NORIP Concept: Nordic Reference Intervals Meeting

1. NORIP, Malmø 27/4-2004

2. NORIP, Malmø 27/4-2004 NORIP concept Common Nordic Reference Intervals NFKK meeting 27/4-2004 Pål Rustad Fürst Medical Laboratory, Oslo http://www.furst.no/norip/

3. NORIP, Malmø 27/4-2004 NORIP concept • 102 labs participated • Each lab collected samples from >25 ref. individuals evenly distributed on gender and age and froze at -80 °C • Lab received controls CAL, X, P, HIGH, LOW on dry ice • Lab measured ref. samples and controls in one series • 10 CAL and 3 of each of the other • Lab submitted • reference samples for storage in bio-bank (NOBIDA) • data on reference individual, measurement system and measurements • Reference intervals were calculated centrally

4. NORIP, Malmø 27/4-2004 Reference samplesInclusion criteria The reference individual should • be feeling subjectively well • have reached the age of 18 • not be pregnant or breast-feeding • not been an in-patient in a hospital nor been subjectively dangerously ill during the last month • not had more than 2 measures of alcohol (24 g) in the last 24 hours • not given blood as a donor in the last five months • not taken prescribed drugs other than the P-pill or estrogens (female sex hormone) during the last two weeks • not smoked in the last hour prior to blood sampling

5. NORIP, Malmø 27/4-2004 Preanalytical conditions • Reference individual • Sitting at least 15 min before sampling • Sample collection • Li-heparin plasma or serum, EDTA-blood for haematology • Standard procedure • Minimal stasis • Sample handling (plasma and serum) • Stored in the dark • Storage in room temperature before centrifugation serum: 0.5-1.5 h, plasma: max 15 min • Centrifugation: 10 min at min 1500 g • Distributed to secondary tubes within 2 h • Stored at -80 °C within 4 h

6. NORIP, Malmø 27/4-2004 ControlsCommutability and traceability • Commutability • CAL, X and P • prepared from fresh donors blood • collected in dry bags and allowed to coagulate • pooled, filtered, mixed • dispensed in polypropylene vials • frozen at –80 C without further processing • HIGH, LOW • HIGH: Pool concentrated ~1.3 times by a freeze-drying procedure • LOW: HIGH diluted 1:2 by a sodium/calcium solution • Traceability to reference methods Exceptions • non-enzymes: HDL cholesterol, TIBC • (enzymes: ALP, AMY, AMY-P, AST, LD)

7. NORIP, Malmø 27/4-2004 Transferred valuesDeviation from reference method values

8. NORIP, Malmø 27/4-2004 Creating the data poolof reference values • Correction by CAL for non-enzymes • Exclusions • methods (non IFCC for enzymes etc.) • reference individuals • quality goals (no exclusions) • large differences between materials • i.e. thawed serum against fresh serum for a reference individual • reduction of biological variation • CK (physical activity) • Glucose (fasting, diabetes in family) • Triglyceride (fasting)

9. NORIP, Malmø 27/4-2004 MeasurementInstrument manufacturers

10. NORIP, Malmø 27/4-2004 Effect of correctionCalcium: Mean of lab. reference values

11. NORIP, Malmø 27/4-2004 Comparison of distributions of not corrected and corrected ref. values Reference interval: 2.15 - 2.51 mmol/L

12. NORIP, Malmø 27/4-2004 Calculationof reference intervals • Nonparametric 2.5 and 97.5 percentiles • Partitioning <0.9% or >4.1% of subpopulation outside common reference limit • Gender • Age • Age limit(s) decided by investigating reference limits for each decade (18-29, 30-39, 40-49, 50-59, 60-69, >70 years)

13. NORIP, Malmø 27/4-2004 Reference intervalsnon-enzymes

14. NORIP, Malmø 27/4-2004

15. NORIP, Malmø 27/4-2004 Reference intervalsEnzymes

16. NORIP, Malmø 27/4-2004 Reference intervalsHaematology1800 ref. individuals from mainly Finland and Sweden

17. NORIP, Malmø 27/4-2004 Documentation • NORIP home site http://www.furst.no/norip/ • Klinisk Biokemi i Norden, no 2, 2003 • Clinical Chemistry and Laboratory Medicine (CCLM), in press • Scandinavian Journal of Clinical and Laboratory Investigation (SJCLI), in press

18. NORIP, Malmø 27/4-2004 SJCLI 1. The Nordic Reference Interval Project 2000 - recommended reference intervals for 25 common biochemical properties 2. Prerequisites for Establishing Common Reference Intervals 3. Minimally processed fresh frozen human reference sera. Preparation, Testing, and Application to International External Quality Assurance 4. The Nordic Trueness Project 2002 – Use of Reference Measurement Procedure Values in a General Clinical Chemistry Survey 5. Certificate of analysis: NFKK Reference Serum X - a reprint 6. Reference individuals, sampling conditions and treatment of samples in the Nordic Reference Interval Project for routine clinical biochemical properties 7. Descriptive analytical data and consequenses for calculation of common reference intervals in the Nordic Reference Interval Project 2000 8. Reference intervals for eight enzymes in blood of adult women and men measured in accordance with the IFCC reference system at 37°C - A part of the Nordic Reference Interval Project 2000 9. A multicenter study of reference intervals for haemoglobin, basic blood cell counts and etythrocyte indices in the adult population of Nordic countries 10. Effect of analytical quality on establishing the common reference intervals and their use 11. Are the Common Reference Intervals Truly Common? Case Studies on Stratifying Biochemical Reference Data by Countries Using Two Partitioning Method 12. Nordic Reference Interval Project Bio-bank and Database (NOBIDA). A source for future reference interval estimation and retrospective evaluation 13. Letter: Creatininium reference intervals for corrected methods

19. NORIP, Malmø 27/4-2004 Spinoff effects • Trueness verification with NFKK Reference serum X • Local • Measurement system manufacturers • Roche, Ortho (Vitros), Abbott, Konelab • Creatinine • Ortho (Vitros) back to reference method level • Creatinine-free serum from EQUALIS • NFKK projects? • Reference limits contra decision limits • Reference limits for children