Harmonization status of procalcitonin measurements: what do comparison studies and EQA schemes tell us?

Abstract

Sepsis represents a global health priority because of its high mortality and morbidity. The key to improving prognosis remains an early diagnosis to initiate appropriate antibiotic treatment. Procalcitonin (PCT) is a recognized biomarker for the early indication of bacterial infections and a valuable tool to guide and individualize antibiotic treatment. To meet the increasing demand for PCT testing, numerous PCT immunoassays have been developed and commercialized, but results have been questioned. Many comparison studies have been carried out to evaluate analytical performance and comparability of results provided by the different commercially available immunoassays for PCT, but results are conflicting. External Quality Assessment Schemes (EQAS) for PCT constitute another way to evaluate results comparability. However, when making this comparison, it must be taken into account that the variety of EQA materials consist of different matrices, the commutability of which has not yet been investigated. The present study gathers results from all published comparison studies and results from 137 EQAS surveys to describe the current state-of-the-art harmonization of PCT results. Comparison studies globally highlight a significant variability of measurement results that nonetheless seem to have a moderate impact on medical decision-making. For their part, EQAS for PCT provides highly discrepant estimates of the interlaboratory CV. Due to differences in commutability of the EQA materials, the results from different peer groups could not be compared. To improve the informative value of the EQA data, the existing limitations such as non-harmonized conditions and suboptimal and/or unknown commutability of the EQA materials have to be overcome. The study highlights the need for commutable reference materials that could be used to properly evaluate result comparability and possibly standardize calibration, if necessary. Such an initiative would further improve the safe use of PCT in clinical routine.

Comprehensive Comparison of the Capacity of Functionalized Sepharose, Magnetic Core, and Polystyrene Nanoparticles to Immuno-Precipitate Procalcitonin from Human Material for the Subsequent Quantification by LC-MS/MS

“…So far, neither a reference material to standardize and trace PCT measurements, nor a higher-order reference method exist to quantify the absolute amount of PCT in human samples. The current heterogeneity of PCT measurements in clinical diagnostics is also reflected by the regular monitoring of national external quality assessment programs (EQAs) [ 23 , 24 ].…”

Immunoaffinity LC–MS/MS Quantification of the Sepsis Biomarker Procalcitonin Using Magnetic- and Polystyrene-Bead Immobilized Polyclonal Antibodies

“…19,20 Despite PCT's high relevance for sepsis diagnosis, evaluation of analytical performance and comparability of results of the different commercially available immunoassays for PCT have rendered conflicting results. 21 The need for harmonization of PCT quantification results has been highlighted, 22,23 yet neither reference material to standardize and trace PCT measurements nor an orthogonal method of higher order of reference exists. 21,24 Activities to harmonize and standardize PCT quantification are currently ongoing by the PCT working group of the International Federation of Clinical Chemistry (IFCC WG-PCT).…”

“…21 The need for harmonization of PCT quantification results has been highlighted, 22,23 yet neither reference material to standardize and trace PCT measurements nor an orthogonal method of higher order of reference exists. 21,24 Activities to harmonize and standardize PCT quantification are currently ongoing by the PCT working group of the International Federation of Clinical Chemistry (IFCC WG-PCT). 25 To our knowledge, only three studies using LC−MS/MS for quantification of PCT in human serum have been reported.…”

Candidate High-Resolution Mass Spectrometry-Based Reference Method for the Quantification of Procalcitonin in Human Serum Using a Characterized Recombinant Protein as a Primary Calibrator

“…However, the source of such variability remains unclear. 12 A proposed route to improve comparability and accuracy of the results is developing reference calibration materials, which have been value-assigned with a higher-order reference measurement procedure (RMP). 13 − 15 Such a higher-order reference measurement system is still missing for PCT.…”

“…Different studies underlined discrepancies of results provided by various commercially available PCT assays. − These discrepancies may impact clinical decisions at cut-offs, leading to disease misclassification and inappropriate antibiotic treatment decision. However, the source of such variability remains unclear . A proposed route to improve comparability and accuracy of the results is developing reference calibration materials, which have been value-assigned with a higher-order reference measurement procedure (RMP). − Such a higher-order reference measurement system is still missing for PCT.…”