Skip to main content
SpringerLink
Log in

Planning Animal Experiments

  • Chapter
  • First Online:
Experimental Design and Reproducibility in Preclinical Animal Studies

Part of the book series: Laboratory Animal Science and Medicine ((LASM,volume 1))

  • 861 Accesses

Abstract

Despite efforts to improve the planning of animal experiments by better reporting, there is still great room for improvement. Many scientists appear to be unaware of the impact which apparently insignificant routines in an animal facility can have on their experiments, and they rely upon the facility staff to take care of these. The same applies to the more mundane aspects of their research such as handling, injection techniques and blood sampling. The aim of this chapter is to demonstrate the need for close collaboration between scientists and facility staff from day 1 of the planning process. This collaboration will have a win-win effect: improving experimental design, implementing the three Rs, optimising animal welfare and safeguarding all of those affected, directly or indirectly, by the research. The chapter underlines the importance of advice and checklists for planning animal research and testing, such as those embodied in the PREPARE guidelines.

The views expressed in this chapter are the author’s, and not necessarily those of Norecopa.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kilkenny C, Parsons N, Kadyszewski E, et al. Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One. 2009;4:e7824. https://doi.org/10.1371/journal.pone.0007824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Smith JA, Birke L, Sadler D. Reporting animal use in scientific papers. Lab Anim. 1997;31:312–7.

    Article  CAS  Google Scholar 

  3. Avey MT, Moher D, Sullivan KJ, et al. The devil is in the details: incomplete reporting in preclinical animal research. PLoS One. 2016;11:e0166733. https://doi.org/10.1371/journal.pone.0166733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kilkenny C, Browne WJ, Cuthill IC, et al. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412. https://doi.org/10.1371/journal.pbio.1000412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Reichlin TS, Vogt L, Wurbel H. The researchers’ view of scientific rigor-survey on the conduct and reporting of in vivo research. PLoS One. 2016;11:e0165999. https://doi.org/10.1371/journal.pone.0165999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Begley CG, Ellis LM. Drug development: raise standards for preclinical cancer research. Nature. 2012;483:531–3. https://doi.org/10.1038/483531a.

    Article  CAS  PubMed  Google Scholar 

  7. Garner JP. The significance of meaning: why do over 90% of behavioral neuroscience results fail to translate to humans, and what can we do to fix it? ILAR J. 2014;55:438–56. https://doi.org/10.1093/ilar/ilu047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Howells DW, Sena ES, Macleod MR. Bringing rigour to translational medicine. Nat Rev Neurol. 2014;10:37–43. https://doi.org/10.1038/nrneurol.2013.232.

    Article  CAS  PubMed  Google Scholar 

  9. van der Worp HB, Howells DW, Sena ES, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7:e1000245. https://doi.org/10.1371/journal.pmed.1000245.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov. 2011;10:712. https://doi.org/10.1038/nrd3439-c1.

    Article  CAS  PubMed  Google Scholar 

  11. Karp NA, Reavey N. Sex bias in preclinical research and an exploration of how to change the status quo. Br J Pharmacol. 2018; https://doi.org/10.1111/bph.14539.

  12. Karp NA, Mason J, Beaudet AL, Benjamini Y, Bower L, Braun RE, et al. Prevalence of sex dimorphism in mammalian phenotypic traits. Nat Commun. 2017;8:15475. https://doi.org/10.1038/ncomms15475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sorge RE, Mapplebeck JCS, Rosen S, Beggs S, Taves S, Alexander JK, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18:1081–3.

    Article  CAS  Google Scholar 

  14. Enserink M Sloppy reporting on animal studies proves hard to change. Science 29. 2017;357(6358):1337–8. https://doi.org/10.1126/science.357.6358.1337.

    Article  Google Scholar 

  15. Wallach JD, Boyack KW, JPA I. Reproducible research practices, transparency, and open access data in the biomedical literature, 2015–2017. PLoS Biol. 2018; https://doi.org/10.1371/journal.pbio.2006930.

