scholarly journals Implementation of metrological traceability in laboratory medicine: where we are and what is missing

2020 ◽  
Vol 58 (8) ◽  
pp. 1200-1204 ◽  
Author(s):  
Mauro Panteghini ◽  
Federica Braga
Keyword(s):  
Mass Spectrometry ◽  
Measurement System ◽  
Task Force ◽  
Metrological Traceability ◽  
Laboratory Medicine ◽  
Isotopic Dilution ◽  
Clinical Samples ◽  
Reference Measurement ◽  
Reference Measurement System

AbstractBackgroundThe Joint Committee on Traceability in Laboratory Medicine (JCTLM) has recently created the Task Force on Reference Measurement System Implementation (TF-RMSI) for providing guidance on traceability implementation to in vitro diagnostics (IVD) manufacturers. Using serum creatinine (sCr) as an example, a preliminary exercise was carried out by checking what type of information is available in the JCTLM database and comparing this against derived analytical performance specifications (APS) for measurement uncertainty (MU) of sCr.ContentAPS for standard MU of sCr measurements were established as a fraction (≤0.75, minimum quality; ≤0.50, desirable quality; and ≤0.25, optimum quality) of the intra-individual biological variation of the measurand (4.4%). By allowing no more than one third of the total MU budget for patient samples to be derived from higher-order references, two out of the four JCTLM reference materials (RMs) at least allow minimum APS to be achieved for the MU of patient samples. Commutability was explicitly assessed for one of the JCTLM-listed matrixed RMs, which was produced in compliance with ISO 15194:2009 standard, whereas the remaining three RMs were assessed against the ISO 15194:2002 version of the standard, which only required the extent of commutability testing to be reported. Regarding the three listed reference methods, the MU associated with isotopic dilution-mass spectrometry coupled to gas chromatography (ID/GC/MS) and isotopic dilution-mass spectrometry coupled to liquid chromatography (ID/LC/MS) would allow APS to be fulfilled, while the isotope dilution surface-enhanced Raman scattering (ID/SERS) method displays higher MU.SummaryThe most recently listed RM for sCr in the JCTLM database meets the ISO 15194:2009 requirements with MU that would allow APS to be fulfilled and has had commutability demonstrated for use as a common calibrator in implementing traceability of sCr measurements. Splitting clinical samples with a laboratory performing ID/GC/MS or ID/LC/MS provides an alternative but would also require all components of uncertainty of these materials to be assessed.OutlookUsing appropriately derived APS to judge whether reference measurement system components are fit for purpose represents a novel approach. The TF-RMSI is planning to review a greater number of measurands to provide more robust information about the state of the art of available reference measurement systems and their impact on the ability of clinical measurements to meet APS.

scholarly journals Towards an SI-Traceable Reference Measurement System for Seven Serum Apolipoproteins Using Bottom-Up Quantitative Proteomics: Conceptual Approach Enabled by Cross-Disciplinary/Cross-Sector Collaboration

2020 ◽  
Author(s):  
Christa M Cobbaert ◽  
Harald Althaus ◽  
Ilijana Begcevic Brkovic ◽  
Uta Ceglarek ◽  
Stefan Coassin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cardiovascular Disease ◽  
Measurement System ◽  
Protein Quantification ◽  
Test Results ◽  
Conceptual Approach ◽  
Reference Measurement ◽  
Lipid Panel ◽  
Mass Spectrometry Technology ◽  
Reference Measurement System

