IFCC in its 60 th YEAR Achievements and Future Opportunities. Mathias M. Müller

Transcription

1 IFCC in its 60 th YEAR Achievements and Future Opportunities Mathias M. Müller

2 ADULT INFANT ELDERLY

3 ESSENTIALS IN PREANALYTICS Prevalence of a clinical condition Diagnostic guidelines Diagnostic algorithms Usefulness of a test Diagnostic validities Patient preparation Timing / frequency of testing Sample / handling of specimen Oosterhuis W. P. et al 2004

4 to use or not to use a test Decision Org. impact Clinical impact S. Sandberg Diagnostic Studies Cost effectectiveness Diagnostic Performance Technical Performance

5 ESSENTIALS IN ANALYTICS Validated measurement procedure Analytical characteristics Detection limits, sensitivity, specificity Interferences Quality assurance: bias, imprecision Laboratory requirements Turnaround time Qualification, competence of laboratorians Equipment Integrated systems

6 ANALYTICAL BIAS ± 2SD Reference Method All Routine Methods One Routine Method R. DYBKAER 1975 Quantity - Result

7 Establishment of a global needs collaboration and mutual recognition between Professionals, Metrology Institutes, Regulators, and IVD-Industry A JOINT VENTURE OF PROFESSIONALS for STANDARDISATION

8 JCTLM Joint Committee of Traceability in Laboratory Medicine Chairs: J. Thijssen, J.C. Forest, M. M: Müller Reference Measurement Procedures Certified Reference Materials Reference Laboratories A joint venture of professionals, metrology institutes, regulators and ivd-industry

9 Reference System for HbA1c HbA1c - N-(1-deoxyfructosyl)-haemoglobin-ß-chain in blood SI-Unit: mmol/mol Measurand IRMM Certification Primary reference materials (IRMM 466 and 467) Secondary reference materials (blood panels) IFCC reference measurement procedure (HPLC-CE or HPLC-MS) IFCC Network Manufacturer s working calibrator Manufacturer s internal reference measurement procedure Manufacturer s standing measurement procedure Manufacturer Manufacturer s product calibrator Patient Sample Routine measurement procedure Individual laboratory

10 JCTLM Database Result of the search for reference measurement methods/procedures: HbA1c Your search criteria: Reference measurement methods/procedures; Analyte: HbA1c; Analyte category: -; Matrix category: High performance liquid chromatography methods for HbA1c in whole blood Applicable matrice(s) Full description of technique(s) IFCC method for HbA1c (Two equivalent detection methods) whole blood Hemoglobin samples treated with endoproteinase Glu-C followed by HPLC and electrospray ionisation mass spectrometry or in a two-dimensional approach using HPLC and capillary electrophoresis with UV-detection Reference(s) Clin. Chem. Lab. Med., 2002, 40, Clin. Chem., 2000, 46, Comparability assessment study(ies) JCTLM DB identification number Reference method for diabetes control and complications trial Applicable matrice(s) Full description of technique(s) Reference(s) whole blood Cation-exchange HPLC using Bio-Rex 70 resin Goldstein, et al., Measurement of glycosylated hemoglobin: High performance liquid chromatographic and thiobarbituric acid There are two proposed reference measurement procedures listed for HbA1c. colorimetric methods. In: Methods in diabetes One, based on chromatography has been the reference used for a number of years. A research, more recent Volume procedure II: (endorsed Clinical Methods, by the IFCC) Clarke more WL, rigorously determines Larner the relative J and amounts Pohl SL, of eds. HbA1C NY: and Wiley has been and proposed Sons, Inc: to replace earlier method. The methods have , been demonstrated 1986 to correlate (precisely) with one another but result in different reference values and limits. While the IFCC recommended procedure might be considered a higher method relative to the chromatographic method, C1RMP_P17 both are higher order to a manufacturer's method. JCTLM DB identification number C1RMP_P16

11 JCTLM Database Result of the search for reference materials: HbA1c Your sear ch criteria: Higher-order reference materials; Analyte: HbA1c Sort by : Analyte Matrix/Material Organization Select Analyte Analyte category Matrix/Material Organization glycated human proteins IRMM haemoglobin haemolysate hemoglobin in HbA1c proteins HEC TEF buffer glycated haemoglobin in human haemolysate Institute for Re ference Materials and Measurements (IRMM), European Union Phone: +3 2 (0 ) jrc-irmm-rm-sales@ec.europa.eu Fax: +3 2 (0 ) Web: Name of the reference material BCR-405, glycated haemoglobin Quantity Peak area fraction (HPLC) Analyte certified/assigned value 6.29 % Expanded uncertainty 0.18 % Traceability SI CRM listing List I HbA1c in hemoglobin in buffer HECTEF Standard Reference Center Foundation (HECTEF), Japan Phone: umem@hec tef.com Fax: Web: tef-src.or.jp/ Name of the reference material JDS Lot 2, HbA1c Quantity Mass fraction Analyte certified/assigned value 4.04 % to % Expanded uncertainty 0.08 % to 0.13 % (level of confidence 95%) Reference(s) on commutability Japan Diabetes Society Survey, IFCC HbA1c WG intercomparison study Traceability SI CRM listing List I

