‫بسم هللا الرحمن‬
‫الرحيم‬
Professor of Clinical Pathology (Clinical Chemistry)
Faculty of Medicine, Mansoura University
The Laboratory test begins with a
physician deciding which test to order
and
ends
with
that
physician
evaluating the test result. A process of
brain to brain transmission of medical
in formation.
Problems arise primarily from imperfect
processes, not from imperfect people.
The quality problems are primarily
management problems because only
management has the power to change
work process.
The total system for a health care
organization involves the interaction
of all of the following processes as
well as many others:
Physicians might view a health
care organization as a provider of
processes for:
A. Patient examination.
B. Patient testing.
C. Patient diagnosis.
D. patient treatment.
Health care administrators might
view the activities in terms of
processes for :
A. Admitting
B. Patient services
C. Discharging patients
D. Billing for costs of service
Laboratory
directors
might
understand their responsibilities in
terms of processes for:
A. Acquisition of specimens
B. Processing of specimens
C. Analysis of samples
D. Reporting of test results
Laboratory analysts might view their
work as processes for:
A. Acquiring samples
B. Analyzing samples
C. Performing quality control
D. Releasing patient test results
Report
Written order
Specimen
Measurement
Specimen
preparation
Patient preparation
Quality Assurance (Q.A)
The five Q framework
Defines how quality can be managed
using the scientific method or the PDCA
cycle Plan do check Act:
• Quality planning
• QLP
Includes analytical process and the general
policies, practices and procedures that
define how all aspects of the work get done.
• Q.C.
• Statistical.
• Non statistical:
e.g.: Linearity checks , reagent and
standard checks and procedure.
• Q.A. quality assessment concerned with:
Measures and monitors
performance as:
of
laboratory
Turaround
Specimen identification
Patient identification
Test utility
• Q.I. quality improvement:
Provides a structural problem-solving process
With better analytical quality a lab can eliminate
repeat run requests for test (this work is waste).
If quality are improved waste will be reduced
which reduce cost and provide a competitive
advantage.
If quality means conformance to requirements,
then quality costs must be cost of conformance
and cost of non-conformance.
To customer requirement
PREVENTION
(To prevent problem)
For appraising
performance
For poor analytical
performance
For analytical quality
Essential Elements for Q.A.
I.
II.
III.
IV.
V.
Commitment.
Facilities and Resources.
Technical Competence.
Technical Procedures.
Problem solving Mechanism.
• Input from QC technologist or supervisors to initiate the
mechanism.
• In service training program.
• Specialized trouble shooting skills.
• Quality team responsible for problem solving (small groups).
Essential elements for Q.A.
Essential elements for Q.A.
Essential elements for Q.A.
Essential elements for Q.A.
Technical procedures
Technical procedures
Methodology
Technical procedures
Standardization and calibration:
Reference calibrator material (RCM)
(primary calibrator): by definitive
method (absolute physical quantity
such as mass) e.g. isotope dilution mass
spectroscopy.
Test
calibrator
material
(TCM)
(secondary calibrator): by reference
method and high quality staff.
Structure of an accuracy-based measurement system showing
relationships among reference methods and materials .
Technical procedures
Documentation
of
analytical
protocols and procedures.
Monitoring of critical equipment
and materials.
Technical procedures
The Monitoring of analytical quality by
the use of: Q.C.
SD, bias and 6 sigma
• Levey – Jennings chart
• Westgard multirules
• Cum Sum
P.T.
Q.C.
Levey Jennings control chart:
Analyze control 20 different days 
mean ± SD.
Construct Control chart.
Control limits set as the mean ± 3s.
Concentration is plotted on the y-axis versus
time (run number) on the x- axis.
Introduce the control into each run & record
the value.
Control limit:
±
2
SD
observation
when
(n)
the
is
number
one
rejection problem (Pfr).

± 3 SD when n = 2 or more
detection (Ped is low).

of
false
error
Concentrations
Q.C.
Levey Jennings chart
M+3SD
M+2SD
M+1SD
Mean
M
M-1SD
M-2SD
M-3SD
1
2
3
4
5
6
7
8
9
10
Q.C.
Westgard Multirules Chart
If the control is within mean ± 2SD  in control:
I2s
one excced mean ± 2SD ( warning that initiate testing
of other control rules).