  16. Bradbury AG, Eddleston M, Clutton RE. Pain management in pigs undergoing experimental surgery: a literature review (2012–14). Br J Anaesth. 2016;116:47–5. https://doi.org/10.1093/bja/aev301.

    Article  Google Scholar 

  17. Leung V, Rousseau-Blass F, Beauchamp G, Pang DSJ ARRIVE has not ARRIVEd: support for the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines does not improve the reporting quality of papers in animal welfare, analgesia or anesthesia 2018; PLoS One https://doi.org/10.1371/journal.pone.0197882 .

  18. van Assen MALM, van Aert RCM, Nuitjen MB, Wicherts JM Why publishing everything is more effective than selective publishing of statistically significant results. 2014; PLoS One, doi:https://doi.org/10.1371/journal.pone.0084896.

  19. Chalmers I, Bracken MB, Djulbegovic B, et al. How to increase value and reduce waste when research priorities are set. Lancet. 2014;383:156–65. https://doi.org/10.1016/s0140-6736(13)62229-1.

    Article  PubMed  Google Scholar 

  20. Macleod MR, Michie S, Roberts I, et al. Biomedical research: increasing value, reducing waste. Lancet. 2014;383:101–4. https://doi.org/10.1016/s0140-6736(13)62329-6.

    Article  Google Scholar 

  21. Munafò MR, Nosek BA, Bishop DVM, et al. A manifesto for reproducible science. Nat Hum Behav 2017; 1: 0021. Perspective. https://doi.org/10.1038/s41562-016-0021

  22. Russell WMS, Burch RL. The principles of humane experimental technique. Wheathampstead: Universities Federation for Animal Welfare; 1959.

    Google Scholar 

  23. Ellery AW. Guidelines for specification of animals and husbandry methods when reporting the results of animal experiments. Lab Anim. 1985;19:106–8.

    Article  CAS  Google Scholar 

  24. Öbrink KJ, Försöksdjurs-kunskap WM. Refinement, reduction, replacement. Lund: Studentlitteratur AB; 1996.

    Google Scholar 

  25. Smith JA, Birke L, Sadler D. Reporting animal use in scientific papers. Lab Anim. 1997;31:312–7.

    Article  CAS  Google Scholar 

  26. Öbrink, Rehbinder. Animal definition: a necessity for the validity of animal experiments? Lab Anim. 2000;34:121–30.

    Article  Google Scholar 

  27. Hooijmans CR, Leenaars M, Ritskes-Hoitinga M. A gold standard publication checklist to improve the quality of animal studies, to fully integrate the three Rs, and to make systematic reviews more feasible. Altern Lab Anim. 2010;38:167–82.

    Article  CAS  Google Scholar 

  28. Brattelid T, Smith AJ. Guidelines for reporting the results of experiments on fish. Lab Anim. 2000;34:131–5.

    Article  CAS  Google Scholar 

  29. Institute for Laboratory Animal Research NRC. Guidance for the description of animal research in scientific publications. Washington, DC: National Academies Press; 2011.

    Google Scholar 

  30. Altman DG, Simera I, Hoey J, et al. EQUATOR: reporting guidelines for health research. Lancet. 2018;371:1149–50. https://doi.org/10.1016/s0140-6736(08)60505-x.

    Article  Google Scholar 

  31. Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):e3000410. https://doi.org/10.1371/journal.pbio.3000410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Poole T. Happy animals make good science. Lab Anim. 1997;31:116–24.

    Article  CAS  Google Scholar 

  33. Guidance documents to fulfil the requirements under the Directive 2010/63/EU. http://ec.europa.eu/environment/chemicals/lab_animals/pubs_guidance_en.htm

  34. Strategic Planning for Research Programmes. https://frame.org.uk/resources/research-planning/

  35. Smith MM, Clarke EC, Little CB. Considerations for the design and execution of protocols for animal research and treatment to improve reproducibility and standardization: DEPART well-prepared and ARRIVE safely. Osteoarthr Cartil. 2017; https://doi.org/10.1016/j.joca.2016.10.016.

