 Okay. I'd like to resume, please. We have still two more reports to go. The advisory council has four working groups, one of which is for genomic medicine. And one of the requirements of a working group council is to prepare, present an annual report to the full council. The genomic medicine working group, I think Carol Bult and Dan Rodin are the two council members that serve on that. Oh, we have a third. And now Pat DeBurke. Oh, now Pat. Welcome aboard, Pat. Okay. So we have three of you. So Teri is going to give the annual report for the working group. Great. Thank you, Rudy. And thank you to current GMWG members as well as several past members. Rex Chisholm is a member who was a past council member, which you didn't realize, Pat, when we put you on, there's no escape, you never get off. So we do appreciate it. Here's the list of members shown here. And then four folks from NHGRI who are involved. Just to remind those of you who may be new to our... You can't hear me. Oh, dear. All right. I'll hold it. Can you hear me now? Great. Okay. I'm Teri Manol. No. Okay. Just to remind those of you who may be new to how we kind of conceptualize genomic medicine, keep in mind that there's a very large portfolio that NHGRI has focusing on sort of discovery research, biology of disease, genotype, phenotype associations in that. And then we take that information, try to relate it to medical and health outcomes and treatments, and then figure out how to implement that. It's these latter two components that we consider to be genomic medicines. This is somewhat of a narrow definition, but we're a small institute. So this is the area that our group is focusing on. Our charge is to assist in advising the institute and the council on research needed to evaluate and implement genomic medicine, including reviewing current progress, identifying research gaps in ways that we can fill them, identify and publicize key advances. This is a question that we're often asked, well, what has genomic medicine done for us lately, and takes up a fair amount of our time, actually. We have a series of genomic medicine meetings that I'll tell you about, and this group plans them and co-chairs them, actually, on timely themes to facilitate collaborations and coordination, and then explore models for infrastructure and sustainability of these efforts. The notable accomplishments is something that we do on monthly conference calls, and in between we ask members to sort of send us papers or announcements that they feel are worthy of being cited in this way. This is our division's webpage, and on it is a site that shows genomic medicine activities. And if you go to notable accomplishments in genomic medicine, it's sort of the first bullet below that, and if you click on that, you'll then get a series of papers, links to papers that are broken down into these six areas, and then a variety of papers that we basically try to identify things that we feel are ready for implementation or could change practice or should be used to change clinical practice. So many things that are foundational are not shown here, but will be once their value in clinical care becomes known. Just a couple of examples from pharmacogenomics. This is actually from Singapore. Their health agency tailoring recommendations to reduce severe cutaneous adverse drug reactions. The New England Journal just recently, genetic and pharmacologic inactivation of Angptl3 and cardiovascular disease. Papers like that are we put into this list, and you're welcome to take a look at it. The group also plans a series of meetings that we use to try to identify research areas and other gaps and priorities that we might like to address. Our first one was held shortly after the group was formed, actually shortly after our strategic plan was published. When we got together, as many groups as we knew of that were doing implementation of genomics in clinical care, we then actually published a paper from that that kind of gave a road map for how one might go about doing this kind of work. Our second meeting was to build collaborations. We had a third with stakeholders, a fourth on physician education, and you can see each of them sort of had a topic or an area that it focused on. The most recent one was just this past early May research directions and clinical implementation of pharmacogenomics, and we're currently planning an 11th one for next April. These meetings are also figuring prominently on our website. You can see just below the notable accomplishments. There's a site that shows them all with the dates. If you click on this one, it brings up the webpage of the meeting, and you can get the meeting summary, an executive summary. If you don't have the patience to read the meeting summary, tweets. This is actually from this particular one, a resource that we heard about during the meeting that was presented, and it didn't have a home, and so we offered to host it until they could give it a home. And then much as we do for the council meetings, are all of the presentations, the topics are available, and they're a video cast and web archived. The group has published, as I mentioned, a paper from its first meeting that kind of gave a road map for genomic medicine implementation. The second meeting actually was the in between meeting that we held growing out of the first that described the need for a resource that eventually became ClinGen, as you can see here. Our fourth meeting focused on education of practitioners, and we ended up with a commentary on genetics and medicine on the role of professional societies in education and genomics. Global implementation came out of our sixth meeting. The ninth meeting that Carol kindly chaired with me on bedside back to bench was published in Cell just recently. And we have our tenth meeting. There's a paper in preparation from that. So it keeps us busy, but also we think is a productive effort. And then just kind of showing things that have grown out of our genomic medicine meetings. The ClinAction group, as I mentioned, came out of the first meeting that eventually evolved into ClinGen and now has a partner in the FDA called Precision FDA that we are working with and sharing information with. We also added pharmacogenomics. You heard a little bit about earlier today from Rex into the Emerge project. Our second meeting, about six months later, was focusing on collaborative programs. And from that almost directly grew the Ignite program, the first phase of it. Our third meeting was focusing on payers. We had a subsequent meeting with payers that was a little bit challenging to get to everybody on the sort of same