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BasicQCBooklet (2005)
BasicQCBooklet (2005)
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©1991 Bio-Rad Laboratories, Inc. • Lit. No. Q-1102 4/05 • All Rights Reserved • Printed in the USA
QUA LI TY CON TROL FO R THE CLI NI CA L L ABOR AT O RY 1
Mean
The mean is defined as the
arithmetic average of a set of
data points. It is expressed as:
where:
xi = each data point
n = the number of
data points in the set
The mean describes the "central tendency"
of the data set. In the clinical lab, the mean identifies the "target
value" of a set of data points, usually QC or patient data.
2 QUA LI TY CON TROL FO R THE CLI NI CA L L ABOR AT O RY 3
Only about 4.5% of future data should be less than 107.3 IU/L or (5.03 IU/L / 117.4 IU/L)(100) = 4.3%
greater than 127.5 IU/L; i.e., only one result in 20 should be beyond The CV is useful for comparisons of precision at diffe re n t
these limits. concentrations as long as the materials used are similar and CVs are
The 3s range (limit) is calculated as: determined under similar conditions. This statistic is commonly
used to compare manufacturer claims, CAP survey results, and peer
(Mean) +/– (3)(s)
group QC reports. It can also be used as a par t of the internal
117.4 IU/L – (3 x 5.03 IU/L) = 102.3 IU/L quality control system when performing patient precision testing,
117.4 IU/L + (3 x 5.03 IU/L) = 132.5 IU/L which is presented later.
The 3s range is 102.3 IU/L to 132.5 IU/L.
Standard Deviation Index
O n ly about 0.3% of future data should be less than 102.3 IU/L or
Another statistic which is helpful to evaluate performance is the
gre ater than 132.5 IU/L. It would be ve ry unusual to obtain a re s u l t
standard deviation index (SDI). This statistic, which is usually
beyond these limits.
obtained by participation in an external QC or proficiency testing
In the clinical lab o ratory, these ra n ges (limits) are used to program, is used to compare a laboratory's results to its peer group.
d e t e rmine the acceptability of a test run not only on the basis of a It allows the lab to gauge its performance when compared to the
single data point but on groups of data points as well. This topic is peer group.
p resented in the next section.
The SDI for the mean is calculated as follows:
S t a n d a rd dev i ation is also va l u able when comparing methods or
eva l u ating new instruments. A method or instrument with a low SDI = (lab mean – peer group mean)
s t a n d a rd dev i ation produces consistent results. The lab using an peer group standard deviation
i n s t rument or method wh i ch has high standard deviations will have
less certainty about the accura cy of diagnosis or the effe c t ive n e s s The target SDI is 0.0. This would indicate that the lab's
of tre atment because of test result va ri ab i l i t y. In other wo rd s , high p e r fo rmance is identical to the peer group ave rage. Accep t able
s t a n d a rd dev i ations (poor pre c i s i o n , gre ater variability) can affe c t SDI values are between +/–1.0. Any test/method/instrument wh i ch
the integrity of all results. has an SDI between +/–1.0 and 1.5 may have a pro blem and the
l ab should inve s t i gate. The lab must tro u bleshoot and correct any
The method or instrument selected should provide a standard test/method/instrument wh i ch has an SDI of +/–2.0 or gre at e r. The
deviation wh i ch is medically accep t abl e.4 re l at ive importance of the SDI statistic does dep e n d, however, on
the size of the peer gro u p .
6 QUA LI TY CON TROL FO R THE CLI NI CA L L ABOR AT O RY 7
The SDI statistic can be used also as part of the lab o rat o ry ' s NOTE: If any of the following rules is violat e d, the tech n o l ogist
i n t e rnal QC system wh i ch is presented later in this document. It is must rev i ew the perfo rmance of the test, consult
also useful in interp reting pro ficiency testing. The lab o rat o ry ' s tro u bleshooting guides, perhaps perform maintenance, c o rrect
rep o rted result replaces the lab mean in the equation for SDI. In a ny identified pro blems or dep a rt u re from protocol, and notify
this case, SDI values exceeding 2 or 3 suggest a pro bl e m . the supervisor who will make decisions about rep o rting results
and re running the test.
