 All right, why don't we come back into session? I'll turn this over to Rudy to introduce the next two presentations. Right. So we have a couple of concepts to present to Council, and I'll just remind the Council members that before an Institute in IH can release funding opportunity announcement that has dedicated funds associated with it, the concept has to be approved by an advisory committee in an open session, something that the public has access to. NHGRI always uses the advisory council, and that's so that you guys always know everything that's come across the transom here. So we'll have a presentation. There'll be an opportunity for discussion, and when the discussion is completed, I will ask for a vote from the Council. I'll be asking you to approve the concept. So the first concept is for the Center for LC Resources and Analysis, and it's going to be presented by Nicole Lockhart, Division Director in the Division, sorry, Program Director in the Division of Genomics and Society. Madam Division Director, go forward. I know. I was excited. Maybe you had inside information. I didn't know. Good afternoon, everyone. I am presenting on behalf of a team from the Division of Genomics and Society. So over the past year, we have gathered feedback both informally and formally on challenges within the LC research community. Overall, these challenges can be categorized into two general areas, access and analytical. In terms of access, we have heard from multiple distinct groups that LC research findings are often less known and used outside of areas where NHGRI is a central influence, despite potential broad applicability to other research areas. Accordingly, the implementation and policy relevance of LC research may be under-realized. Although measuring such impacts is challenging, researchers, policymakers, practitioners, and the media could stand to benefit from LC expertise, but they often don't know where to turn. While the diversity of disciplines and methodologies used in LC research is a strength, it also results in LC research studies being more difficult to locate. There is no established means of sharing LC research data, tools, or products. Further, the wide range of methods used in LC research leads to publication in a wide variety of journals, with currently over 400 different journals represented in our LC database. Finally, there is no single society or meeting outside of the LC Congress, which fully captures the breadth of LC research. In terms of analytical challenges, the breadth of methods can make cross-study analyses difficult, and it can be particularly challenging where studies employ methods from different disciplines. Systematic synthesis of LC findings across studies from different disciplines would be valuable and could serve as a state of the field on a particular issue. Our methods assessment could improve rigor and study design. And as you are all aware, NIH has a renewed focus on rigor and reproducibility. Making measures and instruments publicly available and easily located would improve rigor, reproducibility, efficiency, and access. After an initial consultation with the Genomics and Society Working Group of Council about some of these challenges in the fall of 2017, the LC program held two public webinars in March to gather broader feedback. The webinars were attended by approximately 80 participants from across the full spectrum of LC research in terms of discipline, career stage, and mechanism of NIH funding. Participants urged ongoing and increased collaboration between LC research, genomics, and other fields of biomedical and clinical research to ensure that research findings are translated into meaningful outcomes. Most participants supported the general idea of broader sharing of instruments, measures, and tools utilized in NHGRI-funded LC research. Such an effort was viewed as a means of increasing multidisciplinary research, rigor, reproducibility, and transparency. Sharing was also seen as particularly important for trainees or new investigators who may still be building their collaborative networks. However, opinions about sharing primary LC data were mixed, with some participants favoring increased data sharing using existing resources as a means of increasing transparency and rigor. But other participants were unsure of whether such sharing would be worthwhile, particularly for qualitative data where the context of how the data was collected is very important. Support was also heard for efforts to summarize and or conduct meta-analyses across LC research, either focused on a particular topic or to summarize findings in genomics LC for potential application to other fields. A combined executive summary from the two webinars is currently available on our LC website. The purpose of the Center for LC Resources and Analysis would be to provide LC researchers with an established platform to share their research tools and products related to genomics, to serve as a resource for curating and synthesizing research on key topics in the field, highlighting new findings and providing access to these works, and to convene LC researchers for both small and larger scale transdisciplinary projects and meetings to develop a more synergistic and integrated LC research community. In regards to the first objective related to resource sharing and coordination, the Center will provide LC researchers with established and stable platform to share their research tools and products. The Center will collect, index, store, and make publicly available data collection instruments, data dictionaries, and study methods from NHGRI funded LC research and ensure appropriate annotation of such resources. Further, the Center will track and maintain a central database of LC scholarship and its products, including journal articles, books, websites, tools for genomic researchers, and clinical and educational interventions. The Center will collaborate with the NHGRI to identify and prioritize research tools and products for inclusion. And where appropriate, the Center will collect and coordinate information on how to access data from NHGRI funded LC studies, including data that