Tip:
Highlight text to annotate it
X
Teri Manolio: And first is Debra Leonard from the College
of American Pathologists.
Debra Leonard: Well, thank you for inviting us to participate
in this conference. We're very excited, and I was a little daunted when I got this list
of topics that we were supposed to cover so I will try to -- I targeted my talk simply
to address the questions that were asked. And so we will look at the first two together:
member needs assessments completed or planned, and state of genomic science and practice
by members.
We are toward the end of a five-year process of what we call the Pathology Transformation
Process, which was driven by changing pathologist demographics, as well as health care delivery
reform and genomics. Those were kind of the three major driving forces of this. In 2010
we did a member survey of genetic/genomic knowledge, and we were rather pleased to find
that, you know, 61 percent of people, pathologists, practicing pathologists, and this is a thousand
of our 17,000 practicing pathologists, were familiar with whole genome sequencing or analysis,
which we were very surprised to find. Now, we did not test them, so we don't know what
they mean by familiar, but -- and then we also asked about gene panel tests and single
gene tests, and, of course, the familiarity went up.
So from 2009 to 2012, we basically defined the pathology transformation strategy, which
I think any practice subspecialty you could take this and just change pathology to pediatrics,
or medicine, or whatever. Enable our members to control their professional economic destinies.
Focus our support on pathology practices, because, classically, the College of American
Pathologists had been focused on the individual pathologists, so it's just a technical point.
And help them create greater value, especially in embedding new genomics and informatics
capabilities in their work, get paid for this in the context of coordinated care. So it's
a very simple strategy.
And we are going to implement a multi-year series of initiatives starting this year and
moving forward. And one of the aspects is to take the analysis that we've already done
and develop a specific genomics strategy, or genomic medicine strategy of what initiatives
are going to have the greatest impact in helping pathologists move toward the practice of genomic
medicine.
So we were next asked to talk about the short- and long-term pace of change in genomics use.
So in pathology practice, we are currently standardly doing single or few mutation or
single gene pathogen detections, or a few genes. But we are moving to incorporating
next-gen sequencing, basically, or genomic analysis into our practices, doing predominately
gene panels or exome sequencing. Right now, research -- this slide may be rapidly becoming
dated, but genome and transcriptome sequencing, we are beginning to think about doing clinically,
but pretty much remain in the realm of research. And we feel like all of the research will
build back flow [spelled phonetically] to help us understand the clinical usefulness
of the sequencing that we are doing over time. So this is what we call genomic analysis by
next-gen sequencing.
So what you need to understand about pathology or molecular pathology tests is that not all
molecular pathology tests can move over into next-gen sequencing platforms. So we do a
lot of tests: *** viral loads, CMV/EVV viral loads, bone marrow engraftment analysis. Those
will have to stay on their current platforms and can't really be done by next-gen sequencing.
But there are a lot of genetic and cancer-related tests that are better done by next-gen sequencing
either as gene panels, and that would be for cancer or specific inherited disorders where
you know the sets of genes used for that or causative of that disease, or exome sequencing,
also for cancer or for unidentified inherited disorders, exome or genome.
So we, in the process of doing this transformative strategy investigation, looked at the early
adopters of genome/exome sequencing or gene panels, next-gen sequencing technology in
clinical laboratories. And there was quite a rise in the number of laboratories doing
this. And this is in 2011, just when the MiSeq and Ion Torrent smaller instruments became
available, which are really the game changers.
So I will go very rapidly through this, that the first genome was done on ABI sequencers,
which cost a lot of money, moving into next-gen sequencing mostly in research but it was an
instrument that cost $750,000, and it had a one-week data processing time -- I mean,
data generation time. But the MiSeq and Ion Torrent basically are in a clinically-relevant
price range and a clinically-relevant turnaround time. So this is what is the game changer
for us. And we're moving on to an ion proton and other instruments that will have clinically-relevant
costs and turnaround times. So we are seeing much, much greater adoption of next-gen sequencing
technologies, predominately for gene panels in clinical laboratories.
So the current plans to address genomics literacy by the College, and I am going to talk about
different categories of initiatives, and one is assuring the quality of the genomic tests
that are being performed because the College also is an accrediting body for clinical laboratories
under -- with deemed status under CLIA. And so we have developed an NGS inspection checklist
series of questions that address both the wet bench aspects of generating the data as
well as the bioinformatics pipeline. And it [inaudible] dominantly on proper validation
and documentation, and applies to any instruments or tests being done by next-gen sequencing
technology. And those became available on July 2012, and we are updating those this
year in 2013.
