Quality Assurance

Quality
Assurance
 refers to planned and
systematic processes
that provide confidence
of a product's or
service's effectiveness
Effect of Pre-analytical variables
on the Quality of lab testing
 Pre-analytical variables is the most important
 Accounts to up to 75% of lab errors
 Analytical phase and post-analytical are dependent
on the specimen submitted in the laboratory
Pre-analytical errors
Analytical phase
 Standardization
 Calibrators
 Reagents
 Test condition

 Quality Control
 External Quality Assurance
 Internal Quality Assurance
 Analytical Methods
 Reliable analytical methods are obtained through careful process of:
 Selection
 Evaluation
 Implementation
 Maintenance
 Control
Analytical methods
 Should contain the following characteristics:

1. Accurate
2. Precise
3. Reliable
4. Sensitive
5. Specific
 Analytical methods
 To determine how good a given
method/test is at detecting disease or
condition, the following are used:

 Diagnostic sensitivity
 Diagnostic specificity
 Positive predictive value
 Negative predictive value
Errors
Quality Control
 Select high quality controls
 Collect at least 20 control values over a period of 20-30 days for each level
of control
 Perform statistical analysis
 Develop Levey-Jennings chart
 Monitor control values using the Levey- Jennings chart and/or Westgard
rules
 Take immediate corrective action, if needed
 Record actions taken
Control materials - Calibrators
 Has known concentration of the substance
being measured
 Used to adjust instrument, kit, test system in
order to standardize the assay
 Sometimes called standard, although usually
not a true standard
 This is not a control
Control materials - control
 Important characteristics
 Similar to the test specimen (matrix)
 Available in large quantity
 Stored in small aliquots
 Ideally, should last for at least 1 year
 Often use biological material, consider bio-hazardous
 Sufficient material from same lot number or serum
pool for one year’s testing
 May be frozen, freeze-dried, or chemically preserved
 Requires very accurate reconstitution if this step is
necessary
Control materials – control
 Assayed
 mean calculated by the manufacturer
 must verify in the laboratory

 Unassayed
 less expensive
 must perform data analysis

 Homemade” or “In-house”
 pooled sera collected in the laboratory
 Characterized
 preserved in small quantities for daily use
QC Data Analysis
 Need data set of at least 20 points, obtained over a 30 day period
 Calculate mean, standard deviation, coefficient of variation; determine target
ranges
 Develop Levey-Jennings charts, plot results
Measurement variability
 Make sure that there is procedural variation – different operators / different
times of a day
 A certain amount of variability will naturally occur when a control is tested
repeatedly.
 Variability is affected by operator technique, environmental conditions, and
the performance characteristics of the assay method.
 The goal is to differentiate between variability due to chance from that due to
error.
 QC statistics
 Measure of
central
tendency
 Mean, Median,
Mode
 Measure of
dispersion
 SD, CV,
Range,
Variance
Measure of dispersion or variability
 SD is the most commonly used
Normal Distribution
 All values are symmetrically distributed around the mean
 Characteristic “bell-shaped” curve
 Assumed for all quality control statistics
RULE in QC
 In general, laboratories use the ± 2SD (95%) criteria fpr the limits of the
acceptable range for a test
 When QC measurement falls within the range, there is 95.5% confidence that
the measurement is correct
 Only 4.5% of the time will a value fall outside of the range due to chance;
more likely it will be due to error
Monitoring QC Data
 Use Levey-Jennings chart
 Plot control values each run, make decision regarding acceptability of run
 Monitor over time to evaluate the precision and accuracy of repeated
measurements
 Review charts at defined intervals, take necessary action, and document
Levey-Jennings Chart
Findings over time
 Ideally should have control values clustered about the mean (+/-2 SD) with
little variation in the upward or downward direction
 Imprecision = large amount of scatter about the mean. Usually caused by
errors in technique
 Inaccuracy = may see as a trend or a shift, usually caused by change in the
testing process
 Random error = no pattern. Usually poor technique, malfunctioning
equipment
Trend
 Upward:
 Expired lamp/photocells
 Denatured standard
 Contamination of reagents

 Downward
 Standard that are too concentrated
 Contamination of reagents
Shift
 Upward
 Partial electric failure
 New standard is over diluted
 Denatured standard that has
stabilized
 Improperly prepared reagent
 Inaccurate timer
 Deterioration of indicator
 Dirty glassware
 Downward
 Overheating in temperature  Increase concentration of standard and reagents
sensitive analysis
 Contaminated reagents
 Inaccurate timer
 Underheating in analysis
 Contaminated glassware
Outlier
 A single point in the chart suddenly out of range
 Contamination of a single specimen
 Faulty pipet
 Incorrect dilution of test
Westgard Multirule
 “Multirule Quality Control”
 Uses a combination of decision criteria or control rules
 Allows determination of whether an analytical run is “in-control” or “out-of
control”
Systematic Errors
 Shift/trends
 Calibration materials are impure
 Improper preparation of standards
 Unstable/contaminated
 Unstable blanks
 Faulty equipment
 Inadequate calibration
 Incorrect concentration of stock standard
Random Errors
 Wideness of curve – increased in SD; suggests poor precision (difficult to
control and identify)
 Lack of reproducibility
 Pipeting of samples and reagents
 Reconstituting reagents (lyophilized)
 Mixing
 Temperature stability
 Timing regulation and in photometry and other sensors
 Technique variation; temperature fluctuation; use of inaccurately calibrated pipets