scholarly journals IFCC Working Group Recommendations for Correction of Bias Caused by Noncommutability of a Certified Reference Material Used in the Calibration Hierarchy of an End-User Measurement Procedure

2020 ◽  
Vol 66 (6) ◽  
pp. 769-778 ◽  
Author(s):  
W Greg Miller ◽  
Jeffrey Budd ◽  
Neil Greenberg ◽  
Cas Weykamp ◽  
Harald Althaus ◽  
...  
Keyword(s):  
Reference Material ◽  
Certified Reference Material ◽  
Clinical Laboratory ◽  
Metrological Traceability ◽  
Measurement Procedure ◽  
Clinical Samples ◽  
End User ◽  
Assigned Value ◽  
The Difference ◽  
Specific Correction

Abstract Establishing metrological traceability to an assigned value of a matrix-based certified reference material (CRM) that has been validated to be commutable among available end-user measurement procedures (MPs) is central to producing equivalent results for the measurand in clinical samples (CSs) irrespective of the clinical laboratory MPs used. When a CRM is not commutable with CSs, the bias due to noncommutability will be propagated to the CS results causing incorrect metrological traceability to the CRM and nonequivalent CS results among different MPs. In a commutability assessment, a conclusion that a CRM is commutable or noncommutable for use with a specific MP is made when the difference in bias between the CRM and CSs meets or does not meet a criterion for that specific MP when compared to other MPs. A conclusion regarding commutability or noncommutability requires that the magnitude of the difference in bias observed in the commutability assessment remains unchanged over time. This conclusion requires the CRM to be stable and no substantive changes in the MPs. These conditions should be periodically reverified. If an available CRM is determined to be noncommutable for a specific MP, that CRM can be used in the calibration hierarchy for that MP when an appropriately validated MP-specific correction for the noncommutability bias is included. We describe with examples how a MP-specific correction and its uncertainty can be developed and applied in a calibration hierarchy to achieve metrological traceability of results for CSs to the CRM’s assigned value.

scholarly journals Documenting metrological traceability as intended by ISO 15189:2012: A consensus statement about the practice of the implementation and auditing of this norm element

2019 ◽  
Vol 57 (4) ◽  
pp. 459-464 ◽  
Author(s):  
Marc Thelen ◽  
Florent Vanstapel ◽  
Pika Meško Brguljan ◽  
Bernard Gouget ◽  
Guilaine Boursier ◽  
...  
Keyword(s):  
Metrological Traceability ◽  
Measurement Procedure ◽  
Medical Laboratory ◽  
Clinical Samples ◽  
End User ◽  
Worst Case ◽  
Iso 15189 ◽  
Value Assignment ◽  
Traceability Chain ◽  
Medical Laboratories

Abstract ISO15189:2012 requires medical laboratories to document metrological traceability of their results. While the ISO17511:2003 standard on metrological traceability in laboratory medicine requires the use of the highest available level in the traceability chain, it recognizes that for many measurands there is no reference above the manufacturer’s selected measurement procedure and the manufacturer’s working calibrator. Some immunoassays, although they intend to measure the same quantity and may even refer to the same reference material, unfortunately produce different results because of differences in analytical selectivity as manufacturers select different epitopes and antibodies for the same analyte. In other cases, the cause is the use of reference materials, which are not commutable. The uncertainty associated with the result is another important aspect in metrological traceability implementation. As the measurement uncertainty on the clinical samples is influenced by the uncertainty of all steps higher in the traceability chain, laboratories should be provided with adequate and appropriate information on the uncertainty of the value assignment to the commercial calibrators that they use. Although the between-lot variation in value assignment will manifest itself as part of the long-term imprecision as estimated by the end-user, information on worst-case to be expected lot-lot variation has to be communicated to the end-user by the IVD provider. When laboratories use ancillary equipment that potentially could have a critical contribution to the reported results, such equipment needs verification of its proper calibration and criticality to the result uncertainty could be assessed by an approach based on risk analysis, which is a key element of ISO15189:2012 anyway. This paper discusses how the requirement for metrological traceability as stated in ISO15189 should be met by the medical laboratory and how this should be assessed by accreditation bodies.

scholarly journals IFCC Working Group Recommendations for Assessing Commutability Part 2: Using the Difference in Bias between a Reference Material and Clinical Samples

