Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry-recommended reference measurement procedure and reference materials for glycated albumin determination

Thrombin, the proteolytic enzyme that catalyzes the transformation of soluble fibrinogen to the polymerized fibrin clot, participates in multiple reactions in blood coagulation in addition to the clotting reaction. Although reference materials have existed for many years, structural characterization and measurement of biological activity have never been sufficient to permit claims of clear metrological traceability for the thrombin preparations. Our current state-of-the-art methods for protein characterization and determination of the catalytic properties of thrombin now make it practical to develop and characterize a metrologically acceptable reference material and reference measurement procedure for thrombin. Specifically, α-thrombin, the biologically produced protease formed during prothrombin activation, is readily available and has been extensively characterized. Dependences of thrombin proteolytic and peptide hydrolytic activities on a variety of substrates, pH, specific ions, and temperature are established, although variability remains for the kinetic parameters that describe thrombin enzymatic action. The roles of specific areas on the surface of the thrombin molecule (exosites) in substrate recognition and catalytic efficiency are described and characterized. It is opportune to develop reference materials of high metrological order and technical feasibility. In this article, we review the properties of α-thrombin important for its preparation and suggest an approach suitable for producing a reference material and a reference measurement procedure that is sensitive to thrombin’s catalytic competency on a variety of substrates.

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Statistical Methods for Monitoring the Relationship between the IFCC Reference Measurement Procedure for Hemoglobin A1c and the Designated Comparison Methods in the United States, Japan, and Sweden

Clinical Chemistry ◽

10.1373/clinchem.2008.103556 ◽

2008 ◽

Vol 54 (8) ◽

pp. 1379-1385 ◽

Cited By ~ 56

Author(s):

Andrea Geistanger ◽

Sabine Arends ◽

Christoph Berding ◽

Tadao Hoshino ◽

Jan-Olof Jeppsson ◽

...

Keyword(s):

Statistical Methods ◽

Consensus Statement ◽

Clinical Chemistry ◽

International Diabetes Federation ◽

The United States ◽

Measurement Procedure ◽

Reference Measurement ◽

Reference Measurement Procedure ◽

Comparison Methods ◽

The Relationship

Abstract Background: The American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)/International Diabetes Federation (IDF)/IFCC Consensus Statement on the worldwide standardization of HbA1c states that “… [HbA1c] results are to be reported world-wide in IFCC units … and derived NGSP units … , using the IFCC-NGSP master equation.” Methods: We describe statistical methods to evaluate and monitor the relationships as expressed in master equations (MEs) between the IFCC Reference Measurement procedure (IFCC-RM) and designated comparison methods (DCMs) [US National Glycohemoglobin Standardization Program (NGSP), Japanese Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC), and Mono-S in Sweden]. We applied these statistics, including uncertainty calculations, to 12 studies in which networks of reference laboratories participated, operating the IFCC-RM and DCMs. Results: For NGSP and Mono-S, slope, intercept, and derived percentage HbA1c at the therapeutic target show compliance with the respective MEs in all 12 studies. For JDS/JSCC, a slight deviation is seen in slope and derived percentage HbA1c in 2 of the 12 studies. Using the MEs, the uncertainty in an assigned value increases from 0.42 mmol/mol HbA1c (IFCC-RM) to 0.47 (NGSP), 0.49 (JDS/JSCC), and 0.51 (Mono-S). Conclusions: We describe sound statistical methods for the investigation of relations between networks of reference laboratories. Application of these statistical methods to the relationship between the IFCC-RM and DCMs in the US, Japan, and Sweden shows that they are suitable for the purpose, and the results support the applicability of the ADA/EASD/IDF/IFCC Consensus Statement on HbA1c measurement.

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State of the Art in Trueness and Interlaboratory Harmonization for 10 Analytes in General Clinical Chemistry

Archives of Pathology & Laboratory Medicine ◽

10.5858/2008-132-838-sotait ◽

2008 ◽

Vol 132 (5) ◽

pp. 838-846

Author(s):

W. Greg Miller ◽

Gary L. Myers ◽

Edward R. Ashwood ◽

Anthony A. Killeen ◽

Edward Wang ◽

...

