Quality Control in Clinical Chemistry

1. Rotational Training in Chemical Pathology
Lesson No 11 & 12
Interactive Lecture on
Quality Control
by
Brig Aamir Ijaz (Retd)
MCPS, FCPS, FRCP (Edin), MCPS-HPE
Prof and Consultant Chemical Pathology
RMI Peshawar

2. Specific Learning
Outcome
At the end of this lecture the
students will be able to describe the
processes involved in Quality
Management.

3. • Write FIVE Qs of total quality
management
Task 1

4. TQM Framework

5. MCQ No 1
A laboratory manager is concentrating on the measures like
reducing turnaround time, specimen identification, patient
identification and test utility. Which of the following term best
describes these processes:
A. Quality Assurance
B. Quality Control
C. Quality Improvement
D. Quality Laboratory Processes
E. Quality Planning
•
A. Quality Assurance

6. 6
Quality Assurance/Assessment (QA)
• An all inclusive / comprehensive system
monitoring the accuracy of test results where
all steps before, during and after the testing
process are considered.
• It includes pre-analytic, analytic and post
analytic factors
• Provides a structure for achieving lab and
hospital quality goals

7. 7
Quality Control (QC)
• QC systems monitor the analytical process; detect and
minimize errors during the analysis and prevent
reporting of erroneous test results.
• It is like ‘product testing’ in an industry
• It uses statistical analysis of test system data
• Requires following published rules
• Westgard Rules

8. Types of QC
Internal
When to run QC
• Daily
• Establishment of reference ranges
• Validation of a new reagent lot and/or
shipment
• Following instrument repair
8

9. Types of QC
External
Also Called ‘Proficiency Testing’
• Determination of laboratory testing performance
by means of inter-laboratory comparisons
• NEQAPP in Pakistan
• CAP, CLIA, The Joint Commission requirement
• Must be integrated within routine workload and
analyzed by personnel who are running the tests.
• Ongoing evaluation of results to correct for
unacceptable results
• Used to access employee competency
9

10. MCQ No 2
Which of the following is mostly a cause of Random
Error?
A. Change in reagent or calibrator lot numbers
B. Deterioration of reagents or calibrators
C.Fluctuation in power supply
D.Improperly prepared reagents
E. Wrong calibrator values
D. Fluctuation in power supply

11. Random Error
• Imprecision of the test system
causing a scatter or spread of
control values around the mean
11

12. Causes of Random Error
• Air bubbles in reagent
• Improperly mixed reagents
• Reagent lines, sampling, or reagent syringes
• Improperly fitting pipette tips
• Clogged or imprecise pipettes
• Fluctuations in power supply
12

13. Systematic Error
• Systematic change in the test system
resulting in a displacement of the mean
from the original value
• Systematic error of an analytic system
is predictable and causes shifts or
trends on control charts that are
consistently low or high
13

14. Causes of Systematic Error
• Change in reagent or calibrator lot numbers
• Wrong calibrator values
• Improperly prepared reagents
• Deterioration of reagents or calibrators
• Inappropriate storage of reagents or calibrators
• Variation in sample or reagent volumes due to pipettor
misalignments
• Variation in temperature or reaction chambers
• Deterioration of photometric light source
• Variation in procedure between technologists
14

15. Accuracy and Precision
• The degree of fluctuation in the measurements is
indicative of the precision of the assay.
• Precision-refers to the ability to get the same (but not
necessarily ‘true’) result time after time.
• The closeness of measurements to the true
value is indicative of the accuracy of the assay.
• Accuracy - An accurate result is one that is the ‘true’
result.
15

16. What this diagram indicates

17. • •
Systematic Error Random Error

18. Shifts and Trends
Shift
• QC data results are distributed on
one side of the mean for 6-7
consecutive days
Trend
• Consistent increase or decrease of
QC data points over a period of 6-7
days
18

19. Bias
• Bias – the amount by which an
analysis varies from the correct
result.
• Example, If the Expected Value
is 50 units, and the result of an
analysis is 47, the bias is 3 units.
19

20. MCQ No 3
In a tertiary care hospital a Consultant Chemical Pathologist has
joined the department after getting training from Japan. He launches
a new programme for a marked reduction of the lab errors and sets a
target of < 3.4 errors per million.
Which of the following QM procedure he is trying to introduce in
his lab:
A. Delta Check
B. External Quality Assurance
C. Internal Quality Control
D. Quality Planning
E. Six Sigma
E. Six Sigma

21. MCQ No 5
Six Sigma Matrix are commonly used in Medical Field to
assess overall quality programme. Following is a list of
error logs of various laboratories in terms of Six Sigma.
Which lab is performing the best:
A. Lab No. 1 is 3.5
B. Lab No. 2 is 5.8
C. Lab No. 3 is 2.2
D. Lab No. 4 is 3.9
E. Lab No. 5 is 4.7
B. Lab No. 2 is 5.8

