 So, I mentioned earlier there are four working groups to the council, and it was time to get reports from two of them. So Terry Monoglio is going to report on activities from the past year, the Genomic Medicine Working Group. Great. Thank you, Rudy. Can everyone hear me? All right. Good. So, thank you very much. I'm glad we have an opportunity to give you an update. Since my name is on here, I couldn't resist the opportunity to cite my alma mater and welcome Dr. Reese to our table. It's wonderful to have someone here, someone else here from the University of Maryland School of Medicine. The Genomic Medicine Working Group is made up of many members past and present of council. You see the list here. Several of them are still around the table, and I'll be asking them to comment after I finish here. And then there are five of us from NHGRI who also work with the group. Just as a reminder to those of you who are new to our council, what we consider Genomic Medicine to be, a lot of groups will include kind of discovery research looking at associations between genotypes and phenotypes in the rubric of genomic medicine. We also see that clinical validation, assessing outcomes after using genetics to direct therapy, that's something that almost everyone will agree on. And clinical implementation, developing processes for performing these tests, making sure that they're available to everyone and that they're cost effective. But here at NHGRI, the discovery research is not considered to be part of what we consider a rather narrow definition of genomic medicine. So in focusing on this, it's not going to be on the gene disease associations but on validation and implementation. The charge of the group is to assist the council in advising the institute on research that's needed to evaluate and implement genomic medicine in clinical care. And in that is reviewing current progress, identifying research gaps and approaches for filling them, something that all of our working groups and you are charged with doing. We also ask this group to identify and help us publicize key advances. So when new papers pop up that we feel are worthy of clinical notice, we make those known, and I'll show you how we do that. We also have a series of genomic medicine meetings that began actually with our first one in 2011, and we've had 10 of them since then. The idea of being to address timely topics in genomic medicine, particularly in implementation, and also to sort of build a community. So we video and livestream and archive all of these meetings. We invite as many people as we can fit in the room to come and we really try to make it an event. We also try to facilitate collaboration coordination and explore models for long-term infrastructure and sustainability. So if you look, when I mentioned that we try to identify notable accomplishments on the Division of Genomic Medicine webpage, you'll see genomic medicine activities and just under there, notable accomplishments. If you click on that, it will bring up a group of links to papers in these various areas, clinical implementation being kind of the top one. So in July, we identified this paper from the Ignite Network on implementing a sustainable genomic medicine program, lessons learned from Ignite. In the disease findings area, we identified this Cara and Katharysen paper that has already come up in discussion this morning, and similar papers to that we do try to identify and make them available. In addition, the genomic medicine meetings that I mentioned, we've held 11 of them so far, starting with the first one in June of 2011 that actually led with a public, resulted in a publication on sort of a roadmap for implementing genomics and clinical care. Our second meeting in December of 2011, so barely six months later, was focused on developing collaborations. We held a stakeholders meeting in May of 2012, a physician education meeting about six or seven months later. Had a group of federal agencies and sort of exploring federal strategies for implementing genomics and clinical care. We had a global leaders meeting, very much like our initial colloquium, where we were trying to bring together everybody, in this case, everybody in the world who was doing this kind of implementation, as opposed to just in the U.S. Our seventh meeting was on genomic clinical decision support. We took a step back in our eighth meeting, really trying to say, okay, we have a number of programs up in the field now. How does that look? Are they working well together? How can we make them better? Our ninth meeting was bedside back to bench, really trying to link the functional and clinical communities. Our tenth meeting was on implementation of pharmacogenomics. And then, as Eric mentioned, the 11th was on clinical implementation, so implementation of things in addition to pharmacogenetics. Not quite sure what our 12th meeting is going to hold, and if you have suggestions for that, we would welcome them. So, when you, again, go to our webpage, if you're so inclined, you can find a part of the page that will point you to our genomic medicine meetings. This lists all of the meetings, including their titles and dates and where they are, and if you click on one of them, like this one that just happened a couple of weeks ago, we have actually posted before the meeting even happened so that people can log in, look at it, watch it on Genome TV if they want, even come to the meeting if there's space. We post the agenda as soon as, after the meeting as we can, we post the slides, so all of the slides are available, and then the videos are eventually posted as well. So that would look like this is from the tenth meeting, and you see here's the video playlist. We also post a meeting summary, an executive summary, and more recently, we've been collecting tweets from the meeting, so we have that up there as well. And again, all of this sort of geared toward building a community and getting feedback and making resources available. We've been fortunate enough to be able to publish several things from these meetings, so I mentioned the first one that came up with a roadmap published in Genetics and Medicine. This followed, one of the