Deploying elements of scoping review methods for adverse outcome pathway development: a space travel case example

Abstract

Purpose

Health protection agencies require scientific information for evidence-based decision-making and guideline development. However, vetting and collating large quantities of published research to identify relevant high-quality studies is a challenge. One approach to address this issue is the use of adverse outcome pathways (AOPs) that provide a framework to assemble toxicological knowledge into causally linked chains of key events (KEs) across levels of biological organization to culminate in an adverse health outcome of significance to regulatory decision-making. Traditionally, AOPs have been constructed using a narrative review approach where the collection of evidence that supports each pathway is based on prior knowledge of influential studies that can also be supplemented by individually selecting and reviewing relevant references.

Objectives

We aimed to create a protocol for AOP weight of evidence gathering that harnesses elements of both scoping review methods and artificial intelligence (AI) tools to increase transparency while reducing bias and workload of human screeners.

Methods

To develop this protocol, an existing space-health AOP in the workplan of the Organisation for Economic Co-operation and Development (OECD) AOP Programme was used as a case example. To balance the benefits of both scoping review tools and narrative approaches, a study protocol outlining a screening and search strategy was developed, and three reference collection workflows were tested to identify the most efficient method to inform weight of evidence. The workflows differed in their literature search strategies, and combinations of software tools used.

Results

Across the three tested workflows, over 59 literature searches were completed, retrieving over 34,000 references of which over 3300 were human reviewed. The most effective of the three methods used a search strategy with searches across each component of the AOP network, SWIFT Review as a pre-filtering software, and DistillerSR to create structured screening and data extraction forms. This methodology effectively retrieved relevant studies while balancing efficiency in data retrieval without compromising transparency, leading to a well-synthesized evidence base to support the AOP.

Conclusions

The workflow is still exploratory in the context of AOP development, and we anticipate adaptations to the protocol with further experience. To further the systematicity, future iterations of the workflow could include structured quality assessment and risk of bias analysis. Overall, the workflow provides a transparent and documented approach to support AOP development, which in turn will support the need for rigorous methods to identify relevant scientific evidence while being practical to allow uptake by the broader community.

Keywords:

• AOP
• radiation
• risk assessment
• systematic evidence mapping
• scoping review
• space flight health

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is funded by the Canadian Space Agency, a Health Canada Solutions Fund and partially by the Genomics Research and Development Initiative. Tatiana Kozbenko has been supported through a University of Ottawa Admission Scholarship. Carole L. Yauk acknowledges the Canada Research Chairs Program.

Notes on contributors

Tatiana Kozbenko

Tatiana Kozbenko, M.Sc. student in Biology and Bioinformatics at the University of Ottawa, and a Research Affiliate with the Consumer and Clinical Radiation Protection Bureau at Health Canada.

Nadine Adam

Nadine Adam, M.Sc., is a Laboratory Biologist at Health Canada, and previously worked with the Consumer and Clinical Radiation Protection Bureau. She completed her M.Sc. studies in Biochemistry at the University of Ottawa.

Vita Lai

Vita Lai, M.Sc., is a contract research technician at the Ionizing Radiation Health Sciences Division of the Consumer and Clinical Radiation Protection Bureau at Health Canada.

Snehpal Sandhu

Snehpal Sandhu is a student at the University of Ottawa studying Biomedical Sciences with an option in Neuroscience and is working in a co-op placement at Health Canada.

Jacqueline Kuan

Jacqueline Kuan is a University of Ottawa student studying Biopharmaceutical Science, former co-op student, and current part-time employee of the Health Canada Consumer and Clinical Radiation Protection Bureau.

Danicia Flores

Danicia Flores is a Carleton University student studying Biology with a concentration in Health Science and was in a co-op placement with Health Canada before continuing on as a laboratory technician.

Meghan Appleby

Meghan Appleby is a Carleton University student studying Neuroscience and Mental Health and is in a co-op placement with Health Canada

Hanna Parker

Hanna Parker is a University of Ottawa undergraduate student majoring in Biomedical Science and completing an Honour’s Thesis project.

Robyn Hocking

Robyn Hocking, MLIS, is a Research Librarian at the Health Canada Library.

Katya Tsaioun

Katya Tsaioun, Ph.D., Executive Director, Evidence-based Toxicology Collaboration at Johns Hopkins Bloomberg School of Public Health (EBTC). She is a systematic review methodologist, who leads multistakeholder working groups aiming to bring evidence-based approaches, like Systematic Literature Reviews and Systematic Maps, to the field of toxicology.

Carole Yauk

Carole Yauk, Ph.D, is a Professor in the Department of Biology, University of Ottawa, where she holds the Canada Research Chair in Genomics and the Environment. Dr. Yauk serves as a Canadian delegate to the OECD's Extended Advisory Group on Molecular Screening and Toxicogenomics. Within this group, she contributed to the development of the AOP Users' Handbook and is an AOP developer and reviewer.

Ruth Wilkins

Ruth Wilkins, Ph.D, is the Division Chief of the Ionizing Health Sciences Division at the Consumer and Clinical Radiation Protection Bureau. of Health Canada. She is the Canadian alternate representative of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR).

Vinita Chauhan

Vinita Chauhan, Ph.D, is a Senior Research Scientist at the Consumer and Clinical Radiation Protection Bureau of Health Canada. She is a Canadian delegate of the HLG-LDR and Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) of the OECD. She chairs the HLG-LDR Rad/Chem AOP Joint Topical Group and is the co-founder of Canadian Organization of Health Effects from Radiation Exposure (COHERE) initiative.