22. Please write the following control materials
in the order of the accuracy and reliability:
A. Lyophilized, bovine, un-assayed controls
B. Lyophilized, bovine, assayed controls
C. Liquid, human, and assayed controls
Task 2

23. QC Materials
• A QC material is a patient-like material ideally
made from human serum.
• It can be a liquid or Lyophilized (freeze dried)
• It can be assayed with given values, target value
and range or it can be un-assayed
• Liquid, human and assayed are the best ones
23

24. Some Basic Statistics

25. MCQ No 6
Normal data means:
A. Labs own generated values
B. Result of disease free subjects
C. Result of healthy individuals
D. Symmetrical distribution
E. Values within reference range
D. Symmetrical distribution

26. Gaussian/Normal Distribution
• All values are
symmetrically
distributed around the
mean
• Characteristic “bell-
shaped” curve
• Assumed for all quality
control statistics
26

27. MCQ No 7
Which of the following is NOT a
measure of central tendency?
A. Average
B. Mean
C. Median
D. Mode
E. Standard deviation
D. Standard Deviation

28. Measures of Central Tendency
• Mean (x̄ ) - the mathematical average of a group of numbers,
determined by adding a group of numbers (events) and dividing the
result by the number of events
• Median - determined as the ‘middle’ of a group of numbers that have
been arranged in sequential order. That is to say, there are an equal
number of numbers on either side of the ‘middle’ number. In an odd #
of observations, it is the middle observation. In an even # of
observations, average the two middle values.
• Mode - the number that appears most frequently in a group of
numbers. There can be more than mode, or none at all.
28

29. 29
Standard Deviation (SD)
Is a mathematical expression of the dispersion of a group of data
around a mean.
 
 
SD
x x
n




2
1

30.  
 
SD
x x
n




2
1
x
Standard Deviation :
n = the number of observations (how many numerical values )
Σ = the sum of … in this case, the sum of
= the mean value
X = the value of each individual observation
The Standard Deviation is an expression of dispersion … the greater the
SD, the more spread out the observations are
 x x
2

31. Standard Deviation and
Probability
• For a set of data with a
normal distribution, a
value will fall within a
range of:
• +/- 1 SD 68.2 % of
the time
• +/- 2 SD 95.5% of
the time
• +/- 3 SD 99.7% of
the time
31

32. 32
Which is a better assay?
Analyte:
FSH Concentration
SD
1 0.09
5 0.25
10 0.40
25 1.20
100 3.80

33. 33
Coefficient of Variation (CV) %
Analyte:
FSH Concentration
SD CV
1 0.09 9.0
5 0.25 5.0
10 0.40 4.0
25 1.20 4.8
100 3.80 3.8
•The smaller the CV, the more reproducible the
results: more values are closer to the mean.
•Useful in comparing 2 or more analytical
methods
•Ideally should be less than 5 %

34. 34
Coefficient of Variation (CV)
• Indicates what percentage of the mean is represented by the
standard deviation
• Reliable means for comparing the precision or SD at different
units or concentration levels
• Expressed as a percentage
• CV% =
Standard deviation X 100
mean

35. Establishment of a QC System
Two or three levels of control material used
• A control is a material or preparation used to
monitor the stability of the test system within
predetermined limits
• Measure of precision and reproducibility
• Purpose: verify the analytic measurement range of
instrument for a specific analyte
35

36. 36
Establishment of a QC system
Collecting data
• Run assay on control sample & manually enter control
results on chart
• One chart for each analyte and for each level of control
•

37. 37
Collecting Data for QC
Charting techniques
• Levey Jennings chart is a graph that plots QC values in
terms of how many standard deviations each value is from
the mean
•

38. 38
Use of Standard
Deviation
• Once you have determined the standard deviation,
must use the information to evaluate current/ future
analysis.
• Most labs make use of ± 2 SD or 95% confidence
limit. To put this into a workable form, you must
establish the range of the ± 2 SDs

39. 39
So, how do we determine the
range of acceptable results ?
Scenario
• Mean of group of control values = 104 mg/dL
• Standard Deviation = ± 5 mg/dL
• Determine the Range of ± 2SD; (which will allow
you to evaluate acceptability of performance of
the control on subsequent days.)
• Is a control value of 100 mg/dL acceptable?

