External validity for in vitro toxicity studies: an important but challenging concept.

In this paper, we present an operational conceptualisation of external validity for in vitro studies, to support the development of the forthcoming INVITES-EX tool. We define external validity as consisting of a concept of applicability and a concept of generalisability, and explain how it applies to in vitro comparative effect size studies. We argue that external validity assessment is relevant at two stages of evidence synthesis, during study screening and during evidence integration. Because evidence integration is complex and likely best supported by guidance, we conclude that INVITES-EX should be targeted at assessing the applicability of individual studies and used when screening studies for inclusion in a systematic review or chemical assessment.