 I think I drew the short straw on our committee to make the opening remarks and set the context for I think the discussion, the rich discussion that I hope we have today about whether or not there is value in all of the government agencies participating together in a coordinated national strategy for genomic medicine, if so, how we might proceed. And I thought I'd do this by maybe highlighting a couple of other nations' efforts in this regard and see if we could stimulate ourselves to think about doing something perhaps similar or perhaps even different. Do I control the slides yet? Yes. Okay. So as Rex said, I'm not going to repeat what he said about the last series of GM meetings. Just save to say that it's been an amazing 23 months when you think about it, how productive this effort has been, ranging from a real grassroots series of initiatives that many medical centers have undertaken without the benefit of federal support and now with some benefit of federal support to leading to the demonstration projects, two RFAs from NHGRI, the inter-society group that Rex mentioned, and I hope that this GM5 will be as productive as the last series of GMs and coalescing around some tangible deliverables. Being somewhat of a genome nerd, I thought I'd also put it in this context that 23 or 24 months ago, there were a number of activities going on, fairly independently, an array of genome, genomic medicine activities across the nation. And through GM1 through GM4, we've really organized these into some sort of cohesive map of activities where we recognize some common themes that cut across many of the organizations in this room. And our aspiration is that we might actually coalesce this into a more orchestrated series of network activities. I think there's a lot of potential networks that could be derived from this and hopefully will engage many of you in those discussions in the coming day and a half. As I see it, the opportunity for this group is to really think about how we accelerate the implementation of genomic medicine, genomics research findings, where it is appropriate to do so to improve the quality of healthcare, to also to create some standards where they often don't exist about implementation, about outcome measures across the various agencies that are playing in this field, and also to coordinate a number of the implementation initiatives that we'll hear about over the next day. Think about how we might engage the private sector, which has been significantly absent from GM1 through 5, and also think about the future workforce needs that we will have in order to really realize our common goals. I thought I'd discuss a little bit what the United Kingdom has been doing and the House of Lords implemented or set in motion a human genomic strategy group several years ago to articulate the UK's overarching strategy in genomic medicine to monitor the field and think about what was right for implementation to build the necessary strategies to ensure effective and efficient translation and importantly to create the infrastructure that will allow genome sciences as well as genomic medicine to take hold and also to put in place a series of national genetic testing laboratories that would help serve the needs of the British population to work on training the NHS and the UK workforces to realize these goals to be cognizant of the policy and ethical and legal strategies that would be needed and to also actively engage the public and make them aware of the potential benefits of genomic medicine and I would argue that certainly these probably harmonize a lot with our aspirational goals collectively of the groups in this room. In their report which was released in January of 2012, they put in set to motion I think a fairly bold vision that within the next seven years the National Health Service would be a dominant force in enabling genomic medicine as well as to diffuse and embrace the technologies of genomics for the betterment of public health that this type of information would be tantamount to medicine not just genomic medicine but it would be essentially practiced as medicine with a very engaged and knowledgeable healthcare workforce as well as a very engaged and knowledgeable public. Now arguably the United States is quite a different healthcare system than the UK. They have the benefit of a highly centralized healthcare delivery system in the National Health Service as well as initiatives that have gone on for many years to centralize both the data as well as the electronic medical records in that system. They've also as I've mentioned developed a number of key infrastructure initiatives to support genetic testing across the UK and probably not too different than us a very strong university system with a number of premier investigators in the genomics field as well as a key component of infrastructure which is the UK Biobank. Now the UK Biobank actually started several years before the Human Genome Strategy Group really put its plans in motion but I think it really illustrates the power and the foresight as well as the fortitude of the UK in creating such an initiative. You may recall that Francis Collins I think attempted to create a gene and environmental cohort of about 500,000 several years ago which failed to get off the ground but nonetheless the UK has started this in 2006. 