Abstract Current dyslipidemia management in patients with atherosclerotic cardiovascular disease (ASCVD) is based on traditional serum lipids. Yet, there is some indication from basic research that serum apolipoproteins A-I, (a), B, C-I, C-II, C-III, and E may give better pathophysiological insight into the root causes of dyslipidemia. To facilitate the future adoption of clinical serum apolipoprotein (apo) profiling for precision medicine, strategies for accurate testing should be developed in advance. Recent discoveries in basic science and translational medicine set the stage for the IFCC Working Group on Apolipoproteins by Mass Spectrometry. Main drivers were the convergence of unmet clinical needs in cardiovascular disease (CVD) patients with enabling technology and metrology. First, the residual cardiovascular risk after accounting for established risk factors demonstrates that the current lipid panel is too limited to capture the full complexity of lipid metabolism in patients. Second, there is a need for accurate test results in highly polymorphic and atherogenic apolipoproteins such as apo(a). Third, sufficient robustness of mass spectrometry technology allows reproducible protein quantification at the molecular level. Fourth, several calibration hierarchies in the revised ISO 17511:2020 guideline facilitate metrological traceability of test results, the highest achievable standard being traceability to SI. This article outlines the conceptual approach aimed at achieving a novel, multiplexed Reference Measurement System (RMS) for seven apolipoproteins based on isotope dilution mass spectrometry and peptide-based calibration. This RMS should enable standardization of existing and emerging apolipoprotein assays to SI, within allowable limits of measurement uncertainty, through a sustainable network of Reference Laboratories.

scholarly journals Optimizing Available Tools for Achieving Result Standardization: Value Added by Joint Committee on Traceability in Laboratory Medicine (JCTLM)

2021 ◽  
Author(s):  
Mauro Panteghini ◽  
Federica Braga ◽  
Johanna E Camara ◽  
Vincent Delatour ◽  
Katleen Van Uytfanghe ◽  
...  
Keyword(s):  
Task Force ◽  
Certified Reference Materials ◽  
Clinical Sample ◽  
Metrological Traceability ◽  
Value Added ◽  
Higher Order ◽  
Measuring System ◽  
Clinical Samples ◽  
Field Methods ◽  
Reference Measurement

Abstract Background The JCTLM created a Task Force on Reference Measurement System Implementation (TF-RMSI) to provide guidance on metrological traceability implementation for the in vitro diagnostics (IVD) community. Content TF-RMSI investigated the reference measurement systems (RMS) for 13 common measurands by applying the following procedural steps: (a) extracting data from the JCTLM database of available certified reference materials (CRMs) and reference measurement procedures (RMPs); (b) describing the RMS to which each recruited CRM or RMP belongs; (c) identifying the intended use of the CRMs, and, if used as a common calibrator for IVD measuring systems and/or trueness assessment of field methods was included, checking the CRM’s certificate for information about commutability with clinical samples; and (d) checking if the CRM or RMP measurement uncertainty (MU) has the potential to be small enough to avoid significantly affecting the analytical performance specifications (APS) for MU of clinical sample results when the MU from the IVD calibrator and from the end-user measuring system were combined. Summary We produced a synopsis of JCTLM-listed higher-order CRMs and RMPs for the selected measurands, including their main characteristics for implementing traceability and fulfilling (or not) the APS for suitable MU. Results showed that traceability to higher-order references can be established by IVD manufacturers within the defined APS for most of the 13 selected measurands. However, some measurands do not yet have suitable CRMs for use as common calibrators. For these measurands, splitting clinical samples with a laboratory performing the RMP may provide a practical alternative for establishing a calibration hierarchy.

scholarly journals PENETAPAN SISTEM ACUAN DAYA AC UNTUK LABORATORIUM STANDAR NASIONAL BERDASARKAN STANDARD WATT CONVERTER

2016 ◽  
Vol 17 (1) ◽  
pp. 11
Author(s):  
Agah Faisal
Keyword(s):  
Measurement System ◽  
Reference System ◽  
Digital Voltmeter ◽  
National Standard ◽  
National Metrology Institute ◽  
Standard Laboratory ◽  
Reference Measurement ◽  
Power Meter ◽  
Ac Power ◽  
Reference Measurement System

