 Okay, so I had the opportunity to present two initiatives that we actually presented, grew out of our efforts in genomic medicine that you've heard about over the past year or so. These come from strategic plan implementation efforts that we've presented to you in May and September. The disease-oriented genomic medicine working group that Rick and Rex have served on and Dave Valley and George Jeff Ginsburg were on previously. And then the new genomic medicine working group that Rex and Pearl are currently on. This also arises from the genomic medicine colloquium that we held in June in Chicago, which showed over 20 active genomic medicine centers at varying stages of implementation. And so we were really asking the question in June, is there anything going on out there, having heard of a few things. And we were surprised to hear how much there actually was going on. Those were supported through multiple institutional, primarily institutional, in fact, funds very limited NIH funding, although some of them have built on the CTSAs and the Clinical Translational Science Awards, and also on the Pharmacogenomics Research Network, particularly their new translational pharmacogenomics project. And what we heard was that there were numerous, relatively similar efforts, a lot of shared needs, a lot of common barriers, just a brief glimpse of the kinds of programs that we heard about. Jeff Ginsburg's Mitri at Duke, the PGRN I've already mentioned, particularly their TPP. Cleveland Clinic has a genomic medicine program, so it is Vanderbilt. This is part of St. Jude, part of the PGRN again. Medical College of Wisconsin doing a sequencing program as is the undiagnosed disease program at NIH. Partners has a similar effort. The NCI has an F or so, and Howard's got the PG&E program at UNC Chapel Hill. So there's a lot that's going on here. Relatively disconnected, and one of the arguments for having the meeting in June that Jeff Ginsburg made very cogently was there's a need to get these groups together and see where they can sort of share expertise and lessons learned. If you wanted to group some of the major efforts that are ongoing in this area, they would include screening for highly penetrant germline mutations, particularly in cancer, integrating patient-reported family history into electronic medical records and providing clinical decision support based on that, integrating pharmacogenomic variants into decision support-enabled EMRs for drug selection, genomic sequencing for diagnosis or individual treatment. But there are a number of other efforts as well. And again, the sources of support, I'm just showing a few, certainly not all of them, but there's heavy institutional support at those four institutions. And the federal support I've already mentioned, including also the CDC's GapNet or Genomic Applications in Practice and Prevention Networks, the CTSAs, PGRN and the NCI's program. Common barriers that we heard about in June and have heard about since are at the level of both institutions and clinicians, some skepticism about whether this stuff really makes a difference. A lot of that may be fueled by perhaps some past promises and failures to deliver as well as relatively limited evidence to this point that this actually does make a difference. So there's some resistance on the part of these groups. And there's also institutional inertia. This involves a fair amount of changing and re-engineering of workflows, medical records, and other things, and that's a challenge. There are some fairly high expectations for evidence, some expecting evidence of impact on morbidity and mortality, which for the large part is not there yet. Needs for CLIA certification and IRB approval. And again, sort of treading that difference or that boundary if there is one between clinical practice and research. Some confusion over consent and counseling models, difficulty in integrating the results with existing EMR systems, and there's been some work to work with the major EMR vendors to try to address that. Interestingly, a lot of these centers are doing that individually with each of the EMR vendors, which makes little sense. The burden of interpreting and following up with our view is being potentially massive numbers of results. And I think if you can, at an institution, get them to relax a little bit and say, we're only talking about a few to begin with. Obviously, that's the slippery slope, but it gets you somewhere. And some reluctance to be sort of the first to adopt a novel patient care strategy. So if we can make more obvious the sites that are in the lead and are having some success with this, we may get sort of a follow-up leader approach here. So what we're proposing then is demonstration projects in genomic medicine. We consider genomic medicine to be incorporating patients' genomic findings into their clinical care, and we'd like to demonstrate the feasibility of that, hence the demonstration research, and assess it in sort of real world settings, hopefully in diverse areas. Goals would be to expand existing genomic medicine efforts and develop new projects and methods in diverse settings, a variety of practice settings, as well as a variety of populations. Contribute to the evidence base regarding the outcomes of implementing genomic medicine. So if we can get these efforts to be broad enough or large enough, can they actually provide us some evidence we can use in terms of obsessing effectiveness? Defining and disseminating the processes of genomic medicine implementation and the diffusion and sustainability in diverse clinical settings. So the lessons learned from these sites will be enormously valuable, we expect, in getting