Clinicians trust medical laboratories to provide reliable results on which they rely for clinical decisions. Laboratories fulfil their responsibility for accurate and consistent results by utilizing an arsenal of approaches, ranging from validation and verification experiments to daily quality control procedures. All these procedures verify, on different moments, that the results of a certain examination procedure have analytical performance characteristics (APC) that meet analytical performance specifications (APS) set for a particular intended use. The APC can in part be determined by estimating the measurement uncertainty component under conditions of within-laboratory precision (uRw), which comprises all components influencing the measurement uncertainty of random sources. To maintain the adequacy of their measurement procedures, laboratories need to distinguish aspects that are manageable vs. those that are not. One of the aspects that may influence uRw is the momentary significant bias caused by shifts in reagent and/or calibrator lots, which, when accepted or unnoticed, become a factor of the APC. In this paper, we postulate a model for allocating a part of allowable uRw to between-reagent lot variation, based on the need for long-term consistency of the measurement variability for that specific measurand. The allocation manages the ratio between short-term and long-term variation and indicates laboratories when to reject or correct certain variations due to reagent lots.

Association of Clinical Biochemists in Ireland Dublin Ireland

Belgium and Department of Public Health Laboratory Medicine University Hospital Leuven Biomedical Sciences Group Leuven Belgium

Clinical Chemistry Laboratory Spedali Civili Brescia Italy

Clinical Laboratory Hospital Kladno Kladno Czech Republic

Department of Biomedical and Clinical Sciences Luigi Sacco and Research Centre for Metrological Traceability in Laboratory Medicine University of Milan Milano Italy

Department of Clinical Biochemistry Medical School Attikon University General Hospital National and Kapodistrian University of Athens Haidari Greece

Department of Clinical Chemistry University Clinic for Respiratory and Allergic Diseases Golnik Slovenia

Department of Laboratory Medicine Radboud University Medical Centre Nijmegen The Netherlands

Department of Medical Biochemistry Faculty of Pharmacy University of Belgrade Belgrade Serbia

Dept of Genetics Rare Diseases and Personalized Medicine Rare Diseases and Autoinflammatory Unit CHU Montpellier Univ Montpellier Montpellier France

Interdisciplinary Stem Cells and Regenerative Medicine Ankara University Stem Cell Institute Ankara Turkey

Linko Q Solutions Helsinki Finland

Regional Laboratoriemedicin Sahlgrenska Universitetssjukhuset Trollhättan Sweden

Result Laboratory for Clinical Chemistry Amphia Hospital Breda The Netherlands

Servicio Bioquímica Análisis Clínicos Hospital Universitario Puerta de Hierro Madrid Spain

Clin Chem Lab Med. 2022 Feb 23;60(5):645-646. doi: 10.1515/cclm-2022-0128. PubMed

Clin Chem Lab Med. 2023 Jun 01;61(11):e215-e217. doi: 10.1515/cclm-2023-0430. PubMed

Zobrazit více v PubMed

International Organization for Standardization . Medical laboratories – Practical guidance for the estimation of measurement uncertainty . ISO/TS 20914:2019; 2019.

Infusino, I, Panteghini, M. Measurement uncertainty: friend or foe? Clin Biochem 2018;57:3–6, https://doi.org/10.1016/j.clinbiochem.2018.01.025 . DOI

Braga, F, Pasqualetti, S, Aloisio, E, Panteghini, M. The internal quality control in the traceability era. Clin Chem Lab Med 2020;59:291–300, https://doi.org/10.1515/cclm-2020-0371 . DOI

Schoenmakers, CHH, Naus, AJM, Vermeer, HJ, van Loon, D, Steen, G. Practical application of sigma metrics QC procedures in clinical chemistry. Clin Chem Lab Med 2011;49:1837–43, https://doi.org/10.1515/CCLM.2011.249 . DOI

Katzman, BM, Ness, KM, Algeciras-Schimnich, A. Evaluation of the CLSI EP26-A protocol for detection of reagent lot-to-lot differences. Clin Biochem 2017;50:768–71, https://doi.org/10.1016/j.clinbiochem.2017.03.012 . DOI

CLSI . User evaluation of between-reagent lot variation. CLSI guideline EP26-A . Wayne, PA: Clinical and Laboratory Standards Institute; 2013.

CLSI . Verification of Comparability of Patient Results Within One Health Care System. CLSI guideline EP31-A-IR . Wayne, PA: Clinical and Laboratory Standards Institute; 2012.

Thompson, S, Chesher, D. Lot-to-lot variation. Clin Biochem Rev 2018;39:51–60.

Kristensen, GBB, Meijer, P. Interpretation of EQA results and EQA-based trouble shooting. Biochem Med 2017;27:49–62, https://doi.org/10.11613/bm.2017.007 . DOI

Don-Wauchope, AC. Lot change for reagents and calibrators. Clin Biochem 2016;49:1211–2, https://doi.org/10.1016/j.clinbiochem.2016.04.003 . DOI

Miller, W, Erek, A, Cunningham, TD, Oladipo, O, Scott, MG, Johnson, RE. Commutability limitations influence quality control results with different reagent lots. Clin Chem 2011;57:76–83, https://doi.org/10.1373/clinchem.2010.148106 . DOI

Kim, S, Chang, J, Kim, S-K, Park, S, Huh, J, Jeong, T-D. Sample size and rejection limits for detecting reagent lot variability: analysis of the applicability of the Clinical and Laboratory Standards Institute (CLSI) EP26-A protocol to real-world clinical chemistry data. Clin Chem Lab Med 2020;59:127–38, https://doi.org/10.1515/cclm-2020-0454 . DOI

