaan, kirurgiaan ja muihin teknikoihin.
humaanit Huomioi 3R (Korvaaminen, Vähentäminen, Parantaminen) ja 3S (Good Science, Good Sense, 14. Humaani lopet-
päätepisteet Good Sensibilities/Hyvä tiede, Hyvä tarkoitus, Hyvä herkkyys) -periaatteet. taminen, vapauttamin- Tarkista asianmukainen lainsäädäntö ja ohjeistus hyvissä ajoin ennen tutkimusta.
en, uudelleenkäyttö tai Määrittele ensisijaiset ja kiireelliset humaanit lopetusmenetelmät.
Harkitse ennakkoilmoitusta ja negatiivisten koetulosten julkaisemista. uudelleensijoittaminen/
Suorita Hyöty-Haitta-arviointi ja perustele kaikki mahdollinen haitta eläimille. kotiuttaminen Varmista näitä toimenpiteistä mahdollisesti suorittavien henkilöiden pätevyys.
Pohdi oppimistavoitteita, jos eläintä käytetään opetus- tai harjoittelutarkoituksessa.
15. Ruumiinavaus Valmistele systemaattinen suunnitelma ruumiinavauksen jokaiseen vaiheeseen, mukaan lukien kaikkien
Arvioi projektille vakavuusluokitus (Severity Classification)
eläinten ja näytteiden sijainti ja tunnistettavuus.
Määrittele objektiiviset, helposti mitattavat ja yksiselitteiset humaanit päätepisteet.
Määrittele perustelu kuolemalle päätepisteenä, jos sellainen on tarkoituksenmukaista.
Viitteet
1. Smith AJ, Clutton RE, Lilley E, Hansen KEA & Brattelid T. PREPARE:Guidelines for Planning Animal Research and Testing.
4. Koesuunnittelu Harkitse pilottitutkimuksia, tilastollista voimakkuutta ja merkitsevyysastetta.
Laboratory Animals, 2017, DOI: 10.1177/0023677217724823.
ja tilastollinen Määrittele koeyksikkö ja päätä eläinmäärät. 2. Kilkenny C, Browne WJ, Cuthill IC et al. Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research.
PloS Biology, 2010; DOI: 10.1371/journal.pbio.1000412.
analyysi Valitse satunnaistamismenetelmät, ennaltaehkäise tarkkailijasta aiheutuva vääristymä (observer bias)
ja valitse kriteerit mukaanlukemiselle ja poissulkemiselle.
Lisätietoa
https://norecopa.no/PREPARE | post@norecopa.no | @norecopa
https://norecopa.no/prepare/prepare-checklistIn addition to the checklist, much more information is available on:
norecopa.no/PREPAREnorecopa.no/PREPARE Links to quality guidelines worldwide on e.g. blood sampling, injection volumes, housing and husbandry, analgesia, humane endpoints, experimental design
PREPARE
The PREPARE Guidelines Checklist The ARRIVE Guidelines Checklist
Planning Research and Experimental Procedures on Animals: Recommendations for Excellence Animal Research: Reporting In Vivo Experiments
Adrian J. Smitha, R. Eddie Cluttonb, Elliot Lilleyc, Kristine E. Aa. Hansend & Trond Brattelide 1 2 3 4 5
Carol Kilkenny , William J Browne , Innes C Cuthill , Michael Emerson and Douglas G Altman
a
Norecopa, c/o Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, Norway; bRoyal (Dick) School of Veterinary Studies, Easter Bush, 1
The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, UK, 2School of Veterinary
Midlothian, EH25 9RG, U.K.; cResearch Animals Department, Science Group, RSPCA, Wilberforce Way, Southwater, Horsham, West Sussex, RH13 9RS, U.K.;
Science, University of Bristol, Bristol, UK, 3School of Biological Sciences, University of Bristol, Bristol, UK, 4National Heart and Lung
d
Section of Experimental Biomedicine, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Institute, Imperial College London, UK, 5Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
Sciences, P.O. Box 8146 Dep., 0033 Oslo, Norway; eDivision for Research Management and External Funding, Western Norway University of Applied
Sciences, 5020 Bergen, Norway.
Section/
ITEM RECOMMENDATION Paragraph
PREPARE1 consists of planning guidelines which are complementary to reporting guidelines such as ARRIVE2.
PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: Title 1 Provide as accurate and concise a description of the content of the article
1. Formulation of the study as possible.
2. Dialogue between scientists and the animal facility
3. Quality control of the components in the study Abstract 2 Provide an accurate summary of the background, research objectives,
including details of the species or strain of animal used, key methods,
The topics will not always be addressed in the order in which they are presented here, and some topics overlap. The PREPARE principal findings and conclusions of the study.
checklist can be adapted to meet special needs, such as field studies. PREPARE includes guidance on the management of animal
facilities, since in-house experiments are dependent upon their quality. The full version of the guidelines is available on the Norecopa INTRODUCTION
website, with links to global resources, at https://norecopa.no/PREPARE. Background 3 a. Include sufficient scientific background (including relevant references to
The PREPARE guidelines are a dynamic set which will evolve as more species- and situation-specific guidelines are produced, previous work) to understand the motivation and context for the study,
and as best practice within Laboratory Animal Science progresses. and explain the experimental approach and rationale.
b. Explain how and why the animal species and model being used can
Topic Recommendation address the scientific objectives and, where appropriate, the study’s
relevance to human biology.