CAP also has a proficiency testing program that we offer to laboratories and so we are
looking at how you do proficiency testing for next-gen sequencing based tests. We are
going to use highly characterized genomes, and I can go into detail about how we are
characterizing those. And then each laboratory would perform their [inaudible] on those -- a
characterized genome or more sent to them, and it will assess both the sequence data
generation and bioinformatics processes.
We also have developed what we call Resource Guides. And we actually have four Resource
Guides. There are two related to genomics. There is a Genomic Analysis Resource Guide
and a Molecular Diagnosis Resource Guide. So some pathologists need to get up to speed
with the now routine molecular testing. But then there is also one for Genomic Analysis.
And here you can see the table of contents -- I won't read through it -- of the Genomic
Analysis Resource Guide. But there are pearls from early adopters, there is technology information.
We do it by -- we have information for different types of testing being done, standards and
accreditation, and in 2013, we are going to be adding a bioinformatics section to this
Resource Guide. So many pathologists have given us very positive feedback that these
are very, very useful to them.
Education realm, we had 37 molecular or genomic courses at CAP '12. I know relative to ASHG
every single one of their courses is related to genetics or genomics, but this is a big
change for the College. And there is a range of topics, some involving next-gen sequencing,
but others molecular testing, molecular hematopaths [spelled phonetically], molecular microbiology.
So we have to consider the molecular and genomics of all kinds of applications, from inherited
disorders to cancers to infectious diseases and pharmacogenetics.
We also have three pharmacogenomics online courses and other -- we have a total of 16
online courses that pathologists can use for CME or SAMs. SAMs is what we -- it's the continuing
education for reaccreditation at the 10-year period. And out of the committee that I run
we also have a webinar series that's been going on for three years. And it focuses in
three areas: genomic testing, around next-gen sequencing of panels, exomes, or genomes;
molecular pathology testing, so, you know, not next-gen; and then organ-based molecular
pathology, which predominately focuses on cancer. And these webinars have reached -- more
than 4,500 CAP members have attended one or more webinars. And so we're having a pretty
significant impact in reaching pathologists with the webinar series.
And these are some of the upcoming topics: Molecular Microbiology in Community-Based
Practice, Pathologist's Role in Breast Cancer Diagnosis. You can see many of them are -- we
always have a talk on DNA Day that is available nationally, but it's done at the College of
American Pathologists headquarters in Chicago.
And we are also providing tools for practicing pathologists. We call these SPECS; don't ask
how that happened. But they're short presentations on emerging concepts. And what they are, are
short PowerPoint presentations of five to 10 slides that can be used to describe testing
that is relevant and impacts patient care directly now. And they are not branded with
CAP logos or anything. They are to be used by the practicing pathologist, and we also
provide key references because some practicing pathologists actually do not have easy access
to PubMed, believe it or not. And so they can customize these for their local conferences,
tumor boards, or to talk with their hospital administrators. And we are tracking the use,
and we are providing updated materials, so when you download, you have to register that
you are getting this. And then as we update the information, we would push out the updated
information to anyone who's already downloaded previous versions of these.
And so we have five of these in existence. Our plan is to develop two more and update
these: one on the workup of colorectal cancers, so that's somatic mutations; and then inherited
colorectal cancer, metastatic melanoma, BRAF testing in thyroid cancer, and workup of polycythemia
and thrombocytosis, JAK2.
So what's the process for genomics practice guidelines development for diagnosis and treatment?
We have what we call the CAP Pathology and Laboratory Quality Center to ensure that they're
-- so, basically, this is our area of the College that develops guidelines, uses evidence
to support development of practice guidelines and protocols, and we usually are doing that
development in the context of a multidisciplinary approach, working with either specialists
from other subspecialty areas or other professional organizations. And it facilitates the coordination
of the consensus activities in the absence of evidence-based practice guidelines.
And so this is the process we -- ideas for guidelines that are needed are submitted,
and so we select the ones we are going to work on, and so we develop the scope and form
the work group, do the research and literature reviews, solicit and develop the guidelines,
solicit public comments, complete recommendations, review and approve, publish and implement.
And then we haven't yet quite figured out the process for maintaining. Well, actually
we do, I mean, because we have some guidelines that are out. So there are two guidelines
developed in collaboration with ASCO around breast cancer testing. We have one in press
around the selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors,
and two more that are in development around acute leukemia and colorectal cancer.
What you can see from this is that, for pathologists, the reality is we make our money around surgical
pathology practice. And so the cancer genomics is much more important and sellable to practicing
pathologists than is inherited disorders that we don't have a lot of familiarity with. But
we are trying to impact that.
So activities by associated specialty boards to include genomics and certification processes.
Our residency training program requirements currently require one to three months of training
in molecular pathology, not necessarily specifying genomics. So those centers that have training
programs that are incorporating next-gen sequencing and genomic testing into their molecular pathology
laboratories are providing that as part of their training. Others that don't have it
are not. So there aren't any specific requirements for genomics, per se.