is shared through existing repositories or resources. However, the Center will not serve as a repository for primary LC research data as these data tapes are too heterogeneous to be effectively aggregated at this point. The Center will conduct usability testing and evaluation activities to assess the ongoing needs of LC and genomic investigators and other relevant stakeholders to improve utility of the Center. The intent of such testing is to ensure that the diverse set of potential users are able to find, access, and effectively use Center resources. All resources and tools developed by the Center will be portable and easily transferred if needed. In terms of the second objective related to data integration, synthesis, and translation, the Center will also serve key analytical functions, including summarizing LC scholarship via meta-analysis and literature review, integrating and synthesizing LC research data to identify areas of consensus, disagreement, and research gaps. And they will conduct or organize methods assessments to improve rigor and reproducibility. Finally, the Center will coordinate and support convening of LC researchers around common issues. Examples could include planning and executing the biennial LC Research Congress. Organizing topic-centered webinars, workshops, or meetings generating scholarship. Such activities could be focused on particular areas identified through the Center's data to integration and synthesis activities, or on more general topics related to methods or translation of findings to policy. The Center will also facilitate LC scholars' response to current and emerging issues. This function will help address two phenomena, the lag time between the time issues emerge and results from investigator-initiated research are published, and issues being raised in the media or policy circles that LC research has previously tackled. These activities will combine to help build a more synergistic integrated LC research community and in some cases to broaden the LC audience. As a means of achieving these objectives, the Center will develop and execute an outreach and engagement plan to help bring LC research and center products to the widening set of potential users. In order to be successful, the Center will need to effectively engage diverse expertise and end users. This plan should include innovative strategies to encourage and incentivize participation in the Center. Such participation would include contribution of tools and resources, access and use of such resources, and participation in center activities related to synthesis and integration. Their plan should also describe how they will connect LC researchers more directly to one another and to the Center itself. How they will ensure that genomic researchers, practitioners, trainees, funders and policymakers are aware of relevant NHGRI funded work, both past and present, and inform the LC community about the expanding genomic landscape. In terms of scope, while LC research is relevant to many fields of clinical and biomedical research, the scope of this Center will focus on LC research related to genetics and genomics. The Center will initially focus on NHGRI supported research as activities ramp up, but collaboration with international LC research efforts related to genetics and genomics will be considered in scope, particularly as the Center matures. The Center will also provide broad access to tools and products, including to researchers outside of genomics, in order to encourage the application of LC findings to other areas of science and medicine. Regular input on center activities will be provided by an external scientific panel with diverse expertise, including quantitative and qualitative research methods, outreach and engagement strategies, and data management and analysis. The external scientific panel will help assess milestones and ensure that the needs of the LC research community are considered in an unbiased and inclusive manner. The proposed Center would bring together LC research tools and products from across NHGRI, including from investigator-initiated researchers, the Centers of Excellence in LC Research, or SEAR program, and relevant consortia. And the Center would add value by further synthesizing and collating research on key topics. The Center would provide more equitable access for a broad spectrum of LC researchers, which may be particularly valuable for trainees and new and early-stage investigators. The Center would increase the availability and visibility of LC products and resources to other relevant NIH programs and international genomics efforts facing similar issues, and would serve as a key convener and source of expertise for the larger research and policy communities. While this Center would not replace existing NHGRI coordinating centers that are meeting the needs of specific programs or consortia, it would provide a central resource of LC tools, products, and expertise that could be consulted by and coordinated with other NHGRI consortia. We are currently envisioning a single U24 award starting in FY19. Total costs will be limited to $6 million over a five-year budget period, with annual, total annual costs not to exceed $1.5 million a year. We're envisioning that the annual budget will be less in the first two years as the Center ramps up to full functionality, and structuring the budget this way will hopefully allow some flexibility while still putting a cap on total costs. And we are currently in the process of consulting with other institutes and centers about possible interest or co-funding. This concept was developed by the whole team within our division. I would particularly like to thank Joy, Larry, and Dave for all of their help throughout this process. And our outgoing program analysts, Aaron Curry, was essential in developing a landscape analysis for us early on in our executive summary from the webinars. And our analyst, Maggie, was essential in making sure our webinars ran smoothly. And both of them are off to medical school, and we are very proud of them. I'd be happy to take any questions or comments you might have. Yeah, this is a wonderful idea, so