<p>Abstrak</p><p><br />Puslit KIM-LIPI telah mengembangkan suatu sistem pengukuran acuan daya AC untuk laboratorium standar nasional dengan ketelitian pengukuran yang lebih baik dari 75 ppm pada faktor cakupan 2 dan tingkat kepercayaan 95%. Sistem tersebut berbasis Standard Watt Converter (SWC), beban semu, dan digital DC voltmeter yang telah diketahui koreksinya melalui proses kalibrasi kepada standar yang dimiliki Lembaga Metrologi Nasional Australia (NMIA) dan Lembaga Metrologi Nasional Indonesia (Puslit KIM-LIPI). Metode perbandingan terhadap sistem acuan tersebut telah diterapkan pada suatu Unit Under Calibration (UUC) yang berupa power meter berketelitian tinggi. Hal ini dilakukan untuk menampilkan unjuk kerja sistem acuan daya AC dalam proses pengukuran koreksi pembacaan dari power meter. Hasil evaluasi pada titik-titik pengukuran 120 V, 5 A, dan 53 Hz menunjukkan bahwa koreksi pembacaan terbesar adalah 133 ppm. Nilai tersebut berkesesuian dengan kelas akurasi power meter ZERA RMM3001 yaitu 0,02% atau sebesar 200 ppm. Dari hasil unjuk kerja sistem pengukuran ini maka penetapan acuan daya AC untuk laboratorium standar nasional seperti Puslit KIM-LIPI mencukupi.<br />Kata kunci: sistem pengukuran acuan, daya AC, standard watt converter, koreksi pembacaan, power meter.</p><p><br />Abstract</p><p><br />Puslit KIM-LIPI has developed an AC power reference measurement system for a national standard laboratory with a measurement precision better than 75 ppm at coverage factor 2 and confidence level 95 %. The system was based on the instruments of a standard watt converter, a phantom load, and a standard digital voltmeter, which the corrections of those readings are known by calibration processes to both National Metrology Institute of Australia (NMIA) and Puslit KIM-LIPI. The comparison method of the AC power reference system has been applied to the high precision power meter as a unit under calibration (UUC). This was done to show the measurement performance of AC power reference system in the process to find the reading correction of the power meter under calibration. The measurement evaluation at 120 V, 5 A, and 53 Hz showed that the worst reading correction was 133 ppm. That value was on the agreement with the class accuracy of ZERA RMM3001 power meter which is 0,02 % or 200 ppm. The performance of the measurement system indicated that the establishment of the ac power reference for a national standard laboratory such as Puslit KIM-LIPI was adequate.<br />Keywords: reference measurement system, AC power, standard watt converter, reading correction, power meter.</p>

scholarly journals A rigorous evaluation of optimal peptide targets for MS-based clinical diagnostics of Coronavirus Disease 2019 (COVID-19).

2021 ◽  
Author(s):  
Andrew T Rajczewski ◽  
Subina T Mehta ◽  
Dinh Duy An Ngyuen ◽  
Björn Andreas Grüning ◽  
James E Johnson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Direct Detection ◽  
Clinical Diagnostics ◽  
Clinical Proteomics ◽  
Clinical Samples ◽  
P Value ◽  
Upper Respiratory Tract ◽  
Proteomics Data ◽  
High Throughput Analysis

The Coronavirus Disease 2019 (COVID19) global pandemic has had a profound, lasting impact on the world's population. A key aspect to providing care for those with COVID19 and checking its further spread is early and accurate diagnosis of infection, which has been generally done via methods for amplifying and detecting viral RNA molecules. Detection and quantitation of peptides using targeted mass spectrometry-based strategies has been proposed as an alternative diagnostic tool due to direct detection of molecular indicators from non-invasively collected samples as well as the potential for high-throughput analysis in a clinical setting; many studies have revealed the presence of viral peptides within easily accessed patient samples. However, evidence suggests that some viral peptides could serve as better indicators of COVID19 infection status than others, due to potential misidentification of peptides derived from human host proteins, poor spectral quality, high limits of detection etc. In this study we have compiled a list of 636 peptides identified from Sudden Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples, including from in vitro and clinical sources. These datasets were rigorously analyzed using automated, Galaxy-based workflows containing tools such as PepQuery, BLAST-P, and the Multi-omic Visualization Platform as well as the open-source tools MetaTryp and Proteomics Data Viewer (PDV). Using PepQuery for confirming peptide spectrum matches, we were able to narrow down the 639 peptide possibilities to 87 peptides which were most robustly detected and specific to the SARS-CoV-2 virus. The specificity of these sequences to coronavirus taxa was confirmed using Unipept and BLAST-P. Through stringent p-value cutoff combined with manual verification of peptide spectrum match quality, 4 peptides derived from the nucleocapsid phosphoprotein and membrane protein were found to be most robustly detected across all cell culture and clinical samples, including those collected non-invasively. We propose that these peptides would be of the most value for clinical proteomics applications seeking to detect COVID-19 from a variety of sample types. We also contend that samples taken from the upper respiratory tract and oral cavity have the highest potential for diagnosis of SARS-CoV-2 infection from easily collected patient samples using mass spectrometry-based proteomics assays.

