Impact of an Intervention to Improve Compliance With the ARRIVE Guidelines for the Reporting of In Vivo Animal Research

Emily Sena,1 for the Intervention to Improve Compliance With the ARRIVE Guidelines (IICARus) Collaborative Group


To conduct a randomized controlled trial to determine whether journal-mandated completion of an ARRIVE checklist (requiring authors to state on which page of their manuscript each checklist item is met) improves full compliance with the ARRIVE guidelines.


Manuscripts submitted to PLOS One between March 2015 and June 2015 determined in the initial screening process to describe in vivo animal research were randomized to either mandatory completion and submission of an ARRIVE checklist or the normal editorial processes, which do not require any checklist submission. The primary outcome was between-group differences in the proportion of studies that comply with the ARRIVE guidelines. We used online randomization with minimization (weighted at 0.75) according to country of origin; this was performed by the journal during technical checks after submission. Authors, academic editors, and peer reviewers were blinded to the study and the allocation. Accepted manuscripts were redacted for information relating to the ARRIVE checklist by an investigator who played no further role in the study to ensure outcome adjudicators were blinded to group allocation. We performed outcome adjudication in duplicate by assessing manuscripts against an operationalized version of the ARRIVE guidelines that consists of 108 items. Discrepancies are being resolved by a third independent reviewer.


We randomly assigned 1689 manuscripts, with 844 manuscripts assigned to the control arm and 845 assigned to the intervention arm. Of these, 1299 (76.9%) were sent for review, and of these, 688 (53.0%) were accepted for publication. All 688 manuscripts were dual assessed, and reconciliation of discrepancies is ongoing. Agreement between reviewers was high in relation to questions of the species reported (93%) and measures to reduce the risk of bias (73%-91% for 6 questions) and lowest for reporting the unit of analysis (50%). Data analysis is ongoing. We will present data for between-group differences in the proportion of studies that comply with the ARRIVE guidelines, each of the 38 subcomponents of the ARRIVE checklist, each of the 108 items, and the proportion of submitted manuscripts accepted for publication.


Our study will determine the effect of an alteration of editorial policy to include a completed ARRIVE checklist with submissions on compliance with the ARRIVE guidelines in the work when published. These results will inform the future development and further implementation of the ARRIVE guidelines.

1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK, emily.sena@ed.ac.uk

Conflict of Interest Disclosures:

The study management committee included a representative from the Public Library of Science (Catriona MacCallum), but other than providing general advice during the design of the study and organizing the provision of PDFs of included manuscripts, they had no role.


The Medical Research Council, National Centre for the Replacement Refinement and Reduction of Animals in Research, Biotechnology and Biological Sciences Research Council, and Wellcome Trust pooled resources without a normal grant cycle to fund this project.

Role of the Funder/Sponsor:

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract. The funders used their social media streams to publicize the study and recruit outcome assessors. National Centre for the Replacement, Refinement, and Reduction of Animals in Research employees were not allowed to enroll as outcome assessors because of their possible conflict of interest as sponsors of the ARRIVE guidelines.

Group Members:

The IICARus Collaborative group includes the following members: University of Edinburgh, Edinburgh, UK: Emily Sena, Cadi Irvine, Kaitlyn Hair, Fala Cramond, Paula Grill, Gillian Currie, Alexandra Bannach-Brown, Zsanett Bahor, Daniel-Cosmin Marcu, Monica Dingwall, Victoria Hohendorf, Klara Zsofia Gerlei, Victor Jones, Anthony Shek, David Henshall, Emily Wheater, Edward Christopher, and Malcolm Macleod; University of Tasmania, Hobart, Tasmania: David Howells; University of Nottingham, Nottingham, UK: Ian Devonshire and Philip Bath; Public Library of Science, Cambridge, UK: Catriona MacCallum; Imperial College London, London, UK: Rosie Moreland; Mansoura University, Mansoura, Egypt: Sarah Antar, Mona Hosh, and Ahmed Nazzal; University of New South Wales, Kensington, NSW, Australia: Katrina Blazek; Animal Sciences Unit, Animal and Plant Health Agency, Addlestone, UK: Timm Konold; University of Glasgow, Glasgow, UK: Terry Quinn and Teja Gregorc; AstraZeneca, Wilmington, Delaware, USA: Natasha Karp; Nuffield Research Placement Student, London, UK: Privjyot Jheeta and Ryan Cheyne; GlaxoSmithKline, Middlesex, UK: Joanne Storey; University College London, London, UK, and École Normale Supérieure, Paris, France: Julija Baginskaite; University Medical Center Utrecht, Utrecht, the Netherlands: Kamil Laban; University of Rome Sapienza, Rome, Italy: Arianna Rinaldi; Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands: Kimberley Wever; University of Southampton, Southampton, UK: Savannah Lynn; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil: Evandro Araújo De-Souza; University of Birmingham, Birmingham, UK: Leigh O”Connor; Hospital Research Center of the Sacred Heart of Montreal, Montreal, QC, Canada: Emmanuel Charbonney; National Cancer Institute, Milano, Italy: Marco Cascella; Federal University of Santa Catarina, Florianópolis, Brazil: Cilene Lino de Oliveira; University of Geneva, Geneva, Switzerland: Zeinab Ammar; British American Tobacco, London, UK: Sarah Corke; Ministry of Health, Cairo, Egypt: Mahmoud Warda; Vita-Salute San Raffaele University, Milan, Italy: Paolo Roncon; University of Hertfordshire, Hertfordshire, UK: Daniel Baker; University of Veterinary Medicine Hanover, Hanover, Germany: Jennifer Freymann.