Basic Issues In Laboratory Quality Assurance

1. Basic Issues In Laboratory Quality Assurance By Mohamed Hanafy M.B,B.Ch., M.Sc., M.D.,Clin. Path. Lecturer Of Hematology Al-Azhar Faculty Of Medicine - Demiatte Certificate OF Program Office for Laboratory Quality Management Department of Pathology and Laboratory Medicine University of British Columbia - Canda

2. LABORATORY CYCLE 1 Quality control (QC) 2 Internal Quality Control 3 WestgardMultirules 4 Types Of IQC Errors 5 6 MAIN POINTS Content

3. What can we do about the errors? Quality Management Quality Improvement Quality System Quality Assurance Quality Control

4. Quality control (QC) is a system used to maintain a determined level of accuracy and precision. Proper quality control helps ensure that reported results of patient laboratory testing are correct. Quality control applies not only to specimen testing, but also to collection, storage, and transportation . Quality control procedures are performed in a clinical laboratory to help the laboratorians ensure that patients' results are reliable. Reliability refers both to accuracy (how close a test is, on average, to patients' true results) and precision (the consistency of tests performed at different times).

5. Quality System Quality Assurance Quality Control

6. LABORATORY CYCLE

7. Quality system begins and ends with the patient

8. Pre-examination Processes

9. Examination Processes

10. Post-examination Processes

11. Internal and External Quality Control • Internal Quality Control Internal quality control is set up within a laboratory to monitor and ensure the reliability of test results from that laboratory. • The primary tool for internal quality control is called a control. A control is a specimen with a predetermined range of result values, called control values, that is processed in the same manner as a patient sample. • Control samples are processed with each series or run of patient samples.If the result of a test on a control sample is different from its known value, this indicates a problem in the equipment or the methods being used.

12. Internal Quality Control Program An internal quality control program depend on the use of internal quality control (IQC) specimens, Shewhart Control Charts, and the use of statistical methods for interpretation. Internal Quality Control Specimens IQC specimens comprises either (1) commercial products or (2) Home-made

14. Control Materials • Control materials are made to match patient samples in physical and chemical characteristics. Control samples are often made with biological material.Control samples are tested in the same way as patient samples. If the results from testing a control sample are not within the acceptable ranges, we assume there has been a problem in the test procedure, equipment, or the samples themselves. There are many criteria for rejecting a test based on the control samples measurements. • Patient results are not reported until the cause of the problem has been found, the problem resolved, and the controls re-run to verify that everything is working normally.

15. Quality Control Methods • Assayed or Unassayed stabilized material (Commercial) • Previously analyzed patient samples • Easily obtained • Cost effective • Results and samples readily available

16. QC Methods: Assayed or Unassayed Stabilized Material • Commercially available • Known values (Assayed only) • Analyze low, normal and high control • Results stored in the instrument computer (Pentra only) • Monitored with Levy-Jennings charts • - Easily illustrates trends and shifts

17. Assayed and Unassayed Controls • Commercially prepared controls come in either assayed or unassayed forms. Assayed controls are tested by multiple methods before sale, and are sold with the results of the tests. Assayed controls: • are more expensive than unassayed controls • are used to evaluate accuracy and precision • avoid laboratory errors in determining control values • may only be suitable for specific methods or conditions • While the manufacturer's control values can be used to some extent to measure accuracy, the best measure of accuracy is certified reference material.

18. Unassayed controls • are not tested by the manufacturer before they are sold. The control values for these materials must be determined by the individual laboratory. Unassayed controls: • are less expensive than assayed controls • are used to evaluate precision only • avoid manufacturer error in determining control values • control values are customized to the laboratory's own methods and conditions • A final note: although commercially available control materials are screened for hepatitis antigens and HIV antibodies, control materials should still be handled with precautions, since they contain biological materials and could contain infectious agents.