2018 ◽  
Vol 64 (3) ◽  
pp. 455-464 ◽  
Author(s):  
Göran Nilsson ◽  
Jeffrey R Budd ◽  
Neil Greenberg ◽  
Vincent Delatour ◽  
Robert Rej ◽  
...  
Keyword(s):  
Reference Material ◽  
Quality Assessment ◽  
Working Group ◽  
External Quality Assessment ◽  
Clinical Samples ◽  
External Quality ◽  
Amount Of Substance ◽  
Specific Effects ◽  
Fit For Purpose ◽  
The Difference

Abstract A process is described to assess the commutability of a reference material (RM) intended for use as a calibrator, trueness control, or external quality assessment sample based on the difference in bias between an RM and clinical samples (CSs) measured using 2 different measurement procedures (MPs). This difference in bias is compared with a criterion based on a medically relevant difference between an RM and CS results to make a conclusion regarding commutability. When more than 2 MPs are included, the commutability is assessed pairwise for all combinations of 2 MPs. This approach allows the same criterion to be used for all combinations of MPs included in the assessment. The assessment is based on an error model that allows estimation of various random and systematic sources of error, including those from sample-specific effects of interfering substances. An advantage of this approach is that the difference in bias between an RM and the average bias of CSs at the concentration (i.e., amount of substance present or quantity value) of the RM is determined and its uncertainty estimated. An RM is considered fit for purpose for those MPs for which commutability is demonstrated.

Certified reference material of bioethanol for metrological traceability in electrochemical parameters analyses

Talanta ◽  
2012 ◽  
Vol 99 ◽  
pp. 99-103 ◽  
Author(s):  
Isabel Cristina Serta Fraga ◽  
Carla Matos Ribeiro ◽  
Sidney Pereira Sobral ◽  
Júlio Cesar Dias ◽  
Mary Ane Gonçalves ◽  
...  
Keyword(s):  
Reference Material ◽  
Certified Reference Material ◽  
Metrological Traceability ◽  
Electrochemical Parameters

Harmonization and Standardization: Where Are We Now?

2020 ◽  
Author(s):  
W Greg Miller ◽  
Neil Greenberg
Keyword(s):  
Reference Materials ◽  
Certified Reference Materials ◽  
Metrological Traceability ◽  
Medical Laboratory ◽  
Clinical Samples ◽  
End User ◽  
Laboratory Service ◽  
Fit For Purpose ◽  
Diagnosis Therapy ◽  
Traceable Calibration

Abstract Background The purpose of a medical laboratory test is to provide information on the pathophysiologic condition of an individual patient as an aid in diagnosis, therapy, or assessment of risk for a disease. For optimal laboratory service, results from different measurement procedures (MPs) for the same measurand should be equivalent (harmonized) within stated specifications, enabling the results to be used reliably for medical decisions. The term “harmonization” refers to any process that enables establishing equivalence of reported values among different end-user MPs. The term “standardization” refers to achieving harmonization by metrological traceability of patients’ results to higher order reference materials and/or reference measurement procedures. Content New procedures for harmonization and standardization were published in 2020 by the International Organization for Standardization (ISO) and by the IFCC. ISO 17511:2020 provides revised requirements for establishing metrologically traceable calibration hierarchies for end-user MPs used in clinical laboratories. ISO 21151:2020 provides new requirements to implement a harmonization protocol to address the situation when there are no fit-for-purpose certified reference materials or reference MPs available for a measurand. The IFCC Working Group on Commutability published recommendations for applying a correction for noncommutability of a certified reference material to enable using that material in a metrologically traceable calibration hierarchy for an end-user MP. Summary We review metrological traceability and how these new approaches will improve the capability to achieve harmonized results for clinical samples.

scholarly journals Thrombin: An Approach to Developing a Higher-Order Reference Material and Reference Measurement Procedure for Substance Identity, Amount, and Biological Activities

2020 ◽  
Vol 125 ◽  
Author(s):  
Craig M. Jackson ◽  
M. Peter Esnouf ◽  
David L. Duewer
Keyword(s):  
Reference Material ◽  
Reference Materials ◽  
Biological Activities ◽  
Metrological Traceability ◽  
Catalytic Efficiency ◽  
Measurement Procedure ◽  
Protein Characterization ◽  
Reference Measurement ◽  
Reference Measurement Procedure ◽  
Hydrolytic Activities

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.

