National Pathology Programme Standardisation and Harmonisation Gifford Batstone National Pathology Programme © The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit April TRUD Release • Revised list of units of measurement • PBCL and NLMC • New entries – 294 • Inclusion of sample type • Corrections to names eg BNP • Deletions – 299 • Duplications • Linked to corrections © The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit Supplementary File • Guidance at present/mandatory in future • Linking analytes (with analysed specimen type) to a single unit of measurement • Addition of Data Combination Indicators • • • • • 0 = test not used to trend 1 = OK to assume combination 2 = requires a factor 3 = don’t even think about it 4 = not yet agreed © The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit Why? - PQAR ‘The continued development of the NLMC to ensure consistency of data and information across the NHS in England should remain a priority. The professional bodies, the IVD manufacturers and others should work towards minimising the differences between analytical processes, requesting and reporting.’ Recommendation 4.66 Pathology Quality Assurance Review Why? - PQAR ‘Laboratory processes should be harmonised so that patients can be confident about the consistency of their test results, especially as they start to gain access to their personal health records that may contain reports from different pathology services’ Press Release, Pathology Quality Assurance Review Ref Range Variation • Self reported reference intervals for TSH and fT4. • Each bar represents a different laboratory • Each colour represents a single analytical method • Statistical analysis 750,000 TSH reports gives 0.5 - 5.5 mU/L but ?variation - age, method • Data Finlay MacKenzie UKNEQAS 09/2012 © The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit TSH values: Geometric Mean before (A) and after (B) mathematical recalibration 16 immunoassays from 9 different manufacturers analysing the same sample in triplicate. Report of the IFCC Working Group for Standardization of Thyroid Function Tests; Part 1: Thyroid-Stimulating Hormone Thienpont L et al; Clinical Chemistry 56:6 902–911 (2010) Serum Albumin Variation – Age and Sex Gary Weaving et al 46 male albumin (g/L) 45 44 43 female 42 41 40 39 38 10 80 - 90 70 - 80 8 60 - 70 50 - 60 6 40 - 50 30 - 40 4 20 - 30 2 Age group © The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit Average Albumin by laboratory 50 male 48 48 46 46 44 44 42 42 40 40 38 38 36 36 34 34 32 32 30 female age group © The Strategic Projects Team 7 8 9 80 - 90 6 70 - 80 5 60 - 70 4 50 - 60 3 40 - 50 2 30 - 40 10 20 - 30 80 - 90 8 70 - 80 6 50 - 60 40 - 50 30 - 40 4 60 - 70 30 2 20 - 30 albumin (g/L) 50 10 age group Hosted by the Greater East Midlands Commissioning Support Unit Effect of assay on dose Mike Bosomworth Method Mean Creatinine (μmol/l) Enzymatic 50 Kinetic Jaffe 64 Jaffe - Compensated 60 O'Leary 67 Endpoint Jaffe 68 IDMS Value 50 Variability 34% © The Strategic Projects Team Female, 45y, 55kg C&G Carboplatin (ml/min) (mg) 108.5 801 85.4 663 90.8 695 81.2 637 80.8 635 109.2 805 34% 26% Hosted by the Greater East Midlands Commissioning Support Unit Comparison of 5 PTH methods Mean values of NEQAS distributions of Synthetic PTH - Sanjay Khanna Reference Ranges 1.17- 9.22 1.59 - 7.27 1.48 - 7.63 1.27 - 9.33 1.59 - 6.89 Taking PTH results from 1735 CKD 5 patients in Brighton; Data transformed from Roche to other analytical methods and UKRA ULN applied No. of CKD stage 5 patients 1800 1600 490 499 >9xULN (HTBD) 364 526 478 1400 1200 <2xULN (LTBD) 1000 891 800 830 869 415 367 890 887 600 400 200 0 2-9xULN (optimal) 480 319 370 Traceability Categories from ISO 17511 Standardization Category Reference measurement procedure Primary (pure substance) reference material Secondary (value assigned) reference material Examples 1 Yes Yes Possible Electrolytes, glucose, cortisol 2 Yes No Possible Enzymes 3 Yes No No Hemostatic factors 4 No No Yes Proteins, tumor markers, HIV 5 No No No Proteins, EBV, VZV Harmonization Miller 2012 Standardisation of Reports The emphasis is on the reports More than one approach: • Standardisation of analytical techniques • Use of WHO and similar reference materials • Mathematical alignment of methods – Mean values of different methods • Where no international reference materials – To WHO reference based methods Questions and Comments please Same labs Adj Calcium Females average total calcium average adjusted calcium 2.55 2.50 2.45 2.45 2.40 2.40 calcium (mmol/L) 2.50 2.35 2.30 2.25 2.35 2.30 2.25 2.20 2.20 2.15 2.15 2.10 5 6 7 age group 8 9 80 - 90 4 70 - 80 3 60 - 70 2 50 - 60 10 40 - 50 9 30 - 40 60 - 70 age group 8 20 - 30 7 80 - 90 6 70 - 80 5 50 - 60 4 40 - 50 3 30 - 40 2.10 2 20 - 30 calcium (mmol/L) 2.55 10 Effect of adj to age related alb calcium adjusted by lab calcium re-adjusted for age differences in albumin mean +/- 2sd mean +/- 2sd 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 30 22 80 - 90 70 - 80 28 60 - 70 50 - 60 26 40 - 50 30 - 40 24 20 - 30 20 20 28 female 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 26 24 22 18 male male female 30 16 14 12 12 10 1.8 80 - 90 70 - 80 18 60 - 70 50 - 60 16 40 - 50 30 - 40 14 20 - 30 10 1.9 2.0 2.1 2.2 2.3 2.4 calcium (mmol/L) 2.5 2.6 2.7 2.8 1.8 1.9 2.0 2.1 2.2 2.3 2.4 2.5 calcium (mmol/L) 2.6 2.7 2.8 Comparison of range of results produced with laboratory reference range Females age 20 – 30 yr 3.0 reference range width 2.0 1.0 0.0 -1.0 -2.0 -3.0 Spread of results vs mean of results 3.0 acceptable? > 10 % 2.0 1.5 1 – 10 % 1.0 0.1 – 10 % 0.5 0 – 0.1 % mean -1.5 -1.0 -0.5 0.0 % results lower than reference range 0.5 1.0 <1 % -2.0 1 – 10 % -2.5 10 – 20 % -3.0 20 - 40 % 0.0 < 40 % % results lower than reference range 2.5 F, age 20 -30 spread Adjusted Calcium