40. LJ Plot
104
mg/dl
109
mg/dl
114
mg/dl
99
mg/dl
94
mg/dl
100
mg/dl

41. 41
Westgard Multirule System
• Multi-rule system developed
by Dr. James O. Westgard
based on statistical concepts
• Combination of decision
criteria or rules to assess if a
system is in control
• Used when at least 2 levels
of control are run with the
examination run
• Cannot be used with only one
control
Dr. Westgard

42. 12s refers to the control rule that is commonly used with
a Levey-Jennings chart when the control limits are set
as the mean plus/minus 2s. In the original Westgard
multirule QC procedure, this rule is used as a warning
rule to trigger careful inspection of the control data by
the following rejection rules.
12s Rule

43. 13s refers to a control rule that is commonly used
with a Levey-Jennings chart when the control limits
are set as the mean plus 3s and the mean minus 3s. A
run is rejected when a single control measurement
exceeds the mean plus 3s or the mean minus 3s
control limit.
13s Rule

44. 22s - reject when 2 consecutive control measurements
exceed the same mean plus 2s or the same mean
minus 2s control limit.
22s Rule

45. R4s - reject when 1 control measurement in a group
exceeds the mean plus 2s and another exceeds the
mean minus 2s.
R4s Rule

46. 41s - reject when 4 consecutive control measurements
exceed the same mean plus 1s or the same mean
minus 1s control limit.
41s Rule

47. 10x - reject when 10 consecutive control
measurements fall on one side of the mean.
10X Rule

48. Task No 2
a. Identify the rule at: 3,4,7,9,10,11,12,14,20
b. Name type of error
High: mean=250 and s=5) Low: mean=200 and s=4

49. a. Both control results exceed
their respective +2s limits,
therefore there is a 22s rule
violation across materials.
b. A systematic error is most
likely occurring and is
affecting the results
throughout the critical
analytical range from at
least 200 to 250 mg/dL.
Run 3

50. a. The high control result is
below its -2s limit, which
is a warning of a possible
problem. Inspection with
the 13s, 22s, and R4s
rejection rules that can be
applied within the run do
not confirm a problem.
b. Note that the across-runs
rules would not be applied
because the previous run
was rejected.
Run 4

51. a. The high control result
exceeds its +3s limit, therefore
there is a 13s control rule
violation.
b. This most likely indicates
random error.
Run 7

52. a. The high control result is
below its -2s limit.
b. Inspection of the control
results by the rejection
rules does not confirm a
problem.
Run 9

53. a. The control chart for the
high control material
shows that the last two
measurements have both
exceeded the -2s limit,
therefore a 22s rule
violation has occurred
within material and across
runs.
b. This situation would be
consistent with a loss of
linearity that is beginning
to affect the high end of
the analytical range.
Run 10

54. There is a 12s warning on the
high level control material, but
inspection doesn't show any
other rule violations, therefore,
the patient test results in this
run can be reported.
Run 11

55. The control charts for the high
and low materials show that
the last four control
observations have exceeded
their respective +1s limits,
therefore a 41s rule violation
appears to have occurred
across materials and across
runs.
Run 12

56. a. The control results for the
high material exceeds its
+2s limit and the control
result for the low material
exceeds its -2s limit,
therefore an R4s rule
violation has occurred.
b. This most likely indicates a
random error.
Run 14

57. a. The last five control results
on the high material and
the last five results on the
low material all are lower
than their respective
means, giving a total of ten
consecutive control results
on one side of the mean.
There is a 10x rule
violation across runs and
across materials
b. It indicates that a
systematic error most
likely has occurred.
Run 20

58. Summary of Westgard System
58
Is 1
control
> 2 SD?
12S
No

Yes
No

No

No

No

Yes
No
Violation
random
indicates
error
Violation
random
indicates
error
indicates
error
systematic
Violation
indicates
error
systematic
Violation
Reject
run
Report
Results
Is 1
control
> 3 SD?
13S
Are 2
controls
> 2 SD
on same
side of
mean?
22S
Is SD
controls
between
difference
any 2
> 4?
R4S
Are 4
controls
> +/- 1 SD?
consecutive
42S
Accept
run
Accept
run
Are 10
controls
consecutive
on same
side of
mean?
10X
Report
Results
Reject
run
Reject
run
Reject
run
Reject
run
indicates
error
systematic
Violation
Yes
Yes
Yes
Yes
Test
remaining
rules
Test
remaining
rules
Test
remaining
rules
Test
remaining
rules

59. Quantitative QC-Module 759
Task No 3
Using the Westgard Multirule
System, describe the control
values for each day in the
following slide.

60. Quantitative QC-Module 760

61. Quantitative QC-Module 761
Answers for activity
• Day 21, 22, 24, 26, 27, 30, 31, 33, 34, 36-44 – in control
• Day 23, 28, 29 – 12s
• Day 25 - 13s
• Day 32 – 22s
• Day 35 - R4s

62. Hands-on Exercise

63. Thanks and
Best of Luck