62 million pounds which I believe at that time was about $150 million. They completed the enrollment of 503,000 participants in four years with highly detailed sociodemographic clinical and environmental phenotypes. They've recently committed to 10 million pounds to analyzing the genomes of series of subsets of this cohort and have also received funding to put in imaging data as part of the phenotypic data into the Biobank database and as of March of 2012 they opened up this as a resource to genome science investigators with about 20 projects now well underway so I expect that we'll hear more about discoveries about genetic predisposition, gene environment interactions from this incredible resource in the UK. David Cameron announced in December the commitment to sequence 100,000 British genomes to really enable both sequencing at scale for the National Health Service really help that service, that system understand how to integrate genomic sequencing information into its electronic record system, how it would be represented but importantly how that information might impact health outcomes. So this is very much an outcomes oriented 100,000 genomes project which I'm sure catalyze a number of other corollary initiatives both in terms of the types of skill sets that will be required to deliver on this as well as discoveries that will be made across the cancer rare diseases and other common complex diseases. Now also aligned with this is a significant investment in creating the future workforce for the UK importantly with national oversight something that I think as was highlighted by GM4 is somewhat lacking in the United States with a clear priority to deliver bioinformatic and statistical and quantitative skill sets will be needed to tackle the kinds of data that will be coming from genomic medicine initiatives and expanding the specialist capacity of genetics and genomics to both primary care as well as specialty care as well as investment in innovative learning tools to disseminate the knowledge and keep the workforce up to date. Another country that I think has made a significant investment in this as well as made significant progress in this arena has been Canada. Genome Canada was an organization started more than a decade ago both to provide infrastructure to the country of Canada in terms of genome technologies and centers that would be enabling to a variety of investigators and healthcare delivery systems. I think many of you in the room have probably sat on genome Canada review panels to help them decide which projects to go forward and which not to. And in collaboration with the C I H R which is the NIH equivalent in Canada they had put out this genomics and personalized medicine RFA last year to the tune of about $160 million of investment that would be in part from genome Canada and C I H R and in part from industry. So 17 projects were funded in 2013 roughly at $10 million apiece and these were heavily oriented towards implementation and outcomes research. So you can see here are some of the projects that receive funding this year using mutations to guide therapy for pediatric glioblastoma measuring clinical outcomes. Comparative effectiveness of different technologies for noninvasive prenatal testing. Sequencing of lymphomas to guide therapy with cost effective analyses baked in the use of biomarkers to diagnose and treat exacerbations of COPD again guiding therapy and measuring outcomes. Full-time surveillance of HIV patients monitoring drug resistance and actively changing therapies on the basis of genomic information from both the host and from the pathogen. So I think this gives you a flavor of the kinds of investments that Canada is making in specific projects that are meant to really prove the value of the clinical utility of a lot of genomic technologies that have been discovered by many, many of you in the room as well as others across the globe. Now I also wanted to take this as an opportunity to highlight a group that won't be speaking here today but I'm as well as several of you are on the Institute of Medicine's round table for translating genomic based research for health. I want to acknowledge Adam Berger who you met earlier who has been one of the internal leaders. He's a senior program officer for this round table which began around 2006 and 2007 to really begin to think about what strategies might be necessary for effective translation. As you know, any of you from working with the IOM, it's a neutral convener. It has this capacity as this group now seems to have of really bringing together many, many stakeholders in this arena from government, academia, industry as well as non-government organizations. And the charge of this particular round table was to really explore, define and maybe refine some of the strategies that might be used to improve the translation of genomic information into healthcare. We began in 2007 with three different work streams, one related to diagnostics, the second related to drug development, the third related to public health, all centered around the theme of genomics, genetics and genomic information. This is the current composition of the round table and I think you can see it's widely represented from both academia, professional organizations, integrated healthcare delivery systems, industry, some journals, the military, a very nice cross-section I think of the stakeholders that are extremely interested in moving genomics information into healthcare and healthcare delivery. As I mentioned, molecular diagnostics was one of the main focal areas. I would say that over the last three or four years there have been at least 12 to 14 workshops. I may be missing a few here that have focused on really articulating some of the challenges and barriers and the strategies to overcome them. This one was led by Deborah Leonard, this particular focus area in molecular diagnostics and you can see the products of three of the workshops that took place over the last several years, highlighting the need and the strategies for evidence generation for enforcing the notion of clinical utility of diagnostic testing as well as the path to delivery of diagnostics, particularly highlighting the regulatory coverage and reimbursement challenges and strategies. I should mention that each of these proceedings are available through the NAS website and I think if you're truly interested in receiving copies for whatever reason, you might want to talk to Adam during the break. I led the Drug Discovery and Development Genomics-enabled Drug Discovery and