ANALYTICAL ERRORS

DR. SRIKRISHNA
 Error is an action which means mistake in analytical
chemistry the difference between the true value or a
standard value and observed value is called error.

 Analytical Errors – these errors occur during actual

analysis of sample.
 Analytical errors in laboratory and increased data
variability may result from instrument malfunctions,
inability to follow up proper procedures, undetected
failures in quality control, sample misidentification,
and/or test interference.

 The analytical phase errors are very important because

they lead to inaccurate test results that may harm patients
as well as increase the cost of business.
CAUSES OF ANALYTICAL ERRORS
Incorrect results due to the inability to follow proper
laboratory procedures can be due to –

 The unexpected delay in sample processing --- Delays in

centrifugation or removal of the cell serum can result in
alterations in the concentration of several analytes.

 Incorrectly printed barcode on the sample tube – can lead to

missing out tests or wrong test selection or sample mixups.

 Instrument interfacing issues also play a very important role.

The value transferred from one end to another will be
erroneous.
CAUSES OF ANALYTICAL ERRORS
 A very little volume of sample in vacutainer issues or
reagent tube – If the volume is way below the required
limit. the pipette may not pick up the sample properly
which can lead to an erroneous report/value.

 Test systems are not properly calibrated.

 Undetected failure of quality control and frequency of

running quality control needs to define based on sample
workload and working.
CAUSES OF ANALYTICAL ERRORS
 Improper quality control data and machine maintenance
– Before samples arrive in the lab, it is important to
evaluate machine preparation and maintenance to keep
challenges at bay. Quality control in clinical laboratory
data analytics can help to know if there is any problem
with machines or are ready for testing.

 Reporting of results when controls are out of range.

 Reagent stored inappropriately.

CAUSES OF ANALYTICAL ERRORS
 Linearity and dilution errors can give you invalid or
misleading test results affecting the patient’s treatment. A
proper understanding of dilution is important to not only
get correct results but save costs too.

 Analytical phase in laboratory optimization– we should

also look into making the system lean – which sample to
be run early. For example, a vitamin d test takes keeps
the machine occupied for a longer time.
Accurate and precise – all the results are
close to the actual value and fall close lo
each other. This is the desired situation

Precise but not accurate – the results lie

close to each other but are removed from the
true value

Accurate but not precise – all results are

close to the true value but do not fall close to
each other

Not precise and not accurate – the results

are scattered and not even close to the true
value.
TYPES OF ERRORS IN
ANALYTICAL MEASUREMENTS
 Systematic or determinate errors

 Random or indeterminate errors

SYSTEMATIC AND RANDOM ERRORS
 Systematic errors – it affects every test in a constant,
predictable manner
Inaccuracy (bias)

 Random errors – it affects individual sample in a random

and unpredictable manner.
Imprecision (CV%)
SYSTEMATIC ERROR – SHIFT CAUSES
• Sudden failure or change in light source
• Change in reagent Formulation
• Major Instrument Maintenance
• Sudden change incubation temperature(enzymes)
• Room Temperature
• Failure in the sampling system/reagent dispensing
• Inaccurate calibration
RANDOM ERROR CAUSES
 Improperly mixed /dissolved reagents
 Air bubbles in reagents and reagents lines, sampling or
reagents syringes.
 Pipette tips is not fitting properly.

 A clogged pipettor (Clot).

 Unstable temperature and incubation.

 Unstable power supply.

 Poor operator technique.

 Improper mixing of processed samples.

 Incorrect reconstitution of the control material

SYSTEMATIC AND RANDOM ERRORS
 Systematic errors can be determined, quantified and can
be avoided. These comprise errors of a method,
instrument errors and reagent errors.
 Random errors manifest due to variations in a number of
observations made by same observer with greatest care
under as nearly identical conditions as possible.
Generally such errors are not errors of the technique but
personal errors of the observer.
 Total error = systematic error + random error

 Bias = mean value- true value

 Imprecision = CV%

 Total error = Bias + ( Z factor x CV%)

= Bias + ( 1.65 x CV%)
ACTIONS CAN BE APPLIED TO
REMOVE OR ELIMINATE SYSTEMATIC
ERRORS:
 Calibration of instruments and volumetric apparatus against
reference standards and applying the correction factors
 Use of high purity reagents and chemicals

 Validation of method before use

 Running blanks under identical conditions as for sample

analysis and applying correction factor
 Comparison of results through independent methods or
interlaboratory comparisons
 Using corrective methods such as standard addition or internal
standards
 Increasing analyte concentration prior to an analysis or
derivatization with specific reagents
COMMON PERSONAL ERRORS FOR
RANDOM ERRORS
 Incomplete drying of sample before weighing
 Material loss during transfer of precipitates

 Errors in transfer of solutions

 Parallax errors in reading the rates and pipettes

 Errors in making dilutions

 Errors in observation of colour change during titrations

 Transcription errors

Personal errors cannot be eliminated totally but can be

reduced through proper training and introduction of
automated analysis systems
CONSEQUENCES OF ANALYTICAL
ERRORS
 Any error during the laboratory testing process can affect
patient care,
 including delay in reporting,

 unnecessary redraws,

 misdiagnosis, and

 improper treatment.
QC CONTROL PROCEDURES IN DETECTING
AND PREVENTING ANALYTICAL ERRORS
Quality Control (QC):
 Defined as “part of quality management focused on
fulfilling quality requirements.”

 Quality control is more the inspection aspect of quality

management.

