Getting the Right Answer The Importance of Traceability

Transcription

1 Getting the Right Answer The Importance of Traceability Graham Jones MBBS, BSc, DPhil, FRCPA, FAACB Department of Chemical Pathology St Vincent s Hospital, Sydney

2 Acknowledgements

3 Contents Interpreting laboratory results Performing measurements The science and practice of Metrology How are we going? What can we do?

4 Traceability Terminology Measurement Traceability Trueness Bias (from what) (Accuracy) Getting the right answer Accurate Results for Patient Care (JCTLM)

5 Laboratory Medicine Our goal: To improve patient health Our tools: Laboratory tests Our mechanism: Support medical decisions

6 Numerical laboratory results Example: Mr Bill Bloggs (DoB 1 Jul 1950) Sample Collected: 21 Aug 2012, 10:00 am Test Result Units Serum creatinine: 125 umol/l How is this number interpreted?

7 Interpreting laboratory results All results are interpreted by comparison. Comparison may be with: A clinical decision point (literature) A population reference interval A previous result from the patient Professor Per-Hyltoft Peteresen, Sydney 2005

8 Interpreting laboratory results For Valid comparisons. Assay must be unbiased from: A clinical decision point Method(s) used in trials(s) A population reference interval Method used for Ref Int Study A previous result from the patient Method used for previous result Professor Per-Hyltoft Peteresen, Sydney 2005

9 Are Unbiased Results Important?

10 Bias: Adverse clinical effects Biased results Wrong diagnosis Wrong management Incorrect monitoring patient harm

11 Bias: Applying Evidence Comparison may be with: A clinical decision point Derived from the medical literature Comparable results required for evidence-based medicine

12 Bias: Financial issues? Unnecessary testing costs due to analytical factors (patient recalls, follow-up, treatment): Germany 1.5 Billion US$ per year German Health Report 1998 USA 7.5 Billion US$ per year Willie May, Chief Analytical Chemistry NIST Wasteful Murphy KE et al. J. Anal. At. Spectrom., 2002, 17,

13 Bias: E-Health Combining results in an Electronic Medical Record Valid only if results comparable The public expects this! IT Ready

14 Without comparable results.. Laboratory Medicine is: Not safe Not evidence-based Wasteful Not IT Ready

15 Laboratory Measurements

16 Laboratory Measurements All numerical laboratory measurements are made by comparison Analyte concentration in the sample is compared with concentration in the assay calibrators. Done using a standard curve Value assignment of calibrators establishes assay trueness (bias)

17 Materials Methods Calibration Hierarchy calib. or Traceability chain

18 Materials Methods calib.

19 Materials Methods

20 Alternative traceability chain for some in-house assays Supplier Laboratories

21 Ref A Ref B Result Method A Result Method B

22 The top of the traceability chain All assays are anchored in one of the following A Material A Method (eg Enzymes)

23 Reference Materials Certified Reference Materials Produced by National Measurement Institutes Highly purified Purity verified (and certified) Very accurately weighed (and certified) Reconstituted very accurately May also be Matrix matched eg urine, serum Values assigned by comparison with pure materials

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25 Other Reference materials International conventional calibrator Eg WHO standards Other suppliers Eg US Pharmacopoeia, commercial suppliers Manufacturer s In-house materials

26 Reference Methods For some analytes the a method defines the true result Examples: IFCC methods for AST, ALT, ALP Assays NOT calibrated with pure material For most analytes reference methods are calibrated by a material Examples: Isotope Dilution Mass Spectrometry

27 Who decides? The top of the chain is vital to accuracy. What Reference Material or Method is the top of the Traceability Chain?

28 Joint Committee on Traceability in JCTLM - Joining of: Laboratory Medicine Metrology Community (BIPM) Laboratory Medicine Community (IFCC) Accreditation Community (ILAC) Different languages, different journals, different traditions, different history Aim to bring rigour and processes of metrology to laboratory medicine

29 Metrology - BIPM Bureau International de Poids et Mesures (International Bureau of Weights and Measures) (Pont de Sevres, Paris)

30 Systeme Internationale

31 The kilogram This international prototype, made of platinum-iridium, is kept at the BIPM under conditions specified by the 1st CGPM in 1889

32 VIM International Vocabulary of Metrology Measurand Measurement Uncertainty Traceability

33 Guide to the Uncertainty of Measurement GUM

34 Measurements in general Weighing a reagent Pipetting a volume Measuring absorbance Timing a reaction These are all possible because of metrology!

35 JCTLM Output Database of higher Order Reference Materials Reference Methods Reference Laboratories Meets traceability requirements of European Union Based on ISO standards

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38 JCTLM Database

39 Further Information (

40 Traceability

41 3 Pillars of Laboratory Standardisation 1. Primary reference material 2. Primary reference method 3. Primary reference laboratory 41

42 4 Pillars of Laboratory Standardisation 1. Primary reference material 2. Primary reference method 3. Primary reference laboratory 4. External Quality Assurance Traceable, commutable 42

43 How well are we doing (1)? CK Amylase Glucose 5.7% 5.6% 3.0% 3.1% 6.1% 2.8% 3.1% Mg 1.9% Urate RCPAQAP Liquid Serum Chemistry 2016 data 2.9% 2.3%

44 How well are we doing (2)? Ferritin LH Bicarb 7.9% 11% 6.1% 9.9% 10% 5.5% 9.1% FT4 9.9% Testo RCPAQAP Liquid Serum Chemistry 2016 data 5.7% 24%

45 5 Pillars of Laboratory Standardisation 1. Primary reference material 2. Primary reference method 3. Primary reference laboratory 4. External Quality Assurance 5. Reference Intervals / Clinical Decision limits

46 URL URL URL Reference Intervals (RCPAQAP) CK Urate Amylase LRL LRL LRL

47 Common Reference Intervals Australian Project Common tests Sodium, Potassium, Calcium

48 Jones GRD, Koetsier S Ann Clin Biochem 2016

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51 Jones GRD, Koetsier S Ann Clin Biochem 2016

52 2017

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54 What can we do? Professional Organisations Manufacturers Laboratories Measurement Institutes Regulators Accreditation agencies Researchers

55 National Measurement Institutes Manufacturers Professional Organisations Laboratories

56 A Global Issue Major manufacturers: sell to all parts of the world Scientific Literature: from all parts of the world People: move round the world Needs Global solutions (where possible)

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58 NGSP: HbA1c

59 The role of Manufacturers 1. Actions Traceable to best international references (JCTLM) Good traceability practice (low uncertainty) Confirmed low bias of final product 2. Words Describe references used (JCTLM) Describe uncertainty Demonstrate quality of final product Include in IFU / sales material

60 Manufacturers: Align methods PO4 CK

61 Manufacturers Align methods Digoxin Manufacturer A Method A Manufacturer A Method B

62 Routine Laboratories Choose methods which are: Traceable to good references (JCTLM listed) Have low uncertainties for calibrators Minimise changes over time Select and promote unbiased comparators Common decision points Common reference intervals Confirm performance with traceable EQA Reduce Confusion Same units, same test names

63 Professional Organisations Local: RCPA, AACB, ASCEPT International: IFCC, WASPaLM, AACC, EFLM, APFCB, IATDMCT, JCTLM Define issues / problems Collaborate with clinicians Develop reference materials / methods Encourage uptake Engage with regulators Communication

64 Conclusions Assay traceability is vital for lab medicine Patient safety Cost effectiveness Evidence based medicine IT-application Metrology already backs most of what we do Weights, volumes, currents, lights Traceability is a global activity We all need to play our role in traceability Good results are our contribution to healthcare