 At the end of the Lesson the students

are able to:

› Define Quality control
› Differentiate the types of QC
› Determine the basic statistics for quality
control
 A system of ensuring accuracy and
precision in the laboratory by including
quality control reagents in every series
of measurements.
 A process of ensuring that analytical
results are correct by testing known
samples (control solutions) that
resemble patient samples.
 It involves the process of monitoring
the characteristics of the analytical
processes and detects analytical errors
during testing.
 It is one component of the quality
assurance system.
 Statistical process
 Used to monitor
 And evaluate
 The analytical process
 That produces patient results
 Regular testing of quality control
procedures along with patient samples
 Comparison of quality control results to
specific statistical limits (ranges)
 Diagnostic test
› Result
 Patient result
 Quality control result
 Quantitative (a number)
 Qualitative (positive or negative)
 Semi-quantitative (limited to a few
different values)
 Are used to validate whether the
instrument is operating within pre-
defined specifications
 Inferring that patient tests results are
reliable
 Let’s assume the measured value of
potassium in a patient serum is 2.8
mmol/L (a unit of measure, millimoles
per liter)
 Result is abnormally low and indicates
an inappropriate loss of potassium.
 But how does the person
performing the test known
that this result is truly
reliable?
 It could be possible that the instrument
is out of calibration and the patient’s
true potassium value is 4.2 mmol/L –
normal result.
 The question of reliability for most
testing can be resolved by regular use
of quality control materials and
statistical process control.
 Reliability
- the ability of an analytical method to
maintain accuracy and precision over
an extended period of time during
which equipment, reagents and
personnel may change.
 Practicability
The degree by which a method is easily
repeated
 Precision or reproducibility
The ability of an analytical method to
give repeated results on the same
sample that agree with one another.
 Accuracy
The nearness or closeness of the
assayed value to the true or target
value
 Is the ability of an analytical method to
measure only the analyte of interest
 Sensitivity
Is the ability of an analytical method to
measure the smallest concentration of
the analyte of interest
1. Intralab (Internal QC)
2. Interlab (External QC)
 It involves the analyses of control
samples together with the patient
specimens.
 It detects changes in performance
between the present operation and the
“stable” operation
 It is important for the daily monitoring
of accuracy and precision of analytical
methods
 Detects both random and systematic
errors
 It involves proficiency testing programs
that periodically provide samples of
unknown concentration of analytes to
participating laboratories
 It is important in maintaining long-term
accuracy of the analytical methods.
 It is also used to determine estimates
of the state-of-the-art interlaboratory
performance
 Difference of >2 in the results indicates
that a laboratory is not in aggrement
with the rest of the laboratories
included in the program.
1. To check the stability of the machine
2. To check the quality of reagents
3. To check technical errors
 Is a patient-like material ideally made
from human serum, urine or spinal fluid
 It can be a liquid or freeze-dried
(lyophilized) material and is composed
of one or more constituents (analytes)
of known concentration.
 It is tested in the same manner as
patient samples.
 Normal control product
› Contains normal levels of the analyte being
tested
 AbnormaL control product
› Contains the analyte at a concentration
above or below the normal range for the
analyte.
EXAMPLE
 Normal range for a potassium level is
about 3.5 – 5.0 mmol/L
 Normal control = ?
 Abnormal control = ?
1. Resembles human sample
2. Inexpensive and stable for long
periods
3. No communicable diseases
4. No matrix effects/known matrix effects
5. With known analyte concentrations
6. Convenient packaging for easy
dispensing and storage
 At least daily to monitor analytical process
 Test stable for 24 hours or some change
has occurred – controls should be assayed
more frequently
 Regular testing of QCPs– creates a
database that the laboratory uses to
validate the test system.
 Validation occurs by comparing daily QC
results to a laboratory-defined range of
QC values.
Test: Instrument: Instrument Unit of Measure:
Potassiu No. 1 mmol/L
m
Level I Level II Patient Results
Normal Control Abnormal Control
Range 3.7 – 4.3 6.7 – 7.3 mmol/L
mmol/L
1 November 4.0 7.0 4.2, 4.0, 3.8, 5.0, 5.8, 4.2
2 November 4.1 7.0 3.8, 4.4, 4.6, 3.9, 4.8, 4.4,
3.9
3 November 4.0 6.9 4.4, 3.9, 3.7, 4.7
4 November 4.2 7.1 4.7, 5.6, 4.2, 3.7, 4.3
5 November 4.1 7.0 4.2, 4.3, 4.1, 4.3
6 November 4.1 7.0 4.6, 4.4, 5.5, 3.8, 3.2
 QC statistics for each test performed in
the laboratory are calculated from the QC
database collected by regular testing of
control products. The data collected is
specific for each level of control.
 Consequently, the statistics and ranges
calculated from this data are also
specific for each level of control and
reflect the behavior of the test at
specific concentrations. The most
fundamental statistics used by the
laboratory are the mean [x] and
standard deviation [s].
 The mean (or average) is the
laboratory’s estimate of the analyte’s
true value for a specific level of control.
 The formula for Where:  = sum
calculating the xn = each value in
mean [x] is: the data set
 xn/n n = number of
values in the data
set
 To calculate a mean for a specific level of
control, first, add all the values collected
for that control. Then divide the sum of
these values by the total number of
values.
 For instance, to calculate the mean
for the normal control (Level I) in
Table 1, find the sum of the data
{4.0, 4.1, 4.0, 4.2, 4.1, 4.1, 4.2}.
The sum [] is 28.7 mmol/L.
 The number of values is 7 (n=7).
Therefore, the mean for the normal
potassium control in Table 1 from 11/1
to 11/7 is 4.1 mmol/L (or 28.7 mmol/L
divided by 7).
• Calculate the normal and/ or abnormal control mean
for each of the following sets of control data
• Laboratory A
Level I (Normal Control)
Unassayed Chemistry Control, Lot. No. 12345
Test: Creatinine Kinase
Instrument: ABC
Units: U/L
Control Values are:
{94, 93, 97, 95, 95, 100, 100, 99, 100, 99}
 xn/n
 xn = 972
 N = 10
Therefore:
mean = 972/ 10
mean = 97. 2 U/L
• Laboratory A Level II (Abnormal
Control)
Unassayed Chemistry Control, Lot. No.
12345
Test: Creatinine Kinase
Instrument: ABC
Units: U/L
Control Values are:
{327, 325, 321, 323, 315, 308, 304, 298,
327, 334}
 xn/n
 xn = 3182
 N = 10
Therefore:
mean = 3182/10
mean = 318.2
• Laboratory B
Unassayed Chemistry Control, Lot. No.
12345
Test: Aspartate Aminotransferase (AST)
Instrument: ABC
Units: U/L
Control Values are:
{183, 185, 182, 181, 182, 180, 182,
181, 179, 181}
 xn/n
 xn = 1816
 N = 10
Therefore:
mean = 1816/10
mean = 181.6
 Standard deviation
› Is a statistic that quantifies how close
numerical values (i.e. QC values) are in
relation to each other.
› The term precision is often used
interchangeably with standard deviation.
› Another term, imprecision, is used to
express how far apart numerical values
are from each other.
 Is calculated for control products from
the same data used to calculate the
mean
 It provides the laboratory an estimate
of test consistency at specific
concentrations.
 The repeatability of a test may be
consistent (low standard deviation, low
imprecision)
 Or inconsistent (high standard
deviation, high imprecision)
 Inconsistent repeatability may be due
to the chemistry involved or to a
malfunction.
 If it is a malfunction, the laboratory
must correct the problem.
 It is desirable to get repeated
measurements of the same specimen
as close as possible.
 Good precision is especially needed for
tests that are repeated regularly on the
same patient to track treatment or
disease progress.
 For example, a diabetic patient in a
critical care situation may have glucose
levels run every 2 to 4 hours.
In this case, it is important for the
glucose test to be precise because lack
of precision can cause loss of test
reliability.
If there is a lot of variability in the test
performance (high imprecision, high
standard deviation), the glucose result
at different times may not be true.
May also be used to monitor on-going
day-to-day performance.

