MTH60-315/315E Techniques and Instrument in Medical Technology Laboratory, semester 2/2565, 2(1-3-4)

Quality control
Asst. Prof. Moragot Chatatikun, Ph.D.
Kantapich Kongpol, Ph.D.
School of Allied Health Sciences, Walailak University
E-mail: moragot.ch@wu.ac.th
kantapich.ko@wu.ac.th
 Learning objectives
v To define quality control terms
v To understand and evaluate Levey Jennings Chart for accepting or
rejecting results based on Westgard’s multirules

2
 Quality control (QC)
§ A procedure or set of procedures intended to ensure that
manufactured product or performed service adheres to a defined as
set of quality criteria or meets the requirements of the client or
customer.
ใ การส →ตรวจประเ นผล → ออกไปพ อม ผล
บ คนไ
§ QC in medical laboratory is a statistical process used to monitor and
evaluate the analysis process that produces patient results.

§ QC refers to the measures that must be included during each assay

run to verify that the test is working properly.

§ The aim of QC is simply to ensure that the results generated by the

tests are correct.
3
 Laboratory tests are influenced by
• Condition
- Laboratory environment
• Human
- Knowledgeable staff, competent staff
• Equipment
- Installation, validation, maintenance, calibration, troubleshooting, service and
repair, records
• Machines
• Methods
- Sensitivity, Specificity
- Accuracy, Precision
• Process management: Laboratory Information System (LIS)
• Process of control
- Quality control
- Sample management
ป
ใ ผล ดเ ยน
- Method validation
4
- Method verification
 Quality control (QC) for what?

อนเ น น
มาก
คคล าญ
น า1 mi
ทน าง→ จ ย ใผล ดพลาด
I.

หมดอา
a software ญหา?
me 5
Quality control (QC)
นอก ก.ทดสอบ

ทดสอบ ส
ลอง 0ท0วน

เ ค✓

มาใจ งในอง
lab ไปพ
แก อม บQC

6
 Basic measurement of data
Each day, high-volume clinical laboratories generate thousands of results. This
wealth of clinical laboratory data must be summarized and critically be reviewed to
monitor test performance. The foundation for monitoring performance (known as
QC) is descriptive statistics.

7
 Basic measurement of data
กระจาย ปก
ว

↳หา Meanแเ ย1

เจอ
เยอะ
lfy
LMedianแบบเ
รยฐาน1

บน h Madeฐาน ยม

Mean –average
Median –middle point (skewed distribution)
Mode –two centers (bimodal)
8
 Normal distribution (Gaussian curve)
ไง
mom±isp • All values are symmetrically distributed
around the mean.
หาากลาง อ ลาย → Mean
• Characteristic “bell-shaped” curve
หาบไ deviationกา หา มะ เ น ระ ค า
±µ • Standard (SD) แ– a ป ง
น measure of
the scatter of the sample values around
95
the mean.
SDๆ ไ
นวณ
• Coefficient of variation (CV)
±3sD rm → ค. แ อย
%CV = (SD/mean) x 100
aai. nnn
• CV –reliable means for comparing the
precision or SD at different units or
(A) ≈68% of the results within ±1 SD (1s or 1σ)
(B) 95% of the results within ±2SD (2s or 2σ)
• ยมใ concentration levels.
ไป
เอา 9
(C) ≈99% of the results within ±3SD (3s or 3σ).
 Reference interval (normal distribution)
ปกอ าง อย 120คน
คน
• Reference interval –less than or greater
than a certain value
• A pair of medical decision points that span
the limit of results expected for a given
condition.
• Reference interval are commonly defined as
the range of values into which 95% of
nondisease individuals will fall.
• 5% of nondisease individuals can have lab
results outside the reference interval.
• Reference interval can be used to separate
Gaussian curve (central 95% of value) normal from abnormal values.
• Minimum 120 healthy peoples 10
Reference interval (skewed distribution)
เ องอ ล→หาา ฐาน
1ศตารงกลาง

• Nonparametric determination เ ขวา

• Not normally distributed
• Central 95% of values
• Rank from lowest to highest (2.5th percentiles to 97.5th percentile)
11
 Reference interval
int..แ

µ,

Comparison of an ideal and true laboratory values for

healthy and abnormal populations

Parameters: Sensitivity, Specificity, False positive (FP), False negative (FN)