page in terms of what we might be able to do together. But from that, we've been able to develop a collaboration now with Optum in United Health Care who actually, we reached out to try to get them more engaged in some of our work at the recommendation of some of the planners of the Pharmacogenomics meeting. And I'll tell you a little bit more about those efforts in a moment. The fourth meeting, as I mentioned, on education produced the Inner Society Coordinating Committee for Practitioner Education in Genomics, or ISCC, as we call it. And you heard a little bit about that this morning. The fifth meeting was a federal strategies meeting, again, trying to bring together the various agencies, particularly of the Department of Health and Human Services. But also we engaged the Department of Defense, many of the medical leaders in DOD who had a growing interest in this area, as you heard earlier from Wendy. Our sixth meeting was of global efforts at implementation. From that grew a genomic medicine collaborative that was sort of incubated by the National Academy of Medicine. We held this meeting in conjunction with. From that, we went on to have a meeting on, whoops, uh-oh, something bad happened. OK, a meeting on Steams Johnson syndrome, toxic epidermal necrolysis, and particularly efforts in other parts of the globe in Southeast Asia to implement genetic screening and prevention of that condition. From that, we then produced a program announcement in serious adverse drug reactions. We've also recently asked the global genomic medicine collaborative to lead a summit of international cohorts based on a request from the heads of international research organizations, or HEROS, as Eric mentioned earlier this morning. Our seventh meeting was on clinical decision support, led to a collaboration with the Digitized Consortium, also part of a collaborative, also a part of the National Academy of Medicine's efforts. Our eighth meeting was actually an overview of sort of all of our programs. We wanted to step back and kind of see where we are and where we're going. We heard at that meeting and learned about efforts building on the Genomics England program, which is an implementation program that was established by David Cameron when he was prime minister and has grown into a 100,000 genome project. This is the health education effort, which we were encouraged to try to collaborate with and develop joint educational programs with, which we are working on with the ISCC. My apologies. And also, the NHS England, which is the parent body for health education England, now has a chief medical officer report on genomic medicine implementation that we are going to try to leverage off. And I'll tell you a little bit about that in a moment. And then our ninth meeting, I mentioned the 10th meeting. I'll go over a little bit more what has happened from them. So from the ninth meeting, the bedside back to bench meeting, the idea was to particularly focus on variants of unknown significance in clinically relevant genes and figure out ways that we might be able to determine how important those might be clinically. So one of the key recommendations was at least let basic scientists know what the clinically relevant genes are so that they could be prioritized for functional studies. And there were a variety of ways of doing that, but we recommended some in the cell paper and at the meeting. And then encourage development of high throughput assays and animal models from these genes. And I was delighted, Jay, to see this paper that you're a key member of that was actually just in last week's or this week's American Journal of Human Genetics. Lee Sterida and Doug Fowler were both participants in our workshop and were key contributors in that. And basically, they proposed approaches to doing high throughput screening for testing variants of unknown function. They proposed in this paper, multiplex assays of variant effect, or MAV, and describe a couple of technologies for doing that. And then set a goal for genomics should be to develop a data-driven prediction for every variant in every clinically relevant gene, which is they're not thinking small, which is good, but also something that we would see as being quite important if it can be done at scale. In addition to those, we were advised to develop larger reference variant databases linking to phenotypes, much like the NOMAD and the one that preceded it, which I can't think of the name, but you know what I mean, the Exxon 1. And develop, yeah, y'all know, development adopt standards for phenotype description and data sharing and promote cross-disciplinary understanding and opportunities for interaction. This is one of the toughest ones, because people already go to a whole host of meetings and trying to get them to come to more is even more difficult. We do try to include basic scientists in our clinically relevant meetings, in our pharmacogenomics meeting, for example, and in other similar meetings. So hopefully that effort can continue. For our 10th meeting, as I showed you the website of it here, the goals were to survey national and international landscapes of research programs in implementation of pharmacogenomics, sort of where are we, how did we get here, review current advances in clinical applications, and then discuss limitations and obstacles to that clinical implementation, identify evidence gaps and studies to address them, and then discuss potential strategies for a large-scale evaluation and implementation of pharmacogenomics in clinical care in the US. We recognize that there are studies of this on a large scale going on in Europe. And we're hoping that something similar might be possible within the US, at least in a way that would not conflict with what comes out of other studies has happened to us, unfortunately, in the past. Other prominent recommendations included identifying minimum quality standards for pharmacogenetic testing because the standards currently vary quite a bit. One doesn't know when a given gene is testing. Are they testing only a single SNP? Are they testing multiple SNPs? Are they sequencing it? If they do, to what depth, et cetera. So coming up with standards for that, and there was interest among the professional societies in doing that, developing an improved coding system for genetic testing that could conceivably augment or even replace the CPT's current something. Procedural terminology, thank you. Codes of which there are only 200 to cover all of the genome, which clearly is not a workable system. We had strong encouragement from the payer side to try to do this, since it's almost impossible for