POC in motion—the changing face of mobile testing
The future of point-of-care testing could yield a wide array of options
for consumers, clinicians, and labs, including
one possibility that could drive
out the central laboratory almost entirely.
testing “would be the final triumph of consumerism,”
says Larry Kricka, DPhil, professor of pathology and laboratory
medicine and director of general chemistry, University of Pennsylvania
Medical Center, Philadelphia. “This vision would perhaps see
the demise of the central lab.” Thanks to microchip technology,
he says, we might all carry a “personal laboratory”
in our pockets that can monitor clinical indicators.
Dr. Kricka and
other experts participated in a March and April audioconference
series presented by the American Association for Clinical Chemistry,
which covered subjects ranging from the future of POC testing to
using brain natriuretic peptide and troponin at the point of care.
testing would require social, technological, and regulatory changes,
Dr. Kricka says. POC testing is already expanding beyond the hospital,
into physicians’ offices and the home. As micro technologies
shrink the instruments needed for tests, consumers will do more
of the tests themselves, and the results will be transmitted to
physicians. Further into the future are implantable microlab devices.
however, will not become commonplace unless they are convenient
to store and to use. In particular, “people won’t want
to stick themselves to provide specimens,” Dr. Kricka says,
so less-invasive technology will be needed. In addition, consumers
want “all-in-one tests,” for which they simply add a
substance to produce a result.
“takes a complicated system from the lab and condenses it
into something effective, easy, cheap, and small,” he says.
Such technology already exists, as with the GlucoWatch, which is
worn on the wrist and uses an electrode-based biosensor to sense
glucose through the skin and produce a reading.
is the Persona contraceptive system, used by a woman to identify
her fertile period. The GlucoWatch and Persona represent “micro
miniaturization of extremely complicated tests,” Dr. Kricka
used by labs, such as the i-Stat portable analyzer, which contains
a silicon chip with reagents for a series of tests, could conceivably
be used by consumers someday, he adds.
are also using chip-based assays. One example is a combination gas
chromatograph, acoustic wave sensor, and preconcentrator that tests
air for biowarfare agents. “The fruits of this technology
will be available for medical use,” Dr. Kricka predicts.
want a personal lab menu to include common chemistry, immunoassay,
genetic, and proteomic tests. The latter two are difficult to run
and remain the “exclusive domain of central labs,” but
that could change, Dr. Kricka says.
testing, he adds, will be needed for pharmacogenomics—tailoring
drug therapy to individual genetics. In this case, the personal
lab could be used in a physician’s office to perform a genetic
test to determine which drug should be prescribed. “This is
one of the most compelling reasons to do POC tests,” Dr. Kricka
says. “It’s a win-win-win. The doctor prescribes the
correct drug, the patient gets a drug that works, and the pharmaceutical
company finds its drugs used effectively.”
Dr. Kricka described
how a POC genetic test could work using existing technology. “All
the components are there already,” he says. The blood sample
could be drawn via a laser or microneedle and then applied to a
chip that isolates the white blood cells and performs PCR. The resulting
products could be run through a microchip with channels to separate
out the DNA and look for a particular fragment or fragments.
will not only run tests but also provide a portable medical record.
“The personal lab could have a wireless download to a virtual
doctor,” says Dr. Kricka, “where someone would look
at the results and suggest courses of action.”
brave new world arrives, however, the medical community must address
ethical issues. For example, the personal labs will have to contain
lockout mechanisms because “you don’t want someone else
looking at your data or analyzing your tissue.” There’s
even the possibility of “genomic blackmail” if someone
obtains your personal genetic information, suggests Dr. Kricka.
But there are
compelling reasons for personal labs: consumers’ demand for
more control over their health, ease of use, and improvement in
health care delivery if routine wellness tests were to become commonplace.
For this to become reality, Dr. Kricka sums up, “the benefits
would have to be shown in terms of overall health.”
a shorter-term vision, Kent Lewandrowski, MD, associate
chief of pathology at Massachusetts General Hospital, Boston, predicts
that hospital-based POC testing will grow in popularity as more
tests become available. Although patients who are hospitalized are
sicker than in the past, cost constraints reduce their lengths of
stay. Consequently, “there’s great pressure to streamline
care and get patients through the system more quickly,” he
Not only have
POC technologies themselves improved, particularly with bedside
glucose testing, but “we’re getting better at managing
POC,” Dr. Lewandrowski says. POC testing accounts for eight
percent of laboratory tests at Massachusetts General and continues
to increase in share.
General uses POC testing for glucose, urinalysis, fecal occult blood,
gastric occult blood, blood gases, provider microscopy, and pregnancy.
