Unveiling the patterns in TDM data ‘dots’
You can think of a lab report as a lab report. Or you can
think of it as a nightmarishly jumbled, neo-Cubist connect-the-dots
diagram. Suppose the patient’s test results are right there on the
page, in neat rows and columns. Is the change in test A over the
first three columns clinically significant? Is the value of test
B in the second column more or less important than usual when considered
in combination with the value of test C on the second page of the
Connecting the dots of these diagrams to reveal clinically important
patterns is like trying to duplicate a Picasso in your head. Some
of the patient’s dots may not connect to anything on the page. Some
dots may obscure or distract from others. Important dots may be
missing, located elsewhere, or drawn in a different colored ink.
Clinicians faced with the task of connecting the dots may retreat
to a superficial comparison of the most recent results with reference
ranges, losing the deeper view.
Now James H. Harrison Jr., MD, PhD, has devised a way to make
the dots connect beautifully. Dr. Harrison, associate professor
and associate director of pathology informatics, University of Pittsburgh
Medical Center, has spent a decade tinkering on computers, old and
new, and devised software to translate time-sensitive laboratory
data into graphs that are easy on the eyes.
In more technical terms, Dr. Harrison has written a program that
ingests and analyzes therapeutic drug-monitoring results from hundreds
of patients. Comparing the actual data with patterns specified in
the program, his software can alert the user when several days’
worth of laboratory data from a particular patient or a large population
of patients conform toor diverge froma stipulated pattern
of clinical interest.
You want to know if three of four sequential trough values for
gentamicin were elevated? You can’t remember if there have been
more than two lithium values in the last three days? Or you recall
too many patients showing variable peaks for vancomycin? Dr. Harrison’s
LabScanner program will show you the data.
As someone with a longstanding interest in therapeutic drug monitoring
and a doctorate in pharmacology, Dr. Harrison has a measured opinion
of his medical colleagues’ abilities to watch key values over any
interval longer than 24 hours. He understands that busy clinicians
and laboratory professionals cannot be expected to sit down with
pencils and graph paper and spend the morning drawing a few hundred
charts. LabScanner is a tool to identify quickly data patterns that
may warrant attention.
But it may be helpful to clarify what LabScanner does not do.
Dr. Harrison does not expect his software to issue critical alerts
or perform delta-checking for any value that demands immediate action
by a physician. He knows existing laboratory information system
products already provide such warnings. Rather, LabScanner is intended
for clinical followup and teaching purposes, even to support consultation,
and to allow pathologists to add value to the information that leaves
their laboratories. Nothing controversial there.
Dr. Harrison does see problems with the traditional ways
in which laboratory data are presented to physicians: The data are
generally arranged in a table or as a list of numbers, sometimes
for a single day, sometimes for a few days. Either way, he says,
those columns of numbers make it hard to discern macroscopic trends.
"We don’t really do a very good job of providing physicians with
data that express temporal changes well," Dr. Harrison says. "The
best you can do is columns of numbers progressing with dates across
the top in a spreadsheet-like format. That kind of reporting has
been standard for years. And then the way it was done on paper was
translated into the typical computer systems. Some computer systems
are now providing a graphical display as an alternative. But no
one has time to use individual graphical displays to search for
Dr. Harrison has data to support his view. Many years ago, primarily
as an intellectual exercise, he asked his institution’s computer
staff for a month’s worth of cases involving phenytoin. He knew
monitoring phenytoin was something that tested even experienced
clinicians. The computer staff gave him 90 cases, all exported from
the LIS into a generic text file, and he went to work with pencil
"I plotted them all and looked at the profiles to see the sorts
of things that were really happening. Some of them were pretty interesting,"
Dr. Harrison says. The charts of 20 patients, he felt, deserved
a closer inspection. And the values for two of those proved eye-opening.
In both cases, for a week or so, phenytoin levels were in the target
range, leading to discharge. In the charts of both patients, physicians
dutifully noted phenytoin levels were in the range that would permit
the patient to be discharged.