What are the performance challenges?
The perfo rmance ch a l l e n ges consist of seve ral rules wh i ch define 13S This rule detects random erro r.
specific perfo rmance limits. These rules are commonly re fe rred to Vi o l ation of this rule may also
as We s t ga rd rules. If any of the rules is violat e d, then the analy t i c a l point to systematic erro r. Th e
run is considered out of contro l
run may be invalid and the test results unaccep t able. The We s t ga rd
when one control value exceeds
rules are va ri e d. Some are designed to detect random error; others the mean +/–3s. This rule is
detect systematic error wh i ch may indicate a bias in the system. applied within the run only.
Six rules are commonly used by laboratories in va rious
c o m b i n ations. Rule combinations are selected by the lab o rat o ry 22S This rule detects systemat i c
and are based on the number of control levels run with each erro r. It should be applied within
and across runs. This rule is
a n a lytical run. The ove rall objective is to obtain a high pro b ab i l i t y
v i o l ated within the run wh e n
of error detection and a low fre q u e n cy of false rejection of runs. two consecutive control values
(or 2 of 3 control values when 3
The six commonly used rules are: levels are being run) exceed the
"same" (mean +2s) or (mean
12S This is the "wa rning rule." –2s) limit. The rule is violated
If one control measurement a c ross runs when the previous
exceeds the mean +/– 2s, then value for a particular contro l
the tech n o l ogist must consider level exceeds the "same" (mean
other controls in the run +2s) or (mean –2s) limit.
("within-run") and in previous
runs ("across-run") befo re R4S This is a "ra n ge" rule and it
a c c epting the run and rep o rting detects random erro r. This rule is
the results. applied within the run only. Th i s
rule is violated when the
Laborat o ries wh i ch use this rule alone in perfo rming their quality diffe rence in standard deviation
c o n t rol will fre q u e n t ly reject runs wh i ch are va l i d. According to b e t ween two consecutive contro l
values (or 2 of 3 control values
Westgard1, fa i l u re to allow for valid points between 2s and 3s will
when 3 levels are being run)
result in falsely rejecting: exceeds 4s.
• 5% of all analytical runs when using one level of contro l ;
• 10% of all analytical runs when using two levels of control; and
• 14% of all analytical runs when using three levels of control.
8 QUA LI TY CON TROL FO R THE CLI NI CA L L ABOR AT O RY 9
standard deviation. The laboratory establishes an upper and lower Table 1. Possible CUSUM Scenario
threshold for each level of control. Any result beyond the thresholds Control: Assay. Chem. Lot: 10001 Month: Jan 1998
Test: LDH Mean: 117 IU/L s = 5 IU/L
triggers calculation of the CUSUM. The CUSUM calculation
Lower Threshold: 112 Upper Threshold: 122 Control Limit: +/–13.5
continues for successive results until the cumulative sum either
Date Run Value Diff CUSUM
exceeds the control limit and identifies an "out of control" situation 1/1 1 120
for the test under observation, or changes sign, and the calculation 1/1 2 117
1/2 1 108 – 4.0 – 4.0 Initiate CUSUM
is stopped. 1/3 1 123 + 11.0 + 7.0 End CUSUM
1/4 1 119
Westgard recommends a (threshold/control) limit combination of 1/5 1 126 + 4.0 + 4.0 Initiate CUSUM
1/6 1 127 + 5.0 + 9.0
+/– (1s/2.7s) or +/– (0.5s/5.1s) for more particular practioners of
1/6 2 127 + 5.0 + 14.0 Out of Control
this technique.5 These combinations yield low frequency of false
rejection of valid runs and high systematic error detection. Using In the example above, the first two control results do not violate
the LDH example with a mean of 117 IU/L and a standard either the lower or upper threshold limit. Perfo rmance is
d ev i ation of 5 IU/L, the CUSUM threshold/control limit a c c ep t able. The third control result (108) violates the lowe r
combination +/– (1s/2.7s) would result in a lower threshold of 112 threshold limit by – 4 units. The fourth control result (123) is high
or (mean –1s) and an upper threshold of 122 or (mean +1s). The but for calculation of CUSUM is compared to the lower threshold
control limit would be +/– 13.5 or (±/2.7s). limit which was first violated. The difference is +11 units. The
CUSUM becomes +7. Calculation of CUSUM ends and returns to
Each control result for the test being monitored is reviewed. If the
a value of zero because the CUSUM sign changed from negative to
result exceeds either threshold limit, CUSUM is initiated. The
TABLE 1 positive. The sixth control result violates the upper threshold limit.
