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Report of the Synthesising Epidemiological Evidence Subgroup (SEES) of the Committee on Toxicity and Committee on Carcinogenicity

Publication date: 

27 Sep 2018


September 2018


Anna Hansell, Derek Bodey, Alan Boobis, Janet Cade, David Lovell, Neil Pearce, Julian Peto, Lesley Rushton, Heather Walton.

Publication type: 



The Synthesising Epidemiology Evidence Subgroup (SEES) of the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) and Committee on Carcinogenicity (COC) was set up in 2015. Its aim was to review and document current practice, given recent international and national development of methods by which evidence is synthesised, and to make recommendations for COT/COC guidance. Human studies can provide direct evidence of health impacts of particular exposures. However, much of the evidence comes from observational epidemiological studies, where control of chance, bias (including exposure misclassification) and confounding may be problematic. Systematic review and meta-analysis are gold standard methods for combining epidemiological studies, but may not be available, or practical or possible to conduct for many of the questions considered by COT/COC. Epidemiological reviews leading to statements or opinions in the last 10 years by COT/COC were identified and reviewed. A wide range of topics were identified relating to infant feeding, alcohol consumption, asbestos exposure, organophosphate exposure and vitamin E intake. The review methods used by the Committees varied by topic and requirement. Evidence synthesis in the World Health Organization (WHO), the International Agency for Research on Cancer (IARC) and European Food Safety Authority (EFSA) was discussed and a number of well documented major systems for evidence synthesis were reviewed. These were: • Systems initially designed for clinical medicine but now applied more widely, the Cochrane collaboration, GRADE (Grading of Recommendations Assessment Development and Evaluation) and SIGN (the Scottish Intercollegiate Guidelines Network). GRADE, with modifications, is being increasingly used in systematic reviews of environmental exposures. • US Federal programmes, the National Toxicology Program (NTP)-OHAT, National Toxicology Program (NTP)-Report on Carcinogens and EPA-IRIS – these programmes were considered too time-consuming and resource intensive to be replicated in their entirety for COT/COC • The Navigation Guide, first published in 2014, designed to speed up implementation of health protection measures for hazardous chemicals in the environment. SEES considered evidence synthesis methodologies and tools available in order to draw up guidance points for scoping, conducting and reporting. For systematic reviews and meta-analysis, SEES recommended use of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Quality assessment of studies was considered an integral part of review. A large number of numerical scoring tools are available; the subgroup did not recommend any one tool and considered that if employed, these should be used (i) to aid narrative assessment rather than in place of it and (ii) can help direct sensitivity analyses of the meta-analysis e.g. by exclusion of low-scoring studies. Specific issues related to quantitative risk assessment and meta-analysis were identified, particularly around consideration of study heterogeneity. Documentation of uncertainty and of (potential conflict of) interests was considered important. SEES also considered methods for combining epidemiological and toxicological evidence. These are less well developed than those for systematic review, particularly in a quantitative framework. There 4 are currently international initiatives in this area e.g. the Systematic Review and Integrated Assessment (SYRINA) and COT/COC will need to keep this methodological area under regular review.