Keyword(s):

Uric Acid ◽

State Of The Art ◽

Clinical Chemistry ◽

Peer Groups ◽

Measurement Procedure ◽

Reference Systems ◽

Reference Measurement ◽

Clinical Laboratories ◽

Routine Measurement ◽

Fresh Frozen

Abstract Context.—Harmonization and standardization of results among different clinical laboratories is necessary for clinical practice guidelines to be established. Objective.—To evaluate the state of the art in measuring 10 routine chemistry analytes. Design.—A specimen prepared as off-the-clot pooled sera and 4 conventionally prepared specimens were sent to participants in the College of American Pathologists Chemistry Survey. Analyte concentrations were assigned by reference measurement procedures. Participants.—Approximately 6000 clinical laboratories. Results.—For glucose, iron, potassium, and uric acid, more than 87.5% of peer groups meet the desirable bias goals based on biologic variability criteria. The remaining 6 analytes had less than 52% of peer groups that met the desirable bias criteria. Conclusions.—Routine measurement procedures for some analytes had acceptable traceability to reference systems. Conventionally prepared proficiency testing specimens were not adequately commutable with a fresh frozen specimen to be used to evaluate trueness of methods compared with a reference measurement procedure.

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Proposed Serum Cholesterol Reference Measurement Procedure by Gas Chromatography–Isotope Dilution Mass Spectrometry

Clinical Chemistry ◽

10.1373/clinchem.2010.158766 ◽

2011 ◽

Vol 57 (4) ◽

pp. 614-622 ◽

Cited By ~ 30

Author(s):

Selvin H Edwards ◽

Mary M Kimberly ◽

Susan D Pyatt ◽

Shelton L Stribling ◽

Kara D Dobbin ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Serum Cholesterol ◽

Isotope Dilution ◽

Isotope Dilution Mass Spectrometry ◽

Measurement Procedure ◽

Standard Reference Materials ◽

Reference Measurement ◽

Reference Measurement Procedure ◽

The Mean

BACKGROUND Our purpose was to establish a mass spectrometry reference measurement procedure (RMP) for cholesterol to use in the CDC's standardization programs. We explored a gas chromatography–isotope dilution mass spectrometry (GC-IDMS) procedure using a multilevel standard calibration curve to quantify samples with varying cholesterol concentrations. METHODS We calibrated the mass spectrometry instrument by isotope dilution with a pure primary standard reference material and an isotopically enriched cholesterol analog as the internal standard (IS). We diluted the serum samples with Tris-HCl buffer (pH 7.4, 0.05 mol/L, 0.25% Triton X-100) before analysis. We used 17 serum pools, 10 native samples, and 2 standard reference materials (SRMs). We compared the GC-IDMS measurements with the CDC's modified Abell–Levy–Brodie–Kendall (AK) RMP measurements and assessed method accuracy by analyzing 2 SRMs. We evaluated the procedure for lack of interference by analyzing serum spiked with a mixture of 7 sterols. RESULTS The mean percent bias between the AK and the GC-IDMS RMP was 1.6% for all samples examined. The mean percent bias from NIST's RMP was 0.5% for the SRMs. The total %CVs for SRM 1951b levels I and II were 0.61 and 0.73%, respectively. We found that none of the sterols investigated interfered with the cholesterol measurement. CONCLUSIONS The low imprecision, linear response, lack of interferences, and acceptable bias vs the NIST primary RMP qualifies this procedure as an RMP for determining serum cholesterol. The CDC will adopt and implement this GC-IDMS procedure for cholesterol standardization.