12
 Sensitivity & Specificity
Diagnostic Sensitivity
Positive test result in the presence of disease
โอกาส ④ใน
ใ ผล เ นโรค
คน
น.$%&'!(!)
!". น *+), $"-+)+.& )&-)
Diagnostic sensitivity = าน
!". "/ $%&'!(!) +!0+.+01(2 )&-)&0 จน งครร งหมด
คน
3%1& $"-+)+.& (35)
=
3%1& $"-+)+.& 35 7 8(2-& !&'()+.& (89)

Diagnostic Specificity
Negative test result with no disease
ใ ผล⑦ใน
โอกาส คนไ เ นโรค
!". !"!$%&'!(!) *+), !&'()+.& )&-)
Diagnostic specificity = !". "/ !"!$%&'!(!) +!0+.+01(2
cfn nnn
)&-)&0

3%1& !&'()+.& (39)

= 13
3%1& !&'()+.& 39 7 8(2-& $"-+)+.& (85)
 Sensitivity & Specificity
คนสองเอคน False positive (FP)
me
8

True negative (TN)

้
2

! ! & &
Sensitivity = = or 80% Specificity = = or 70%
!"# $% &"' $%

14
Predictive value
Positive predictive value (PPV) นาย
ผลบวก
refers to the probability of an individual having the
disease if the result is abnormal
คนใ ผล①เ นโรค
โอกาส จ ง
!". $%&'!(!) *+), $"-+)+.& )&-)
PPV =
น
!". *+), $"-+)+.& )&-) ผลบวก
ด
แหม
0
คน
เออคน
ใ ผลบวก า
=
/%0& $"-+)+.&
ๆ
/%0& $"-+)+.&12(3-& $"-+)+.&
า2คน
นาย ลบ
Negative predictive value (NPV) ผล
refers →to ① ไ จ ง that a patient does not
เ นโรค
the →probability
have a disease if a result is within the reference
range (test is negative for the disease)

0 NPV =
!". !"!$%&'!(!) *+), !&'()+.& )&-)
!". *+), !&'()+.& )&-)

/%0& !&'()+.&
=
/%0& !&'()+.&12(3-& !&'()+.&
15
 Sensitivity & Specificity

0
8 mIU/ml
r
ม

ราม r ท
area
(A) Using a high cutoff, sensitivity is low, (B) As the คม
cutoff is lowered, the sensitivity
and specificity is high. เพาะ improves at the expense of specificity.
เ มน senลดลง
A high sensitivity↳
confirm กานดวง for
is desirable for a screening test, whereas a high specificity is appropriate
confirmation testing. 16
 Accuracy & Precision
Accuracy ค. ก อง
The degree of closeness of measurements of a quantity to the actual (or accepted)
value.

Precision ค.แ น
The degree to which repeated measurements show the same results.

17
 Quality control (QC)
v Control material: Sample with
known concentration for
controlling the techniques and
methods over period of time to gain
confidence in the results for
diagnosis and treatment (3 levels:
low, normal, high) r าเ ยว
Calibrator
v Calibrator (standard): Material Lไรเ ยบมาตรฐาน
Control 3 levels
with known components from (low, normal,
high levels)
↳ เ าวงก
• อง
standard method and must have
the certificate. 18
 Quality Assurance
• Measure taken to ensure the reliability of laboratory sampling, testing and
reporting

Internal Quality Control (IQC) External Quality Assessment (EQA)

• Ensures precision เ อค.แ น • Retrospective analysis comparing
• Day to day consistency of results for results between laboratories and
reporting between methods ระห างรพ.
ก อง
Can use stable control or patient data • Need accurate result
•
• Organized by the laboratory ในองป การ น the agencies
• Organized by

19
 น ก ①เ นQuality control (QC) chart
• Levey and Jennings Chart
• A visual presentation of daily control
แ1 ไ
นาน
values plotted on chart using mean, SD,
and +/- 3 SD range criteria.
าง อย น า อ าง อย20 น
ก นอ ละ
• Analyze the QC material by the _ นส|เวลา
analytical method to be controlled on at
least 20 times under optimal conditions
and calculate the mean, SD, %CV.
• Construct control chart
X axis –days
ตนµ นอน 20
Y axis –control value
 Quality control (QC) chart
v Confidence interval (CI) คาาว
มเ อน 95
- Range of values that include a specified probability, usually 90% or 95%.
- Confidence intervals serve to convey the variability of estimates and quantify the variability.
v Reliability
- Generally defined the ability of a product to perform as expected, over certain time (same
result on repeated trials under the same time). ออก นอกวง
- Reliability is achieved by minimizing the effect of randomๆerrors.
v Finding the errors
- Finding the errors are caused by faults in some stepsหา
ไหน
orไthe instrument used in the analysis.
มาจาก