things we identified in that first meeting was, gee, nobody really knows how to define clinical action ability, so what is it that should be reported back now that seems old hat, but in 2012, 2013, this was not old hat, it was subject of a great deal of debate. So my colleague Aaron Ramos led a workshop that came out of these meetings to try to address that. We had one on educating physicians that Genetics and Medicine was generous enough to take Science Translational Medicine, published our Global Implementation of Genomic Medicine paper. The bedside back to bench one that Carol was instrumental in leading ended up in cell, that they were quite interested in that, and then my colleague Simona put together this report from the Genomic Medicine 10 meeting on pharmacogenetics that was published in clinical pharmacology and therapeutics. So outgrowth from these meetings, and we do, or I do at least, peg a lot of things back to what's happened or what we've identified in these meetings because we feel it has provided us the broadest input. So I mentioned after the first meeting, we held our clinical action meeting. We think we're among the first to define clinical action ability as being sort of a subset of what's actually having clinical utility versus what has clinical validity and the fact that this is a little bit elastic. So it really depends a lot on the setting that a particular patient is in as well as what their wishes are and what their clinician is able to do. Directly from that clinical action meeting, we brought to you the proposal for the ClinGen consortium and that was subsequently funded. A lot of things have come out of that. I focus on the precision FDA efforts that ClinGen is now being considered to be an expert database for that effort. So really building links for us with our federal partners. We also developed a collaboration with the National Institute of General Medical Sciences which had a pharmacogenetic array that they had developed and we implemented that in our Emerge program called the Emerge PDX. Our second meeting on collaborations led directly to the release of the program that eventually became the Ignite Consortium. Our third meeting with payers ran into a bit of a brick wall. But we think we may have a way through this and I'll tell you about that as an outcome of our most recent meeting. So maybe a little bit of sunshine coming in there. Our fourth meeting on physician education led to the establishment of our Inter-Society Coordinating Committee on Practitioner Education and Genomics which is now led by our sister division, Laura's group in the division of policy, communication and education. The fifth meeting was a sort of a federal strategies meeting. It did help us to build some links with both CMS and FDA. That is an ongoing project and one that we are continuing again through the auspices of Laura's group to try to push and promote. The sixth meeting was the global leaders meeting and that one actually led to a whole host of things. So one of the things that was identified at that meeting was a really nifty way to identify people who were at high risk for Stevens-Johnson syndrome or toxic epidural necrolysis after taking certain drugs. And so we held a whole workshop on that, tried to get other institutes interested in participating in research in that area and then we're able to release a program announcement that Jeff String and Sumona both be are leading on serious adverse drug reactions. Just this past spring, Francis Collins and Jeremy at the Wellcome Trust, Jeremy, anyway. Thank you, Jeremy, for our, at the Wellcome Trust. I don't know if you're in the room. That's right. Hopefully he's not watching. Hopefully he's not. Sorry, Jeremy. At any rate, commission the G2MC to hold a, he may take his money back, to hold a summit on large scale cohort studies and we brought together over 50 cohorts around the world basically, trying to figure out how we could get these groups to work together to generate gene disease associations as well as evidence of the impact of genomic medicine implementation. That has since led to an international 100K cohort consortium or IHCC that is just getting off the ground that G2MC is leading and the All of Us Research Program and the Office of the Director at NIH are helping to support. So this has been an effort that really sort of took off. The seventh meeting on genomic clinical decision support led to a collaboration with the National Academy of Medicine in digitized effort, which was an effort in clinical decision support, which is I believe ongoing, although it's sort of winding up at this point. Our eighth meeting really brought us, made us aware of some very exciting work going on in the Genomics England Program with the National Health Service, particularly the Health Education England effort to provide research, I'm sorry, educational modules to lots of different levels of clinicians and researchers as well and so we've been working with them since then to try to adapt some of these for our educational efforts. Our ninth meeting on bringing sort of bedside back to bench stimulated our and encouraged our colleagues within both the what you may be aware of as a group focused on function and another group focused on genomic medicine to come together as well as genomic structure and say, okay, can we put together a program announcement in variants functioned in disease and that has been recently released. Our tenth meeting led to an interesting collaboration with Optum, which is a subsidiary of United Healthcare and in particular they were concerned about not being able to track the genetic tests that are being ordered on their patients. They insure about 140 million some people and there are only at present two or 300 codes that can be used to track these tests. There are 70,000 genetic tests in the GTR and each of those has a number and so they're having a basically a pilot program to try to use those in billing to see if that will be an acceptable and feasible way to track information on genetic tests that are being ordered. So sort of more to follow on that but it's something that's being implemented now. It's very exciting from our