scholarly journals Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification

2019 ◽  
Vol 57 (8) ◽  
pp. 1197-1206 ◽  
Author(s):  
Evanthia Monogioudi ◽  
Joanna Sheldon ◽  
Pier Luigi Meroni ◽  
Dana Petronela Hutu ◽  
Heinz Schimmel ◽  
...  
Keyword(s):  
Reference Material ◽  
Certified Reference Material ◽  
Certified Reference Materials ◽  
Feasibility Studies ◽  
Autoimmune Disorder ◽  
Accurate Diagnosis ◽  
Clinical Samples ◽  
Appropriate Use ◽  
Comparability Of Results

Abstract Background The importance of the standardisation of immunoassays for autoantibodies has been widely discussed. The appropriate use of certified reference materials (CRM) could contribute to a more accurate diagnosis and follow-up of a series of diseases such as small vessel-associated vasculitis. This is a systemic autoimmune disorder during which two autoantibodies can be present, MPO ANCA IgG and PR3 ANCA IgG. Results from different commercially available immunoassays used for PR3 ANCA IgG measurement can vary significantly. Therefore the potential for improvement using a suitable certified reference material was assessed and led to the development of a CRM. Methods Thirty clinical samples were evaluated using 10 immunoassays. The correlation between results from these assays was assessed in a pairwise manner. Feasibility studies were conducted in order to find a reference material format most suitable for the preparation of a CRM. Results The evaluation of two sets of 30 clinical samples with 10 assays showed that differences between assays can result in different interpretations for individual clinical samples. Most of the samples had the same result classification in all assays. However, six of the samples tested led to inconsistent results. Conclusions The correlation between results from clinical samples was systematically good for combinations of eight of those assays. Therefore, it should be possible to improve the comparability of results using a commutable CRM for calibration. Based on these studies, a final format for the CRM was selected and eventually produced and certified for its PR3 ANCA IgG content.

scholarly journals DEVELOPMENT OF REFERENCE MATERIAL OF HOLMIUM OXIDE FOR SPECTROMETERS WAVELENGTH CALIBRATION: FEASIBILITY STUDIES

2018 ◽  
Vol 15 (29) ◽  
pp. 243-250
Author(s):  
D. E. GONÇALVES ◽  
J. F. S. GOMES ◽  
A. P. D. ALVARENGA ◽  
T. de O. ARAUJO ◽  
P. P. BORGES
Keyword(s):  
Quality Assurance ◽  
Reference Material ◽  
Wavelength Range ◽  
Certified Reference Material ◽  
Metrological Traceability ◽  
Feasibility Studies ◽  
Wavelength Calibration ◽  
Material Production ◽  
Important Requirement

The use of certified reference material (CRM) in chemical analyzes is an important requirement in quality assurance systems, since it allows the metrological traceability of results, thus achieving valid and comparable results. This work describes the development and production of holmium oxide reference material that, after certification, will be used in the calibration of the wavelength range of UV-Vis spectrometers and also the necessary feasibility studies to establish the measurement parameters to be used in the next steps of the material production and certification.

scholarly journals Metrological assurance of dioxin measurements. A certified reference material for measuring the dioxin mass fraction in animal fat

2019 ◽  
Vol 14 (3-4) ◽  
pp. 17-32 ◽  
Author(s):  
A. G. Budko ◽  
A. Y. Mikheeva ◽  
A. I. Krylov
Keyword(s):  
Reference Material ◽  
Certified Reference Material ◽  
Mass Fraction ◽  
Metrological Traceability ◽  
Isotopic Dilution ◽  
Animal Fat ◽  
Measurement Results ◽  
Mass Fractions ◽  
Certified Values ◽  
Good Agreement

The paper presents information on the development of a new certified reference material (CRM) for mass fraction of dioxins in animal fat, with established metrological traceability. A procedure for preparing and certifying CRM material is given. The GC–LRMS method with isotopic dilution was used as an analytical method for establishing certified characteristics. The uncertainties due to inhomogeneity and instability of the CRM material were estimated in order to account for their contribution to the uncertainty of certified values. In addition, the results of interlaboratory comparisons (ILC) for an experimental batch of the developed CRM are presented. Measurement results provided by ILC participants are shown to be in good agreement with the certified characteristics of the CRM. The certified values of dioxin mass fractions (PCDF group) in the CRM material are established to vary from 1 to 1000 ng / kg, with the relative expanded uncertainty ranging from 10 to 20 %.

