Overcoming Clinical Validation Challenges for an In Vitro Diagnostic Biodosimetry Test

Area of Science:

• Medical Devices
• Radiation Biodosimetry
• Public Health Preparedness

Background:

• High-level radiation exposure during mass-casualty events necessitates effective triage tools.
• Current lack of US Food and Drug Administration (FDA)-authorized biodosimetry tests hinders preparedness.
• Regulatory challenges in biodosimetry test development are a significant barrier.

Purpose of the Study:

• To develop and validate a software tool, CellRADx, for mass-casualty radiation triage.
• To establish a novel validation approach compliant with FDA medical device regulations.
• To enable FDA authorization for biodosimetry tools for mass-casualty events.

Main Methods:

• CellRADx utilizes complete blood count (CBC) results, age, and time post-exposure to estimate radiation dose (>2 Gy).
• A novel validation approach combines real-world CBC data, an in silico cell depletion model, and dose distribution models.
• This method facilitates software device validation for clinical performance assessment.

Main Results:

• CellRADx demonstrated high sensitivity (92%) and specificity (78%) across the general population.
• Similar performance was observed in subpopulations with potentially confounding conditions.
• The validation approach proved effective for assessing clinical performance.

Conclusions:

• The developed validation method supports FDA authorization for biodosimetry devices.
• This advancement is crucial for implementing effective triage tools during mass-casualty radiation events.
• Improved preparedness can significantly save lives following radiological incidents.