Introduction to
Quality Control
1
Learning Objectives
Define Quality & QMS
Define quality control and describe
its relationship to the overall quality
management system.
Describe differences in quantitative,
qualitative, and semi-quantitative
examinations.
Introduction to Quality Control-Module 6 2
What is Quality?
Introduction Laboratory Quality Management System-Module 1 3
Definition of Laboratory Quality
Laboratory quality can be When making measurements,
defined as accuracy, there is always some level of
reliability, and timeliness inaccuracy. The challenge is
to reduce the level of
of the reported test
inaccuracy as much as
results. The laboratory possible, given the limitations
results must be as of our testing systems. An
accurate as possible, all accuracy level of 99% may at
aspects of the laboratory first glance appear
operations must be acceptable, but the resulting
reliable, and reporting 1% error can become quite
must be timely in order to large in a system where many
be useful in a clinical or events occur, such as
laboratory testing.
public health setting.
Introduction to Quality Control-Module 6 4
Achieving a 99% level of quality
means
accepting a 1%
1% error rate
Introduction Laboratory Quality Management System-Module 1 5
5
In France a 1% error rate
would mean everyday
14 minutes without water or electricity
50,000 parcels lost by postal services
22 newborns falling from
midwives’ hands
600,000 lunches contaminated
by bacteria
3 bad landings at Orly Paris airport
Introduction Laboratory Quality Management System-Module 1 6
Result: 1% failure
Introduction Laboratory Quality Management System-Module 1 7
7
Essential to all aspects of
health care are laboratory
results that are
accurate,
reliable, and
timely
Introduction Laboratory Quality Management System-Module 1 8
Laboratory errors cost in
time
personnel
effort
patient
outcomes
Introduction Laboratory Quality Management System-Module 1
9
Quality Management System Definition
Coordinated activities to direct and
control an organization with regard
to quality (ISO,CLSI).
All aspects of the laboratory
operation need to be addressed to
assure quality; this constitutes
a quality management system.
Introduction Laboratory Quality Management System-Module 1 10
Simple QMS Definition
A System established to meet the
challenge of Achieving, Maintaining and
Improving:
Accuracy
Timeliness
Reliability
Introduction to Quality Control-Module 6 11
Why QMS?
Countries worldwide have committed
themselves to build national capacities
for detection of and response to Public
Health events of International concern.
Only a sound Management of Quality in
health labs. Will enable countries to
produce test results that the
international community will trust in
cases of international emergency.
Introduction to Quality Control-Module 6 13
Organization Personnel Equipment
Purchasing Process Information
& Control Management
How do we
Inventory
achieve
excellent Documents
&
Occurrence
Management
Assessment
performance Records
in the
laboratory? Process
Improvement
Customer
Service
Facilities
&
Safety
Introduction Laboratory Quality Management System-Module 1 14
Complexity of a Laboratory System
Reporting Patient/Client Prep
Sample Collection
Personnel Competency
Test Evaluations
•Data & Laboratory
Management
•Safety
•Customer Service
Sample Receipt and
Accessioning
Record Keeping
Sample Transport
Quality Control
Testing
Introduction Laboratory Quality Management System-Module 1 15
Path of Workflow
THE PATIENT Test selection Sample Collection
Preexamination Phase
Sample Transport
Laboratory Analysis
Examination Phase
Report Transport Report Creation
Result Interpretation Postexamination Phase
Introduction Laboratory Quality Management System-Module 1 16
WHY is the Path of Workflow essential
to consider in health laboratories?
The entire process of managing a
sample must be considered:
the beginning: sample collection
the end: reporting and saving of results
all processes in between.
