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Reed Pyeritz: Thank you very much. Appreciative of the opportunity
to comment. I also appreciate Maureen and Wendy having put their slides together well
in advance. I put my couple of slides together this afternoon as we were listening to them.
And so these are just a couple of the points that I wanted to emphasize.
And I think that we all know in our own minds what ELSI refers to. There's actually been
relatively little work in eMERGE on legal issues, very little comment about it today.
Some of us may appreciate that but others probably see major opportunities going forward,
and so I would just highlight the fact that that has been a relative desert.
I also have always felt that economics belongs in ELSI, not just because it begins with E,
but it is a science, albeit the dismal science, but nonetheless there is room for much formal
investigation as to how economic issues impact virtually everything that we've been discussing
and will discuss today.
We need to involve the stakeholders, obviously; payers and administrators have been mentioned.
But even beyond that I think they will respond best to accurate, valid data that the eMERGE
Network itself could begin to generate formally. And so that would be one important, I think,
recommendation going forward. There was an RFA not too long ago that began to address
some of these issues but there's clearly much more that could be done.
As Eric Green emphasized this morning, there are a number of consortia that are addressing
a number of aspects of genomic medicine. And most of them involve an ELSI component by
necessity; certainly point to the CSER projects and IGNITE. And of course there are the ELSI
CEERs that have been in existence for going on a decade now. Many of us have been working
in these areas independent of eMERGE, and I think it would be very useful if there were
some mechanism for bringing those of us working on ELSI issues together to discuss what we've
all been finding. Whether this is the annual gathering of the CEERs or some other form,
it might be useful to ensure that we're not reinventing wheel, as it were, to have dedicated
discussions -- opportunities for discussion around some of these issues.
I noted in both Maureen's and Wendy's comments, and in the title of this particular session
that the notion of education and governance were subsumed by ELSI. I think that's fine.
We've certainly heard some ideas about who to educate and about what. IRBs are the low-hanging
fruit, I would maintain. And certainly providers are important, and here, the IFCC effort,
a number of people on this webinar are involved in IFCC, is another forum that is actively
engaged. And certainly anything that's being done through eMERGE should make use of what
IFCC and other groups are contemplating and testing in the realm of education. And I think
NHGRI generally needs to be applauded for their work in public education, in particular
the Smithsonian Exhibition. But there's clearly more that needs to be done in this regard.
Can we have the final slide, please?
So the one issue that hasn't been discussed but I think falls into the general realm of
ELSI-related activities is the generation of policy. And we have to ask ourselves how
important policy is for effective implementation of any of the recommendations coming out of
eMERGE or any of the other genomic medicine consortia that are actively engaged at this
point in time. I would suggest that policy can be very helpful. It can also be a flash
point, as the ACMG recommendations on mandatory return of incidental findings emphasizes.
But nonetheless, I think we need to consider whether developing, or at least recommending,
policy is an important activity that could be done by the eMERGE consortium.
A particular area, and I'll end on this note, of interest to me is the whole notion of the
duty to re-contact when we're smarter. Clearly, interpretations change. Heidi has presented
an example of how, from the laboratory perspective, this can be implemented. But I'm also concerned
from a number of other perspectives, particularly the clinician's perspective, of what are our
responsibilities to get back to patients when we do change the interpretation of something
we counseled them about at some point in the past.
So, those are my thoughts. I'm very interested in what our other panelist, Laura Beskow,
Ingrid Holm, Kathy McCarty [spelled phonetically], and Tracy Trotter, most of whom have identified
themselves as being online, have to contribute. So I'll first ask Laura to comment.
Laura Beskow: Great. This is Laura Beskow at Duke. Hopefully
you all can hear me. I'm an associate professor at the Duke Clinical Research Institute, and
I have had the pleasure of actually working as sort of an external person with a couple
of different of the ELSI projects in eMERGE; and have found those both fun and beneficial,
you know, a combination that I very much appreciate. So it's been great and a lot of good work
being done that I look forward to continuing.
