Pbio.1000412 1.5

Improving Bioscience Research Reporting: The ARRIVEGuidelines for Reporting Animal Research Carol Kilkenny1*, William J. Browne2, Innes C. Cuthill3, Michael Emerson4, Douglas G. Altman5 1 The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, United Kingdom, 2 School of Veterinary Science, University of Bristol, Bristol, United Kingdom, 3 School of Biological Sciences, University of Bristol, Bristol, United Kingdom, 4 National Heart and Lung Institute, Imperial College London, United Kingdom, 5 Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom animals used (i.e., species/strain, sex, and the study and the reliability and validity of the findings. There should also be enough mously, with many filling specialised niches information to allow the experiment to be reflecting new disciplines and technologies.
or blinding (86%) to reduce bias in animal The emergence of open-access journals has how to ensure that all relevant information 70% of the publications that used statisti- is included in research publications.
shows that across many areas, the reporting precision or variability [5]. These findings of biomedical research is often inadequate, are a cause for concern and are consistent leading to the view that even if the science is themselves are not ‘‘fit for purpose,’’ searchers and peer reviewers would benefit should be provided in a research article.
and scientific practice [1–21]. A recent mised controlled clinical trials was one of the first guidelines developed in response there is considerable cumulative waste of been the mainstay of ‘‘quality control’’ for to this need [24,25]. Since publication, an research process, including as a result of experiments are reported, in terms of the publications that are unusable due to poor level of detail of methods and the presen- their instructions to authors [26,27]. As a reporting [22]. It is unlikely that this issue is tation of key results, is crucial to the peer confined to clinical research [2–14,16–20].
quent utility and validity of the knowledge transparency of reports of clinical trials and to report results appropriately there- base that is used to inform future research.
fore has potential scientific, ethical, and search process and the reputation of those articles include all relevant information to involved in it. This is particularly true for duplicating studies and performing redun- search, most of which have been published versial areas of science. The largest and dant experiments. Ideally scientific publi- in the last ten years (see http://www.
cations should present sufficient informa- animal research undertaken to date, to our [30,31]). Guidelines have also been devel- sions in the way research using animals is and to assess the biological relevance of specific bioscience research areas includ- reported [5]. The survey, commissionedby the National Centre for the Replace- Citation: Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research. PLoS Biol 8(6): e1000412. doi:10.1371/ Copyright: ß 2010 Kilkenny et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, the hypothesis or objective of the study, provided the original author and source are credited.
and the number and characteristics of the Funding: This project was initiated, funded, and led by the National Centre for the Replacement, Refinementand Reduction of Animals in Research (NC3Rs).
Competing Interests: The authors have declared that no competing interests exist.
The Perspective section provides experts with aforum to comment on topical or controversial issues Abbreviations: ARRIVE, Animals in Research: Reporting In Vivo Experiments; NC3Rs, National Centre for the Replacement, Refinement and Reduction of Animals in Research June 2010 | Volume 8 | Issue 6 | e1000412 from Nature Cell Biology, Science, Laboratory Animals, and the British Journal of Pharmacol- animal research that have been carried out to assess the efficacy of various drugs and interventions in animal models [8,9,13,52– draft set of guidelines that were then used as the basis for a wider consultation with the studies are the essential building blocks scientific community, involving research- the Nuffield Council for Bioethics [38–41].
ers, and grant holders and representatives constructed. The reviews have found that, addition to the limitations of the animal The Royal Society (see Table 1). Feedback reaching any useful conclusion about theefficacy of the drugs and interventions was incorporated into the final version of content utility of the guidelines is encour- found that 4% of the 271 journal articles collective efforts of authors, journal edi- tors, peer reviewers, and funding bodies.