other sites to adopt this and evaluate it. So the proposed approach would be to link early adopter sites to some less experienced groups, expand the numbers and types of sites at which implementation is being done, including health maintenance organizations and integrated health care systems, community hospitals, potentially private practices, even the military or veterans' care. There is a military program in the Air Force, a very forward-looking view on the part of the surgeon general of the Air Force, underserved and indigent populations. And from this experience really try to develop best practices for doing this so that each group doesn't have to reinvent the wheel every time they try to go out and begin this. And then collect evidence of the impact on outcomes because many of these are unanswered questions or open questions in terms of their effectiveness. So what this might look like is we start with a lead site like some of those that we had in June or others that could define themselves as such, and then really link them up with other partner sites in various places, either nearby or distantly, that might have different capabilities and be diverse in terms of their practice settings. We could have a number of these. They could be of varying sizes. Presumably each of these multi-center projects would be addressing a different clinical problem or genomic medicine implementation project, although that might not be necessary, and again that would be something that would be in the details of a solicitation. We would also have a coordinating center that would link these together and to do many of the things that Lucia was describing in terms of collecting and stimulating group processes and identifying lessons learned, and also to find a way for the other consortia that are working in this space to have sort of one point of contact rather than four or 16 or 20. Characteristics that we would encourage in the lead and the partner sites would include institutional endorsement, involvement of practitioners, as well as patients willing to participate, potentially an identified group of clinicians who are interested in learning about receiving and acting upon genotyping results. So there has to be sort of a ready audience. We're hoping that someday, even those that are more reluctant that may not be ready to do this would join at some point. But right now we're starting with a cohort of the willing, as it were. There would need to be capabilities for CLIA-certified genotyping, efficient workflow for assaying or reporting results, a process for integrating the genotyping results into patients' medical records and providing appropriate clinical decision support. And alternative, potentially non-computerized processes for settings without sophisticated EMRs if there's an approach for doing that. Also, would definitely want sites to propose what outcomes they would want to assess. These could be as simple as either patient or clinician satisfaction or frustration in dealing with these results. But hopefully something even a little more advanced such as uptake of the recommended interventions, impact on cost or resource utilization would be great if there could be some morbidity outcomes. But these are small projects and that may be a desert rottum at the moment. We would expect approaches for collecting and assessing outcomes. A plan for making this sustainable and possibly even expanding successful implementation projects. Currently the state of the art is that to sustain these efforts they need to be essentially reimbursed by third-party payers. And so understanding what it takes to be able to do that and driving toward that is one aspect of sustainability that there may be others. Leveraging institutional support and other resources and identifying a clear path as I mentioned toward sustainability and the ability to contribute objective evidence that's most likely to influence uptake, to convince both payers and institutions and patients that this is a useful thing would also be encouraged. The role of the coordinating center would be to collect and disseminate protocols for example for successful implementation in a variety of settings. So what works in the Air Force may not necessarily work in other settings and likewise if one's doing this in a pediatric setting it may not work in a different kind of hospital or practice. We would also hope that they would organize the coordinating center in particular would organize broader more open meetings of the genomic medicine community such as the three or four that Eric described to you in his director's report. We are hoping to continue this because we do recognize there's a lot to be learned amongst these centers from each other and we have a lot to learn from them as well. And the PGRN used this model very effectively where they began with a very open meeting that was largely informational, forgive me if I'm misspeaking, initially say a first day and then a second day would be the PGRN investigators themselves who were really focused on how to make the work of their grants move forward. Coordinating with related NHGRI and NIH projects such as you heard about previously the CSER Consortium Emerge, PGRN. Obviously NHGRI staff plays some role in that. We would hope, but we would also hope that our coordinating centers and the consortia would be interested and eager to do that. And exploring the potential to expand projects potentially beyond the initial lead and partner sites. Maybe not to new partner sites because there may not be resources to do that, but there might not be a good reason that a network that's focusing on family history couldn't then take on one from our