I'm also a member of the Regulatory and Ethics Core of the NIH Health Care Systems Research
Collaboratory. And I was quite struck this morning with the discussion about EHR phenotyping,
and, you know, moving into implementation and sort of the area between quality improvement
and research and so on, just the real synergies between eMERGE and the NIH Collaboratory,
that I'm really wondering if there are ways to more explicitly collaborate in some way.
The NIH Collaboratory already has relationships, for example, with PCORI, certain ways that
we interact with CTSA on some projects. And so it really -- I think there could be some
really good interactions with eMERGE as well.
Many of the comments -- I had an opportunity to see the slides, and so many of the comments
I had were already incorporated, and so I'll just make a few additional comments. I think
that the sort of ELSI component of eMERGE has really done such a fantastic job in terms
of incorporating an ethics perspective throughout a lot of its different teams and has done
a lot of really good work on soliciting stakeholder input, whether that's through descriptive
sort of research, community consultation, and so on. And so those are very important
foundational efforts.
And I think in eMERGE III what I would personally love to see is very focused effort on building
on that sort of exploratory descriptive work to actually develop and test interventions
designed to address some of these ethical issues. So, for example, in the area of consent,
obviously a lot of work in the model language, and that's continuing, it sounds like, with
the pediatric language, and I think that that's fantastic language. But I think it'd also
be interesting to actually then go ahead and test that language, try to find out about
the uptake with that language, see how participants react to it, find ways to assess comprehension
and improve comprehension. So building on that initial work to actually test and see
what sort of an effect and ways that things can be improved.
On the regulatory front, my ears perked up this morning with the talk of the eMERGE sites
coming together on the data-sharing agreement. And I really wondered if there was a way that
eMERGE could also demonstrate that sort of interaction on the IRB front and find ways,
whether it's a central IRB model or some collaborative IRB model, to really demonstrate sort of a
streamlined way that different institutions could work together and sort of get through
some of those IRB issues. That would be great to see.
With the EHR phenotyping, I think that that presents a lot of very interesting ethical
issues. One that I think was alluded to this morning a bit was the idea of if you find
folks with a particular genotype of interest, possibly a rare gene variant, that the idea
of being able to contact them and do more in-depth phenotyping. That is a topic that
I personally have done some work on. David Goldstein and I had a paper a couple of years
ago where we talked about what happened at Duke when we tried that. It raised some interesting
issues, and so, to me, that's an example of where some descriptive work has been done.
And so finding out -- exploring that in more robust detail, including coming up with interventions
on good ways to do that sort of thing and being able to really make use of the combination
of EHR data as well as genomic data.
So I'll just conclude with saying I really would hope that eMERGE could become a showcase
of robust empirical bioethics, similar to the way that, you know, eMERGE has been really
a great resource in terms of creating large sample sizes across the different sites. I
think that same benefit could apply to bioethics research. I think some of the limitations
in some work to date has been things like small sample sizes and so on. And so with
the expertise that eMERGE has, as well as being able to work collaboratively across
all the sites, I think that really gathering data to address some of these ethical issues
is an important contribution that eMERGE could make. So I'll stop there.
Reed Pyeritz: Thank you very much. Is Ingrid Holm on the
conference?
Ingrid Holm: Physically.
Male Speaker: Yes.
Ingrid Holm: Yeah. Yeah. But yeah this is Ingrid. So my
comment I think part of it is, is that, you know, Maureen and I, we're working together
and kind of [inaudible], so I think this is [inaudible] and I really appreciate everybody's
input, thinking of Reed and Laura, your perspective on it. I think from my perspective I feel
like that what our group can do at this point kind of going forward in eMERGE is probably
on the education piece of it, and I think the idea of educating IRB in particular is
crucial and just -- you know, as an example, Maureen and I are now dealing with developing
the survey across all the sites, and we've had IRB issues, you know, already across the
sites and it's been rather challenging. So I think -- and I sit on my IRB and I'm always
educated, so I think that one of the things that we can do as a group is try to, you know,
educate IRBs.
