1. A proposal for Derivation of Analytical Quality Goal for Precision
Nuthar Jassam
Consultant Clinical Biochemist
Harrogate

2. My Proposal
I propose to derive practical analytical quality goals that are individually tailored to the four main analytical ( Siemens, Roche COBAS, Beckman and Abbott) platforms’ true technical capability and relate the analytical performance to clinical decision.
Why?
How?

3. Setting Analytical Quality Goal
Clinical requirement/Outcome
Specifications based on biological variation
Specifications based on professional recommendations
Quality specifications laid down by EQAS organisers
Based on the state of arts
Is there a need for a new analytical goal?
Stockholm Meeting in 1999
15 years after Stockholm 2014 meeting
Scand J Clin Lab Invest 1999;59 :

4. Current Quality Goals What is the right goal?
Biological variation data ( Carmen Ricos)
CLIA
Australian MAPS
Rilibak- Germen guidelines for quality
EQA
- Different EQA schemes have apparently different limits of acceptability
Why are quality requirements different
Biological variation database and quality specifications for imprecision, bias and total error (desirable and minimum). The 2014 update.
Royal College of Pathologists of Australasia Allowable Limits of Performance.
CLIA Requirements for Analytical Quality CLIA
Rilibak - German Guidelines for Quality.

5. ? Test with a very narrow biological variation
Cas Waykamp CCLM 2016

6. Cas Waykamp CCLM 2016

7. UK data: Biological variation (Desirable)
Creatinine:< 25% of the labs meet CV of 2.7%
HbA1c: only 60% meet a CV of 2.5%
Cholesterol:100% meet a CV of
2.7%
N.Jassam et al. Clin Chem Lab Med 2013; 51(8): 1579–1584

8. My approach
One size fits all

9. Creatinine assay performance – Yorkshire ? Method dependant
NKDEP based CV
CV%
% CV range ( )

10. eGFR Bias in Yorkshire - Pilot study
The Dutch Ave bias for Jaffe methods
At creatinine of 100 umol/L
? Commutability of EQA sample at assigning the standardisation factor.
Interference in Jaffe ( Abbott)

11. Yorkshire Region: Analytical Goal for Creatinine
Case 1
50 Yr old , ? AKI
1st creat 100 µmol/L
AKI = Creat increase by Δ of 26
CV%
RCV 1%
11 umol/L 4%
13 umol/L 5%
15 umol/L
CV% vary from %
Up to CV of < 5% at Creat values < 150 has no detrimental impact on the clinical decision for AKI patients.
N.Jassam et al Clin Chem & Lab med

12. Chol =Ave TE score is 98%
Jansen R. Clin Chem Acta 2014

13. Estimation of analytical impact on clinical goal for AFP
Performance level
%CVA
% CVTotal
95% dispersion interval at AFP of 5 kU/L
Optimal 3 24
4 - 6
Desirable 6 26
Minimal 9 29
Current 13 35
3 - 7
If we run AFP in replicate, how much improvement would we achieve ?
CV Total= ± 1.96 (CVa2 / n +CVI2)1/2
Number of run
%CV Total
95% dispersion interval at AFP of 5 kU/L
Duplicate 29
( )
Triplicate 27
( )
N. Jassam et al. Ann Clin Biochem 2011: 48: 136

14. The way forward Define the ultimate goal based on the clinical need
Assess the technical capability of current technologies
Derive analytical goal incorporating current technical capabilities but addresses clinical requirements
N.Jassam et al. Clin Chem Lab Med 2013; 51(8): 1579–1584

15. Analytes General Chemistry Immunoassay Enzymes Drugs Na Ca125 AST
Digoxin K
PSA
ALT
Phenytoin Cl
Cortisol
Amylase
Creat
AFP
ALP Ca
HCG CK
Glucose
GGT
Trigs
LDH
Chol
HDL
Alb

16. Ten General chemistries: chosen due to their association for the clinical assessment of ischemic heart disease
Five immunoassay analytes : chosen as the results are clinically significant due to being used as a screen test in national guidelines, having cut off values or used for monitoring or marker of recurrence of a tumour.
Seven enzymes: chosen due to the availability of IFCC method and availability of performance data in previous studies.
Two therapeutic drugs : chosen due to clinical importance and to establish a method for setting analytical goal for drugs.

17. Method of development of analytical goal
Assessment of technical capability.
80 biochemical tests
Clinical cut off has been defined for each test
Quality specifications, mainly relevant the clinical need.
CVa < 0.25 [(2T/t-1)/(2T/t+1)]* 100
TE allowable = 1.65 (k CVI2 ) + k`(CVI2 + CVG2)1/2
where k values are; 0.25, 0.5 and 0.75
k` values are ;0.125, 0.25 and for optimal, desirable and minimal performance
Jassam N et al. Ann Clin Biochem 2011;48:

18. Required Data IQC data from 4 different analytical platforms
A single month worth of data from a single analyser
A mix of teaching and general district hospitals
IQC supplier and batch number

19. Thank you