Quality Control in clinical laboratory. Kanit Reesukumal, M.D. Assistant Professor Clinical Pathology Mahidol University

Transcription

1 Quality Control in clinical laboratory Kanit Reesukumal, M.D. Assistant Professor Clinical Pathology Mahidol University

2 Outline Internal Quality Control Calculation Levey-Jennings Charts Westgard Rules Six sigma Additional Quality Control Statistics Out of control limit corrective action Quality control products

3 Introduction Achieving quality in the medical laboratory requires the use of many tools Procedure manuals Maintenance schedules Calibrations A quality assurance program Training Quality control

4 Precision vs Accuracy Internal quality control Repetitive assay Assess precision External quality assessment Test result compared to consensus value Assess accuracy

5 Internal Quality Control Internal quality control is a statistical process used to monitor and evaluate the analytical process that produces patient results The question of reliability for most testing can be resolved by regular use of quality control materials and statistical process control

6 Regular Testing Good laboratory practice requires testing normal and abnormal controls for each test at least daily to monitor the analytical process. If the test is stable for less than 24 hours or some change has occurred which could potentially affect the test stability, controls should be assayed more frequently

7 Comparison of Quality Control Results to Specific Statistical Limits Test Potassium Instrument Unit Range LV1 control mmol/l LV2 control mmol/l Out of control for abnormal high K on May 6 Patient Results 1 May , 3.8, 5.0, May , 4.4, 3.9, May , 3.9, 3.7, May , 4.5, 3.7, May , 4.5, 3.8, May , 3.6, 6.0, 7.0 The range defined for each level of control is fundamental of the quality control system

8 Calculations Where: s = standard deviation x = mean (average) of the QC values Σ(x n - x) 2 = the sum of the squares of differences between individual QC values and the mean n = the number of values in the data set

9 Gaussian (bell-shaped) curve 4.5% of value will fall outside 2 SD range

10 Levey-Jennings Charts Using a Levey-Jennings Chart to Evaluate Run Quality Systematic Error Random Error

11 Levey-Jennings chart

12 Systematic error

13 Trend Deterioration of the instrument light source Gradual accumulation of debris in sample/reagent tubing or electrode surfaces Aging of reagents Gradual deterioration of control materials, incubation chamber temperature (enzymes only), light filter integrity, and calibration

14 Shift Sudden failure or change in the light source Change in reagent formulation or reagent lot Major instrument maintenance Sudden change in incubation temperature (enzymes only) Change in room temperature or humidity Failure in the sampling system, reagent dispense system Inaccurate calibration/recalibration

15 Random error Any deviation away from an expected result There is acceptable (or expected) random error as defined and quantified by standard deviation. There is unacceptable (unexpected) random error that is any data point outside the expected population of data (e.g., a data point outside the ±3s limits).

16 Westgard rules Dr. James Westgard, 1981 Based on principles of statistical process control used in industry nationwide since the 1950s Six basic rules 1 2S 1 3S 2 2S R 4S 4 1S 10x

17 1 2S Warning rule About 4.5% of all results fall between 2s and 3s limits Acceptable if No source of error identified

18 1 3S Unacceptable random error The beginning of a large systemic error

19 2 2S Criteria Two consecutive QC results Greater than 2s On the same side of the mean Systematic error Within run: both levels Across run: previous run

20 R 4S Identified random error only Applied only within the current run At least a 4S difference between control values within a single run

21 Criteria 4 consecutive results Greater than 1s On the same side of the mean Systematic bias Within control material: single area of the method curve Across control materials: broader concentration 4 1S

22 On the same side of the mean regardless of the specific standard deviation in which they are located Systematic bias Within control material: single area of the method curve Across control materials: broader concentration 10 X (or 8 X )

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24 Out of control limit corrective action

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26 Additional Quality Control Statistics Coefficient of Variation [CV] Coefficient of Variation Ratio [CVR] Standard Deviation Index [SDI]

27 Coefficient of Variation [CV] The ratio of standard deviation to the mean Compare precision for two different methods SD increases as the concentration of the analyte increases CV = (SD/mean) x 100 CV = Total allowable error/3

28 Monthly CV review

29 Comparative evaluations Instrument manuals and test method description Proficiency surveys Interlaboratory QC programs CLIA proficiency limits

30 Instrument manuals and test method description Published expectations for between-run and within-run precision Reflect ideal condition Results higher than specifications may indicate a possible problem exists Should compare to proficiency reports which are more indicate of real world experience

31 Proficiency surveys (EQA) Receive a set of unknown sample Report results to the proficiency agency Test result reported by each laboratory is compared to consensus value Laboratory is graded for accuracy Can be used to compare and assess day-to-day laboratory precision

32 Interlaboratory QC programs Monthly data The data are combined with data from other laboratories which use the same instrument Benefit over a proficiency program Statistics collected from repeated daily testing whereas proficiency program provides statistics collected from single events that occur only 3 times a year

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34 CLIA proficiency limits Published performance limits for commonly tested analytes in the United States CLIA regulation CLIA proficiency testing criteria for acceptable analytical performance, as printed in the Federal Register February 28, 1992;57(40):

35 Coefficient of Variation Ratio [CVR] Less than 1.0 Precision is better than the peer group Greater than 1.0 Larger imprecision Greater than 1.5 Need to investigate Greater than 2.0 Need for trouble shooting and corrective action

36 Standard Deviation Index [SDI] 1.25 or less Acceptable Marginal performance, some investigation may be required Marginal performance, investigation is recommended 2.0 or greater Unacceptable

37 Quality Control Products A quality control product is a patient-like material ideally made from human serum, urine or spinal fluid. Control product can be a liquid or freeze dried (lyophilized) material and is composed of one or more constituents (analytes) of known concentration. Control products should be tested in the same manner as patient samples.

38 Choosing a Quality Control Products Selecting a Control Product Shelf Life Box Pricing Clinically Relevant Decision Levels Interlaboratory Comparison Programs

39 Third party control A control that has not been designed for a particular test system or analyzer An independent control Manufacturer independently of reagents and calibrators Provides an unbiased assessment of performance

40 Selecting a Control Product Cheaper products Short shelf life after opening Not sufficient similar to patient specimens (serum, urine, spinal fluid or plasma) Not have all analytes at medically relevant decision levels Misled by box pricing

41 Shelf Life It is necessary to know the approximate volume of control to be used each day Shelf life becomes an important issue when low volume of control is used Waste

42 Clinically Relevant Decision Levels Some analytes need 3 level of quality control Low level Normal level High abnormal level Example: TSH with AMR µiu/ml TSH (µiu/ml) Vendor 1 Vendor 2 Low level Normal High abnormal level

43 Box Pricing Different volume and vials Always ask for quality control product quotes on a per ml basis and not box price

44 Interlaboratory Comparison Programs Highly recommend Easy method to assess reliability and imprecision Compare the within-laboratory method means and standard deviations to other laboratories using the same instrument and method (peer group)

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48 Conclusion QC: monitoring reliability of the test results IQC: precision EQA: accuracy Systematic error: 2 2s, 4 1s, 10x Trend Shift Random error: 1 3s, R 4s Coefficient of variation: compare precision for two different methods Peer group: CVR and SDI Good QC materials: matrix, shelf life, price per ml, clinical relevant, interlab QC