Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency and internal validity of preclinical studies, mostly publishing expert consensus and experience. While many of the points raised in these various guidelines are identical or similar, they differ in detail and rigour. Most of them focus on reporting, only few of them cover the planning and conduct of studies. The aim of this systematic review is to identify existing experimental design, conduct, analysis and reporting guidelines relating to preclinical animal research. A systematic search in PubMed, Embase and Web of Science retrieved 13 863 unique results. After screening these on title and abstract, 613 papers entered the full-text assessment stage, from which 60 papers were retained. From these, we extracted unique 58 recommendations on the planning, conduct and reporting of preclinical animal studies. Sample size calculations, adequate statistical methods, concealed and randomised allocation of animals to treatment, blinded outcome assessment and recording of animal flow through the experiment were recommended in more than half of the publications. While we consider these recommendations to be valuable, there is a striking lack of experimental evidence on their importance and relative effect on experiments and effect sizes.
- scientific rigor
- internal validity
- preclinical studies
- animal studies
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Review history and Supplementary material
Correction notice This article has been corrected since it was published Online First. ORCIDs have been added for authors.
Collaborators The EQIPD WP3 study group members are: Jan Vollert, Esther Schenker, Malcolm Macleod, Judi Clark, Emily Sena, Anton Bespalov, Bruno Boulanger, Gernot Riedel, Bettina Platt, Annesha Sil, Martien J Kas, Hanno Wuerbel, Bernhard Voelkl, Martin C Michel, Mathias Jucker, Bettina M Wegenast-Braun, Ulrich Dirnagl, René Bernard, Esmeralda Heiden, Heidrun Potschka, Maarten Loos, Kimberley E Wever, Merel Ritskes-Hoitinga, Tom Van De Casteele, Thomas Steckler, Pim Drinkenburg, Juan Diego Pita Almenar, David Gallacher, Henk Van Der Linde, Anja Gilis, Greet Teuns, Karsten Wicke, Sabine Grote, Bernd Sommer, Janet Nicholson, Sanna Janhunen, Sami Virtanen, Bruce Altevogt, Kristin Cheng, Sylvie Ramboz, Emer Leahy, Isabel A Lefevre, Fiona Ducrey, Javier Guillen, Patri Vergara, Ann-Marie Waldron, Isabel Seiffert and Andrew S C Rice.
Contributors JV wrote the manuscript, mainly designed and conducted the systematic review and organised the process. ES and ASCR supervised the process and the designing and conduction of the systematic review and helped in writing the manuscript. All other authors helped in designing and conducting the systematic review and corrected the manuscript.
Funding This work is part of the European Quality In Preclinical Data (EQIPD) consortium. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 777364. This joint undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Competing interests None declared.
Ethics approval Not applicable.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on Figshare doi:10.6084/m9.figshare.9815753
Open data The data are available at https://figshare.com/articles/SyR_results_guidelines_preclinical_research_quality_EQIPD_csv/9815753.
Open materials The materials used are widely available.
Preregistration The systematic review and meta-analysis reported in this article was formally preregistered and the protocol published in BMJ Open Science doi:10.1136/ bmjos-2018-000004.
Open peer review Prepublication and Review History is available online at http://dx.doi.org/10.1136/bmjos-2019-100046.
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