Thaler, MA, Iakoubov, R, Bietenbeck, A, Luppa, PB. Clinically relevant lot-to-lot reagent difference in a commercial immunoturbidimetric assay for glycated hemoglobin A1c. Clin Biochem 2015;48:1167–70, https://doi.org/10.1016/j.clinbiochem.2015.07.018 . DOI

Vos, SJB, Visser, PJ, Verhey, F, Aalten, P, Knol, D, Ramakers, I, et al.. Variability of CSF Alzheimer’s disease biomarkers: implications for clinical practice. PLoS One 2014;9: e100784, https://doi.org/10.1371/journal.pone.0100784 . DOI

Sasaki, M, Sasaki, K. Significance of the control serum measurement in infectious disease tests – a case of lot-to-lot variation of anti-HIV antibody assay kit. Rinsho Byori 2002;50:717–20.

Algeciras-Schimnich, A, Bruns, D, Boyd, J, Bryant, S, Fortune, K, Grebe, S. Failure of current laboratory protocols to detect lot-to-lot reagent differences: findings and possible solutions. Clin Chem 2013;59:1187–94, https://doi.org/10.1373/clinchem.2013.205070 . DOI

Liu, J, Tan, CH, Loh, TP, Badrick, T. Detecting long-term drift in reagent lots. Clin Chem 2015;61:1292–8, https://doi.org/10.1373/clinchem.2015.242511 . DOI

International Organization for Standardization . In vitro diagnostic medical devices – Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples . ISO 17511:2020.

Braga, F, Panteghini, M. The utility of measurement uncertainty in medical laboratories. Clin Chem Lab Med 2020;58:1407–13, https://doi.org/10.1515/cclm-2019-1336 . DOI

Braga, F, Panteghini, M. Performance specifications for measurement uncertainty of common biochemical according to Milan models. Clin Chem Lab Med 2021;59:1362–8. PubMed DOI

Cotlove, E, Harris, EK, Williams, GZ. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. 3. Physiological and medical implications. Clin Chem 1970;16:1028–32, https://doi.org/10.1093/clinchem/16.12.1028 . DOI

EFLM Biological Variation . Available from: https://biologicalvariation.eu/ [Accessed 1 Dec 2021].

Kristensen, GBB, Christensen, NG, Thue, G, Sandberg, S. Between-lot variation in external quality assessment of glucose: clinical importance and effect on participant performance evaluation. Clin Chem 2005;51:1632–6, https://doi.org/10.1373/clinchem.2005.049080 . DOI

Jansen, RTP, Cobbaert, CM, Weykamp, C, Thelen, M. The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability. Clin Chem Lab Med 2018;56:1673–84, https://doi.org/10.1515/cclm-2017-0796 . DOI

Calleja, J. Parallel processing and maintaining adequate alignment between instruments and methods. Clin Biochem Rev 2008;29:S71–7.

Miller, WG, Greenberg, N. Harmonization and standardization: where are we now? J Appl Lab Med 2021;6:510–21, https://doi.org/10.1093/jalm/jfaa189 . DOI

Regulation (EU) 2017/746 of the European parliament and of the council of 5 april 2017 on in vitro diagnostic medical devices and repealing directive 98/79/EC and commission decision 2010/227/EU (text with EEA relevance). 2017. Available from: http://data.europa.eu/eli/reg/2017/746/oj/eng [Accessed 2 Aug 2021].

Ngo, A, Gandhi, P, Miller, WG. Frequency that laboratory tests influence medical decisions. J Appl Lab Med 2017;1:410–4, https://doi.org/10.1373/jalm.2016.021634 . DOI

Georgiou, A, Sezgin, G, Li, L, Wilson, R, McCaughey, EJ, Lindeman, R, et al.. Who gets a laboratory test in hospital, why, and how often? A retrospective observational study of 4 Australian hospitals. J Appl Lab Med 2019;4:343–54, https://doi.org/10.1373/jalm.2018.028688 . DOI

Barber, J, Guo, M, Nguyen, LT, Thomas, R, Turin, TC, Vaska, M, et al.. Sociodemographic correlates of clinical laboratory test expenditures in a major Canadian city. Am J Clin Pathol 2017;148:91–6, https://doi.org/10.1093/ajcp/aqx052 . DOI

Hardwick, DF. Pathology—medicine’s search for meaning in the new millennium. Hum Pathol 2002;33:1, https://doi.org/10.1053/hupa.2002.31752 . DOI

Vacellio, E. Australian Government Department of Health. Examination of variation in hospital pathology investigations by diagnosis-related groups and associations with outcomes and costs: report to Commonwealth of Australia . Sydney: Department of Health, Quality Use Pathology Committee. Report to Commonwealth of Australia, Department of Health, Quality Use of Pathology Committee. Australian Institute of Health Innovation, Macquarie University; 2015.

Braga, F, Infusino, I, Panteghini, M. Performance criteria for combined uncertainty budget in the implementation of metrological traceability. Clin Chem Lab Med CCLM 2015;53:905–12, https://doi.org/10.1515/cclm-2014-1240 . DOI

Loh, TP, Sandberg, S, Horvath, A. Lot-to-lot reagent verification: challenges and possible solutions. Clin Chem Lab Med 2022;60:675–80. PubMed DOI