Application of Westgard multi rules in medical laboratories Dr. Meliyanthi Gunatillaka Consultant Chemical Pathologist National Hospital of Srilanka Colombo

Internal Quality Control (IQC) 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 26 April 2017

Components of Quality Assurance cont… External Quality Assessment (EQA) Organized Inter-laboratory comparison Tool to assess IQC to improve performance Performed by an independent agency Retrospective and periodic 26 April 2017

Validated analytical methods Control of analytical phase Validated analytical methods Calibration of analytical procedure using traceability established calibration material Quality control material in the assay Monitor the performance by Levy Jennings charts Application of Westgard multi rules Equipment & Reagents 26 April 2017

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 measurand. Measurement error has 2 components: Random error & systematic error 26 April 2017

Measurement Accuracy Is the extent of the agreement between the result of a measurement and the true value. ( True value of an analyte is obtained by using a reference method and CRM with stated uncertainties and traceability.)( Practically not possible) (Approximations are obtained using QC material) Accuracy encompasses the concepts of precision and trueness ( Earlier it was only the trueness) 26 April 2017

ACCURACY PRECISION Is the extent of agreement between independent results of repeated measurements Imprecision :Expressed as SD or Coefficient ofVariation CV mmol/L or CV % TRUNESS Is the extent of agreement between the mean value of repetitions and the true value of the measured Expressed as a % of difference between the mean value of multiple repetitions and the true value. 26 April 2017

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. 26 April 2017

Possible causes of imprecision are Wrong pipetting technique Variable reaction timing and temperature of measurement procedures Instrument instability 26 April 2017

Systematic error (bias) Constant systematic bias denotes a constant difference between the true value and the observed value regardless of the concentration level. Proportional systematic bias denotes a difference between the true value and the observed value, which changes proportionally as the concentration level changes. 26 April 2017

Possible causes of systematic errors 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(affect the individual samples) 26 April 2017

Calculations Mean If the distribution of results is a normal Gaussian curve the mean is the total score of all the measurements divided by the number of measurements. If not, remove the outliers (values with > 3SD) and recalculate the mean. 26 April 2017

Coefficient of variation Standard deviation A descriptor of the extent of dispersion of a population of test values (set of measurement data) _ SD = √(X – X )2 ÷ (N – 1 ) Coefficient of variation Relates the SD to the actual measurement so that measurements at different levels can be compared. CV = SD CV = SD x 100 mean mean 26 April 2017

Selection of Quality control material Control materials should be used as they were patients samples and each and every one of the steps and stages that make up measurement procedure should be followed Essential characteristics Homogenicity: No significant differences between the parts that make up a lot of the control material (dispensing errors, variability in lyophylization due to residual water and reconstitution errors) ( Check the procedure for reconstitution of QC) 26 April 2017

The component that is analysed must be stable over a Stability The component that is analysed must be stable over a sufficient period of time. Once recontituted the aliquoted vials should be stored in appropriate temperatures according the manufacturers instructions. Labels : date of reconstituition No freezing and thawing cycles. ( ALP increases if stored at 2- 80 C) 26 April 2017

Value of the control quantity Value should be close to the clinical decision level or cut off levels If various cut off values exist, a number of control material can be used with different concentrations Physiological level : upper limit of reference range Pathological ranges : low, medium & high Commutability The QC material must respond to the changes or alterations in the measurement procedure in the same way as patients samples. 26 April 2017

Matrix varies from lot to lot Types of QC material Defined matrix material : non biological or systhetic matrix in the form of buffers, stabilizing agents Biological matrix: Derived from biological fluids, blood,plasma,serum & urine Matrix varies from lot to lot Human origin : especially for immunoassays Animal origin: cheaper and less risk of infections 26 April 2017

If not : peer review world wide values : local agent iif Quality Control materials with assigned values Manufacturers assigned value Method & instrument specific value Details of the certified reference material used ( with UM & stated references) Range and standard deviation should be given Laboratory assigned value The mean value obtained following minimum of 20 repititions should fall within the 2SD of the method & instrument specific assigned value of the manufacturer ( preferably within the UM) If not : peer review world wide values : local agent iif 26 April 2017

How do we find the mean glucose value of the in-house QC sample? Perform the glucose test under optimum conditions for minimum 20 times Example 01- Obtained Readings 1-120, 2-120, 3-120, 4-120, 5-119, 6-120, 7-120, 8-121, 9-120,10 -120, 11-120, 12 -120, 13-120, 14-120, 15-119, 16- 120, 17-120, 18- 121, 19-120,20 -120, Mean = 120.0 Standard Deviation = 0.45 +1 s = 120.0 + 0.45 = 120.45 - 1s = 120.o - 0.45 = 119.55 +2s = 120.0 + 2x 0.45 = 120.9 - 2s = 120.0 - 2x0.45 = 119.1 +3s = 120.0 + 3x 0.45 = 121.35 -3s = 120.0 - 3x 0.45 = 118.65 26 April 2017