congratulations on putting this together. Really only a couple quick comments about this. I think you've done a nice job in sort of assessing community needs with the outreach. So I think the process has been appropriate to put this thing together. Seems to me the main challenge is going to be outreach to those communities that are less typically integrated within the existing LC community. Everybody in the LC community is going to know about this sort of thing pretty quickly. It's those folks who are yet to be pulled in, the philosophers and sociologists and different people who will have to, you'll have to think about a creative marketing scheme for them. I agree with the notion of no primary data in the data set, but with some discussion about how primary data ought to be shared or more easily shared among investigators, certainly would be part of perhaps the center's activities. Any other idea I had with this with maybe a bit of a wild hair, but it seems to me a lot of folks coming to the LC world don't have a lot of genetics background. And a lot of the LC issues are pretty contingent on some of the subtleties of the technologies. And you want these folks to get up to speed as quickly as possible. So whether this might also serve as a resource for sort of educated descriptions of emerging technologies that make folks aware of strengths and weaknesses gaps with existing technology. So where would I go if I were a philosopher to learn a little bit more about CRISPR-Cas9 and how that, what is that thing and how do I understand a little bit more about it? And that enables them to be perhaps more educated in some of these issues, as well as to serve as an educator for others within their disciplines to have the tools, the illustrations, the concepts. So just an idea. Thank you, Jeff. I think we definitely would view this as kind of a bridge between the LC research community and the genomics community and some of that communication going both ways. I think the idea of what role it should play in terms of education and outreach is a really key concept and that's something we'll think a little bit more about in terms of how far we want them to push in terms of education. We do have a concern that we don't want their scope to be too broad when they're first getting started, but I think you raise an important issue that we can think about whether we should do that within this center or in some other way to help those who want to get engaged in LC research but maybe haven't had much exposure to genetic, to genetic surgeonomics, how to get them up to speed. I think that's really valuable. Yes, Gail? Yeah, I agree with Jeff. I think this is a really, is a much-needed initiative. I think you've covered an awful lot of topics and issues that I might have asked about. I'm thinking about how it'll look in a couple years and the role of expert advisor seems really important there because on the one hand, and I guess some of my experience with tools. Okay, so let me step back. I would like you to give some examples to the group who are not intimately thinking about tools, what different kinds of tools you mean. But one of the things that I, because I had the privilege of being part of our CSER 1.0 project at UNC, was working with a group who were not mandated to harmonize the tools of, let's say, trying to assess psychosocial distress upon hearing negative, positive, uncertain, genomic results from their sequencing. And then there were, you know, a lot of people have favorite measures. So then, you know, I think in the next round with CSER 2.0, there's been more of a mandate to say, you know, there really are some better and some worse ones. And regardless, it's crazy to have all these studies go on and not use the same measures. So, but that's embedded LC that's, those are projects that are, you know, that really are supposed to work together. And at the other end of the spectrum though, you know, you've got R1s or R21s that are, you know, innovation testing, et cetera. And I guess I'm wondering, I'm a little worried, but I'm interested in the question of the authority of this group. To say, you know, this is, you know, what you're using that is, you know, isn't scientifically valid. Would they say that to somebody who's like trying to, who's got a favorite tool? So one big question is the extent to which the second part of your data integration synthesis and translation part, which has this capacity, I think, to really offer advice about what's good and what's not good. How do you really quiz people and inform consent? You know that there's never going to stop being debates about that. So, so in the interest of trying to harmonize what, you know, what people are using, in the interest of saying, you know, 20 years ago, we've looked at that there's a lot of papers, you just don't know about it because you're too young, but it, but in, but I would just say, you know, there's some things about which there's going to be real debate and disagreement. And, and where would the room for that be in, in having a center like this? Because I think that might tend to alienate people not in the LC community. If they're not somehow, if that isn't sort of articulated as part of the objective, bring in opposing views on, you know, on methods, on tools, et cetera. Oh, okay, just a little too long, sorry about that. So this is something we've talked a lot about Gail, is the right balance here. And I, what we're currently thinking of is that this group would not necessarily serve as the arbiter of the right measure or the best measure, but I don't think I'm doing that. How many of I keep talking? Okay, so, but instead would collect those measures. So maybe instruments, maybe surveys, maybe interview guides and describe how they had been used. This tool was validated in this specific population for this reason. And describe how it had been used. Maybe you used a validated measure but made some adjustments based on your patient population, based on the community you're using it in. So would describe that, so it would be a resource for someone who's trying to figure out I don't know which scale to use for anxiety. I