13The five Q frameworkDefines how quality can be managed using the scientific method or the PDCA cycle Plan do check Act:Quality planningQLPIncludes analytical process and the general policies, practices and procedures that define how all aspects of the work get done.
14e.g.: Linearity checks , reagent and standard checks and procedure. Q.C.Statistical.Non statistical:e.g.: Linearity checks , reagent and standard checks and procedure.Q.A. quality assessment concerned with:Measures and monitors of laboratory performance as:TuraroundSpecimen identificationPatient identificationTest utilityQ.I. quality improvement:Provides a structural problem-solving process
15With better analytical quality a lab can eliminate repeat run requests for test (this work is waste).If quality are improved waste will be reduced which reduce cost and provide a competitive advantage.If quality means conformance to requirements, then quality costs must be cost of conformance and cost of non-conformance.
17Essential Elements for Q.A. Commitment.Facilities and Resources.Technical Competence.Technical Procedures.Problem solving Mechanism.Input from QC technologist or supervisors to initiate the mechanism.In service training program.Specialized trouble shooting skills.Quality team responsible for problem solving (small groups).
24Standardization and calibration: Technical proceduresStandardization and calibration:Reference calibrator material (RCM) (primary calibrator): by definitive method (absolute physical quantity such as mass) e.g. isotope dilution mass spectroscopy.Test calibrator material (TCM) (secondary calibrator): by reference method and high quality staff.
25Structure of an accuracy-based measurement system showing relationships among reference methods and materials .
26Documentation of analytical protocols and procedures. Technical proceduresDocumentation of analytical protocols and procedures.Monitoring of critical equipment and materials.
27Q.C. The Monitoring of analytical quality by the use of: Technical proceduresThe Monitoring of analytical quality by the use of:Q.C.SD, bias and 6 sigmaLevey – Jennings chartWestgard multirulesCum SumP.T.
28Levey Jennings control chart: Q.C.Levey Jennings control chart:Analyze control 20 different days mean ± SD.Construct Control chart.Control limits set as the mean ± 3s. Concentration is plotted on the y-axis versus time (run number) on the x- axis.Introduce the control into each run & record the value.
29Control limit:± 2 SD when the number of observation (n) is one false rejection problem (Pfr).± 3 SD when n = 2 or more error detection (Ped is low).
30Q.C.Levey Jennings chartM+3SDM+2SDM+1SDMeanConcentrationsMM-1SDM-2SDM-3SDRun number
31Westgard Multirules Chart Q.C.Westgard Multirules ChartIf the control is within mean ± 2SD in control:I2s one excced mean ± 2SD ( warning that initiate testing of other control rules).I3s one excced mean ± 3SD ( Random error )22s 2 consecutive control excced mean ± 2SD (systemic error)R4s 2 consecutive excced mean plus and minus 2SD)( Random error)41s 4 consecutive excced mean ± 1SD ( syst. errors )10x` consecutive deviation Less than 1SD on one side (system errors)
32Q.C Westgard chart Run number 13s (random)M+3SD12s (warning )22s systemic4s (Random)M+2SD41s systemicM+1SDMeanConcentrationsMM-1SDM-2SDM-3SDRun number
33Pfr is kept low Ped is improved Westgard Multirule Chart A word from Dr. WestgardWestgard Multirule ChartPfr is kept lowPed is improved
34Introduce two control specimens into each analytical run : Q.CWestgard chartIntroduce two control specimens into each analytical run :When both fall with 2s limits accept the analytical run and report the patient results.When one exceeds 2s limit hold the patients results and inspect the control data using l3s, R45, 22s and 10x-When one of these rules is out of control, reject the analytical run & don’t report the analytical results .When all of these rules indicate that the run is in control , accept the analytical run and report the patient results
35This effectively increases n and improve the Ped of the procedure Q.CWestgard chartR4s is applied only within a run –between Run interpritted as RERule may be applied "across" materials one observations can be on the low, concentration and the other on the high concentration as long as they are within the same run .Rules 22s, 41s and 10x rules can be applied across runs and materials.This effectively increases n and improve the Ped of the procedure
36Systemic error: caused by variations in: Q.C.Systemic error: caused by variations in:InstrumentsTechniqueReagents or other materialRandom error:Appear despite, Tightly Controlled, Analytical methodSample pipttingDissolving reagentMixing sample and reagentsBaths temp instability.
37Q.C.The overall objective of these rules is to obtain a high probability of error detection and a low frequency of false rejection of runs:If the rules are violated it must:
38QC performance characteristics Different QC procedures have different sensitivities or capabilities for detecting analytical errors.The best is that with lowest Pfr and highest Ped.