The hospital recently added rapid cardiac markers, rapid strep,
and rapid influenza. Dr. Lewandrowski expects POC tests to come
on board soon for continuous blood gas analysis, drugs of abuse,
transcutaneous bilicheck, and thromboelastography. “The menu
is expanding, and the technologies are getting more sophisticated,”
advises labs not to focus solely on unit cost when considering where
to add POC testing. “If we focus on high-acuity patients,
the unit cost per laboratory test is not the issue, but unit effectiveness.”
For example, producing rapid cardiac markers for patients with chest
pain can be important in influencing treatment and deciding whether
to admit. Lab testing represents roughly four percent of the hospital
budget but influences almost all clinical decisions, Dr. Lewandrowski
points out. “When you look at the costs of these new technologies,”
he says, “consider the impact on utilization, patient care,
efficiency, and outcome.”
General had a problem with overly lengthy stays in the emergency
department, “the lab was challenged to help reduce those lengths
of stay,” Dr. Lewandrowski recounts. “We didn’t
know if changing lab turnaround time would affect turnover of patients,
but it was worth trying.”
and his colleagues set up a POC testing lab to do urinalysis, pregnancy,
glucose, cardiac markers, and rapid strep and influenza. “We
cut turnaround time by 87 percent,” he says. Emergency department
physicians’ overall satisfaction with lab turnaround time
doubled, while satisfaction with test accuracy was similar to what
it had been with the central lab.
lengths of stay declined an average of 41 minutes per patient after
POC testing was implemented in 2000. The number of diversions—times
when the emergency department was overcrowded and had to send patients
to other hospitals—also declined (Lee-Lewandrowski E, et al.
Arch Pathol Lab Med. 2003;127:456–460).
can streamline care in the emergency department. EDs typically use
necrosis markers, such as troponin and CK-MB, but only 13 percent
of patients can be ruled out at presentation using these, Dr. Lewandrowski
says. “The vast majority of patients fall into a gray zone.”
A potentially better measure of risk for acute myocardial infarction,
he adds, is a new test, ischemia-modified albumin. In a study of
low-risk chest pain patients, IMA presumably had a nearly 100 percent
negative predictive value, he says, “although more studies
will be needed to confirm these optimistic numbers.” (See
“Better cardiac calls.")
IMA, and an electrocardiogram, suggests Dr. Lewandrowski. “IMA
doesn’t replace previous technologies but augments them and
allows the patient to be evaluated more effectively.” In another
study, adding IMA to the mix allowed a hospital ED in London to
rule out 35 percent of patients. “More hospitals need to evaluate
this marker,” he says.
Not all POC
tests perform as well as those done in the central lab, notes Dr.
Lewandrowski. For instance, studies have shown significant differences
in performance in hypoglycemic monitoring of neonates using bedside
glucose devices versus central lab testing. Glucose meters may deviate
from the true value by as much as 35 percent. “Bedside glucose
does not perform well in this setting [intensive-care neonates],”
he says. “Some technologies designed for one setting won’t
work in an alternative setting for which they weren’t intended.”
On the other
hand, the transcutaneous monitor for bilirubin in neonates, which
is placed on the forehead and produces a readout, “performs
very well compared to the central lab,” Dr. Lewandrowski says.
“It’s simple, noninvasive, and provides rapid results.”
of a useful new POC technology, he says, is a system for continuous
noninvasive monitoring of blood gases and electrolytes during surgery.
This replaces repetitive testing by the central lab, which can provide
only intermittent results.
The use of cardiac markers in a POC setting was also discussed
during the AACC audioconference. Rob Christenson, PhD, professor
of pathology and director of the rapid response laboratories at
of Maryland, Baltimore, discussed standard brain (B-type) natriuretic
peptide, or BNP, and the metabolite NTproBNP (N-terminal pro-B-type
peptides are hormones and their metabolites that can help track
the remodeling of myocardial tissue that occurs when the homeostatic
fluid balance is disrupted, as it is in congestive heart failure.
About half of CHF patients are asymptomatic, Dr. Christenson says.
have much evidence that there is a difference in performance”
between BNP and NTproBNP in diagnosing heart failure, he adds. NTproBNP
is cleared by the kidneys and has a longer half-life in the body—one
to two hours compared with 20 minutes for BNP. “There may
well be utilization differences in renal insufficiency patients
and in therapeutic monitoring,” he says, “but we don’t
know for sure yet.”
want to test for natriuretic peptides at the point of care, say
in the emergency department,” says Dr. Christenson, “then
the standard BNP test is the only option.” NTproBNP must be
done on the Roche Elecsys in the central lab. Biosite offers a point-of-care
BNP test. “There is no evidence that one is better than the
other for most presently approved applications, so at our hospital
we’re doing it as POC,” he adds.
are just starting to use the marker may want to begin with BNP,
because it doesn’t require as much training and the initial
cost probably will be lower. “BNP is much simpler to implement
and you don’t have to bring in a big instrument to run a single
test,” he says. “Of course, if you already have an Elecsys,
then performing NTproBNP is a viable option.”
