EFSA’s framework for evidence-based scientific assessments: A case study on uncertainty analysis

Main Article Content

Elisa Aiassa, Caroline Merten, Laura Martino
[show affiliations]


To provide sound scientific advice in support of the European decision-making process in food and feed safety, the European Food Safety Authority (EFSA) has defined the principles for producing “evidence-based scientific assessments” (impartiality, methodological rigor, transparency, and engagement) and, to help fulfil them, has developed cross-cutting methodological approaches. This paper focusses on two of these approaches: conducting scientific assessments in four steps – with an emphasis on developing a protocol for the assessment a priori – and analyzing uncertainty. An overview of the 4-step approach and of the methods for addressing uncertainty is given, and a case study on uncertainty analysis, developed in collaboration with the German Federal Institute for Risk Assessment, is illustrated. The main advantage related to the implementation of protocols and uncertainty analysis is improvement of the scientific value of the outputs. However, experience and further capacity-building is needed to better incorporate uncertainty analysis into the planning phase (protocol) of the scientific assessment process. The case study is based on exposure in humans. Nonetheless it provides an example of a framework for evidence-based scientific assessments that is applicable also to other types of evidence, including evidence arising from new approach methodologies. Adopting the proposed framework, which covers an analysis of uncertainties in the planning and implementation phase, is expected to foster the integration of multiple evidence sources, including alternative methods and testing strategies, in the regulatory scientific assessment process.

Article Details

How to Cite
Aiassa, E., Merten, C. and Martino, L. (2022) “EFSA’s framework for evidence-based scientific assessments: A case study on uncertainty analysis”, ALTEX - Alternatives to animal experimentation, 39(3), pp. 451–462. doi: 10.14573/altex.2004211.
Articles Special Issue

Bell, S. M., Chang, X., Wambaugh, J. F. et al. (2018). In vitro to in vivo extrapolation for high throughput prioritization and decision making. Toxicol In Vitro 47, 213-227. doi:10.1016/j.tiv.2017.11.016

Casati, S. (2018). Integrated approaches to testing and assessment. Basic Clin Pharmacol Toxicol 123, Suppl 5, 51-55. doi:10.1111/bcpt.13018

EC – European Commission (2002). Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. OJ L 31, 1-24. http://data.europa.eu/eli/reg/2002/178/oj

EC, Directorate-General for Research and Innovation, Group of Chief Scientific Advisors (2019). Scientific Advice to European Policy in a Complex World. Publications Office. doi:10.2777/80320

EFSA – European Food Safety Authority (2008). Safety of aluminium from dietary intake - Scientific opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC). EFSA J 6, 754. doi:10.2903/j.efsa.2008.754

EFSA (2010). Application of systematic review methodology to food and feed safety assessments to support decision making. EFSA J 8, 1637. doi:10.2903/j.efsa.2010.1637

EFSA (2014). Guidance on expert knowledge elicitation in food and feed safety risk assessment. EFSA J 12, 3734. doi:10.2903/j.efsa.2014.3734

EFSA (2015). Principles and process for dealing with data and evidence in scientific assessments. EFSA J 13, 4121. doi:10.2903/j.efsa.2015.4121

EFSA (2016). EFSA Strategy 2020. Trusted Science for Safe Food. Protecting Consumers’ Health with Independent Scientific Advice on the Food Chain. European Food Safety Authority. doi:10.2805/397609

EFSA (2017). Workshop on the trial of the EFSA guidance document on uncertainty analysis in scientific assessments 22-23 June 2017 Parma, Italy. EFSA Supporting Publications 14, 1313E. doi:10.2903/sp.efsa.2017.EN-1313

EFSA, Gundert-Remy, U., Bodin, J. et al. (2017). Bisphenol A (BPA) hazard assessment protocol. EFSA Supporting Publications 14, 1354E. doi:10.2903/sp.efsa.2017.EN-1354

