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Quality Control and reference

values in clinical Chemistry

Abdul Rohman
Fakultas Farmasi UGM
Yogyakarta
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Introduction some thoughts


When evaluating laboratory results, how do we
determine that is normal or acceptable? That is:
What is normal or OK?
When does a laboratory test result become
weird or abnormal ? When do be become
uncomfortable with a result?
Statistics are used to determine the lines of
normal and acceptable.

Introduction some thoughts

Statistics is used to draw lines in the sand for


patient specimens, control specimens and
calibrators
If the results are normal we re comfortable
about them and dont worry
But if theyre abnormal, were uncomfortable and
we fear that there is something wrong with the
patient
or just as bad, something is wrong with the test
procedure .
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Key Terms in statistics and quality control

Accuracy*
Control specimen*
Dispersion
Histogram
Precision
Quality Assurance
Quality Control
Random error
Reference method
Shift*
Standard specimen
Trend*

Standard Deviation (SD)*


Coefficient of Variation (CV)*
Mean*
Average*
Mode*
Median*
Gaussian Curve*
Pre analytic (error)
Analytical error
Post analytic (error)
Range*
Z - Score

Statistical Concepts
Statistics is a (science of ) branch of mathematics that collects,
analyzes, summarizes and presents information about
observations.
In the clinical lab, these observations are usually numerical test
results
A statistical analysis of lab test data can help us to define normal
ranges for patients ( normal and abnormal ) and acceptable ranges
for control specimens ( in and out of control )
Descriptive statistics information about one group of
observation
Inferential statistics ways to compare different groups of
observations
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Common Descriptive techniques


Mean - Average value
Median - Middle observation
Mode - Most frequent observation

Common Descriptive techniques


Mean

- Average value

T h e s u m o f a ll th e o b s e r v a tio n s
th e n u m b e r o f o b s e r v a tio n s

Common Descriptive techniques


Median - Middle observation
List all the observations in order of
magnitude and pick
the observation thats in the middle
In a odd # of observations = Middle
observation
In an even # of observations = Average of
the 2 middle values

Mode - Most frequent observation


The observation that occurs most
frequently
There may be more than one mode, or

Graphical presentation
histograms and bar-charts

Standard Deviation (SD) and CV


SD Is a mathematical expression of the
dispersion of a group of data.

SD

n 1

Coefficient variation (CV)


a way of expressing standard deviation
in terms of average value of the
observations used in the calculation
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Quality Assurance & Quality


Control
Quality Assurance (QA)
Includes pre-analytic, analytic and post analytic
factors (to be discussed)
All systematic actions necessary to provide
adequate confidence that the laboratory services
will satisfy given medical needs for patient care.
In other words: Quality assurance is an all
inclusive / comprehensive system monitoring the
accuracy of test results where all steps before,
during and after the testing process are considered.
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Quality Control (QC)


is the system used in the clinical laboratory to
recognize and minimize the analytic errors.
QC system is to monitor the analytical process;
detect errors during the analysis and prevent
reporting of erroneous test results.
It uses statistical analysis of test system data

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Quick Review of Quality Control


objectives
Record of precision
Early warning of shifts and trends
Permits a valid judgment on the
accuracy of a measurement
Facilitates comparison of test methods
Monitor equipment performance
Indicates the analytical abilities of a
tech
Accumulate a body of knowledge to
satisfy outside accrediting agencies
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Two aspects are important for IQC


1. Analysis of control materials such as CRM or
spiked samples to monitor trueness (Accuracy)
2. Replication of analysis to monitor precision

VERIFICATION

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Accuracy

The accuracy of an analytical procedure


expresses the closeness of agreement
between the value which is accepted
(either as a conventional true value or an
accepted reference value ) and the value
found.
This is sometimes termed trueness.

