Geoffrey Ginsburg:All right.
We're running about 10 or 15 minutes late, so I will prevent you from eating your lunch
for the next 15 minutes.
So, I'm going to talk about one of NHGRI's newest consortia called IGNITE, which this
acronym causes a lot of consternation amongst Teri Manolio --
[laughter]
-- who fails to remember what it stands for, so I can take the blame or the credit for
that.
But it has -- it's a really cool logo, and I have to give credit to the University of
Pennsylvania crack artist staff for making this acronym for IGNITE.
The IGNITE Consortium really emerged out of the need to address issues and the right to
domains that you saw from Eric Green's presentation yesterday of -- on NHGRI's strategic plan
is how do we really think about taking reasonably well-validated genomic technologies and putting
them into medical practice, and do they actually work in a way that produces desirable outcomes
amongst patients and other stakeholders?
So, coming out of our first and second GM meetings -- genomic medicine meetings -- of
which this is the sixth, as you recall, one of the things that the group came together
to discuss is whether there could be some pilot demonstration projects.
And I think that meeting, if I recall, was in late 2011, and it was -- no, late 2010,
and RFA came out in early 2011, which is stated -- which you're seeing here to really propose
projects that would develop methodology, feasibility for incorporating genetic and genomic information
into the care of a patient, and see if that actually translates into outcomes.
So, the IGNITE network was established after, as you'll see, three projects were funded.
The goals of the network were to build on existing activities that were taking place
at various organizations that we've learned about through this series of meetings and
see if we could expand those in meaningful ways, not just in academic medical centers,
which have a significant amount of expertise and capabilities, but in other environments
where the challenges may be greater, diverse healthcare environments, underserved populations,
rural populations, et cetera, I think is among what this network is trying to address.
So it sort of levels the playing field for genomic medicine; and in doing so, to build
a better evidence base for the clinical utility of these technologies.
And through our -- the network's efforts to articulate some best practices, both in the
area of implementation science but also the area of how to design studies that would actually
be best used to generate the kind of evidence that we are striving for for things that we've
heard about today and over the last two days.
So, this is a snapshot of this consortium, and by the way, I have to tell you I'm not
going to show you any data because this consortium -- really funding streams began in July of
2013, so we're just about six months old.
Like the other consortia you just heard about, we have a coordinating center.
Steve Kimmel, who's in the back -- maybe you want to raise your hand, Steve -- is the PI
of that coordinating center from the University of Pennsylvania, and one of his colleagues,
Reed Pyeritz, who you just heard ask a question, is also from that coordinating center.
And there are three demonstration projects, one led by Julie Johnson who was here yesterday.
Maybe some of you had a chance to meet her.
A superb pharmacologist down from the University of Florida who's looking at pharmacogenetics,
and I'll go into the -- more detail about these projects in a few moments.
Erwin Bottinger, who is also in the room -- Erwin, maybe you could just say hello, raise your
hand -- is the PI from Mount Sinai who's looking at the use of genetic information -- genetic
risk information to alter behaviors in African-Americans.
And again, I'll talk about that in a little bit more detail.
And myself, looking at the use of electronic family history information delivered to providers
to alter screening behaviors amongst a variety of patients in diverse settings.
So as you've just heard from Lucia, there is a coordinating center here.
This really serves as an integrative hub for the network.
It's meant to really facilitate communication and interactions amongst the sites.
We have three sites, so it's not particularly challenging right now, I don't think, and
we had our -- one of our steering committee meetings just a couple of days ago, and the
-- I can say that both the coordinating center did an excellent job, but also the fluidity
and communication amongst the sites is really superb, and we're beginning to try to understand
where the potential overlap in the Venn diagram of our projects is coming so we can begin
to harmonize across the different projects.
Importantly, we want to create a centralized repository of data, both for our own purposes
but also to share with groups like this, and also to begin to think about how do we connect
to other implementation programs and networks, particularly within NHGRI that you've heard
about, such as CSER, such as the Newborn Screening Network, which are all implementation science
-- implementation programs, as well as eMERGE and the PGRN.
And we will, for the first time, have our program reviewed by an expert scientific panel
later this year.
So let me just give you a quick snapshot of the three projects.
This is the one from the University of Florida run by Julie Johnson and colleagues.
She's the dean of the School of Pharmacy there.
She's had ongoing interests in working with the Pharmacogenetics Research Network in delivering
pharmacogenetic information to clinicians and studying how they use the tests and the
outcomes as a result.