point of view. And then the eleventh meeting that we just held a couple of weeks ago that Eric mentioned. So just to remind you the objectives of that we're summarizing the current status of implementation research, identifying obstacles, defining where we could or should be five to 10 years from now and how we can get there. And then we also had a segment that was designed to help us inform the NHGRI strategic planning process specifically regarding genomic medicine. Among the recommendations in the meeting summary is just still in preparation but should be out soon. But one was that we find a way to establish guideline development process similar to the clinical pharmacogenomic implement pharmacogenetic implementation consortium or CPIC which is a group that looks specifically at pharmacogenetics but to do that for relevant genes that are not related to pharmacogenetics but still are important. The ACMG, the American College of Medical Genetics and Genomics has done some of this but more of it needs to be done. Another was potentially to create a registry of patients who have had either genotyping array or sequence data collected particularly to the degree that they're linked to their medical records and follow them for outcomes. Many of those have been obviously tested within our programs but there are many others out there as well. Potentially developing a limited training program for the majority of common complex disorders such as diabetes, heart disease, et cetera that will help average clinicians not geneticists to be able to use genomic information in the care of those patients. And even potentially certifying people as sort of genomic consultants where they could then provide this kind of information as a consult to others within their medical system. And interestingly, one strong recommendation and one that we're already following up on is it was to engage employers as key stakeholders. The point was made that as we try to pursue insurers and payers that in many ways payers are not really paying they're using somebody else's money and that somebody else is typically employers who have a lot more at stake potentially. And so this was a recommendation and this came particularly from a panel that Pat led on what evidence is needed. One of the strong, well, one of the frustrations that we've run into is that we come up with evidence and then we go to payers and they say well that's not quite enough. And so what is it that they actually need and it's very difficult to get sometimes a clear answer. I'm not sure that they know themselves to be fair. But the recommendation given to us was don't be held hostage by there not being enough evidence. There is some and we should get on with it. And in that way, the only way that you're gonna generate evidence is to actually do this and collect it. The point was made that employers may have a lower threshold than payers because their consumers, their employees are going to be important drivers of what they adopt. And employers will also be an important force in moving this forward. They didn't advise us to reduce the emphasis on educating everyone involved which I thought was an interesting. We all think this stuff is fascinating but not everybody has time to be educated in it so we have to figure out effective ways of doing that. And then the suggestion that we find a way to provide some consulting help on the ground as companies are trying to do this. We were advised that we need research that show that employers will benefit from adopting genomics in clinical care. And really to utilize the evidence being generated even if it's imperfect it's still something that we can gain value from. And we were urged to convene a group of employers and work with them to ensure that we're rolling this out in a way that the evidence can be captured and could eventually be analyzed and published based on pooled efforts from a group of employers. They are already self-aggregating into consortia. We've heard about one of the big three groups that are putting together a consortia. And we should take advantage of this and try to find a way to use it for research. We were encouraged to try to develop sort of a basic genomics formulary that employers could then say, okay, here's a list of the tests that we recognize are useful in this subset of patients, in this set of conditions. And can we work together to develop that? And they did recognize that public payers are still very difficult, tough nut to crack and we'll keep trying. So following up on that, we are planning to convene a sort of a genomic medicine meeting focused on employers where we'll try to determine what employers' needs are for this kind of formulary of basic and enhanced genetic testing or other kinds of guidance that an expert group might be able to provide to them. Maybe explore a project to deploy a program like this within an employer health plan and then measure and publish the clinical and health economic impact of that deployment. And then maybe explore some additional collaborative opportunities like pooling data from their health data systems, et cetera. So with that, I'd just like to thank everyone within NHGRI who's doing this work as well as the investigators in our many research programs, our Genomic Medicine Working Group and of course all of the participants in our major studies. I think I'll stop there and I'll ask Pat if you'd be willing to, if you wanted to make any comments or add on. I thought you did a great job summarizing that. The only point that I would say is just marrying what you were saying with employers with the whole purpose of our meeting which was implementation science. And there I think it's clear that both practice and research should coexist. And so in doing these kinds of pilots, I think we still want to hold out a little bit of equipoise for deciding whether or not in the real world how the implementation of things that we think have clinical utility, sort of the tier one CDC test for example, how does that actually play out in employer based settings? And we're still gonna face all the same issues with lack of integration of genomic information in the electronic health