Accuracy : A measure of how close the


observations are to the true or correct value
Right on target !
Close enough?
Keep your day job

In the laboratory we need to report tests with accuracy and precision, but how
accurate do we need to be? Its not possible to hit the bulls-eye every time.
So how close is close enough?
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Recovery as function of analyte


concentration

Precision :
Observations that are reproducible or
repeatable.
If you repeatedly test / assay a sample and
get wide variation in the assayed results,
you have low precision.

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The levels of precision

RSD as a function of analyte level

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Precision
3 possible testing outcomes - Hitting the target
x

x
x

x xxx
xx

xxxx

Lacks precision and accuracy


x

Has good precision but poor accuracy

Good precision and good accuracy

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Classification of Error
***The variables:
Pre-analytical variables,
right specimen from right patient and in right
condition

Analytical variables
all parts of testing procedure performed properly,
controls in range

Post analytical variables


Correct report to correct person, interpreted correct

All the phases of the testing process are


subject to errors and must be closely
monitored, to maintain Quality Assurance.
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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.

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Classification of error
identify examples of:

Pre-analytical error Poor collection

Analytical error
Random or indeterminate
Systematic or determinate

Post-analytical error
Misinterpreted, etc.

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Controls in clinical chemistry

Use of assayed and un-assayed


controls in clinical chemistry
Assayed controls:
Un-assayed controls:
Compare cost vs convenience

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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

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Collecting Data for QC


Minimum number of determinations
Statistically should have at least 20
determinations to establish acceptable
mean and practical standard deviation.

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But what if your control specimen is out of control?

Out of control means that there is too much


dispersion in your result compared with the rest of
the results its abnormal
This suggests that something is wrong with the
process that generated that observation
Patient test results cannot be reported to
physicians when there is something wrong with the
testing process that is generating inaccurate
reports
Remember No information is better than wrong
information
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Out of control: The analytical process should


be investigated
one point outside the action lines
Two successive points outside the same
warning line
eight successive points lying on one specific
side of the target value line
Provision can also be made for stopping a
process in cases where the plotted mean values
show a trend (e.g. six increasing or decreasing
points in succession, even if the points are
within the warning
lines)
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But what if your control specimen is out of control?

Things that can go wrong and what to


do: ie. Corrective methods
Instrumentation malfunction ( fix the
machine)
Reagents deteriorated, contaminated,
improperly prepared or simply used up
(get new reagents)
Tech error (identify error and repeat the
test)
Control specimen is deteriorated or
improperly prepared (get new control)
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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
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Use of Standard Deviation to obtain


the range of acceptable results
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?
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Z Score
An evaluation of any one
determination to see how far it is
away from the mean.

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Example:
Average = 109 mg/dl
SD
= 20 mg/dl
George = 105 mg/dl

Z Score = Patient - Mean


SD

105m g / dl 109 m g / dl
F or G eorge :
0 .2 S D
2
0
m
g
/
d
l
What is the Z Score of Georges fasting plasma glucose?

Georges glucose value was 0.2 SD below the mean

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Establishment of Reference Ranges

Factors affecting reference ranges

Age
Sex
Diet
Medications
Physical activity
Pregnancy
Personal habits ( smoking, alcohol )
Geographic location ( altitude )
Body weight

Laboratory instrumentation ( methodologies )


Laboratory reagents

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An Example of the Standard Deviation to determine patient reference range.


A minimum of 20 observations should be sampled in order to obtain valid
results ( but Ill use just 6 to save time )
Lets determine the normal range for fasting plasma glucose using 6 people:
Johns glucose
= 98 mg/dl
Pauls glucose
= 100 mg/dl
Georges glucose = 105 mg/dl
Ringos glucose = 150 mg/dl
Micks glucose = 102 mg/dl
Erics glucose
= 101 mg/dl

Average = 109 mg/dl


SD
= 20.0 mg/dl
2 SD
= 40.0 mg/dl

That means that the normal range for this group is from 109 40, or 69 - 149
which is 2.0 SD from the mean
Ringo is considered abnormal if we use this commonly accepted criteria to define normal and abnormal
By the way, the CV for this group of observations is about 18% - a fairly big dispersal about the mean

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