For instance, if during the next week of

testing, the standard deviation
calculated in the example for the normal
potassium control increases from 0.08 to
0.16 mmmo/L, this indicates a serious
loss of precision. This instability may be
due to a malfunction of the analytical
process.
 Investigation of the test system is
necessary and the following questions
should be asked:
 Has the reagent or reagent lot changed
recently?
 Has maintenance been performed routinely
and on schedule?
 Does the potassium electrode require
cleaning or replacement?
 Are the reagent and sample pipettes
operating correctly?
 Has the test operate changed recently?
 Where:  = sum
 s = standard deviation
 x = mean (average) of
(xn – x)2 the QC values
 (x – x)2 = the sum
n-1 n
of the squares of
differences between
individual QC values
and the mean
 n = the number of
values in the data set
 x = 4.0 + 4.1 + 4.0 +4.2 + 4.1
+ 4.1 + 4.2 mmol/L
 x = 28.7 mmol/L /7

 x = 4.1 mmol/L
 x x- x (x-x)2
4.0
4.1
4.0
4.2
4.1
4.1
4.2
Mean = 4.1 (xn – x)2?
 x x- x (x-x)2
4.0 -0.1 0.01
4.1 0 0
4.0 -0.1 0.01
4.2 0.1 0.01
4.1 0 0
4.1 0 0
4.2 0.1 0.01
Mean = 4.1 (xn – x)2? =
0.04
 Therefore
 n=7

s= 0.04
7-1
s= 0.04
6

s = 0.0816 or 0.1 (Rounded)

 The standard deviation for one week of
testing of the normal potassium control
is 0.082 mmol/L.
 Now that the amount of precision is
known, some assumptions can be
made about how well this test is
performing.
 Calculate the standard deviation of the
following:
• Laboratory A
Level I (Normal Control)
Unassayed Chemistry Control, Lot. No. 12345
Test: Creatinine Kinase
Instrument: ABC
Units: U/L
Control Values are:
{94, 93, 97, 95, 95, 100, 100, 99, 100, 99}
• Laboratory A Level II (Abnormal
Control)
Unassayed Chemistry Control, Lot. No.
12345
Test: Creatinine Kinase
Instrument: ABC
Units: U/L
Control Values are:
{327, 325, 321, 323, 315, 308, 304, 298,
327, 334}
• Laboratory B
Unassayed Chemistry Control, Lot. No.
12345
Test: Aspartate Aminotransferase (AST)
Instrument: ABC
Units: U/L
Control Values are:
{183, 185, 182, 181, 182, 180, 182,
181, 179, 181}