CLINICAL CHEMISTRY QUALITY MANAGEMENT OUTLINE • Quality Management o Quality Management System o Quality Assurance o Total Quality Management (TQM) o PDCA Cycle o Why do Laboratory Error’s Occur? • Quality Control o Quality Control (QC) o Parameters of Quality Control o Kinds of QC o Conduct of External QC Testing o Interpretation of QC Result o QC Reagents o Method Evaluation o Variations QUALITY MANAGEMENT QUALITY MANAGEMENT SYSTEM • “A set of key quality elements that must be in place for an organization’s work operations to function in a manner to meet the organization’s stated quality objectives” - CLSI • Involved three concepts: o Quality Control → Quality Assurance → total Quality Management • Quality Control o Involves the analytical phase • Quality Assurance o Includes quality control o Involves the pre-analytical, analytical and post-analytical phase. o Includes general policies, practices, policies and procedures of the laboratory. o Assesses the entire quality of the laboratory • Total Quality Management o Includes Quality Control and Quality Assurance. o Includes the entire management where the laboratory is under (hospital, company, etc.) WHY QUALITY MANAGEMENT? • Majority of clinical decisions are based on laboratory data. • How reliable is the result? • What does this value mean to the patient? • “ It is important that we provide confidence in the laboratory data we generate .” QUALITY ASSURANCE • Aka Quality Assurance System • Concerned with the total process happening inside the laboratory. • Monitors quality of the entire laboratory performance. • From pre-analytical phase to post-analytical phase. • Used to represent practices that are generally recommended for ensuring that desired quality goals are achieved. • Monitors the quality of the entire laboratory performance • Pre-analytical Phase - Includes factors in acquiring, handling, transporting, and processing a patient specimen prior to actual analysis • Analytical Phase - Includes factors related to the analysis (methodology, procedures etc.) • Post-analytical Phase - Includes factors after testing (turn -around time, clerical works, etc . ) CONSEQUENCES OF POOR QUALITY IN THE LABORATORY • Inappropriate Action o Over treatment o Non treatment o Over investigation o Under investigation o Delayed Action • Loss of credibility o Does not support the provision of high-quality health care o Non-credibility of the laboratory o No confidence in Laboratory Result • Legal Action o Suspension or revocation of license: ▪ Laboratory ▪ Pathologist ▪ Medical Technologist ▪ Hospital TOTAL QUALITY MANAGEMENT (TQM) • It provides both a management philosophy for organizational development and a management process for improvement of quality in all aspects of work. • All concepts fall under the umbrella of TQM
TQM FRAMEWORK • 5 components working together in a feedback loop • Continuous Quality Improvement • Includes Quality Control and Quality Assurance (both embedded in laboratory practice.) • TQM Framework Components 1. Quality Laboratory Process (QLP) ▪ includes analytical processes and the general policies, practices and procedures that define how all aspects of the laboratory are done (Quality Assurance) 2. Quality Control (QC) ▪ emphasizes statistical control procedures, but also includes non-statistical check procedure such as linearity checks, reagents and standard checks and temperature monitoring 3. Quality Assessment (QA) ▪ concerned primarily with broader measures and monitoring of laboratory performance (TAT, patient ID, test utility). 4. Quality Improvement (QI) ▪ a structured problem solving process to help identify the root cause of a problem and a remedy for that problem. 5. Quality Planning (QP) ▪ provides the planning to eliminate problems identified by QI. PDCA CYCLE • Plan o Provides the planning step o Answers Who, What, Where and How o “QP” • Do o Establish standard policies and procedures o “QLP” • Check o Provides measures for checking how well things are done o “QA and QC” • Act o Provides mechanism for acting on those measures o “QI\ WHY DO LABORATORY ERRORS OCCUR? QUALITY CONTROL QUALITY CONTROL (QC) • Process of ensuring accuracy and precision in the laboratory by including quality control reagents that resembles patient samples in every series of measurement. • It involves the process of monitoring the characteristics of analytical processes and detects analytical errors during testing, and ultimately prevent reporting of inaccurate patient test result. • Objective of QC : 1. To check the stability of machines 2. To check the quality of reagents 3. To check technical errors PARAMETERS OF QUALITY CONTROL 1. Sensitivity 2. Specificity 3. Accuracy 4. Precision 5. Practicability 6. Reliability 7. Diagnostic Sensitivity 8. Diagnostic Specificity
