Abstract
International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established reference measurement procedures (RMPs) for the most popular enzymes. Manufacturers should assign values to commercial calibrators traceable to these RMPs to achieve equivalent results in clinical samples, independent of reagent kits, instruments, and laboratory where the measurement is carried out. The situation is, however, far from acceptable. Some manufacturers continue to market assays giving results that are not traceable to internationally accepted RMPs. Meanwhile, end-users often do not abandon assays with demonstrated insufficient quality. Of the enzyme measurements, creatine kinase (CK) is satisfactorily standardized and a substantial improvement in performance of marketed γ-glutamyltranspeptidase (GGT) assays has been demonstrated. Conversely, aminotransferase measurements often exceed the desirable analytical performance because of the lack of pyridoxal-5-phosphate addition in the commercial reagents. Measurements of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and α-amylase (AMY) still show major disagreement, suggesting the need for improvement in implementing traceability to higher-order references. This is mainly the result of using assays with different analytical selectivities for these enzymes. The definition by laboratory professionals of the clinically acceptable measurement uncertainty for each enzyme together with the adoption by EQAS of commutable materials and use of an evaluation approach based on trueness represent the way forward for reaching standardization in clinical enzymology.
Acknowledgments
The authors acknowledge the long cooperation and the fruitful discussion with Prof. Ferruccio Ceriotti, Chair of the IFCC Committee on Reference Systems in Enzymology.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Panteghini M, Bais R. Serum enzymes. In: Rifai N, Horvat AR, Wittwer C, editors. Tietz textbook of clinical chemistry and molecular diagnostics, 6th ed. St. Louis: Elsevier Saunders, 2016.Search in Google Scholar
2. Ferraro S, Braga F, Panteghini M. Laboratory medicine in the new healthcare environment. Clin Chem Lab Med 2016;54:523–33.10.1515/cclm-2015-0803Search in Google Scholar PubMed
3. Panteghini M. Traceability as a unique tool to improve standardization in laboratory medicine. Clin Biochem 2009;42:236–40.10.1016/j.clinbiochem.2008.09.098Search in Google Scholar PubMed
4. Braga F, Panteghini M. Verification of in vitro medical diagnostics (IVD) metrological traceability: responsibilities and strategies. Clinica Chimica Acta 2014;432:55–61.10.1016/j.cca.2013.11.022Search in Google Scholar PubMed
5. Infusino I, Bonora R, Panteghini M. Traceability in clinical enzymology. Clin Biochem Rev 2007;28:155-61.Search in Google Scholar
6. Infusino I, Schumann G, Ceriotti F, Panteghini M. Standardization in clinical enzymology: a challenge for the theory of metrological traceability. Clin Chem Lab Med 2010;48:301–7.10.1515/CCLM.2010.075Search in Google Scholar PubMed
7. Panteghini M. Implementation of standardization in clinical practice: not always an easy task. Clin Chem Lab Med 2012;50:1237–41.10.1515/cclm.2011.791Search in Google Scholar PubMed
8. ISO 18153:2003. In vitro diagnostic medical devices – Measurement of quantities in biological samples – Metrological traceability of values for catalytic concentration of enzymes assigned to calibrators and control materials. ISO, Geneva, Switzerland.Search in Google Scholar
9. Panteghini M, Ceriotti F, Schumann G, Siekmann L. Establishing a reference system in clinical enzymology. Clin Chem Lab Med 2001;39:795–800.10.1515/CCLM.2001.131Search in Google Scholar PubMed
10. Frusciante E, Infusino I, Panteghini M. Stima dell’incertezza della misura della concentrazione di attività catalitica dell’alanina amminotransferasi (ALT) nel siero mediante il metodo di riferimento IFCC. Biochim Clin 2011;35:20–5.Search in Google Scholar
11. Rami L, Canalias F. An approach to establish the uncertainty budget of catalytic activity concentration measurements in a reference laboratory. Clin Chem Lab Med 2015;53:743–51.10.1515/cclm-2014-0579Search in Google Scholar PubMed