I also think that, you know, eMERGE II is kind of all -- is [unintelligible] kind of
genomic medicine, and integrating genomics into the EHR and, I think, clinical care.
And I think to me, like going the next step in terms of how physicians -- being involved
in how that information is used, and particularly from kind of the patient perspective and using
patient portals, and just, I guess kind of in general, how -- and this is one of the
comments that Maureen made too, is that how people are -- take this information, how they
use it, and kind of they feel about it. It seems to me that that's kind of going the
next step beyond getting the medical record and looking at kind of clinical support or
decision making in terms of PGx and going kind of further on with that. And a number
of people have mentioned the fact that I think, you know, these patient portals may give us
the opportunity to kind of do that.
And I really like what Laura was saying about this idea of not just kind of developing policies
and developing consents but really testing them. So, for example, testing consent forms
and seeing how -- kind of getting feedback from participants in terms of using things
like consent forms. So I think as we are in -- right now in our CERC group getting feedback
from participants about how they feel about broad consent, we can do -- I think in eMERGE
III get more information back from participants about how they view genomic data that they're
getting and how the view the consent forms that we're talking. So really kind of get
out in the community and looking up what kind of patients stakeholders -- or participant
stakeholders I think would be kind of a good next step from our perspective for eMERGE.
Reed Pyeritz: Thank you very much. Kathy McCarty?
Kathy McCarty: Yep, I'm here as well, and similar to our
previous speakers, I have say [unintelligible] as well. But Laura mentioned potential collaborations
with the Collaboratory, how the Collaboratory have ensured collaborations with PCORI, and
it strikes me that so much of what we've done already is very well aligned with what PCORI
is doing in their initiatives, and the methodology around including and engaging our patient
as, you know, truly as partners. And what can we do to more formally work with PCORI
would be something to explore.
We've talked in the past about how do we engage payers, very important if we're doing AMD,
macular degeneration, genomic medicine pilot here at Ascentia, and one of our questions
as we're following up with participants is to see whether or not they would be willing
to pay for genetic costs out of pocket. And that's been interesting -- some of them "Yes,"
I mean, varying costs, that almost all of them would want to talk to their payers about
whether or not they would cover genetic tests. But how do we try to actively engage them?
And I know for myself I found that challenging when I went to [unintelligible] Marshall Clinic
in Wisconsin, to contacted the statewide organization of HMOs and just found it challenging to -- for
them to even identify somebody to come and sit on a panel with us; we were just concerned
about doing that. How can we try and engage them as part of the community to engage...
IRB education, also really important, so I have a new hat here at Ascentia, I've taken
on the role of the IRB chair so I can [unintelligible] a little bit on that behalf. Nine of our office
sites within the eMERGE Network are part of the HMO Research Network, and there's currently
a document going around about cleaning and having a central IRB within the HMRN, [unintelligible],
and I think by the end of this month, and it'll be interesting to see what we get because
we have almost always have some changes to that document every time it goes through any
of the legal departments. And so we need to remember engage our legal counsel early on
in the process when I'm looking at that.
And then Barbara Keenan [spelled phonetically] has been our voice all along, and I want to
bring her voice back again. When we're educating IRB, how do we educate them about the importance
of the engagement of [unintelligible], and incorporating their feedback into our IRB
applications, really important, so that we can develop potentially have some [unintelligible]
for IRBs. [unintelligible] absolutely of great contribution to the wider community.
Reed Pyeritz: Thank you very much. And finally, Tracy Trotter.
Tracy Trotter: Reed, thank you. I think about a month ago
I was traded to the Panel 7 pediatric team for an expert to be named later, but I still
have a couple comments, because you called on me. One is the overall comment as a pediatrician
is all the ELSI and consent issues of course become more complex when dealing with pediatric
patients, and possibly even more complex when we get into newborns and sequencing and things
like that. So I look forward to the model language. I think it's important that we get
as many people on the same train as we can on this thing. And I look forward to somebody
coming up with good answers about updating new information and updating information as
it changes over the lifespan because when your patient's 4 months old, when the information
is gathered you got a lot of time to think about that and how to do it correctly and
how to do it well. And I'll save the rest for my own panel. Thank you.
