Evidence Based Commutability: Bias 2 Study. Janice Gill Manager RCPAQAP Chemical Pathology Adelaide SA

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1 Evidence Based Commutability: Bias 2 Study Janice Gill Manager RCPAQAP Chemical Pathology Adelaide SA

2 Australian Bias Studies conducted by Gus Koerbin, ACT Pathology on behalf of AACB Harmonisation Committee Bias 1 Study Aim to assess between method bias to see whether it would be possible to use a common reference interval for an analyte Conducted in Australasian labs analysed 33 serum samples for 27 common analytes Na K Cl urea creatinine Ca Mg PO 4 ALT AST CK LD GGT Na, K, Cl, urea, creatinine, Ca, Mg, PO 4, ALT, AST, CK, LD, GGT, ALP, total protein, albumin, urate, cholesterol, triglycerides, HDL cholesterol, CRP, iron, transferrin, lipase, glucose, total bilirubin, bicarbonate

3 Bias 1 Study 8 major chemistry platforms Abbott Architect, Roche Modular, Roche Integra, Beckman Coulter (Dx Series), Beckman Coulter (Olympus), Siemens Advia, Siemens Dimension, OCD Vitros Provided reagent manufacturer & lot no., QAP method code, calibrator manufacturer, lot no. traceability, analyser age Labs asked kdto assay the appropriate QAP samples concurrently However the return on the QAP data was too low to analyse

4 Bias 1 Study Patient Samples Results reviewed using RCPAQAP Allowable Limitsof Performance (ALP) Analytes aytescass classified edusing the eta traffic light tsystem Green All results fall within the ALP Regression line does not cross the ALP within the current RI Amber No more than 4 results fall outside the ALP Regression line does not cross the ALP within the current RI Red Greater than 4 results fall outside the ALP Regression crosses the ALP within the current RI

5 Bias 1 Study Sodium Cholesterol Albumin Bicarbonate Potassium Triglycerides ALT Total Bilirubin Chloride HDL AST GGT Creatinine Glucose CRP (Vitros LOD) LD Iron Urea (DxC) Lipase Total protein Adjusted Ca Mg CK Transferrin (units) Urate (RxL) PO4 (Vitros) ALP (Vitros, AU2700)

6 Bias 2 Study An extension of Bias1 Post 2012 Harmonisation Workshop To provide evidence on someofof the questions raised by the workshop 30Labs, 9 frozen serum samples with extended concentration ranges where possible Plus 5 levels of RCPAQAP General Serum Chemistry samples 22 analytes, including ferritin, TSH, Free T4, Total PSA

7 Bias 2 Study Sodium (DXc) Cholesterol Albumin (BCP/BCG, cobas) Total Bilirubin (samples) Potassium Ti Triglycerides id ALT (P 5 P) P) GGT (methods) ( serum/plasma) Chloride HDL AST (P 5 P) LD (methods) Creatinine Glucose CRP (Vitros LOD) Lipase (methods) Iron Urea (DxC) Ferritin Total protein Urate (RxL) TSH Adjusted Ca (calculation) Mg CK Transferrin (units) PO4 (Vitros) ALP (Vitros, AU2700) Bicarbonate (Architect) t) FT4

8 Bias 2 Study An opportunity to compare patient vs QAP samples to investigate whether the QAP material is commutable Comparison against combined data of Bias 1 & 2

9 Sodium - Patient Samples Sodium DXc slightly lower than other instruments Ob btained (mmo ol/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Integra Roche Cobas Siemens Dimension Vitros Fusion Low ALP High ALP Linear (Low ALP) Linear (High ALP) Average (mmol/l)

10 Sodium QAP Samples (mmo140.0 Ob btained ol/l) DXc within ALP Vitros >145mmol/L Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Vitros Fusion Low ALP High ALP Linear (Vitros Fusion) Linear (Low ALP) Linear (High ALP) Median (mmol/l)

11 Urea Patient Samples Urea Obtain ned (mmol/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Integra Roche Cobas Siemens Dimension Vitros Fusion Low ALP High ALP Average (mmol/l) DxC slightly lower than other instruments at lower concentrations

