Towards Improved Reliability in Laboratory Medicine. Universal Metrological Traceability

Transcription

1 Towards Improved Reliability in Laboratory Medicine Universal Metrological Traceability Lothar Siekmann Medical Faculty University of Bonn Institute of Clinical Chemistry and Pharmacology Reference-Institute of Bioanalytics German Society of Clinical Chemistry and Laboratory Medicine

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4 IMPACT of LABORATORY MEDICINE in MEDICAL DIAGNOSTICS About 70 % of all diagnostic medical decisions are based on results from laboratory medicine!!

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7 Measurement Traceability (VIM) property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties

8 SI-Unit Definition of the Measurand µ c (y) BIPM, CGPM Traceability Certification of a reference material (purity) Primary calibrator Secondary calibrator Manufacturer s working (master) calibrator Mf. s product calibrator Primary reference measurement procedure Secondary reference measurement procedure Manufacturer s standing measurement procedure End-user s routine measurement procedure NMI NMI, ARML NMI, ARML ARML, ML ML,ARML ML ML ML Manufacturer and/or End-user BIPM: Bureau International of Weights and Measures CGPM: General Conference on Weights and Measures NMI: National Metrology Institute ARML: Accredited Reference Measurement Laboratory ML: Manufacturer s Laboratory Routine sample RESULT End-user End-user ISO 17511

9 Joint Committee for Traceability in Laboratory Medicine Working Group I: - Reference Materials (ISO 15194) - Reference Measurement Procedures (ISO 15193) Working Group II: - Reference Measurement Laboratories (ISO 15195)

10 Identification of Reference Laboratories Reference Measurement Laboratories will be Identified - according to the metrological level of the applied reference procedures of high specificity and trueness ; - on the basis of accreditation according to ISO and ISO as reference/calibration laboratory; - on the basis of their ability to demonstrate performance in regular inter-laboratory comparisons (ring trials).

11 Zur gas-chromatographisch-massenspektrometrischen Bestimmung von Steroidhormonen in Körperflüssigkeiten unter Verwendung eines Multiple Ion Detectors (Fragmentographie) L. Siekmann, H.-O. Hoppen und H. Breuer Z. Anal. Chem. 252, (1970)

12 MEASUREMENT OF CREATININE BY ISOTOPE DILUTION MASS SPECTROMETRY SERUM Addition of [ 13 C, 15 N 2 ]Creatinine Ion Exchange Chromatography on 50W-X2 Formation of the Trimehtyl-silyl-derivative Selected Ion Recording at m/z 329 and 332 Calculation of the Creatinine Concentration from Isotope Ratios in Samples and Standard Mixtures

13 Injection Vacuum Valve Magnet Carrier gas Mass Spectrometer Ion Source Gas Chromatograph Detector M+ m/z Mass Spectrum min Selected ion recording

14 Sample ID: AMU28 Sb (5,46.33 ) 100 Acquired on 22-Jan-2003 at 21:02: SIR of 2 Channels EI e5 RT [ 15 N 2, 13 C]Creatinine TMS m/z 332 % 0 AMU28 Sb (5,46.33 ) 100 Creatinine TMS m/z SIR of 2 Channels EI e5 RT % rt

15 Sample ID: Acquired on 22-Jan-2003 at 21:02:38 AMU28 Sb (5,46.33 ) 100 [ 15 N 2, 13 C]Creatinine TMS m/z SIR of 2 Channels EI e5 RT % 0 AMU28 Sb (5,46.33 ) SIR of 2 Channels EI e5 RT Creatinine TMS m/z 329 % rt

16 Identification of Reference Laboratories Reference Measurement Laboratories will be Identified - according to the metrological level of the applied reference procedures of high specificity and trueness ; - on the basis of accreditation according to ISO and ISO as reference/calibration laboratory; - on the basis of their ability to demonstrate performance in regular inter-laboratory comparisons (ring trials).

17 ISO 15195:2002(E) ISO TC 212/SC ISO TC 212/SC /WG 2 Secretariat: ANSI Laboratory medicine Requirements for Reference Measurement Laboratories ISO/IEC 17025:1999(E) ISO/IEC 1999 INTERNATIONAL STANDARD ISO/IEC First edition General requirements for the competence of testing and calibration laboratories

18 Identification of Reference Laboratories Reference Measurement Laboratories will be identified - according to the metrological level of the applied reference procedures of high specificity and trueness ; - on the basis of accreditation according to ISO and ISO as reference/calibration laboratory, - on the basis of their ability to demonstrate performance in regular inter-laboratory comparisons (ring trials).