genetic implementation projects or take on a cancer medicine implementation project. And we would encourage that, recognizing that it might be challenging to do with the resources available. The hope really is to create a cadre of institutions that are evaluating and implementing genomic medicine protocols and collecting and disseminating the successful approaches. Anticipated funding would be $3 million in fiscal 13 and about four and a half per year projects. These things do take time and that may be a little bit optimistic and we welcome your advice on that. We would propose to support three to five multi-center demonstration projects, each with one lead and maybe three to five partner sites plus a small coordinating center using a UL-1 cooperative agreement mechanism and as always we would seek support from other NIH institutes. And would very much like to thank particularly those who were at the December meeting of one of many December meetings that we held and the Genomic Medicine Working Group, actually Rex who chaired that session. So happy to take any questions. Thank you. Howard? One of the things you just mentioned was the timeline for this work. And I think the projects that are going to be going to be earth shattering in terms of moving the field forward will certainly take four to five years or seven years or whatever it is. But there's some very process-oriented type work that needs to be done to like it seems to be back. Right now when I talk to general practitioners and others that are in that area that don't know a thing about this, they don't think it can be done in their practice setting. And so I think there's some work that is maybe only a one-year horizon or a two-year horizon that just shows that it can be done and lays some of the foundation for the road that then we can drive on whatever an algae you want to take. So I think a blend there, if all we do is come out with a bunch of four or five year projects, I'm not sure that we're doing the field as much of a favor as if we have a bit of a tiered approach. Super. No, that's an excellent point. Thank you. We'll try to aim for that. Other comments? Rex? I was just curious about the focus on experienced versus sort of unexperienced sites. My sense of this is that there's no site that's experienced across the board. I mean everybody's struggling with this. This is really hard to do. So I guess I would encourage you to think about blurring the focus between experienced and unexperienced because I think everybody's pretty unexperienced in this and even the most experienced sites can learn from other sites that might be involved. So I wouldn't focus too much. I would encourage you to not just focus too much on experienced versus unexperienced because I think you might get some more synergies if you had a few sort of medium experienced sites involved in that as well. Excellent point. Thank you. I think it is going to be challenging to figure out how do you get that balance where you've got folks who can actually do this kind of work as well as we do want to spread this a little bit. So perhaps some kind of a mix as you said of medium experience would be a good thing. Yes, Ross. So with these concept clearances you can definitely see an emphasis on moving towards the clinics and this is getting a little outside my expertise but I think it might be helpful to hear a little bit more about this. We just I'd like a little more clarity about how this program is different from some other programs that at least to people who are not so closely related sound kind of similar. So the CSER clinical sequencing exploratory research is supposed to be, it is. We just funded people to look at the application of genomic sequence data to the care of patients which sounds to me kind of like what this is. And so please verify that. Yeah, no it's obviously they're related and we want them to be related it's important that they build on each other. The CSER program is focused entirely on sequencing this would use other technologies but more importantly this is really sort of at the end where you're using this in a patient's clinical care in ways that the CSER program may not be doing and we don't know exactly what those would be but I think because we would entertain things outside of sequencing including family history, pharmacogenomics, a whole variety of other stuff that is probably ready to begin at this point. I think it would add on to and we may decide that there's really nothing more that needs to be done in clinical sequencing in patients at this time because that is well covered and I think that would be something we'd have to look at carefully. Does that help a little? It kind of helps some. I mean obviously there's more technologies being brought to bear. I guess that question I had is that the plan is to move these efforts to more institutions but the fundamental question of efficacy is sort of being addressed towards the end. And server data on effectiveness would certainly promulgate without having to push. But those priorities. That's a good point and I welcome Jim and Rex to comment in terms of the clear evidence pushing this to be being accepted because there are such institutional barriers to getting this sort of thing done that that's really what this program is designed to try to address is how do you get the politics and frankly it is a lot of it, politics. How do you convince your lab director that it's worth getting CLIA certified? A lot of really ugly sausage making basically that goes on in doing this and I think that's where the emphasis here would be. Brad may want to make a comment about the CSER program but before you do Jim and Rex Howard