But, as Dr. Harrison’s exercise revealed, there were clear upward
trends in both patients that suggested neither may have been ready
to leave the hospital. (One of the patients later returned to the
hospital and was readmitted and detoxified.)
"The patients were not stable. The physicians had done a data
reduction in their heads each time they had looked at the results,"
Dr. Harrison recalls. "It’s unrealistic to think that physicians
would remember many individual numbers over several days. They would
classify them as ‘in’ or ‘out’ and remember that. They were losing
data, and they had not perceived that it was important data. They
figured that if it stayed in the target range for a week, it was
going to be okay. That was not the case."
To say the least, the experience suggested the existing manner
in which laboratory results were presented and analyzed could be
improved. "That’s a situation where just because the pattern wasn’t
perceived, the patient was discharged with a subsequent fairly significant
expense involved in having missed the data pattern," Dr. Harrison
He began to ruminate on a tool to help pathologists present data
more effectively. Dr. Harrison continues: "I really wasn’t wanting
physicians to graph every result on every patient. They just don’t
have time to do that." What he had in mind emerged from his own
training and a sense of what other doctors might find useful. Dr.
Harrison asked himself this question: "Would it be possible to create
a system that would examine these profiles and select the ones that
would be important to review?" The answer turned out to be yes.
Fortunately for pathology informatics, Dr. Harrison was willing
to teach himself a bit of programming to accomplish the task. He
hoped to help pathologists recognize problem patterns in therapeutic
drug monitoring and communicate them to clinicians.
His first task was to prove that a computer could identify patterns
of clinical import. He published such a paper in the American
Journal of Clinical Pathology in 1995. But the tedious work
of polishing a software program that any laboratory professional
or clinician could use took a few years. His program now functions
more or less identically on Windows and Macintosh machines and is
surprisingly sophisticated for a homegrown endeavor.
Perhaps most importantly, LabScanner creates small graphs. These
include linear regressions and half-life calculations. For every
drug, on every graph, the reference range is easily seen in a gray
horizontal band. Users of the program can select just a few laboratory
results and graph only those. Need to print them? LabScanner remembers
the selected set and prints just that. Need to focus only on results
from patients younger than 18 months? No problem. "The first idea
is to just identify these patterns and display them," Dr. Harrison
says. "You don’t have to sit down with a computer to figure out
what it is. You can seat-of-the-pants look at it, figure out what
might be going on." The computer connects the dots and lets physicians
interpret the line according to their abilities.
Since last summer, LabScanner has been refined and is now
available free through Dr. Harrison’s University of Pittsburgh Internet
Give-away software, known as freeware, generally is respected
in the computer industry. Software reviewers typically give higher
praise to freeware and open-source software than to commercial products.
(The most notorious case is Linux, an operating system popular among
those displeased with Windows.) Dr. Harrison’s aim, naturally, is
not just computational: He also wants physicians to really see laboratory
data over longer intervals.
To accomplish that, Dr. Harrison acknowledges, he needs the help
of colleagues. In the computer realm, such allies are called "beta
testers," intrepid souls who download software that is in development
via the Internet, test it, and suggest improvements. Such beta testers
could be crucial to enhancing LabScanner.
This is not to say using developmental software is risk-free.
Bugs may exist in LabScanner, Dr. Harrison warns. His program includes
advisories and instructions, and he suggests it be operated on noncritical
computers. "This is developmental software. It’s not commercial
levelyetwhich may, correctly, scare off some people.
But it should run as advertised for most people who use it."
Dr. Harrison does not believe pathologists and laboratory directors
should approach LabScanner with dread, just caution. "They should
treat this like a new lab test, in that they should do confirmation
testing against what amounts to control datadata that they’ve
put together and know what’s in it, so that they can make sure it’s
behaving correctly. If it doesn’t behave correctly, I want to know
What’s in it for the beta testers? They can shape the program
with their suggestions. Says Dr. Harrison: "The hope is that I can
find some pathologists and laboratory directors who are not only
interested in using this and using its current capabilities, but
in communicating with me about additional features they’d like,
and helping design those."