Introduction Laboratory Quality Management System-Module 1 17
The Quality Management System
Organization Personnel Equipment
Purchasing Process Information
& Control Management
Inventory
Documents Occurrence
& Assessment
Management
Records
Process Customer Facilities
Improvement Service &
Safety
Introduction to Quality Control-Module 6 18
Laboratory tests are influenced by
laboratory environment
knowledgeable staff
competent staff
reagents and equipment
quality control
communications
process management
occurrence management
record keeping
Introduction Laboratory Quality Management System-Module 1 19
Definition
Quality Control (QC) is part of quality
management focused on fulfilling quality
requirements ISO 9000:2000 (3.4.10)
QC is examining “control” materials of
known substances along with patient
samples to monitor the accuracy and
precision of the complete examination
(analytic) process.
Introduction to Quality Control-Module 6 20
Complexity of a Laboratory System
Reporting Patient/Client Prep
Sample Collection
Personnel Competency
Test Evaluations
•Data & Laboratory
Management
•Safety
•Customer Service
Sample Receipt and
Accessioning
Record Keeping
Sample Transport
Quality Control
Testing
Introduction Laboratory Quality Management System-Module 1 21
Purpose
The goal of QC is to detect
errors and correct them before
patients’ results are reported
Introduction to Quality Control-Module 6 22
Quantitative Examinations
Measure the quantity of a particular
substance in a sample
Measurements should be both
accurate and precise
Introduction to Quality Control-Module 6 23
Quantitative Tests
measure the quantity of a particular
substance in a sample
quality control for quantitative tests
is designed to assure that patient
results are:
accurate
reliable
Quantitative QC - Module 7 24
Qualitative Examination Methods
Examinations that do not have
numerical results:
growth or no growth
positive or negative
reactive or non-reactive
color change
Introduction to Quality Control-Module 6 25
Semi-quantitative Examination Methods
Results are expressed as an estimate
of the measured substance:
“trace amount”, “moderate amount,” or
“1+, 2+, or 3+”
number of cells per microscopic field
titers and dilutions in serologic tests
Introduction to Quality Control-Module 6 26
Establish
Establish
written include
written corrective
policies
policiesand
and actions
procedures
procedures
Review
Review QC Program Train
Train
QC
QCdata
data Steps all
allstaff
staff
Assure
Assure
complete
complete
documentation
documentation
Introduction to Quality Control-Module 6 27
Implementation steps
establish policies and procedures
assign responsibility, train staff
select high quality controls
establish control ranges
develop graphs to plot control values -
Levey-Jennings charts
monitor control values
develop procedures for corrective action
record all actions taken
Quantitative QC - Module 7 28
What is a Control?
material that contains the substance
being analyzed
include with patient samples when performing
a test
used to validate reliability of the test
system
run after calibrating the instrument
run periodically during testing
Quantitative QC - Module 7 29
Calibrators vs. Controls
Quantitative QC - Module 7 30
Calibrators Controls
A substance with a specific A substance similar to
concentration. patients’ samples that
has an established
Calibrators are used to set concentration.
(calibrate) the measuring
points on a scale. Controls are used to ensure
the procedure is working
1 2 3 4 5 properly.