Development workshop or focus groups, working group I should say which has had three workshops and a fourth that will happen later next month. One about the designing the frameworks for pre-competitive collaborations between industry and academia genome-based strategies for targeted therapeutics development, the concepts of data sharing, clinical data sharing and biospecimen sharing and drug repurposing, genomics-enabled drug repurposing workshop which will take place as I said on June 24th here in D.C. The Genomic Medicine and Public Health Group which was spearheaded by Muin as well as Bluesh Blumberg and others focused on early on the implementation strategies for diffusion of technologies, understanding which genome technologies might provide the greatest value and importantly where health IT needs to be in the future as well as what are some of the economic frameworks that are important to consider in thinking about enabling genomic technologies to move to the fore. So I think one of the questions we struggle with at the IOM is what is its impact be it clearly has elevated the dialogue across the stakeholder community. There's no question about that and it has fostered collaborations, some that have actually resulted in initiatives such as the clinical trial comparator arm partnership looking at control trials from and genomic data and biospecimens from control trials of industry-led clinical trials. There have been a number of connections between the policy messages of the IOM and a number of policy initiatives even that the NIH and several groups in the room have undertaken and clearly the IOM is a resource. I would argue that one of the things we might want to achieve in the future not necessarily for this meeting is to make the IOM much more connected to many of the stakeholders and have an efferent arm of activity that might help move some of the IOM's statements forward in the field of genomics and genomic medicine. I just wanted to mention that in the coming year we're slowly disbanding the three focus groups that I just mentioned and we're going to be spending our time on conflict of interest, on education, on the notion that a health care system can actually be a learning health system for genomic and precision medicine and the processes for evidence evaluation when it comes to genetics and genomics. So in closing I just also wanted to highlight the fact that I think that what we have in the room represented by many of you is an ecosystem that's really thinking about how to optimize the synergies between one another, reduce the redundancies, and really perhaps create a more effective series of strategies when it comes to genomic medicine. And one way at least that I thought about to frame this a little bit and you can disagree is to take from the songbook of Muin who has really helped us along with the IOM and the CDC articulate what are the different barriers to translating genomics from the laboratory on the left to health care related outcomes on the right. And you can see the four traditionally now mount iconic barriers from T1 to T4 highlighted here. And I would say that each of the groups in the room is playing along this translational continuum with, for example, the NIH and NHGRI much more in the realm of thinking through how to overcome the barriers to moving the science into man for the first time, the T1 and the T2 spaces, whereas perhaps the VA and the CDC and some of the groups in ARC are really focused on thinking about how does genomics get diffused into the hands of the providers and professionals that need to know how to use those tools to treat patients as well as how do we measure, importantly measure the outcomes that demonstrate the value proposition for the entire community, not just the patients, the providers, the payers, but the whole health care delivery system as a whole. And I think one of the opportunities we have today is to really think about how to perhaps better organize this such that we as a team of federal agencies can be more effective. So maybe to echo some of the things that both Brex, Terry, and Eric said, I think what we are here to do is try to understand your issues in where you're focused in the area of genomic medicine, what are your major challenges in enabling this strategy. And then through that dialogue, perhaps achieve some hopeful consensus about whether a strategy is really the way we should coordinate a strategy is something that we should consider going forward. And if so, what would be our priorities, what may be some of the obstacles and challenges that we might choose to take on together and what would some tangible next steps be at the close of the meeting. So with that I'll stop and maybe take some questions or whatever our chairs would like us to do. Yeah, let's have some comments or questions. So, Caroline Clancy, just thank you for a lovely presentation. I downloaded the Cliff Notes version of the UK strategy late last week. And one thing I noted was that at least in the Cliff Notes version it really puts a great deal of emphasis on equity. And I would think as government agencies working together that we would want to retain that focus as well, particularly as our country gets more diverse. Yeah, and the notion of making sure that if I understand the term equity that we're not we're really addressing how genomics might create disparities in medicine. Yes, absolutely. So I was interested both for the UK and for Canada. And I don't know if you're going to know the answer and we have a lot of military colleagues here, maybe you know the answer. And those two countries, does the military get their healthcare on their own or are they part of, especially like in the UK part of the NHS? And the reason I'm asking that question is I'm curious if the activities that you describe will naturally sweep in the military or whether it's a situation like we have here where there might be different things going on in