 Okay. So last summer, NHGRI convened a workshop to look at the research opportunities associated with the implementing genomics in practice, or what we call the IGNITE network. Major purpose of the workshop was to gather information from the research community about how the goals and objectives of IGNITE should be fine tuned associated with our intention to or at least look at the question of should we renew the IGNITE consortium. So Council Member Shanita, who is Halbert, attended that workshop and was a moderator for one of the sessions. And we've asked her to present the report to the Council. And this will serve as a staging or backdrop for the concept that Ebony Madden will next present. Shanita. Okay. Thank you. So I'm really glad to have an opportunity to share with you the discussion and outcomes of the workshop that was held to discuss the IGNITE consortium. So as you can see here, this workshop was held in August of last year. And one of the things we wanted to do as part of the workshop was to discuss the scientific opportunities for the evolving area of clinical genomics implementation and to identify and provide recommendations on directions for the next phase of research. The workshop also provided an opportunity to talk about and review the scientific contributions of the IGNITE network. So you can see here that the IGNITE network, just a little bit of background about the program was established in 2013 and really serves, I think, as a unique model for exploring the science of genomic medicine implementation. And one of the things that we all acknowledge and we've discussed in this context several times is how difficult it is for integrating genomic information into routine clinical care. And IGNITE was established to work to find solutions for how to share these solutions with the scientific community. So the network consists of diverse clinical settings and populations. I think one of the things I remember being really excited about was the diversity of the organizations which really led to a diversity of the types of patients who were being included in the workshop and the center projects, rather. The other thing I think is important to acknowledge about IGNITE is that it does provide a unique opportunity for linking existing efforts in genomic medicine while contributing to the evidence base, supporting genomic medicine, and developing creative real-world solutions. Some of those examples of real-world solutions include clinical decision support strategies which are really designed to support the integration of genomic information into the electronic health record. Some of the additional goals of IGNITE are shown here, and one is to think about and address genomic literacy, which we all know is really critical to the success of integrating or implementing genomic medicine into clinical practice. IGNITE has been dealing with the challenges of varying levels of genomic literacy among patients, clinicians, researchers, and payers. One of the ways that IGNITE is overcoming these barriers is to create educational tools and resources for these different diverse communities. It is also, I think, really leading the way in how to engage stakeholders actively. The other component of IGNITE related to that is that it's developing the evidence base for demonstrating that genomic medicine can be used to inform patient care through genotyping, sequencing, and family health history. And we really know that these are the future of medicine. So lastly, IGNITE is working to define, share, and disseminate best practices for implementation, diffusion, and sustainability. So the IGNITE network, as I've mentioned, is very diverse. It includes six demonstration projects that have sort of a hub and spoke design. IGNITE was funded in two ways with the first set of grants awarded in 2013, and the second grant set of grants were awarded in 2014. And so these healthcare settings are already integrating genomic medicine projects, mainly at academic centers, and they've partnered with adopter sites. And so they really have, I think, a unique way of thinking about how to disseminate best practices in genomic medicine implementation to diverse settings. And what's interesting is that these adopter sites have less experience with genomic medicine. So it's really not a case of, you know, the high resource institution sort of talking with the high resource institutions, it's really thinking about how to improve the performance and the delivery of genomic medicine across all different types of settings, one of which is minority serving hospitals, family practice and primary care settings, and military and veteran affairs hospitals. So there's a diversity of clinical settings involved in the IGNITE network. The Coordinating Center is currently located at Duke University, serves as the administrative core for IGNITE. And this center supports and coordinates network activities and engages with external groups to develop collaborations and develops methods for facilitating the dissemination of best practices from the network. So you can see here that the IGNITE centers are located throughout the country. And it includes 22 institutions here in the U.S. And again, emphasizing the point that it, within the IGNITE network are minority serving hospitals, family practices, primary care settings, military and VA hospitals. Non-NHGRI funded affiliate members have also been invited to join the network and develop collaborations but these non-affiliated members do not receive grant support from NHGRI. These members are really included to increase the reach of IGNITE and to represent the diverse healthcare settings. So I've mentioned that there are six demonstration projects within IGNITE that are examining the challenges of incorporating genomic medicine into healthcare settings. Just to summarize what these projects are addressing. So first Duke University is using family health history data to deliver more effective healthcare and geographically and ethnically diverse clinical care contacts. These investigators are using MeTree, which is a web-based family history and clinical decision support software platform. The software, I think, which is exciting, was developed to be incorporated into the clinical workforce of primary care providers across five different healthcare systems. And what's, I think, unique about this approach is that family health history can be incorporated into a variety of practice environments and populations. So as a result of this effort, a significant number of