1 2 3 4 5
Quantitative QC - Module 7 31
Characteristics of Control Materials
appropriate for the diagnostic sample
values cover medical decision points
similar to test sample (matrix)
available in large quantity; ideally
enough for one year
can store in small aliquots
Quantitative QC - Module 7 32
Types of Control Materials
may be frozen, freeze-
dried, or chemically
preserved
requires very accurate
reconstitution if this step
is necessary
Quantitative QC - Module 7 33
Sources of Controls Materials
commercially prepared
made “in house”
obtained from another laboratory,
usually central or reference
laboratory
Quantitative QC - Module 7 34
Control Materials
Target value predetermined
ASSAYED
Verify and use
Target value not predetermined
UNASSAYED
Full assay required before using
In-house pooled sera
“IN-HOUSE”
Full assay, validation
Quantitative QC - Module 7 35
Choosing Control Materials
values cover medical decision points
similar to the test sample
controls are usually available in high, normal, and
low ranges
Quantitative QC - Module 7 36
Preparation and Storage of
Control Material
adhere to manufacturer’s
instructions
keep adequate amount
of same lot number
store correctly
CONTROL
Quantitative QC - Module 7 37
Measurement of Variability
Variability is a normal occurrence
when a control is tested repeatedly
Affected by:
Performance
Operator Environmental characteristics
technique conditions of the
measurement
The goal is to differentiate between
variability due to chance from that due
to error
Quantitative QC - Module 7 38
Steps in Implementing Quantitative QC
obtain control material
run each control 20
times over 30 days
3SD
calculate mean and +/-
2SD
1,2,3 Standard Deviations
1SD
Mean
1SD
2SD
Quantitative QC - Module 7 3SD 39
Measures of Central Tendency
Although variable, sets of data are
distributed around a central value
F
r
e
q
u
e
n
c
y
Measurement
Quantitative QC - Module 7 40
Measures of Central Tendency
Mode the value which occurs with the
greatest frequency
Median the value at the center or
midpoint of the observations
Mean the calculated average of the
values
Quantitative QC - Module 7 41
Not all central values are the same
Mean Mode
F Median
r
e
q
u
e
n
c
y
Measurement
Quantitative QC - Module 7 42
Symbols Used in Calculations
∑ is the sum of (add data points)
n = number of data points
x1 - xn = all of the measurements (1
through n)
__
X represents the mean
Quantitative QC - Module 7 43
Calculation of Mean
X 1 X 2 X 3 ... X n
X
n
X = Mean
X1 = First measurement
X2 = Second measurement
Xn = Last measurement in series
n = Total number of measurements
Quantitative QC - Module 7 44
Example
Calculation of Mean: ELISA Tests
Run controls 20 times in 30 days. Record
both OD and cut off (CO) values for each
measurement.
Divide the OD by the CO (OD/CO) for each
data point or observation. This standardizes
the data.
Add the ratios and divide by the number of
measurements to get the mean.
Quantitative QC - Module 7 45
Data showing outlier
1. 192
mg/dL 11. 204 mg/dL
2. 194
mg/dL 12. 208 mg/dL
3. 196
mg/dL 13. 212 mg/dL
4. 196
mg/dL 14. 198 mg/dL
5. 185
mg/dL 15. 204 mg/dL
6. 196
mg/dL 16. 208 mg/dL
7. 200
mg/dL 17. 212 mg/dL
8. 200
mg/dL 18. 198 mg/dL
9. 202
mg/dL 19. 192 mg/dL
10. 270 mg/dL 20. 196 mg/dL
Quantitative QC - Module 7 46
Normal distribution
all values symmetrically distributed
around the mean
characteristic “bell-shaped” curve
assumed for all quality control
statistics
Frequency
mean
Quantitative QC - Module 7 47
Quality Control is used to monitor
the accuracy and the precision
of the assay.
What are
accuracy and
precision?
Quantitative QC - Module 7 48
Definitions
Accuracy The closeness of
measurements to the true
value
Precision The amount of variation in
the measurements
Bias The difference between the
expectation of a test result
and an accepted reference
value
Quantitative QC - Module 7 49
Accuracy and Precision
Accurate Precise
and Precise but Biased Imprecise
Accurate = Precise but not Biased
Quantitative QC - Module 7 50
Standard Deviation and Probability
For a set of data with a
X
normal distribution, a
Frequency
random measurement
will fall within:
68.2%
+ 1 SD 68.3% of the time
95.5%
+ 2 SD 95.5% of the time 99.7%
-3s- 2s -1s Mean +1s +2s
+ 3 SD 99.7% of the time +3s
Quantitative QC - Module 7 51
Standard Deviation (SD)
SD is the principle measure of
variability used in the laboratory
2
(x1 x )
SD n 1
Standard Deviation – Statistical Formula
Quantitative QC - Module 7 52
Coefficient of Variation
The coefficient of variation (CV) is the SD
expressed as a percentage of the mean.
