Abstract
The BJP has been and remains an active advocate of the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010a) that were established by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in 2010. The ARRIVE guidelines need no introduction and we will not rehearse the arguments in depth here, other than to restate that the lack of key in vivo experimental details has been identified as a major contributing factor to the poor reproducibility of pre-clinical research. This fact was the primary driver for establishment by the NC3Rs of the first version of the ARRIVE guidelines. ARRIVE provided a 20-point checklist, specifying all of the experimental details (procedures and fixed factors) that should be included in manuscripts for proper reporting of animal research. The guidelines were rapidly endorsed internationally by funding bodies, universities, learned societies and, importantly, Life Science journals. Currently there are 1,046 journals endorsing ARRIVE including BJP, which was one of the original six influential journals that published the guidelines in full in 2010 (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010b). However, ARRIVE has not had the effect that was originally hoped for, despite this widespread support and endorsement. In 2016 and in 2018 assessments of adherence of articles published in endorsing journals identified a lack of engagement. As an example, one systematic review of reports of studies investigating acute lung injury revealed that, of the items expected for ARRIVE compliance, only 45% of those advised for inclusion in the Methods, and only 29% of those for inclusion in the Results section, were present (Avey et al., 2016). Moreover, formal endorsement of the ARRIVE guidelines by journals did not necessarily improve compliance (Leung, Rousseau-Blass, Beauchamp, & Pang, 2018). Such disappointing reports of outcome triggered a reappraisal of the guidelines led by the NC3Rs who, in 2018, established a new, international Working Group to review and update the ARRIVE guidelines to generate ARRIVE 2.0 (Percie du Sert et al., 2018). As with the team of experts brought together to establish the first iteration of ARRIVE, the Editor in Chief of the BJP is a member of the new team that was assembled. As such, the BJP has been well-placed to influence the content, testing and final publication of both iterations of the guidelines. In 2015, the BJP published an editorial reporting findings from a survey of compliance with ARRIVE in articles published in 2014 in two issues of the journal (McGrath & Lilley, 2015). The results were not as had been hoped for, as was also evident from assessments elsewhere, and revealed scope for improving compliance in respect of both the design of the (animal) experiments and the description of experimental procedures. To help remedy this problem, a checklist was developed that provided an aide memoire of the details of the animals and research procedures that should be reported in manuscripts submitted to the journal. A further editorial focussed on experimental design and data analysis (Curtis et al., 2018) for all types of experimental data published in the journal, including those emanating from experiments with animals, was also published. A key issue with many of the studies reported in BJP prior to this related to inadequate experimental design and inappropriate statistical analysis. At the same time, the Instructions to Authors were revised, to include the new rubric, and the editorial scrutiny of these aspects of the peer review process was tightened up. As a further prompt, in 2016, authors were required to make a Declaration as part of the submission process, to confirm that their manuscript was ARRIVE compliant. In addition to these measures, two new 'specialist' editors were appointed: a Design & Analysis Advisor and a Consulting Editor in ARRIVE Guidelines and Animal Welfare. The brief of the latter was to monitor ARRIVE compliance in BJP publications and to assist Senior Editors with their appraisal of manuscripts. All these changes still remain in place with the addition of a Consulting Editor in Statistical Analysis to ensure that the research reports match BJP criteria and so qualify for publication. ARRIVE 2.0 together with an 'Explanation and Elaboration' document was loaded onto the NC3Rs website in July 2019 as a preprint (i.e., before peer review (Percie du Sert et al., 2019)), and is now published in full in PLOS Biology (Percie du Sert et al., 2020), with simultaneous publication in several international journals, including this issue of the BJP (Percie du Sert et al., 2020). In preparation for the publication of the new guidelines we conducted surveys assessing compliance to ARRIVE in the BJP over 4 years, the results of which can be seen in Table 1. These data together with the July 2019 preprint of ARRIVE 2.0 were discussed extensively by the Senior Editorial