scholarly journals One-Step Quantitative Molecular Approach for Detection of BCR/ABL1 Rearrangement and for Monitoring of Minimal Residual Disease in CML Patients: An Inter Laboratory Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5423-5423
Author(s):  
Filomena Daraio ◽  
Maria Teresa Bochicchio ◽  
Barbara Izzo ◽  
Claudia Venturi ◽  
Santa Errichiello ◽  
...  
Keyword(s):  
Reference Material ◽  
Clinical Samples ◽  
Assigned Value ◽  
Direct Testing ◽  
Individual Laboratory ◽  
European Reference Material ◽  
One Step ◽  
The Mean ◽  
The One ◽  
The Individual

Abstract Molecular tests are the best way to monitor CML course in patients under treatment with tyrosine kinase inhibitors (TKI). International guidelines indicate the absolute copy number of the control gene ABL1 as reference for the definition of the sensitivity of the analytical method. A general implementation of the International Guidelines (EUTOS) and the moving forward of current technologies towards one-step reactions, that allow direct testing from the patient RNA, require continuous verification of the method performances. Here, as Italian laboratory network for the standardization of CML diagnosis (LabNet), we performed a comparative study across the three reference laboratories in order to evaluate the inclusion of "BCR-ABL P210 ELITe MGB® Kit" (ELITechGroup S.p.A.) one-step assay among the technologies indicated in the Laboratory Recommendations and Indications (R.I.L.) of the Italian Network for CML monitoring. "BCR-ABL P210 ELITe MGB® Kit" is a new assay that allows to perform in a unique reaction the retro-transcription and the amplification of the extracted RNA sample. In this study 30 RNA extracted from whole blood samples of CML patients at different stages of the disease and centrally distributed to the other reference labs have been analyzed. All laboratories tested 300 ng per reaction of each RNA according the one-step approach and the same RNA according each own routine method. Moreover, in the same experiments, the European Reference Material certified plasmid ERM-AD623 has been evaluated. Our results show an increased analytical sensitivity in detection of both genes (BCR/ABL1 and ABL1): the limit of detection of the one-step reaction is as low as 0.001% IS BCR/ABL1. By testing the ERM-AD623 at 1 copy/reaction the rate of PCR positivities is 63%, and the average estimated quantity is 2.5 (SD = ± 1.5) copies/reaction. The linear measurement range of BCR/ABL1 and of the control gene ABL1 evaluated using the ERM-AD623 reference material are linear and equivalent in the range of 102-107 copies/reaction. Quantifications obtained with this kit are aligned to the European Reference Material. Using 7500 Fast Dx Real-Time PCR Instrument or 7900 Real-Time PCR System (Applied Biosystem, Thermo Fisher Scientific), we confirm that the calibrator of the "BCR-ABL P210 ELITe MGB® Kit" is aligned to the ERM-AD623 DNA international standard and we demonstrated the inter-laboratory low variability and good linearity of the method by processing the secondary reference material aligned to WHO primary reference material. By analysis of 30 RNA of CML patients we observed high results reproducibility among laboratories (figure 1). In addition, at comparison with the individual routine methods (ipsogen BCR-ABL1 Mbcr IS-MMR DX, P210 PHILADELPHIA Q-PCR Alert kit. and an home-made assay) we report up to 97.4% correlation of BCR-ABL P210 ELITe MGB® kit results. In conclusion, our data demonstrate that "BCR-ABL P210 ELITe MGB® Kit" is a rapid, reproducible assay, aligned and calibrated towards the current goal standards BCR/ABL1 assays. It allows direct testing from RNA samples while maintaining the desired sensitivity. By requiring reduced hands on time of the operators and by allowing direct testing of RNA, "BCR-ABL P210 ELITe MGB® kit" will provide a significant improvement in the standardization of the molecular approach to CML monitoring. Figure 1 BCR-ABL P210 ELITe MGB® Kit reproducibility with clinical samples. Data of the individual laboratory were plotted against the mean assigned value. The regression fit of all data is R-Sq=96.8%. Figure 1. BCR-ABL P210 ELITe MGB® Kit reproducibility with clinical samples. Data of the individual laboratory were plotted against the mean assigned value. The regression fit of all data is R-Sq=96.8%. Disclosures Castagnetti: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD Pharmaceuticals: Consultancy, Honoraria. Martinelli:ARIAD: Consultancy; Genentech: Consultancy; Roche: Consultancy; Amgen: Consultancy; MSD: Consultancy; Pfizer: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Genentech: Consultancy; Amgen: Consultancy; Novartis: Speakers Bureau; MSD: Consultancy; Roche: Consultancy; ARIAD: Consultancy; Pfizer: Consultancy, Speakers Bureau. Saglio:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

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