There is no single simple or rapid solution, the results sections [5]. Reporting animal research using laboratory animals, and the numbers is essential so that the biological and statistical significance of the experi- ments. The guidelines will be published in mental results can be assessed or the data several leading bioscience research jour- nals simultaneously [56–60], and publish- experimental methods are to be repeated.
by including them in their journal Instruc- details will maximise the availability and tions to Authors subsequent to publication.
to be mandatory or absolutely prescriptive, nor to standardise or formalise the struc- journals adopting the guidelines, and with future. To address this, we led an initiative checklist that can be used to guide authors to produce guidelines for reporting animal quality assurance, to ensure completeness The NC3Rs gratefully acknowledges the exper- tise and advice that all the contributors have given to developing the guidelines. We would particularly like to acknowledge the contribu- tion of the other members of NC3Rs Reporting publications reporting research using ani- contributed to these guidelines were advising and specific characteristics of animals used animals by optimising the information that in their personal capacity and their input does (including species, strain, sex, and genetic is provided in publications on the design, not necessarily represent the policy of the conduct, and analysis of the experiments.
organisations with which they are associated): bandry; and the experimental, statistical, Professor David Balding, Department of Epide- and analytical methods (including details miology & Public Health, Imperial College, London UK; Dr Colin Dunn Editor Laboratory randomisation and blinding). All the items Animals (Royal Society of Medicine press); Dr.
Stella Hurtley, Senior Editor Science; ProfessorIan McGrath Editor-in-Chief British Journal of Pharmacology (Wiley Blackwell publishers); and porting to allow an accurate critical review Dr. Clare Stanford, Department of Psychophar- of what was done and what was found.
macology, University College, London UK. We Biotechnology and Biological Sciences Research would also like to thank NC3Rs grant holders, corner-stones of the guideline development the Medical Research Council, Biotechnology process [51]. To maximise their utility, the and Biological Sciences Research Council, Wellcome Trust, Parkinson’s Disease Society,British Heart Foundation and their grant consultation with scientists, statisticians, Association of Medical Research Charities holders and funding committee members who journal editors, and research funders. We prising researchers and statisticians from a range of disciplines, and journal editors June 2010 | Volume 8 | Issue 6 | e1000412 Table 2. Animal Research: Reporting In Vivo experiments: The ARRIVE guidelines.
Provide as accurate and concise a description of the content of the article as possible.
Provide an accurate summary of the background, research objectives (including details of the species orstrain of animal used), key methods, principal findings, and conclusions of the study.
Include sufficient scientific background (including relevant references to previous work) to understand the motivation and context for the study, and explain the experimental approach and rationale.
b.
Explain how and why the animal species and model being used can address the scientific objectives and, where appropriate, the study’s relevance to human biology.
Clearly describe the primary and any secondary objectives of the study, or specific hypotheses beingtested.
Indicate the nature of the ethical review permissions, relevant licences (e.g. Animal [Scientific Procedures]Act 1986), and national or institutional guidelines for the care and use of animals, that cover the research.
For each experiment, give brief details of the study design, including:a.
The number of experimental and control groups.
Any steps taken to minimise the effects of subjective bias when allocating animals to treatment (e.g., randomisation procedure) and when 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).
A time-line diagram or flow chart can be useful to illustrate how complex study designs were carried out.
For each experiment and each experimental group, including controls, provide precise details of allprocedures carried out. For example:a.
How (e.g., drug formulation and dose, site and route of administration, anaesthesia and analgesia used [including monitoring], surgical procedure, method of euthanasia). Provide details of any specialistequipment used, including supplier(s).
b.
Where (e.g., home cage, laboratory, water maze).
Why (e.g., rationale for choice of specific anaesthetic, route of administration, drug dose used).
Provide details of the animals used, including species, strain, sex, developmental stage (e.g., mean or median age plus age range), and weight (e.g., mean or median weight plus weight range).
b.
Provide further relevant information such as the source of animals, international strain nomenclature, genetic modification status (e.g. knock-out or transgenic), genotype, health/immune status, drug- or test-naı¨ve, previous procedures, etc.
Housing (e.g., type of facility, e.g., specific pathogen free (SPF); type of cage or housing; bedding material; number of cage companions; tank shape and material etc. for fish).
b.
Husbandry conditions (e.g., breeding programme, light/dark cycle, temperature, quality of water etc.
for fish, type of food, access to food and water, environmental enrichment).
c.
