Analytical Performance Validation of the PULS Cardiac Test
Niamh Nolan, Lilian Tee, Swathi Vijayakumar, Ivana Burazor, Evangelos Hytopoulos, William H Biggs, Michael Beggs, Cynthia French, Douglas S Harrington
Coronary heart disease (CHD) remains prevalent despite efforts to improve CHD risk assessment. The authors developed a multi-analyte immunoassay-based CHD risk assessment (CHDRA) algorithm, the PULS Cardiac Test, clinically validated in a multi-center study, to improve risk assessment in intermediate risk individuals.
Clinical laboratory validation of the CHDRA biomarker assays’ analytical performance.
Analytical measurements of the CHDRA panel proteins (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3 and sFas) exhibited acceptable accuracy (80 – 120%), cross-reactivity (< 1%), interference (< 30% at high concentrations of bilirubin, lipids, hemoglobin and HAMA), sensitivity and reproducibility (< 20% CV across multiple runs, operators and instruments). Recoveries from donor sera subjected to typical clinical laboratory pre-analytical conditions were within 80 – 120%. The pre-analytical variables did not substantively impact the CHDRA scores.
The PULS Cardiac Test (CHDRA) analytical validation in a clinical laboratory meets or exceeds the specifications established during the clinical utility studies. Risk score reproducibility across multiple test scenarios suggests the assays are not susceptible to clinical laboratory pre-analytical and analytical variation.
The authors have demonstrated acceptable analytical performance of the PULS Cardiac Test panel of assays in a commercial clinical laboratory thus validating its analytical capability for assessing a person’s risk of experiencing a cardiac event in the next 5 years. Successfully calculating the scores for 58 out of 60 first attempts at risk determinations demonstrates a 97% level of assay completion and efficiency necessary for routine use in the clinical lab.