I3s
one excced mean ± 3SD ( Random error )
22s
2 consecutive control excced mean ± 2SD (systemic
error)
R4s 2 consecutive excced mean plus and minus 2SD)
( Random error)
41s 4 consecutive excced mean ± 1SD ( syst. errors )
10x` consecutive deviation Less than 1SD on
(system errors)
one side
Concentrations
Q.C
Westgard chart
13s (random)
M+3SD
22s systemic
12s (warning )
4s (Random)
M+2SD
41s systemic
M+1SD
Mean
M
M-1SD
M-2SD
M-3SD
1
2
3
4
5
6
7
8
9
10
A word from
Dr. Westgard
Westgard Multirule Chart
Pfr is kept low
Ped is improved
Q.C
Westgard chart
Introduce two control specimens into each analytical run :
When both fall with 2s limits accept the analytical
run and report the patient results.
When one exceeds 2s limit hold the patients results
and inspect the control data using l3s, R45, 22s and
10xWhen one of these rules is out of control, reject the
analytical run & don’t report the analytical results .
When all of these rules indicate that the run is in
control , accept the analytical run and report the
patient results
Q.C
Westgard chart
R4s is applied only within a run –between Run
interpritted as RE
Rule may be applied "across" materials one
observations can be on the low, concentration
and the other on the high concentration as
long as they are within the same run .
Rules 22s, 41s and 10x rules can be applied
across runs and materials.
This effectively increases n and improve the
Ped of the procedure
Q.C.
Systemic error: caused by variations in:
Instruments
Technique
Reagents or other material
Random error:
Appear despite,
Analytical method
Tightly
Controlled,
Sample piptting
Dissolving reagent
Mixing sample and reagents
Baths temp instability.
Q.C.
The overall objective of these rules is to
obtain a high probability of error
detection and a low frequency of false
rejection of runs:
If the rules are violated it must:
QC performance characteristics
Different QC procedures have
different sensitivities or capabilities
for detecting analytical errors.
The best is that with lowest Pfr and
highest Ped.
QC
Cumulative sum CUSUM chart
Calculate difference between mean & the
result (e.g. mean 100 , result 110 the diff =
10) -add this difference to the following each
day.
Interpret the chart data .
Steep slope of the Cusum Line, suggest
systemic errors and the run is out of control.
QC
CUSUM
QC
CUSUM
The Same as before but the difference is
calculated between the estimated control
value and k1 or ku (mean ±SD):
The cusum calculation do not start until a control
value exceeds a certain threshold above (Ku) or below
(K1) of the expected mean (X).
QC
CUSUM
This difference summated for 2 weeks
If the summation exceed the control
Limit  the method out of control
changed to
If the sign changed (+ 
- or the
reverse  the calculation stopped 
the method is in – control
Calculations and Tabular Record for Decision
Limit Cusum For Control Material.
With X=100, S=5.0, kU = 105 , K1 =95,hu=13.5,h1=13,5).
QC
CUSUM
Q.C using patients data
(Its efficiency is relatively low)
Clinical correlation:
• Correlate clinical diagnosis with laboratory
test results e.g. impossible test result such
as normal serum bilirubin in a highly
jaundiced patients.
Correlation with other laboratory
tests e.g. T4 and TSH, urea and
creatinine.
Q.C using patients data
Inter laboratory duplicate:
• Divide sample into 2 aliquots and
do analysis.
This is a simple Q.C. procedure used in
absence of stable control material.
Q.C using patients data
Delta checks with previous test:
• To
detect
certain
errors
identification or labelling.
e.g.
• Compare laboratory test results with
value obtained on previous specimens
from the same patients.
Delta check limit based on 3-day interval in
term % of change from the initial value e.g.
Na+ 5%, CK 99%.
Q.C using patients data
Limit checks:
• Patients test results should be reviewed
to check that they are within the
physiological ranges compatible with
life.
Low warning
S. Albumin (g/dl)
1.5
S. Uric acid (mg/dl) 1.0
S. Sodium (mmol/L) 120.0
High warning
6.0
12.0
150
External Q.C.
Analyze the same Lot of control material:
N. ± 1-1.5.
> 2 Indicate that the Lab is not in agreement
with the test of other Laboratories in the
program.