record, mentioned education, et cetera. So we'll still need to confront that but I think that implementation science construct is another piece that we're gonna be able to bring to really help look at what is the best evidence in the real world. So that was it. Great, thank you. Dan, did you want to comment? No, I didn't. Well then don't. But I'll just say that, so this exercise started in 2011, 2012, something like that and it seems to go in sort of baby steps but when you cast your mind back over the last seven or eight years, Emerge, Caesar, Ignite and all those other initiatives have resulted in a real change in the landscape of the way people think about genomic medicine and integration of genomic medicine into healthcare. So I sort of say that to congratulate you and by extension congratulate other members of the working group, including me. The specifics of the last meeting were pretty interesting because we have been, as you show the little brick wall and the brick wall is the payers, is the ethnos and the blue crosses of this world and they just sort of seem really intransigent and I can't remember who it was who brought it to our attention that the people who really pay for this are Boeing and General Electric and IBM and they're very interested in preventing early onset breast cancer or early onset myocardial infarction. So going at it through them rather than through the payers and they can deal with all those other people seems like a really innovative and interesting way of getting the right people at the table. So pretty exciting way of bringing down that brick wall. Thanks. And Carol, I know I just want to call on Carol. I know you weren't able to be at this meeting but did you want to comment on other activities of the working group? The working group does a great job. No, and I'm sorry I couldn't make it to the last meeting but in terms of looking forward to a meeting centered on employers, was there a strategy for how to select the employers that would be invited or did I, oh another wall? No, no. So actually the four or five kind of stakeholders that comprised that panel were very, very active and contributory in that. One of them in particular has been advising us since then and we've gotten in touch with a couple of others and we'll probably try to look for a broad spectrum of employers as well as probably some of the larger ones because we want to be sure that we have some impact on that but suggestions on how to do that would be most welcome. Jeff? I guess things have evolved since the whole first generation of LC work was focused on health and employment discrimination based on genetic information. So I guess I have to raise some concerns about engaging employers in a domain where I think a lot of people be pretty nervous about having their employer know genetic information about them so no doubt you've been thinking about how to engage this community without sort of backtracking on what a lot of protections have been put in place over the last 20 years or so. No, that's a very important caution and one that I think we need to pay much more attention to. It's right now the dynamic has been gee, you have employers who are really very eager to put this into their medical plans because their employees are asking for it. We haven't dealt with the, it seems as though and I might ask Laura Rodriguez to comment but it seems as though the Gina protections are things that the most part employers are accepting at least those that we've been talking to and particularly the Optum people have basically said we can't even look at these results because of Gina. So I think there are more protections in place than there were but we really could use some advice on how to, is Laura here and did you want to comment on that or? Hi, I'm on the phone, can you hear me? Yes, we can. And as you have something that we need to think about, I think what we're talking to is again, them as purchasers of the coverage and what access they have to medical records is further downstream and I would assume it would be governed by all the rules that they might already have about how they can look at an employee's records relative to what they're willing to pay for or purchase from the payers. But it is definitely something we need to be careful about with something we need to be careful about even in just messaging that we're talking to them about this. So thank you for the concern and we will definitely be keeping it front and center as we go forward in these discussions. Great, thanks Laura. Other comments? Yes, Phil. So I think it's a good idea to go to employers and I commend you for that and at least opening up that discussion. I'm a medical geneticist, I still see patients occasionally. And one thing I want to caution is too much focus on complex genetics or polygenic risks. The insurance companies still don't get monogenic risks. And they won't pay for the right patient to be tested a lot of times. And so if we're trying to sell polygenic risk assessments and delivery without first fixing the monogenics, I think we're missing the boat a little bit. So I think we're approaching the payers with the idea that there will be some small change in the way we get genetic testing covered in large populations. I don't think we would go from where we are now to whole genome sequence in everybody who works for General Motors. But the kinds of things that we had been talking about were Lynch syndrome testing, BRCA1 and 2 testing, FH testing in people who were appropriately counseled beforehand. And in the New York times today, there's another sort of screed or article or plea for large scale BRCA1 and 2 testing in appropriate populations. So I think that's, we'd start with that baby step, that's at least the way I thought about it. And whether you throw in the pharmacogenetic variants along the way, which everybody sort of used to say, yeah, we'll do those as well. Like there's no problem in doing them as well. So, but that would, the idea would be to sort of make some progress in some area as opposed to getting whole genomes covered in everybody immediately. Yeah, I guess I would echo the caution about employers. I mean, my sense, again, as