on page 11 difference between the result and the threshold limit is logged
Subsequent control results cause a violation of the upper control
provides along with the sign of the difference. Each subsequent control
a simple limit (+13.5) and the test is considered to be out of control.
example of
result is compared to the threshold first violated and a cumulative
CUSUM calculation ends when the method is declared out of
this protocol sum of the differences is maintained. This continues until the
control and receives corrective action.
cumulative sum changes signs or the
control limit is exceeded.
Although no Westgard rules have been broken, this scenario
demonstrates a possible bias in the system. Six of eight values are
above the mean and three values almost exceed the mean +2s limit,
which would have triggered the 12s warning, indicating the need to
review compliance with other Westgard rules. Any corrective
actions taken in response to CUSUM violation or potential
violation should be noted on the table or on a separate log sheet.
12 QUA LI TY CON TROL FO R THE CLI NI CA L L ABOR AT O RY 13
Anion Gap The other system re q u i res the use of normal and/or abnormal patient
A fre q u e n t ly neglected tool used to spot ch e ck perfo rmance of samples and the CV for the corresponding control level. In this
e l e c t ro lyte analy ze rs is calculation of the anion gap wh i ch is system, the CV is applied to the initial patient result to define an
defined as:2 accep t able rep l i c ate ra n ge.6 When the sample is retested,the rep l i c at e
value is compared to the predefined ra n ge. Calculated limits for
Na – (CO2 + Cl) = 5 to 14
allowable diffe rences are applicable only over a narrow ra n ge over
This simple fo rmula can be applied to electro lyte data at specific wh i ch the standard dev i ation (or CV) is fairly constant. Th u s , specific
intervals (time, runs, or tests) to monitor possible analytic error. If concentration ra n ges must be defined for selecting patient specimens
several samples fail this simple screen during any one day or run, for use as controls.
then all of the patient results should be reviewed for possible
a n a lytical erro r. Patient precision test results can be interp reted as follows:
1. Westgard, J. O., Barry P. L.,Hunt, M.R., Groth, T., A multi- 1. Westgard, J. O., Koch, D. D., Oryall, J. J.,Quam, E. F.,
rule Feldbruegge, D. H., Dowd, D. E., Barry, P.L., Selection of
Shewhart chart for Quality Control in Clinical Chemistry. medically useful Quality Control procedures for individual
CLIN. CHEM. 27/3, 493-501 (1981) tests done in a multitest analytical system.
CLIN. CHEM. 36, 230 (1990)
2. Weisbrot, M.D., I. M., Statistics for the Clinical Laboratory,
J.B. Lippincott Company, Philadelphia, (1985) 2. Howanitz, Peter J. and Joan H., Laboratory Quality Assurance,
McGraw-Hill Book Company (1987)
3. National Committee for Clinical Laboratory Standards.
Internal quality control: principles and definitions; Tentative
Guideline. NCCLS document C24-A. Villanova, Pa;
NCCLS; (1991)
For more information on ECS products and the Quality Control Program:
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