Must correct any test method instrum.
trouble shooting.
External Q.C.
SDI for the same instruments and
techniques:
=
External Q.C.
Comparison of Lab. Mean and
group mean by t-test.
If significant (<0.05), the Lab.
Result is biased.
Role of proficiency testing (PT) in Accreditation
According to Clinical Laboratory Improvement Amendments (CLIA88)
Study 5 samples 3 times per year so as to
improve
the
capability
of
detecting
"unacceptable“ performance.
The lab. must produce correct results on 4 out
of 5 specimens for each of the analytes in that
category and have an overall score of at least
80% for 3 consecutive challenges.
The criteria of PT failure is:
Two of five incorrect results on two of three
consecutive PT surveys
If there are 2 incorrect results for any analyte ,
The Lab. is considered "on probation " Lab .
Suspended Lab:
If the lab .has 2 or more incorrect results for any
analyte or has any score less than 80% on two of
three consecutive surveys.
Suspended Lab. must cease all analytes in that
specialty category until it is reinstated .
Target value (% or absolute value):
The mean of all responses after removal of
outliers (more than 3SD).
Or the mean established by definitive or reference
method (acceptable by the national committee of
standard NCS).
Comparative method may be used in absence of
the former methods.
Post Analytical Goals and Clinical
Interpretation of Lab. Procedures
The following questions must be asked
for test results:
Screening : Is an apparent disease present ?
Pathoghysiology : What is the disease process ?
Confirmation : How can Confidence in the tentative
diagnosis be increased ?
Prognosis : How Severe is the disease process ?
Monitoring : Has a change occurred since the Last
observation ?
Is it significantly different from previous
result ?
The probability that the difference between
two result is analytically significant (p< 0.05)
is 2.8 times the analytical SD (SDA of
repeated measurements of a single quality
normal control serum).
To decide whether an analytical change is
clinically significant, it is necessary to consider
the extent of natural biological variation
(means of SDB for repeated measure ments
made at weekly intervals in healthy subjects
over 10 weeks).
The effects of analytical and biological
variation can be assessed by calculating the
overall standard deviation of the test by:
If the difference between two test results
exceeds 2.8 times the SD of the test, it can be
considered of potential clinical significant:
Is it consistent with clinical findings ?
LAB. TESTING PROCESSES AND
THEIR POTENTIAL ERRORS
LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
Process Potential Errors
•Inappropriate test
Test
ordering
•Handwriting not legible
•Wrong patient identification
•Special requirements not specified
•Cost or delayed order
LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
Process
Potential Errors
•Incorrect tube or container
•Incorrect patient identification
•Inadequate volume
Specimen
•Invalid specimen
acquisition
(e.g. hemolyzed
or too dilute)
•Collected at wrong time
•Improper transport conditions
LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
Process
Potential Errors
•Instrument not
•calibarted correctly
Analytical
•Specimen mix –up
measurement •Incorrect volume of specimen
•Interfering substance present
•Instrument precision problem
LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
Process
Potential Errors
•Wrong patient identification
•Report not posted in chart
Test reporting •Report not legible
•Report delayed
•Transcription error
LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS
Process
Test
interpretation
Potential Errors
•Interfering substances not recognized
•Specificity of test not understood
•Precision limitations not recognized
•Analytical sensitivity not appropriate
•Previous values not available for comparison
Six Sigma
Six Sigma
Today’s competitive environment leaves
no room for error
This is why six sigma quality must be a
a part of our culture.
What is six sigma
It is a process that helps us focus on
developing and delivering near perfect
products and services.
Why sigma
Six Sigma
The word is a statistical term that measures
how far a given process deviates from
perfection.
The central idea behind six sigma is
that you can measure how many”
Defects” you have in a process, you can
systematically figure out how to
eliminate them and get as close to “zero
defects” as Possible.
Six Sigma
The principles of Six Sigma go back
to Motorola’s approach to TQM in
the
early
1990s
and
the
performance goal that “6 sigmas or
6 standard deviations of process
variation should fit within the
tolerance limits of the process”;
hence, the name Six Sigma.
