 This is an update on PCORI, as you know, a non-governmental agency created by the funding agency, research funding agency, created by the Patient Protection and Affordable Care Act. From that legislation, you'll see that we have a broad mandate and it's about supporting decision-making. So it's to assist patients, clinicians, purchasers, and policymakers in making informed health decisions. So that implies that one has a choice to do something or not to do it or to do this versus that. And we do it through funding research, including evidence synthesis, and we also do it through dissemination of research findings. So that's kind of our, that's about as specific as the legislation gets. We could do research in any area where arguably there are choices to be made. But I'll show you one piece of evidence that explains maybe why I thought I'd be here. Research shall be designed as appropriate to take into account the potential for differences in effectiveness of health care treatment, services, and items as used with various subpopulations. And I, for this meeting, I also highlighted the part, one of the ways that patient populations and subpopulation differ is genetic and molecular subtypes. So right in our legislation is the notion that we should be attending to that. So I always expected that we would. PCORI, Board of Governors, was also mandated to come up with its national priorities for research. And these are they. And again, you see the first one is assessment of prevention, diagnosis, and treatment options. And I can't really see the screen from here, but I know that it says something about their potential differences in response to therapy in patient subgroups and studies of patient preferences for various outcomes. So again, it seems like it has high relevance. But some of the other priorities also improving health care systems in the way that we support patients in doing self-care. And coordinate care and evaluate decision-making by patients. Communication and dissemination research, the ways that information is shared between patients and clinicians and systems and shared decision-making is supported. And then addressing disparities. So you'll see that all four of those first four of the five priorities, you can build a case that research into genomic medicine could fit different aspects of it could fit in those. I'll tell you a secret. Everybody else with their research interests sees the same thing. But nonetheless, that's part of being broad. And the fifth one is you may know the fifth one is about building infrastructure for doing comparative effectiveness research. And you may know that we have a very large initiative on the street right now, $70 million in total. And it encourages people to build system-based clinical data research networks that have, among other things, patient and clinician and system involvement in governance and the building of large clinical data repositories along with patient-reported data and but certainly including biospecimens in the mix of data. So all five of the priorities seem to hold some promise for supporting research in the area of genetic medicine. We, unlike many entities these days in D.C., we actually do have money to spend. This is how much flows into the PCORI trust fund each year. And you see in 2013, $300 million flows into the trust fund in beginning in 2014, $500 million. 20% of that comes off the top and goes back to HHS. But that leaves 80% that PCORI itself allocates. And we are front-loading that funding. So we aim to commit about $350 million this year and about $500 million in each of the next two years. And these are the requirements we make of applicants. That, in fact, the research that you're proposing addresses a question that's relevant to choices faced by patients, clinicians, it should say policymakers, and that it considers patient-relevant outcomes. So we put a lot of stock in. Patients should be engaged as you formulate your research question and should endorse the outcomes that you're studying. So that does suggest that we want outcomes that patients would resonate with, would say are relevant. The studies indeed do need to be comparative. We're called upon to do comparative clinical effectiveness research. I think you had a little discussion this morning about cost-effectiveness research, and we do not do cost-effectiveness research. We tend to not measure qualities, and we certainly don't make or recommend decisions about coverage on the basis of anything like qualities, but we absolutely do fund and really only fund comparative clinical effectiveness research with the patient-relevant outcomes. We, the research, any research that comes to us has to speak to the possibility and ask the state how they will look, in fact, for possible differences in treatment effectiveness across population subgroups. We look for research in real-world populations in relevant patients, including patients with multiple comorbid conditions, and we insist that they include relevant patients and stakeholders on the research team. So this is something that's driven researchers a little crazy, just figuring, especially seasoned researchers. New researchers have no trouble figuring out how to do it, because it's the first time they're putting teams together. But people who've been doing research, NIH, ARC-funded research, for a long time pause when it comes to the part of the application guidelines about be sure that you've got patients and other relevant stakeholders, not as the subjects of your research, but on your research team. Be sure and discuss in your research application the potential for dissemination and implementation, and don't include, in fact, cost-effectiveness analysis, and don't really compare overall costs either. And this is just our working definition of comparative clinical effectiveness research. It's pretty much what I just showed you, but maybe a difference or two. That addresses practical questions, those of interest to patients and providers in particular, but policymakers too. Usually we're looking for head-to-head comparisons, but in this context here, it might be a comparison between doing genetic testing prior to making a treatment assignment and not doing it. It's conducted in typical patients and typical care delivery systems. That's the kind of research we're looking for. Considering the full range of outcomes of interest to patients, looking for the differences in treatment effectiveness. They may be RCTs, they may be observational studies. So I will just say in closing that we have funded about $150 million in research already. We have standing announcements that are open. These are broad announcements to which we would be delighted to see submissions around questions related to genetic medicine. And we also have now built a set of four advisory panels that advise us and help us prioritize questions that we would then target research in. We would devote more research, more resources to a particular area. So we could have a discussion about the fact that we ought to have a specific initiative in genetic medicine. If people felt that that was, that the time was ripe for that. But we are, you will see over time that PCORI will move from being almost exclusively a funder that funds, that issues broad solicitations. Program announcements that solicit R01s, for example, toward an agency that has a good part of its portfolio dedicated to targeted areas. And one of them most certainly could be around genetic medicine. So I think I've said enough and I will stop and entertain questions. Thank you