wonder if anyone's ever tried this in a similar population. In terms of the second objective, there we're really trying to think about some of the issues you raised, things like return of results or informed consent where there's a large body of work, but that data covers so many different disciplines and methodologies in terms of, you know, there might be legal data, interviews, focus groups, surveys in different populations. We know there are some gaps, maybe there are some populations that haven't really been studied, but we know there is some overlap. So trying to kind of in a systematic way look at ourself as a field and say, you know, what have we learned and where do we still need to go. Okay, so one more point and that is about the audience. So to a certain extent, do you see yourselves as being the audience of this? And so to answer the very question you ended there. I think we could be a potential audience. I don't think we're the main audience because even there with research gaps, one approach would be for us to write an RFA, so we need research in this area, but another approach would be R01 investigators could look at that resource and say, I never realized there was this key gap and I'm perfectly situated to address it. So we would be one audience, but I think we aren't building it for ourselves. Hopefully, I think there'd be a lot of other audiences, both the people currently in the LC research community and then as kind of a secondary goal, others who are maybe in a peripheral research area or others at NIH. NHGRI is really the leader in terms of funding LC research and bioethics research and we want to help our colleagues at other institutes and center fund work that's relevant to them. Yes, Rudy? So at the webinars, did you get an indication of who the users might be? In other words, did anything come out of the webinar that would indicate who the audience is for this? I think the people on the webinar, which were largely LC grantees already, but they were from a wide variety of backgrounds. So we had people who are current SEER investigators, R01 investigators. We had a lot of representation from trainees and a lot of them said pretty vocally, this would be really useful to me. Everyone is good about sharing, but you have to know who to ask. And when you're just getting started, you don't always know who to ask or you hear maybe someone did a study or has a tool. But so I think we did hear from a lot of the people we would view as potential users. I could. We also heard of a need for this from some other NIH program directors from different ICs. One of them, I forget, I won't say which I see it was, said they've been at meetings at scientific meetings and someone will stand up and say, someone should look at return of research results. Someone should study informed consent. And they have no idea that there's a whole body of work that would be relevant to them. So they were also saying, we know you exist because we are in contact with them, but our grantees need to know that this exists and find a way to learn more about it and to apply it to their own work. So, Nicole, I'm just very, very supportive of this. As you said, none of it. We don't need to reinvent the wheel and this just improves the efficiencies. I just, this is I think well set up as a U mechanism in the sense that one of the things is I think anyone on the outside continues to need to work with program staff a lot to continue to understand both throughout NIH and to be able to understand the programs that are going forward. So I hope it ends up being, you know, a very interwoven program in terms of program staff working with whoever does get the grant. Yes, we would certainly be involved. We will rely on them for a lot of expertise, but in terms of connecting them to different groups. That's, I think that's where we would see our role. So thanks, Nicole. I agree with primarily with what Jeff and Gail and Wendy have just said. I'm very supportive of this. I, you laid out a very clear rationale. I just had a couple of questions. So one thing was the emphasis on meta-analysis and synthesis, and yet primary data are not going to be shared. So if you could just say a little bit more about sort of what you'll be conducting these analyses on, and then really the rationale for not, it seems a little counterintuitive that we encourage data sharing and other aspects of genomic research, but here we're saying no primary data. And then my final thing was around the external scientific advisory committee, which obviously the merits are clear, but I'm wondering if you also thought about including representatives of the public or patients on that advisory committee. So those are my questions. So in terms of the primary data sharing, this is something we talked about with the genomics and study working group and both of the webinars and leaving it very open, so we weren't going to bias anyone. I think some of the reasons we are not currently thinking of doing that is there are repositories where you can share LC research data currently. They tend to be discipline specific, so they aren't really integrated. We didn't want to replicate those activities by having to build something that would work for all the different data types that our investigators collect. We didn't think we were necessarily the experts in how to do that, and we weren't sure if we'd be able to do it effectively. So instead we're taking the approach of encouraging sharing of data and put your data where it makes sense for you if you're a qualitative data researcher and you want to use this resource over here, that's fine, just tell us so we know. I think the other thing we heard pretty strongly from a couple different people is concerns around sharing qualitative data in particular that it's harder to share because it's very difficult to de-identify, and there was seen to be fewer potential uses for resharing or re-analyzing that data because the context of how it's collected is so specific, and someone coming in from the outside may not really be able to understand enough about the particular situation to really analyze it. With that being