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Review
. 2025 Jan 8:6:1484895.
doi: 10.3389/ftox.2024.1484895. eCollection 2024.

Validation framework for in vivo digital measures

Szczepan W Baran  1 , Susan E Bolin  2 , Stefano Gaburro  3 , Marcel M van Gaalen  4 , Megan R LaFollette  5 , Chang-Ning Liu  6 , Sean Maguire  7 , Lucas P J J Noldus  8   9 , Natalie Bratcher-Petersen  10 , Brian R Berridge  10
Affiliations
Review

Validation framework for in vivo digital measures

Szczepan W Baran et al. Front Toxicol. .

Abstract

The adoption of in vivo digital measures in pharmaceutical research and development (R&D) presents an opportunity to enhance the efficiency and effectiveness of discovering and developing new therapeutics. For clinical measures, the Digital Medicine Society's (DiMe) V3 Framework is a comprehensive validation framework that encompasses verification, analytical validation, and clinical validation. This manuscript describes collaborative efforts to adapt this framework to ensure the reliability and relevance of digital measures for a preclinical context. Verification ensures that digital technologies accurately capture and store raw data. Analytical validation assesses the precision and accuracy of algorithms that transform raw data into meaningful biological metrics. Clinical validation confirms that these digital measures accurately reflect the biological or functional states in animal models relevant to their context of use. By widely adopting this structured approach, stakeholders-including researchers, technology developers, and regulators-can enhance the reliability and applicability of digital measures in preclinical research, ultimately supporting more robust and translatable drug discovery and development processes.

Keywords: 3Rs (replace reduce refine); digital biomarkers; drug discovery and development; preclinical; rodents; translation; validation; verification.

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Conflict of interest statement

Author SWB was employed by VeriSIM Life. Author SEB was employed by AbbVie Inc. Author SG was employed by Tecniplast SpA. Author MvG was employed by Evotec. Author ML was employed by The 3Rs Collaborative. Author C-NL was employed by Pfizer. Author SM was employed by GSK. Author LN was employed by Noldus Information Technology BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
In vivo V3 Framework. this framework builds confidence in the accuracy and relevance of digital biomarkers in preclinical biomedical research. The figure visually represents the 3 stages of verification, analytical validation, and clinical validation including the data supply chain framework. This figure is adapted and expanded from Berridge et al. (2023).
See this image and copyright information in PMC

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