a clinical gen, I was just reading another email from my counselor about what did or didn't get approved for Wednesday's clinic, which is the weekly email, essentially, I would be careful because my sense of employers is that, they've got a million options when they're buying these plans and there are dozens of these different options and genetics is just easy to leave out. So unless they're really hearing from their patients, they're covered lives, I don't know how much hearing nationally, so I don't have, what I guess what I'm saying is, I don't have a sense. It's a little bit like when we talk with our hospital about Epic and having genomic modules added, they just don't view it as a high priority. So I just don't know from the point of view of employers who are deciding on what to cover, how much they view this as a high priority and maybe you've heard this in prior meetings and that's kind of the genesis of this, but I'd be cautious that you might engage employers that are just like, this is not the big issue for us. No, that's a well-placed caution, Sharon, and we haven't heard this before. I mean, when it was said, it was sort of like, oh, we hadn't really thought of that in the past. What we're doing before we kind of bring a group together is really trying to survey some of the major players in this range. I mean, we had five of them that said, yeah, this is something that we really need to address, but we obviously need to do more of that before we bring a group together. Mary is walking to the mic. I just want to make a quick comment and a follow-up to Jeff's comment and Laura's take on this. So we're working with folks at the University of Maryland Law School who have been looking into, it's making a light. It's on, it's on. Yeah, okay. On what the web of protections are from your employer knowing your health information. And there is a web between ACA, HIPAA, GINA, and the Rehabilitation Act. So employers will not be getting this information anytime soon, nor are they allowed to get it. They can pay for third parties to hold it. And of course, that web of protection that exists now could go away. Well, maybe I'm being naive, but what's really changed, right? Employers purchase health insurance and consumer employees consume. Why does genetics change anything? I think what has changed is that employees are starting to ask for this. So whatever we've done has sort of gotten that out into the lay public. Right, but is it simple fear and loathing? Why would people be any more concerned? Why would employees be any more concerned that their genetic information is available in their medical files? So I'll ask people who know far more about this than I about genetic exceptionalism and why this might be particularly worrisome. Well, I'm gonna guess that I think one element is simply the predictive nature of it and that folks would, you know, a lot of health information is out there because people have health conditions and that may be evident to a lot of people, but it's still highly private. But the genetics world and a lot of sensitivity here has been around the predictive testing and whether employees might be tempted to use that and the employment process to sort people in various ways. And so, you know, good to hear that this is all being discussed in the context of the protections that are out there. So, you know, that's great, but dealing with it on that perception issue, and I do think that there's a perception of some genetic exceptionalism here. And I think people tend to be nervous about having this type of information shared much more than their blood pressure or their cholesterol level. The other thing that's different is it's often not covered. I've never met an insurance policy that says we don't cover MRIs, period. There are lots of insurance policies that we just didn't sign up for genetic testing. So I think that is one thing that's different is many employers just opt to not cover it at all. And so I think that's one of the reasons it gets raised is that it's been kind of selected as an area of medicine that they can just opt out of. So, one of the reasons that we were enthusiastic about this at the meeting in San Diego was that we had people there from the payer community as well as from the interface between their companies that sort of deal with payers indirectly and help them construct their plans. And they said that there's a lot of interest on the part of some payers and we thought that was a reasonable way forward. This has been a really helpful discussion and I think Terry will report back to this group as to whether it works or not. But until now we've sort of been butting our heads against the wall. I can't count how many times we've heard from Blue Cross or about their attitudes towards this. And they always just say, well, there's another SNP. Let's have a randomized clinical trial in 10,000 patients to see if that works or not for outcomes. So this feels like a different way forward for at least some of the low hanging fruit for lack of a better term. So I think that we're not married to it but it really feels like an exciting new way of getting this done. And just to say there was more recent angst because of a genetics community having to beat back an effort in Congress to alter laws in a way that would have basically gutted gena protections. So I mean, I think there may be more concern on the part of employees now about the possibility that gena protections just go away with the mark of a pen. And because that we did come perilously close to that happening last year and the entire genetics community had to pull together to really get that off of the table. So it's all prohibited now. And this, I agree, it sounds very positive to get uptake of genetics, get it into the insurance that is offered to employees. But ostensibly this was to, I mean, this could have mandated getting genetic testing done and removed the current prohibition against employers having access to the information and in fact allow them to sell it on the open market if they so chose. So it's a, gena is potentially ephemeral and it's something that we have to watch out for. Thank you very much, Terry.