LABORATORY QUALITY CONTROL

1. LABORATORY QUALITY CONTROL Course Code RIT 2.2 Revision C

2. Definitions: • Quality Control:- • the process of detecting errors • Quality Assurance:- • the systems or procedures in place to avoid errors occurring

3. … to ensure the reliability of the test results to give the best patient care !

4. Unreliable Performance ? • Potential consequences include:- • patient misdiagnosis • delays in treatment • increased costs • avoidable retests cost US 200million USD per year • Even a small calibration bias can effect treatment rates: • 1% +ve bias in cholesterol result • 5% increase in patients exceeding the treatment cut-off • 3% +ve bias • 15% increase in patient treatment.

5. Error Classification.. • Pre-analytical:- • errors before the sample reaches the laboratory • Analytical:- • errors during the analysis of the sample • Post-analytical:- • errors occurring after the analysis

6. Pre - Analytical Errors.. • Improper preparation of the patient:- • patient fasting • glucose test • stress and anxiety • urinary protein

7. Pre - Analytical Errors.. • Improper preparation of the patient • Improper collection of the blood sample:- • sample haemolysis • LDH, potassium or inorganic phosphate • insufficient sample volume • unable to carry out all requested tests • collection timing • 24 hour urine

8. Pre - Analytical Errors.. • Improper preparation of the patient • Improper collection of the blood sample • Incorrect specimen container:- • serum or plasma • fluoride tubes for glucose • to inhibit glycolysis • EDTA unsuitable anti-coagulant for calcium

9. Pre - Analytical Errors.. • Improper preparation of the patient • Improper collection of the blood sample • Incorrect specimen container • Incorrect specimen storage:- • sample left overnight at room temperature • falsely elevated K, Pi and red cell enzymes • delay in sample delivery • falsely lowered levels of unstable analytes

10. Other Factors.. • The sex of the patient • male or female • The age of the patient • new born / juvenile / adult / geriatric • Dietary effects • low carbohydrate / fat • high protein / fat • When the sample was taken • early morning urine collection pregnancy testing • Patient posture • urinary protein in bed-ridden patients

11. Other Factors.. • Effects of exercise • creatine kinase / CRP • Medical history • heart disease / diabetes / existing medication • Pregnancy • hormonal effects • Effects of drugs and alcohol • liver enzymes / dehydration

12. Analytical Errors.. • labelling • barcoding / aliquoting • preparation • centrifugation / aspiration • storage temperature • short –term refrigeration • medium term freezing at –20oC • long term freezing at -80oC • correct test selection • Laboratory Information Management System (LIMS) • The sample:

13. Analytical Errors.. • used incorrectly • contaminated • poorly calibrated • reuse of pipette tips • The sample: • Glassware / pipettes / balances:

14. Analytical Errors.. • poor quality • inappropriate storage • correct temperature • badly maintained fridges or freezers • stability • shelf-life / working reagent • incorrect preparation • The sample: • Glassware / pipettes / balances: • Reagents / calibrators / controls:

15. Analytical Errors.. • incorrect analytical procedures • poorly optimised instrument settings • The sample: • Glassware / pipettes / balances: • Reagents / calibrators / controls: • The application:

16. Analytical Errors.. • operational limitations • temperature control/read times/mixing/carry-over • lack of maintenance • worn tubing / optics / cuvettes / probes • The sample: • Glassware / pipettes / balances: • Reagents / calibrators / controls: • The application: • The instrument:

17. Other Factors.. • Calculation errors: • incorrect factor / wrong calibration values • Transcription errors: • Dilutions errors: • incorrect dilution or dilution factor used • Lack of training: • The human factor: • tiredness / carelessness / stress

18. Post - Analytical Errors.. • The prompt and correct delivery of the correct report on the correct patient to the correct Doctor. • How the Clinician interprets the data to the full benefit of the patient.

