Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies?

Abstract

The availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately evident, the potential challenges need to be carefully considered to avoid any effect which could lower the sensitivity of an animal study to detect adverse events, safety thresholds, target organs, or biomarkers. In our brief communication, we summarize the current discussion regarding VCGs and propose a path forward how the replacement of concurrent control with VCGs resulting from historical data could be systematically assessed and to come to conclusions regarding the scientific value of the concept.

The road to virtual control groups and the importance of proper body-weight selection

“…The ongoing maturation of the concept of VCGs (Golden et al, 2024;Steger-Hartmann and Clark, 2023) involves the evaluation of the VCG performance on legacy studies using them as a benchmark: a virtual control group can be considered "well performing" if the legacy study results can be reproduced after the CCG was replaced by VCGs (Gurjanov et al, 2023).…”