It is obviously desirable that the analytical range
cover the entirety of the pathophysiological range of
values for the analyte measured by the method. If
the analytical range falls short, explicit rules need to
be devised to deal with samples that have analyte
concentrations outside of the analytical range. In
practice, this problem is almost always due to
samples with analyte concentrations that are above
the upper limit of the analytical range. The question
in such cases is if appropriate dilution of the sample
will yield a valid measurement. If so, the dilution
procedure and the means for calculating a corrected
result need to be included in the method procedure.
If not, the manner of reporting the out-of-bound
result needs to be specified in the procedure.
METHOD COMPARISON
The purpose of a method comparison is to ascer-
tain if the test results for a set of clinical specimens
as obtained from one field method are, on average,
the same as those obtained by another field method.
The comparison amounts to a exploration of the
clinical equivalence of the two methods. Clinically
equivalent methods can be freely substituted for one
another. The substitution of a method for another
with which it is not clinically equivalent requires the
establishment of a new reference interval for the
analyte being measured and the development of a
conversion formula that can be used to equate test
results from the old method with test results from
the new study.
Motivation
A complete report of a method comparison
includes the components listed in Table 2.6. The
first component is a statement of the motivation for
the comparison. The most common motivation is
the contemplated replacement of a method with one
that possesses greater practicability.
The following excerpt from Turpeinen
et al.
(1995) explains their motivation for undertaking a
comparison of three different methods for measuring
hemoglobin A
1c
(HbA
1c
). HbA
1c
is a stable adduct of
glucose and hemoglobin A. The percent of
hemoglobin present as HbA
1c
depends upon the
blood glucose concentrations to which the hemoglo-
bin is exposed over the life-span of the red cell and
is, therefore, a useful clinical marker of long-term
blood glucose concentration control in patients with
diabetes.
. . . the methods currently used for [HbA
1c
]
measurement in clinical chemistry laboratories
show large differences between reported
values, and comparison of results from differ-
ent laboratories is difficult.
At present there is no accepted standard or
acknowledged reference method. Recently,
calibration based on a cation-exchange HPLC
method has been shown to increase the
comparability between various analytical
methods (5,6).
In this study we compare our own high-
resolution HPLC cation-exchange method
(PolyCAT A) with two other assays: a
boronate affinity binding assay (IMx) and an
automated system for [glycohemoglobin]
analysis by cation-exchange chromatography
(Diamat ™).
The motivation for this method comparison is to
compare two commercially available methods for the
determination of HbA
1c
. In addition,
the methods
are compared with a high-resolution version of the
methodology that has been gaining support as a
calibrating
method,
cation-exchange
chromatography. In this instance, it can be appreci-
ated that the employment of cation-exchange as a
calibrating method can be taken as tacit acknowledg-
ment that it is of adequate accuracy for routine
laboratory practice and, indeed, is probably more
accurate than most other methods in routine use.
Analytical methods
When comparing methods, it is of course essen-
tial that it be clear exactly what the methods are. It
therefore behooves the laboratorian to thoroughly
describe the methods under study. In fact, it is
appropriate to provide the same degree of complete-
ness in the method description as one would for a
method evaluation. However, it may be possible to
Laboratory Methods
2-23
Table 2.6
Components of a Method Comparison Report
1. Statement of the motivation for the comparison
of the methods
2. Description of the analytical methods
3. Description of the study population
4. Evaluation of concordance of the methods
5. Assessment of clinical equivalence