12 Cholesterol Measurements Improved Cholesterol Measurement Accuracy Saves Health Care Dollars False Negatives False Positives % % % % %* % Untreated Unnecessary Disease Treatments Death Wasted $$$ NIST Contributions to National Reference System for Cholesterol 1967 Pure Cholesterol SRM (SRM 911) 1980 Cholesterol in Serum Definitive Method 1981 First Cholesterol in Human Serum SRM (SRM 09) 1988 New Suite of Cholesterol in Serum SRMs at MedicalDecision Points 1997 New Suite of Fresh-Frozen Serum SRMs designed to address clinical analyzer commutability issues; Total-, HDL-, and LDL-Cholesterol and Triglyceride Values Improvement in precision and accuracy since 1968 has been estimated to save $100M/yr in treatment costs Correct Value *Data from GAO and CAP

13 ESSENTIALS IN POSTANALYTICS Medical decision limits Diagnostic validities Sensitivity, specificity Predictive values Likelihood, ROC analysis Interpretation of results Intra-individual variation Critical limits Diagnostic Algorithms

14 OUTLOOK Laboratory Diagnostics Diagnosis Analytics Consolidation - Integration Expanding Diagnostic Fields Traceability - Comparison of results - CE-Label of ivd-products New Technologies Mass-Spectrometry Microarrays POCT BCA Impedance measurement Risk Assessment Gene Sequencing Medication - Individualisation Pharmacogenetics Integration of Research in Diagnostics

15 Pharmacogenetics Genetic polymorphisms influence: rate of metabolism transporter proteins Impact on pharmacodynamics Interest in: Oxidative enzymes Cytochrome P450 Thiopurinmethlytransferase (TPMT) Dihydropyrimidine dehydrogenase (DPD) Methyltetrahydrofolate reductase (MTHFR) Drug efflux pump P-glycoprotein (P-gp) in enterocytes Multiple drug resistance gene-1 (MDR-1) Impact on individual dosage requirements Legislation in Austria: No restriction like genetic testing of diseases, since pharmacogenetic testing prohibits adverse drug reactions

16 Drugs with Genetic Information in Their Labels Indication Gene or Genotype Effect of Genotype Clinical Directive on Label Abacavir HIV-1 HLA-B*5701 Hypersensitivity Screening for HLA-B*5701 Azathioprine Transplantation,rheumatoid arthritis TPMT*2, TPMT*3A, and TPMT*3C Severe myelotoxicity TPMT genotyping or Phenotyping Carbamazepine Carbamazepin Epilepsy, trigeminal neuralgia HLA-B*1502 Stevens Johnson syndrome High-resolution HLA-B*1502 typing Cetuximab Imclone Metastatic colorectal cancer KRAS mutations in codon 12 or 13 no treatment benefit Treatment not recommended in tumors with KRAS mutation. Clopidogrel Anticoagulation CYP2C19*2*3 poor metabolizers Consider alternative treatment strategies Camptosar Cancer UGT1A1*28 Diarrhea, Neutropenia Reduction in the starting dose for homozygous for the UGT1A1*28 allele Panitumumab Amgen Metastatic colorectal cancer KRAS mutations in codon 12 or 13 Efficacy not shown Treatment not reommended for colorectal cancer with these mutations. Trastuzumab (Herceptin) breast cancer, HER2 expression Efficacy: Detection of HER2 Overexpression of HER 2 is necessary for metastatic gastric cancer selection of patients herceptin therapy Warfarin Venous thrombosis CYP2C9*2*3 and VKORC1 variants Bleeding complications Therapeutic Doses Based on CYP2C9 and VKORC1 Genotypes. TPMT = thiopurine methyltransferase, UGT1A1 UDP = glucuronosyltransferase 1 family polypeptide A1 VKORC1 = vitamin K epoxide reductase complex subunit 1. K.L. Hudson, NEJM 2011: 365, 1033

17 OUTLOOK The Lab and the Health Care System Reporting & Diagnosis External Environment Hospital & Health Care Internal Environment Hospital & Health Care Patient & Doctor Analytics Workflow & Logistics The Lab is not a Factory! IMPORTANT ACTIONS OF IFCC Integration of patient data for FOR THE establishing DIAGNOSTIC individual LABORATORY diagnostic strategy Costs and benefits Improved Communication communication with external with physicians environment Evidence - based Patients diagnostic strategies - Doctors in the clinical guidelines - Hospitals Use Insourcing of LIS, HIS, of Web services informations Measurement Specialisation of outcome of labtesting in patient management

18 INTERESTS and EXPECTATIONS CLINICIANS, PATIENTS Risk assessment Diagnosis of diseases Monitoring of treatment Prognosis assessment No mutual understanding No confidence in service LABORATORIANS Analytical procedures Technologies, automation Standardisation Quality assurance Quality management Laboratory organisation workload, workflow Certification, accreditation When communicating with clinicians, one must think like a clinician! R. H. Christenson 2007

19 IFCC International Appearance Better understanding of different cultures and health care systems Zur Anzeige wird der QuickTime Dekompressor TIFF (Unkomprimiert) benötigt.

20 Zur Anzeige wird der QuickTime Dekompressor TIFF (Unkomprimiert) benötigt. Zur Anzeige wird der QuickTime Dekompressor TIFF (Unkomprimiert) benötigt.

21 Zur Anzeige wird der QuickTime Dekompressor TIFF (Unkomprimiert) benötigt.

22 WORLDLABS - EUROMEDLABS Gathering of Laboratorians to various countries

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24 IFCC will make LABS FIT for the PURPOSE LAB = DIAGNOSTIC CENTRE OF EXCELLENCE DIAGNOSTICS INFORMATICS PATIENT MANAGEMENT