 An alternate definition is “the operational techniques

and activities used to fulfil requirements for quality.”
INTERNAL QUALITY CONTROL
 Recognition of errors which arise within the laboratory
during examination stage (testing)
- Taking steps to minimize errors.
- Equipment calibration and method verification /
validation.

 Quality control checks for both quantitative and

qualitative tests.
IQC FOR QUANTITATIVE TESTS
• Levy Jennings’s (LJ) chart is the most common graphical
tool to plot daily QC values.
When one level QC is used Reject test run if following
errors occur: -

 Value is outside 3 SD

 2 consecutive values are outside 2 SD on the same side,

but within 3 SD

 10 consecutive values or above or below the mean, but

within 2 SD
When two level QC are used: Reject test run if following errors occur:
-

 Either QC value is outside 3 SD

 Both QC values are outside 2 SD on the same side, but within 3SD
-----Difference between the two level QC values is >4 SD i.e. one level
QC is >2 SD and other level QC is < 2 SD –
------10 consecutive values of the same level QC are above or below
the mean, but within 2 SD

 5 consecutive values of one level QC and 5 consecutive values of the

other level QC are above or below the mean, but within 2 SD
IQC FOR QUALITATIVE TESTS
 For qualitative tests, positive and negative controls
should be included with each run.
 For staining procedures, gram stains require both Gram
positive and Gram negative control organisms to be used
once per week.
 QC should also be run whenever a new lot of the stain
procedure kit is used and/or any of the four components
of the stain procedure kit is replaced with a new lot.
REAGENT LOT VERIFICATION
 Each change in reagent lots can adversely affect the
consistency and quality of patient results.
 Assuring lot-to-lot uniformity is particularly important
for those analytes that are serially measured over time
such as CBC, HbA1c, TSH, tumor markers and liver
enzymes, etc.
 Performance of a new lot of reagents should be
compared against the existing lot before the existing lot
is finished.
Other alternatives to patient samples preferred for checking
lot to lot variability may be
 Reference materials or QC products provided by the
method manufacturer with method-specific and reagent-
lot-specific target values.
 Proficiency testing materials with peer-group established
means
EXTERNAL QUALITY
ASSESSMENT/ PROFICIENCY
TESTING (EQA/PT)
 EQA/PT is the evaluation of participant performance
against pre-established criteria by means of inter
laboratory comparisons.

 Participation in EQA/PT program is the best measure of

accuracy of a test for clinical laboratories.

 Hence, clinical laboratories should enroll for all tests in

this program, as far as feasible.
Benefits of EQA/PT participation:
- Assesses the overall performance of laboratory for each
test
- Serves as an early warning system for problems
- Identifies systematic problems
- Provides objective evidence of laboratory quality
- Identifies training needs
STEPS OF EQA/PT SCHEMES
1. The laboratory enrolls in a EQA/PT scheme/s

2. The EQA/PT provider sends EQA/PT items to

participating laboratories at defined interval.

3. The participating labs analyze the samples and return

their results to the EQA/PT provider within the timeline,
usually through a web portal.
STEPS OF EQA/PT SCHEMES
4. The results are evaluated by the EQA/PT provider and
the laboratories are provided with statistical data and
performance score (e.g.: z score, SDI, etc.). The
laboratory can review its own performance and also
compare with other participants/peers.

5. The laboratories must take appropriate corrective and

preventive actions when the score deviates from the
acceptable limits.

6. The participating laboratories are expected to use the

information regarding their performance to make
appropriate changes and improvements in their
operational processes, as and when needed
IF EQA/PT PROGRAM FOR A PARTICULAR
ANALYTE IS NOT AVAILABLE Ɂ
An appropriate inter-laboratory comparison or any other
alternate method (retesting of retained item, testing by
different personnel, use of certified reference materials
etc.) is recommended.
 EQA/PT providers who run these programs get
accreditation under ISO/IEC 17043:2010
REDUCING ERRORS IN THE CLINICAL
LABORATORY
 Earning Continuing Education Test
 Opportunities for improving pre-analytical quality.

 Rethinking analytical quality control.

 Determining acceptable risk of patient harm from

erroneous results for an analyte.
 Predicting the probability of producing erroneous results
for a QC strategy.
KPI OF LAB
 Laboratory Key Performance Indicators (KPIs) are
measures of the performance of the laboratory and its
activities, such as projects, processes, products, or
services. KPIs in laboratories are also used to track the
performance of the inventory, devices, environment,
data, and results.

 Keeping the lab in good condition is the basic

requirement to ensure you produce high-quality data.
 In this set of KPIs, you will measure how you’re doing
in terms of processes, inventory and environment.
EXAMPLES OF KPIS RELATED TO
PROCESSES
 Quality control
 The time your staff spends at the bench

 Turn-around-time for the analyses

 Uptime of devices

 Total space and free space on ELN or LIMS storage

 Uptime of ELN (Electronic Lab Notebook) or LIMS

(Laboratory Information Management System )
EXAMPLES OF KPIS RELATED TO
INVENTORY
 Monthly consumable use
 Amount of wasted consumables

 Consumable use per analysis

 Free space in refrigerators

 Consumables inventory size and reserve

ENVIRONMENTAL KPI
 Environmental KPIs are also very important but often
overlooked, particularly in the research labs. Some
regulations require you to daily monitor the temperature
in refrigerators and facilities.
ETHICAL CONSIDERATIONS
Principle of voluntariness
Principle of non-exploitation
Principle of social responsibility
Principle of ensuring privacy and confidentiality
Principle of risk minimization
Principle of professional competence
Principle of maximization of benefit
Principle of institutional arrangements
Principle of transparency and accountability
Principle of totality of responsibility
Principle of environmental protection
THANK YOU