Reference Intervals. Graham Jones / Gus Koerbin

Transcription

1 Reference Intervals Graham Jones / Gus Koerbin

2 Adult CRI - Harmonisation Harmonisation : (13 tests + 1 calculation) Harmonisation : Confirm 2012 recommendations. Discussed: albumin, globulin, AST & ALT (+/- P5P), GGT, bilirubin, Lipase (KC, GC). Aussie normal, Bias 2 study (GK) Harmonisation : summary of data used for decision making and between lab analytical differences (AoN, local and international). Flagging rates for common analytes on different systems raw data included (KS). IMPLEMENT! Next analytes: Albumin, globulin, bilirubin, GGT, lipase Harmonisation : ALT x 40 (M); X-35 (F) X=5? (Non-P5P) AST x -35 (M), x 30 (F) (Non P5P) X=5? Albumin: recommend age-related. Bilirubin: x-20 (labs to decide X) Data for CK, GGT, Lipase, Urea Harmonisation : Uptake of CRI (1 st set of analytes), baseline for 2 nd set of analytes) Next analytes: albumin, urea, TF, blood gases, FBC, Common intervals (GC) Harmonisation : Urea intervals recommended Discussion on: blood gases, iron studies

3 Adult CRI - Publications Tate et al. for AACB WP on CRI. Harmonising adult and paediatric common reference intervals in Australia and New Zealand for a first panel of chemistry analytes. Clin Biochem Rev 2014;35: Vasikaran et al. Harmonised Australian Reference Intervals for Serum PINP and CTX in Adults. Clin Biochem Rev 2014;34(4): Graham Jones and Sabrina Koetsier. RCPAQAP First Combined Measurement and reference interval survey. Clin Biochem Revs 2014: Jones GRD, Koetsier S. Uptake of recommended common reference intervals for chemical pathology in Australia. Ann Clin Biochem 2017;54: G Jones, K Sikaris, Jan Gill. Allowable Limits of Performance for External Quality Assurance Programs an Approach to Application of the Stockholm Criteria by the RCPA Quality Assurance Programs. Clin Biochem revs. 2012;33: Koerbin G et al. for AACB WP on CRI. Harmonising Adult Reference Intervals Mini-Review Harmonising Adult Reference Intervals in Australia and New Zealand the Continuing Story. Clin Biochem rev 2016;37:131-4 [CK, ALT, AST, GGT, Lipase] Maxine Reed. The New Zealand Approach to harmonised reference intervals. Clin Biochem Revs, 2012;33: Gus Koerbin et al for AACB WP on CRI. Bias Assessment of General Chemistry Analytes using Commutable Samples. Clin Biochem Revs 2014;35: Graham Jones, Reiner Haeckel, Alex Katayev, Y. Ozarda, Tze Ping Loh, Ken Sikaris IFCC C- RIDL: Indirect methods for reference interval determination - Review and recommendations. CCLM 2018

4 Paediatric CRI Harmonisation : proposed paediatric reference intervals (7 tests) Harmonisation : Confirmed 2012 recommendations. Harmonisation : common analytes data mining data available on line!! Age partitioning definitions (RF) Harmonisation : TFT (Caliper + manufacturers), Ammonia Harmonisation : Update (Tina Yen) sweat testing, ammonia, benchmarking, dynamic testing, AMH, neonatal bilirubin, egfr (Schwartz), new analytes

5 Pregnancy CRI Harmonisation : proposed pregnancy reference intervals (16 tests + 2 calculations) Harmonisation : Detailed data (Na, K, Cl, urea, creatinine, osmolality, AG, bicarbonate) (N Hadlow). Conclusions: Na ; Cl ; K (serum); urea ; creat Timing of gestation (Peter Ward) recommendations Rasied: urate, AG, bicarbonate, albumin, FBC, urine protein, urine albumin Harmonisation : Proposed intervals and flagging rates. Raw data available (KS) Harmonisation : TFT (Zhong Lu, Ken Sikaris) Harmonisation : (Zhong Lu, Ken Sikaris) Thyroid function testing in pregnancy (Dr Simon Forehan) Pregnancy RI review (Ken Sikaris); LIS issues (Tina yen) Publications Narelle Hadlow and Ken Sikaris. Aspects to consider in adopting pregnancy specific reference intervals. Clin Biochem Revs 2015;36: Alan McNeil and Phoebe Stanford. Reporting thyroid function tests in pregnancy. Clin Biochem Revs. 2015;36:109-26