Welfare-related assessments and interventions that were carried out before, during, or after the Specify the total number of animals used in each experiment and the number of animals in each Explain how the number of animals was decided. Provide details of any sample size calculation used.
Indicate the number of independent replications of each experiment, if relevant.
Give full details of how animals were allocated to experimental groups, including randomisation or Describe the order in which the animals in the different experimental groups were treated and Clearly define the primary and secondary experimental outcomes assessed (e.g., cell death, molecularmarkers, behavioural changes).
Provide details of the statistical methods used for each analysis.
Specify the unit of analysis for each dataset (e.g. single animal, group of animals, single neuron).
Describe any methods used to assess whether the data met the assumptions of the statistical For each experimental group, report relevant characteristics and health status of animals (e.g., weight,microbiological status, and drug- or test-naı¨ve) before treatment or testing (this information can often betabulated).
Report the number of animals in each group included in each analysis. Report absolute numbers (e.g.
If any animals or data were not included in the analysis, explain why.
Report the results for each analysis carried out, with a measure of precision (e.g., standard error orconfidence interval).
Give details of all important adverse events in each experimental group.
Describe any modifications to the experimental protocols made to reduce adverse events.
June 2010 | Volume 8 | Issue 6 | e1000412 Interpret the results, taking into account the study objectives and hypotheses, current theory, and other relevant studies in the literature.
b.
Comment on the study limitations including any potential sources of bias, any limitations of the animal model, and the imprecision associated with the resultsa.
c.
Describe any implications of your experimental methods or findings for the replacement, refinement, or reduction (the 3Rs) of the use of animals in research.
Comment on whether, and how, the findings of this study are likely to translate to other species orsystems, including any relevance to human biology.
List all funding sources (including grant number) and the role of the funder(s) in the study.
aSchulz, et al. (2010) [24].
doi:10.1371/journal.pbio.1000412.t002 1. Simera I, Altman DG (2009) Writing a research systematic review. BMJ 334: 197. doi:10.1136/ 28. Plint AC, Moher D, Morrison A, Schulz K, article that is ‘‘fit for purpose’’: EQUATOR Altman DG, et al. (2006) Does the CONSORT Network and reporting guidelines. Evid Based 14. Macleod M (2005) What can systematic review checklist improve the quality of reports of and meta-analysis tell us about the experimental randomised controlled trials? A systematic review.
Porritt MJ, Rewell S, et al. (2010) Can Animal Int J Neuroprot Neuroregener 1: 201.
29. Kane RL, Wang J, Garrard J (2007) Reporting in 15. Tooth L, Ware R, Bain C, Purdie DM, Dobson A randomized clinical trials improved after adop- Studies? PLoS Med 7: e1000245. doi:10.1371/ (2005) Quality of reporting of observational tion of the CONSORT statement. J Clin Epide- longitudinal research. Am J Epidemiol 161: 30. Altman DG, Simera I, Hoey J, Moher D, Howells DW, Macleod MR (2010) Publication 16. Pound P, Ebrahim S, Sandercock P, Bracken MB, Schulz K (2008) EQUATOR: reporting guide- Bias in Reports of Animal Stroke Studies Leads to Roberts I (2004) Where is the evidence that lines for health research. Lancet 371: 1149–1150.
Major Overstatement of Efficacy. PLoS Biol 8: animal research benefits humans? BMJ 328: e1000344. doi:10.1371/journal.pbio.1000344.
Altman DG (2010) A catalogue of reporting 4. Sargeant JM, Thompson A, Valcour J, Elgie R, 17. Bennett LT, Adams M A (2004) Assessment of guidelines for health research. Eur J Clin Invest Saint-Onge J, et al. (2010) Quality of reporting of ecological effects due to forest harvesting: ap- clinical trials of dogs and cats and associations proaches and statistical issues. J Appl Ecol 41: 32. Wager E, Field EA, Grossman L (2003) Good with treatment effects. J Vet Intern Med 24: publication practice for pharmaceutical compa- 18. Morris CE, Bardin M, Berge O, Frey-Klett P, nies. Curr Med Res Opin 19: 149–154.
