 Thank you all. Welcome back from lunch. I hope it was a pleasant experience. You had good company and good food. We're going to resume with the open session agenda here. Terry Monoglio is going to give you a presentation from the Genomic Medicine Working Group of Council. One of the requirements of council working groups is to make at a minimum an annual report back to the full council, and Terry's going to do that for you today. Great. Thank you. And good afternoon. So this is probably the fourth report we've done of the Genomic Medicine Working Group to the council. We try to do them every September. Just a reminder of who's on the working group. We have three current council members, Carol, Howard, and Dan. Those of you who are rotating off council, be assured that you're not off the council working group. You'll notice Jeff was on quite some time ago, as was Rex and a few others, and yet they're still on our list. So we welcome you just to stick around. And just a reminder that the sort of the areas that our working group addresses are sort of the latter two domains that were added in the 2011 strategic plan. So the advancing the science of medicine, improving the effectiveness of healthcare, is where most of our emphasis is. The charge to the working group is to assist in advising us on research needed to evaluate and implement Genomic Medicine by reviewing current progress, identifying gaps, publicizing key advances, planning Genomic Medicine meetings, which I'll talk about in some detail, facilitating collaborations and exploring models for infrastructure and sustainability of the programs that we propose. So I think I've described to this group in the past that we kind of began this whole effort shortly after the strategic plan was released. It was about June of 2011 when we held a meeting at O'Hare Airport of about 20 different groups that we were aware of were doing implementation of genomics in clinical care. And we just invited people to come and spend a day with us, which they did. And from that, we sort of learned that there was a whole lot more going on than we had expected, but a lot of it was going on in isolation. And one of the things we needed to do was to develop some joint programs. But we also produced sort of a roadmap from that of how one can go about implementing genomics in clinical care that was published in genetics and medicine. Our second meeting about six months later was to focus on forming collaborations. We had a third meeting with stakeholders and payers. It was one of many efforts we've had at engaging the payer community and others. The fourth was on physician education in January of 2013. Then we had one with federal agencies trying to work with our federal partners to try to develop strategies for implementation. The sixth was a global leaders meeting where we invited everybody that we knew in the world as opposed to in the U.S. to do much of what we had done in the first meeting. And then one on clinical decision support for genomics in medical care. An eighth one about a year ago that was kind of an overview of our existing programs just a little bit of a step back to see where we are. And we reported on that one I think about a year ago, maybe six months. And then just recently held one in April on a bedside back to bench that Carol's going to tell you about once I'm finished. So all of the meeting or content is webcast. Everything since the first one. And the slides and summaries and all of background materials and that are all available on the Genomic Medicine website. So if you just Google NHGRI Genomic Medicine, it should come right up. Outgross of these meetings, there have been many. Probably the one that came out most immediately was to have a meeting that we called ClinAction, which was a workshop right around the time of the second Genomic Medicine workshop actually two days before that was to try and figure out what variants are actionable. How does one go about determining this and how can we do it in a collaborative way so that we didn't have 20 different groups doing it 20 different times and coming up with largely the same answers. That then led to the solicitation for the clinical genomics resource or ClinGen that you heard Eric talk about. That has led to a close collaboration with the FDA. This line is dotted so we don't suggest that ClinGen actually produced the FDA. But it did produce a collaboration with it. We also out of that developed a collaboration with the National Institute of General Medical Sciences in their pharmacogenomics research network to apply a targeted sequencing panel in the Emerge cohort that we called Emerge PGX. The second meeting led directly to the solicitation for the Ignite program. The third payers meeting is a work in progress but continues to be an effort that we're trying to stimulate. The fourth led to the Inner Society Coordinating Committee on Practitioner Education that is now led by our division of education and communication. The fifth one on federal strategies produced collaborations again with the FDA and with Centers for Medicare and Medicaid Services and also produced a trans NIH working group of centers that are institutes and centers across NIH that are interested in application of genomics. I should say that given the conversations that we had earlier today with NHLBI and others, most of the institutes are not doing implementation in clinical care. What they're doing is primarily genomics in the biology of disease and still are a few steps away from actually applying it in clinical use. So we are sort of out in front on that. The Global Genomic Medicine meeting led directly to a workshop on Stevens-Johnson Syndrome, Toxic Epidermal Macrolysis, a devastating skin reaction to certain drugs in certain genetically susceptible individuals that was identified at the GM 6 meeting as being something that we could all coalesce around and actually do a collaborative research and intervention project in. And that then led to a program announcement that was released just recently, maybe within the past month or two for serious adverse drug reactions. And this is a collaboration of about five or six different institutes. Again, these