said, we are funding currently an R01 to Jim DeWa at Washington University who is looking at qualitative data sharing practices, and how to find solutions to some of those challenges. So that's something we are interested in. It just didn't seem like something we could kind of realistically do right now. In terms of the meta-analysis and synthesis, I think you raise a good point that that will be harder without primary data, and so for some of those activities we might need to try and get primary data or work with the investigators whose data is most relevant. I think it probably will be kind of case dependent, depending on what the particular issue is, and in some cases it might just be kind of collating. Here are particular studies that are very relevant to a certain issue. There's not always going to be specific, this is the finding from the research, right? It's usually more nuanced than that. So I think that will be a challenge of how to do those analyses, and that is something that we of course will want, if this moves forward, we would want potential applicants to describe how they propose to take that challenge on. In terms of your third question about the external scientific panel, we've kind of only roughly talked about who we think should be on that panel. I think we could think about whether someone from the public would play a role. Is there a particular expertise you're thinking of, or a particular viewpoint you're thinking of? Yeah, I mean ultimately the results are going to be of greatest importance to the patients and the public. So I think they do have a very valuable perspective. Certainly there's organizations like PCORI that routinely have those perspectives on advisory committees. They're not just on specific research teams, but on advisory committees. And in terms of priority setting, as you make trade-offs between sort of what things you are going to be focusing on as you ramp up, I think that is always a very valuable perspective. And the only other thing I'd say about the meta-analyses is I get worried about the sort of inferences that you would draw if you didn't have sort of a complete data set, right, only from the people who were willing to share. So I'm sure you've thought about all those things because I do think that one of the values of this is, to Gail's point, you know, if we've already answered return of results multiple, multiple times across studies, then I think it's about, and we don't want people to repeat the same sorts of studies. It would be nice to be able to pull together all those disparate studies and make some sort of conclusion overall, you know, with all the usual limitations of meta-analyses or reviews. That's it. Thank you. This sounds like a much-needed resource, but it also sounds like yet another knowledge base. And what are the plans for long-term sustainability and funding? I thought you might ask that. So I think, especially coming after John Lorsch's presentation, that's a very relevant question, I think the thing that we are having a difficult time with is the other institutes at NIH fund very little biowethics research. So part of where we are now is trying to spread some of that and have them realize that this research is relevant to them and they should fund research in their own areas and that there's not only ethical, legal, or social implications of genomics research. Other people need to fund this work, too. So I think we are not at the point now where an NIH-wide solution will work. We are going to explore co-funding with other institutes and we have some interest from other institutes. And we will definitely follow up on that. We are pretty proactive in co-funding with other institutes in kind of both directions because there are a lot of cases where it's sequencing of children or sequencing of cancer patients or other things that kind of cross boundaries and we are happy to work with them and also co-fund something to encourage them. At this point we are thinking of this as more of an experiment or pilot. Right now there's not very much in this space at all. So I think we are willing to make an investment for the community and we'll see how it works and where the greatest strengths are here. But that's certainly something we're mindful of. We're a small program and we can't solve everyone's problems and that's part of why we're limiting to genomics and genetics. Yes, Jeff. So a million dollars a year is a lot of money. I wouldn't anticipate that there's a whole lot of infrastructure material costs here. Do you have a sense of what a staff center would look like, what sorts of expertise and time commitments this would entail? I'm going to make Dave answer that because he did a budget for this. That's a good question, Jeff. I mean, I think that you'd need, we think we'd need different kinds of expertise. You'd probably want either junior level or research staff, faculty to help. You can imagine one designated to do sort of analytical functions, one to do organizational and database functions. And we do imagine there will be a fair number of, so maybe two full-time sort of junior staff and then we want senior staff and probably in different areas of expertise, those might not all be at the same place. But we want people to be able to commit to the leadership and the analysis that have expertise in these areas. So substantial commitment from some PI level folks, I think. And then I think the other cost that we can imagine that gets you, goes up pretty quickly and gets you there is the idea of having some, the ability to convene groups, have meetings, travel people either to the center or somewhere else to have some productive workshops and start to create broader community, tighten our community and broaden it at the same time. I think that, so the meetings kind of add up quickly as well. 10 second rule on concepts. Any other questions for the staff? Okay, can I have a motion to approve the concept? Second. All in favor? Any opposed? Any abstentions? You're abstaining, Rafa. Okay. And Dan and Aviv and Jonathan Pritchard on the phone, if you just want to email your votes to me, that would be fine. So thank you, Nicole.