19. Accuracy ? How correct your result is.

20. Precision ? The reproducibility of your results.

21. Accurate and Precise..

22. Imprecise but Accurate !

23. Precise but Inaccurate !

24. Specificity ? • The ability of a method to measure solely the component of interest. • A lack of specificity will affect accuracy • falsely elevated values • hormones and drugs • falsely low values • BCP method with bovine albumin

25. Sensitivity ? • The ability to detect small quantities of a measured component. • will affect both precision and accuracy at the bottom end of the assay range.

26. Normal Distribution.. Mean value (x) Values fall randomly about a mean value. Frequency Measured value

27. Precision ? • How disperse the values are. • Quantified by measuring the Standard Deviation (SD) of the set of results.

28. Standard Deviation (SD).. The lower the SD the better the Precision.

29. Example: Mean result (x) = 100 mmol/L Standard deviation (SD) = 1.0 mmol/L Number of results (n) = 100

30. Mean +/- 1SD.. x -1SD +1SD Values fall randomly about a mean value. 68% Frequency 99 100 101

31. Mean +/- 2SD.. x -2SD +2SD Values fall randomly about a mean value. 95% Frequency 98 100 102

32. Which is more Precise ? Potassium SD = 0.1 mmol/L Sodium SD = 2.0 mmol/L

33. Coefficient of Variation.. A %CV takes into consideration the magnitude of the overall result.

34. Example: Sodium has the better CV and in this example is performing better than potassium. Potassium %CV = (0.1 / 5.0) x 100% = 2.0% Sodium %CV = (2.0 / 140) x 100% = 1.4%

35. 10  40 unacceptable performance 41  50 need for improvement 51  70 acceptable 71  100 good 101  120 excellent Interpretation..

36. TS Calculations V = (Result - Mean for Comparison) x 100 Mean for Comparison • The mean for comparison could be either: • the all method mean • your method mean • your instrument mean

37. TS Calculations TS = Log10 (3.16 x TCV) x 100 V TCV is Target Coefficient of Variation

38. TS Calculations TS = Log10 (3.16 x TCV) x 100 V • 3.16 is selected as a constant because: • the log10 of 3.16 is 0.5 • so if V = TCV, then the target score will be 50

39. TS = log10 3.16 x TCV x 100 V = log10 3.16 x 3.7 x 100 3.7 = log10 (3.16) x 100 = 50

40. How can Analytical Quality be Controlled ?

41. Internal Quality Control (IQC). • daily monitoring of quality control sera • External Quality Assessment (EQA). • comparing of performance to other laboratories.

42. Internal Quality Control.. • Daily monitoring • precision • accuracy • Quality control sera • results within control limits indicates that analytical systemis running satisfactorily

43. A sodium control has a target value of 140 mmol/L What is Acceptable ? 139 mmol/L 140 mmol/L 141 mmol/L 120 mmol/L 160 mmol/L 180 mmol/L Acceptable ! Unacceptable !

44. What is Acceptable ? • A range of acceptable values is established • Sodium Control:- 137  143mmol/L.

45. What are the Options ? • Unassayed serum: • the cheaper option ! • but the laboratory must establish its own ranges • cannot be used to assess accuracy ! • no externally assigned target values • Assayed serum: • with predetermined targets and ranges • established by the manufacturer.

46. Unassayed Serum.. • Analysed extensively by the laboratory. • a minimum of 20 sets of data generated • a mean +/- 2SD range established • 95% of results acceptable • some laboratories may adopt tighter ranges

47. Assayed Serum.. • Targets and ranges generated by the manufacturer: • abc utilises RIQAS • database of 5,000 laboratories • method / instrument / temperature specific values

49. Levey Jennings Chart +2SD 143 +1SD 141.5 X X X X X X Mean X 140 X X X X X X X X -1SD 138.5 X X -2SD 137

50. Levey Jennings Chart +2SD 143 +1SD 141.5 X X X X X Mean X 140 X X X X X X X X X X -1SD X 138.5 -2SD 137