2. Quality Control & Reference Ranges Flashcards
What is Quality Control (QC)?
One of the most important impacts on laboratory testing; ensures and verifies both precision and accuracy of patient sample results
e.g. Clinical labs use management of documentation as well as incorporation of a continuous improvement process to streamline the overall quality control process
What is the result of successful/effective QC?
It is able to find and correct flaws in the analytical processes of a lab before potentially incorrect patient results are released
What is the result of unsuccessful/ineffective QC?
Can result from “clerical, methodological, technical, PT materials stability, and random errors”
What is the purpose of QC samples expecting to be identical/being tested identically to patients?
The purpose of repeated QC testing is to validate precision and accuracy of the results of patient sample testing
e.g. A glucose quality control reagent is expected to produce results of 96, 98, 101, 92, 93, 88, 92, 93, 91, 90, and 98 mg/dL. These results would indicate a low bias result in the instrument
Precision
The degree of agreement among repeated measurements of the same characteristic on the same sample
Accuracy
How close results are to what is expected from a test
What are alternative methods of QC?
1) Peer testing
2) Alternative monthly review of QC trends
3) Clinical Laboratory Efficiency Testing (PT) Programs
Quality Assurance Program (definition)
Broad spectrum of plans, policies, and procedures that together provide an administrative structure for a laboratory’s efforts to achieve quality goals
Quality Assurance Program (purpose)
To determine whether acceptable quality is being achieved, to plan effective strategies for improving quality, or to design procedures to attain a specified level of quality
What are the elements of a Quality Assurance Program?
1) Commitment: dedication to quality service must be central
2) Facilities and Resources: labs must have adequate space, equipment, materials, supplies, staff, and supervisory personnel, and budgetary resources
3) Technical Competence: high quality personnel are essential for high quality service
Quality Assurance Procedures: Control of PREANALYTICAL Variables
- Test request protocol, patient preparation and identification, specimen collection and transport, specimen processing and storage, etc.
- Lab must provide instructions (procedure manual) for proper patient preparation, specimen collection, and transport
Quality Assurance Procedures: Control of ANALYTICAL Variables
Analytical methods, calibration, documentation of analytical protocol and procedures, monitoring of equipment and materials, preparation and storage of reagents, lot to lot variations, daily, monthly preventative maintenance
Quality Assurance Procedures: Control of POSTANALYTICAL Variables
Recording and reporting of patient data to the physician within the appropriate time interval
What is an example of a Problem Solving Mechanism and what is its purpose?
There needs to be a mechanism for solving problems and implementing changes
e.g. Quality Improvement Team
Outline for a Procedure Manual
1) List primary name of the procedure first, alternative name next
2) List commonly used abbreviations
Quality Assurance Procedures: Clinical Significance
1) Give a brief explanation of how the test is used in clinical medicine
2) Include reference intervals for specific diseases and recommended diagnostic and therapeutic action limits
Quality Assurance Procedures: Principle of the Method
Statement of the principles on which the method is based
Quality Assurance Procedures: Specimen Requirements
1) List the type of specimens that can be used, recommended volume, as well as minimum volume
2) Indicate conditions that render the specimen unacceptable such as hemolysis or lipemia
3) List patient preparation procedures
4) Provide instruction for specimen handling prior to testing
Quality Assurance Procedures: Reagent and Equipment Requirements
1) Provide a list of reagents in order of their use, including standards
2) Indicate the names and addresses of suppliers of detailed instructions for preparation, including check to be performed prior to use
3) List equipment used and special precautions required
Quality Assurance Procedures: Procedure
1) Step-by-step description, including calibration and quality control procedures
2) Enough detail so that assay could be performed by a person unfamiliar with the test
3) Necessary calculations and equations should be included
Quality Assurance Procedures: Reference Ranges
1) List reference ranges for healthy subjects
2) Indicate factors such as age, gender, or race that affects reference values
Quality Assurance Procedures: Comments
Include:
1) Any special analytical variables affecting the test, such as pH or temperature
2) Effects of commonly used drugs, any dangers or personal hazards in the procedure, and any special safety precautions and procedures
Quality Assurance Procedures: References
Give primary literature references which describe the method, or references upon which the method is based
QC Material
Commercially Prepared Biological Material; has a known value for each analyte, but it is treated exactly the same as the patient sample
How is Quality Control Material used?
- It is treated as an unknown sample, but we know the correct value
- Ensures that calibration, reagents, and instruments work properly
- Ensures reliability of each measurement performed on a patient sample
Gaussian Distribution: Definition
A theoretical distribution in which the mean, median, and mode are equal
Mean vs. Median vs. Mode
Mean: average
Median: middle value
Mode: value that occurs most often
Gaussian Distribution Curve: What value should the SD fall under?
+/- 1 SD = 68.2%
+/- 2SD = 95.5%
+/- 3SD = 99.7%
** The shape of the curve will vary based on the precision of the test method
Degree of Variance: What does it tell us?