In fact, Dr. Harrison’s program can already be customized fairly
easily. "Anyone can set up data-scanning rules right away," he explains.
"It comes with preset patterns that I’ve found useful, but people
can add rules to it or subtract those of mine, or edit mine. They
have complete freedom. LabScanner can find levels outside a defined
range, tell you about increasing or decreasing values, monitor testing
frequency, and find variability between values. Those are the four
classes of rules that people can play with. Using those four classes,
you can detect a lot."
Take digoxin as an example. The rule that comes with the program
for digoxin has 10 subcomponents that were carefully considered
by Dr. Harrison. For a reference range of 0.9 to 2.2 ng/mL, the
program will flag a specimen if three of four sequential values
for digoxin are less than 0.9. Likewise, it will issue an alert
if three of four values show an increase of greater than 0.1 ng/mL
per day and the last value is greater than 2 ng/mL. If the data
about digoxin are unexpected in eight other respects, alerts will
be issued. Best of all, anyone who has different thresholds of concern
about the drug can easily tinker with LabScanner and adjust the
In a larger sense, the power of LabScanner is not merely that
the computer mechanically checks whether the last value for, say,
theophylline violates a rule or not. It is that the computer can
check all of the laboratory results for a thousand patients receiving
50 medications and note all of the instances in which the rules
have been violated.
The technical term for casting such a broad net is "data mining."
But the starting point is radically simple. All LabScanner needs
as its raw material is the generic text output from a conventional
LIS. "The data mining is simple in that all you’re really doing
is scanning through a large text file," Dr. Harrison says. "The
goal is the same: to select out patterns of data that match certain
The data mining has been especially useful as an educational aid,
helping Dr. Harrison find good cases for teaching clinical pharmacology.
His medical students are given a puzzling LabScanner graph and asked
to investigate the patient to explain the clinical or physiological
circumstances behind the graph. To Dr. Harrison’s delight, attending
physicians responsible for such patients have asked for a copy of
the medical students’ LabScanner printouts to add to patient charts,
confirming the value of this data presentation.
What’s more, in the course of such teaching exercises,
Dr. Harrison and his colleagues have used LabScanner to identify
more systemic problems throughout the hospital.
Helping colleagues monitor digoxin is a perennial issue. But during
his time as a young professor at Tulane University, for example,
the program also shed light on the dosing of aminogly-coside antibiotics.
"There were patients who had a trough drawn, and then a peak drawn,
and the peak was lower than the trough," he explains. "What was
going on? This wasn’t a case of unusual pharm-acokinetics needing
dosage individualization. In the graphical display, this really
looked like a problem with medical processes."
By that, Dr. Harrison means all of the vagaries introduced by
the interaction of nurses, pharmacists, and house staff. LabScanner
can identify patterns of laboratory values that are awry, and a
pathologist can then investigate these as a part of laboratory quality
With the aminoglycosides, Dr. Harrison says, "When patterns like
this occurred, they were viewed by the physician and nursing staff
as laboratory error. Any time they got something that was bizarre,
they would just go, ’Oh, it was a lab error,’ and would not follow
up. When we showed this stuff to the pharmacy, they were extremely
After investigation, the pharmacy changed its procedures to prevent
IV bags from being sent to patients with IV solution but no drug.
"That’s an example of one of the ways this thing can be used for
quality assurance," Dr. Harrison says. "You can detect these patternsproblems
in drug treatment and drug sampling-and optimize those processes.
Pathologists can be important in recognizing the significance of
clinical data patterns and figuring out who in a health care enterprise
is best able to follow them up so that patients benefit."
