Role of a high throughput biodosimetry test in treatment prioritization after a nuclear incident

Purpose: We introduce and evaluate a high throughput biodosimetry test system (REDI-Dx) suitable for testing of thousands of potential radiation victims following a mass scale nuclear event caused by detonation of a nuclear device or a nuclear accident, as part of an overall strategy for effective medical management of the crisis. Materials and methods: The performance of a high throughput biodosimetry test was evaluated by collecting samples of both non-irradiated presumed healthy donors as well as irradiated subjects collected as part of either cancer treatment regimens or banked from previous studies. The test measures the gene expression of a set of radiation responsive genes based on the DxDirect® genomic platform. The potential diagnostic accuracy of REDI-Dx was evaluated as a predictor of actual dose of radiation. While the REDI-Dx test has been calibrated to provide a quantitative measure of actual absorbed dose, we compared the performance of the REDI-Dx test (sensitivity and specificity) as a qualitative result at the most commonly applied thresholds 2.0 Gy and 6.0 Gy. Results: The test demonstrated high specificity and lack of effect of medical conditions. Using receiver operating characteristic (ROC) curve analysis, REDI-Dx was shown to be a good predictor of actual dose for determining treatment category based on either 2.0 or 6.0 Gy, with a 98.5% sensitivity and 90% specificity for 2.0 Gy, and 92% sensitivity and 84% specificity for 6.0 Gy. Results were reproducible between clinical laboratories with an SD of 0.2 Gy for samples ≤2.0 Gy and a CV of 10.3% for samples from 2.0 to 10.0 Gy. Conclusions: Use of a biodosimetry test, like REDI-Dx test system would provide valuable information that would improve the ability to assign patients to the correct treatment category when combined with currently available biodosimetry tools, as compared to the use of existing tools alone. The REDI-Dx biodosimetry test system is for investigational use only in the U.S.A. The performance characteristics of this product have not been established.