It tells us what’s acceptable; acceptable degree of variation
e.g. +/- 2 SD from the mean, 95% Confidence, 5% Error Rate
Accuracy: Definition
Relative exactness by which a value represents the true value (usually depends upon the analytical method)
e.g. definitive analytical methods, reference methods
What type of error is associated with accuracy?
Systematic error
Precision: Definition
The relationship between identical samples and how closely they reproduce
What error is associated with precision?
Random error
e.g. increase in random error will increase SD and broaden the Gaussian Curve
What does the random error depend upon?
- Well tested, suitable analytical method
- Well-trained laboratory personnel
- Decrease manipulations (automation)
- Maintain quality reagents and equipment
Calibration Standards (Calibrators): Definition
Known-Knowns
- Usually Reagent Grade Chemical in an aqueous or protein base solution
- Used to calibrate an instrument
- Known quantities of the analyte used for testing and adjusting test system
- Subjected to the same conditions as unknown samples
QC: Material
Known-Unknowns
- Subjected to the same conditions as the patient samples
- Resembles the patient samples with the same physical and chemical characteristics
- Ensures the reliability of each measurement performed on the patient sample
Preparing QC Material: Type of pipette used to reconstitute? Type of diluent used?
Reconstitute with the proper amount and type of diluent
- Pipette: Volumetric Class A
- Type of Diluent: Read Instructions on the Bottle
- ** Let stand for 15-30 minutes
QC Program: Why must you not shake the solution?
Swirl instead of shake because protein denaturation can occur
e.g. any mishandling will invalidate the QC values.
Establishing QC Values: How is this calculated?
• Run the same QC Lot # for at least 20 days (each test)
• calculate the mean
• calculate the +/- 2 SD
• calculate the control range = mean +/- 2 SD
• recalculate the mean, +/- 2SD, and control range each month using the
previous month’s QC values provided they are the same lot number
Westgard Rules (Multi-Rule Shewart Procedure): interpreting points on a graph
Points that are closer to the mean are good, while outliers aren’t considered
e.g. 1-2s, 2-2s, 1-3s rule violation
Why do we apply the Westgard Rules?
Applying the Westgard Rules is a method which analyzes usually two quality control sample results (one normal and abnormal) to determine whether or not there are Random or Systematic Errors in the test method
Westgard Rules: 1-2s (YELLOW LIGHT)
One control exceeding the mean +/- 2SD; A warning rule
Westgard Rules: 1-3s (RED LIGHT)
One control exceeding the mean +/-3SD; A rejection rule that is primarily sensitive to random
error
Westgard Rules: 2-2s
Two consecutive controls exceeding the same mean + 2 SD or mean – 2 SD
- Can be the same control on 2 consecutive days or 2 controls on the same day
- A rejection rule sensitive to systematic error.
e. g. there may be something wrong in reagents
Westgard Rules: R-4s
One control exceeding the mean +2SD and another control exceeding the mean -2SD in the same run; A rejection rule sensitive to random error
Westgard Rules: 4-1s
Four consecutive controls exceeding the same mean + 1SD or mean –1SD; Rejection rule sensitive to systematic error
Random Error Rules vs. Systematic Rules: How are they categorized?
Random Error Rules: 1-3s, R-4s
Systematic Rules: 2-2s, 4-1s
Quality Control Charts: Trend & Possible Causes
A gradual change in one direction away from the mean
POSSIBLE CAUSES:
- slow changes/deterioration of Reagents
- slow changes/deterioration of Calibrators
- slow changes/failure of an Instrument component.
*** Change in Accuracy, therefore Systematic Error
Which Westgard Rules would identify a Trend? What would you do?
2-2s, 4-1s
- Check calibration
- Check reagents
Shift: Definition & Possible Causes
An abrupt change in an analytical system that continues at the new level above or below the mean
POSSIBLE CAUSES
- New Calibration Standards
- New Lot of Reagent
- Sudden changes in Instrument Sensitivity
*** Change in Accuracy, therefore Systematic Error
Which Westgard Rules would identify a Shift? What would you do?
2-2s, 4-1s
- Recalibrate
- Identify New Lots of Reagent in Maintenance Log Book and on QC charts
Outlier: What happens if a result is greater than +/- 3SD?
Change in Precision, therefore Random Error
Which Westgard Rules would identify an Outlier? What would you do?
1-3s, R-4s
- Check the Pipetting System
- Check the Instrument for Stability
Formula for Calculating Standard Deviation: calculate the mean of 20 or more numbers
• Round to match the significant number (X)
• Subtract the Mean from each number (X)
• Square the difference
• Divide the sum of the squared differences by n-1
• Take the square root. Equal to 1 SD
• Multiply +/1 SD by 2 to get +/2 SD
• Calculate the Control Range = Mean +/- 2 SD
** Refer to formula in pwpt
Coefficient of Variation: Purpose + Formula
Used to compare test methods based on their precision
%CV = +/- 1 SD / Mean x 100%
What is the relationship between %CV and precision?
Indirectly proportional relationship: the lower the % CV, the better the method’s precision
