Preparatory work on how to report, use and interpret historical control data in (eco)toxicity studies
Disclaimer: The present document has been produced and adopted by the bodies identified above as author(s). In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the author(s) in the context of the grant agreement GP/EFSA/ENCO/2020/02 between the European Food Safety Authority and the author(s). The present document is published complying with the transparency principle to which the Authority is subject. It cannot be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.
Historical control data (HCD) are information about control animals of toxicity studies and clinically healthy animals that have not received any treatment. The term describes the spontaneous incidence of a finding or the background variation in continuous parameters, observed in the same species and the same type of toxicity study as the study under evaluation. Although the principles and general conditions for submission of HCD across different regulatory frameworks may sound very similar, understanding of the purpose and interpretation of these data is very heterogeneous, and can end up in differences in the interpretation of study results and final risk assessment for one and the same compound. EFSA has recognised the need for closer understanding on the criteria regarding the use, reporting and interpretation of historical control data in the evaluation of toxicity studies submitted under the substance classes primarily under the EFSA remit. Within the framework of this project and in order to better explore the community perception on HCD, three activities have been considered critical. Under the first activity, a literature search was conducted and retrieved relevant publications were summarised and allocated to thematic clusters. Most of the relevant papers were related to long‐term/carcinogenicity studies, developmental toxicity, and statistics. In addition, public databases containing HCD (Charles River, MARTA, NTP, RITA) and relevant OECD documents (Testing Guidelines, Guidance documents and Guidance Notes) were screened for further information concerning HCD. Topics identified from the literature have been used on the one hand to draft specific questions for a worldwide survey (second activity), in order to capture the experience of toxicologists and risk assessors on the use of HCD. On the other hand, the identified topics were aimed to explore the relevant points for discussion in the workshop organised with relevant stakeholders (third activity). The feedback captured by the survey showed that there is very high interest in the topic and strong need for more harmonisation on requirements for use of HCD has been expressed. This has been confirmed in the workshop, held as virtual event from May 3 to 5, 2022, where the main conclusions were that clear set of criteria need to be fulfilled before HCD are taken into account for interpretation of results, that high level of granularity in HCD is necessary when these are compiled and submitted and that close exchange between different domains (toxicology, statistics) is crucial when HCD are included in the interpretation of study results. Outcome of the project activities will be considered by EFSA PPR Panel in drafting a Scientific Opinion on use, reporting and interpretation of HCD.