First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay – Lp(a) SRM 2B

2004 ◽  
Vol 42 (6) ◽  
Author(s):  
Francesco Dati ◽  
Jillian R. Tate ◽  
Santica M. Marcovina ◽  
Armin Steinmetz
Keyword(s):  
Disease Risk ◽  
Clinical Chemistry ◽  
Cardiovascular Disease Risk ◽  
Metrological Traceability ◽  
Reference Method ◽  
Laboratory Medicine ◽  
Expert Committee ◽  
International Reference ◽  
Lipoprotein A

AbstractLipoprotein(a) is an important predictor of cardiovascular disease risk. The lack of internationally accepted standardization has impeded the broad application of this lipoprotein in laboratory medicine. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lipoprotein(a) and together with research institutions and several diagnostic companies, have succeeded in developing an international reference material that is intended for the transfer of a lipoprotein(a) concentration to manufacturers' master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert Committee on Biological Standardization as the ‘First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay’. The assigned unitage of 0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus reference method for lipoprotein( a) and will enable conformity by diagnostic companies to the European Union's Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials.

Irregular analytical errors in diagnostic testing – a novel concept

2018 ◽  
Vol 56 (3) ◽  
pp. 386-396 ◽  
Author(s):  
Michael Vogeser ◽  
Christoph Seger
Keyword(s):  
Quality Control ◽  
Measurement Uncertainty ◽  
Measurement System ◽  
Clinical Chemistry ◽  
Individual Sample ◽  
Reference Measurement ◽  
Analytical Error ◽  
The Individual ◽  
Analytical Errors ◽  
Reference Measurement System

AbstractBackground:In laboratory medicine, routine periodic analyses for internal and external quality control measurements interpreted by statistical methods are mandatory for batch clearance. Data analysis of these process-oriented measurements allows for insight into random analytical variation and systematic calibration bias over time. However, in such a setting, any individual sample is not under individual quality control. The quality control measurements act only at the batch level. Quantitative or qualitative data derived for many effects and interferences associated with anindividualdiagnostic sample can compromise any analyte. It is obvious that a process for a quality-control-sample-based approach of quality assurance is not sensitive to such errors.Content:To address the potential causes and nature of such analytical interference in individual samples more systematically, we suggest the introduction of a new term called theirregular(individual)analytical error. Practically, this term can be applied in any analytical assay that is traceable to a reference measurement system. For an individual sample an irregular analytical error is defined as an inaccuracy (which is the deviation from a reference measurement procedure result) of a test result that is so high it cannot be explained by measurement uncertainty of the utilized routine assay operating within the accepted limitations of the associated process quality control measurements.Summary:The deviation can be defined as the linear combination of the process measurement uncertainty and the method bias for the reference measurement system. Such errors should be coinedirregular analytical errorsof the individual sample. The measurement result is compromised either by an irregular effect associated with the individual composition (matrix) of the sample or an individual single sample associated processing error in the analytical process.Outlook:Currently, the availability of reference measurement procedures is still highly limited, but LC-isotope-dilution mass spectrometry methods are increasingly used for pre-market validation of routine diagnostic assays (these tests also involve substantial sets of clinical validation samples). Based on this definition/terminology, we list recognized causes of irregular analytical error as arisk catalogfor clinical chemistry in this article. These issues include reproducible individual analytical errors (e.g. caused by anti-reagent antibodies) and non-reproducible, sporadic errors (e.g. errors due to incorrect pipetting volume due to air bubbles in a sample), which can both lead to inaccurate results and risks for patients.

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