Clinical Chemistry I 0202304 PDF

Clinical Chemistry I 0202304 Instructor: Mohammad QABAJAH E-mail: [email protected] Week 09-10 Control of Analytical Variables 2 Objectives I. Compare internal quality control with external quality assessment programs, including needs,...

Clinical Chemistry I 0202304 Instructor: Mohammad QABAJAH E-mail: [email protected] Week 09-10 Control of Analytical Variables 2 Objectives I. Compare internal quality control with external quality assessment programs, including needs, requirements, and features II. Explain the need of use the control material in the clinical laboratory III. Explain the use of control charts in the clinical laboratory IV. Describe how control limits are calculated V. Assess Levey-Jennings control chart for error and out of-limit data VI. Explain the Westgard multirules used for interpretation of laboratory control data. Control of Analytical Phase - Validated analytical methods - Calibration of analytical procedure - Quality control material in the assay - Monitor the performance by Levy Jennings charts - Application of Westgard multi rules - Equipment & Reagents Control of Analytical Variables Ensure accurate measurements by accurate methods Reliable analytical methods are obtained through careful process of: I. Selection II. Evaluation III. Implementation IV. Maintenance V. Control Control Material Control and Standards Control should be (Selection of Quality Control Material) - Appropriate for the diagnostic sample - Values cover medical decision points - Similar to test sample (matrix) - In stable form - In aliquots or vials of suitable vol. - Used over an extended period of time Composition of control What is a Control? Material that contains the substance being analyzed - Include with patient samples when performing a test Used to validate reliability of the test system - Run after calibrating the instrument - Run periodically during testing Control vs Calibrator Control Calibrator A substance similar to patients’ A substance with a specific samples that has an established concentration. concentration. Calibrators are used to set Controls are used to ensure the (calibrate) the measuring points procedure is working properly. on a scale. Control Material Types: - Frozen, freeze-dried, or chemically preserved Sources: - Commercially prepared - Made “in house” - Obtained from another central or reference laboratory Preparation and Storage: - adhere to manufacturer’s instructions - keep adequate amount of same lot number - store correctly Control Material - Target value predetermined ASSAYED - Verify and use - Target value not predetermined UNASSAYED - Full assay required before using - In-house pooled sera “IN-HOUSE” - Full assay, validation Components of Quality Assurance Internal Quality Control (IQC) Steps taken by all health care professionals in their day to day activities to ensure generation of reliable laboratory results. (Prospective activity) - Pre-analytical phase - Analytical phase - Post-analytical phase 11 Components of Quality Assurance External Quality Assessment (EQA) - Organized Inter-laboratory comparison - Tool to assess IQC to improve performance Performed by an independent agency Retrospective and periodic 12 Steps in Implementing Quantitative QC I. Obtain control material 3SD II. Run each control 20 times over 30 days 2SD 1SD Mean III. Calculate mean and +/-1,2,3 SD 1SD 2SD 3SD Measurement Procedure - Is used to determine the value of a quantity - This estimate contains a measurement error, which is the difference between the obtained value and the true value of the measured. - Measurement error has 2 components: Random error & systematic error 14 Random Error Is an unpredictable analytical variation which influence each measurement differently in either a positive or negative direction and to a different extent in magnitude. Possible causes of imprecision are - Wrong pipetting technique - Variable reaction timing and temperature of procedures - Instrument instability 15 Systematic Errors Possible causes: - Errors in the assigned value to the calibrator - Deterioration of calibration material - Incorrect sample or reagent volume pipetted - Incorrect reaction timing or temperature - Incorrect instrument setting (wavelength) - Calculation errors - Presence of interferents in samples 16 Steps in Implementing Quantitative QC