Clinical Chemistry 48, No. 7, 2002
blood groups. Two factors contribute
to the probability of discrepancy and
thus to the power of this method: the
power will be higher if the number of
blood groups is higher or if the frequencies are more similar.
References
Janne Suvisaari1,2*
Martti Syrjälä2
1
Department of Clinical Chemistry
University of Helsinki
FIN-00029 HUS Helsinki, Finland
2
HUCH Laboratory Diagnostics
Helsinki University Central Hospital
FIN-00029 HUS Helsinki, Finland
* Address correspondence to this author at: HUCH Laboratory Diagnostics,
Helsinki University Central Hospital, PO
Box 340, FIN-00029 HUS, Finland. Fax
358-9-471-75656; e-mail janne.suvisaari@
helsinki.fi.
Guidelines and Recommendations in
Laboratory Medicine
To the Editor:
Dr. Keffer (1 ) has provided a
thought-provoking report on the
noncompliance of physicians with
most clinical practice guidelines
(CPGs). He also refers to the Laboratory Medicine Practice Guidelines
(LMPGs) produced by the National
Academy of Clinical Biochemistry
(NACB). As contributors to several
LMPGs (2– 4 ) and active participants
in the NACB LMPG program, we
offer some insights into the rationale
of NACB and how the NACB LMPG
process differs from that of CPGs
authored by other professional societies. We discuss some reasons for
the difficulty in assessing impact and
suggest unrecognized impacts of
these guidelines.
opinions of the local community of
laboratory practitioners.
Dr. Keffer (1 ) attempted to show
through a Medline search and other
means that there are few, if any,
published evaluations of the NACB
guidelines. We suggest that the impact of guidelines can be better measured by citations in laboratory procedure manuals (in hospitals and
commercial laboratories), manufacturers’ literature and product labeling, and internal documents used by
industry to set performance requirements for their products. These occurrences are difficult to monitor, but
we believe they are more accurate
measures of the value of NACB
LMPGs.
Clinical and laboratory guidelines
are reached by consensus-building
and may not alter practice in most
settings because they are already
based, at least in part, on what most
practitioners feel should be the standard of practice. That standard is
largely established based on the collective current practical experiences
of those practitioners. This concept
has recently been addressed in the
area of clinical practice in an editorial
by van Walraven (8 ). Guidelines of
this nature thus are likely to change
practices more drastically at the
fringes than they are to move the
central tendencies of practitioners.
Indeed, it is our opinion that they
may not be accepted as guidelines in
the mainstream of clinical practice
unless they represent the practices
already in use by the mainstream
and that the mainstream often has
little to change to be in compliance
with these guidelines.
The alternative view is that just
because everyone is adhering to a
particular practice does not make it
optimal. Eventually, widely used but
antiquated tests and methods must
be replaced with new ones. Ultimately, recommendations must be a
balance between consensus and an
evidence-based approach. However
recommendations are derived, codification can document and firmly establish a standard from which to
build.
Dissemination of guideline information requires improvement. The
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1. Nosanchuk JS, Gottmann AW. CUMS and delta
checks. A systematic approach to quality control. Am J Clin Pathol 1974;62:707–12.
2. Iizuka Y, Kume H, Kitamura M. Multivariate delta
check method for detecting specimen mix-up.
Clin Chem 1982;28:2244 – 8.
3. Hanley JA, Lippman-Hand A. If nothing goes
wrong, is everything all right? Interpreting zero
numerators. JAMA 1983;249:1743–5.
Most CPGs are aimed at physicians and have focused on clinical
practices for a disease (e.g., asthma)
or symptom (e.g., chest pain). By
contrast, the intended audience for
LMPGs includes not only physicians,
but also clinical laboratorians and
manufacturers of clinical assays.
These guidelines include recommendations on the appropriateness of
offering certain tests for particular
clinical situations and for denying
or limiting the availability of other
assays. These changes and their effects may be difficult to document,
but consensus recommendations can
prompt manufacturers to construct
new assays, such as the urine immunoassay for methylenedioxymethamphetamine (Ecstasy) as recommended (3 ).
Because of their potential impact,
all NACB LMPGs are presented and
thoroughly discussed in sessions at
national meetings, and an estimation
of the degree of consensus is sought.
The proposed guidelines are also
presented at other meetings where
pertinent disciplines are represented
(e.g., cardiologists, emergency medicine physicians, clinical toxicologists,
and endocrinologists). This may be
unlike some CPGs that are prepared
and published by experts, but without open presentation.
Although traditional “evidencebased” documentation is noted for
many NACB recommendations [e.g.,
randomized control trials (5, 6 )],
other recommendations do not lend
themselves to support by outcome
studies. The NACB guideline for
testing of newborns (7 ), for example,
recommended that testing for alkaline phosphatase isoenzymes not be
performed. It was impractical to perform a randomized trial to support
this recommendation. In the NACB
guideline for emergency toxicology
testing (3 ), a 1-h turnaround time
was recommended for reporting of
test results. There are no outcome
studies to show that this improves
the clinical management of intoxicated patients or reduces length of
stay in an emergency department. It
is expected, nonetheless, that external expert opinion (in the consensus
guidelines) will lend credence to the
1135
1136
sions of the guidelines on the NACB
web page and invited e-mail commentaries. This combined approach
has led to more widespread recognition of their existence and broader
participation in formulating the recommendations made therein.
We applaud Dr. Keffer’s efforts in
bringing this important issue to the
forefront. The process of creating
new guidelines warrants discussion
to improve the products and assess
their impact.
