Biochemistry Mini Review

International Journal of Clinical And Diagnostic Research ISSN 2395-3403

Volume 5, Issue 5, Sep-Oct 2017

QUALITY CONTROL IN CLINICAL BIOCHEMISTRY LABORATORY: A GLIMPSE

Samreen M Sheik* & Wilma Delphine Silvia CR

Abstract

Quality is defined as the conformance to satisfying the needs and expectations of the customers.
Quality control is one of the components of quality assurance program. In Clinical Biochemistry it
refers to maintenance of quality of the laboratory tests during [Link] types of quality
control are practiced in clinical biochemistry: Internal and external quality controls. The purpose
of Quality control is to ensure the reliability of each measurement performed on a sample. This
mini review summarizes the utmost importance of quality control in clinical biochemistry.

Author Affiliations:
Department of Biochemistry, Akash Institute of Medical Sciences and Research Centre,
Devanahalli, Bengaluru- 562110

Keywords: Quality control, Levey Jenning chart, Westgard multirule

*Corresponding Author:

Ms. Samreen M Sheik

Department of Biochemistry, Akash Institute of Medical Sciences and Research Centre,
Devanahalli, Bengaluru- 562110
Email ID: [Link]@[Link]
Contact No: 9483916786
represents the wise choice of many
alternatives”[1].The principles of quality
Introduction:
management, assurance and control have
“Quality is never an accident; it is always the become the foundation by which the clinical
result of high intention, sincere effort, laboratories are managed and operated.
intelligent direction and skillful execution; it Today`s health care system is dependent on
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Samreen M Sheik et al., Quality Control in Clinical Biochemistry: A Glimpse….

laboratory reports for clinical diagnosis, in this prognosis, or treatment planning. The question
context laboratory diagnosis and quality of reliability for most testing can be resolved
control has gained tremendous importance. by regular use of quality control materials and
statistical process control [2].
What is Quality control? QC Material
Total laboratory automation has replaced
Quality control material is a pool of specific
manual testing of parameters but still
biological fluid and contain analytes which are
laboratory errors like preexamination
determined by the laboratory ideally in
/preanalytical, examination/ analytical and
concentration close to the decision limits
post examination/ post analytical errors are in
where medical decision is required. Control
the rise. The only way to keep a check on
samples with same analytes but different
laboratory errors is by quality control at all
concentrations are called levels.
phases of testing. Quality control in the
medical laboratory is a statistical process used Two levels of QC should be run at least once
to monitor and evaluate the analytical process on the day of performing the test irrespective
that produces patient results and establishing of the size of the laboratory. If the laboratory
conditions such that the quality of all tests is operational 24X7, two level controls should
performed in the medical lab assists clinicians be run in the peak hour subsequently one level
in practicing good medicine. When a every 8 hours.[3] Laboratory quality control
diagnostic test is performed in the medical material is also run after an instrument is
laboratory, the outcome of the test is a result. serviced, when reagent lots are changed, after
The result may be a patient result or it may be calibration, and whenever patient results seem
a quality control (QC) result. The result may inappropriate.
be quantitative (a number) or qualitative Quality control materials should have the
(positive or negative) or semi-quantitative following characteristics. They should have
(limited to a few different values). QC results the same matrix as patient specimens,
are used to validate whether the instrument is including viscosity, turbidity, composition,
operating within pre-defined specifications, and color. Both freeze-dried and liquid
inferring that patient test results are reliable. stabilized control materials are subject to
Once the test system is validated, patient inherent errors. There may be instability in
results can then be used for diagnosis, certain analytes (for example Creatine kinase,
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bicarbonate) after reconstitution (freeze-dried) routinely carried out. There is thus continuous
or thawing (liquid stable). The act of evaluation of the reliability of the work of the
reconstitution can introduce an error far laboratory. Hence IQC primarily checks the
greater than the inherent error of the rest of the precision of lab work. Each laboratory should
analytical process and there may be establish its own mean and control limits for
contamination from the diluent. [4] daily monitoring of IQC. The mean for each
parameter should be calculated by taking into
Each laboratory should perform stability
consideration values for at least twenty days
testing for control material after reconstitution
then standard deviation and Coefficient of
or thawing and for material in long term
variation should be calculated. [5,6]
storage. This should be supported by
manufacturer’s documentation.[4]  Allowable Error Limit (AEL) for each
analytes:
Types of Quality control programs:

Internal and external quality control This can be calculated as %AEL=

programmes are the two different monitoring [0.25xReference Interval/Mean of normal

procedures and complementary to each other. range] x 100

Internal QC checks for day to day variation in For eg: Glucose the normal range is 70-
laboratory in the form of precision and 110mg/dl.
external quality control is for accuracy of the
result given by the laboratory by comparing Hence, %AEL =[0.25x110-70/70+110/2] x

the results with peer group and by analyzing 100 = 10/90x100=11.11%

proficiency testing material. If the result fall outside this limit it should be
[7]
1. INTERNAL QUALITY CONTROL rejected.

