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.
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Source: http://researchservices.anu.edu.au/ori/animal/docs/ARRIVE%20Guidelines.pdf