patients were found to be at risk for common complex and hereditary conditions. And this resulted in one in four patients being recommended for cancer genetic counseling and 18% recommended for colonoscopies. And so the systematic approach for risk assessment, we think is a really powerful tool for increasing the efficiency in the healthcare system and in reducing the overuse of expensive testing and resources. So moving on, the ingenious study at Indiana University is evaluating the impact of implementing a CLIA-certified pharmacogenomics panel for 24 widely used drugs and 14 genes for 44 variants across a large number of hospital settings which primarily serve a low-income, under-insured and vulnerable population. A quarter of those who were tested had clinically actionable pharmacogenomic variant that warranted a change in the medication selection or dose. So one of the things that has been, this has been an example of an early success. So and based on this, institutional leaders at Indiana University have made the decision to expand this model across the statewide university health system. So the guard study is being conducted at Mount Sinai in New York and it's a randomized trial that is working to determine the effects and challenges of incorporating APO-L1 information into primary care management of adults who have hypertension and self-reported African ancestry. The studies, the primary outcomes for the study includes blood pressure reduction and renal surveillance as well as secondary psychobohavioral outcomes. So participants have been really engaged in exploring the intersection of race, ancestry, genomics and chronic disease testing and chronic disease. And so among the participants who went testing for APO-L1, there was limited concern about testing in general. One of the other findings was that clinicians expressed a willingness to incorporate testing into patient care if they were equipped with the information to confidently return results to patients and to use the results as part of overall patient care and management. So I think this really speaks to some of the ELSI issues that have been raised in this, in our council meetings with respect to physician and patient priorities and preferences and concerns. Next is the personalized medicine program at the University of Florida which is using pharmacogenetic testing of cardiac catheterization patients as an approach for optimizing patient care. Patients in this study who were tested for the SIP-2C19 variants to determine if treatment should continue with collarge pill, I'm going to mispronounce that so I'll skip over it, or if they should switch to a drug to another antiplatelet therapy was warranted was as part of reducing adverse effects and the chances for readmission. So those are two really key quality indicators that I think all healthcare systems are struggling with which is reducing adverse effects and lowering rates of readmission. So this testing at this center has prompted the creation of a professional education and training programs for students and practicing healthcare providers. The personalized diabetes medicine program at the University of Maryland which as I remember it was one sort of, it was very different from the other projects that are part of this clinic but it's using a sustainable approach to detect, diagnose and promote individualized therapy for patients who have a monogenic form of diabetes by using a web-based screening tool and follow-up sequencing. So this combination of screening and testing as a result of this combination of screening and testing physicians have been able to improve the accuracy of diagnosis and reduce unnecessary testing. And so ultimately this has improved patient care and treatment. And so lastly the integrated, individualized and intelligent prescribing program which is titled I3P, I think these projects will come up with some really snazzy acronyms, is using genotyped guided prescribing in two projects. So the first one is the personalized cancer medicine initiative which provides routine multiplex tumor gene mutation testing for patients who have non-small cell lung cancer and melanoma. And then the pharmacogenomic resource for enhanced decisions in cancer and treatment is prospectively testing patients for germline pharmacogenomic variants that are associated with responses to target medications and places genomic results and guidance into the electronic health record. And so ultimately their goal is to tailor therapy to reduce adverse drug side effects based on germline and somatic gene variants of known significance. So I think all of these projects really illustrate a couple of points. One is that they have direct clinical relevance and impact on patient care and clinical management. They're dealing with issues that I think all health care systems are focused on such as readmissions and reducing adverse effects and also addressing critical, important ethical legal and social issues related to implementation of genomic medicine into practice. The other thing, way that I think this ignite has been really important is that it really has worked to ensure that there is a diversity not only in clinical sites but also in the patients that these projects are targeting. So as you can see here the majority of participants in ignite projects are white, non-Hispanic, but there's a modest number of underrepresented minority groups. One of the things we talked about at the workshop was how to address this issue and really place the inclusion of diverse populations as a priority for ignite. So some of the contributions that ignite has made to genomic medicine as shown here, first in the area of informatics, ignite has contributed to the knowledge base of how to incorporate genomic information into the electronic health record and how to use clinical decision support effectively in the clinical setting and how to effectively translate the relationship between genetic variants and phenotype. The clinical decision support knowledge base or CDS-KB is an online resource, is one example is an online resource that supports sharing clinical decision support experiences with the scientific community and this really does provide a great opportunity to reduce redundancies in developing clinical support tools and to learn from experienced groups. So there's a built-in dissemination and implementation component to ignite. Ignite has also been very active in developing the evidence base to inform payers about coverage decisions. This group has been extremely diligent in