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External validity for in vitro toxicity studies: an important but challenging concept
Paul Whaley1, Gunn E Vist2, Heather M Ames2
1Norwegian Scientific Committee for Food and Environment, Norwegian Institute of Public Health, Oslo, Norway; Lancaster Environment Centre, Lancaster University, Lancaster, UK.
Regulatory Toxicology and Pharmacology : RTP
|July 20, 2026
Summary
This study defines external validity for in vitro studies, separating it into applicability and generalisability. The proposed framework supports the INVITES-EX tool for evidence synthesis in systematic reviews and chemical assessments.
Area of Science:
- Toxicology
- Biomedical Research
- Evidence Synthesis
Background:
- External validity is crucial for interpreting in vitro study findings.
- Current methods for assessing external validity in in vitro studies are limited.
- A structured approach is needed to evaluate the generalizability of in vitro data.
Purpose of the Study:
- To operationalize the concept of external validity for in vitro studies.
- To define applicability and generalisability as components of external validity.
- To support the development of the INVITES-EX tool for evidence synthesis.
Main Methods:
- Conceptual analysis of external validity in the context of in vitro studies.
- Definition of applicability and generalisability for comparative effect size studies.
- Identification of stages in evidence synthesis where external validity assessment is relevant.
Main Results:
- External validity is conceptualized as comprising applicability and generalisability.
- External validity assessment is relevant during study screening and evidence integration.
- The INVITES-EX tool is proposed for assessing study applicability during screening.
Conclusions:
- A clear conceptualization of external validity enhances the reliability of in vitro study interpretations.
- The INVITES-EX tool can improve the efficiency and accuracy of systematic reviews and chemical assessments.
- Focusing INVITES-EX on applicability assessment during screening provides practical support for evidence synthesis.
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