12. Schumann G, Bonora R, Ceriotti F, Clerc-Renaud P, Ferrero CA, Férard G, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 2. Reference procedure for the measurement of catalytic concentration of creatine kinase. Clin Chem Lab Med 2002;40:635–42.10.1515/CCLM.2002.110Search in Google Scholar PubMed
13. Schumann G, Bonora R, Ceriotti F, Clerc-Renaud P, Ferrero CA, Férard G, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase. Clin Chem Lab Med 2002;40:643–8.10.1515/CCLM.2002.111Search in Google Scholar PubMed
14. Schumann G, Bonora R, Ceriotti F, Férard G, Ferrero CA, Franck PF, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase. Clin Chem Lab Med 2002;40:718–24.10.1515/CCLM.2002.124Search in Google Scholar PubMed
15. Schumann G, Bonora R, Ceriotti F, Férard G, Ferrero CA, Franck PF, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase. Clin Chem Lab Med 2002;40:725–33.10.1515/CCLM.2002.125Search in Google Scholar
16. Schumann G, Bonora R, Ceriotti F, Férard G, Ferrero CA, Franck PF, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 6. Reference procedure for the measurement of catalytic concentration of γ-glutamyltransferase. Clin Chem Lab Med 2002;40:734–8.Search in Google Scholar
17. Schumann G, Aoki R, Ferrero CA, Ehlers G, Férard G, Gella F-J, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37°C. Part 8. Reference procedure for the measurement of catalytic concentration of α-amylase. Clin Chem Lab Med 2006;44:1146–55.Search in Google Scholar
18. Schumann G, Klauke R, Canalias F, Bossert-Reuther S, Franck PF, Gella F-J, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: Reference procedure for the measurement of catalytic concentration of alkaline phosphatase. Clin Chem Lab Med 2011;49:1439–46.10.1515/CCLM.2011.621Search in Google Scholar
19. Jones GR, Jackson C. The Joint Committee for Traceability in Laboratory Medicine (JCTLM)-its history and operation. Clin Chim Acta 2016;453:86–94.10.1016/j.cca.2015.11.016Search in Google Scholar
20. Toussaint B, Ceriotti F, Schimmel H, Rej R, Besozzi M, Gella FJ, et al. Commutability study on candidate materials for three new enzyme certified reference materials. Clin Chem Lab Med 2014;52:S1657.Search in Google Scholar
21. Panteghini M, Ceriotti F. Obtaining reference intervals traceable to reference measurement systems: is it possible, who is responsible, what is the strategy? Clin Chem Lab Med 2012;50:813–7.10.1515/cclm.2011.828Search in Google Scholar
22. Ceriotti F, Henny J, Queralto J, Ziyu S, Ozarda Y, Chen B, et al. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) in serum: results from an IFCC multicenter. Clin Chem Lab Med 2010;48:1593–601.10.1515/CCLM.2010.315Search in Google Scholar
23. Pagani F, Panteghini M. Reference interval for lactate dehydrogenase catalytic activity in serum measured according to the new IFCC recommendations. Clin Chem Lab Med 2003;41:970–1.10.1515/CCLM.2003.148Search in Google Scholar
24. Schumann G, Klauke R. New IFCC reference procedures for the determination of catalytic activity concentrations of five enzymes in serum: preliminary upper reference limits obtained in hospitalized subjects. Clin Chim Acta 2003;327:69–79.10.1016/S0009-8981(02)00341-8Search in Google Scholar
25. Ichihara K, Ceriotti F, Tam TH, Sueyoshi S, Poon PMK, Thong ML, et al. The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes. Clin Chem Lab Med 2013;51:1429–42.10.1515/cclm-2012-0421Search in Google Scholar PubMed
26. Han L, Wang J, Zhang Q, Ke P, Wu X, Wan Z, et al. Development of reference intervals for serum alkaline phosphatase among adults in Southern China traced to the new IFCC reference measurement procedure. Clin Chem Lab Med 2016;54:659–65.10.1515/cclm-2015-0732Search in Google Scholar PubMed
27. Férard G, Piton A, Messous D, Imbert-Bismut F, Frairi A, Pyonard T, et al. Intermethod calibration of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) results: application to Fibrotest and Actitest scores. Clin Chem Lab Med 2006;44:400–6.10.1515/CCLM.2006.078Search in Google Scholar PubMed