EFSA, Aiassa, E., Martino, L. et al. (2018). Implementation of PROMETHEUS 4-step approach for evidence use in EFSA scientific assessments: Benefits, issues, needs and solutions. EFSA Supporting Publications 15, 1395E. doi:10.2903/sp.efsa.2018.EN-1395

EFSA (2018a). Protocol for the scientific opinion on the tolerable upper intake level of dietary sugars. EFSA J 16, e05393. doi:10.2903/j.efsa.2018.5393

EFSA (2018b). Evaluation of the impact of glyphosate and its residues in feed on animal health. EFSA J 16, e05283. doi:10.2903/j.efsa.2018.5283

EFSA, Hart, A., Maxim, L. (2019). Guidance on communication of uncertainty in scientific assessments. EFSA J 17, e05520. doi:10.2903/j.efsa.2019.5520

EFSA and BfR (2019). International conference on uncertainty in risk analysis. EFSA Supporting Publication 16, 1689E. doi:10.2903/sp.efsa.2019.EN-1689

EFSA Panel on Animal Health Welfare (2017). Bluetongue: Control, surveillance and safe movement of animals. EFSA J 15, e04698. doi:10.2903/j.efsa.2017.4698

EFSA Panel on Biological Hazards (2016). Evaluation of the safety and efficacy of Listex™ P100 for reduction of pathogens on different ready-to-eat (RTE) food products. EFSA J 14, e04565. doi:10.2903/j.efsa.2016.4565

EFSA Panel on Contaminants in the Food Chain (CONTAM), Knutsen, H. K., Alexander, J. et al. (2018). Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food. EFSA J 16, e05333. doi:10.2903/j.efsa.2018.5333

EFSA Panel on Food Additives and Nutrient Sources added to Food (2015). Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones. EFSA J 13, 4246. doi:10.2903/j.efsa.2015.4246

EFSA Panel on Nutrition Novel Foods (NDA), Turck, D., Castenmiller, J. et al. (2019). Dietary reference values for sodium. EFSA J 17, e05778. doi:10.2903/j.efsa.2019.5778

EFSA Panel on Plant Health (PLH), Jeger,M. Bragard, C. et al. (2017). Pest risk assessment of Eotetranychus lewisi for the EU territory. EFSA J 15, e04878. doi:10.2903/j.efsa.2017.4878

EFSA Scientific Committee , Hardy,A., Benford, D. et al. (2017a). Guidance on the use of the weight of evidence approach in scientific assessments. EFSA J 15, e4971. doi:10.2903/j.efsa.2017.4971

EFSA Scientific Committee, Hardy, A., Benford, D. et al. (2017b). Guidance on the assessment of the biological relevance of data in scientific assessments. EFSA J 15, e4970. doi:10.2903/j.efsa.2017.4970

EFSA Scientific Committee, Benford, D., Halldorsson, T. (2018a). Guidance on uncertainty analysis in scientific assessments. EFSA J 16, e5123. doi:10.2903/j.efsa.2018.5123

EFSA Scientific Committee, Benford, D., Halldorsson, T. et al. (2018b). The principles and methods behind EFSA’s guidance on uncertainty analysis in scientific assessment. EFSA J 16, e05122. doi:10.2903/j.efsa.2018.5122

EU (2019). Regulation (EU) 2019/1381 of the European Parliament and of the Council of 20 June 2019 on the transparency and sustainability of the EU risk assessment in the food chain. OJ L 231, 1-28. http://data.europa.eu/eli/reg/2019/1381/oj

EU ANSA (2018). Approaches to Assess and Manage Scientific Uncertainty: Examples from EU ANSA Agencies. Luxembourg: Publications Office of the European Union. doi:10.2805/936107

Groothuis, F. A., Heringa, M. B., Nicol, B. et al. (2015). Dose metric considerations in in vitro assays to improve quantitative in vitro-in vivo dose extrapolations. Toxicology 332, 30-40. doi:10.1016/j.tox.2013.08.012