  36. STAIR Consensus Conferences. http://www.thestair.org

  37. Smith AJ, Clutton RE, Lilley E, Hansen KEA, Brattelid T. PREPARE: Guidelines for planning animal research and testing. Lab Anim. 2018;52(2):135–41. https://doi.org/10.1177/0023677217724823.

    Article  CAS  PubMed  Google Scholar 

  38. PREPARE https://norecopa.no/PREPARE

  39. Relationship between PREPARE and ARRIVE. https://norecopa.no/PREPARE/comparison-with-arrive

  40. PREPARE checklist https://norecopa.no/PREPARE/prepare-checklist

  41. What is Ethical Review? https://science.rspca.org.uk/sciencegroup/researchanimals/ethicalreview

  42. Culture of care https://norecopa.no/coc

  43. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. http://eur-lex.europa.eu/LexUriServ/LexUri Serv.do?uri=OJ:L:2010:276:0033:0079:en:PDF

    Google Scholar 

  44. Louhimies, S Refinement facilitated by the Culture of Care. In Proceedings of the EUSAAT 2015-Linz 2005 Congress, Linz, Austria, 20–23 September 2015; Vol 4, p. 154. http://eusaat-congress.eu/images/2015/Abstractbook_EUSAAT_2015_Linz_2015.pdf

  45. Maestre FT. Seven steps towards health and happiness in the lab. Nature. 2018; https://doi.org/10.1038/d41586-018-07514-7. https://www.nature.com/articles/d41586-018-07514-7

  46. Norecopa’s 3R Prize. https://norecopa.no/about-norecopa/3r-prize

  47. Rowsell HC. The ethics of biomedical experimentation. In: The future of animals, cells, models, and systems in research, development, education, and testing. Washington, DC: National Academy of Sciences; 1977. p. 267–85.

    Google Scholar 

  48. Smith AJ, Hawkins P. Good Science, Good Sense and Good Sensibilities: The Three Ss of Carol Newton. Animals. 2016;6(11):70. https://doi.org/10.3390/ani6110070.

    Article  PubMed Central  Google Scholar 

  49. The Three S’s. https://norecopa.no/3S

  50. Newton CM. Biostatistical and biomedical methods in efficient animal experimentation. In: The Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing: National Academy of Sciences, Washington, DC; 1977. p. 152–69.

    Google Scholar 

  51. AMS; BBSRC; MRC; Wellcome Trust. Reproducibility and reliability of biomedical research: improving research practice. Symposium report, 2015.

    Google Scholar 

  52. Eisen JA, Ganley E, CJ MC. Open science and reporting animal studies: Who’s accountable? PLoS Biol. 2014;12 https://doi.org/10.1371/journal.pbio.1001757.

  53. Newton DP. Quality and peer review of research: an adjudicating role for editors. Account Res. 2010;17:130–45.

    Article  Google Scholar 

  54. Rowsell HC, AA MW. The right animal for the right reason. In: Proceedings of the Canadian Association for Laboratory Animal Science 1978–1979, Canadian Association for Laboratory Animal Science Convention, Ottawa, ON, Canada, 28 August–1 September 1978. Calgary: CALAS National Office; 1978. p. 211–20.

    Google Scholar 

  55. Morris TH. Dose estimation among species. In: Hawk CT, Leary SL, Morris TH, editors. Formulary for laboratory animals. 3rd ed. Ames: Blackwell Publishing.

    Google Scholar 

  56. Mellor D. Updating animal welfare thinking: moving beyond the “Five Freedoms” towards “a Life Worth Living”. Animals. 2016;6 https://doi.org/10.3390/ani6030021.

  57. Morton DB, Berghardt GM. Smith JA animals, Science, and ethics—section III. Critical anthropomorphism, animal suffering, and the ecological context. Hast Cent Rep. 1990;20:S13–9.

    Article  Google Scholar 

  58. Klein HJ, Bayne KB. Establishing a culture of care, conscience, and responsibility: addressing the improvement of scientific discovery and animal welfare through science-based performance standards. ILAR J. 2007;48:3–11.

