Validation of the Cepheid Xpert Flu A Real Time RT-PCR detection panel for Emergency Use Authorization

Abstract

Background In April 2009, the United States Secretary of the Department of Health and Human Services declared a public health emergency concerning the 2009 influenza H1N1 outbreak. This declaration allowed the FDA to issue Emergency Use Authorization (EUA) of approved in vitro diagnostics to detect the 2009 influenza H1N1 in clinical specimens. Objectives This report outlines the validation testing of the Cepheid Xpert Flu A Panel for the qualitative detection of 2009 H1N1 viral RNA. Study design This study was a multi-site, dual-method clinical evaluation comparing the results of testing between the Xpert Panel assay to the FDA-cleared Luminex Molecular Diagnostics xTAG™ Respiratory Viral Panel (Luminex RVP) assay and the EUA-granted Focus Diagnostics Influenza A/H1N1 (2009) Real Time RT-PCR (Focus H1N1) assay. Results When compared to Luminex RVP ( n = 300) for influenza A detection, the Xpert Panel had a sensitivity of 91.2% (95% CI: 85.1–95.4), specificity of 99.4% (95% CI: 96.7–100), positive predictive value (PPV) of 99.2% (95% CI: 95.6–100), and a negative predictive value (NPV) of 93.1% (95% CI: 88.3–96.4). When compared to the Focus H1N1 ( n = 258) for detection of H1N1, the Xpert Panel had a sensitivity of 92.1% (95% CI: 82.4–97.4), specificity of 100% (95% CI: 98.5–100), PPV of 100% (95% CI: 95.0–100), and a NPV of 97.5% (95% CI: 94.3–99.2). Conclusions The results show the Cepheid Xpert Flu A Panel to be comparable to both the Luminex RVP and the Focus H1N1 assays. The Cepheid Xpert Panel was granted an EUA on 24 Dec 2009.