Hardy, A., Dorne, J. L. C. M., Aiassa, E. et al. (2015). Editorial: Increasing robustness, transparency and openness of scientific assessments. EFSA J 13, e13031. doi:10.2903/j.efsa.2015.e13031

Heinemeyer, G., Mosbach-Schulz, O., Kreienbrock, L. et al. (2015). Guidelines on uncertainty analysis in exposure assessments. Recommendation of the committee for exposure assessment and standardisation of the Federal Institute for Risk Assessment (BfR). Series: BfR-Wissenschaft 03/2015. Berlin, Germany: BfR. https://www.bfr.bund.de/cm/350/guidelines-on-uncertainty-analysis-in-exposure-assessments.pdf

Heseker, H., Oeppining, A. and Vohmann, C. (2003). Verzehrsstudie zur Ermittlung der Lebensmittelaufnahme von Säuglingen und Kleinkindern für die Abschätzung eines akuten Toxizitätsrisikos durch Rückstände von Pflanzenschutzmitteln (VELS). Paderborn, Germany: Universität Paderborn.

Higgins J. P. T., Thomas, J., Chandler, J. et al. (eds.) (2019). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). https://training.cochrane.org/handbook

ICCVAM – Interagency Coordinating Committee on the Validation of Alternative Methods (2018). A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States. doi:10.22427/NTP-ICCVAM-ROADMAP2018

IPCS – International Programme on Chemical Safety (2017). Guidance Document on Evaluating and Expressing Uncertainty in Hazard Assessment, second edition. IPCS Harmonization Project Document No. 11. Geneva, Switzerland: World Health Organisation. http://www.inchem.org/documents/harmproj/harmproj/harmproj11.pdf

Kerr, N. L. (1998). HARKing: Hypothesizing after the results are known. Pers Soc Psychol Rev 2, 196-217. doi:10.1207/s15327957pspr0203_4

Munafo, M. R., Nosek, B. A., Bishop, D. V. M. et al. (2017). A manifesto for reproducible science. Nat Hum Behav 1, 0021. doi:10.1038/s41562-016-0021

NRC – National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC, USA: The National Academies Press. doi:10.17226/11970

OHAT-NTP (2019). Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration. https://ntp.niehs.nih.gov/ntp/ohat/pubs/handbookmarch2019_508.pdf

SAPEA – Science Advice for Policy by European Academies (2019). Making Sense of Science for Policy under Conditions of Complexity and Uncertainty. Berlin, Germany: SAPEA. doi:10.26356/masos

Schendel, T., Jung, C., Lindtner, O. et al. (2018). Guidelines for uncertainty analysis: Application of the respective documents of EFSA and BfR for exposure assessments. EFSA Supporting Publication 15, 1472E. doi:10.2903/sp.efsa.2018.EN-1472

Shamseer, L., Moher, D., Clarke, M. et al. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ 349, g7647. doi:10.1136/bmj.g7647

Wetmore, B. A. (2015). Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment. Toxicology 332, 94-101. doi:10.1016/j.tox.2014.05.012

WHO – World Health Organisation (2012). WHO Handbook for Guideline Development. http://apps.who.int/iris/bitstream/10665/75146/1/9789241548441eng.pdf

Wilk-Zasadna, I., Bernasconi, C., Pelkonen, O. et al. (2015). Biotransformation in vitro: An essential consideration in the quantitative in vitro-to-in vivo extrapolation (QIVIVE) of toxicity data. Toxicology 332, 8-19. doi:10.1016/j.tox.2014.10.006

Woodruff, T. J. and Sutton, P. (2014). The navigation guide systematic review methodology: A rigorous and transparent method for translating environmental health science into better health outcomes. Environ Health Perspect 122, 1007-1014. doi:10.1289/ehp.1307175

Most read articles by the same author(s)