12 Urea QAP Samples Ob btained (mmo ol/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Vitros Fusion Low ALP High ALP Median (mmol/l) DXcwithin ALP

13 Creatinine Patient Samples (umo180.0 Ob btained l/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Integra Roche Cobas Siemens Dimension Vitros Fusion Low ALP High ALP Median (umol/l)

14 Creatinine QAP Samples l/l) Ob btained (umo Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Vitros Fusion Low ALP High ALP Median (umol/l) Architect, cobas at higher concentrations

15 ALT Pyridoxal-5-Phosphate Activator Positive bias with methods using P 5 P P as an activator Bias less pronounced with ALT concentrations >30 IU/L (15 32%) 60.0% 48.0% Differrence e (%) Platform - Average 36.0% 24.0% 12.0% 0.0% -12.0% -24.0% ALT (U/L) Assays using P-5-P P activation Assays not using P-5-P activation

16 ALT Patient Samples Siemens ADVIA Obtained (IU/L L) Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Architect P5P Vitros P5P Average (IU/L)

17 ALT QAP Samples Obtained (IU/L L) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Architect P5P Linear (High ALP) Median(IU/L)

18 Calcium Patient Samples Ob btained (mmo ol/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Integra Roche Cobas Siemens Dimension Vitros Fusion Linear (ALP Low) Average (mmol/l)

19 Calcium QAP Samples Ob btained (mmo ol/l) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Vitros Fusion Average (mmol/l)

20 GGT Patient Samples Obtained (U/L L) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Integra Roche Cobas Siemens Dimension Vitros Fusion Low ALP High ALP Linear (Low ALP) Linear (High ALP) Average (U/L) Glutamyl 4 nitroanilide Substrate

21 GGT QAP Samples Obta ained (IU/L) Siemens ADVIA Abbott Architect Beckman Coulter AU Beckman Coulter DxC Roche Cobas Vitros Fusion Low ALP Median (IU/L)

22 Commutability Do the QAP samples behave in different methods with the same numerical relationship as is seen with patient samples? Not a simple yes/no answer Yes for some analytes eg GGT DxClow in patient and QAP samples For some analytes, the majority of methods behave in the same manner but 1 method may not eg DxC sodium low in patient samples but not in QAP RCPAQAP Chemical Pathology

23 Commutability How to evaluate this data? Evaluate using the same criteria as Bias Study Allowable Limits of Performance If a method is outside the ALP in patient samples; is it also outside the ALP in QAP samples? And vice versa Classify according to the traffic light system Green = agreement Orange = 1 method different Red = >1 method different RCPAQAP Chemical Pathology

24 QAP Samples Commutability Potassium Urate (DxC) Sodium (Vitros,DxC) Chloride Urea (DxC in) Albumin (BCP vs BCG) Bicarbonate ALP (DxC) Phosphate (Vitros, DxC) Creatinine ALT (P5P) Iron (DxC, Vitros, AU) Calcium AST (P5P) LD Magnesium Total Protein GGT Ferritin Transferrin ft4 TSH PSA Not Performed T Bilirubin (low pt samples) Glucose CK Cholesterol Triglyceride HDL Lipase CRP

25 Lyophilised QAP Samples Advantages Increased concentration ranges Linearly related End of cycle statistics Ease ofstorage Stable samples Transportation globally Disadvantages Not commutable for all analytes

26 Fresh Patient Samples Advantages Commutable material Disadvantages Limited concentration ranges Statistical summaries difficult Collection challenges Volume challenges Globaltransport difficulties

27 The Way Forward Lyophilised material Supplemented with fresh patient samples General Serum Chemistry + Liquid Serum Chemistry Glycohaemoglobin Lyophilised + Fresh Whole Blood Immunosuppressant Lyophilised + Fresh Whole Blood

28 Acknowlegements Gus Koerbin AACB Harmonisation Committee All the participating laboratories RCPAQAP Chemical Pathology