TY - JOUR
T1 - Optimizing hepcidin measurement with a proficiency test framework and standardization improvement
AU - Aune, Ellis T.
AU - Diepeveen, Laura E.
AU - Laarakkers, Coby M.
AU - Klaver, Siem
AU - Armitage, Andrew E.
AU - Bansal, Sukhvinder
AU - Chen, Michael
AU - Fillet, Marianne
AU - Han, Huiling
AU - Herkert, Matthias
AU - Itkonen, Outi
AU - Van De Kerkhof, Daan
AU - Krygier, Aleksandra
AU - Lefebvre, Thibaud
AU - Neyer, Peter
AU - Rieke, Markus
AU - Tomosugi, Naohisa
AU - Weykamp, Cas W.
AU - Swinkels, Dorine W.
PY - 2020
Y1 - 2020
N2 - Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization. We developed a pilot PT together with the Dutch EQA organization Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) that included 16 international hepcidin MPs. The design included 12 human serum samples that allowed us to evaluate accuracy, linearity, precision and standardization potential. We manufactured, value-assigned, and validated a high-level calibrator in a similar manner to the existing low- and middle-level sRM. The pilot PT confirmed logistical feasibility of an annual scheme. Most MPs demonstrated linearity (R2>0.99) and precision (duplicate CV>12.2%), although the need for EQA was shown by large variability in accuracy. The high-level calibrator proved effective, reducing the inter-assay CV from 42.0% (unstandardized) to 14.0%, compared to 17.6% with the two-leveled set. The calibrator passed international homogeneity criteria and was assigned a value of 9.07 ± 0.24 nmol/L. We established a framework for future PT to enable laboratory accreditation, which is essential to ensure quality of hepcidin measurement and its use in patient care. Additionally, we showed optimized standardization is possible by extending the current sRM with a third high calibrator, although international implementation of the sRM is a prerequisite for its success.
AB - Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization. We developed a pilot PT together with the Dutch EQA organization Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) that included 16 international hepcidin MPs. The design included 12 human serum samples that allowed us to evaluate accuracy, linearity, precision and standardization potential. We manufactured, value-assigned, and validated a high-level calibrator in a similar manner to the existing low- and middle-level sRM. The pilot PT confirmed logistical feasibility of an annual scheme. Most MPs demonstrated linearity (R2>0.99) and precision (duplicate CV>12.2%), although the need for EQA was shown by large variability in accuracy. The high-level calibrator proved effective, reducing the inter-assay CV from 42.0% (unstandardized) to 14.0%, compared to 17.6% with the two-leveled set. The calibrator passed international homogeneity criteria and was assigned a value of 9.07 ± 0.24 nmol/L. We established a framework for future PT to enable laboratory accreditation, which is essential to ensure quality of hepcidin measurement and its use in patient care. Additionally, we showed optimized standardization is possible by extending the current sRM with a third high calibrator, although international implementation of the sRM is a prerequisite for its success.
KW - external quality assurance
KW - hepcidin
KW - iron metabolism
KW - proficiency testing
KW - secondary reference material
KW - standardization
UR - http://www.scopus.com/inward/record.url?scp=85092785865&partnerID=8YFLogxK
U2 - 10.1515/cclm-2020-0928
DO - 10.1515/cclm-2020-0928
M3 - Article
C2 - 33001847
AN - SCOPUS:85092785865
SN - 1434-6621
JO - CLINICAL CHEMISTRY AND LABORATORY MEDICINE
JF - CLINICAL CHEMISTRY AND LABORATORY MEDICINE
ER -