SD
CV x 100 %
mean
CV is used to monitor precision
CV is used to compare methods
CV ideally should be less than 5%
Quantitative QC - Module 7 53
Levey-Jennings Chart
Graphically Representing Control
Ranges
Quantitative QC - Module 7 54
Draw lines for Mean and SDs
(calculated from 20 controls)
Chart name: Lot number:
196.5 +3SD
194.5 +2SD
192.5
+1SD
190.5 MEAN
188.5 -1SD
186.5 -2SD
184.6
-3SD
Days
Quantitative QC - Module 7 55
Levey-Jennings Chart
Plot daily control measurements
196.5 +3SD
194.5 +2SD
192.5 +1SD
190.5 MEAN
188.5 -1SD
186.5 -2SD
184.6 -3SD
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Days
Quantitative QC - Module 7 56
Statistics for Quantitative QC
assay control material at least 20
data points over a 20-30 day period
ensure procedural variation is
represented
calculate mean and + 1, 2 and 3 SD
Quantitative QC - Module 7 57
Number of Controls
Interpretation depends on number of
controls run with patients’ samples.
Good: If one control:
accept results if control is within ± 2SD
unless shift or trend
Better: If 2 levels of controls
apply Westgard multirule system
Quantitative QC - Module 7 58
Westgard Rules
Westgard Rules
Control data should be interpreted with mean and standard deviation (SD) of historical data
Violation of control rules requires subsequent test results to be evaluated
The software tracks the data and applies three of the Westgard rules for statistical analysis.
Control
Data
No
12s Violated Continue Accept
Results
Yes
No
No
13s Violated 22s Violated
Yes Yes
12s (one test result outside ±2 SD
of mean)
13s (one test result outside ±3 SD STOP and TROUBLESHOOT
of mean)
22s (2 sequential results outside
2 SD of mean)
Detecting error
random error: variation in QC results with no
pattern- only a cause for rejection if outside
2SDs.
systematic error: not acceptable, correct
the source of error
Examples:
shift–control on one side of the mean 6 consecutive
days
trend–control moving in one direction– heading
toward an “out of control” value
Quantitative QC - Module 7 61
Levey-Jennings Chart
Shift
196.5 +3SD
194.5 +2SD
192.5
+1SD
190.5 MEAN
188.5 -1SD
186.5 -2SD
184.6
-3SD
Days
Quantitative QC - Module 7 62
Levey-Jennings Chart
Trend
196.5 +3SD
194.5 +2SD
192.5
+1SD
190.5 MEAN
188.5 -1SD
186.5 -2SD
184.6
-3SD
Days
Quantitative QC - Module 7 63
Measurement Uncertainty
represents a range of values in which the
true value is reasonably expected to lie
is estimated at “95% coverage”
the more precise the method, the smaller
the range of values that will fall within 95%
for most instances, a range of + or - 2 SDs
is accepted as measurement uncertainty
that is explained by random variation
Quantitative QC - Module 7 64
If QC is out of control
STOP testing
identify and correct problem
repeat testing on patient
samples and controls after
correction
Do not report patient results
until problem is solved and
controls indicate
proper performance
Quantitative QC - Module 7 65
Solving out-of-control problems
identify problem
refer to established
policies and procedures
for remedial action
Quantitative QC - Module 7 66
Possible Problems
degradation of reagents or kits
control material degradation
operator error
failure to follow manufacturer’s instructions
an outdated procedure manual
equipment failure
calibration error
Quantitative QC - Module 7 67
Organization Personnel Equipment
Questions?
Purchasing Process Information
& Control Management
Inventory
Comments?
Documents Occurrence
& Assessment
Management
Records
Process Customer Facilities
Improvement Service &
Safety
Introduction to Quality Control-Module 6 68