Process Control for Quantitative Tests PDF

Process Control: Quality Control for Quantitative Tests 1  Learning Objectives At the end of this module, participants will be able to: ◼ Differentiate accuracy and precision. ◼ Select control material for the laboratory. ◼ Establish acceptable control limits fo...

Process Control: Quality Control for Quantitative Tests 1  Learning Objectives At the end of this module, participants will be able to: ◼ Differentiate accuracy and precision. ◼ Select control material for the laboratory. ◼ Establish acceptable control limits for a method when only one level of control material is available. ◼ Explain the use of a Levey-Jennings chart. ◼ Describe how to correct “out of control” problems. Quantitative QC - Module 7 2  The Quality Management System Organization Personnel Equipment Purchasing Process Information & Control Management Inventory Documents Occurrence & Assessment Management Records Process Customer Facilities Improvement Service & Safety Quantitative QC - Module 7 3  Quantitative Tests ◼ measure the quantity of a particular substance in a sample ◼ quality control for quantitative tests is designed to assure that patient results are:  accurate  reliable Quantitative QC - Module 7 4  Implementation steps ◼ establish policies and procedures ◼ assign responsibility, train staff ◼ select high quality controls ◼ establish control ranges ◼ develop graphs to plot control values - Levey-Jennings charts ◼ monitor control values ◼ develop procedures for corrective action ◼ record all actions taken Quantitative QC - Module 7 5  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 Quantitative QC - Module 7 6  Calibrators vs. Controls Quantitative QC - Module 7 7 Calibrators Controls A substance with a specific A substance similar to concentration. patients’ samples that has an established Calibrators are used to set concentration. (calibrate) the measuring points on a scale. Controls are used to ensure the procedure is working 1 2 3 4 5 properly. 1 2 3 4 5 Quantitative QC - Module 7 8 Characteristics of Control Materials ◼ appropriate for the diagnostic sample ◼ values cover medical decision points ◼ similar to test sample (matrix) ◼ available in large quantity; ideally enough for one year ◼ can store in small aliquots Quantitative QC - Module 7 9  Types of Control Materials ◼ may be frozen, freeze- dried, or chemically preserved ◼ requires very accurate reconstitution if this step is necessary Quantitative QC - Module 7 10  Sources of Controls Materials ◼ commercially prepared ◼ made “in house” ◼ obtained from another laboratory, usually central or reference laboratory Quantitative QC - Module 7 11  Control Materials 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 Quantitative QC - Module 7 12  Choosing Control Materials ◼ values cover medical decision points ◼ similar to the test sample ◼ controls are usually available in high, normal, and low ranges Quantitative QC - Module 7 13  Preparation and Storage of Control Material ◼ adhere to manufacturer’s instructions ◼ keep adequate amount of same lot number ◼ store correctly CONTROL Quantitative QC - Module 7 14  Steps in Implementing Quantitative QC ◼ obtain control material ◼ run each control 20 times over 30 days 3SD ◼ calculate mean and +/- 2SD 1,2,3 Standard Deviations 1SD Mean 1SD 2SD Quantitative QC - Module 7 3SD 15  Measurement of Variability Variability is a normal occurrence when a control is tested repeatedly Affected by: Performance Operator Environmental characteristics technique conditions of the measurement The goal is to differentiate between variability due to chance from that due to error Quantitative QC - Module 7 16  Measures of Central Tendency Although variable, sets of data are distributed around a central value F r e q u e n c y Measurement Quantitative QC - Module 7 17  Measures of Central Tendency Mode the value which occurs with the greatest frequency Median the value at the center or midpoint of the observations Mean the calculated average of the values Quantitative QC - Module 7 18 Not all central values are the same Mean Mode F Median r e q u e n c y Measurement Quantitative QC - Module 7 19  Symbols Used in Calculations ∑ is the sum of (add data points) n = number of data points x1 - xn = all of the measurements (1 through n) __ X represents the mean Quantitative QC - Module 7 20  Calculation of Mean X 1 + X 2 + X 3... X n X= n X = Mean X1 = First measurement X2 = Second measurement Xn = Last measurement in series n = Total number of measurements Quantitative QC - Module 7 21  Example Calculation of Mean: ELISA Tests ◼ Run controls 20 times in 30 days. Record both OD and cut off (CO) values for each measurement. ◼ Divide the OD by the CO (OD/CO) for each data point or observation. This standardizes the data. ◼ Add the ratios and divide by the number of measurements to get the mean. Quantitative QC - Module 7 22  Data showing outlier 1. 192 mg/dL 11. 204 mg/dL 2. 194 mg/dL 12. 208 mg/dL 3. 196 mg/dL 13. 212 mg/dL 4. 196 mg/dL 14. 198 mg/dL 5. 185 mg/dL 15. 204 mg/dL 6. 196 mg/dL 16. 208 mg/dL 7. 200 mg/dL 17. 212 mg/dL 8. 200 mg/dL 18. 198 mg/dL 9. 202 mg/dL 19. 192 mg/dL 10. 