Thus LabScanner is a sort of crescent wrench that can, in theory,
be used to tighten any bolt in the hospital, helping pathologists
to alert the administration, laboratory, pharmacy, or other physicians
to trends in drug levels or other laboratory tests they would otherwise
miss in the hurly-burly of a typical day. Explains Dr. Harrison:
"This is to detect more subtle patterns that typically develop over
a period of days. When a physician looks across multiple columns
of numbers, the patterns may not be that evidentor to see
them, it would take so long that it would really be a drag on their
That workflow, it would appear, is not yet perfect. Dr. Harrison
has fed several months of laboratory data into LabScanner using
records from 1,944 patients in New Orleans (at Tulane) and 2,560
patients in Boston (at Brigham & Women’s). Dr. Harrison’s analysis
was retrospective, but it suggested that substantial insights could
be gained whenever LabScanner was installed. LabScanner evaluated
6,410 laboratory specimens at Tulane and 10,923 at Brigham & Women’s,
with 27 percent and 52 percent of the samples getting flagged.
At Tulane, LabScanner reported that 3.1 patients per day had values
the program did not expect; at Brigham & Women’s, the number was
8.4 patients per day. This represented about one new patient per
day per 100 hospital beds. The gravity of these flagged specimens
has not yet been established. It’s hard to say whether LabScanner’s
flags are identifying minor issues or major ones. But, at the least,
it does appear Dr. Harrison has statistical support for his position
that eye-numbing tables of laboratory data do not always tell clinicians
what they need to know, that there may be significant trends in
the data of which clinicians on the floor are unaware.
At the same time, Dr. Harrison points out, Cerner and Sunquest, as
well as other vendors, are not oblivious to such issues. Their newest systemssome
of which are being installed at the University of Pittsburghoffer rule-based
searching tools similar to those in LabScanner. "The interesting things about
these is that they are really not targeted to find these temporal patterns,
which may be subtle. They’re more targeted to, if values from several different
tests are within defined ranges, then issue an ’alert.’ They’re looking at a
snapshot of a patient at one point in time."
That’s too bad. Dr. Harrison would prefer the features of his
system be built into a hospital’s bedrock informational infrastructure
from the start. The main impediment to that sort of shift, he notes,
is attitude: helping colleagues become more aware of the importance
of longer time intervals.
"The roadblock for stuff like this being in the big lab systems
really isn’t being able to write the code. They could write code
like this. The issue is demonstrating it’s useful in medical care,"
he explains. "My goal is to lower the barrier of entry enough so
that people will try it and so that I and others can write papers
about it and maybe convince some of the vendors to include technology
like this in their lab systems."
One day, the uses for such tools might be esoteric and ordinary.
On the first score, LabScanner could be systematically used to perform
quality assurance and outcomes analysis, even confirming that procedural
changes are successful. Beyond therapeutic drug monitoring, Dr.
Harrison makes a convincing case that his program could be used
to evaluate platelet counts, length of patient stays, even renal
and liver function, as well as play a role in tumor marker analysis.
In a more down-to-earth way, Dr. Harrison is also hoping to help
his colleagues ask more of their existing laboratory reports. "The
way physicians are presented with data makes it difficult to see
the patterns," says Dr. Harrison. "They see the numbers. But seeing
the patterns is hard. We’d like to make it easy for them to see
the numbers if they need the numbers but still easy for them to
see the patterns if the patterns are important to show."
Dr. Harrison is quick to clarify that the computer is not in any
sense thinking. "It’s not actually taking the place of the physician
and doing an analysis," he says. "Systems like this don’t critically
analyze the data, and, therefore, they don’t take the place of a
clinician or a pathologist. Instead, they augment the physician
by directing his or her attention to important features of the data
so that medical decisions can be made more quickly and accurately."
Mark Uehling is a freelance writer in Chicago.
Dr. Harrison (firstname.lastname@example.org)
is distributing LabScanner free at thelab.upmc.edu/jharrison/labscanner.
He will present a seminar on data mining April 10 at the ASCP/CAP
Spring Meeting in Boston and in October at the ASCP/CAP Fall Meeting
and Exhibits in San Diego.