21
 Levey and Jennings Chart

น เวลา

- Record the mean ± 1SD, mean ± 2SD, mean ± 3SD control limits
- Mean = 120 mg/dL เสน2sDwarningline
- Within ± 2SD à accept
สน งsp action line
- Outside 2SD à out of control →เ อน
- Between 2SD and 3SD à warning à repeat analysis
- ก n à investigate test system
>3SD à reject à stop analysis
nee 22
 Levey and Jennings Chart
Shift 76 อ บน1 าง mean อ างเ ยว → sgstemieerror
When six or more consecutive plots all fall on/above or below the mean
line.

Trend ¥6 น1ลง อ างเ ยว → แ

When six or more consecutive plots all fall in one direction, especially
upward or downward.

23
 QC Quantitative test
qUse 2-3 levels of controlกวด
ไปพ อม บ งาน
(low, normal, high) covering the medical decision points

qAt least 20 control values over a period of 20-30 days for each level of control

qPerform statistical analysis

Ctccharts
qCreate Levey-Jennings charts
กาม
qRun regularly with patient samples
ตรง บ าย
qMonitor control values on chart using Westgard’s multirules → •วขอ าน
qTake immediate corrective action, if needed

qRecord action taken (if any) 24

 Westgard’s multirules
L หนดกฎมา
A set of rules used to evaluate the quality control values as acceptable or
not.
- 12S
- 13S
- 22S
- R4S
- 41S
- 10X
AL = general symbol for a control rule
Cf ด น
นวน เ ด
A is an abbreviation for a statistic, or the number of control measurements.
L เrefers
น
เ นไto
หน ไthe
ป control limits, usually specified by giving the number of standard deviations from the mean; also
can specify the probability for false rejection. 25
 Westgard’s multirules

าา า
เ น2💔
r า า าเ น 3SD

randomerror
• One of two control results fall the
outside of mean ± 2SD.
• Alerting technologist to possible
problems
• WARNING RULE –not cause for
rejecting a run
• Must then evaluate the 13S
• A single control measurement
exceeds the mean ± 3SD
• Run must be rejected.
• Allows high sensitive to random
error nrn
26
 Westgard’s multirules

า2 าเ น2sD
r
น ด น

• Reject นthe one control exceeds the

• Two constitutive control values for the
same level fall outside mean ± 2SD in the
same direction
C
mean by -2SD, and the other exceed
the mean by +2SD
• Patient results cannot be reported or • The range between two results will
→น
rejected. ×2 เ น therefore exceed 4 SD.
• Requires control dataดfrom previous runs
y
• Allows high sensitivity to systemic error
• The rule should only be interpreted
within run, not between run.
• Allows detection of random error

27
 Westgard’s multirules

0
0 าเ นา ตหก บน าง
า

o 0
• Reject when 4 consecutive control • Reject when 10 consecutive control
measurements exceed the same measurements fall on one side of the
mean + 1SD or -1SD control limit mean
• Requires control data from • Or both levels of control have 5
previous runs consecutive results that are on the
• Allows the detection of systemic same side of the mean
error • Requires control data from previous
Tkejeet น runs
• Allows the detection of systemic error
28
 Westgard’s multirules

อในa
๐
เ คา
ตรง บอ นป

ตรงrejat
หาก น
29
 Some modification of 10X rule
นานนม

• Reject when 8 consecutive control • Reject when 12 consecutive control

measurements fall on one side of measurements fall on one side of
the mean the mean
• Allows the detection of systemic • Allows the detection of systemic
error error

30
 Other common multirules

งาน
ใน ด บ ม า เ น28D

• Reject when 2 out of 3 control • Reject when 3 consecutive control

measurements exceed the same
mean +2SD or mean -2SD control
limit
• Allows the detection of systemic
error
measurements exceed the same
mean +1SD or mean -1SD control
limit
• Allows the detection of systemic
error

31
 Other common multirules

• Reject when 6 consecutive control • Reject when 9 consecutive control

measurements fall on one side of measurements fall on one side of the
the mean mean
• Systemic error detected with 6X : • Allows the detection of systemic error
shift.