(A) Formulation of the study
Objectives 4 Clearly describe the primary and any secondary objectives of the study, or
1. Literature Form a clear hypothesis, with primary and secondary outcomes. specific hypotheses being tested.
searches Consider the use of systematic reviews. METHODS
Decide upon databases and information specialists to be consulted, and construct search terms. Ethical statement 5 Indicate the nature of the ethical review permissions, relevant licences (e.g.
Assess the relevance of the species to be used, its biology and suitability to answer the experimental Animal [Scientific Procedures] Act 1986), and national or institutional
questions with the least suffering, and its welfare needs. guidelines for the care and use of animals, that cover the research.
Assess the reproducibility and translatability of the project. Study design 6 For each experiment, give brief details of the study design including:
a. The number of experimental and control groups.
2. Legal issues Consider how the research is affected by relevant legislation for animal research and other areas, e.g.
b. Any steps taken to minimise the effects of subjective bias when
animal transport, occupational health and safety. allocating animals to treatment (e.g. randomisation procedure) and when
Locate relevant guidance documents (e.g. EU guidance on project evaluation). assessing results (e.g. if done, describe who was blinded and when).
c. The experimental unit (e.g. a single animal, group or cage of animals).
3. Ethical issues, Construct a lay summary. A time-line diagram or flow chart can be useful to illustrate how complex
Harm-Benefit In dialogue with ethics committees, consider whether statements about this type of research have study designs were carried out.
Assessment and already been produced. Experimental 7 For each experiment and each experimental group, including controls,
procedures provide precise details of all procedures carried out. For example:
humane endpoints Address the 3Rs (Replacement, Reduction, Refinement) and the 3Ss (Good Science, Good Sense,
a. How (e.g. drug formulation and dose, site and route of administration,
Good Sensibilities). anaesthesia and analgesia used [including monitoring], surgical
Consider pre-registration and the publication of negative results. procedure, method of euthanasia). Provide details of any specialist
equipment used, including supplier(s).
Perform a Harm-Benefit Assessment and justify any likely animal harm.
b. When (e.g. time of day).
Discuss the learning objectives, if the animal use is for educational or training purposes.
c. Where (e.g. home cage, laboratory, water maze).
Allocate a severity classification to the project. d. Why (e.g. rationale for choice of specific anaesthetic, route of
Define objective, easily measurable and unequivocal humane endpoints. administration, drug dose used).
Discuss the justification, if any, for death as an end-point. Experimental 8 a. Provide details of the animals used, including species, strain, sex,
animals developmental stage (e.g. mean or median age plus age range) and
4. Experimental Consider pilot studies, statistical power and significance levels. weight (e.g. mean or median weight plus weight range).
design and Define the experimental unit and decide upon animal numbers. b. Provide further relevant information such as the source of animals,
international strain nomenclature, genetic modification status (e.g.
statistical analysis Choose methods of randomisation, prevent observer bias, and decide upon inclusion
knock-out or transgenic), genotype, health/immune status, drug or test
and exclusion criteria. naïve, previous procedures, etc.
The ARRIVE guidelines. Originally published in PLoS Biology, June 20101
Explanatory sections for each topic in PREPARE
Links to quality guidelines for each topic
A total of 7,600 webpages of 3R resourcesA simple but effective Master Plan
Are we prepared for equipment failure?
Photo: NMBUAnimal Researcher Not
facility applicable
Contract between the animal facility and Animal:
the research group Arrival date
Species
The division of labour and responsibilities
Strain/stock and substrain
Supplier (full name and address) or bred on the premises
between the two parties, with the aim of Number and sex
clarifying all stages of the experiment and Age, weight, stage of life cycle on arrival
ensuring that all necessary parameters are Pre-treatment (surgical or medical) from supplier
recorded.
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
Page 2 of 4Think ”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 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 bestAn example: i.v. injection of a radioactive isotope:
norecopa.no/PREPARE procedureswithcare.org.uk/intravenous-injection-in-the-mouseIntroductory video about PREPARE norecopa.no/PREPARE/presentation The commentary (Word file) and the slides (Powerpoint file) are also available there for free use.
Even experienced pilots use checklists...
https://www.wikivetlive.com/crisis-management-in-anaesthesia
Even experienced pilots use checklists...
meonuk.comThanks 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)
• Norwegian Society for Protection of Animals (Dyrebeskyttelsen Norge)
• 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
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