References
1. Keffer JH. Guidelines and algorithms: perceptions of why and when they are successful and
how to improve them. Clin Chem 2001;47:
1563–72.
2. Wu AHB, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R Jr. National Academy of
Clinical Biochemistry Standards of Laboratory
Practice: recommendations for use of cardiac
markers in coronary artery diseases. Clin Chem
1999;45:1104 –21.
3. Wu AHB, Broussard LA, Hoffman RS, Kwong
TC, McKay C, Moyer TP, et al., eds. Laboratory
medicine practice guidelines: recommendations for the use of laboratory tests to support the impaired and overdosed patient
from the emergency department [Draft Guidelines]. Washington, DC: National Academy
of Clinical Biochemistry (http://www.nacb.org/
Toxicology_LMPG.stm).
4. Warner A, Annesley T, eds. Guidelines for therapeutic drug monitoring services. Washington,
DC: National Academy of Clinical Biochemistry,
1999:110pp.
5. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS,
Seeff LB. Diagnosis and monitoring of hepatic
injury. I. Performance characteristics of laboratory tests. Clin Chem 2000;46:2027– 49.
6. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS,
Seeff LB. Diagnosis and monitoring of hepatic
injury. II. Recommendations for use of laboratory
tests in screening, diagnosis, and monitoring.
Clin Chem 2000;46:2050 – 68.
7. Kaplan LA, Tange SM, eds. Guidelines for the
evaluation and management of the newborn
infant. Washington DC: National Academy of
Clinical Biochemistry, 1998:84pp.
8. van Walraven C. Practice guidelines and practicing physicians—who’s guiding whom? Clin Chem
2002;48:9 –10.
Alan H.B. Wu1*
Roland Valdes, Jr.2
Charles D. Hawker3
1
Department of Pathology
and Laboratory Medicine
Hartford Hospital
Hartford, CT 06102
2
Department of Pathology
and Laboratory Medicine
University of Louisville
School of Medicine
Louisville, KY 40292
3
ARUP Laboratories, Inc.
500 Chipeta Way
Salt Lake City, UT 84108
* Address correspondences to this author at: Department of Pathology, Hartford Hospital, 80 Seymour St., Hartford,
CT 06102. Fax 860-545-3733; e-mail awu@
harthosp.org.
␣1-Microglobulin Is Stable in Human
Urine ex Vivo
To the Editor:
Increased concentrations of urinary
␣1-microglobulin may imply proximal tubular damage (1 ). ␣1-Microglobulin has generally been considered to be stable in human urine
(1, 2 ). Tencer et al. (2 ) observed good
stability in 10 urine samples stored at
room temperature for 7 days, at 4 °C
for 30 days, and at 20 °C for 6
months. In contrast, Donaldson et al.
(3 ) noted significant losses of ␣1microglobulin in urine stored at
20 °C and that this problem was
exacerbated in more acidic (pH 6.0)
urines; they recommend that urine
should be neutralized on receipt. The
manufacturers of our assay recommend that urines be assayed fresh or
stored at 4 °C for a period of less than
1 week and warn against freezing
samples. Urine samples are often
stored before batch analysis. To clarify the appropriate storage conditions for urinary ␣1-microglobulin,
we studied stability under standardized conditions.
Random unpreserved urine samples were collected from 19 patients
at a single nephrology clinic, and
urinary pH was determined (mean
pH 5.87; range, 5.08 – 6.85). Samples
were then divided into two aliquots,
one of which was neutralized (mean
pH 7.58; range, 7.23–7.94) by dropwise addition of 5 mol/L NaOH.
Within 6 h of collection, ␣1-microglobulin and creatinine were measured in both aliquots. Ten (1 mL
each) aliquots of both the untreated
and neutralized urines were stored
in capped polystyrene tubes at room
temperature, 4 °C, 20 °C, or 80 °C
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NACB recently conducted an informal e-mail survey of 2596 foreign
and domestic doctoral members of
AACC and NACB concerning familiarity with and use of the NACB
guidelines. Overall, only 148 replies
were received. This low response
rate alerted the NACB leadership to
a potential need for wider dissemination of these guidelines, and efforts
are underway to use the Internet and
other means to facilitate this.
In the NACB survey, although the
numbers were small, there was an
indication that when the guidelines
were used, they were used in ways
that met the original objectives of
NACB. Among 57 clinical laboratorians who reported that they had used
the guidelines, 60% indicated that
they specifically selected tests, reagent sets, or products that followed
the guidelines; 21% indicated they
told their vendor representatives
what their companies had to do to be
in compliance; and 14% indicated
that they had modified a vendor’s
procedure to be in compliance with
the guidelines. Among 16 industry
laboratorians who responded to industry-focused questions, 6 indicated that their companies used the
guidelines in product design (such as
sensitivity, specificity, and choice of
analytes), and 8 indicated that their
companies use the guidelines in customer education.
One of the reasons for these somewhat less than ideal survey results is
that the first four NACB guidelines
were presented during satellite meetings of the AACC annual meetings,
whereas more recently, the guidelines have been presented at
EduTrak sessions at the AACC meeting in addition to meetings of cosponsoring medical societies. Moreover, the first four guidelines were
published in monograph form only,
whereas the latter guidelines have
also been published in peer-reviewed journals (2, 5, 6 ). With the
exception of the thyroid guidelines,
of which 50 000 copies were distributed, 5000 copies of the monographs were usually printed. More
recently, beginning with the guideline for cardiac markers (2 ), the
NACB has posted preliminary ver-
Letters