19 IFCC EQAS for Reference Laboratories

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29 Hierarchy of Laboratories National Metrology Institutes Accredited Reference (Calibration) Laboratories (universities, hospitals, manufacturers) Routine (Testing) Laboratories

30 Calibration and Measurement Hierarchy in Laboratory Medicine Demonstration of Competence: CIPM MRA Key Comparisons Data Base (KCDB) National Metrology Institutes Responsibility: CIPM Listed: CIPM KCDB List (Appendix C) of National Metrology Institutes Providing Calibration & Measurement Capabilities (CMCs) Services: Realizations of the SI Units providing: a) Certified Values for Reference Materials, b) Calibration and Measurement Capabilities on the Highest Metrological Level for Comparative Measurements e.g. in Ring Trials for Reference Laboratories Demonstration of Competence: a) Accreditation as Calibration Laboratories according to ISO and 15195, b) Use of JCTLM listed Reference Methods, c) Pariticipation in Ring Trials for Reference Laboratories Reference (Calibration) Laboratories Responsibility: JCTLM Routine (Testing) Laboratories Responsibility: National Regulatory Bodies Listed: JCTLM List of Reference Laboratories Services: Reference Measurement Service for a) Diagnostica Manufacturers, b) Regulatory Bodies, c) Certifying Reference Method Values for Ring Trials for Routine Laboratories Demonstration of Competence: a) Accreditation according to ISO 15189, b) Pariticipation in Ring Trials of Proficiency Testing Organisations, Reference Method Values Certified by Reference Laboratories Services: Measurement Service for Patient Samples

31 In Vitro Diagnostica Directive European Union... the traceability of values assigned to calibrators and control materials must be assured through available reference measurement procedures and/or reference materials of higher order...

32 Implementation of the Traceability Concept by - Diagnostic Kit Manufacturers - Organisers of External Quality Assessment Schemes

33 Traceable Target Values in External Quality Assessment according to the Directives of the Federal Medical Board in Germany Reference-Institute of Bioanalytics German Society of Clinical Chemistry and Laboratory Medicine

34 DGKL Reference Procedures Electrolytes: Calcium Chloride Lithium Magnesium Potassium Sodium Metabolites and Substrates: Cholesterol Creatinine Glucose Total Glycerol Uric Acid Urea Bilirubine Lactate Hormones: Aldosterone Cortisol Estradiol-17ß Estriol Progesterone 17-Hydroxy-progesterone Testosterone Thyroxine Tri-Iodothyronine Drugs: Theophylline Digoxin Digitoxin Enzymes; AST ALT CK GGT AMYLASE ALP Total Protein

35 EQA Survey Cholesterol In Serum Germany 1987

36 Cholesterol in Human Serum - DGKL- EQAS Method: CHOD-PAP Manufacturer: Kit - 38 Participants: 99 (680) mg/dl

37 DGKL- EQAS Creatinine in Human Serum Method: Jaffe Participants: 538 (711) Enzymatic 159 (711)

38 DGKL- EQAS Creatinine in Human Serum Method: Jaffe Manufacturer: Kit - 40 Participants: 18 (711) mg/dl

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41 Target Concentrations for Steroid Hormones in a Commercial Control Serum (1987) Aldosterone Cortisol Progesterone Estradiol pmol/l nmo/l nmo/l pmol/l ABBOTT AMERSHAM BAXTER DADE DIR BAXTER DADE AG ER BAXTER DADE AD EXT BIOMERIEUX BIOTEX PREMIX CAMBRID GE MEDICAL CIBA CORNING CLINICAL ASSAYS 99.3 CYBERFLUOR FIAGEN 88.2 DIAGNOSTIC PRODUCTS EURODIAGNOSTICS FARMOS DIAGN IMMUNCHEM COV. COAT LEECO MALLINCKRODT 96.6 NMS PHARMACEUTICALS PANTEX IMMUNO PANTEX IMMUNOCOAT PHARMACIA DELFIA RSL SCLAVO LISO PHASE SERONO SIBAR ELISA SORIN SYVA EMIT TECHLAND RIA 4.77 VITEK SYSTEMS 110.0

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44 Estriol 70 Deviation [%] Year

45 Estriol, unconjugated DGKL -2005/01 Selected Participants: 54(93) Test KIT 44 Ref.Method Target Values : A: 44,3 nmol/l B: 35,4 nmol/l Limits A: nmol/l B: 21,2 49,6 nmol/l

46 Unconjugated Estriol in Serum of Pregnant Women 100 Method Comparison Immunooassay Test Ki 44 nmo/l Ref.Method IDMS nmol/l

47 Estriol, unconjugated DGKL -2011/04 Selected Participants: 11(41) Test KIT 44 Ref. Method Target Values : A: 4.25 nmol/l B: 1.78 nmol/l Limits A: nmol/l B: nmol/l

48 Conclusions Implementation of the traceability concept in laboratory medicine improves accuracy and comparability of test results, avoids costs for unnecessary repetitive measurements of doubtful results, improves medical decisions for the benefit of our patients.