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Verification of Low-Density Lipoprotein Cholesterol Levels Measured by Anion-Exchange High-Performance Liquid Chromatography in Comparison with Beta Quantification Reference Measurement Procedure

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa144 ◽

2020 ◽

Author(s):

Daisuke Manita ◽

Hiroshi Yoshida ◽

Isao Koyama ◽

Masakazu Nakamura ◽

Yuji Hirowatari

Keyword(s):

Anion Exchange ◽

Clinical Laboratory ◽

Measurement Procedure ◽

Calculation Methods ◽

Serum Samples ◽

Cvd Risk ◽

Blood Samples ◽

Reference Measurement ◽

Reference Measurement Procedure ◽

Homogeneous Assays

Abstract Background A new lipoprotein testing method based on anion-exchange HPLC (AEX-HPLC) was recently established. We verified the accuracy of LDL-C levels, a primary therapeutic target for the prevention of cardiovascular disease (CVD), measured by AEX-HPLC comparing with LDL-C levels measured by beta quantification-reference measurement procedure (BQ-RMP), homogenous assays, and calculation methods. Methods We compared LDL-C levels measured by AEX-HPLC (adLDL-Ch: LDL-Ch and IDL-Ch) and BQ-RMP using blood samples from 52 volunteers. AdLDL-Ch levels were also compared with those measurements by homogeneous assays and calculation methods (Friedewald equation, Martin equation, and Sampson equation) using blood samples from 411 participants with dyslipidemia and/or type 2 diabetes. Results The precision and accuracy of adLDL-Ch were verified by BQ-RMP. The mean percentage bias [bias (%)] for LDL-C was 1.2%, and the correlation was y = 0.990x + 3.361 (r = 0.990). These results met the acceptable range of accuracy prescribed by the National Cholesterol Education Program. Additionally, adLDL-Ch levels were correlated with LDL-C levels measured by the 2 homogeneous assays (r > 0.967) and the calculation methods (r > 0.939), in serum samples from patients with hypertriglyceridemia. Conclusions AEX-HPLC is a reliable method for measuring LDL-C levels for CVD risk in daily clinical laboratory analyses.

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Assessment of Digital PCR as a Primary Reference Measurement Procedure to Support Advances in Precision Medicine

Clinical Chemistry ◽

10.1373/clinchem.2017.285478 ◽

2018 ◽

Vol 64 (9) ◽

pp. 1296-1307 ◽

Cited By ~ 18

Author(s):

Alexandra S Whale ◽

Gerwyn M Jones ◽

Jernej Pavšič ◽

Tanja Dreo ◽

Nicholas Redshaw ◽

...

Keyword(s):

Precision Medicine ◽

Copy Number ◽

Digital Pcr ◽

Measurement Procedure ◽

Patient Treatment ◽

Molecular Diagnostic ◽

Reference Measurement ◽

Reference Measurement Procedure ◽

Wide Range ◽

Primary Reference

Abstract BACKGROUND Genetic testing of tumor tissue and circulating cell-free DNA for somatic variants guides patient treatment of many cancers. Such measurements will be fundamental in the future support of precision medicine. However, there are currently no primary reference measurement procedures available for nucleic acid quantification that would support translation of tests for circulating tumor DNA into routine use. METHODS We assessed the accuracy of digital PCR (dPCR) for copy number quantification of a frequently occurring single-nucleotide variant in colorectal cancer (KRAS c.35G>A, p.Gly12Asp, from hereon termed G12D) by evaluating potential sources of uncertainty that influence dPCR measurement. RESULTS Concentration values for samples of KRAS G12D and wild-type plasmid templates varied by <1.2-fold when measured using 5 different assays with varying detection chemistry (hydrolysis, scorpion probes, and intercalating dyes) and <1.3-fold with 4 commercial dPCR platforms. Measurement trueness of a selected dPCR assay and platform was validated by comparison with an orthogonal method (inductively coupled plasma mass spectrometry). The candidate dPCR reference measurement procedure showed linear quantification over a wide range of copies per reaction and high repeatability and interlaboratory reproducibility (CV, 2%–8% and 5%–10%, respectively). CONCLUSIONS This work validates dPCR as an SI-traceable reference measurement procedure based on enumeration and demonstrates how it can be applied for assignment of copy number concentration and fractional abundance values to DNA reference materials in an aqueous solution. High-accuracy measurements using dPCR will support the implementation and traceable standardization of molecular diagnostic procedures needed for advancements in precision medicine.

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