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Methodological standards, quality of reporting and regulatory compliance in animal research on amyotrophic lateral sclerosis: a systematic review
  1. Joana G Fernandes1,2,
  2. Nuno H Franco1,2,
  3. Andrew J Grierson3,4,
  4. Jan Hultgren5,
  5. Andrew J W Furley4,6,
  6. I Anna S Olsson1,2
  1. 1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
  2. 2 IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
  3. 3 Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
  4. 4 Bateson Centre, University of Sheffield, Sheffield, UK
  5. 5 Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden
  6. 6 Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK
  1. Correspondence to I Anna S Olsson; olsson{at}ibmc.up.pt

Abstract

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Objectives The amyotrophic lateral sclerosis (ALS) research community was one of the first to adopt methodology guidelines to improve preclinical research reproducibility. We here present the results of a systematic review to investigate how the standards in this field changed over the 10-year period during which the guidelines were first published (2007) and updated (2010).

Methods We searched for papers reporting ALS research on SOD1 (superoxide dismutase 1) mice published between 2005 and 2015 on the ISI Web of Science database, resulting in a sample of 569 papers to review, after triage. Two scores—one for methodological quality, one for regulatory compliance—were built from weighted sums of separate sets of items, and subjected to multivariable regression analysis, to assess how these related to publication year, type of study, country of origin and journal.

Results Reporting standards improved over time. Of papers published after the first ALS guidelines were made public, fewer than 9% referred specifically to these. Of key research parameters, only three (genetic background, number of transgenes and group size) were reported in >50% of the papers. Information on housing conditions, randomisation and blinding was absent in over two-thirds of the papers. Group size was among the best reported parameters, but the majority reported using fewer than the recommended sample size and only two studies clearly justified group size.

Conclusions General methodological standards improved gradually over a period of 8–10 years, but remained generally comparable with related fields with no specific guidelines, except with regard to severity. Only 11% of ALS studies were classified in the highest severity level (animals allowed to reach death or moribund stages), substantially below the proportion in studies of comparable neurodegenerative diseases such as Huntington’s. The existence of field-specific guidelines, although a welcome indication of concern, seems insufficient to ensure adherence to high methodological standards. Other mechanisms may be required to improve methodological and welfare standards.

  • amyotrophic lateral sclerosis
  • ALS
  • guidelines
  • methodology
  • reporting
  • quality
  • compliance
  • animal welfare
  • reproducibility

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • Prepublication and Review History is available online at http://dx.doi.org/10.1136/bmjos-2018-000016.

  • Contributors Original idea for this study: NHF, IASO. Conception and design of the work: NHF, IASO, AJWF, AJG. Data collection: JGF, NHF. Data analysis and interpretation: NHF, JGF, JH, AJWF, AJG, IASO. Drafting the article: NHF, JGF. Critical revision of the article: AJG, AJWF, JH, IASO. Final approval of the version to be published: NHF, JGF, AJG, AJWF, JH, IASO.

  • Funding NHF was a recipient of a Postdoctoral Research Fellowship from the Portuguese Foundation for Science and Technology (FCT), grant reference SFRH/BPD/85978/2012. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-HEALTH-2013-INNOVATION-1) under grant agreement no 602616 (Project ANIMPACT). Analysis and revision were supported by the project Norte-01-0145-FEDER-000008 - Porto Neurosciences and Neurologic Disease Research Initiative at i3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project ’Institute for Research and Innovation in Health Sciences' (POCI-01-0145-FEDER-007274).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned, externally peer reviewed.

  • Open data Data available in a public, open access repository (https://ckan-rdm.up.pt/dataset/i3s-2019-001).

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