QUALITY CONTROL ❖ horizontal axis

- the numeric value for an individual

➢ A process to periodically examine a
result
measurement procedure to verify that it
❖ vertical axis
is performing according to pre-
- the number of repeated
established specifications
measurements with the same value
➢ Samples or assay on a regular schedule
made on aliquots of a QC material
to verify the laboratory procedures are
❖ red line
performing correctly
- dispersion of results for repeated
➢ Done every day by the medical
measurements of aliquots of the
technologists on duty before they start
same QC material, which is the
running their samples in the morning
random imprecision of the
ANALYTICAL BALANCE AND measurement
IMPRECISION SYSTEMATIC BIAS
➢ The interpretation of quality control result • Difference between the observed mean
is based on acceptance criteria that will and the expected value for a QC material
identify bias, run-in bias or imprecision • Brought about by changes in calibration
that exceed on expected method for
performance attributes ACCURACY

IMPRECISION • The combination of systematic bias and

imprecision that occurred for that specific
• Dispersion of results for repeated measurement.
measurements of aliquots of the same
QC material TRUENESS

STANDARD DEVIATION (SD) ❖ Refer to an average systematic bias that

may be present in a given method.
• Measure of expected imprecision in a
measurement procedure when it is
performing correctly.
➢ Interval of ±1SD – 68% of
measured values
➢ Interval of ±2SD – 95% of
measured values
✓ Correct calibration of a method
eliminates systematic biases

Imprecision of an incorrectly calibrated

method is the same as when correctly
calibrated. All methods have an inherent
imprecision.
Why do we need to measure QC samples? ◼ CALIBRATION AND VERIFICATION
OF CALIBRATION
1. To statistically evaluate the
measuring process • Method calibration is most often
2. To verify that the method continues to performed by the laboratory using
perform within the specification calibrator materials provided by
consistent with acceptable systematic the method or instrument
bias and imprecision manufacturer
3. To identify that the change in
performance occurred that needs to • (E.g. Point-of-care devices) -
be corrected methods are calibrated during the
manufacturing process, and the
laboratory performs a verification
CALIBRATION CONSIDERATION IN of that calibration
QC • Recalibrate methods on a time
➢ Calibration of the analytic measurement schedule that is established
procedure is a key component in based on experience
achieving quality results.
• In vitro device (IVD)
manufacturers frequently specify
calibration intervals

◼ CALIBRATION TRACEABILITY TO A
REFERENCE SYSTEM AND
COMMUTABILITY CONSIDERATIONS
• Calibration of routine methods
should be traceable to a higher-
order reference measurement
procedure or international
reference material (ISO, 2003;
Vesper & Thienpont, 2009; Miller
et al, 2014).

❖ Part 1 shows calibration of a method, OVERVIEW OF QC PROCEDURES

which establishes the relationship
◼ STATISTICAL QC
between the signal measured and the
quantitative value of analyte in the • Evaluates a measurement
calibrator materials. procedure by periodically
❖ Part 2 shows that a method’s current assaying a QC sample for which
calibration can be verified not to have the expected result is known in
changed rather than performing a advance.
recalibration.
• Part of the process management
component of the quality system
that integrates good laboratory
 practices to ensure correct patient
results.
• If QC results is within acceptable
limits of the known value:
- the measurement procedure is
verified to be stable, which
means it is performing as
expected
- the results for patient samples
can be reported with good
probability that they are
suitable for clinical use
• If QC results is not within
acceptable limits of the known
value:
- the measurement procedure is
not performing correctly
- the results for patient samples
are not reported and corrective
action is necessary
LEVEY-JENNINGS/SHEWHART PLOT
• Most common presentation for
evaluating QC results.
• The number of results expected
within the SD intervals is as
follows:
±1SD = 68.3% of observations
±2SD = 95.4% of observations
±3SD = 99.7% of observations
IMPLEMENTING QC PROCEDURES
◼ SELECTION OF QC MATERIALS
• Two different concentrations are
necessary for adequate statistical
QC.
• Analyte concentrations that
monitor the analytic measurement
range of the method, should be
selected for Quantitative Methods.
◼ FREQUENCY TO ASSAY QUALITY
CONTROL SAMPLES
• Analytic stability of the
measurement procedure
• Risk of harm to a patient from
clinical action being taken before
a significant error is detected
• Number of patient results
produced in a period of time when
an error condition existed but was
not yet detected
• Events such as recalibration or
maintenance that may alter the
current performance condition of
the measurement system
• Training and competency of the
test operator, particularly for
 manual or semi-automated
methods
• Risk of failure of the measuring
device
◼ ESTABLISHING QUALITY CONTROL
TARGET VALUE AND STANDARD
DEVIATION THAT REPRESENT A
STABLE MEASUREMENT
OPERATING CONDITION
• A minimum of 20 observations is
recommended for the initial SD
estimate
• Determine the SD for stable
measurement performance from
the cumulative SD over a 6- to 12-
month period for a single lot of QC
material.
• QC target values and acceptable
performance limits
- established to optimize the
probability to detect a
measurement defect that is
large enough to have an
impact on clinical care
• Minimizing the frequency of
“false alerts” due to statistical
limitations of the criteria is used
to evaluate QC results.
◼ PERFORMANCE OF A
MEASUREMENT PROCEDURE FOR
ITS INTENDED MEDICAL USE
➢ Sigma metric
o σ (sigma) = Greek letter
used to denote SD
o Commonly used to assess
how well a method performs
relative to the medical
requirement.
o Compares the variability in a
measurement process (in
SD) VS. the acceptable
variability because it will not
cause an error diagnosis or
treatment of a patient.
◼ ESTABLISHING RULES TO
EVALUATE QUALITY CONTROL
RESULTS
➢ Westgard Rules
o conventional way to express
QC interpretive rules is by
using an abbreviation
nomenclature popularized
among clinical laboratories
*CUSUM (cumulative sum) and EWMA
(exponentially weighted moving
averages) – preferred to monitor for
bias trends
 correspond to any maintenance,
reagent lot change, or calibration
events
❖ The glucose method stability and
performance over the 10 months were
considered acceptable for clinical use

