. 2017 Jul;91(7):2551-2575.

doi: 10.1007/s00204-017-1980-3. Epub 2017 May 13.

A primer on systematic reviews in toxicology

Sebastian Hoffmann^{1

2}, Rob B M de Vries³, Martin L Stephens¹, Nancy B Beck⁴, Hubert A A M Dirven⁵, John R Fowle 3rd⁶, Julie E Goodman⁷, Thomas Hartung⁸, Ian Kimber⁹, Manoj M Lalu¹⁰, Kristina Thayer¹¹, Paul Whaley¹², Daniele Wikoff¹³, Katya Tsaioun¹⁴

Affiliations

¹ Evidence-Based Toxicology Collaboration at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
² seh consulting + services, Paderborn, Germany.
³ SYRCLE (SYstematic Review Centre for Laboratory Animal Experimentation), Department for Health Evidence (section HTA), Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ American Chemistry Council, Washington, DC, USA.
⁵ Norwegian Institute of Public Health, Oslo, Norway.
⁶ Science to Inform, LLC, Pittsboro, NC, USA.
⁷ Gradient, Cambridge, MA, USA.
⁸ Center for Alternatives to Animal Testing at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ University of Manchester, Manchester, UK.
¹⁰ Clinical Epidemiology Program, Regenerative Medicine Program, Department of Anesthesiology and Pain Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
¹¹ US Environmental Protection Agency, Washington, DC, USA.
¹² Lancaster Environment Centre, Lancaster University, Lancaster, UK.
¹³ ToxStrategies, Asheville, NC, USA.
¹⁴ Evidence-Based Toxicology Collaboration at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. ktsaiou1@jhu.edu.

PMID: 28501917
PMCID: PMC5489636
DOI: 10.1007/s00204-017-1980-3

A primer on systematic reviews in toxicology

Sebastian Hoffmann et al. Arch Toxicol. 2017 Jul.

. 2017 Jul;91(7):2551-2575.

doi: 10.1007/s00204-017-1980-3. Epub 2017 May 13.

Authors

Affiliations

¹ Evidence-Based Toxicology Collaboration at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
² seh consulting + services, Paderborn, Germany.
³ SYRCLE (SYstematic Review Centre for Laboratory Animal Experimentation), Department for Health Evidence (section HTA), Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ American Chemistry Council, Washington, DC, USA.
⁵ Norwegian Institute of Public Health, Oslo, Norway.
⁶ Science to Inform, LLC, Pittsboro, NC, USA.
⁷ Gradient, Cambridge, MA, USA.
⁸ Center for Alternatives to Animal Testing at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ University of Manchester, Manchester, UK.
¹⁰ Clinical Epidemiology Program, Regenerative Medicine Program, Department of Anesthesiology and Pain Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
¹¹ US Environmental Protection Agency, Washington, DC, USA.
¹² Lancaster Environment Centre, Lancaster University, Lancaster, UK.
¹³ ToxStrategies, Asheville, NC, USA.
¹⁴ Evidence-Based Toxicology Collaboration at Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. ktsaiou1@jhu.edu.

PMID: 28501917
PMCID: PMC5489636
DOI: 10.1007/s00204-017-1980-3

Abstract

Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

Keywords: Evidence synthesis; Evidence-based toxicology; Narrative review; Review steps; Systematic review.

PubMed Disclaimer

Conflict of interest statement

The contents of this manuscript are solely the responsibility of the authors and do not necessarily reflect the views or policies of their employers. Sebastian Hoffmann, a self-employed consultant, was paid by the Evidence-Based Toxicology Collaboration (EBTC) for his work on this manuscript. Nancy B. Beck was employed by the American Chemistry Council, a trade association of U.S. chemical manufacturers. Sebastian Hoffmann, Martin L. Stephens, John R. Fowle III, Ian Kimber, Nancy B. Beck, Rob de Vries and Katya Tsaouin are members of the Board of Trustees of the EBTC, which is funded by Center for Alternatives to Animal Testing at Johns Hopkins Bloomberg School of Public Health and ExxonMobil Foundation. Hubert Dirven, Julie E. Goodman, Manoj M. Lalu, Kristina Thayer, Paul Whaley and Daniele Wikoff are members of the Scientific Advisory Council of the EBTC. Manoj Lalu was supported by The Ottawa Hospital Anesthesia Alternate Funds Association.

Figures

**Fig. 2**
Flow chart of the study selection (from Moher et al. 2009) (screening is based on title and abstracts)

**Fig. 3**
Representative summary table (a) for the risk of bias assessment [*green cells* with (*plus*): low risk of bias; *yellow cells* with (*question mark*): unknown risk of bias; *red cells* with (*hyphen*): high risk of bias] and representative summary (b) of risk of bias analysis across studies (reproduced from Wever et al. 2015)

See this image and copyright information in PMC

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A primer on systematic reviews in toxicology

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A primer on systematic reviews in toxicology

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Conflict of interest statement

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