very much, Joe. Yes, Mark. So, Joe, there's one thing that you didn't specifically mention that it's probably worth bringing to this group. And that is the specific call out for a rare disease focus as well. And I wonder if you could expand a bit on that and how that's being implemented by PCORI. Thanks, Mark. The legislation also, the legislation has a lot of language in it. Just a very small piece of the phrase, a sentence. But patients with rare diseases are specifically called out in the legislation. And so we call them out in our announcements. We are very interested in studies and we would prioritize a study somewhat higher if it addressed a relevant question and it competed well in the reviews for patients with a rare disease. We also similarly in our infrastructure award, we have a certain amount of that money set aside for patient powered networks. And those we particularly interested in seeing patient organizations, patient communities with rare diseases apply. So yes, and I think again in the context of this group, that's a very relevant point to be aware of. Joe, I wonder if you could comment a bit about, you mentioned that genomic medicine might be a topic that PCORI would pursue. You're probably closer in touch with what patients are interested in than many of us are. Are you hearing from patients that this is an area of interest to them? No, Terry, I can't say that we have yet, no. There's something about the way that you bring patients together that I'm not sure, but it may not set it up for that. Patients often come in and they're patient with multiple conditions and they may be talking more about access or communication. I can't say that I've heard it. I'm sure prepared to believe that there are patient organizations out there that could put that question in that case to us, but I have not heard it yet. Because one could imagine that if it's only those that are the most active or loudest voices that are getting to you, that's obviously a problem as well. And clearly the people that we hear from think this is great, but we don't. You should tell your people to talk to ours. No, we do have, among other things, a website where patients can submit questions. And they haven't been brought to my attention. I have not seen an application specifically about, particularly genetic testing, yet come to our in response to our broad solicitations. I will say just for those of you who work in the grant writing and in the world that the announcements right now are typically invite proposals that cost up to about 1.5 million in direct costs and last for three years. So it's about a half a million a year for three years. We have some, certainly we have some flexibility to make things shorter. We're sometimes open to making things longer. We do like studies that promise some results in the fairly near term. There's at least one in the next round. Good, good. Mark is distinguishing himself among other ways by being one of our committee chairs in our review sections and we're very grateful for that. It's another way that researchers could work with us, in fact, is to let us know you'd be interested in helping us review. Yes. So one of the things I'm interested in is you've indicated that you're intending to move from a more broad investigator initiated, take all comers kind of approach to a more targeted approach and you alluded to some committees that were helping advise you on that. Can you talk a little bit more about that process and how long you imagine that transition would take? And in particular, I'd be interested in, we have a lot of genomic people that are interested in genomic medicine from a variety of perspectives in this room and one of the things we're thinking about is whether we need some kind of coordinated national policy. And so how might that feed into that process as well? Well, let me say this, you can go to our website and in fact find out exactly who sits on these four advisory panels, pretty impressive collections each of the panels. What they do is we receive input suggestions for research questions from a variety of sources. We receive them via the web. We receive them via interactions with professional societies, patient organizations, payers and we have program directors assigned, scientists within PCORI assigned to each of the priority areas and they process these and there's a process of shrinking them down to the ones that are really comparative, removing the redundancies and then doing some preliminary landscape assessment to see which ones really aren't already known, which ones have some likelihood of benefiting from some primary research and then we prepare topic briefs on those and these topic briefs go to the prioritization, the advisory panels which do prioritization and they have very robust discussions. I think over time you will see the advisory panels bringing questions directly to us. I think you'll see our scientists, our program leaders bringing questions to us, to the advisory panel. So they then submit the questions to the board. The board may say do a little more investigation but ultimately the board then approves those topic areas that we move forward with explicit announcements on. It's known that we have an announcement coming out shortly on the treatment of severe asthma in minority populations and we have one coming out on the prevention of falls in the elderly and probably likely one coming out on treatment options for uterine fibroids. So those are those are three areas that the three of our very first targeted areas. Reason I ask about this, one of the things I was really struck by is as you went through some of your earlier slides it really talked a lot about how to identify subpopulations and I think Dan Rodin was talking earlier today about the warfarin work where it may only benefit 20% of those people but for those 22% of those people but for those 2% it makes a huge difference. So I mean is that the kind of thing comparing those that subpopulation to the subpopulation, the broader population at large where that signal might very likely get swamped out? Yeah, I would say that's precisely why the legislation emphasized it and it's certainly why we emphasize it, the vision and genetic medicine fits right into this vision. I think that over time you begin targeting particular therapies toward that subgroup that really stands to benefit and you find something else for the subgroup that doesn't. So that notion is really that's a notion that's pretty widespread in the legislation. I think it was maybe in some ways put in there as an antidote to any simplistic view that comparative effectiveness research was just about comparing means, finding no difference, paying for the cheaper one and not covering the more expensive one. So between you and me and all of you I think that's kind of how the language got in there but it's quite exciting language. I'm sure you would agree that the vision that one person with diabetes is not like everybody else with diabetes and treatments may really, we know that treatments do work differently so that vision of eventually getting the right medication to the right person is kind of a mantra, the right treatment. And it works just as well in system interventions as it does with medications too. System interventions don't work the same for everyone either so. Great. All right. Thank you very much. Joe, I hope you can stay with us for the rest of the afternoon. Next we have Wayne Currie who will be speaking for the CDC but also wears a hat at the NCI and so you can get a little bit of both of those.