Is your lab ready for molecular testing?

April 1, 2009
Moderator: Christopher Higgins, Olympus America Inc., Center Valley, PA: Our topic is the readiness of clinical labs to host molecular testing — is your lab ready for molecular testing? What are the greatest barriers and, conversely, the greatest opportunities involving the growth of molecular diagnostics and molecular testing in your own lab? There was publicity recently about cancer tests in women and the OvaSure, which was developed by Yale.

Bruce A. Friedman, MD, active Emeritus Professor of
Pathology; Department of Pathology, University of Michigan Medical School;
Ann Arbor, MI:
Academic departments with large molecular-diagnostic labs
are more ready than the smaller hospital labs. To a certain extent, the
answer depends on how quickly some of these tests are made into kits and,
thus, can be performed fairly easily in hospital labs. The development of
such kits depends on the in vitro diagnostics (IVD) companies.
Complex molecular test panels accompanied by interpretive algorithms
referred to by the Food and Drug Administration (FDA) as in vitro
diagnostic multivariate index assays (IVDMIAs) are being heavily scrutinized
by the agency. Much depends on how quickly the technology evolves.

Keith J. Kaplan, MD, Mayo Clinic, Rochester, MN: There are levels of complexity and algorithms and multiple markers. One
thing we have seen is a high percentage of false positives, which cause
unnecessary anxiety in some cases, especially with breast and ovarian
cancers. Of course, unnecessary testing also drives costs up. There are
issues with both false positives and false negatives.

Dr. Friedman: I am very enthusiastic about close
coordination between radiology and pathology regarding diagnoses because of
this complexity. You cannot just look at these biomarkers by themselves
anymore. Cancer requires tight integration, with the various types of
medical imaging going hand-in-hand with in vitro diagnosis.

Higgins: Do you see a more formal relationship
emerging between radiology and pathology in the lab? Do you envision
development of new procedures and workflow elements that do not exist now?

Dr. Friedman: I believe that it is inevitable. I also
think there will be a whole new market for workflow software that will
govern the handoffs between in vitro testing and in vivo
testing via medical imaging. On this basis, Result A, such as a biomarker
test result, will eventually prompt Imaging Test B, which will prompt Lab
Test C, which will prompt Medical Imaging Test D. And it is going to be
scientifically challenging, because these handoffs from area to area will be
very dynamic and must be evidence based. While I do not support regulatory
oversight over these processes, I do think we need quality oversight.

Higgins: What will entice them to invest the money in
formalizing a process that may be starting to occur informally already?

Dr. Friedman: Companies may be afraid that the FDA
will begin to regulate them — and most of the companies want quality output,
with minimal false positives or false negatives. They definitely want to
begin this process; the question is whether they can do this independently,
without FDA oversight. Of course, problems or errors stemming from the use
of a test can be related to multiple factors: inappropriate ordering by the
physicians; the test not being scientifically valid; or perhaps insufficient
evidence underpinning the claims made for the test, the vendor overreaching
with its claims.

Dr. Kaplan: Everyone is trying to get a handle on
personalized, predictive, preemptive medicine, but I am not sure the testing
is quite there yet. The biggest spin right now is on the predictive end, but
I think establishing prognosis and, perhaps, treatment modalities may be
more fruitful in the long run.

Higgins: Dr. Cobb, would your lab want to feed this
kind of molecular testing to outside labs, or is your lab interested in
expanding its own capability in that area?

Camilla Cobb, MD, Loma Linda University Medical Center,
Loma Linda, CA:
We send many things out for molecular testing. Before we
would bring a test in-house, we would have to evaluate how often we would be
utilizing it. If you do just a few tests, quality assurance and proficiency
testing are necessary. Cost is a big factor and probably why I do not sense
much discussion at my facility about bringing in large quantities of new
molecular testing.

Dr. Friedman: These decisions need to be based on the
anticipated volume of tests in a particular lab, the skill level of its
personnel, and the cost of the test. Most labs are continually going through
that process — looking at their test send-outs and then making decisions on
whether to make or buy the test going forward. There is another option as
well. Some esoteric labs may create a partnership with hospital labs, a
hybrid-type relationship that allows the hospital to collect the sample, do
the upfront processing and, perhaps, some of the sophisticated back-end
processing. The esoteric lab may then finish the testing and provide much of
the interpretive component of the report. This way, there is a partnership
between the receiving hospital lab and the esoteric lab.

Higgins: Are pathologists ready for this?

Dr. Kaplan: Molecular pathology fellowships have
become popular over the past three to five years. Even community hospitals
are forming anatomic pathology divisions.

Dr. Friedman: What is interesting is that although
molecular diagnostics is exploding, IT within lab medicine and pathology is
moving at a much slower pace by comparison.