This is based on monitoring the biochemistry Analysis and monitoring Developing data
test procedure that is performed in the for Levey– Jennings chart:
laboratory. It includes measurement on
 SD is a measurement of variation in a set
specially prepared materials and repeated
of results. It is very useful to the
measurements on routine specimens, as well
laboratory in analyzing QC results. The
as statistical analysis day-by-day of date
obtained from the test which has been

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Samreen M Sheik et al., Quality Control in Clinical Biochemistry: A Glimpse….

formula for calculating standard deviation then be drawn, showing the mean value as
is: well as + 1, 2, and 3 SD. The mean is shown
by drawing a line horizontally in the middle of
the graph and the SD are marked off at
appropriate intervals and lines drawn
horizontally on the graph, as shown below. In
Where S represents the standard deviation,
order to use the Levey–Jennings chart to
means summation of all the (xi - )2 values, xi
record and monitor daily control values, label
is n individual control result, is the mean of
the x-axis with days, runs or other intervals
the control results, the number of independent
used to run QC. Label the chart with the name
data points (values) in a data set are
of the test and the lot number of the control
represented by “n”. Calculating the mean
being used.[8]
reduces the number of independent data points
to n – 1. Dividing by n –1 reduces bias. The Interpreting quality control data
values of the mean, as well as the values of +
For example in the below Levey–Jennings
1, 2 and 3 SDs are needed to develop the chart
chart,the value which fall around the mean
used to plot the daily control values. To
190.5 is within 1SD and 193.5 which is
calculate 2 SDs, multiply the SD by 2 then
between 1SD & 2 SD are acceptable. The
add and subtract each result from the mean.
mean value 185.6 which is in between 2SD
To calculate 3 SDs, multiply the SD by 3, then
and 3 SD is considered as warning sign. The
add and subtract each result from the mean.[7]
mean value beyond 3SD should be rejected.
Once the appropriate range of control values
have been established, the laboratory will find
it very useful to represent the range
graphically for the purpose of daily
monitoring. The common method for this
graphing is the use of Levey–Jennings charts.
In order to develop Levey–Jennings charts for
daily use in the laboratory, the first step is the
calculation of the mean and SD of a set of 20 Fig 1: Quality control data
control values. A Levey–Jennings chart can

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Samreen M Sheik et al., Quality Control in Clinical Biochemistry: A Glimpse….

[9]
Westgard Rules: continue the same way mathematically
changing the mean. Common causes are when
The following control rules are used to
new reagent or quality control material has
interpret the control data:
been used, change in the internal temperature
1. 12s – One control observation exceeding the or dirty cuvettes and when the calibration not
mean ±2SD used only as a “warning” rule that accurate.
initiates testing of the control data by the other
A trend is when the QC value slowly moves
control rules
up or down from the mean and continue
2. 13s- One control observation exceeding the moving the same direction overtime. Trends
mean ±3SD primarily sensitive to random can be caused by calibration that is failing,
error. deterioration of reagents, tubing, or light
3. 22s – Two consecutive control observations sources.
exceeding the same mean +2SD or mean
Shifts and trends can occur without loss of
-2SD primarily sensitive to systematic error. precision and can occur together or
independently. The occurrence of shifts and
4. R4s – One observation exceeding the mean
trends on the Levey Jennings control chart is
+2SD and another exceeding the mean
the results of either proportional or constant
-2SD is primarily sensitive to random error. error. [10]

5. 41s– Four consecutive observations

exceeding the mean +1SD or the mean Important steps to follow in case of quality
-1SD primarily sensitive to systematic error. control failure
 Stop testing samples/release of reports
6. 10x– 10 consecutive control observations
 Search for recent events that could have
falling on one side of the mean(above or
caused the changes
below, with no other requirement on size of
 Examine environmental conditions
the deviations) - sensitive to systematic error.
 Follow manufacturer’s troubleshooting
Shifts & Trends: guide

