Overcoming Clinical Validation Challenges for an In Vitro Diagnostic Biodosimetry Test.

INTRODUCTION: In the aftermath of a nuclear detonation or other mass-casualty radiological event, thousands to millions of people may be exposed to high levels of radiation. Effective triage tools are needed to identify those with potentially life-threatening exposure requiring emergency medical care. To ensure these tools will be available to support a mass-casualty radiation event, US Food and Drug Administration (FDA) authorization is required. However, currently, no FDA-authorized biodosimetry tests are available to support a mass-casualty radiological event, due largely to the significant challenges in developing regulatory strategies for biodosimetry tests. MATERIALS AND METHODS: We have developed a tool, called the CellRADx Software Application, to help address this mass-casualty triage need. CellRADx utilizes complete blood count (CBC) results from a single test, along with other inputs such as age and time post-exposure, to determine if an individual has absorbed more than 2 Gy of ionizing radiation. As part of the development of CellRADx, we have created a novel approach to facilitate the complete validation of the software device in compliance with FDA's medical device regulations. This novel approach employs a combination of real-world CBC data, an in silico radiation-induced cell depletion model, and nuclear event dose distribution models to validate clinical performance. RESULTS: Performance of CellRADx across the general population has been demonstrated with high sensitivity (92%) and high specificity (78%). Additional subpopulations with potentially confounding conditions were also tested using this approach and have demonstrated similar performance results. CONCLUSION: The ability to validate a biodosimetry device using a method that can support FDA authorization is a key enabling development that will facilitate implementation of tools that can improve preparedness for a mass-casualty nuclear event and help save many lives.