So this is really building on a lot of expertise at that particular site by her group, taking
well-validated tests that have information already in FDA labels and that have also been
fully vetted and analyzed by the Clinical Pharmacogenetics Implementation Consortium
that is -- has been spearheaded by Mary Relling, who's in the room, and also Dan Roden and
other colleagues from the Pharmacogenetics Research Network.
So in this case, they are implementing, in a preemptive fashion similar to what is happening
in the eMERGE network, genetic information into electronic medical records and developing
the information systems that are required to deliver that information just in time to
the clinicians.
The goal is to look at outcomes such as process outcomes, just simply how do we actually get
this information into the right place at the right time and how is this information utilized
by the patients and by the providers, what actions are taken, and to also develop the
understanding of, in this case, with the CYP2C19 program, to look at things that are safety
and efficacy outcomes.
This is just a snapshot of the overall organization of the program, so extending their reach into
other practices outside of the university setting to community-based health systems
and other cardiology practices throughout the Florida area.
They're also going to begin to work on IL28B for Hepatitis C sometime in the near future.
Dr. Bottinger's program at the Mount Sinai School of Medicine -- Dr. Bottinger is a nephrologist.
He's had a long-standing -- he and colleagues have a long-standing interest in understanding
progressive renal disease, and there's been in a lot of literature published on the APOL1
variant and its associated risk in African-Americans for progression to end stage renal disease
in those that have hypertension.
So the overarching hypothesis of his study is that informing patients about their risk
of developing renal disease and educating them about renal disease will incur behaviors
that will improve their compliance to medications for hypertension and overall reduce in the
future their progression to dialysis-dependent kidney disease.
So he's conducting this study in New York City across a diverse set of practices.
There are academic setting practices as well as a strong partnership with a community family
medicine practice also in the New York and New York metropolitan area.
Importantly, this is a cluster randomized perspective study, so there are control practices
and there are practices that are going to have the active intervention.
And, again, the endpoints that are being measured are having to process measures about the way
that recommendations are delivered, the understanding of those recommendations, both particularly
at the patient level, certainly whether this translates into better control of blood pressure,
and also at the provider level whether the appropriate monitoring tests are being used.
And there's this whole series of qualitative assessments that are being done through questionnaires
that you see at the bottom of this slide.
The last study, my own study, is building on a project that we've been running for several
years to develop a patient-facing electronic family history tool, meaning that the patients
entered the information, it's not done necessarily in the physician's office, the information
is captured and put through a series of clinical decision support rules that deliver guideline-specific
recommendations about genetic counseling and screening tests to the patient and to the
provider so two reports are generated, and putting this into the -- into a number of
diverse care settings that I'll show you in a second.
So our goals, you see on the left hand side, is to optimize how this process occurs, to
facilitate the integration of the clinical decision support rules as well as the reports
themselves in the electronic medical record, and also, through a cluster randomized prospective
study with a number of control practices and intervention practices, show both -- demonstrate
both the clinical utility as well as the personal utility of an adequately-collected family
history.
This gives a sense of the sites.
We're in 34 clinics across the United States.
You see their geographic locations.
They're very diverse, ranging from academic health centers to rural and underserved clinics,
particularly in the northwestern United States, and we have a number of process managers that
-- and implementation science methodology measures that we're using across this study.
I think that you're not intended to read the -- what's in the cells here, but the point
is, the kinds of outcomes that we're looking at are at the patient, provider, and at the
system level, and as you can see, we're trying to capture data -- and I think this is true
for most of the studies in this consortium -- at the behavioral, biological, clinical,
and financial levels, and we're looking for ways to do this as part of usual care.
So, in some cases, we'll administer questionnaires, but for the most part, the data that we're
capturing is in electronic medical records or in administrative databases.
Like the other consortia, we have a number of working groups.
These are cross-cutting.
There's one on implementation science, another one on dissemination, outreach, education,
economics and sustainability, and then a third that's on process and effectiveness measures.
And our goals are not only to begin to standardize these aspects of how we do implementation
of genomic medicine, but also to be a vehicle to communicate this information across other
consortia that is -- that are part of the NIH genomic medicine working space.
I think this is my last slide, which is just coming out of our last steering committee
meeting on Tuesday.
We know that there's another RFA who was -- another call was made.
There are other proposals that have been -- that are under review, so the network, we hope,
will expand to other sites and other initiatives.
