QUALITY CONTROL Practicability
• A system of ensuring accuracy and precision in the • The degree by which a method is easily repeated
laboratory by including quality control reagents in
every series of measurements Reliability
• A process of ensuring that analytical results are • The ability of an analytical method to maintain
correct by testing known samples (control sol'n) accuracy and precision over an extended period
that resemble patient samples of time during which equipment, reagents and
• One component of quality assurance (QA) system personnel may change
Diagnostic sensitivity
Sensitivity
• It is the ability of an analytical method to measure the • Ability of the test to detect the proportion of
smallest concentration of the analyte of interest individuals with that disease who test positively
for the disease
Specificity Diagnostic specificity
• It is the ability of an analytical method to measure • The ability of the test to detect the proportion of
only the analyte of interest individuals without the disease who test
negatively for the disease
Accuracy
• The nearness or closeness of the assayed value to Positive Predictive Value (PPV)
the true or target value
• % of time that a positive result is correct
Precision “reproducibility"
• The ability of an analytical method give repeated
results on the same sample that agree with one
another
Negative Predictive Value (NPV)
• % of time that a negative result is correct
Objectives of QC
✓ Check the ability of machine
✓ Check quality of reagents
✓ Check technical errors
Characteristics of an Ideal OC
1) Resembles human sample
2) Inexpensive and stable for long period
3) No communicable disease
4) No matrix effects/known matrix effects
5) With known analytes concentration
6) Convenient packaging for easy dispensing and
storage
Notes to remember
• QC materials should resemble human sample and be
available for a minimum of one year (same lot number)
• Human control materials are preferred but due to limited
sources and biohazard considerations, bovine control
materials are used
• Bovine based QC material is NOT the choice for
immunochemistry, dye-binding and certain bilirubin
assays
• Matrix effects results of improper product manufacturing,
use of unpurified human and non-human analyte
additives and altered protein components
Additional Notes
GRADES OF CHEMICALS
AUCU Na Te Co
• Analytical Reagent (A)
• Ultrapure Reagent (U)
• Chemically Pure (CP)
• US Pharmacopeia (USP)
• National Formulary (NF)
• Technical / Commercial
Types of QC
• Intralab (Internal QC) QC Centrifuge
• Interlab (External QC) • calibration: QUARTERLY
• disinfection: WEEKLY
Intralab (Internal QC)
• Involves the analyses of control samples together used to calibrate centrifuge:
with the patient specimens TACHOMETER (optical RPM sensor)
• Detects changes in performance between the
present operation and the "stable" operation
• Important for the daily monitoring of accuracy and Types of variations
precision of analytical methods 1) Random error
• Detects random and systematic errors 2) Systematic error
a. Constant error
Interlab (External QC) b. Proportional error (slope/ percent error)
• Involves proficiency testing programs that 3) Clerical error
periodically provide samples of unknown
concentration of analytes to participating Random error
laboratories • aka indeterminate, unpredictable, imprecision error
• It is important in maintaining long-term accuracy of • Present in all measurements; due to chance, can be
the analytical methods both positive or negative
• It is also used to determine estimates of the state- • The basis for varying differences between repeated
of-the-art interlaboratory performance measurements
o reagent dispensing calibrator reconstitution Notes to Remember
o sample evaporation • The first step in method evaluation is the precision
o temperature of analyzer study which estimates the random error.
o electro-optical mechanism
• All error criteria (random, proportional, constant and
o environmental conditions
systematic error) must be less than the allowable error
o instability of instrument
or fixed limits for a method to be considered
o variation in handling techniques: pipetting,
acceptable
mixing, timing variation in operators
• Allowable errors are expressed either in measurement
anticoagulant or drug interference
units of the analyte (mmol/L) or percentage
Systematic error • The length of time lapsed between drawing and the
separation of serum or plasma from the cells can be
• Is an error that influences observations consistently
a factor in analytical testing
in one direction (Constant differences)
• Non-laboratory personnel were responsible for 29% of
• Detected as either positive or negative bias;
the errors with regards to laboratory results
o Dirty photometer, faulty or leaky ISE
o aging reagent, aging calibrators instrument What is the difference between:
components, wear and tear of instrument optical • Screening test: very sensitive
changes • Confirmatory test: very specific
o fluctations in line voltage • Gold standard test: best approximation of a true
o reagent lot variability value
o calibration differences
o technologist interactions Mean
o poorly written procedures • Measure of central tendency
• It is associated with symmetrical or normal
Constant error distribution
• Refers to the differences between the target value • Affects accuracy
and the assay value • sum of observations
• Exist when there is a constant diff bet the
comparative method and the test method Standard Deviation
regardless of the cxn • Measure of the dispersion of values from the
mean
Proportional / Slope / Percent Error • It helps describe the normal curve
• Result in greater deviation from the target value • Measures reproducibility
due to higher sample cxn
• Exist when the difference bet the test method and the
comparative method values are proportional to the Coefficient of variation
analyte concentration • A percentile expression of the mean
• Measures relations magnitude of variability
Types of Clerical Errors • Index of precision or reproducibility
Pre-analytical Error
▪ Improper patient identification Variance
▪ Mislabeled specimen • Called the standard deviation squared
▪ Incorrect order of draw • A measure of variability
▪ Wrong specimen container
▪ Incorrect anticoagulant to blood ratio Median
▪ Improper mixing of sample and additives • Value of the observation that divides the
▪ Incorrect specimen preservation observations into two groups, each containing
▪ Incorrect used of tubes for blood collection equal numbers of observations; 50th centile