Board of the BJP in December 2019. This editorial explains the ensuing changes in the journal's editorial policy as a result of those discussions and how they relate to ARRIVE 2.0. The principle of full disclosure lies at the heart of what we expect from authors wishing to publish in the BJP and in support of this principle is the absence of a word restriction for the Methods section. Judging from articles surveyed, between July 2014 and October 2019, most authors are conscientious about compliance with our 'Instructions to Authors' in respect of confirming ethical approval of the research, specifying the source, species and strain of animals and the inclusion of a statement on the translational relevance of the research study (Table 1). However, a general observation is that, although many manuscripts include lengthy details of the molecular biological or biochemical techniques that were used in the study, when experiments involved the use of animals, both the design of experiments and the description of the experimental procedures are often inadequately detailed making reproducibility challenging. Reporting of the method for killing animals has improved over the years but is still inconsistent, despite the need for manuscripts to be clear about when and how animals were killed. Information on housing and husbandry is often provided but, again, the level of detail is highly variable. Important elements, such as stocking density, configuration of group-housed animals (in respect of littermates, genotypes, or randomised mixed-caging, for example) provision of food (including, ideally, the composition of the laboratory diet) and water and environmental enrichment are not always disclosed, despite increasing recognition that these factors can affect the research findings (Finney et al., 2020; Reardon, 2016). The poor reporting of the provision of analgesia in the surgical context is particularly worrying. Of course, a lack of any mention of analgesia in the manuscript does not mean that none was provided; there could also be a strong scientific justification for withholding analgesia in some experiments. However, that did not apply to any of the manuscripts that were reviewed: in all those cases, analgesia could and should have been provided. Two options were considered by the Senior Editorial Board in December 2019: (i) endorse ARRIVE 2.0 guidelines and adopt them verbatim as official BJP policy or (ii) endorse ARRIVE 2.0 but devise our own reporting policy, which would be particularly relevant for pharmacologists. In considering the results of our surveys and the content of the ARRIVE 2.0 preprint, the Board decided on the latter approach. Authors should be reassured that nothing major has changed in practice. This journal has always taken inspiration from ARRIVE, while adopting a 'bespoke' approach to the reporting of the types of animal research carried out by pharmacologists. Authors should also note that requirements in respect of experimental design and analysis in articles published in BJP have not changed at all and can be found at: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14153 (Curtis et al., 2018). That said, we strongly advise authors to use the NC3Rs Experimental Design Assistant (https://www.nc3rs.org.uk/experimental-design-assistant-eda) (Percie du Sert et al., 2017) when planning the experimental design and the data analysis of their work. The most striking change in the updated ARRIVE guidelines is the subdivision of the original checklist into two tables/checklists: the 'Essential 10' and the 'Recommended set'. The former focuses mainly on aspects of the experimental design that are essential for reducing bias (subjective or systematic), whereas the latter deals with points that pertain to the factors that authors are advised to disclose in order to enable others to replicate the experiment. Our current guidelines for experimental design and statistical analysis address many of the 'Essential 10', and for our modified approach we concentrate on many of the items in the 'Recommended set'. Our updated'BJP Declaration of Transparency and Scientific Rigour: Checklist for Animal Experimentation' is shown in Table 2, along with indicators of how each element connects with ARRIVE 2.0. These amendments do not challenge the importance of either version of ARRIVE. On the contrary, we strongly recommend that all authors read ARRIVE 2.0 (Percie du Sert, Hurst, et al., 2020) and familiarise themselves with the complementary 'Explanation and Elaboration' document (Percie du Sert et al., 2020). Essential 8 Essential 9 Recommended Recommended 12 Recommended 14 Recommended 15 Recommended 16 In terms of the details that should be included in every manuscript submitted to the BJP, the new checklist for reporting animal research will consist of the following six mandatory elements (see also Table 2): Details of the source, species, strain, sex, age a