Guidance on the assessment of the biological relevance of data in scientific assessments

Abstract

EFSA requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a beneficial health effect) or not. The guidance document provides a general framework for establishing the biological relevance of observations at various stages of the assessment. Biological relevance is considered at three main stages related to the process of dealing with evidence: Development of the assessment strategy. In this context, specification of agents, effects, subjects and conditions in relation to the assessment question(s): Collection and extraction of data; Appraisal and integration of the relevance of the agents, subjects, effects and conditions, i.e. reviewing dimensions of biological relevance for each data set. A decision tree is developed to assist in the collection, identification and appraisal of relevant data for a given specific assessment question to be answered. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. SummaryThe European Food Safety Authority (EFSA) requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a beneficial health effect) or not.The guidance clarifies a number of definitions and concepts (such as, responses of a biological system to exposure, mode of action and adverse outcome pathways, thresholds, critical effect, modelling approaches, biomarkers), which are central to biological relevance, in order to achieve that these concepts are used in a consistent way across EFSA areas of activity.The list of generic issues (e.g. nature and size of the biological changes or differences, including the relevance of the biological systems where the effects are observed) to consider when deciding on whether an observed effect is biologically relevant should be applicable to all relevant EFSA Scientific Panels and Scientific Committee.A framework was developed in which biological relevance is considered at three main stages related to the process of dealing with evidence. Development of the assessment strategy, should specify agents, effects, subjects and conditions in relation to the assessment question(s). The collection and extraction of data should follow identification of potentially biologically relevant evidence/data as specified in the Assessment strategy. The third step should include an appraisal and an integration of the biological relevance for each data set of the agents, subjects, effects and conditions. With regard to the ag...

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

“…The implementation of a problem formulation step within the context of combined exposure to multiple chemicals has been thoroughly discussed by a number of scientific bodies including WHO, US EPA, Joint Research Centre of the European Commission and the OECD (US EPA, ; WHO/IPCS, ; Meek et al., ; OECD, , ; SCHER, SCENIHR, SCCS, ; EFSA, ; Meek, ; Bopp et al., ; Solomon et al., ; EFSA Scientific Committee, ,b,c). The reader is referred to the cited references for a comprehensive overview.…”

“…Reporting should be consistent with EFSA's general principles on transparency and reporting (EFSA, ), including the use of the weight of evidence approach, assessment of biological relevance as well as the reporting and communication uncertainties (EFSA Scientific Committee, ,b, ; EFSA, ). In a risk assessment of combined exposure to multiple chemicals, this should include justifying the choice of methods used, documenting all steps of the procedure in sufficient detail for them to be repeated, and making clear where and how expert judgement has been used (EFSA, ).…”

“…178/2002], and these guidance documents provide means to develop consistent methodologies across EFSA panels (EFSA Scientific Committee, ). Recent examples include the use of the weight of evidence approach in scientific assessments, assessment of biological relevance and uncertainty analysis (EFSA Scientific Committee, ,b, ).…”

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

“…levels measured in tissues or concentrations of the compounds in the administered dosing solutions or feed analysed, were considered, Only studies showing endpoints regarded as adverse were selected. Effects such as differential gene expression or enzyme induction could not be linked directly to adverse endpoints and in accordance with the EFSA Guidance on Biological Relevance (EFSA Scientific Committee, ) were therefore excluded in the literature search. On the basis of the retrieved papers, the CONTAM Panel decided to also exclude other identified endpoints considered as ‘intermediate’ and not clearly acknowledged as a risk factor for specific diseases.…”

EFSA Scientific Colloquium 23 – Joint European Food Safety Authority and Evidence‐Based Toxicology Collaboration Colloquium Evidence integration in risk assessment: the science of combining apples and oranges 25–26 October 2017 Lisbon, Portugal

“…In recent years, a founding document was published that addressed the process for dealing with evidence and its guiding principles (EFSA, 2015 -first deliverable of EFSA PROMETHEUS project 2 ) along with a set of horizontal guidance developed by the EFSA Scientific Committee, focusing on approaches for integrating the evidence (EFSA Scientific Committee et al, 2017a), while accounting for the uncertainty inherent in the data and the process (EFSA Scientific Committee et al, 2018) and properly considering the biological relevance of evidence and effects (EFSA Scientific Committee et al, 2017b). A central role is played by the development of guidance to support the implementation of sound methodology for using evidence.…”