different parts of the country. And I would just like to look by analogy and try to see whatever lessons might be learned there. It's a great question. I actually don't know. Because NHGRI has had several, actually multiple conversations with different parts. In fact, some of the people at this meeting, different parts of the military to try to coordinate or just learn from each other. And so it's an area that we're very interested in. And I just wanted to see if there was any lessons that could be learned. I mean, in the UK, for example, I mean, does anybody know if the military gets their medical care from the National Health Service there? Yeah, the UK and Canada both rely on the civilian sector for the predominance of their care. So we're different in that way? Oh, we're very different. Very different. I know we're very different. But I'm talking that way. Okay, thanks. Great. Well, and if I could just comment that it seems as though in a way that the military medical systems may be a sort of a little NHS in and of themselves. And so in some way, I mean, you know, looking at it sort of from the outside looking in, even though I do practice over at Walter Reed, do you see yourselves as being a little bit more flexible and a little bit more perhaps in control of the kinds of things you do unlike trying to tackle the entire US civilian health care system? Ma'am, I would address one aspect of that is, and that is a lot of what we do is operationally related in terms of support to whatever mission. So if it relates to optimal performance under the sea in the air or on it, those are issues that we would first prioritize. And there's the beneficiary aspect, which includes the dependence of the military. And that is a much more broader spectrum of care that's provided in the MTFs. But if your question is do we target certain areas of those beneficiary care sector? I'm not aware we do. Yes, sir. Thank you. Once again, I'm John Forsberg from Naval Medical Research Center. We over the last decade or so have been collecting genomic information from wounded service members and translating that information from wound biopsies, serum, and also pathogenic information into clinical decision support models. Now, one of the main challenges we see is integrating those models similar to the challenges in the civilian community into usable interfaces that clinicians can actually use. And one of the barriers really is our electronic medical record. So maybe that could be one focus area for this group to address. And I know the VA system also has a very robust electronic medical record. And it seems to me that these would be amenable to decision support applications. But you'd be surprised as to how many challenges arise as you go forward. I think this short conversation highlights the fact that the military has healthcare delivery challenges for their personnel and their families just as much as a place like Duke or Geisinger have to deliver healthcare to their patient population. So while it's not to Eric's point, the military is not part of receiving care in the public sector as it is perhaps in the UK, I think one of the common themes we'll hopefully see is that military healthcare delivery systems are similarly challenged and have similar inefficiencies but also some great capabilities that might help inform some of the other programs in the public sector. I'd really like to echo the comment that was made about decision support and actually several other NHGRI funded projects are exploring, such as the Emerge Network are exploring exactly how do you put genomic information into electronic health records, provide decision support for physicians. And so I think there's already a common basis for some really interesting interactions. Yeah, just to continue on that theme, I mean one of the underlying principles for trying to do this in electronic health records is standardization. And it's been somewhat difficult to move at least through the Office of the National Coordinator given their priorities relating to meaningful use. Some of the standards that are going to be necessary to support representing genomic information in data warehouses that can make access by electronic health records in order to drive clinical decision support. If there were a group, hint, hint, that could actually take some of the nascent standards that have been developed by groups like HL7 and some of the others and actually make it into an operational standard, I think there would be a lot of enthusiasm beyond that to adopt since we're really desperate for standards that everybody can use which will ultimately be needed if we're going to have interoperability because the one thing that is different about genomics than most other healthcare data is that it's persistent. And so we need to have information that can follow the patient really throughout a lifespan so that that information can be reused in an efficient manner. I might also comment, as Rex did, that Emerge has been working in the space and a number of other groups are as well. But Mark, there's apparently a clinical decision support society that I just learned of but others might want to know about it. The clinical decision support consortium actually is an HRQ funded activity that is in its third and final year of supplemental funding so it is about to sunset. It's led by Blackford Middleton who's now at Vanderbilt and over the course of the last year the EHR Integration Group which is a part of Emerge has been collaborating with the clinical decision support consortium around some of the issues related to genomic medicine. Geisinger is also a member of the CDSC so I've sort of been the go-between. Interestingly enough, one of the projects, sub-projects of this clinical decision support consortium has been one related to pharmacogenomics and so I've been sitting on that group and they will be putting out a paper including some clinical decision support artifacts