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      Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0

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          Abstract

          Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.

          Abstract

          The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. This article explains the rationale behind each item in the revised and updated ARRIVE guidelines 2019, clarifying key concepts and providing illustrative examples.

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          The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

          Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
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            Effect size, confidence interval and statistical significance: a practical guide for biologists.

            Null hypothesis significance testing (NHST) is the dominant statistical approach in biology, although it has many, frequently unappreciated, problems. Most importantly, NHST does not provide us with two crucial pieces of information: (1) the magnitude of an effect of interest, and (2) the precision of the estimate of the magnitude of that effect. All biologists should be ultimately interested in biological importance, which may be assessed using the magnitude of an effect, but not its statistical significance. Therefore, we advocate presentation of measures of the magnitude of effects (i.e. effect size statistics) and their confidence intervals (CIs) in all biological journals. Combined use of an effect size and its CIs enables one to assess the relationships within data more effectively than the use of p values, regardless of statistical significance. In addition, routine presentation of effect sizes will encourage researchers to view their results in the context of previous research and facilitate the incorporation of results into future meta-analysis, which has been increasingly used as the standard method of quantitative review in biology. In this article, we extensively discuss two dimensionless (and thus standardised) classes of effect size statistics: d statistics (standardised mean difference) and r statistics (correlation coefficient), because these can be calculated from almost all study designs and also because their calculations are essential for meta-analysis. However, our focus on these standardised effect size statistics does not mean unstandardised effect size statistics (e.g. mean difference and regression coefficient) are less important. We provide potential solutions for four main technical problems researchers may encounter when calculating effect size and CIs: (1) when covariates exist, (2) when bias in estimating effect size is possible, (3) when data have non-normal error structure and/or variances, and (4) when data are non-independent. Although interpretations of effect sizes are often difficult, we provide some pointers to help researchers. This paper serves both as a beginner's instruction manual and a stimulus for changing statistical practice for the better in the biological sciences.
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              Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.

              To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. Meta-analyses from the Cochrane Pregnancy and Childbirth Database. The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: VisualizationRole: Writing – original draft
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                14 July 2020
                July 2020
                14 July 2020
                : 18
                : 7
                : e3000411
                Affiliations
                [1 ] NC3Rs, London, United Kingdom
                [2 ] The William Harvey Research Institute, London, United Kingdom
                [3 ] Barts Cardiovascular CTU, Queen Mary University of London, London, United Kingdom
                [4 ] Taylor & Francis Group, London, United Kingdom
                [5 ] Health Science Practice, ICF, Durham, North Carolina, United States of America
                [6 ] Nature, San Francisco, California, United States of America
                [7 ] School of Education, University of Bristol, Bristol, United Kingdom
                [8 ] PLOS ONE, Cambridge, United Kingdom
                [9 ] School of Biological Sciences, University of Bristol, Bristol, United Kingdom
                [10 ] QUEST Center for Transforming Biomedical Research, Berlin Institute of Health & Department of Experimental Neurology, Charite Universitätsmedizin Berlin, Berlin, Germany
                [11 ] National Heart and Lung Institute, Imperial College London, London, United Kingdom
                [12 ] Centre for Evidence Synthesis in Global Health, Clinical Sciences Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                [13 ] Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom
                [14 ] Tasmanian School of Medicine, University of Tasmania, Hobart, Australia
                [15 ] Data Sciences & Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
                [16 ] Prioris.ai Inc, Ottawa, Canada
                [17 ] Hindawi Ltd, London, United Kingdom
                [18 ] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
                [19 ] Academia Europaea Knowledge Hub, Cardiff University, Cardiff, United Kingdom
                [20 ] Medical Research Council, London, United Kingdom
                [21 ] Statistics in Anesthesiology Research (STAR) Core, Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, Florida, United States of America
                [22 ] Discipline of Exercise and Sport Science, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
                [23 ] National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, United States of America
                [24 ] Janssen Pharmaceutica NV, Beerse, Belgium
                [25 ] Veterinary Public Health Institute, Vetsuisse Faculty, University of Bern, Bern, Switzerland
                University Paris Descartes, FRANCE
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: AA is the editor in chief of the British Journal of Pharmacology. WJB, ICC, and ME are authors of the original ARRIVE guidelines. WJB serves on the Independent Statistical Standing Committee of the funder CHDI foundation. AC is a Senior Editor for PLOS ONE. AC, CJM, MM, and ESS were involved in the IICARus trial. ME, MM, and ESS have received funding from NC3Rs. ME sits on the MRC ERPIC panel. STH is chair of the NC3Rs board; trusteeship of the BLF, Kennedy Trust, DSRU, and CRUK; member of Governing Board, Nuffield Council of Bioethics, member Science Panel for Health (EU H2020); founder and NEB Director Synairgen; consultant Novartis, Teva, and AZ; and chair MRC/GSK EMINENT Collaboration. VH, KL, EJP, and NPdS are NC3Rs staff; role includes promoting the ARRIVE guidelines. SEL and UD are on the advisory board of the UK Reproducibility Network. CJM has shareholdings in Hindawi, is on the publishing board of the Royal Society, and on the EU Open Science policy platform. UD, MM, NPdS, CJM, ESS, TS, and HW are members of EQIPD. MM is a member of the Animals in Science Committee and on the steering group of the UK Reproducibility Network. NPdS and TS are associate editors of BMJ Open Science. OHP is vice president of Academia Europaea, editor in chief of Function, senior executive editor of the Journal of Physiology, and member of the Board of the European Commission’s SAPEA (Science Advice for Policy by European Academies). FR is an NC3Rs board member and has shareholdings in GSK. FR and NAK have shareholdings in AstraZeneca. PR is a member of the University of Florida Institutional Animal Care and Use Committee and editorial board member of Shock. ESS is editor in chief of BMJ Open Science. SDS’s role is to provide expertise and does not represent the opinion of the NIH. TS has shareholdings in Johnson & Johnson. SA, MTA, MB, PG, DWH, and KR declared no conflict of interest.

                Author information
                http://orcid.org/0000-0002-9478-0540
                http://orcid.org/0000-0001-7626-6399
                http://orcid.org/0000-0002-8615-9658
                http://orcid.org/0000-0002-8696-3232
                http://orcid.org/0000-0002-6659-6885
                http://orcid.org/0000-0002-1292-0408
                http://orcid.org/0000-0002-5007-8856
                http://orcid.org/0000-0003-0755-6119
                http://orcid.org/0000-0002-0607-6941
                http://orcid.org/0000-0002-2512-7724
                http://orcid.org/0000-0002-8404-2907
                http://orcid.org/0000-0001-9623-2225
                http://orcid.org/0000-0001-9187-9839
                http://orcid.org/0000-0001-6510-0959
                http://orcid.org/0000-0002-8877-6262
                http://orcid.org/0000-0001-7480-6275
                http://orcid.org/0000-0001-6563-7617
                http://orcid.org/0000-0002-3282-8502
                http://orcid.org/0000-0002-9927-5121
                http://orcid.org/0000-0002-2934-3010
                Article
                PBIOLOGY-D-19-01864
                10.1371/journal.pbio.3000411
                7360025
                32663221
                39493d65-9d84-4e14-a6bb-ffa12b94964e

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                Page count
                Figures: 6, Tables: 2, Pages: 65
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000849, National Centre for the Replacement, Refinement and Reduction of Animals in Research;
                Award Recipient :
                This work was supported by the National Centre of the Replacement, Refinement & Reduction on Animals in Research (NC3Rs, https://www.nc3rs.org.uk/). NPdS, KL, VH, and EJP are employees of the NC3Rs.
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