identifying the required evidence that supports the clinical utility and validity of genetic testing and working closely with the payer community. I think this is really important because ultimately where the rubber meets the robe will be the extent to which these tests are covered by payers. So Ignite and collaborators have worked closely together to demonstrate that using genetic data to guide changes in anti-platelet therapy reduced the percentage of deaths, heart attacks and strokes by nearly half. So it's really showing some clinical impact in outcomes and those are the things that we know that payers are really concerned about and interested in in terms of seeing with respect to their decision making about what to cover and how much to cover. Also Ignite has demonstrated that 60 percent of patients who had a genetic deficiency were given a medication that was more effective. So having timely access to this genetic information can reduce adverse drug reactions which we know is a significant health care cause. So lastly Ignite has been addressing the growing need for provider and patient genetic education. Ignite has worked to develop guidelines that have been developed to help clinicians communicate more, communicate genetic risk information more effectively. And then so just another Ignite contribution to the field of genomic medicine is the network SPARC toolbox which is shown here. So SPARC stands for supporting practice through application resources and knowledge and it was developed to provide real world tools and guidance for genomic medicine implementation. This resource was developed with researchers and clinicians as the primary target audience. Although many of the tools are also appropriate for patients or insurance providers. So the toolbox is really neat in that it provides access to resources that address key challenges to implementing genomic medicine through the best practices that have been developed through Ignite. So this will be released so beginning in summer of 2017. The toolbox will be one of the things that's featured prominently on the Ignite website, the Ignite homepage. And so you can check out this link here to sort of check it out and see how it can benefit everyone. So one of the things that was accomplished as a goal for the workshop was to evaluate these contributions of the Ignite projects within the context of identifying gaps and opportunities that remain. So two main questions were addressed. How do we make genomic medicine part of routine clinical care and what are the outstanding barriers and challenges to genomic medicine adoption? There were, the workshop was structured around four research topics which are shown here. Genomic medicine implementation and diverse healthcare settings and populations, clinical informatics for varied electronic health record systems, clinical evidence for genomic medicines, sustainability, and economic considerations. And so each panel was charged with discussing the state of the science and gaps, highlights and opportunities, and moderated a general discussion with the larger group. Attendees included Ignite network members, Ignite external scientific panel members, Ignite affiliate members, and scientists who were engaged in genomic medicine implementation research. So there were a total of 86 participants including six council members. And so next what I want to do is just briefly describe the recommendations from each of the four sessions. So first with respect to implementation, one of the things that was recommended is that there would be more robust collaborations between academic and community centers. And as part of this we should also support initiatives that will foster the dissemination of established best practices and strategies for genomic medicine implementation. So as we looked to moving forward, it was recommended that and acknowledged that it was vital to continue to prioritize inclusion of underrepresented groups and increase the participant diversity in its research, particularly targeting Latino and Asian patients in genomic medicine studies. So in addition, Ignite can also better focus on different types of diversity because race and ethnicity is just one aspect of diversity. And so some of the ways that we can think about increasing diversity is by considering geographic factors such as rural populations and the size of the clinics, so including smaller clinics within the network, and also considering socioeconomic diversity. Also it was recommended that in order as part of increasing access to genomic medicine among diverse populations, that future genomic medicine research should consider collaborating with health insurers and other payers. And to this end, NHGRI should consider creating a genomic resource, a genomic medicine resource center that has a formalized translation services and educational materials, or perhaps a genomics and disparities working group within the NHGRI advisory council. With respect to clinical informatics, it was recognized that one of the key barriers to clinical decision support come about as a result from organizational boundaries between institutions. So one institution, many institutions have different electronic health records. And so that leads to the development and use of different clinical decision support systems. So it was recommended that current clinical decision support capabilities be characterized. And in the future, data and informatics sources for clinical decision support systems should be harmonized via standard terminology and data exchange standards. Participants in the workshop also felt that it was critical to develop interfaces for clinical decision support systems that are capable of transmitting different types of data from many different types of vendors, and that this information should be made available to the scientific community through a public repository. And lastly, it was recommended that the future NHGRI consortia should consider engaging EHR vendors early in developing clinical decision support systems so that we can understand this variation and develop a platform that's more responsive to the diversity that exists in the electronic health record systems. With respect to clinical evidence, workshop participants noted that the value of large genomic medicine study that span multiple sites. So studies that have large sample sizes generate strong clinical evidence for the benefits of genomic medicine. So one of the recommendations within the context of clinical evidence was that future studies should