Trueness evaluation and verification of inter-assay agreement of serum folate measuring systems

Federica Braga 1 , 2 , Erika Frusciante 3 , Simona Ferraro 3 , and Mauro Panteghini 3
  • 1 Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Università di Milano, Milan, Italy
  • 2 UOC Patologia Clinica, ASST Fatebenfratelli Sacco, via GB Grassi 74, 20157 Milano, Italy
  • 3 Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Milano, Italy
Federica Braga
  • Corresponding author
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Università di Milano, Milan, Italy
  • UOC Patologia Clinica, ASST Fatebenfratelli Sacco, via GB Grassi 74, 20157 Milano, Italy
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, Erika Frusciante
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Milano, Italy
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, Simona Ferraro
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Milano, Italy
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and Mauro Panteghini
  • Research Centre for Metrological Traceability in Laboratory Medicine (CIRME), Milano, Italy
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Abstract

Background

Definitive data to establish if the use of the WHO International Standard (IS) 03/178 as a common calibrator of commercial measuring systems (MSs) has improved the harmonization of serum total folate (tFOL) measurements to a clinically suitable level are lacking. Here, we report the results of an intercomparison study aimed to verify if the current inter-assay variability is acceptable for clinical application of tFOL testing.

Methods

After confirming their commutability, the IS 03/178 and National Institute for Standards and Technology SRM 3949 L1 were used for evaluating the correctness of traceability implementation by manufacturers and the MSs trueness, respectively. The inter-assay agreement was verified using 20 patient pools. The measurement uncertainty (U) of tFOL measurements on clinical samples was also estimated. An outcome-based model for defining desirable performance specifications for bias and imprecision for serum tFOL measurements was applied.

Results

The majority of evaluated MSs overestimated the WHO IS value of +5% or more with the risk to produce an unacceptably high number of false-negative results in clinical practice. The mean inter-assay CV on all pools and on those with tFOL values >3.0 μg/L (n = 15) was 12.5% and 7.1%, respectively. In neither case the goal of 3.0% was fulfilled. The residual bias resulted in an excessive U of tFOL measurement on clinical samples.

Conclusions

The implementation of traceability of tFOL MSs to the WHO IS 03/178 is currently inadequate, resulting in an inter-assay variability that does not permit the use of a common threshold for detecting folate deficiency.

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