Validating animal models for preclinical research: a scientific and ethical discussion

Abstract

The use of animals to model humans in biomedical research relies on the notion that basic processes are sufficiently similar across species to allow extrapolation. Animal model validity is discussed in terms of the similarity between the model and human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. In the present paper we discuss the potential and limitations of validating preclinical animal models for proof-of-concept studies using an approach similar to that applied to alternative non-animal methods in toxicology and safety testing. A major challenge in devising a validation system for animal models is the lack of a clear gold standard to compare results with. While a complete adoption of the validation approach for alternative methods is probably inappropriate for research animal models, key feature such as making data available for external validation and defining a strategy to run experiments in a way that permits meaningful retrospective analysis remain relevant.