6 Reference Interval harmonisation DATA FOR KEY COMPONENTS Methods give close enough results EQA data, GKs sample swap, average of normal data Reference interval to share Data from manufacturers; Aussie normals, current lab usage (EQA); literature; data mining (Sonic + others) Effect of intervals Flagging Rates

7 1 st Common Reference Intervals Clinical Biochemist Reviews 2014;35:

8 Analyte Male Female Calcium Phosphate Magnesium LDH [L to mmol/l mmol/l mmol/l U/L P]IFCC Sodium Potassium Chloride Bicarbonate mmol/l mmol/l mmol/l mmol/l Creatinine umol/l umol/l ALP U/L AST <40 <35 ALT <40 <30 Total Protein g/l

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10 Jones GRD, Koetsier S Ann Clin Biochem 2016

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13 Jones GRD, Koetsier S Ann Clin Biochem 2016

14 2017

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16 Common Reference Intervals Actual

17 Why Not? Unaware Not important enough / too busy No problems here mate! Insufficient evidence Specific scientific objection Unable to get local agreement Keep local customers happy Were we wrong before? Multiple factors

18 Manufacturers - Instruments

19 Sodium 83% 90%

20 Sodium (average of normal)

21 Potassium (yellow = OCD) 92% 57%

22 Magnesium 90% 72%

23 Bicarbonate 75% 90%

24 Bicarbonate LSC 2017 DIFFERENCE FROM MEDIAN (mmol/l) Abbott Siemens Advia Siemens Dade Roche Hitachi Ortho Beckman AU DIFFERENCE / Reference interval Width Abbott Siemens Advia Siemens Dade Roche Hitachi Ortho Beckman AU

25 Phosphate (yellow = OCD) 56% 90%

26 ALP (Beckman AU in Yellow) ~70% ~45%

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28 CK (OCD in yellow) CRI: U/L (M <60 years) 30%

29 ALT (no P5P in yellow) CRI: 5 35 U/L (female) <5%

30 GGT CRI: 5 50 U/L (male) 28% 45%

31 Lipase CRI: U/L 15% 40%

32 Common Reference Intervals nd round

33 Urea M40 F40

34 Albumin (BCP in yellow)

35 Iron

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37 Calculations WP 2017 Meeting

38 Anion Gap (with K) (75/89) AG: Siemens Advia (median = 13) AG: Roche Hitachi (median = 21)

39 Anion Gap Liquid Serum Chemistry - sample Siemens Advia Siemens Dade Abbott Beckman AU OCD Roche Hitachi Median Mean S.D %CV 19% 12% 10% 14% 10% 10% Pred CV 6% 4% 6% 5% 3% 6%

40 Calculations WP 2017 Meeting

41 Calculations WP 2017 Meeting

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43 Calcium

44 Bicarbonate

45 Chloride

46 egfr

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49 Cholesterol

50 HDL Cholesterol

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52 Adult Reference Intervals Urea Recommendations Common reference intervals for Urea (all) (methods suitable) Age and sex related intervals (17:3; Aust v NZ) Intervals:

53 Adult Reference Intervals Iron Studies Iron Can share intervals (assays suitable based) Limited data on methods Data mining less useful Reference interval studies difficult NSW Health Pathology Have compared methods Have surveyed intervals Prepared to share information (thank you)

54 S1 S2 Albumin g/l Amylase U/L Cholesterol mmol/l Creatinine umol/l Glucose mmol/l Lactate U/L LDH U/L Lipase U/L Osmolality mmol/kg ph Protein g/l Sodium mmol/l Triglycerides mmol/l

55 Albumin Body Fluids Pilot

56 Amylase Body Fluids Pilot

57 Glucose Body Fluids Pilot

58 Lactate Body Fluids Pilot

59 Total protein Body Fluids Pilot

60 Triglycerides Body Fluids Pilot

61 CEA Body Fluids Pilot

62 Triglycerides Mid -2SD +2SD Target Max between method bias 0.2 mmol/l

63 Total Cholesterol Mid -2SD +2SD Target Max between method bias 0.7 mmol/l ( )

64 HDL Cholesterol Mid -2SD +2SD Target Max between method bias 0.25 mmol/l ( )

65 Non-HDL Cholesterol Mean Average -2SD +2SD

66 LDL Cholesterol