SENSITIVITY VS SPECIFICITY • Sensitivity o • Aka Detection Limit o The ability of an analytical method to measure the smallest concentration of analyte of interest. • Specificity o The ability of analytical method to measure the only analyte of interest. ACCURACY VS PRECISION • Accuracy o Closeness of assayed value to the target value/true value. o Estimation of Accuracy : ▪ Recovery Study -Determines how much analyte can be identified in the sample ▪ Interference Study - Determines if specific compound affect laboratory test ▪ Patient Sample Comparison Study - Assess presence of error in actual patient sample • Precision o Aka Reproducibility o The ability of an analytical method to give repeated result on the same sample that agree with one another PRACTICABILITY VS RELIABILITY • Practicability o The degree by which a method is easily repeated • Reliability o The ability of analytical method to maintain accuracy and precision over an extended period of time DIAGNOSTIC SENSITIVITY • The ability of analytical method to detect the portion of individuals with the disease • Indicates the ability of the test to generate more true-positive and few false-negative. • Screening test require high sensitivity so that no case is missed. DIAGNOSTIC SPECIFICITY • The ability of analytical method to detect the portion of individuals without the disease. • It reflects the ability of the method to detect true-negatives with very few false-positive • Confirmatory test require high sensitivity to be certain of diagnosis DIAGNOSTIC EFFICIENCY • “The test implies that there is 95% chance that a positive tests means than an individual have the disease and 96% of negative tests means that the individual does not have the disease.” • Diagnostic Efficiency Predictive Values o Positive Predictive Value (PPV) ▪ Refers to the probability of an individual to have the disease if tested positive ▪ PPV = # of positive tests with the disease x 100 total # of positive tests ▪ PPV = True positive x100 True positive + False positive o Negative Predictive Value (NPV) ▪ Refers to the probability of an individual to not have the disease if tested negative. ▪ NPV = # of negative tests w/o the disease x 100 total # of negative tests ▪ NPV = True negative x 100 True negative + False negative KINDS OF QC • Intralab Quality Control o aka Internal QC o Involves analyses of control samples together with patient specimens. o Detects changes in performance between the present operation and the stable operations o Purpose: Daily monitoring of accuracy and precision of analytical methods(short-term) o Detects both random and systematic errors in a daily basis.
• Interlab Quality Control o aka External QC o Involves proficiency testing program that provides unknown samples toparticipating laboratories. o Hematology, Serology, Microbiology – once a year o Clinical Chemistry – once a month o Purpose: maintains long-term accuracy of analytical methods. o College of American Pathologist (CAP) Proficiency Program – gold standard for clinical laboratory external QC testing. CONDUCT OF EXTERNAL QC TESTING • A series of unknown samples are sent to the laboratory from the reference laboratory • What? – analyses of unknown samples from reference laboratory with the present method of the laboratory. o Clinical Chemistry – Lung Center of the Philippines o Hematology, Blood Banking – National Kidney and Transplant Institute o Serology of infectious diseases - San Lazaro Hospital o Microbiology, Parasitology, Transfusion-transmitted Infections – Research Institute for Tropical Medicine o Drug testing, Water Bacteriology, Toxicology, Micronutrient Assay etc . – East Avenue Medical Center • Who? – laboratorian who regularly performs analysis of patient using the same analytical method • When? – monthly (should be completed within the usual time as routine samples) • How? – should be treated like patient specimen • Why? – maintains long-term accuracy of analytical method INTERPRETATION OF EXTERNAL QC RESULT • Laboratories using the same method are evaluated by comparing them with the group. • Difference of >2SD – laboratory is not in agreement with the rest of the laboratories included in the program o If laboratory failed to resolve the error – recommendation for closure QC REAGENTS STANDARD SOLUTION • A known analytical solutions whose value is known and given, always measures together with unknown sample. • Most specific known analytical solution o Every vial contains only one analyte. • The value of standard tells you the concentration of your unknown sample. • • Wherein: o C unknown – conc. of unknown o A sample – absorbance of unknown o A standard – absorbance of standard o C standard – conc. of standard (indicated in the vial) ▪ CONTROL SOLUTIONS • A known analytical solutions whose value is known and given, always measures together with unknown sample. • Each vial contains several analytes. • Resemble patient samples. • Used to determine the accuracy and precision of analytical method. • Control levels: o