Analytical performance validation of a coronary heart disease risk assessment multi-analyte proteomic test
Niamh Nolan1, Lilian Tee, Swathi Vijayakumar
1Aviir, Inc., Irvine, CA 92618, USA.
Insights
A new multi-analyte immunoassay for coronary heart disease risk assessment (CHDRA) shows reliable analytical performance in clinical laboratory validation. This assay is robust against pre-analytical variations, improving risk prediction for intermediate-risk individuals.
Area of Science:
- Cardiovascular diagnostics
- Biomarker assay development
- Clinical laboratory science
Background:
- Coronary heart disease (CHD) remains a significant public health concern, necessitating improved risk assessment strategies.
- Current CHD risk assessment methods may not adequately identify individuals at intermediate risk.
- A multi-analyte immunoassay-based algorithm, Coronary Heart Disease Risk Assessment (CHDRA), was developed to enhance risk stratification.
Purpose of the Study:
- To conduct a clinical laboratory validation of the analytical performance of the CHDRA biomarker assays.
- To assess the accuracy, sensitivity, specificity, and reproducibility of the CHDRA assays.
- To evaluate the impact of pre-analytical variables on assay performance and CHD risk scores.
Main Methods:
- Multiplexed immunoassay panels for seven CHDRA assays were evaluated using donor sera.
- Analytical performance was assessed for specificity, sensitivity, interfering substances, and reproducibility.
- The effects of pre-analytical specimen processing on assay results were investigated.
Main Results:
- CHDRA panel proteins demonstrated acceptable accuracy (80-120%) and low cross-reactivity (<1%).
- Assays showed minimal interference (<30%) from common substances and high reproducibility (<20% CV).
- Pre-analytical variables did not significantly affect CHDRA scores, with recoveries within 80-120%.
Conclusions:
- The CHDRA panel's analytical validation in a clinical laboratory meets established specifications.
- Assay reproducibility across various test scenarios indicates robustness against pre-analytical and analytical variations.
- The validated CHDRA assays are suitable for clinical use in improving CHD risk assessment.
Background:
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, clinically validated in a multicenter study, to improve CHDRA in intermediate risk individuals.
Objective:
Clinical laboratory validation of the CHDRA biomarker assays' analytical performance.
Methods:
Multiplexed immunoassay panels developed for the seven CHDRA assays were evaluated with donor sera in a clinical laboratory. Specificity, sensitivity, interfering substances and reproducibility of the CHDRA assays, along with the effects of pre-analytical specimen processing, were evaluated.
Results:
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.
Conclusions:
The CHDRA panel 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.
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