Fromin N (2002) Microbial biodiversity: Ap- Festing MFW, Cuthill IC, et al. (2009) Survey proaches to experimental design and hypothesis Sherlock G, Spellman P, et al. (2001) Minimum of the Quality of Experimental Design, Statistical testing in primary scientific literature from 1975 information about a microarray experiment to 1999. Microbiol Mol Biol Rev 66: 592–616.
(MIAME) — toward standards for microarray 19. Smith JA, Birke L, Sadler D (1997) Reporting animal use in scientific papers. Lab Anim 31: 6. Sargeant JM, Elgie R, Valcour J, Saint-Onge J, Kristal BS, Baker DJ, et al. (2007) Proposed 20. McCance I (1995) Assessment of statistical Thompson A, et al. (2009) Methodological quality minimum reporting standards for data analysis in procedures used in papers in the Australian and completeness of reporting in clinical trials metabolomics. Metabolomics 3: 231–241.
Veterinary Journal. Aust Vet J 72: 322–328.
conducted in livestock species. Prev Vet Med 91: 35. Stone SP, Cooper BS, Kibbler CC, Cookson BD, 21. Pocock SJ, Hughes MD, Lee RJ (1987) Statistical problems in the reporting of clinical trials. A 7. Macleod MR, Fisher M, O’Collins V, Sena ES, guidelines for transparent reporting of outbreak survey of three medical journals. New Engl J Med Dirnagl U, et al. (2009) Good laboratory practice.
reports and intervention studies of nosocomial Preventing introduction of bias at the bench.
infection. J Antimicrob Chemother 59: 833–840.
22. Chalmers I, Glasziou P (2009) Avoidable waste in the production and reporting of research evi- 36. Peters JL, Sutton AJ, Jones DR, Rushton L, 8. Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small 23. Festing MF, Altman DG (2002) Guidelines for the systematic reviews and meta-analyses of animal vessel disease? A systematic review. J Cereb Blood design and statistical analysis of experiments using experiments with guidelines for reporting.
laboratory animals. ILAR J 43: 244–258.
J Environ Sci Health B 41: 1245–1258.
9. Rice ASC, Cimino-Brown D, Eisenach JC, 24. Schulz KF, Altman DG, Moher D, the CON- 37. O’Connor AM, Sargeant JM, Gardner IA, Kontinen VK, Lacroix-Fralish ML, et al. (2008) Dickson JS, Torrence ME, et al. (2010) The Animal models and the prediction of efficacy in ment: updated guidelines for reporting parallel REFLECT statement: Methods and processes of clinical trials of analgesic drugs: a critical group randomised trials. BMJ 340: c332.
creating reporting guidelines for randomised appraisal and call for uniform reporting stan- 25. Moher D, Schulz KF, Altman DG for the controlled trials for livestock and food safety.
10. Sherwin CM (2007) Animal welfare: reporting statement: revised recommendations for improv- 38. International Committee of Medical Journal details is good science. Nature 448: 251.
ing the quality of reports of parallel-group Editors. Uniform Requirements for Manuscripts 11. Jafari P, Azuaje F (2006) An assessment of randomised trials. Lancet 357: 1191–1194.
Submitted to Biomedical Journals. Available: recently published gene expression analyses: 26. Altman DG (2005) Endorsement of the CON- http://www.icmje.org/urm_full.pdf. Accessed reporting experimental design and statistics.
SORT statement by high impact medical jour- nals: survey of instructions for authors. BMJ 330: 39. Council of Science Editors – Editorial Policy 12. Hackam DG, Redelmeier DA (2006) Translation Committee (2008–2009) CSE’s White Paper on of research evidence from animals to humans.
27. Hopewell S, Altman DG, Moher D, Schulz KF promoting integrity in scientific journal publica- tions, 2009 Update. Available: http://www.
13. Perel P, Roberts I, Sena E, Wheble P, Briscoe C, ment by high impact factor medical journals: a councilscienceeditors.org/editorial_policies/ et al. (2006) Comparison of treatment effects survey of journal editors and journal ‘instructions whitepaper/entire_whitepaper.pdf. Accessed 22 between animal experiments and clinical trials: June 2010 | Volume 8 | Issue 6 | e1000412 40. Committee on publication ethics (COPE). COPE nuffieldbioethics.org/go/browseablepublica- international animal experiments on fluid resus- best practice guidelines for journal editors.
tions/ethicsofresearchanimals/report_490.html.