28. Xia C, Tong Q, Wang Q, Tang Z, Qi L, Chi S, et al. Application of five frozen human-pooled serum samples assigned by the international federation of clinical chemistry and laboratory medicine reference procedure in a traceability investigation of gamma-glutamyltransferase catalytic concentration measurements in China. Ann Clin Biochem 2010;47:189–94.10.1258/acb.2009.009210Search in Google Scholar PubMed
29. Dati F. The new European Directive on in vitro diagnostics. Clin Chem Lab Med 2003;41:1289–98.10.1515/CCLM.2003.196Search in Google Scholar PubMed
30. Jansen R, Schumann G, Baadenhuijsen H, Franck P, Franzini C, Kruse R, et al. Trueness verification and traceability assessment of results from commercial systems for measurement of six enzyme activities in serum. An international study in the EC4 framework of the Calibration 2000 project. Clin Chim Acta 2006;368:160–7.10.1016/j.cca.2005.12.033Search in Google Scholar PubMed
31. Jansen R, Jassam N, Thomas A, Perich C, Fernandez-Calle P, Faria AP, et al. A category 1 EQA scheme for comparison of laboratory performance and method performance: an international pilot study in the framework of the Calibration 2000 project. Clin Chim Acta 2014;432:90–8.10.1016/j.cca.2013.11.003Search in Google Scholar PubMed
32. Goossens K, Van Uytfanghe K, Thienpont LM. Trueness and comparability assessment of widely used assays for 5 common enzymes and 3 electrolytes. Clin Chim Acta 2015;442:44–5.10.1016/j.cca.2015.01.009Search in Google Scholar PubMed
33. Cattozzo G. Survey of analytical methods and result reporting for the measurement of catalytic activity of serum enzymes. Biochim Clin 2015;39:575-84.Search in Google Scholar
34. Braga F, Frusciante E, Infusino I, Aloisio E, Guerra E, Ceriotti F, et al. Evaluation of the trueness of serum alkaline phosphatase measurement in a group of Italian laboratories. Clin Chem Lab Med 2016.10.1515/cclm-2016-0605Search in Google Scholar PubMed
35. Panteghini M. Application of traceability concepts to analytical quality control may reconcile total error with uncertainty of measurement. Clin Chem Lab Med 2010;48:7–10.10.1515/CCLM.2010.020Search in Google Scholar PubMed
36. Braga F, Infusino I, Panteghini M. Performance criteria for combined uncertainty budget in the implementation of metrological traceability. Clin Chem Lab Med 2015;53:905–12.10.1515/cclm-2014-1240Search in Google Scholar PubMed
37. Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem 2011;57:1670–80.10.1373/clinchem.2011.168641Search in Google Scholar PubMed
38. Ceriotti F. The role of external quality assessment Schemes in monitoring and improving the standardization process. Clin Chim Acta 2014;432:77–81.10.1016/j.cca.2013.12.032Search in Google Scholar PubMed
39. Cobbaert C, Weykamp C, Franck P, de Jonge R, Kuypers A, Steigstra H, et al. Systematic monitoring of standardization and harmonization status with commutable EQA-samples – Five year experience from the Netherlands. Clin Chim Acta 2012;414:234–40.10.1016/j.cca.2012.09.027Search in Google Scholar PubMed
40. Sandberg S, Fraser C, Horvath AR, Jansen R, Jones G, Oosterhuis W, et al. Defining analytical performance specifications: consensus statement from the 1st strategic conference of the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2015;53:833–5.10.1515/cclm-2015-0067Search in Google Scholar PubMed
41. Ceriotti F, Fernandez-Calle P, Klee GG, Nordin G, Sandberg S, Streichert T, et al. Criteria for assigning laboratory measurands to models for analytical performance specifications defined in the 1st EFLM Strategic Conference. Clin Chem Lab Med 2017;55:189–94.10.1515/cclm-2017-0772Search in Google Scholar PubMed
42. Carobene A, Braga F, Roraas T, Sandberg S, Bartlett WA. A systematic review of data on biological variation for alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase. Clin Chem Lab Med 2013;51:1997–2007.10.1515/cclm-2013-0096Search in Google Scholar PubMed
43. Bartlett WA, Braga F, Carobene A, Coşkun A, Prusa R, Fernandez-Calle P, et al. A checklist for critical appraisal of studies of biological variation. Clin Chem Lab Med 2015;53:879–85.10.1515/cclm-2014-1127Search in Google Scholar PubMed
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