© The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit 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

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

© The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit 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 mU/L but ?variation - age, method Data Finlay MacKenzie UKNEQAS 09/2012

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)

© The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit Age group albumin (g/L) male female Serum Albumin Variation – Age and Sex Gary Weaving et al

© The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit age group malefemale Average Albumin by laboratory

© The Strategic Projects Team Hosted by the Greater East Midlands Commissioning Support Unit Effect of assay on dose Mike Bosomworth Female, 45y, 55kg Method Mean Creatinine (μmol/l) C&G (ml/min) Carboplatin (mg) Enzymatic Kinetic Jaffe Jaffe - Compensated O'Leary Endpoint Jaffe IDMS Value Variability34% 26%

Comparison of 5 PTH methods Mean values of NEQAS distributions of Synthetic PTH - Sanjay Khanna Reference Ranges

Taking PTH results from 1735 CKD 5 patients in Brighton; Data transformed from Roche to other analytical methods and UKRA ULN applied >9xULN (HTBD) 2-9xULN (optimal) <2xULN (LTBD)

Standardization Harmonization Traceability Categories from ISO 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

age group age group average total calciumaverage adjusted calcium Same labs Adj Calcium Females

male female male female calcium (mmol/L) calcium adjusted by lab calcium re-adjusted for age differences in albumin mean +/- 2sd Effect of adj to age related alb

Comparison of range of results produced with laboratory reference range Females age 20 – 30 yr reference range width

0 – 0.1 % 0.1 – 10 % 1 – 10 % > 10 % % results lower than reference range <1 % 1 – 10 % 10 – 20 % % < 40 % % results lower than reference range Spread of results vs mean of results spread mean F, age Adjusted Calcium acceptable?