We also are thinking very carefully about how we share data, how we put data sharing
plans into place, communicating best practices, as I mentioned, and also, as we discussed
a little bit yesterday, and as Anna Kolbe had mentioned, that we really want to also
engage payers into our community so we begin to understand what they're looking for in
terms of clinical utility, because, ultimately, sustainability is going to be dependent on
reimbursement, as we've acknowledged in several of the discussions we've had over the last
two days.
So I don't have a final slide, which is the acknowledgment slide, but clearly I want to
acknowledge NHGRI, and Teri Manolio and her team, Ebony Madden [spelled phonetically]
who is our project officer, and Heather Junkins, as well as Erwin, Steve, Julie, and their
teams at -- for making this a really exciting series of projects that I hope to report back
to you on with data going forward.
Thank you.
[applause]
So I have time to ask myself a few questions.
[laughter]
No.
Okay, I'm going to -- so I'm going to ask you a question.
What does IGNITE stand for?
[laughter]
No, I'm just kidding.
Male Speaker:[inaudible]
Geoffrey Ginsburg: Please.
Male Speaker:So this is open for everybody to join -- I mean for -- or only for the U.S.?
Geoffrey Ginsburg:Well, that's a question I think we're going to discuss this afternoon.
I mean, to the fact -- I think we would want to see perhaps opportunities to take pilot
projects.
We've heard about a number of pilot projects, not just these, over the last couple of days
and decide whether they are ones that might be amenable, feasible, and desirable to do
on an international scale of some type.
I would just say that I think -- and Teri or Eric, you can correct me if I'm wrong -- that
these consortia, while they have their -- the funded groups, I think there's a way to participate
in them as a visitor or an outsider just --
Teri Manolio:[inaudible]
Geoffrey Ginsburg: -- so you can learn -- pardon?
Okay.
I'll let Teri comment on that.
Teri Manolio:Sure, and I'll ask the eMERGE group people to do as well.
So actually NHGRI, as you've probably heard, and NIH in general, really tries to encourage
these kinds of collaborations, recognizing that it does take some time, you know, away
and focus away from the parent group.
But the ENCODE Consortium, which is a functional genomics consortium, did a very nice job in
encouraging what they call, I believe, ancillary auxiliary members.
There's maybe a better term than that, but at any rate, they had a whole policy for doing
that.
We then took that and moved it into eMERGE and have that opportunity.
So, actually, the Air Force has a personalized genomics project that is participating now
as an auxiliary member of eMERGE, and they sit on our steering --
Male Speaker:Affiliated.
Teri Manolio:Affiliated.
Thank you.
Thank you so much.
One of those A words, yeah.
[laughter]
But at any rate, we could do the same sort of thing in IGNITE, and we would encourage
that.
To some -- at some point, you know, it becomes a little bit unwieldy and difficult to manage.
The policies are not terribly odious.
It's mainly that you're willing to share your data and willing to maintain the privacy of
the data that are available.
I know, Tim, you have done these kinds of things in ENCODE.
Yeah.
So do you want to comment on how that's worked?
Tim Hubbard:I think that it's worked very well in terms of it -- you know, it's essentially
signing up to the common data sharing platform within the consortia and adopting those policies
and turning up at the consortia meeting, but generally people are keen to do that because
that's information exchange.
Teri Manolio:I see my colleague Jeff Schloss in the audience.
Jeff, could you comment?
Are there other programs in addition to ENCODE that does this sort of affiliate membership?Jeffrey
Schloss: That's the main one I'm aware of.
What about 1,000 Genomes?
Teri Manolio:Oh, 1,000 Genomes?
Jeffrey Schloss:That they were all funded by different ways, but --
Male Speaker:Yeah, they were all -- I mean, I think that's --
Male Speaker:[inaudible]
Teri Manolio:Yeah.
Male Speaker:Yeah, there's no point --
Teri Manolio:Yeah, there's no [inaudible], so that's another -- yeah.
Male Speaker:-- because --
Teri Manolio:Well, they may have their own --
Male Speaker:-- which is different --
Teri Manolio:Right.
Yeah.
Geoffrey Ginsburg:All right.
I think we've arrived -- thank you very much for that discussion.
We've arrived at lunch time, which I think is the same drill as it was yesterday.
We have an hour.
Also, breakout groups, you should have received an email from Rita Chambers last night that
was -- with the list of breakout sessions, and it's also out on the reception table outside
the room with the room assignments and the breakout leaders.
So, enjoy lunch, and we'll see you all back here at 2:45.