them to know with 200 codes even what they're paying for, let alone whether it works and whether they should be reimbursing that. And the suggestion came up maybe basing that on NCBI's genetic testing registry, and we're looking into the possibility of doing that. And then possibly encouraging development of plug-in modules for electronic medical records, for drug gene interactions, much like the drug-drug interaction software that's currently available, hopefully a little bit better than that, because sometimes it can be a little bit cumbersome. But if we can promote that kind of development, and particularly building it on solidly founded guidelines, that was felt to be a high priority as well. So and then a number of others trying to reuse data from genotype data in prior trials, creating registries. One that we do struggle with a bit is that when we bring groups together, we're in a bit of an echo chamber. We have sort of all of the positive folks, but sometimes not the negative folks. And so we really, when we discuss the potential for evidence generation through randomized clinical trial, this was the group of folks who said it's not ethical to randomize people, because we know this makes a difference. Obviously, when you do a clinical trial, you need an equal number of folks saying it's not ethical to randomize people, because we know it doesn't make any difference. And so that's the area, the point of what's called clinical equipoise. We need to get some of those skeptics in the room. And so that was a suggestion to try to examine how we could do this kind of study. And potentially consider approaches such as a staggered rollout, where even if you're a believer, you can't possibly roll this out into every clinic in every site all at once. And so if there were some timed or phased rollout, particularly if that was done in a somewhat random way, one could then compare early rollout folks to the later rollouts as control. So things that we're talking about and hoping to try to pursue. And then we have a few irons in the fire. Collaborating with payers, as I mentioned, Optum and UnitedHealthcare. I've made two visits to us so far, and I've been to at least one of their seminars and another coming up. We would like to develop a collaborative evidence generation project. They have a huge, huge database. They don't have the greatest genetic testing information, as I described, but they do have the opportunities to try to make that better. And potentially working with them to develop a revised genetic testing coding system, promoting genomic medicine through common policy and public engagement opportunities that they have not only within their system and their physicians, but also with other payers. And they are particularly interested in having something that would engage other payers, as are we, because we don't want to just be working with one group, accessing their data for the outcomes of genetic testing and getting their advice. And the advice of others, similar stakeholders on compelling outcomes and other aspects of design of implementation studies. So when we do an implementation study, if we came up with this finding measured in this way, would that be convincing to you? And if not, what is it that would be convincing to you? So trying to pin them down a little bit on that. Several members of the group have also worked with the National Quality Forum and groups like that to try to define quality measures that could be implemented into clinical care. As you may be aware, there are a variety of metrics that hospitals and clinicians are measured on. Do you vaccinate patients for pneumonia? Do you prevent bed sores? A number of things. And could we get some of those kinds of measures into national quality standards? This is a long and painful and very expensive process to do and involves evidence reviews and evidence generation as well as agreeing on standards and ways to collect them. But it's a discussion that we've started. Rex Chisholm and Mark Williams in particular, and Al Pat is getting enmeshed in these discussions as well. Trying to present to them some areas that we feel really are ready and should be implemented clinically and used as quality measures, such as tumor-based screening for colorectal cancer patients for Lynch syndrome, followed by cascade screening in relatives to the degree that a health care system can do that, BRCA1 or 2 testing in all ovarian cancer patients. This was something that was proposed. And in breast cancer patients meeting certain criteria, again, followed by cascade screening, possibly genetic testing in patients with sustained elevated cholesterol levels with cascade screening, pharmacogenetic testing. These were the ones that seemed to our group to be sort of at the, with the highest level of evidence and the easiest, quote unquote, to implement. And in working with the NQF, they are considering them, but their consideration process takes a while. And so we will continue to push with them on this. And then the possibility of an evidence generation project building on a system that's already going to be implementing anyway. So why not try to take advantage of that? This is the generation genome report from the chief medical officer of NHS England, Dame Sally Davies, came out a month or two ago, and Jeff Ginsburg highlighted it for us and said, gee, they're already implementing a huge number of things. Can we not build on that to learn a little bit more about what works and what doesn't? Recognizing there are major differences between the health care systems, but there are also some similarities that we could work with. So they are planning to roll out genomic medicine services based on what they learned from Genomics England in early 2019. Could we put an evidence-generating research project on top of that? Looking at not only clinical impact, but public engagement in education, the impact of provider education, which they are doing far more effectively, I think, than anything that we've seen here in the US, and feedback from providers, and then policy and regulatory strategies. So hopefully these conversations are ongoing, and you'll hear more about that soon. And with that, I'd like to thank everyone at NHGRI, who's very heavily involved in all the things that make the Genomic Medicine Working Group work, particularly, of course, the Genomic Medicine Working Group members, and then the members of our Genomic Medicine programs and their investigators. So thank you. I'll be happy to take any questions. Questions for Terry. Crystal Clear? Yeah. Thank you. Didn't get enough caffeine. OK. All right, thanks, Terry.