Reed Pyeritz: Great. So, I think it's time now to open it
up to general discussion.
Marc Williams: Marc Williams again. So I just wanted to come
back to the E [spelled phonetically] that you posed Reed. For those of you that were
paying attention to the sidebar discussion earlier, there was a fair amount of back and
forth about the role of adding a component of, you know, eMERGE III to look at economic
or value-based propositions and proposals and how to study that. Clearly that would
be something that is of interest related to implementation, and we do have precedent in
that the newborn sequencing RFA that was referenced did explicitly allow for an economic study
to be a component of Subproject 3, which was the ELSI, and to my knowledge, that was the
first one that specifically called that out.
Clearly there would be methologic issues that would arise, much as had been encountered
related to variability in IRB, variability in phenotyping et cetera. But in some sense,
if we could develop a model across the network of doing this type of economic analysis, not
only would that be valuable for the implementation of genomic medicine, but I think it would
provide some methods for shared economic research that would be broadly applicable. So I would
endorse a consideration of an economic arm to eMERGE III.
Susan Wolf: Can I pipe in also on Reed's suggestion -- it's
Susan Wolf -- a legal -- a more robust legal component. I think that's really critical
because successful integration of genomics in the clinical care requires support of law,
and conversely, if institutional leaders perceive or misperceive a legal barrier, that may stop
the train in its tracks. So if you were thinking of a short list of high-impact legal loci,
they would include the CLIA issue we've already discussed, the HIPAA implications, because
as soon as you talk about reaching out to family and even posthumous -- use of posthumous
information, HIPAA doesn't die when a person dies, and so that's a big set of problems.
The recontact issue that was already raised. The return of results itself raises a lot
legal issues including rights to refuse and whether you do need consent for incorporation
into the electronic health record.
I loved Heidi's idea -- I think it was Heidi -- about mapping responsibilities within the
EHR environment that has a lot of legal pieces to it including for the biorepository. And
lastly, you know, the invention of the proposed rulemaking is a proposed regulatory change.
So it's both ethics and law. So there's a great and really important lesson, I think,
on the legal front.
Female Speaker: Thanks, Ellen. And I guess I'll echo both
-- what Marc and Ellen both said, that I think both the economic and legal pieces are important.
And I guess I'll expand on the economic piece that people have proposed population genetic
screening for BRCA mutations, and for Lynch syndrome mutations. Israel is already doing
population screening for BRCA mutations. And since we have mostly population-based samples,
we could really seek to the economics of screening and down-the-road costs.
Reed Pyeritz: Another interesting aspect of an economic
study is that genomic data is different from other healthcare data in that it is persistent.
And so if you think about an initial investment in genotyping, that information can then be
reused over an extensive period of time based on different clinical contexts. And that's
a very different type of economic assessment of an investment. I'm just not aware of anything
else in health care that has that type of persistence which I think would be very interesting
to study.
Male Speaker: On the IRB front, one interesting connection
is that among the NIH BD2K workshop was one that I was able to co-chair in September on
the research uses of clinical data. And for the entire workshop, Jerry Menikoff, who is
the director of OHRP, was present and engaged. And one of the observations he made was that
delegation models are very familiar, and IRB uses a central IRB or delegates to some other
member of a consortium. And his personal view is that resulted in no education. The IRB
was no better for the next project they reviewed if they delegate. And he was very interested
in OHRP actually supporting and engaging in some experiments of IRB consultation and education
with one another that might improve the performance of the network in a persistent way.
So that was OHRP inviting, I thought, organizations like eMERGE to say, "Let's do some interesting
experiments of IRBs that are not just like business as usual of delegation or central
IRBs."