I. Obtain control material 3SD II. Run each control 20 times over 30 days 2SD 1SD Mean III. Calculate mean and +/-1,2,3 SD 1SD 2SD 3SD Measurement Procedure Imprecision: Expressed as - SD - Coefficient of Variation CV % 18 Standard Deviation: SD Coefficient of Variation CV = SD CV % = SD x 100 Mean Mean 19 QC Charts and Rules Shewhart/Levey-Jennings Chart: Analyze the QC material by the analytical method to be controlled on at least 20 times under optimal conditions and calculate the mean, standard deviation and CV % (OCV) Remove the outliers Construct the control chart : Y axis-control value X axis-days 20 21 QC Charts and Rules Shewhart/Levey-Jennings chart must include: - Test name - Method of analysis - Date - Source of control (lot #, patch #, etc.) - Statistical data Importance of QC Charts - Detect errors during analysis - Prevent reporting incorrect data Mean glucose under routine conditions ◦ Perform the glucose under routine conditions for 30 days ◦ 120, 74, 124, 120, 117, 116, 122, 126, 191, 126, 120, 123, 124, 120, 117, 116, 122, 126, 130, 126, 64, 123, 124, 120, 117, 116, 122, 126, 200, 126 Corrected (After removal of outliers) ̵ Mean 123.2 120.6 ̵ SD 24.0 19.5 ̵ ±1s 147.2 – 99.2 140.1-101.1 ̵ ±2s 171.2- 75.2 159.6 -81.6 ̵ ±3s 195.2 – 51.2 179.1- 62.1 23 Levey-Jennings Chart 179.1 +3SD 159.6 +2SD 140.1 +1SD 120.6 MEAN 101.1 -1SD 81.6 -2SD 62.1 -3SD Days  QC Charts and Rules +3SD Action Within ±2SD – Accept +2SD Warning Between 2SD & 3SD – Warning +1SD > 3SD – Reject Mean Trend? -1SD Shift? -2SD Warning -3SD Action Examining QC Charts Imprecision - Variability in pipeting - Inattention to details by the operator Inaccuracy - Trend - Deterioration of reagents and standards - Deterioration of instrument performance - Shift - Introduction of something new into assay procedure - New lots - Malfunction of instrument, immediate & permanent Control (Levey-Jennings) Chart Continuous surveillance of control values Visual and statistical Interpretation of Control Chart Acceptance of results - True acceptance - False acceptance Rejection of results - True rejection - False rejection QC Charts and Rules Westgard Multirule Chart Introduce two control specimens into each analytical run one for each of the two concentrations (NORMAL & ABNORMAL) Plot the charts with mean and SD 28 Westgard Multi-Rule control chart 12s: One control value exceeding x ± 2s limits warning 13s: One control value exceeding x ± 3s limit, random, rejection 22s: Two consecutive control values exceeding x ± 2s limits, systematic, rejection R4s: One observation exceeding x+2s, and the other exceeding x-2s, random, rejection 41s: Four consecutive values exceeding x ±1s limit, systematic, rejection 10x: ten consecutive values falling on the same side of x, rejection  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 12s : When the control limits are set as the mean plus/minus 2s. In the original Westgard multirule QC procedure, this rule is used as a warning rule to trigger careful inspection of the control data by the following rejection rules.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 13s : When the control limits are set as the mean plus 3s and the mean minus 3s. A run is rejected when a single control measurement exceeds the mean plus 3s or the mean minus 3s control limit.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 22s - reject when 2 consecutive control measurements exceed the same mean plus 2s or the same mean minus 2s control limit.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD R4s - reject when 1 control measurement in a group exceeds the mean plus 2s and another exceeds the mean minus 2s.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 41s - reject when 4 consecutive control measurements exceed the same mean plus 1s or the same mean minus 1s control limit.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 10x - reject when 10 consecutive control measurements fall on one side of the mean. 35  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 2 of 32s - reject when 2 out of 3 control measurements exceed the same mean plus 2s or mean minus 2s control limit;  +3SD +2SD +1SD MEAN -1SD -2SD -3SD 7T - reject when seven control measurements trend in the same direction, i.e., get progressively higher or progressively lower.  +3SD +2SD +1SD MEAN -1SD -2SD -3SD Shift See YOU Next Lecture ☺