Available: http://publicationethics.org/files/u2/ 55. Horn J, de Haan RJ, Vermeulen M, Limburg M Best_Practice.pdf. Accessed 22 January 2010.
¨ brink KJ, Rehbinder C (2000) Animal defini- (2001) Nimodipine in animal model experiments 41. Nuffield Council on Bioethics: The Ethics of Re- tion: a necessity for the validity of animal of focal cerebral ischemia: a systematic review.
search involving Animals (2005) Chapter 15: Discu- experiments? Lab Anim 34:: 1 21–130.
ssion and Recommendations; pp 313, paragraph 49. Boisvert DPJ (1997) Editorial policies and animal 56. Kilkenny C, Brown WJ, Cuthill IC, Emerson M, 15.58. Available: http://www.nuffieldbioethics.
welfare. In Animal Alternatives, Welfare and Altman DG (2010) Animal Research: Reporting org/fileLibrary/pdf/RIA_Report_FINAL-opt.pdf.
Ethics Zutphen LFM, Balls M, eds. Elsevier. pp In Vivo Experiments: The ARRIVE guidelines.
42. Drummond GB (2009) Reporting ethical matters 50. Working Committee for the Biological character- 57. Kilkenny C, Brown WJ, Cuthill IC, Emerson M, in The Journal of Physiology: standards and isation of laboratory animals/GV-Solas (1985) Altman DG (2010) Animal Research: Reporting In Guidelines for specification of animals and Vivo Experiments: The ARRIVE guidelines. Exp 43. Osborne NJ, Payne D, Newman ML (2009) husbandry methods when reporting the results Physiol. doi: 10.1113/expphysiol.2010.053793.
Journal editorial policies, animal welfare, and the of animal experiments. Lab Anim 19: 106–108.
58. Kilkenny C, Brown WJ, Cuthill IC, Emerson M, 51. Moher D, Schulz K, Simera I, Altman DG (2010) Altman DG (2010) Animal Research: Reporting 44. Hooijmans C, Leenars M, Ritskes-Hoitinga M Guidance for developers of health research In Vivo Experiments: The ARRIVE guidelines.
(2009) Improving the quality of publications on reporting guidelines. PLoS Med 7: e1000217.
J Physiol. doi: 10.1113/jphysiol.2010.192278.
animal experiments to make systematic reviews 52. Mignini LE, Khan KS (2006) Methodological 59. Kilkenny C, Brown WJ, Cuthill IC, Emerson M, 45. Wurbel H (2007) Publications should include an quality of systematic reviews of animal studies: a Altman DG (2010) Animal Research: Reporting animal welfare section. Nature 446: 257.
survey of reviews of basic research. Biomed In Vivo Experiments: The ARRIVE guidelines.
46. Alfaro V (2005) Specification of laboratory animal Central Medical Research Methodology 6: 10.
Br J Pharmacol. doi:10.1111/j.1476-5381.
use in scientific articles: Current low detail in the journal’s instructions for authors and some Donnan GA (2004) Pooling of animal experi- 60. Kilkenny C, Brown WJ, Cuthill IC, Emerson M, proposals. Methods Find Exp Clin Pharmacol mental data reveals influence of study design and Altman DG (2010) Animal Research: Reporting In publication bias. Stroke 35: 1203–1208.
Vivo Experiments: The ARRIVE guidelines. Lab- 47. Nuffield Council on Bioethics (2005) The ethics of 54. Roberts I, Kwan I, Evans P, Haig S (2002) Does oratory Animals. doi:10.1258/la.2010.0010021.
research involving animals. London: Ed Nuffield animal experimentation inform human health- Council on Bioethics, Available: http://www.
care? Observations from a systematic review of June 2010 | Volume 8 | Issue 6 | e1000412

Source: http://www.3rs-reduction.co.uk/assets/applets/ARRIVE_guidelines.pdf