A shift is when the QC values move suddenly

upword or downword from the mean and

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 Root cause analysis (RCA), corrective and i. Gradual accumulation of debris in

preventive actions (CAPA) should be sample and/or reagent probe
taken
Determine the type of error 2. EXTERNAL QUALITY CONTROL
 Random error may be due to:
A system designed to objectively assess the
a. Bubbles in the reagents
quality of results obtained by laboratories, by
b. Inadequately mixed reagents
means of an external agency. The objectives
c. Unstable temperature and
of External Quality Assurance Scheme
incubation
(EQAS) are to provide a measure for
d. Unstable electrical supply
individual laboratory quality. To supplement
e. Fibrin /clot in the sample/ probe
internal quality control procedures, provide a
 Systematic error may be due to – A trend measure of the “state of the art” for a test. To
or shift away from the laboratory obtain consensus values when true values are
established mean unknown. To investigate factors in
a. Change in reagent lot and performance (methods, staff etc). To act as an
calibrator lot educational stimulus to improvement in
b. Improperly prepared reagents performance IFCC 1977
c. Deterioration of
reagents/calibrators/ control EQAS report should show laboratory

material performance, comparison with target value,

d. Inadequate storage of comparison with all results, comparison with

reagents/calibrators method group and performance over time,

e. Change in sample or reagent Scientific reliability and validity, accredited

volume due to pipette proficiency testing scheme provider,

maladjustment international accreditation, Conformity

f. Change in temperature of Assessment – General Requirements for

incubators and reaction blocks Proficiency Testing assures that the EQA

g. Deterioration of a photometric provider itself has a quality policy. EQAS

light source educates us about Frequency of methods used,

h. Change in procedure from one Performance of methods used, accuracy and

operator to another precision, Susceptibility of methods to

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interference including other analytes and laboratories and the appropriate values must
matrix and Interpretation of results.[11] be assigned with reference to ±2 SD

Several external quality control programmes  Performance Evaluation

are available. The participating laboratory is
Performance is evaluated by calculating
sent vials of controls without reference ranges.
VIS(Variance Index Score) :
Statistical Analysis includes:

 Homogeneity Testing
Where Xlab is the result from the
Homogeneity test is performed to check for participants, AV the assigned values from
the presence of vial-to-vial variations using reference laboratory value/peer group value
the IUPAC Protocol (2006). 10 % of the and CCV is the chosen coefficient of variation.
control sample for each level are randomly When the (i) VIS is lying between 0 and 50
selected and analyzed in duplicates. The the performance is graded as excellent, (ii)
results must be subjected to Cochran’s t test VIS 51–100 as very good (iii) VIS 101–150 as
for outliers and compared with critical values good performance, (vi) VIS 151–200 as
[12]
at 95 % confidence interval. acceptable performance, (v) VIS 200–250 as
performance needs improvement (vi) VIS
 Stability Testing
>250 as unacceptable. The maximum VIS is
In order to study the stability of lyophilized up to 400 and the sign is ignored. [12]
serum, a single level control sample must be
stored at two different temperatures, 4–8 °C
Evaluation of Cause of Errors in EQAS
and −20 °C and are analyzed in 3, 5, 7 and
8 months. Results are statistically analyzed
1. Clerical error may be due to
using SPSS program and tested for equality of
Transcription error
variance by Levene’s test and t test.[12]
(Typing/Calculation) & Wrong
 Setting Assigned Values method registered for analysis

Samples of each level must be analyzed for 2. To rule out methodological errors:

3 days in duplicate at the three ISO certified Check for instrument function,
daily instrument maintenance,
instrument calibration , reagents/
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Samreen M Sheik et al., Quality Control in Clinical Biochemistry: A Glimpse….

sample reconstitution details, laboratory's internal analytical process prior to

storage temperature after sample the release of patient results, in order to
receipt/reconstitution, alignment of improve the quality of the results reported by
instrument probe, pipette the laboratory.
calibration and environomental
CONCLUSION:
conditions
3. To rule out technical errors: Check Reliability of Clinical Biochemistry laboratory

for delayed testing after performance relies on day-to-day monitoring

reconstitution, QC material run of QC data. Application of these techniques

within expiry date, Acceptability will help to reduce errors, achieve quality

of QC result on the day of run, QC goals and thus release of quality reports and

data showing a specific trend, give both the laboratory and the clinician

Manual pipetting/dilution proper, confidence in the results.

labeling of Secondary tubes and

ACKNOWLEDGEMENT:
sample processed correctly
4. Proficiency testing materials error The authors thank Ms. Vidya S for technical

may be due to: Incorrect support.

volume/sample received, CONFLICT OF INTEREST

hemolysed sample. Authors have no conflict of interest to declare.

5. Error due to evaluation of results REFERENCES:

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