will come in as investigator initiated applications. They are simply, it describes an interest of the various institutes in receiving applications in this area, which up until this time there had been relatively few. The decision, clinical decision support meeting led to an interaction with the National Academy of Medicine's Genomics Roundtable and their Digitized Electronic Health Record Genomics Project. Our eighth meeting I referred to, and I'll talk more about efforts that are still being developed from that. One of them is Harnessing Quality Improvement Efforts, another international education efforts that you heard alluded to by Eric, and a third, developing a knowledge base of genomic medicine programs. And it led directly to the ninth meeting, the Bedside to Bench, where there was a strong push to get basic scientists more heavily involved in genomic medicine and our planning. And Carol will talk a little bit about an outgrowth of that, prioritizing genes for functional studies. We are in the early stages of planning for our tenth meeting. We hold these meetings about every six to 12 months or so. This one is going to be a good year after the last one, primarily because trying to schedule meetings nine months after a meeting in April puts you in the middle of the winter, which makes it challenging. But at any rate, what we anticipate doing is focusing on research directions in pharmacogenomics, particularly as implemented in clinical care. So we will be surveying the national and international landscape of these programs, looking for synergies and promoting collaborations as we do in all of our meetings, looking for evidence gaps and what's needed to fill them, and then designing some strategies for large-scale evaluation and implementation of pharmacogenomics and clinical care focused on the U.S. So I thought I'd take most of the time today to talk about what GMWG has been doing since the last time you heard about us, and that has been focused primarily on the recommendations from the eighth meeting that we held back in April of, sorry, that's nine. When was it? At any rate, I was in June, sorry, June of 2015. And as I said, one of the big outgrowths was the ninth meeting that you'll hear about from Carol in just a moment. But in addition to engaging basic scientists, we also were encouraged to create an implementation commons for sharing tools for implementing genomic medicine. This was basically affected by the Ignite program, and we sort of had a feeling this was on its way. This is the Spark Toolbox, supporting practice through application resources and knowledge. Currently, it is primarily populated with resources from the Ignite program, but it accepts resources from everywhere, and we are hoping that this will become sort of the go-to place for implementation resources. We are also encouraged to develop dedicated programs for non-European ancestry populations to fill the gaps that we've talked about this morning, as well as many times around this table. A first sort of start on that was the effort in the Caesar renewal to have centers with enhanced diversity, as well as our usual centers, even those centers, increasing the diversity that they had typically provided. So this is an RFA that has now closed, but applications are in, and we'll be telling you more about them. This is just a baby step, we think, on starting down this road of trying to redress some of the imbalances in populations that have been studied and work that's been implemented, but we think it's an important step. We were also asked to maximize sharing of quality improvement projects. There was a lot of discussion about the fact that many hospitals are conducting these, and I'll talk about that in a moment, to explore joint training opportunities with other organizations and other countries, and to establish and maintain a knowledge base of ongoing genomic medicine studies. So looking at the first, quality improvement projects are conducted by many organizations. They are using this sort of model as a way of implementing genomic medicine projects. Dan, I believe the Vanderbilt project is largely done as a QI project, not as a research project. There are advantages and disadvantages to doing that, just as a definition, the Health Resource and Service Administration and the National Academy of Medicine describe quality improvement as a systematic, continuous actions that lead to measurable improvement in health care services and the health status of targeted patient groups, so really improving the quality of health care through a variety of venues. Such projects typically are individualized to meet the needs of a specific health service delivery system. They are evidence based. They're designed to improve patient safety and outcomes, and very often they're complex and multidisciplinary. Almost every hospital or large center conducts these. It's one of the ways that one demonstrates a commitment to quality, and actually in many of the sub-specialties, there's a requirement for continuous quality assessment and improvement. These are among the groups that are engaged in this area. The National Quality Forum is one of the major national groups. The ISQA, International Society for Quality Improvement, is an international group, and the AHRQ, Agency for Health Care Research and Quality, obviously funds research in this area, HRSA, helps to implement it. So these are all groups that we are working with and trying to coordinate with and doing this kind of work. We sort of started out, we thought we'd start small, by talking to having the members of the Genomic Medicine Working Group who were practicing in hospitals or working in hospitals who had quality improvement programs to contact their chiefs and just sort of ask them, are you doing anything in genomics? So what is it? If not, would you like to, and how could we work together to try to do this sort of thing? For the most part, those who were doing anything in genomics were doing it because of the Genomic Medicine Working Group members' involvement, so we knew mostly about those. But also there was a considerable interest in the potential of possibly bringing some of these