Dr. Kaplan: We are wrangling with that here. In the
past 18 months, we have seen that the bioinformatics piece is missing. The
ability to warehouse and data-mine, and make sound conclusions about what
the tests mean vis-`a-vis outcome data is missing.

Higgins: We have been talking mostly about tumor
markers. But we have heard about markers for everything from cystic fibrosis
to obesity. How far will this go, and what other areas beside liquid and
solid tumors show the greatest potential in your estimation?

Dr. Friedman: I am more interested in proteomic
testing. Among the biggest challenges in healthcare today are a host of
chronic but non-malignant diseases such as osteoarthritis and metabolic
syndrome, both in terms of diagnosis and treatment. It is attractive to look
at tumor markers; but this will expand rapidly into all sorts of other
chronic diseases, the most prominent ones being diabetes, metabolic
syndrome, osteoarthritis, and coronary diseases.

Dr. Cobb: This group discussed patients ordering
their own tests. This might be an area where patients would be very
interested in self-ordering.

Higgins: Do you think our government is moving at the
right pace with regard to the standardization of reimbursements in this

Dr. Friedman: So few labs are involved in complex
molecular diagnostics that there is no political ground swell about this. It
is a fairly small number of labs, as in the case of OvaSure. There is an
incentive for the labs offering the tests to obtain reasonable reimbursement
for it so that there is an incentive for the hospital labs receiving the
patients and specimens to send out that test or to accept the clinician's
order for the test.

Higgins: What does the whole reimbursement picture
have to look like for labs to get more involved in this?

Dr. Friedman: Keith says these fellowships in
molecular diagnostics are in great demand because it is such a growing area,
and there is a need for specially trained people. The vast majority of
pathologists and physicians probably are not that knowledgeable about this
type of testing. Newly trained individuals coming out of fellowships are
going to have the greatest understanding in terms of both performing and
interpreting these tests.

Dr. Cobb: I am curious. What kind of employment do
people who do fellowships in molecular pathology get? Are they primarily
doing molecular pathology, or do the groups just want someone with that
expertise on board while they are primarily doing other things?

Dr. Kaplan: What we are seeing here is that often,
these people are gaining employment as directors of molecular-diagnostic
sections or divisions. There is another group that does two years'
post-anatomic-/-clinical-pathology training combined with surgical pathology
or hematopathology, each combined with a year of molecular. Those folks that
have additional training can fulfill either a generalist or specialist.

Dr. Cobb: But that is happening primarily at the
larger specialty labs.

Dr. Friedman: Industry and large reference labs are
also hiring these people.

Dr. Kaplan: We have graduate students and PhDs doing
the same molecular fellowships but more on the R&D side, who are going into
industry, more often as PhD directors with molecular training.

Higgins: Though this field is somewhat small and
specialized now, we are seeing more and more about this topic. People seem
to think this is where testing is going ultimately. Do you agree with that?

Dr. Friedman: Yes, I believe both tissue and serum
biomarkers will be critical components in the future of pathology and,
coupled with molecular imaging, may in a decade or so supplant much of the
practice of surgical pathology. In my view, this is the future, particularly
when coupled with advanced types of medical imaging. The challenge here is
that they are going to require the surgical pathologist to validate the
imaging techniques, because the gold standard for diagnosis will continue to
be H&E histopathology. But we have been seeing the same type of transition
in hematopathology, and that is a great model. Hematopathologists are as
well versed in the biochemistry of leukemic cells as they are their
morphology. They are the first of our subspecialties to effortlessly
integrate and combine anatomic and clinical pathology; they are great role
models for the rest of us.

Higgins: We all know how hard it is to get our labs
adequately staffed with capable people right now; and, of course, our
society is aging and requiring more medical services. What do you see as the
ramifications of these new developments? If each diagnosis is now going to
have two, three, or four steps or sections, will not that require that much
more training and that many more potential staff people? Or do you see some
kind of automated equipment being able to do more of this? How do you see
the laboratory facing the staffing challenge?

Dr. Friedman: Molecular diagnostics will definitely
be more automated. This is one of the reasons that large national reference
labs like LabCorp want to be in this business. The profit margins are so
attractive. LabCorp, when it talks to financial analysts, frequently makes
reference to the revenues that come from molecular diagnostics.

Dr. Kaplan: It is an interesting question because
I have seen this in a few labs; and it actually provides the allied
health professionals another level to their position, in providing
career options that previously did not exist. Instead of a screening
bench tech moving up to supervise people doing what they used to do, the
explosion in molecular testing may provide students with new
possibilities. Some of the shortages that we thought we were going to
have in cytology may be overcome by the fact that there is a career path
that provides better incentives. The same thing applies for histology
technicians in their field; people come into our schools asking about
the molecular component because they know it is the future.