Standardisation and Harmonisation

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

National Pathology Programme

Standardisation and Harmonisation

Gifford BatstoneNational Pathology Programme


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


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


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

TSH values: Geometric Mean before (A) and after (B) mathematical recalibration16 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 HormoneThienpont L et al; Clinical Chemistry 56:6 902–911 (2010)


20 -

30

30 -

40

40 -

50

50 -

60

60 -

70

70 -

80

80 -

90

Age group

38

39

40

41

42

43

44

45

46

2 4 6 8 10

albu

min

(g/L

)

male

female

Serum Albumin Variation – Age and Sex Gary Weaving et al


20 -

30

30 -

40

40 -

50

50 -

60

60 -

70

70 -

80

80 -

90

30

32

34

36

38

40

42

44

46

48

50

2 4 6 8 10

albu

min

(g/L

)

30

32

34

36

38

40

42

44

46

48

50

2 3 4 5 6 7 8 9 10

20 -

30

30 -

40

40 -

50

50 -

60

60 -

70

70 -

80

80 -

90

age group age group

male female

Average Albumin by laboratory


Effect of assay on doseMike Bosomworth

Female, 45y, 55kg Method Mean Creatinine (μmol/l)

C&G (ml/min)

Carboplatin (mg)

Enzymatic 50 108.5 801Kinetic Jaffe 64 85.4 663Jaffe - Compensated 60 90.8 695O'Leary 67 81.2 637Endpoint Jaffe 68 80.8 635IDMS Value 50 109.2 805Variability 34% 34% 26%

Comparison of 5 PTH methodsMean values of NEQAS distributions of

Synthetic PTH - Sanjay Khanna

Reference Ranges

1.17- 9.221.59 - 7.271.48 - 7.631.27 - 9.331.59 - 6.89

Taking PTH results from 1735 CKD 5 patients in Brighton; Data transformed from Roche to other

analytical methods and UKRA ULN applied

Abbot Architect

Beckman Access

Roche Elecsys

Siemens A Centaur

Siemens I2000 Fam.0

200

400

600

800

1000

1200

1400

1600

1800

415 367480

319 370

830 869

891

890887

490 499364

526 478

No.

of C

KD st

age

5 pa

tient

s

>9xULN (HTBD)

2-9xULN (optimal)

<2xULN (LTBD)

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

4 No No Yes Proteins,

tumor markers, HIV

5 No No No Proteins,

EBV, VZV

3 Yes No No Hemostatic factors

Sta

ndar

diza

tion

Harmonization

Traceability Categories from ISO 17511

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

2.10

2.15

2.20

2.25

2.30

2.35

2.40

2.45

2.50

2.55

2 3 4 5 6 7 8 9 10

calc

ium

(mm

ol/L

)

2.10

2.15

2.20

2.25

2.30

2.35

2.40

2.45

2.50

2.55

2 3 4 5 6 7 8 9 10

calc

ium

(mm

ol/L

)

20 -

30

30 -

40

40 -

50

50 -

60

60 -

70

70 -

80

80 -

90

age group

20 -

30

30 -

40

40 -

50

50 -

60

60 -

70

70 -

80

80 -

90

age group

average total calcium average adjusted calcium

Same labs Adj Calcium Females

10

12

14

16

18

20

22

24

26

28

30

1.8 1.9 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.810

12

14

16

18

20

22

24

26

28

30

1.8 1.9 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8

20 - 3030 - 4040 - 5050 - 6060 - 7070 - 8080 - 90

20 - 3030 - 4040 - 5050 - 6060 - 7070 - 8080 - 90

20 - 3030 - 4040 - 5050 - 6060 - 7070 - 8080 - 90

20 - 3030 - 4040 - 5050 - 6060 - 7070 - 8080 - 90

mal

efe

mal

e

mal

efe

mal

e

calcium (mmol/L) calcium (mmol/L)

calcium adjusted by lab calcium re-adjusted for age differences in albumin

mean +/- 2sdmean +/- 2sd

Effect of adj to age related alb

-3.0

-2.0

-1.0

0.0

1.0

2.0

3.0

0.00 1 0.00 2 0.00 3 0.00 4 0.00 5 0.00 6 0.00 7 0.00 8 0.00 9 0.00 1 00.00

Comparison of range of results produced with laboratory reference range

Females age 20 – 30 yr

refe

renc

e ra

nge

wid

th

0 – 0.1 %

0.1 – 10 %

1 – 10 %

> 10 %

% re

sults

low

er th

an re

fere

nce

rang

e

<1 %

1 –

10 %

10 –

20

%

20 -

40 %

< 40

%

0.0

0.5

1.0

1.5

2.0

2.5

3.0

-3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0

% results lower than reference range

Spread of results vs mean of results

spre

ad

mean

F, age 20 -30Adjusted Calcium

acceptable?

Documents

Standardisation and Harmonisation