programs together and not only disseminating them to other groups, but also trying to get them to coalesce a bit and improve sample sizes for actually doing some research along with the QI. So we're going to start out by organizing a small meeting to discuss the opportunities in genomics and how we can get other groups interested in those. One way would be to present genomic seminars at annual meetings of these groups. Unfortunately, their meetings have either just happened or are about to happen and it wasn't possible to get on their agendas, but that's a work in progress that we'll be following up on. Exploring joint training opportunities, this kind of came up during the eighth Genomic Medicine meeting when someone described very briefly the incredible investment that Genomics England is making in genomics education of providers who are going to be receiving basically the results of the 100,000 Genomes Project being conducted in England. This is an infrastructure building effort to actually make England basically genomically enabled for clinical care within the next three years, and it's about 25 million pounds being dedicated to this. They also have a mandate to share their information and expand internationally. In addition to that program, you heard mention of the University of Miami's Concurrent Master of Science in Genomic Medicine. This is actually concurrent with the MD degree, so students can apply and become part of it in their second semester of the first year of medical school and then follow through for four years. I think there are about 40 students now in that program across all four years, and they just graduated their first class last year. The Inter-Society Coordinating Committee for Practitioner Education in Genomics, or ISCC, is the one that grew out of the fourth Generate Medicine meeting that is run from here within collaboration with the professional societies. Jackson Labs has a number of valuable resources, including one of their most recent Precision Medicine for your practice series for education for the non-geneticist practitioner, and obviously the SHG, the college and our division of communications and education have a number of training programs, all of which we wanted to try to bring together, see where there were synergies, where we could collaborate and share materials, et cetera. So we held a meeting in August of this year that included the Genomics Education Program. They have a master's program that actually has a number of steps to reach the masters at any point in which you can kind of step off and receive a certificate. It's designed not only for physicians, but for nurses and others in the healthcare professions, and it's available online. They have a session on sequencing that's actually starting up in a week that will be available to, and you can sign up, I think, at the time I signed up, there were about 400 people that had signed up for it, and that was a month or so ago. Australia has the Australian Genomics Health Alliance, which is basically a national roadmap for the adoption of genomics and clinical care. They have a fairly substantial program in health education. Genetics Education Canada has this clever acronym, GECO, and they are doing something similar. This is based in Ontario, but their expectation is they will expand it throughout Canada. The G2MC that was a spin-off of our sixth genomic medicine meeting has a series of monthly ground rounds that are done by WebEx. These are a little bit challenging to do when you have sites in Singapore and India and Britain and the US, et cetera, but I think they usually happen about 11 at night in the US, in the Eastern time zone at least, and then the University of Miami's program I mentioned to you as well. So you'll be hearing more about this meeting at the February meeting. Heather Jenkins will give you a summary of it, and many thanks to Heather and Jean Jenkins, our colleague in DPCE for putting this program together. We should have a summary of it available very shortly up on the web, and we'll be pursuing a collaborative relationships with these other programs that we can tell you about in February. A third recommendation was to develop a knowledge base of genomic medicine studies. I always cringe when people say, gee, it would be really nice to have a list of all of the things that do X, Y, or Z. Many of you may be aware that the GWAS catalog started that way, that we thought gee, it would be awfully nice to have a list of how many of these could there possibly be, and they're now what, close to 3,000 of them, and show no sign of abating. So when people suggest things like this, I usually go and hide, but happily, we have Carol Bolt on our council, who said gee, you know, we do something like this in the mouse genome database, and you can have people sort of self nominate, and it would be very useful to compile information on implementation projects. It'd be a good way to stimulate collaboration and more effective evidence generation with larger sample sizes, and more generalizable approaches, et cetera. So Carol offered to help us, thank you, develop a self-nomination site with some degree of auto curation that would be modeled on the mouse genome database and on ClinVar, which has a similar kind of model. We thought we would begin with just simple project descriptive information, you know, the title, and the main aims, and the size, and that sort of thing, and then kind of go from there, see how useful it is, and how often, how much it is used. And we would also encourage submission to other databases that are better equipped to be able to handle many specifics of programs. Clinicaltrials.gov is one of them, and I would hasten to point out, clinicaltrials.gov actually has a large proportion, I think more than half, are not clinical trials at all. They're observational studies, and Geno-Wet Medicine implementation programs, whether trials or not would fit very well in there. So that's another opportunity. So many thanks to Carol, and to my colleagues, Cecilia DuPichet, who are working on that. And then lastly, one of the things that the working group has done from its inception is to identify sort of notable