you've done some implementation. Did you want to add or do you agree with? I can give some examples of the kinds of things that I think this program would help us get better hands around. You know, some of the barriers are the fact that physicians have a certain workflow and if you do anything that interrupts with that workflow like present them with an alert it's a problem and so to try to find ways that we can actually give them useful information maybe not in a pop-up but through other mechanisms these are the kinds of things I think that these implementation projects would help us learn about. I think just at our place we find that decision support is extremely variable from division to division to department to clinic. One of the things that we were just talking about at a recent meeting is what happens when you present a recommendation in one clinic and the other clinic doesn't see that recommendation why do these crazy people over in that other division recommend this? So I think there's a lot of issues like this that only projects such as this are going to start to surface and I think implicit in your question is why not wait a little longer until the evidence is there I think A there's a lot of people that think the evidence is already there vis-a-vis all the places that are actually already doing this sort of own these early adopters but the other problem I think is that it's not the evidence in many cases it's these other things like the workflow, like how integration of DHRs goes just what the practice operations are and I think these projects are ones that will inform us a great deal about that kind of barrier and how to get over it. So I think you're right and I think it's a good point to not overlap in a lot of similarity I think that that's okay as long as there's an absolutely maintained focus on the fact that real evidence needs to be generated and real evidence of or lack thereof of patients benefit be critical of these. So I'm not that concerned about redundancy I think that there are some you know there are some different aspects to these programs I think there's a lot to explore and you know something I've railed about I think that we shouldn't be pushing this in these should be framed as opportunities to investigate whether right not just how but whether these new technologies can actually benefit patients so I think it's absolutely critical I don't mind the redundancy I think what has to be inherent to all these efforts is that there be outcome measures that are identified and whether in the end these things actually actually help diagnosis which is where most of the promise is right now eventually therapy etc And this is not going from a four-lane highway to a six-lane highway this is trying to get a dirt road in place of the donkey path so it's it's really trying to at least get something on which a highway can be or a road can be built as opposed to just a little bit of expansion of something that's already rolling in my mind Amy and then Brad Yeah I just want to echo what Jim said which is I think it's critical that all of these efforts particularly this one focuses on the whether it should be translated because there is a sense I think that we're pushing the translation from research into clinical care potentially prematurely and I mean that's a clinical decision it's an ethical decision it's a social decision and doing it without sort of studying whether that should happen I think can come across as being inappropriate so I think that this is a good opportunity to study that exact question of is this appropriate and how should it be done if it is appropriate and if I can add one thing I think that the proliferation that we see of offers for say whole genome and whole exome sequencing by laboratories actually points up the need for this kind of thing because we have to actually figure out whether it's worthwhile right we've seen too many times things being rolled out in medicine because they're fattish and because they sound so good and then in the end didn't really make any difference these so I would not take to heart the accusation that that these efforts are redundant with say commercial offers out there and laboratories offering this stuff because they aren't studying what really needs to be studied which is can this help patient care right so I think by maintaining a focus on that you actually contribute something to the field I mean I completely agree with the last few speakers and I think the in terms of prematurely going out there on one hand we're doing all this stuff on return of research results for what the presumption is that it's helpful and that's already ending up in medical charts and maybe in one clinic not another so I think in many ways the horse is out of the barn on a lot of this and it's to try to look at it in a rational manner maybe pull the horse back in a few places I was just going to say the way I think in the clinical sequencing program the CSER is that that's the laboratory that's where the experimentation is going to drive a lot of the innovation in these areas and so just kind of repeating what Urveils has already said we were careful to put in the title of that program exploratory because we really think that's going to drive some of that innovation the key to that program and I think what needs to be done in this program also is that it's not just do it and figure out how to do it well it's do it, figure out how to do it well and then study whether that's actually effective and if you don't have that last piece of it then it just seems like you're pushing something that there isn't evidence to support the push for at work Jill then Rick but to