270 mg/dL 20. 196 mg/dL Quantitative QC - Module 7 23  Normal distribution ◼ all values symmetrically distributed around the mean ◼ characteristic “bell-shaped” curve ◼ assumed for all quality control statistics Frequency mean Quantitative QC - Module 7 24  Quality Control is used to monitor the accuracy and the precision of the assay. What are accuracy and precision? Quantitative QC - Module 7 25  Definitions Accuracy The closeness of measurements to the true value Precision The amount of variation in the measurements Bias The difference between the expectation of a test result and an accepted reference value Quantitative QC - Module 7 26 Accuracy and Precision Accurate Precise and Precise but Biased Imprecise Accurate = Precise but not Biased Quantitative QC - Module 7 27  Standard Deviation and Probability For a set of data with a X normal distribution, a Frequency random measurement will fall within: 68.2% + 1 SD 68.3% of the time 95.5% + 2 SD 95.5% of the time 99.7% -3s- 2s -1s Mean +1s +2s +3s + 3 SD 99.7% of the time Quantitative QC - Module 7 28  Standard Deviation (SD) SD is the principle measure of variability used in the laboratory  1 − 2 SD = (x x ) n −1 Standard Deviation – Statistical Formula Quantitative QC - Module 7 29  Coefficient of Variation The coefficient of variation (CV) is the SD expressed as a percentage of the mean. SD CV = x 100 % mean ◼ CV is used to monitor precision ◼ CV is used to compare methods ◼ CV ideally should be less than 5% Quantitative QC - Module 7 30  Levey-Jennings Chart Graphically Representing Control Ranges Quantitative QC - Module 7 31  Statistics for Quantitative QC ▪ assay control material at least 20 data points over a 20-30 day period ▪ ensure procedural variation is represented ▪ calculate mean and + 1, 2 and 3 SD Quantitative QC - Module 7 32  Draw lines for Mean and SDs (calculated from 20 controls) Chart name: Lot number: 196.5 +3SD 194.5 +2SD 192.5 +1SD 190.5 MEAN 188.5 -1SD 186.5 -2SD 184.6 -3SD Days Quantitative QC - Module 7 33  Levey-Jennings Chart Plot daily control measurements 196.5 +3SD 194.5 +2SD 192.5 +1SD 190.5 MEAN 188.5 -1SD 186.5 -2SD 184.6 -3SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Days Quantitative QC - Module 7 34 Number of Controls Interpretation depends on number of controls run with patients’ samples. ◼ Good: If one control:  accept results if control is within ± 2SD unless shift or trend ◼ Better: If 2 levels of controls  apply Westgard multirule system Quantitative QC - Module 7 35  Detecting error ◼ random error: variation in QC results with no pattern- only a cause for rejection if outside 2SDs. ◼ systematic error: not acceptable, correct the source of error Examples:  shift–control on one side of the mean 6 consecutive days  trend–control moving in one direction– heading toward an “out of control” value Quantitative QC - Module 7 36  Levey-Jennings Chart Shift 196.5 +3SD 194.5 +2SD 192.5 +1SD 190.5 MEAN 188.5 -1SD 186.5 -2SD 184.6 -3SD Days Quantitative QC - Module 7 37  Levey-Jennings Chart Trend 196.5 +3SD 194.5 +2SD 192.5 +1SD 190.5 MEAN 188.5 -1SD 186.5 -2SD 184.6 -3SD Days Quantitative QC - Module 7 38  Measurement Uncertainty ◼ represents a range of values in which the true value is reasonably expected to lie ◼ is estimated at “95% coverage” ◼ the more precise the method, the smaller the range of values that will fall within 95% ◼ for most instances, a range of + or - 2 SDs is accepted as measurement uncertainty that is explained by random variation Quantitative QC - Module 7 39 If QC is out of control ◼ STOP testing ◼ identify and correct problem ◼ repeat testing on patient samples and controls after correction ◼ Do not report patient results until problem is solved and controls indicate proper performance Quantitative QC - Module 7 40  Solving out-of-control problems ◼ identify problem ◼ refer to established policies and procedures for remedial action Quantitative QC - Module 7 41  Possible Problems ◼ degradation of reagents or kits ◼ control material degradation ◼ operator error ◼ failure to follow manufacturer’s instructions ◼ an outdated procedure manual ◼ equipment failure ◼ calibration error Quantitative QC - Module 7 42  Summary A quality control program for quantitative tests is essential. It should: ◼ monitor all quantitative tests ◼ have written policies and procedures, followed by laboratory staff ◼ have a quality manager for monitoring and reviewing QC data ◼ use statistical analysis, provide for good records ◼ provide for troubleshooting and corrective action Quantitative QC - Module 7 43  Key Messages ◼ A QC program allows the laboratory to differentiate between normal variation and error. ◼ The QC program monitors the accuracy and precision of laboratory assays. ◼ The results of patient testing should never be released if the QC results for the test run do not meet the laboratory target values. Quantitative QC - Module 7 44  Organization Personnel Equipment Questions? Purchasing Process Information Comments? & Control Management Inventory Documents Occurrence & Assessment Management Records Process Customer Facilities Improvement Service & Safety Quantitative QC - Module 7 45