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

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?

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 : 475-585

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. http://www.westgard.com/biodatabase-2014-update.htm Royal College of Pathologists of Australasia Allowable Limits of Performance. http://www.westgard.com/rcpa-australasian-quality-requirements.htm CLIA Requirements for Analytical Quality. http://www.westgard.com/search.htm?ordering=newest&limit=20&searchword= CLIA Rilibak - German Guidelines for Quality. http://www.westgard.com/rilibak.htm.

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

Cas Waykamp CCLM 2016

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

My approach One size fits all

Creatinine assay performance – Yorkshire ? Method dependant NKDEP based CV CV% % CV range ( 1.68 -6.9)

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)

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 1.7- 7% 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 2014

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

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 4 - 6 ( 3.55- 6.45) Triplicate 27 4 - 6 ( 3.65 - 6.35 ) N. Jassam et al. Ann Clin Biochem 2011: 48: 136

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

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

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.

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 0.375 for optimal, desirable and minimal performance Jassam N et al. Ann Clin Biochem 2011;48:136-46.

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

Thank you