see if it's effective there has to be some tie in with the clinic and while you don't want to push things into the clinic prematurely you have some way of doing parallel studies, not invasive not you know because otherwise how do you validate so I think we also have to be careful about what we mean when we say stay out of the clinic, don't translate too early because there has to be some way of working with groups who are involved in clinical trials and that sort of thing because otherwise you're never going to test the efficacy of these approaches you don't necessarily have to make the treatment decision based on what you're learning but you have to, if you can do these things prospectively and then see what the outcome you would have predicted does or doesn't come to pass I mean I don't see how else you validate these things I mean don't you have to if you're going to do a prospective when you have to have ones that you do this is that part of the program I didn't hear that I think because this is a concept Rick so we need to be a little bit broad and we would expect investigators to come in with their best ideas I can tell you many of the groups that we heard from in June are doing exactly that where they're essentially one group is getting it and one group isn't but they've got limited power to do it so one thing I think you said this Terry it's going to differ from case to disease to disease and case to case rare Mendelian sequencing occasionally and there have been a couple of cases where you actually find something and those are pretty compelling you don't want to wait on those but it's not the way most things are going to work I mean we run into this a lot the public people come in all the time I'm sure it happens to the big centers even more that they want to have their genome sequenced or their kids or this or that because they've heard those stories and they're compelling and I feel for them because I would too but you're talking about something mostly different here and I think you're going to have to explain that that's part of that and then the other part is I wanted to actually ask maybe from what Jim said the fact that many of the commercial operations that are offering this now with very poor they're not looking at efficacy at all they want to sell as many as they can and while I understand that that may that's going to probably cause some pushback on this for instance part of this might be to figure out how to fix some of the problems that come up in those situations is that something that's part of the concept or have you guys talked about it much probably haven't addressed that particular issue I think trying to solve American capitalism as applied to medicine maybe a little more than we can handle but not to be facetious but don't be wrong I don't think it's wrong for them to do it but most of the time I mean it depends on what they are the genotyping companies just basically wanted to do as much as possible maybe with sequencing and with really practicing medicine it'll be a little different when people are doing that well I see Jean is standing at the microphone and I might note that probably the Caesar projects are going to have a lot more to inform what the commercial efforts are than this project might but Jean do you want to comment yeah I was just going to say I mean there's a whole discussion I think that's one of the things that we're trying to do in this return of results consortium that's just getting underway which I think obviously is going to have to integrate very closely with what you're talking about as well as all the other initiatives that we already have going on and we specifically within that consortium are including both projects to actually examine this in the context of an active clinical setting because you can't really study this empirically without doing it to some extent but at the same time we funded projects that are absolutely backing up and asking that very fundamental normative question about whether we've rushed ahead too far and whether there are particular problems with this sort of blurring sometimes of the distinction between research and clinical care so I think ideally that that will be the place where a lot of these sort of broader policy issues get discussed and you know and whether we'll be able to reach consensus on a lot of them is unclear but at least that's where the discussion I think will be going on but again I think we're going to have to really coordinate closely with all of these initiatives as well as with the coordinating centers for these initiatives because it's all of this is related Didi? It may well be they so far have not expressed an interest because they're more on the discovery side than the implementation side but I think they're moving Didi to the discovery side sorry to the implementation side so that's a good suggestion we'll do that I was going out and maybe it was even alluded to I mean the biggest budgetary component of NCATS is the CTSA program and the CTSA program I think is going to really sort of be challenged to look at new opportunities and really be looked at under different light now in a new organization and I think probably that part of NCATS has great potential to eventually interact with the kinds of things we're talking about here especially considering the budget considering sorry the budget yes and the CTSA program is very big and this is very small pilot and we think could inform the kinds of things they might be doing three to five years isn't there a good way to leverage yeah oh alright any last comments otherwise I'll bring us to closure on this okay all in favor of the concept any opposed any abstentions