Use and reporting of historical control data for regulatory studies

Abstract

The provision of historical control data (HCD) is a data requirement for pesticide active substances established by European legislation. HCD are data from studies conducted under the same or similar conditions as the toxicity study under assessment (index study). The collation, use and interpretation of HCD is currently not harmonised. The Panel on Plant Protection Products and their Residues developed this Scientific Opinion to elucidate the requirements for the use of HCD for interpretation of studies used for regulatory purposes, clarify how HCD should be compiled as part of the regulatory dossier and assist the interpretation of HCD in the context of the evaluation of regulatory studies. This Opinion proposes a stepwise, quantitative approach using a decision scheme which includes seven distinct steps grouped in three overall clusters of activity: (1) planning, (2) evaluation of the HCD and (3) use of HCD. In the planning phase, a protocol for collating the relevant HCD as well as their expected evaluation and analysis should be developed. Cluster 2 deals with the data requirements for HCD, including their use for quantitative statistical analysis. A final set of HCD is selected and the variability within and between studies is modelled. Statistical comparison of the HCD with the concurrent control data set and integration of the HCD into the analysis of the index study is carried out in cluster 3, including an influence or sensitivity analysis. To demonstrate the application of the decision scheme to different data types, three case studies have been prepared. The Opinion also offers templates to improve harmonisation for data submission and discusses confounding/covariate aspects related to HCD interpretation. Practical application of the Opinion requires a close exchange of toxicological and statistical input in the analysis of data and derivation of conclusions. It is recommended to consider this interaction between the disciplines every time submission and interpretation of HCD is planned.