Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model

Clinical Chemistry and Laboratory Medicine (CCLM)

Panteghini

2021

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Objectives Definition and fullfillment of analytical performance specifications (APS) for measurement uncertainty (MU) allow to make laboratory determinations clinically usable. The 2014 Milan Strategic Conference have proposed models to objectively derive APS based on: (a) the effect of analytical performance on clinical outcome; (b) biological variation components; and (3) the state of the art of the measurement, defined as the highest level of analytical performance technically achievable. Using these models appropriately, we present here a proposal for defining APS for standard MU for some common biochemical measurands. Methods We allocated a group of 13 measurands selected among the most commonly laboratory requested tests to each of the three Milan models on the basis of their biological and clinical characteristics. Both minimum and desirable levels of quality of APS for standard MU of clinical samples were defined by using information obtained from available studies. Results Blood total hemoglobin, plasma glucose, blood glycated hemoglobin, and serum 25-hydroxyvitamin D3 were allocated to the model 1 and the corresponding desirable APS were 2.80, 2.00, 3.00, and 10.0%, respectively. Plasma potassium, sodium, chloride, total calcium, alanine aminotransferase, creatinine, urea, and total bilirubin were allocated to the model 2 and the corresponding desirable APS were 1.96, 0.27, 0.49, 0.91, 4.65, 2.20, 7.05, and 10.5%, respectively. For C-reactive protein, allocated to the model 3, a desirable MU of 3.76% was defined. Conclusions APS for MU of clinical samples derived in this study are essential to objectively evaluate the reliability of results provided by medical laboratories.

Section: Defining Performance Specifications For Measurement Uncertaintymentioning

confidence: 99%

Performance specifications for measurement uncertainty of common biochemical measurands according to Milan models

Clinical Chemistry and Laboratory Medicine (CCLM)

Panteghini

2021

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“…Similarly, for serum total folate, Beckman Coulter in a technical bulletin released in 2011 informed customers that the internal release specification for their calibrators was ±10% from the target value of WHO International Standard 03/178 [25]. Once again, this does not fit with APS for standard MU of folate on clinical samples, which, for assuring a clinically acceptable misclassification rate of individuals with suspected vitamin deficiency, should remain within ±2.5% [29]. Manufacturers should therefore start to conform their internal protocols of trueness transfer from certified reference materials to commercial calibrators to the clinical value of tests and their APS defined according to the aforementioned models.…”

Section: Verification Of Quality Of Ivd Medical Devicesmentioning

confidence: 99%

The utility of measurement uncertainty in medical laboratories

Clinical Chemistry and Laboratory Medicine (CCLM)

Panteghini

2020

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The definition and enforcement of reference measurement systems, based on the implementation of metrological traceability of patient results to higher-order (reference) methods and/or materials, together with a clinically acceptable level of measurement uncertainty (MU), are fundamental requirements to produce accurate and equivalent laboratory results. The MU associated with each step of the traceability chain should be governed to obtain a final combined MU on clinical samples fulfilling the requested performance specifications. MU is useful for a number of reasons: (a) for giving objective information about the quality of individual laboratory performance; (b) for serving as a management tool for the medical laboratory and in vitro diagnostics (IVD) manufacturers, forcing them to investigate and eventually fix the identified problems; (c) for helping those manufacturers that produce superior products and measuring systems to demonstrate the superiority of those products; (d) for identifying analytes that need analytical improvement for their clinical use and ask IVD manufacturers to work for improving the quality of assay performance and (e) for abandoning assays with demonstrated insufficient quality. Accordingly, the MU should not be considered a parameter to be calculated by medical laboratories just to fulfill accreditation standards, but it must become a key quality indicator to describe both the performance of an IVD measuring system and the laboratory itself.

“…In particular, for serum tFOL the outcome-based model for deriving APS measurements should be used because: (a) as humans are unable to synthesize folates, serum folate is not subjected to any homeostatic control, and (b) changes that hold clinical meaning are only one-sided, i.e. vitamin deficiency is diagnosed when values are lower than established thresholds [18]. We applied this model for defining desirable APS for bias and imprecision for serum tFOL measurements yielding a tolerable misclassification rate, defined as 1.7% false-negative results in subjects expected to have overt (tFOL < 2.0 μg/L) or possible (tFOL < 4.0 μg/L) vitamin deficiency.…”

Section: Aps For Tfol Measurementsmentioning

confidence: 99%

“…Accordingly, at tFOL concentration around 2.0 μg/L, an imprecision <12% (as CV) and a bias <11% are allowable. At a tFOL concentration of 4.0 μg/L, APS become more stringent, with the desirable bias being <3.0% when the assay CV is <3.0%, and <2.0% when the CV is <5.0% [18].…”

Section: Aps For Tfol Measurementsmentioning

confidence: 99%

“…Finally, we derived the desirable U goal of serum tFOL measurements at the clinical sample level (mean tFOL concentration of 4.0 μg/L) by consulting the figure 1 of ref. 18 and identifying on the 1.7% misclassification isocontour line the CV corresponding to the allowable bias of 3.0%, multiplied by a coverage factor of 2, which is 5.0%.…”

Section: Aps For Tfol Measurementsmentioning

confidence: 99%

See 1 more Smart Citation

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

Clinical Chemistry and Laboratory Medicine (CCLM)

Frusciante²,

Ferraro³

et al. 2020

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BackgroundDefinitive 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.MethodsAfter 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.ResultsThe 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.ConclusionsThe 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.