National Pathology Programme

Standardisation and Harmonisation

Gifford Batstone National Pathology Programme Hosted by the Greater East Midlands Commissioning Support Unit © The Strategic Projects Team

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

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

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

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 45 44 43 42 41 40 39 38 2 male female 4 6 8 10 Age group Hosted by the Greater East Midlands Commissioning Support Unit © The Strategic Projects Team

Average Albumin by laboratory

40 38 36 34 32 30 2 50 48 46 44 42 4 6 age group © The Strategic Projects Team male 8 10 40 38 36 34 32 30 2 50 48 46 44 42 female 3 4 5 6 7 8 9 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 Jaffe - Compensated O'Leary 64 60 67 Endpoint Jaffe IDMS Value Variability 68 50 34% © The Strategic Projects Team Female, 45y, 55kg C&G (ml/min) 108.5

Carboplatin (mg) 801 85.4

90.8

81.2

80.8

109.2

34% 663 695 637 635 805 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 1800 1600 600 400 200 0 1400 1200 1000 800 490 830 415 499 869 367 364 891 480 526 890 319 478 887 370

>9xULN (HTBD) 2-9xULN (optimal) <2xULN (LTBD)

Traceability Categories from ISO 17511

Category Reference measurement procedure Primary (pure substance) reference material Secondary (value assigned) reference material 1 2 3 4 5 Yes Yes Yes No No Yes No No No No Examples Possible Possible No Yes No Electrolytes, glucose, cortisol Enzymes Hemostatic factors Proteins, tumor markers, HIV 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 2.55

2.50

2.45

2.40

2.35

2.30

2.25

2.20

2.15

2.10

2 3 4 5 6 7 8 9 10 2.55

2.50

2.45

2.40

2.35

2.30

2.25

2.20

2.15

2.10

2 3 average adjusted calcium 4 5 6 7 8 9 10 age group age group

Effect of adj to age related alb

calcium adjusted by lab mean +/- 2sd calcium re-adjusted for age differences in albumin mean +/- 2sd 30 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 28 26 24 22 20 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 18 16 14 12 10 1.8

1.9

2.0

2.1

2.2

2.3

2.4

calcium (mmol/L) 2.5

2.6

2.7

2.8

30 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 28 26 24 22 20 80 - 90 70 - 80 60 - 70 50 - 60 40 - 50 30 - 40 20 - 30 18 16 14 12 10 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 -1.0

-2.0

-3.0

3.0

2.0

1.0

0.0

Adjusted Calcium Spread of results vs mean of results > 10 % 3.0

2.5

2.0

F, age 20 -30 acceptable?

1.5

1 – 10 % 0.1 – 10 % 0 – 0.1 % 1.0

0.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.0

0.5

mean 1.0

% results lower than reference range