19. Use of Controls • An internal quality control program must monitor results in the normal range, and in the abnormal range. For each test, there is one control in the normal range and one or two abnormal controls. Abnormal controls may be in the unhealthy but physiologically possible range, or outside what is physiologically possible, or both. Testing in many ranges ensures that the procedures are accurate for a wide range of patient results. Controls are run at least as often as specified by the instrument manufacturer. Controls should also be run whenever there is:- • concern about the quality of results or • stability of the testing system, or • if the results of previous controls were not acceptable,If a problem is discovered, the samples in previous runs of the instrument may also have been affected. Once the problem(s) are corrected, it may be necessary to go back and re-run previous samples working in reverse order, until the retested results match the original results.

20. Tools for Validation of QC results

21. Shewhart Control Charts A Shewhart Control Chart depend on the use of IQC specimens and is developed in the following manner

22. Shewhart Chart +3 sd +2 sd +1 sd Target value -1 sd -2 sd -3 sd Assay Run

23. Westgard multirules • The formulation of Westgard rules were based on statistical methods. Westgard rules are commonly used to analyse data in Shewhart control charts. • Westgard rules are used to define specific performance limits for a particular assay and can be use to detect both random and systematic errors. • There are six commonly used Westgard rules of which three are warning rules and the other three mandatory rules. • The violation of warning rules should trigger a review of test procedures, reagent performance and equipment calibration. • The violation of mandatory rules should result in the rejection of the results obtained with patients’ serum samples in that assay.

24. Warning rules • Warning 12SD : It is violated if the IQC value exceeds the mean by 2SD. It is an event likely to occur normally in less than 5% of cases. • Warning 22SD : It detects systematic errors and is violated when two consecutive IQC values exceed the mean on the same side of the mean by 2SD. • Warning 41SD: It is violated if four consecutive IQC values exceed the same limit (mean  1SD) and this may indicate the need to perform instrument maintenance or reagent calibration.

25. Mandatory rules • Mandatory 13SD : It is violated when the IQC value exceeds the mean by 3SD. The assay run is regarded as out of control. • Mandatory R4SD : It is only applied when the IQC is tested in duplicate. This rule is violated when the difference in SD between the duplicates exceeds 4SD. • Mandatory 10x : This rule is violated when the last 10 consecutive IQC values are on the same side of the mean or target value.

26. Westgard Rules: 1 3SD +3 sd +2 sd +1 sd Target value -1 sd -2 sd -3 sd Assay Run

27. Westgard Rules: 10X Antibody Units +3 sd +2 sd +1 sd Target value -1 sd -2 sd -3 sd Assay Run VZV IgG ELISA: Target Value = 49 U/ml

28. Follow-up action in the event of a violation There are three options as to the action to be taken in the event of a violation of a Westgard rule: • Accept the test run in its entirety - this usually applies when only a warning rule is violated. • Reject the whole test run - this applies only when a mandatory rule is violated. • Enlarge the greyzone and thus re-test range for that particular assay run - this option can be considered in the event of a violation of either a warning or mandatory rule.

29. Types Of ErrorsRandom Error • An error which varies in an unpredictable manner, in magnitude and sign, when a large number of measurements of the same quantity are made under effectively identical conditions. • Random errors create a characteristic spread of results for any test method and cannot be accounted for by applying corrections. Random errors are difficult to eliminate but repetition reduces the influences of random errors. • Examples of random errors include errors in pipetting and changes in incubation period. Random errors can be minimized by training, supervision and adherence to standard operating procedures.

30. Random Errors

31. Systematic Error • An error which, in the course of a number of measurements of the same value of a given quantity, remains constant when measurements are made under the same conditions, or varies according to a definite law when conditions change. • Systematic errors create a characteristic bias in the test results and can be accounted for by applying a correction. • Systematic errors may be induced by factors such as variations in incubation temperature, blockage of plate washer, change in the reagent batch or modifications in testing method.

32. Systematic Errors

33. {والله أخرجكم من بطون أمهاتكم لا تعلمون شيئا وجعل لكم السمع والأبصار والأفئدة لعلكم تشكرون ْْ}

34. THANK YOU