for two pharmacogenomic use cases and that will be appearing in the very near future since they are sunsetting I think as of the end of June. The issue there as with many of the types of things that we talk about is the sustainability. There's a lot of good work being done but then how do we keep this going when the seed funding in this case the federal government goes away? What's the business case to kind of keep this going? So while there's a lot of enthusiasm we really haven't developed a sustainability model although the hope is that with Blackford at Vanderbilt that is intimately involved in Emerge and others that we can begin to at least take some of the work that they've done and piggyback that into the work that Emerge is doing and move forward a little bit faster. It's not all about decision support either I wonder if there were any other comments from anyone before we moved on. Jeff? No thank you. Do you have something to say? Brad? Can I just ask on the as these big health systems get tied in like the UK project do you know are they also tackling the conundrum of returning results in a big research project like this? I mean we always have a little trouble. Yeah. A little too. So I cannot speak to the specifics the answer is yes but I can't tell you where they are with that dialogue and I think this will be part of you know and we alluded to the fact that there will be an international meeting coming in the fall and a number of these themes that will be brought up today I think or that you've brought up and others will be part of that discussion as well. Carolyn? I guess the last point I'd like to make on your T1324 I don't see how we get to identifying true benefit unless we have payers and others as part of this dialogue. Researchers absolutely can't do this alone and my apologies to Eric who's heard me say this before it doesn't matter how great the genomic interventions are they're going to be lost in a messed up system which is what we have at the moment. So to that extent I don't think it's too early to be anticipating what venues we might be exploiting to engage that voice. I might just add to that for information purposes that as an outgrowth of I think it was GM3 there was a meeting actually convened by NHGRI with payers that happened last October and so there is some work being done that's followed up on that. I think it's a very important point it's a critical stakeholder that we've got to engage fully or we're not going to succeed. Totally agree and we're going to hear an update on that later in this meeting and also we have the benefit of Naomi being here representing a very important pair constituency so hopefully there are at least ears and maybe a voice at the table for your point Caroline. So I just want to follow up on some of the discussion I'm glad this meeting is happening because it's taking almost 15 years where we had sort of a number of similar efforts in the past but I think the time is right because of the sequence being available. I think the issues around equity the issues around evidence the issues around payers I mean we've kind of been exploring them and you know the question I wanted to ask Jeff and others I mean how do we see this kind of interaction going on between the feds because in the past we had advisory committees like SACGT, SACGHS and it's all sort of in a way to not force but get the federal partners together because they all have one boss which is the Department of Health and Human Services and those attempts were done in the past and those committees have come and gone and now have been replaced by non-binding groups like Iowa and the groups, Newborn Screening for example which is an arm of genetics and public health have organized their world around their own secretary's advisory committee that essentially decides what tests should be included in the Newborn Screening Panel or recommended for the 50 states so you know it's easy to implement genomic medicine in the context of Canada and the UK because of their healthcare system it's much more complicated to do it here given that researchers are doing the research and payers are not paying for these services and the evidence is lost in between so one of the things we need to explore is how would that interaction look like as we move forward? Well I think that's an excellent theme for this meeting. I mean I think we recognize that there are lots of differences between the US and some of the countries that I mentioned I don't want to presuppose the outcome of this meeting but it could be something around a constitution of genomic medicine that harmonizes the various states if you will but I was really pleased that in the last meeting that we took a lot of fairly independent and potentially competing groups if you want to look at it that way and really coalesce them into a coordinating society around the professional organizations maybe we could do something along those lines but I think that's the topic for this afternoon that Rex and Eric will lead is really to take the information from this meeting and begin to drive it with a fine point on the exact issue you raised so thanks for bringing it up again. Jeff, as you and I have discussed one of the stakeholders that was central in the Canadian effort is the pharmaceutical industry and sort of an industry more broadly in terms of developing biomarkers commercializing discovery that individual academic laboratories make and it occurs to me that we have that's a constituency that probably needs to be at this table or some table and we as a GM advisory group haven't done that yet but we probably need to add that to our to-do list. I agree, I mentioned it in passing but I think we need to do more than a passing mention of it. All right, I think we should move on but this is actually a nice segue the next presenter will be Debra Leonard who's going to talk about the College of American Pythologists Genomic Policy Framework.