41Cumulative sum CUSUM chart QCCumulative sum CUSUM chartCalculate difference between mean & the result (e.g. mean 100 , result 110 the diff = 10) -add this difference to the following each day.Interpret the chart data .Steep slope of the Cusum Line, suggest systemic errors and the run is out of control.
43QCCUSUMThe Same as before but the difference is calculated between the estimated control value and k1 or ku (mean ±SD):The cusum calculation do not start until a control value exceeds a certain threshold above (Ku) or below (K1) of the expected mean (X).
44This difference summated for 2 weeks QCCUSUMThis difference summated for 2 weeksIf the summation exceed the control Limit the method out of controlIf the sign changed (+ - or the reverse the calculation stopped the method is in – controlchanged to
45QCCUSUMCalculations and Tabular Record for Decision Limit Cusum For Control Material.With X=100, S=5.0, kU = 105 , K1 =95,hu=13.5,h1=13,5).
46(Its efficiency is relatively low) Q.C using patients data(Its efficiency is relatively low)Clinical correlation:Correlate clinical diagnosis with laboratory test results e.g. impossible test result such as normal serum bilirubin in a highly jaundiced patients.Correlation with other laboratory tests e.g. T4 and TSH, urea and creatinine.
47Inter laboratory duplicate: Q.C using patients dataInter laboratory duplicate:Divide sample into 2 aliquots and do analysis.This is a simple Q.C. procedure used in absence of stable control material.
48Delta checks with previous test: Q.C using patients dataDelta checks with previous test:To detect certain errors e.g. identification or labelling.Compare laboratory test results with value obtained on previous specimens from the same patients.Delta check limit based on 3-day interval in term % of change from the initial value e.g. Na+ 5%, CK 99%.
49Q.C using patients dataLimit checks:Patients test results should be reviewed to check that they are within the physiological ranges compatible with life.Low warningHigh warningS. Albumin (g/dl)1.56.0S. Uric acid (mg/dl)1.012.0S. Sodium (mmol/L)120.0150
50External Q.C. Analyze the same Lot of control material: N. ± 1-1.5. > 2 Indicate that the Lab is not in agreement with the test of other Laboratories in the program.Must correct any test method instrum. trouble shooting.
51SDI for the same instruments and techniques: External Q.C.SDI for the same instruments and techniques:=
52Comparison of Lab. Mean and group mean by t-test. External Q.C.Comparison of Lab. Mean and group mean by t-test.If significant (<0.05), the Lab. Result is biased.
53Role of proficiency testing (PT) in Accreditation According to Clinical Laboratory Improvement Amendments (CLIA88)Study 5 samples 3 times per year so as to improve the capability of detecting "unacceptable“ performance.The lab. must produce correct results on 4 out of 5 specimens for each of the analytes in that category and have an overall score of at least 80% for 3 consecutive challenges.
54The criteria of PT failure is: Two of five incorrect results on two of three consecutive PT surveysIf there are 2 incorrect results for any analyte , The Lab. is considered "on probation " Lab .Suspended Lab:If the lab .has 2 or more incorrect results for any analyte or has any score less than 80% on two of three consecutive surveys.Suspended Lab. must cease all analytes in that specialty category until it is reinstated .
55Target value (% or absolute value): The mean of all responses after removal of outliers (more than 3SD).Or the mean established by definitive or reference method (acceptable by the national committee of standard NCS).Comparative method may be used in absence of the former methods.
56Post Analytical Goals and Clinical Interpretation of Lab. Procedures The following questions must be asked for test results:Screening : Is an apparent disease present ?Pathoghysiology : What is the disease process ?Confirmation : How can Confidence in the tentative diagnosis be increased ?Prognosis : How Severe is the disease process ?Monitoring : Has a change occurred since the Last observation ?
57Is it significantly different from previous result ? The probability that the difference between two result is analytically significant (p< 0.05) is 2.8 times the analytical SD (SDA of repeated measurements of a single quality normal control serum).To decide whether an analytical change is clinically significant, it is necessary to consider the extent of natural biological variation (means of SDB for repeated measure ments made at weekly intervals in healthy subjects over 10 weeks).