Mean glucose under routine conditions Perform the glucose under routine conditions for 30 days Example 03 1-120, 2-74, 3-124, 4-120, 5-117, 6-116, 7-122, 8-126, 9-191,10 -126, 11-120, 12 -123, 13-124, 14-120, 15-117, 16- 116, 17-122, 18- 126, 19-130, 20 -126, 21-64, 22 -123, 23-124, 24-120, 25-117, 26- 116, 27-122, 28- 126, 29-200, 30 -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 26 April 2017

Shewhart/Levey and Jennings chart QC Charts and rules Shewhart/Levey and 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 26 April 2017

QC Charts and rules cont… Action +3SD Warning +2SD Mean -2SD Warning -3SD Action 26 April 2017

L-J Chart Analogous models….. variance                     Analogous models….. L-J Chart Symbolic Models Used in Internal Quality Control Days Within ±2SD – accept > 3SD –reject between 2SD & 3SD - warning A Trend is when six or more consecutive plots all fall in one direction, specifically upward or downward. A shift is when six or more consecutive plots all fall on/above or below the mean line. 26 April 2017

QC Charts and rules cont… Introduce a control specimen daily to the analytical run, plot each value on the chart. After 20 days calculate the mean, SD and RCV, remove the outliers & recalculate the mean,SD and construct the chart, plot daily control value and follow the rules to accept/reject the run. 26 April 2017

QC Charts and rules cont… Westgard Multirule Chart and rules Introduce two control specimens into each analytical run one for each of the two concentrations ( NORMAL & ABNORMAL) Plot the charts with mean and SD. 12s ‘’ 1’’ Number of control observations 2s Type of error s – Standard deviation 26 April 2017

QC Charts and rules cont… If both control results are within 2SD from their target the batch is accepted If at least one control result is more than 2SD from the target, the remaining rules are evaluated in turn, and the batch is rejected if any one rule is satisfied. If none is satisfied the batch is accepted. The situation should be investigated before the next batch is analyzed 26 April 2017

Automatic chemistry analysers Normal & abnormal QC : chemistry Daily & 50th /100th and at the end : day time night time : at the start Low,medium & high QC: immunoassays Daily all 3 levels Procedure : calibration of the method QC:all results within 2SD : accept:run the samples IF one QC is out, check the violations of rules in other levels. Find the cause. ( calibration) Re run the QC : IF out again : new aliquot of QC All QC levels satisfactory – Run the samples 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 01 13s refers to a control rule that is commonly used with a Levey-Jennings chart 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. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 02 12s refers to the control rule that is commonly used with a Levey-Jennings chart 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. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 03 22s - reject when 2 consecutive control measurements exceed the same mean plus 2s or the same mean minus 2s control limit. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 04 R4s - reject when 1 control measurement in a group exceeds the mean plus 2s and another exceeds the mean minus 2s. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 05 41s - reject when 4 consecutive control measurements exceed the same mean plus 1s or the same mean minus 1s control limit. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 06 10x - reject when 10 consecutive control measurements fall on one side of the mean. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 07 8x - reject when 8 consecutive control measurements fall on one side of the mean. 26 April 2017

Analogous models….. Westgard multirules variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models….. Westgard multirules Symbolic Models Used in Internal Quality Control 12x - reject when 12 consecutive control measurements fall on one side of the mean. 26 April 2017

Analogous models…. Symbolic Models Used in Internal Quality Control variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models…. Symbolic Models Used in Internal Quality Control What are other common multirules? In situations where 3 different control materials are being analyzed, some other control rules fit better and are easier to apply, such as: 2of32s - reject when 2 out of 3 control measurements exceed the same mean plus 2s or mean minus 2s control limit; 26 April 2017

Analogous models…. Symbolic Models Used in Internal Quality Control variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models…. Symbolic Models Used in Internal Quality Control What are other common multirules? 31s - reject when 3 consecutive control measurements exceed the same mean plus 1s or mean minus 1s control limit. 26 April 2017

Analogous models…. Symbolic Models Used in Internal Quality Control variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models…. Symbolic Models Used in Internal Quality Control What are other common multirules? 6x - reject when 6 consecutive control measurements fall on one side of the mean. 26 April 2017

Analogous models…. Symbolic Models Used in Internal Quality Control variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models…. Symbolic Models Used in Internal Quality Control What are other common multirules? 9x - reject when 9 consecutive control measurements fall on one side of the mean. 26 April 2017

Analogous models…. Symbolic Models Used in Internal Quality Control variance                     13s refers to a control rule that is commonly used with a Levey-Jennings chart 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.                                                                     Analogous models…. Symbolic Models Used in Internal Quality Control What are other common multirules? 7T - reject when seven control measurements trend in the same direction, i.e., get progressively higher or progressively lower. 26 April 2017

Thank you 26 April 2017