Clinical Chemistry
LECTURE / APRIL 13&15 2021 / SISTER’S PPT
QUALITY ASSURANCE & QUALITY CONTROL
DEFINITION OF TERMS
The degree of agreement between
the result obtained and the “true “value
 Known value / true value
 Relationship between 2 values
 Use of standard & controls
Accuracy  Reference Materials
o Normal
o Abnormal High
o Abnormal Low
o Refer if test/analysis
is accurate
The reproducibility and consistency
Precision of the test method
 Depends on test method
Refers to the results being as close as
possible to the “true” value of the
sample on a consistent basis
Reliability
 Is it worth believing
 Compare with true value
 Refers to standard and control
A biological sample, (often serum),
with known concentration of particular
Control
substance
Sample
 Control is serum
(Controls)
 Consistent = samples &
specimen
Normal range
Reference The values are provided by reference
range texts and laboratories that are
considered normal
Indicates the ability of test to detect
true positive results
 Sensitive to analysis or being
Diagnostic
measured
Sensitivity
 Detect substance being
analyze
 Reported/quantitative
Indicates the ability of test to detect
true-negative results
 Diagnosing
Diagnostic
 Doctor: External/Clinical
Specificity
Manifestation
 Medtech: Microscopically
Test/ Internal diagnosis
QUALITY ASSURANCE & QUALITY CONTROL
All those planned and systematic
activities implemented to provide
adequate confidence that an entity will
Quality fulfill requirements for Quality
Assurance  Level of confidence is
established quality control
charts every month , everyday
(standards/control)
The operational techniques and
activities that are used to fulfill
Quality requirements for quality
Control  Mean
 Statistics
 Sd/graph
QUALITY ASSURANCE STEPS
A. Pre –analytical
considerations include those things that occur
during collection of the sample
1 Patient Considerations
 Correct patient identification
 Closely following testing guidelines,
o i.e. fasting,etc.
 Consideration of interfering conditions
o i.e. stress medication
2 Blood sample procurement (to prevent hemolysis
primarily)
 Correct gauge needle (usually 20-22g)
 Tube sterile, room temperature, dry
 Collect with even gentle pressure
 Do not collect over a hematoma
 Decant sample gently into tube
3 Tube information and recommendations
NOTE!
 Improper patient identification
 Mislabeled specimen
 Incorrect order of draw
 Wrong specimen container
 Incorrect anticoagulant to blood ratio
 Improper mixing of sample and additives
B. Analytical Considerations
1 Specimen suitability
 Lack of lipemia
 Hemolysis
 Adequate sample size etc.
2 Proper reagent handling
 Correct tube
 Correct storage time
 Correct temperature
3 Instrument considerations
 Maintenance – follow manufacturer’s
recommendations concerning servicing
and inspection of parts of instruments
 Quality control testing charts should be
maintained for various assays
C. Post-analytical Considerations
1 Recording results in record properly
2 Proper storage of results
3 Proper releasing of results
NOTE!
 Unavailable or delayed lab results
 Incomplete lab results
 Wrong transcription of the patient’s data
and laboratory results
EMSM 1
Clinical Chemistry
LECTURE / APRIL 13&15 2021 / SISTER’S PPT
KINDS OF QUALITY CONTROL
VARIATIONS External Involves proficiency testing programs
Systematic QC that periodically provide samples of
 Error that influences observations (interlab) unknown concentration of analytes to
consistently in one direction participating in laboratories
o Calibration problems Important in long term accuracy of
o Deterioration of reagents analytical methods
o Control Materials Internal It involves the analyses of control
o Failing Instrumentation QC samples together w/patient specimens
o Poorly written procedures (Intralab) Important for daily monitoring of
accuracy and precision
 Note!
o The main change with systematic
errors is seen as gradual shift in the
quality control charts (to be
covered)
o Constant error- diff bet target value
and assay value regardless of the
sample concentration
o Proportional/slope/%error – results
in greater deviation from target
value due to higher sample
concentration
Random
 These errors are due instrument, operator
and environmental conditions (variations in
techniques)
o Pipetting errors
o Mislabeling
o Temperature fluctuation
o Improper mixing of sample and
reagent
 Note!
o These errors cause sudden
unexpected variability in results
o Present in all measurements; due to
chance can be both positive or
negative
o The basis for varying differences
between repeated measurements
o Affects precision

OBJECTIVES FOR QUALITY CONTROL

To check the stability of machine
 To check quality of reagents
 To check technical errors

CHARACTERISTICS OF AN IDEAL QC
Resembles human sample
Inexpensive and stable for long period
No communicable disease
No matrix effects/ known matrix effects
With known analytes concentration
Convenient packaging for easy dispensing and
storage