The American Board of Pathology includes molecular knowledge. We refer to it as molecular pathology
knowledge. Seven to 9 percent of the AP exam is based on molecular pathology, and 10 to
15 percent of the CP. So that's anatomic pathology and clinical pathology. We are the only specialty
that has two primary board certifications. Subspecialty board certification in molecular
genetic pathology is jointly by the American Board of Pathology and the American Board
of Medical Genetics. That has not yet incorporated genomics into their requirements. But, again,
most of the places that have MGP fellowships are at academic medical centers. That's also
where the next-gen sequencing is being adopted mostly. So many of the molecular genetic pathology
fellows are being trained in next-gen sequencing technologies.
And then the College and the Association of Pathology Chairs have actually developed a
Memorandum of Understanding to work together on pathology residency training issues including
genomics, residency education, both at the residency and the fellowship levels.
And then, finally, and this is my last slide, there is a -- Richard Haspel is at Beth Israel
Deaconess, Harvard, and he has been leading an intersociety initiative, interpathology
society initiative to develop a national curriculum in cancer genomics for pathology residents.
We called it TRIG. Actually, it's not just pathology, because the National Society for
Genetic Counselors and other organizations have also been involved in this. And so Rich
just got an NCI R25 to support a five-year project in implementing a curriculum that
we have already begun to develop, but we are going to fill it out a little bit more with
three aims, is to develop the curriculum; evaluate that, and my -- University of Vermont
will be one of the four training sites where this will be tried; and then promote the national
implementation of this curriculum across all -- the goal is greater than 90 percent of
pathology residency training programs nationwide.
So I think I answered the questions. So...
Teri Manolio: Great. Thank you very much Debra. Yeah, that
was a tour de force through the many questions that we [laughs] that we sent you. Thank you.
So we have Mark Ratain, Gene, let's see, Bill, sorry, and then Marc.
Mark Ratain: So, Debra, I appreciate that pharmacogenomics
is one of the areas in which CAP is interested, and I --
Debra Leonard: Yeah.
Mark Ratain: -- and I note on your website that you have
a number of learning opportunities. And I'm just wondering, are you partnering with any
clinical pharmacology organizations to develop these, or is this something CAP is doing on
its own?
Debra Leonard: We have toxicology expertise, and because
we run toxicology laboratories, and so I think it goes along with the pharmacokinetics testing
that we do, and it's growing. So it's a collaboration between toxicology, which is within pathology,
but not necessarily clinical pharmacology.
Mark Ratain: -- such as American Society for Clinical Pharmacology
and Therapeutics, is one example.
Debra Leonard: Well, we clearly are highly collaborative
anyway, so that's a good suggestion.
Teri Manolio: Gene.
Eugene Passamani: Thank you for really a nice summary, Debra.
A couple of questions. One is, in 2008, you or someone said about putting this all together,
and you've got a wonderful product. Can you tell us a little bit about how you did that?
Debra Leonard: Painfully.
[laughter]
It really was the vision of the president of the College of American Pathologists at
the time, as well as several of our board members, who really felt like we needed a
process to move pathology toward what we were then calling personalized medicine. We are
now transitioning that term, because personalized health care/personalized medicine is offensive
to many physicians because we don't go out into the waiting room and say, "Okay, everybody
with pneumonia, come into my office now." You know, it's really -- we personalize the
care that we do now. So we prefer the term genomic medicine or precision medicine. But
genomic medicine really ties it to the genomic information.
But all that was happening, and a big uproar within the College in 2008 because many pathologists
were not incorporating genomics and even reticent around molecular pathology, which is the single-gene
testing. Genomics was kind of like the future at that point. The future is now, [laughs]
in pathology practice. So it's --
Mark Ratain: So there was some resistance to change, I
guess?
Debra Leonard: Yeah. But it became overwhelming to change.
And then I actually chaired -- there were four modules that did a two-year process of
looking at the economics, the demographics of pathologists. I was doing the emerging
technologies, which included not only genomics but also in vivo microscopy and digital pathology,
and then the service models for pathologists. And those four groups then provided information,
and then that became the work of the integration team to put all that together into what we
now call Pathways for Transformation. We have a document that pathologists are actually
reading and embracing because it ties in with the ACO changes and the coordinated care models
of practice in that pathologists have to be out there; we can't sit in our laboratories.
I mean, this is becoming really personal now. Sorry. But, you know, so it ties into a lot
of different aspects of how pathology practice has to change. And genomics is just one of
those.
Mark Ratain: And your regulatory burden or need helps you
get this out to people. Of all pathologists who are practicing, how many do you think
you have actually gotten to with all of this educational stuff?