be designed with specific outcomes in mind to provide evidence to a variety of different stakeholders, such as health insurance companies. Evidence of clinical utility and economic impact should also be documented. And to ensure that diverse perspectives on what constitutes the benefits and costs of genomic medicine are considered, stakeholders from health insurance companies really should be involved throughout the study. So future studies can and should contrast the tradeoffs and cost-effectiveness of standard treatments versus genomic medicine. Findings could also be communicated to a broader clinical audience, not just including healthcare stakeholders, but also different kinds of clinicians, such as nurses and residents. And finally, workshop participants recommended that developing a publicly available curated database that would be designed to collect and evaluate information stemming from genetic studies should be created to synthesize the evidence that's needed to inform decisions. And lastly, with respect to economics, it was recommended that genomic researchers really do work for the strive to demonstrate the societal and personal value of genetic testing. And this would include economic viability. And the future was also recommended that measures of societal, personal, and economic utility of genomic medicine should be developed and assessed. We all know that genomic medicine has a large number of stakeholders with different priorities, including patients and advocates, drug companies, providers, health insurance companies, and clinical labs. And so we really do believe that these stakeholders should be involved with study development throughout the project to ensure that the most important research questions and outcomes are established from the outset. So it really, we really were, there was an advocate or recommendation that a participatory approach be used to address these economic issues. Participants also noted that very few publications to date have a focus on genetics and economics in tandem, partially due to a communication gap. And this really indicates a need for interdisciplinary science, team science. In HGRI, I was also advised to establish an economic data source standards between consortium to improve cooperation and transferability among researchers. And so lastly, the downstream cost of delivering genomic medicine to patients is not reflected in the cost of genetic testing. And there were recommendations to invest in more research to examine more the hidden cost of training, information processing, and data collection. So our group is shown here. And one of the things that we did as part of the workshop was to bring these recommendations back to the group for an exercise in establishing priorities. And so these priorities have facilitated and led to the development of the concept for the Ignite II that Ebony is going to discuss next. So just to conclude, I would like to thank the NHGRI staff for their, for putting the slide deck together, particularly Heather Jenkins who is on maternity leave. We'd also like to take a moment to thank all of the participants for their really thoughtful review and engagement and the recommendations that they put forth. In particular, the meeting planning committee and the council members who took time out of their busy schedules to provide recommendations about the next steps for genomic medicine implementation. So thank you again for your attention. Any questions for Shinida? Carol. So was there any discussion about how willing EHR vendors are to conforming to common sets of standards so that information can be shared more easily? So I don't recall that there was a discussion about their level of willingness, but just an acknowledgement that this was an area that was needed and that they definitely needed to be included at the table as these new, as these systems were being developed. I think that that's an important point, you know, whether or not they would want to talk about it because I would think that there's some proprietary issues that are involved with each different type of EHR. So, but our goal, I think are the final result of our recommendations that they needed to be at the table and, you know, not just to have Epic or, you know, at the table, but there need to be others at the table, not to be disparaging against Epic. Yep. Thank you. That was a great presentation. I do think with regard to the EHR it's an interesting issue because there are only a few vendors in the big hospital systems, but there are a lot more vendors in some of the smaller hospital systems that your network probably involves. I did have a question. There seem to be quite a range of genomic testing, right? It sounded like some of the studies might only be doing a couple of SNPs that are important for specific drugs and at least one, I think, was sequencing 40 genes and another was doing a mutation panel. So, did the RFA allow for kind of that broad, I was just curious, how those very different types of projects interacted with each other? So, the RFA that supported this round of funding was very broad and allowed for institutions to put forth what makes sense from their institutional perspectives and from their expertise about, you know, what was relevant and what needed to be addressed from the perspective of genomic medicine. Yeah, that was quite a tour de force. It sounds like the workshop covered incredible numbers of topics. Was there any consideration of the overlap or ways that it might be maybe synergized with what's going on in the CSER projects? So, that was clearly one of the recommendations from the workshop that there be a greater concerted effort to harmonize across all of the different initiatives that NHGRI is supporting. CSER, I don't recall if it came up specifically, but it must have. I just can't remember that far back. Maybe Ebony can provide some insight. That is something that we are planning to do when it was brought up. CSER was going into CSER 2, so we were waiting until CSER 2 got established and we're hoping to have a joint meeting and plan a way forward together. We're actually considering having joint working groups and everything. Yeah, I would say I think that's pretty critical now between Emerge, CSER and Ignite, because now we're all really looking at measures of efficiency or the plans are all to look at some of the measures you outlined so nicely and to make sure we're using similar measures so we can go, even if we're using different patient populations, it would be really important.