advances or accomplishments in genomic medicine and make these available on our website for largely for us, but also for others when people say, well, you know, what has genomics done for patient care? Well, now there's a list of them, and so if you look on our website, you can see it's divided, and these are overlapping, so it's a little hard sometimes to decide where to put them, but clinical implementation, oncology sequencing, et cetera. And then we, every month when we meet by phone, we review three or four or five papers that we think are candidates for this, and sometimes we decide, no, this isn't quite ready yet, and sometimes we decide, yes, absolutely, this should be on. So it includes papers like this one, recently published looking at CYP2C19, loss of functional leals. Dan was pointing out that this is a very nice example of what we were discussing earlier about the value of diverse populations, because the study was done in, somewhere in the Philippines, sorry, in China, I believe, somewhere in East Asia, forgive me, I'm geographically challenged, but at any rate, and they had, there's a much higher rate of variant alleles in that population, so they were able to detect a very significant impact on risk reduction in patients with TIA, the first time this has been shown, the previous positive findings have been in stent restenosis after coronary stenting. This is another one in practice guidelines from the College of Medical Genetics and Genomics on cancer predisposition assessment, a third on whole exome sequencing tests for detection of point mutations in bills, et cetera. So these are something that we try to update on a regular basis and keep them available for the community to take a look at. So I think I'll stop at that point, I would thank the many people, not only those on the GMWG, but also those who come to our meetings who participate either in person or by phone, it's always a very enthusiastic and lively group, and of course all of my colleagues at NHGRI who are involved in GMWG, and then of course the working group, so I'll stop there and be happy to take questions. Questions for Terry, to overwhelm them with progress. Yeah. What are the thoughts about training in MOOC, for example, fashion in ways that are much more massively, that have a wider reach? Yeah, so massively open online courses. Yeah, so that's, I'm not saying a course, I'm just saying using these kinds of platforms that let you, it always strikes me just from the outside that, especially for computational tools, that's so probably for experimental methods, for computational tools, this should be doable and could reach a much larger number of people. Sure, no, excellent point. It isn't something that we have explored in a large degree, and I haven't included the Institute's education efforts here, because we sort of have those in the training and education programs. We do have new Genomic Medicine T32s, but they are very standard. They are not anywhere near the MOOC model. No, and I was not thinking about MOOC as training for grad students and postdocs. I was thinking about the community of active researchers of any career phase that need to pick up the new tool, the new thing. Today they actually still either have to sit at some workshop or figure it out on their own or go to someone next door to train, and especially as you think about reaching outside the aficionados, whereas, which is where genomics is going, there's a gap there. So that's why I asked. I was just using MOOC as a kind of a metaphor almost. And were you also talking, so you just said for researchers, I was wondering if you also were implying another community of people to think about their healthcare professionals around genomic medicine implementation. Yes, and increasingly this would be the case, right, for people to be able to interpret and so on. So I think the people often think about MOOCs in the context of Coursera and edX serving the undergraduates somewhere else and so on. But even that is a misconception of MOOCs. The vast majority of people who actually use MOOCs effectively are people who are extremely well trained. They might have a PhD and a postdoc and they now want to take the cutting-edge thing and do something, and so they actually go and seek out this training because they're easy to train because they know how to study for a class and so on. And they have a huge level of motivation. I think the same would apply here. There is a lot of demand and there isn't a lot out there and there's the amount of time investment that's needed in order to make these materials well is non-trivial, but if you make the one investment and you have a platform like this and updating it is a lot easier. Yeah, well, and I might ask Sharon or Gail perhaps to comment on the report toolkit that's being developed by CSER, but while they're thinking of that, I might also mention the Genomics England effort actually does make theirs widely available and that's for all practitioners and there are several resources that our Division of Policy, Communication and Education has developed that are available that way too. Sharon, do you want to comment on the CSER effort? Well, so I think the toolkit's quite different from what Aviv was talking about and I was actually just talking with a relative this weekend who works for Merck who's doing exactly what you described. Like she has a very specific issue and she's been using these kinds of online courses for that. So it is something we haven't really thought about like in the CSER consortium or that type of thing. What we're developing is more of a point of care which will be hosted actually on the NHGRI website for practitioner information education, which is really like if you have a genomic, an exome or genome test report in front of you, what do all these sections mean? And we're like trying to be agnostic to laboratory so using all the different synonyms that like incidental findings are referred to. But the goal of that is really much more, there are more and more of these reports that are showing up in electronic health records as PDFs and I get emails from fellows or practitioners in other fields that are seeing the