Six Sigma
Six Sigma
Methods of sigmametric
measurement
Six Sigma
Sigma = (Tea – bias)/cv
Tea = tolerable error or allowable total
error (determined by CLIA)
Bias = inaccuracy
Six Sigma
A shift or bias of 1.5 sigma would
hardly cause any defects in a six
sigma process. The actual rates that
are expected are as follows:
• 3.4 DPM for a six-sigma process;
• 233 DPM for a five-sigma process;
• 6210 DPM for a four-sigma process;
• 66,807 DPM for three-sigma; and
• 308,537 DPM for a two-sigma process
Six Sigma
Six Sigma
Six Sigma
Six Sigma
Six Sigma
Methods with 6 sigma performance
are considered “World class”.
Methods with sigma performance less
than 3 are not acceptable for
production.
Six Sigma
Chemistry
Test or Analyte
CLIA
Acceptable
Performance
Five-Sigma
Precision
Six-Sigma
Precision
Blood gas pCO2
5 mm Hg
or 8% (greater)
1 mm Hg
or 1.6%
0.8 mm Hg
or 1.3%
Blood gas pH
0.04 pH units
0.008 pH
units
0.00067 pH
units
Calcium, total
1.0 mg/dL
0.2 mg/dL
0.17 mg/dL
Chloride
5%
1.0%
0.83%
Cholesterol, total
10%
2.0%
1.7%
Cholesterol, HDL
30%
6.0%
5.0%
Creatine kinase
30%
6.0%
5.0%
Creatinine
0.3 mg/dl
or 15%
(greater)
0.06 mg/dL
or 3.0%
0.05 mg/dL
or 2.5%
Six Sigma
Chemistry
Test or Analyte
CLIA
Acceptable
Performance
Five-Sigma
Precision
Six-Sigma
Precision
ALT
20%
4.0%
3.3%
Albumin
10%
2.0%
1.7%
Alkaline
Phosphatase
30%
6.0%
5.0%
Amylase
30%
6.0%
5.0%
Bilirubin, total
0.4 mg/dL
or 20%
(greater)
0.08 mg/dL
or 4%
0.067 mg/dL
or 3.3%
Six Sigma
Glucose
6 mg/dL
or 10% (greater)
1.2 mg/dL
or 2.0%
1.0 mg/dL
or 1.7%
Iron, total
20%
4.0%
3.3%
LDH
20%
4.0%
3.3%
Magnesium
25%
5.0%
4.2%
Potassium
0.5 mmol/L
0.1 mmol/L
0.08 mmol/L
Sodium
4 mmol/L
0.8 mmol/L
0.67 mmol/L
Total protein
10%
2.0%
1.7%
Urea Nitrogen
2 mg/dL
or 9% (greater)
0.4 mg/dL
or 1.8%
0.33 mg/dL
or 1.5%
Uric acid
17%
3.4%
2.8%
Toxicology Test or Analyte
Alcohol, blood
25%
5.0%
4.2%
Blood lead
10% or
4 mcg/dL (greater)
2.0% or
0.8 mcg/dL
1.7% or
0.67 mcg/dL
Carbamazepine
25%
5.0%
4.2%
Digoxin
20% or
0.2 ng/mL (greater)
4.0% or
0.04 ng/mL
3.3% or
0.033 ng/mL
Ethosuximide
20%
4.0%
3.3%
Gentamicin
20%
4.0%
3.3%
Lithium
0.3 mmol/L or
20% (greater)
0.06 mmol/L or
4.0%
0.05 mmol/L or
3.3%
Phenobarbital
20%
4.0%
3.3%
Phenytoin
25%
5.0%
4.2%
Primidone
25%
5.0%
4.2%
Procainamide
25%
5.0%
4.2%
Quinidine
25%
5.0%
4.2%
Theophylline
25%
5.0%
4.2%
Tobramycin
25%
5.0%
4.2%
Valproic acid
25%
5.0%
4.2%
Six Sigma
Hematology Test or Analyte
Erythrocyte count
6%
1.2%
1.0%
Hematocrit
6%
1.2%
1.0%
Hemoglobin
7%
1.4%
1.2%
Leukocyte count
15%
3.0%
2.5%
Platelet count
25%
5.0%
4.2%
Fibrinogen
25%
5.0%
4.2%
Partial thromboplastin time
15%
3.0%
2.5%
Prothrombin time
15%
3.0%
2.5%