Chemistry: Normal and Abnormal o Immunoassays: High, Normal, Low • Control Limits o Control limits are the expected values represented by intervals of acceptable values with upper and lower limits. o Indicated in the reagent insert. o Calculated from the mean and SD (ideally, +/- 2SD) ▪ In-control – If the control values are within the desired control limits. • The analytical method is accurate and precise ▪ Out-of-control – If the control values are outside the desired control limits. • The analytical method is not accurate nor precise • Sources of Control Solutions : o Human-Based Control Sera ▪ Preferred but not used ▪ Limited sources and biohazardous considerations ▪ 3 Criteria: 1. Non-infectious 2. Non-hemolyzed 3. Non-icteric o Bovine-Control Sera ▪ Used over human based control sera ▪ Resembles human sample and contains the same analytes present in human serum. ▪ Not the choice as QC source for immunochemistry, dye-binding, and certain bilirubin assays CHARACTERISTICS OF AN IDEAL QC SOLUTION : 1. It should resemble patients human sample 2. Inexpensive and stable for long periods 3. No communicable disease 4. No Matrix Effect 5. With known analytical concentration (control limits) METHOD EVALUATION
• Test method must be compared to a method with acceptable accuracy – gold standard • Objective: to determine the total error of test method is less than the allowable error. • To determine Statistical Quality Control (new instrument, new control lot): o Different levels of control material must analyzed (duplicate) for 20 consecutive days • Westgard et al and CLSI: o Duplicate analyses of sample for each method should be done ▪ Duplicate test should be done in different runs and order within 4 hours. o 40 to 100 samples should be run (duplicate) by each method for 8 to 20 days w/in 4 hours. o If 40 samples only, daily analysis of 2 to 5 specimens should be done for 8 days. o Repeated testing – to detect random errors. VARIATIONS • An error encountered in collection, preparation and measurement of samples, including transcription and releasing of laboratory results. • Types of Error: 1. Random Error 2. Systematic Error 3. Clerical Error RANDOM ERROR • It is present in all measurements due to chance • Type of error which varies from sample to sample. • The basis of varying differences between repeated measurement. • Influence Precision • Measured statistically by: o Standard Deviation o Coefficient of Variance • Also known as: o Imprecision o Indeterminate error o Unpredictable error • Mostly due to instruments, operator and environmental conditions • Examples o Mislabelling o Pipetting o Improper mixing of specimen and reagents o Voltage or temperature fluctuations o Dirty optics/light source SYSTEMATIC ERROR • An error that influences observations consistently in one direction (constant difference) • Influence Accuracy • Measured statistically by: o Mean • Also known as: o Inaccuracy o Determinate error o Predictable error • Examples o Improper Calibration of analyzers o Deterioration of Reagents and Control Materials o Improperly made standard solutions o Contaminated Solutions o Unstable and Inadequate Reagent blanks o Leaky Ion Selective Electrode o Failing Instrumentation o Poorly Written Procedures (Impracticability) • Types of Systematic Error o Constant Error ▪ The difference between the target value and the assayed value ▪ Independent of sample concentration ▪ Exists when there is continual difference between the comparative method and the test method regardless of the concentration o Proportional Error ▪ aka slope/percent error ▪ Results in greater deviation from the target value due to higher sample concentration ▪ Exists when the difference between the comparative method and the test method is proportional to the analyte concentration CLERICAL ERROR • Highest frequency of clerical errors occurs with the use of handwritten labels and request forms WHEN DO ERRORS OCCUR? • Pre-Analytical o Mislabeled specimen o Incorrect order of draw o Incorrect patient identification o Wrong specimen container o Mishandled specimen (transport, storage, and/or preservation) o Incorrect use of tubes for blood collection o Missed or incorrect interpreted laboratory request/s • Analytical o Equipment reliability o Reagent stability, integrity, and efficiency o Adequate calibration o Proficiency of personnel and continuous updating of their knowledge o Procedure reliability in terms of ▪ Precision ▪ Accuracy ▪ Analytical Specificity • Post-analytical o Time of release of laboratory result o Laboratory results must be complete ▪ Recorded findings ▪ Any possible remarks ▪ Normal range of results ▪ Significant values must be highlighted (wherever required) ALLOWABLE ERROR (E a ) • Quantity of error that will negatively affect clinical decisions. • If total error of test method: o ≤ E a – acceptable o > E a – corrections must be performed to reduce error