    Article  CAS  Google Scholar 

  59. Kalliokoski O, Teilmann AC, Jacobsen KR, Abelson KSP, Hau J. The Lonely Mouse – Single Housing Affects Serotonergic Signaling Integrity Measured by 8-OH-DPAT-Induced Hypothermia in Male Mice. PLoS One. 2014; https://doi.org/10.1371/journal.pone.0111065.

  60. Jennings M, et al. Refining rodent husbandry: the mouse. Lab Anim. 1998;32:233–59.

    Article  CAS  Google Scholar 

  61. Hurst JL, West RS. Taming anxiety in laboratory mice. Nat Methods. 2010;7(10)

    Google Scholar 

  62. Gouveia K, Hurst JL. Reducing mouse anxiety during handling: effect of experience with handling tunnels. PLoS One. 2013;8:1–8.

    Article  Google Scholar 

  63. Fridgeirsdottir GA, Hillered L, Clausen F. Escalated handling of young C57BL/6 mice results in altered Morris water maze performance. Uppsala J Med Sci. 2014;119:1–9.

    Article  Google Scholar 

  64. Leidinger C, Herrmann F, Thone-Reineke C, Baumgart N. Baumgart J introducing clicker training as cognitive enrichment for laboratory mice. Jove. 2017;121:1–12.

    Google Scholar 

  65. Guidelines for animal research. https://norecopa.no/search?fq=type:%22Guidelines%22&fq=db:%223r %22&sort=name_s%20asc&q=*

    Google Scholar 

  66. Email discussion lists of relevance to laboratory animal science. https://norecopa.no/more-resources/email-discussion-lists

  67. Health risks, waste disposal and decontamination. https://norecopa.no/prepare/8-health-risks-waste-disposal-and-decontamination

  68. Farm animals. https://norecopa.no/farm-animals

  69. Meetings within laboratory animal science and alternatives. https://norecopa.no/meetings

  70. Example guidelines for housing, handling, dosing and sampling in farm animals. A list produced by Dr. Penny Hawkins, Research Animals Department, RSPCA https://norecopa.no/media/6362/guidelines.pdf

  71. Guidelines for wildlife researchhttps://norecopa.no/ search?q=*&fq=cat:%22Wildlife%22&fq=type:% 22Guidelines%22&fq=db:%223r%22.

    Google Scholar 

  72. Division of labour, costs and responsibility. https://norecopa.no/prepare/5-objectives-and-timescale-funding-and-division-of-labour/division-of-labour-costs-and-responsibility

  73. AAALAC International. https://www.aaalac.org

  74. Program Description. https://www.aaalac.org/program-description/

  75. The Swiss cheese model. https://en.wikipedia.org/wiki/Swiss_cheese_model

  76. Reason J. Human error: models and management. BMJ. 2000;320(7237):768–70.

    Article  CAS  Google Scholar 

  77. Johari window. https://en.wikipedia.org/wiki/Johari_window

  78. Pound P, Ritskes-Hoitinga M. Is it possible to overcome issues of external validity in preclinical animal research? Why most animal models are bound to fail. J Transl Med. 2018;16:304. https://doi.org/10.1186/s12967-018-1678-1.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Søren Kierkegaard. https://en.wikiquote.org/wiki/Søren_Kierkegaard

Download references

Author information

Authors and Affiliations

  1. Norecopa, Oslo, Norway

    Adrian J. Smith

Authors
  1. Adrian J. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adrian J. Smith .

Editor information

Editors and Affiliations

  1. Comparative Medicine, Trinity College Dublin Comparative Medicine, Dublin, Ireland

    José M. Sánchez Morgado

  2. University of Bergen, Laboratory Animal Science University of Bergen, Bergen, Norway

    Aurora Brønstad

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Smith, A.J. (2021). Planning Animal Experiments. In: Sánchez Morgado, J.M., Brønstad, A. (eds) Experimental Design and Reproducibility in Preclinical Animal Studies . Laboratory Animal Science and Medicine, vol 1. Springer, Cham. https://doi.org/10.1007/978-3-030-66147-2_11

Download citation

Publish with us

Policies and ethics

Search

Navigation