◼ CORRECTIVE ACTION WHEN A

QUALITY CONTROL RESULT
INDICATES A MEASUREMENT
PROBLEM

• A QC alert occurs when a QC

result fails an evaluation rule,
which indicates that an analytic
problem may exist.
• There is a high probability that the
assay is producing results
unreliable for patient care

❖ The first reagent lot change caused a

step shift to higher values that was too
small to initiate a change in target
value
❖ The second reagent lot change had no
effect on QC results.
❖ Between March and April, a transition
to lower values occurred that did not
 ◼ REVIEWING QUALITY CONTROL ❖ Automated systems to assist in the
DATA review of QC data are acceptable
❖ individual Levey-Jennings charts do
• Immediate impact of QC data is to not need to be examined every
determine if patient results can month.
be reported and used for clinical ❖ A report that compares the mean
decision making
and SD for QC results over a defined
time interval, such as 1 month, to the
REVIEW SCHEDULES OF QC DATA expected values consistent with
Responsible stable assay performance can be
Time Purpose useful to focus the review on assays
Person
Ensure that that may need attention.
correct follow-
up of any QC Major Functions of the QC Review
alerts was
Process:
conducted
Patient samples ✓ It verifies that test procedures
Senior
that may have are stable and meet
Technologist
Weekly had erroneous performance specifications
and/or
results were
Supervisors ✓ Identifies test procedures that
repeated
Ensure that may need intervention to
process was address trends in performance
properly deterioration
documented in
QC records
Address/include
any issues
REAGENT AND CALIBRATOR LOT
identified by the CHANGES
weekly review
➢ Changing reagent lots can have an
process
unexpected impact on QC results.
Examination of
the Levey- ➢ Use of clinical patient samples to verify
Jennings chart* the consistency of results between old
or other tool to and new lots of reagents is necessary
identify trends because of the unpredictability of a
or changes in
matrix-related bias being present for QC
Laboratory assay
Monthly materials
Director performance
that may need o CLSI document EP26 (CLSI,
to be addressed 2013) recommends 3 or more
Review samples
consistency of
reagent lot o Alternate: 10 or more patient
changes, samples that span the analytic
calibrator lot measurement range and use
changes, and Deming regression analysis
any patient (Cornbleet & Gochman, 1979;
data-based QC Linnet, 1993)
procedures
USING PATIENT DATA IN QC
PROCEDURES
➢ Results from patient samples support QC
processes in a laboratory by verification
of:
o Consistency of patient results
when changing lots of reagent
or calibrators for a method
o Identified inconsistent results
using a delta check with a
previous result for a patient
o Consistency of patient results
when an analyte is measured
using more than one
instrument or method in a
health care system
o Method performance using
results from patient samples in
a statistical QC scheme
◼ DELTA CHECK WITH A PREVIOUS
RESULT FOR A PATIENT
• Comparing a patient’s current test
result to a previous result for the
same analyte
• Most useful to detect mislabeled
samples and samples altered by
dilution with IV fluid during
collection from a patient
 ◼ VERIFY CONSISTENCY OF RESULTS
BETWEEN MORE THAN ONE
INSTRUMENT OR METHOD

➢ Round robin
o Clinical patient sample
aliquots are assayed using
each of two or more methods
(or analyzers) to evaluate, and
if necessary adjust the
calibration as needed, to
achieve agreement in results
for patient samples.

PROFICIENCY TESTING or
EXTERNAL QUALITY ASSESSMENT
➢ A program to evaluate method
performance by comparison of results
versus those of other laboratories for the
same set of samples
✓ Each laboratory assays the PT
samples as if they were patient
samples and reports the results
for the PT samples to the PT
provider for evaluation
✓ The PT provider assigns a target
value to the PT samples and
◼ USING PATIENT DATA FOR determines if the results for an
STATISTICAL QUALITY CONTROL individual laboratory are in close
• Patient results can be used to enough agreement with the target
monitor method performance value

• Not widely adopted because of ✓ PT allows a laboratory to verify

lack of consensus guidelines for
use and lack of computer support
from instrument and LIS suppliers.
Average of Normals (AON) /Moving average
• Automated approaches to determine the
mean (or median) for groups of sequential
patient results
that its results are consistent with
those of other laboratories and to
verify that it is using a method in
conformance with the
manufacturer’s specifications.
COMMON CAUSES FOR PROFICIENCY QUALITY MANAGEMENT
TESTING FAILURE
• Refers to the overall process used to
ensure that laboratory results meet the
requirements for health care services to
patients.