EMSM 2
Clinical Chemistry
LECTURE / APRIL 13&15 2021 / SISTER’S PPT
STATISTICAL QC SYSTEM ‎
Statistical Used to interpret the measured
Quality concentrations of control
Control Used to monitor the analytical
System ‎ variations that occur during testing
STEPS
1 Establish allowable limits of variation for
each analytical method
2 Use this limits as criteria for evaluating the
quality control data generated each test
3 Taking remedial action when indicated
(Finding causes of errors, rectifying them, and
re analyzing the patient)
QUALITY CONTROL CHART
CUMULATIVE SUM GRAPH (CUSUM)
It calculates the difference between QC results
and the target means
It identifies consistent has bias problems
This plot will give the earliest indication of
systematic errors
Out of control: slope exceeds 45
The most common method is V-Mask
V-Mask – requires computer implementation
Bias problems  deviations
(outliers found on left side  systematic errors 
causing uniform errors * machine errors)
YOUDEN/TWIN PLOT
It is used to compare results obtained on a high
and low control serum from different laboratories
It displays the results of the analyses by plotting
the mean values for one specimen on the ordinate
and the other specimen at the abscissa
The points falling from the center but not on the
45 degree line suggests a proportional error but if
it’s not, it suggest constant error
 Proportional error- center but not on the
45 degree line
 Constant error - not on the center and 45
degrees line
NOTE:
 The original youden plot. PR_A and PR_B
represent similar samples.
 Notice the two outliers in the upper right
corner of the graph.
 Circle represents 95% coverage probability
 Abscissa (x) – horizontal
 Ordinate (y) - vertical
GAUSSIAN CURVE (BELL-SHAPED CURVE)
It occurs when the data set can be accurately
described by the SD and the mean
It is obtained by plotting the values from multiple
analyses of a sample
It focuses on the distribution of errors from the
analytical method rather than the values from a
healthy population
NOTE!
 Normal distribution curve
 A population probability distribution that is
symmetric about the mean
 Not values of patient
MEASURES OF CENTRAL TENDENCY
Mode The value with the highest frequency
value It is always on the top of energy
(Mo) distribution curve
The value which divides the variable’s
Median
observations in two equal parts
value
It represents the center of the
(M)
distribution
Or average value is equal to the value
Mean
which all the observations should have if
value
they were equal
NOTE!
Low numerical values can be expressed as a
central value
In normal distribution, mean, median, and mode
values coincide
Dispersal/ or how the individual data points are
distributed about the central value
EMSM 3
Clinical Chemistry
LECTURE / APRIL 13&15 2021 / SISTER’S PPT
STANDARD DEVIATION
A measure of dispersion of values from the mean
To determine precision of a method and the
significance of difference between determinations
∑( ̅)
√

s= standard deviation
̅ = mean (average) of a QC values
FORMULA ∑( ̅ ) = the sum of the squares
of the differences between individual
QC values and the mean
n= the number of values in the data
set

VARIANCE
Squared standard deviation that measures
variability
2
V= (SD)
Measures significant difference between groups
of data
COEFFICIENT OF VARIATION (CV)
A percentile expression of the mean
An index of precision
Measures magnitude of variability

ADDITIONAL NOTES
 IMPORTANCE OF QUALITY CONTROLS
SHEWHART LEVEY-JENNINGS OR L-J CHARTS  To check performance
It detects all kinds of analytical errors (random  If the tests is doing right
and systematic) and is used for the estimation of  How are the procedure doing
their magnitude  Sensitive to analytes
It can be used in internal and external quality o Blood sugar
control as well o Electrolytes
When an analytical process is within control, o Enzymes
approximately 68% of all QC values fall with 1  Chemistry department is the busiest
standard (1s).  How to know if test is reliable and credible?
Likewise 95% of all QC values fall within with 2  Test the quality factors
standard (2s) of the mean o Methods/procedure
About 4.5% of all data will be outside the 2  Is it ideal?
limits when the analytical process is the control  Is it sensitive?
Approximately 99.7% of all QC values are found  Sensitive to
to be within 3 standard (3s) of the mean of the substance
mean (analytes)
o Are there errors?
o Machines are doing well?
 Perfectly?
 100%?
o Pipettes and other materials
o Refrigerators and equipment
 To know reliability and credibility
o Test the quality control
o Use statistics
o To assure the laboratory clients
o Check and balance (QA&QC)

EMSM 4
Clinical Chemistry
LECTURE / APRIL 13&15 2021 / SISTER’S PPT

EMSM 5