patient and have questions about these. So it's really designed to be kind of try to help someone walk through the different parts of an exome or genome report and then have it hosted on the web and then the dissemination will be the critical issue. But I think that the idea of MOOCs is important and one point of the dissemination is once we really get it up and test it and beta test it would be to try to ask if laboratories would include the link, for example, on their test report. That's what I was saying. We put together a MOOC like that from UCSF that ran for two years and a couple lessons I learned from it, it was for non-genetics clinicians and health care providers, not necessarily MDs, is that the impact on the international scene is even greater. This is a tremendous need for web-based learning for people that are not in three or four countries that do a lot of genomics. It's really incredible. They're the people we kept getting emails from saying, thank you, thank you, thank you for doing this. Yeah, and I think an important point right now with the data that are being collected with CSER is that CSER is a research project and it's obviously oriented toward moving into the clinical care, but that research clinical interface is thought of really differently across all of the projects. And so, while I think that what Sharon said is absolutely right, that that's what's, it's the point of care, and several of the studies are looking at the ways that non-genetics clinicians are grappling with the information. There's also the issue about what the participants, how the participants are responding and what they do and what they think about the kind of information that they're being told and the reports that they're being given and sort of who's in charge of that because I think a lot of them then take those right back to other practitioners. So there is also that participant slash patient stakeholder, if you will, who's in there and complicates things. Aviv, the other thing worth mentioning is what Terry's representing through this genomic medicine working group, of course, is sort of the extramural research programs, portfolio around genomic medicine. The other place at the institute, and you heard me talk about it in some of the slides in my direction, the other part of the institute that thinks a lot about healthcare professional education, engagement, also general public is our two different branches within the Division of Policy Communication Education, which is not part of the extramural research program. And there are a number of things brewing there that probably are premature for me to talk about quite yet, but I wouldn't be surprised if in the coming months or future council meetings, which might be able to capitalize on some of the ideas. In fact, it's probably more, I mean, if we needed to have research done, it probably would be done within the context of this working group, this council, and so forth. But if there are things that could be done that would just need to materialize or lead it or catalyze whatever words you want to use, it would be, I'm sure, a partnership that would certainly involve Terry's branch, I mean, Terry's division and their expertise, but also other parts of the institute, which is like where the Smithsonian exhibition came out of other educational programs, some of our short courses, et cetera, et cetera, two parts of the other division that are quite focused on that. And as probably that, Genesis, your question is, there's an incredibly acute need for this. And so I think there's a bigger role I'm looking to see NHGRI play, and it'll probably involve many parts of the institute. I have a question for Bob. How many people did you get in your course, Bob? About 8,000, well, I'm the part. So I only have 6,500 in mind, which is still running, called case studies and personalize, but I had to advertise somehow. I agree with Aviva. I mean, it's a gigantic pain in the rear to do it. And I just sent Terry the link, and my comment was two years worth of my gastric lining went into that link. And if I had it to do again, I'm smarter now, and I know how to do it better. But I think with all the audio visual support that NHGRI has and has invested in, it seems like a reasonable thing to think about. I mean, that's what it takes. I mean, you have to have a TV studio and you have to have all this stuff, which you guys have. Case studies and personalized medicine, with a Z, not with an S. The S takes you to some Australian site. Actually, the one thing I would slightly, I think if we were gonna do this and do it well, I'm not sure it would be done internally to the institute. We could facilitate having it done. We'd probably want it done really well. It would require probably real professionals doing this, not just people in their spare time at the institute. So I also want to make the distinction between a full MOOC, which is what Dan was just describing, and I couldn't agree more. It's a huge amount of, it's just endless amounts of work to take even a class that you taught extremely well for years, and it is fully up to date and make it work in this format. But in particular for computational analytics, you could do, you could think kind of in a mini MOOC format. They tend to fall into these little recipes or steps or so on. It doesn't necessarily mean that you have to take a singular large scale endeavor, and you could still get quite a lot of bang for the buck. So if I think of something, it's just off the top of my head, like in variant interpretation, in even an administrative supplement to some of the groups that already do that so that they make a module. Not a big class, a module, a piece, but that piece explains something very well, even a tool that they already developed, such as a variant interpretation, this or that or the other. So I think that's why I said MOOC in the more metaphorical sense, not just we take our class at MIT or at Harvard or at Hopkins or something and we make it into a MOOC, which is a bigger thing to do. Okay, Dary, thank you very much. I think Teri has set the stage quite well for Carol. She's gonna come up and talk about the Genomic Medicine 9 meeting.