BNP tests can
be performed in emergency departments, critical care units, and
physicians’ offices. “Many [CHF] patients weigh themselves
to try to keep track of fluid balance,” says Dr. Christenson.
“There could be a role for a home BNP testing in the future,
provided the testing system is robust, accurate, precise, and easy
For BNP testing,
the Biosite assay requires whole blood or plasma that is stable
for up to about four hours after collection. The test can be run
in about 15 to 20 minutes. NTproBNP uses serum or plasma, which
can be refrigerated for up to three days, and, after sample preparation,
takes about 18 minutes on the Elecsys, he says.
BNP is a strong
indicator of CHF, according to recent studies cited by Dr. Christenson.
The values are significantly higher for CHF patients, and higher
values correlate with greater severity of illness and poorer prognosis.
For patients who come into emergency rooms with shortness of breath,
there’s a 90 percent chance that elevated BNP levels—above
100 pg/mL—will equate to a diagnosis of CHF. With BNP values
below 20 pg/mL, there’s only a 12 percent probability of CHF.
Using BNP to
screen asymptomatic patients, however, is not recommended at present,
Dr. Christenson says. “In a well-run study published in JAMA
[Vasan RS, et al. 2002;288: 1252–1259], the performance was
suboptimal for screening. However, it must be noted that there were
questions about the criteria used to categorize LV dysfunction,
and diastolic dysfunction was not addressed,” he says. This
is a particular problem in women and the elderly. “BNP added
nothing to the ability of clinical indicators to assess left ventricular
function,” Dr. Christenson adds.
there seems to be an age and gender difference in the values. People
younger than 45 show substantially lower values than patients 75
years or older. And NTproBNP values tend to run substantially higher
in women, especially older women, than in men. “So we may
need age- and gender-adjusted reference intervals for these tests,”
Dr. Christenson says.
As with BNP,
elevated levels of NTproBNP show a strong association with a diagnosis
of heart failure. Someone with elevated NTproBNP is at a 22-fold
higher risk for heart failure mortality than someone without an
elevated rate, according to studies cited by Dr. Christenson.
Dr. Christenson says, current evidence suggests that BNP
and NTproBNP are not useful in screening asymptomatic patients,
with symptomatic patients who show up in ERs or physician offices,
“they’re a very powerful tool for predicting whether
the symptoms are from heart failure.”
Troponin, too, has a role in POC testing, says audioconference
speaker Fred Apple, PhD, medical director of clinical labs for the
Hennepin County Medical Center, Minneapolis, and professor of laboratory
medicine and pathology at the University of Minnesota.
results of this marker to assist in detecting AMI within 60 minutes,
preferably within 30 minutes. If the central laboratory can perform
continuous troponin testing with turnaround times of less than an
hour, that’s satisfactory, he says. “If that can’t
be accomplished, implementation of POCT should be considered.”
in troponin levels by itself does not necessarily equate to a heart
attack. “It must be accompanied by symptoms of ischemia,”
Dr. Apple says. For a patient with chest pain, a normal troponin
level results in a diagnosis of unstable angina. If troponin is
elevated, “it’s classified as a heart attack.”
Dr. Apple says
troponin assays at the 99th percentile reference cutoff should have
a total analytical imprecision of 10 percent or less; if not, there’s
a potential for false-positives. No assays meet that goal, however,
so he suggests choosing the lowest concentration that provides the
10 percent imprecision (or coefficient of variation) as the medical
decision cutoff (Apple FS, et al. Am Heart J. 2002;144:981–986).
“As the manufacturers improve the quality of their assays,
that lowest [10 percent CV] concentration will eventually equate
to the 99th percentile,” he says.
is performed at the point of care or in a central lab,
serial sampling should be done at admission, three to six hours,
nine hours, and 12 to 24 hours. Six to nine hours is the minimum
time needed to “optimize sensitivity and specificity for detecting
Dr. Apple says.
does result in higher quality care. Dr. Apple cited studies showing
a two- to fivefold improvement in outcomes based on therapies guided
by troponin results obtained at presentation.
Roche, and Dade-Behring—have approved quantitative POC troponin
assays. And i-Stat and Response Biomedical are developing POC troponin
assays, he says.
County Medical Center put a POC system into its cardiac short stay
unit, the mean turnaround time on a troponin assay declined from
83 minutes to less than 15 minutes, Dr. Apple says. (These data
represent the time from blood draw to result delivery.) And nurses
and physicians have reported positive patient health benefits from
being able to see real-time numbers rather than waiting for results.
In the future,
he says, as assays at the low end improve, “we hope to be
able to triage patients earlier, both as inpatients and outpatients.”
IMA, he adds, has recently been approved by the FDA to help rule
out acute coronary syndrome in low-risk patients. But implementing
IMA, says Dr. Apple, “still requires an evidence base and
Karen Southwick is a writer in San Francisco.