Abstract
Commutability of quantitative standards allows patient results to be compared across molecular diagnostic methods and laboratories. This is critical to establishing quantitative thresholds for use in clinical decision-making. A matrix effect associated with the 1st cytomegalovirus (CMV) WHO international standard (IS) was identified using the Abbott RealTime CMV assay. A commutability study was performed to compare the CMV WHO IS and patient specimens diluted in plasma and whole blood. Patient specimens showed similar CMV DNA quantitation values regardless of the diluent or extraction procedure used. The CMV WHO IS, on the other hand, exhibited a matrix effect. The CMV concentration reported for the WHO IS diluted in plasma was within the 95% prediction interval established with patient samples. In contrast, the reported DNA concentration of the CMV WHO IS diluted in whole blood was reduced approximately 0.4 log copies/ml, and values fell outside the 95% prediction interval. Calibrating the assay by using the CMV WHO IS diluted in whole blood would introduce a bias for CMV whole-blood quantitation; samples would be reported as having higher measured concentrations, by approximately 0.4 log IU/ml. Based on the commutability study with patient samples, the RealTime CMV assay was standardized based on the CMV WHO IS diluted in plasma. A revision of the instructions for use of the CMV WHO IS should be considered to alert users of the potential impact from the diluent matrix. The identification of a matrix effect with the CMV WHO IS underscores the importance of assessing commutability of the IS in order to achieve consistent results across methods.
Highlights
Commutability of quantitative standards allows patient results to be compared across molecular diagnostic methods and laboratories
A goal of laboratory medicine is that results for patient samples be comparable independent of the medical laboratories or methods which produce the results
A goal of laboratory medicine is that results for patient samples be comparable, independently of the medical laboratories that produce the results
Summary
Commutability of quantitative standards allows patient results to be compared across molecular diagnostic methods and laboratories This is critical to establishing quantitative thresholds for use in clinical decision-making. Standardization with a commutable reference ensures that the results for clinical samples assayed by different measurement procedures have numerical values that are equivalent, irrespective of the clinical method used for the measurement. For methods measuring CMV viral load, which can be performed with plasma or whole-blood (WB) patient specimens, depending on the testing laboratory, proper standardization to the CMV WHO IS both within and across matrices is an important consideration. We report the identification of a matrix effect associated with the CMV WHO IS, a commutability study to further characterize the effect, and the mitigation adopted in standardizing the Abbott RealTime CMV assay to address the uncovered bias
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