32
 Other common multirules

→เ น trend → rejed น

7T -reject when 7 control measurements trend in the same

direction, i.e., get progressively higher or progressively lower. This
allows the detection of systemic error (trend).

33
 Application of multirule procedures
Control level 1 Control level 2

o → รวม บก
กราฟ

• Multirules are used to identify errors while minimizing false-error

i
detection.
• Multirules can help identify different types of errors that might occur.

34
Structured Rule Interpretation for Westgard multirule’s
• When controls fall within 2SD’s, accept the run.

• “Warning Rule”. One control ± 2SD limit, hold patient results while
inspecting control data with the 13s , 22s , R4s , 41s , and 10x rules. If any
of these additional rules indicates that the run is “out of control”, reject
the run.

แยก
• When a run is “out of control” determine the type of error occurring
based on the control rule violated.

• Look for sources of that type of error

แไ อ ไ ก อง
• Correct the problem and reanalyze the whole run including controls
35
 Identifying random and systemic errors
Control rule violation Type of error Result Examples of error

12S Random Warn • Sample problems (clots, bubbles, interfering

substances)
• Mechanical variation เค อง แปรปรวน
อ
• Pipetting error
zrn
• Detector variation

13S, R4s Random Reject

ไป
• Electrical interference
ระ
• Sample problems (clots, bubbles, interfering
substances)
• Mechanical variation
• Pipetting error
• Detector variation
• Electrical interference
Systemic ย aeagen
p lot
22S, 2 of 32S, 31S, 41S, 6X, 8X, Reject • Reagent bias
9X, 10X, 12X, shift, trend • Calibration bias

อ
• Within run bias
• Intrinsic method bias
• Instrument bias
36
 Types of errors
เ ยว บ
ค.แ น
r
Random error (unpredictable fashion)
Statistical fluctuations (in either direction) in the measured data due to the precision
limitations of the measurement device.
กก.ค.ก อง
Systematicr error (a constant and predictable manner per every test)
- Reproducible inaccuracies that are consistently in the same direction.
- Systematic errors are often due to a problem which persists throughout the entire
experiment.

37

Quality Control Issue
Imprecision
บ
Values shifting within range
Values shifting out of range
Trend
What are some causes?
Type of error Possible Causes
Random error
•Improper mixing of reactions constituents
•Contamination during testing
•Pipetting variation
•Electrical supply
Systemic error •Inadequate mixing of controls
•Controls left at suboptimal temperature for too long
•Variation between controls (ranges)
•Lot number change
Systemic error Any of the reasons described above
•Improper reconstitution of controls
•Error in control concentration
•Reagent contamination
•Deterioration of controls
•Instrument problem
Systemic error •Instrument change:
o Reaction temperature
o Sampling problem
o Reagent delivery problem
o Detector Problem
38
 When a rule is violated
• Warning rule = use other rules to inspect the control point
• Rejection rule = out of control
1. Stop testing
ห การ
ด
2. Identify and correct problem แ ญ หา
3. Repeat testing on patient samples and control
4. Don’t report patient until problem is solved, and controls indicate proper performance.
• Change one variable at a time to troubleshoot an out of control (> ±2SD) test
• The variables are usually common to all instruments or procedure systems and include
following:
1. Try a fresh vial of QC 1สอนQc
ป
ให (same lot)
0๓
2. Try a new reagent
3. Try a new consumable (water, part, solution, tubing) if applicable
4. Try a new reagent (new lot)
5. Recalibrate (current calibrator)
6. Recalibrate (new lot calibrator)
❤
• If a system cannot be brought into control, notify senior staff. Do not process patient samples
for the test affected.
เ ดญหา บControl องรายงาน วห า องป การ อนเสมอ
39
 References
• https://www.westgard.com
• Bishop, Michael L, Fody, Edward P, and Schoeff, Larry E. Clinical Chemistry
Techniques, Principles, Correlations. (6th edition). Philadelphia: Lippincott
Williams & Wilkins, 2010.
• Burtis, Carl A., Ashwood, Edward R., and Burns, David E. Tietz Fundamentals of
Clinical Chemistry. (6th edition). Philadelphia: Saunders Elsevier, 2008.
• Tony Badrick. Quality leadership and quality control. Clin Biochem Rev.
2003;24(3):81-93.

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