▪ Mishandled specimen (transpo and storage)
▪ Missed or incorrectly interpreted laboratory request Mode
• Most frequent observation
Post-analytical Error
▪ Unavailable or delayed lab results Inferential Statistics
▪ Incomplete lab results
• Are used to compare the means or SD of two
▪ Wrong transcription of the patient's data and
groups of data
laboratory results
T-test
• Used to determine whether there is a statistically
significant difference between the means of two
groups of data
F-test
• Used to determine whether there is statistically
significant difference between the SD of two
groups of data
CUSUM
• Cumulative Sum Graph
• Calculates the difference between QC results and
the target means
• Commonest method is the V-mask; requires
computer implementation
• Identifies consistent bias problems
• This plot will give the earliest indication of
symmetric errors (trend) and can be used with the
13s rule
• Very sensitive to small, persistent errors that
Standard Deviation Index (SDI) commonly occur in the modern, low calibration-
• The difference between the value of a data point frequency analyzer
and the mean value divided by the group's SD
QUALITY CONTROL CHART
✓ Gaussian curve (bell-shaped curve)
✓ Cumulative Sum graph (CUSUM)
✓ Youden/Twin Plot
✓ Shewhart Levey-Jennings Chart
✓ Westgard Rule
Gaussian Curve
• Occurs when the data set can be accurately
described by SD and mean
• Obtained by plotting the values from multiple
analyses of a sample
• A population probability distribution that is
symmetric about the mean
• Occurs when data elements are centered around
Youden / Twin Plot
the mean with most elements close to the mean
• Used to compare results obtained on a high and low
control serum from different laboratories
• Displays results of the analyses by plotting the
mean values for one specimen on the ordinate
and the other is abscissa
OUTLIERS
• Control values that are far from remain set of
values
• Highly deviating values
• Random or systematic errors
Shewhart Levey-Jennings
• Allows laboratorians to apply multiple rules without
the aid of the computer
• A graphic representation of the acceptable limits of
variation in the results of an analytical method
INTERPRETATION OF QC DATA
SHIFT
• Formed by control values that distribute themselves
one side or side or either side of the mean
• sudden or abrupt change
• Shift is the reference range due to transient Westgard Rules
instrument differences • Recognized that the use of simple upper and lower
• Causes: improper calibration of instrument, control limits are not enough to identify analytical
change in reagent formulation, instrument • Error detection rates can increase without increasing
maintenance, failure in sampling system/ rgt. the false rejection rate
Dispense system • Westgard used the term control rule to indicate if
the analytical process is out of control
TREND
• Former by control values that either decrease or Control Rule
increase for six consecutive days • 12s - for screening purposes
• gradual loss of reliability in the test system • 13s - effective in det. random error
• Cause: deterioration of reagents, light source and • 22s - response most often to systematic errors
incubation temp. • 41s - responsive to systematic errors
• R4s - responsive to random errors or. increased
imprecision
• 10x - reject a run when ten consecutive results are
on the same side of the mean; systematic error
Analytical run
• Set of control and patient specimens
assayed, evaluated and reported together
Delta check
• Requires computerization of test data so
that current results can be compared with
past results
Interference experiments
• Used to measure systematic errors or
inaccuracy, caused by substance other
than the analyte
• Hgb, lipids, bili, anticoagulant,
preservatives - interferences
Linear range/ Dynamic range
• Concentration range over which the
measured concentration is equal to the
actual concentration without
modification of the method
Physiologic Limit PIPETTING TECHNIQUES
• Absurd value
• Helps detect sample contamination or
dilution, inadequate sample volume,
inadequate reagent volumes, sudden
major problems with the method, or
incorrect recording or transmission of the
result
POCT
• Analytical testing performed outside the
confines of the central laboratory, usually
by non-laboratorian personnel
Quality Assurance
• Can be envisioned as a tripod with program
development, assessment and monitoring
and quality improvement forming the three
legs 2 TYPES OF PIPETTING TCHNIQUES
FORWARD pipetting (1-2)
Quality Patient Care Steps:
• Includes effective the request forms, clear • Press to 1st stop - Press the plunger to
instruction for patient preparation and the first stop.
specimen handling, appropriate reference • Immerse tip - Place the pipette tip into the
ranges and intelligent result reports liquid (just below the surface).
• Aspirate - Slowly release the plunger to
Recovery Experiment draw up the set volume.
• Will show whether a method measures all • Dispense into container - Touch the tip to
the analytes or any part of it the side of the container and press the
• Estimates inaccuracy or systematic errors plunger to the first stop to release liquid.
• Blow-out - Press all the way to the second
Reference Range stop to expel any remaining liquid in the tip.
• reference intervals, reference values • Withdraw tip - Remove the tip from the
• At least 120 individual at each age and sex container while the plunger is stil pressed
category down.
• Only 20 reference individuals need to be • Release plunger - Let go of the plunger
sampled after removing the tip.
Five factors when establishing Reference FORWARD PIPETTING
Intervals • Most commonly used method
1) The composition of the reference population • Used for: Aqueous (water-based) solutions
(age, sex, genetic, socioeconomic factors) like buffers, diluted samples
2) The criteria used for excluding and including • Draws exactly the amount you need.
the individuals from the reference population • Dispenses all of it, including a final blow-
3) The physiologic and environmental out.
conditions of the reference population (obesity,
lifestyle, habit, food and drug intake etc) REVERSE PIPETTING
4) Specimen-collection procedure, including
• Draws more than needed by pressing to
preparation for testing
the second stop.
5) Analytical method used
• Dispenses only the exact amount (plunger
to the first stop).
• The extra liquid stays in the tip and is
discarded.
• Best for thick, sticky, or foamy liquids like
serum or glycerol).
LABORATORY HAZARDS