Quantitative Assessment of Commutability for Clinical Viral Load Testing Using a Digital PCR-Based Reference Standard

Area of Science:

• Clinical Chemistry
• Molecular Diagnostics
• Biostatistics

Background:

• Commutability of reference materials is crucial for accurate quantitative diagnostic assays.
• Current methods like prediction intervals and correspondence analysis for assessing commutability can yield ambiguous results.
• Advancements in quantitative standards, including WHO international standards, necessitate improved commutability evaluation.

Purpose of the Study:

• To introduce and evaluate a novel
• deviation-from-ideal
• (DFI) approach for assessing the commutability of reference materials.
• To compare the DFI approach with existing methods using Epstein-Barr virus (EBV) load testing.
• To discuss the practical application, advantages, and limitations of the DFI method.

Main Methods:

• Development of the "deviation-from-ideal" (DFI) method for commutability assessment.
• Application of the DFI approach to evaluate Epstein-Barr virus (EBV) load testing across four quantitative PCR assays.
• Utilizing digital PCR as the reference assay for comparison.

Main Results:

• The DFI approach was successfully applied to assess commutability in EBV load testing.
• The DFI method provides a potentially less ambiguous evaluation of reference material commutability compared to existing techniques.
• Digital PCR served as a reliable reference for evaluating quantitative PCR assay performance.

Conclusions:

• The "deviation-from-ideal" (DFI) approach offers a valuable new tool for evaluating reference material commutability in molecular diagnostics.
• This method can enhance the reliability and accuracy of quantitative PCR assays, such as those for EBV.
• Further research should explore the DFI approach's application across diverse diagnostic assays and experimental designs.