58The effects of analytical and biological variation can be assessed by calculating the overall standard deviation of the test by:If the difference between two test results exceeds 2.8 times the SD of the test, it can be considered of potential clinical significant:
60LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
61LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS orderingInappropriate testHandwriting not legibleWrong patient identificationSpecial requirements not specifiedCost or delayed order
62LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS SpecimenacquisitionIncorrect tube or containerIncorrect patient identificationInadequate volumeInvalid specimen (e.g. hemolyzed or too dilute)Collected at wrong timeImproper transport conditions
63LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS AnalyticalmeasurementInstrument notcalibarted correctlySpecimen mix –upIncorrect volume of specimenInterfering substance presentInstrument precision problem
64LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS Test reportingWrong patient identificationReport not posted in chartReport not legibleReport delayedTranscription error
65LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS interpretationInterfering substances not recognizedSpecificity of test not understoodPrecision limitations not recognizedAnalytical sensitivity not appropriatePrevious values not available for comparison
67Six Sigma What is six sigma Today’s competitive environment leaves no room for errorThis is why six sigma quality must be a a part of our culture.What is six sigmaIt is a process that helps us focus on developing and delivering near perfect products and services.
68Six SigmaWhy sigmaThe word is a statistical term that measures how far a given process deviates from perfection.The central idea behind six sigma is that you can measure how many” Defects” you have in a process, you can systematically figure out how to eliminate them and get as close to “zero defects” as Possible.
69Six SigmaThe principles of Six Sigma go back to Motorola’s approach to TQM in the early 1990s and the performance goal that “6 sigmas or 6 standard deviations of process variation should fit within the tolerance limits of the process”; hence, the name Six Sigma.
71Methods of sigmametric measurement Six SigmaMethods of sigmametric measurement
72Tea = tolerable error or allowable total error (determined by CLIA) Six SigmaSigma = (Tea – bias)/cvTea = tolerable error or allowable total error (determined by CLIA)Bias = inaccuracy
73Six SigmaA shift or bias of 1.5 sigma would hardly cause any defects in a six sigma process. The actual rates that are expected are as follows:3.4 DPM for a six-sigma process;233 DPM for a five-sigma process;6210 DPM for a four-sigma process;66,807 DPM for three-sigma; and308,537 DPM for a two-sigma process
78Methods with 6 sigma performance are considered “World class”. Six SigmaMethods with 6 sigma performance are considered “World class”.Methods with sigma performance less than 3 are not acceptable for production.
79Chemistry Test or Analyte CLIA Acceptable Performance Six SigmaChemistry Test or AnalyteCLIA Acceptable PerformanceFive-Sigma PrecisionSix-Sigma PrecisionBlood gas pCO25 mm Hg or 8% (greater)1 mm Hg or 1.6%0.8 mm Hg or 1.3%Blood gas pH0.04 pH units0.008 pH unitspH unitsCalcium, total1.0 mg/dL0.2 mg/dL0.17 mg/dLChloride5%1.0%0.83%Cholesterol, total10%2.0%1.7%Cholesterol, HDL30%6.0%5.0%Creatine kinaseCreatinine0.3 mg/dl or 15% (greater)0.06 mg/dL or 3.0%0.05 mg/dL or 2.5%
80Chemistry Test or Analyte CLIA Acceptable Performance Six SigmaChemistry Test or AnalyteCLIA Acceptable PerformanceFive-Sigma PrecisionSix-Sigma PrecisionALT20%4.0%3.3%Albumin10%2.0%1.7%Alkaline Phosphatase30%6.0%5.0%AmylaseBilirubin, total0.4 mg/dL or 20% (greater)0.08 mg/dL or 4%0.067 mg/dL or 3.3%
81Six SigmaGlucose6 mg/dL or 10% (greater)1.2 mg/dL or 2.0%1.0 mg/dL or 1.7%Iron, total20%4.0%3.3%LDHMagnesium25%5.0%4.2%Potassium0.5 mmol/L0.1 mmol/L0.08 mmol/LSodium4 mmol/L0.8 mmol/L0.67 mmol/LTotal protein10%2.0%1.7%Urea Nitrogen2 mg/dL or 9% (greater)0.4 mg/dL or 1.8%0.33 mg/dL or 1.5%Uric acid17%3.4%2.8%
82Toxicology Test or Analyte Alcohol, blood25%5.0%4.2%Blood lead10% or 4 mcg/dL (greater)2.0% or 0.8 mcg/dL1.7% or mcg/dLCarbamazepineDigoxin20% or 0.2 ng/mL (greater)4.0% or ng/mL3.3% or ng/mLEthosuximide20%4.0%3.3%GentamicinLithium0.3 mmol/L or 20% (greater)0.06 mmol/L or 4.0%0.05 mmol/L or 3.3%PhenobarbitalPhenytoinPrimidoneProcainamideQuinidineTheophyllineTobramycinValproic acid
83Hematology Test or Analyte Partial thromboplastin time Six SigmaHematology Test or AnalyteErythrocyte count6%1.2%1.0%HematocritHemoglobin7%1.4%Leukocyte count15%3.0%2.5%Platelet count25%5.0%4.2%FibrinogenPartial thromboplastin timeProthrombin time