Debra Leonard: I -- well, we -- I don't know. I don't know.
I do know that one of my new faculty at UVM went to a leadership conference led by the
College and came back drinking the Kool-Aid. And I am absolutely delighted because he is
going to lead in changing pathology practice at UVM to be more the transformed model that
we are looking to become.
Teri Manolio: Thanks. Bill.
Bill Oetgen: Yes. Thank you. That was really an excellent
presentation. I am Bill Oetgen. I am a cardiologist who is full time with the American College
of Cardiology, as the senior vice president for Science and Quality. And I have a question
that I think my colleague, who directs our Lifelong Learning Division, would ask, but
she wasn't able to be here. And it's a little bit of minutia, and that is, you mentioned
that 4,500 of your CAP members had attended the webinars over a period of several years.
We think that --
Debra Leonard: That was actually just in 2011.
Bill Oetgen: Oh, just in 2011. Oh --
Debra Leonard: Yes.
Bill Oetgen: -- even more impressive. We think that webinars
are important and promising ways to provide information to our members, but have not had
success in those numbers ever. And so my question is just, basically, how many members -- how
many CAP members are there? I'd kind of like to get an idea of what the denominator is.
Debra Leonard: I knew somebody was going to ask me that.
I know that there are supposedly around 17,000 practicing pathologists in the U.S. But I
don't know how many --
Bill Oetgen: Okay.
Debra Leonard: -- are CAP members. And I must -- one thing
I didn't mention about those webinars: They are not CME, because we can't be nimble enough
and do CME. I hate to say that with the head of ACCME sitting -- you know.
[laughter]
But it's very hard to do that. And we also archive those webinars so that you can go
online. So you can go on to the CAP website and view any of those webinars over the past
three years. They are -- they do become dated because they are on pretty hot topics, usually.
Bill Oetgen: Yeah. Well, that they're not CME is even more
impressive that you have those numbers of attendees. I think that's great. I'd like
to just chat offline about --
Debra Leonard: Sure.
Bill Oetgen: -- about how you're so successful in that.
Debra Leonard: My contact information for the next seven
weeks is in the bulletin. But --
[laughter]
-- my, if you call that number or email me, hopefully it will be forwarded, or my assistant
will say where I can be located.
Bill Oetgen: Okay. Thank you.
Teri Manolio: So Marc.
Marc Williams: Yeah. It is very impressive. Because most
of us have had the experience that Bill related which we -- if you build it, they won't come.
So maybe it says something about the amount of free time pathologists have. I don't know.
[laughter]
So my question is a little --
Debra Leonard: Educational energy that we have.
[laughter]
Marc Williams: Yeah, there you -- okay, fine. Well, you say
tomato, I say tomato.
So you've obviously been tracking the use, which I think is great, and that's a very
useful process metric. But I was wondering if there's been discussion or any efforts
in terms of actually measuring the impact on practice. Have you been able to take a
look and see how is this really fundamentally changing how our members are practicing? It's
much harder to do, and I'm just curious if there's been discussions or attempts.
Debra Leonard: Not in a systematic way. I don't know if the
College has plans to repeat the kind of survey that we did in 2010 to see if the kinds of
things that we were asking about have changed. But I showed one slide from the survey of
the pathologists. But we actually did a survey of other subspecialties, patients, many other
people who don't know anything about pathologists, and it just confirmed that they don't know
anything about pathologists, and we basically hide in a hole. And so that's part of what
we're also trying [inaudible]. I don't know the way to measure that. We have gotten verbal,
I mean, email and other comments back of how individuals would incorporate this information
into their practice, but not any systematic way across all of them.
Teri Manolio: Great. Well, maybe while Robert Saul is heading
up to the podium for the next talk, I might ask Debra. I noticed your meeting topics were,
you know, legion, I think, and it looked like you had a very strong emphasis, as you said,
30-some seminars on genetics. I'm curious. I don't know that a lot of investigators that
NHGRI supports or even some of the other institutes who do molecular genetic type work necessarily
submit to your meeting and recognize that, you know, you don't want to commit to the
College right now or the program committee. Would there be interest in having The Cancer
Genome Atlas, or the Clinical Sequencing Exploratory Research Centers, or other things that are
supported in this space, presenting abstracts or posters at your meetings?
Debra Leonard: The more that pathologists become aware of
the other initiatives going on -- and the college does try to interact with other societies
that are appropriate to whatever projects we're working on. So, yes, our meetings are
in September usually. And so I don't know when abstracts are due, but sometime in early
summer. And you can go on the CAP website and find that out: www.cap.org. It's very
easy.
Teri Manolio: Great. Thank you very much.
All right, Dr. Saul for the American Academy of Pediatrics.