Male Speaker: One related aspect is the rather, I think,
overly legalistic format of most consent documents. From my point of view they impede the consent
process. And I know Mike Gaziano is out there some place, but a project that he did before
the MVP at the VA was instituted was to pilot a brochure with information about the study
versus the formal consent document that had the same information. And participants strongly
preferred the brochure, which probably none of us would be surprised at. But I'm unaware
of many studies of that nature. And so I think it's part of educating the IRB. I don't think
we're going to change CFR 36 quickly, but we might -- we might work towards a better,
you know, getting a document that was actually more user friendly and actually communicated
what we wanted.
Male Speaker: Yeah, we should [inaudible] --
Jeffrey Botkin: Just -- Jeff Botkin, I wanted to make a couple
of quick comments here. In large measure to support much of what was said by the panel,
but people have called for a formal evaluation of the efficacy and impact of the recommendations
that are coming out of the work groups. And I very much support that notion, but those
types of studies, of course, are fairly expensive. So I'm wondering whether the eMERGE network
can support that type of outcome study, or whether this is something we need to look
to NHGRI for an RFA targeted to a particular domain in that respect. Then let me ask the
second question quickly, and then I'll get off.
There's the -- people talk, and they very much support the notion of IRBs as key stakeholders
for the network here. So I think that's just a wonderful idea. So has there been any collaboration
between eMERGE institution and IRBs in support of the network to date?
Female Speaker: I mean, there's been a lot of consultation
at the individual level, and also a large study across IRBs in the country that several
of the sites collaborated on with the GRIP consortia. So while we are suggesting the
incorporation of IRB sort of along with some of our studies, I don't think that has been
done, but certainly there has been consultation and work with IRBs in the network at most
of the sites individually.
Male Speaker: I think the other elephant in the room in
this area is the CTSA Consortium. We are at or affiliated with CTSAs, and one of the three
must-dos this year for the CTSA Consortium is widespread IRB reliance agreements. So,
that is going to completely change the IRB landscape across the CTSA in the next 12 months.
Teri Manolio: Jeff, I wonder -- this is Teri. I wasn't quite
sure you said that -- would eMERGE be able to support that kind of outcome study in terms
of formal evaluations of many of these recommendations. It sounds like a lot of these recommendations
are, you know, things like you can study the impact, or the outcome, or the attitudes,
or that sort of thing. It doesn't sound like a huge outcome study to me, but maybe I misunderstood
what you were suggesting.
Jeffrey Botkin: No, I think that's exactly what I'm suggesting,
and [unintelligible] come forward with what they think would be more appropriate consent
language and formats for conducting this kind of research. I think those sorts of recommendations
are quite welcome, but that's different than actually evaluating their impact in terms
of people's understanding of the elements of the consent process and their response
to the information, et cetera. It may well be that that sort of thing, just in the flow
of research participants through eMERGE, you can look at some of those outcomes relatively
inexpensively. But I know as we try to set up studies to formally evaluate different
approaches to consent, it turns out to be complicated and roughly expensive process
in certain circumstances.
So his question was, can you adequately build on the eMERGE network with some supplemental
funds to get that kind of work done, or do you really need a separate allocation of funds
to do that in a rigorous way.
Teri Manolio: Right, and I guess, you know, the "how" of
how we go about this is maybe a little bit down the road. We're kind of trying to define
the "what" at the meeting today. But I think, you know, just to address the "how," one might
-- or the "who" -- one might also say not all of these questions are uniquely addressable
in eMERGE. And so, you know, there might be other consortia or groups that we could look
at to answer them. But I think rather than getting into that let's try and focus on the
"what." I think we do have to move on.
Male Speaker: Yeah, we're right -- we're right on time.
Male Speaker: But Teri, I think that the "how" is something
we should be thinking about and --
Teri Manolio: Sure.
Male Speaker: -- hence my suggestion that all these different
groups that are thinking about the same things need to get together and chat.
Teri Manolio: [affirmative] No, excellent point.
Male Speaker: Okay, and an excellent discussion on a topic
which segues directly to -- actually we have another presenter in the room here, so Iftikhar
will be the eMERGE presenter for the topic of return of results.