 Okay, so as the slides are coming up, I'm just going to kick off the discussion, and I'm Laura Rodriguez from NHGRI, and I know some of you, but not all of you. And Steve is going to run our slides, so that is why he is standing up there. But our speakers are going to rotate through the slides. So we're going to start off just with Steve to give a basic frame of the issues as we saw it, looking at patient-facing tools and associated other topics that were put into this very broad set of issues for the hour. And then we'll hear from Janet Williams, who has done a survey of the information that is available out there and looked at the information from different programs. And then we will finally hear from Bill Lawrence, who will talk about what we might learn from some work that they've been doing at PCORI, and hopefully that will round us out nicely to move into our discussion for the hour before lunch. So. Great. Thanks, Laura. So we'll do, as Laura said, we'll do a bit of a tag team on this. I guess the first point to make is that implementation of genomic medicine into practice is going to take effective clinician-patient communication, and you all know that. And if you look at this iconic diagram from the base pairs to bedside paper, as you get over to the right side of this diagram, particularly improving the effectiveness of healthcare, this isn't going to happen if we don't get the clinician-patient communication, clinician-family communication part of this right. Now, as you all know, there are substantial challenges in doing this. I hope you'd all agree that the best patient-facing tools or family-facing tools are expert genetic counselors and medical geneticists and others with content expertise in the area, and there's no substitute for that. But at the same time, we have challenges that are going to make it very difficult to rely on that workforce, as we've been talking about over the course of the morning. So if you think about all of the things that genetic counselors do, this from the National Society of Genetic Counselors' website, genetic counseling is the process of helping people understand and adapt to the medical, psychosocial, and familial implications of genetic contributions to disease, including interpretation of family and medical histories to assess the chance of disease occurrence, education about inheritance, testing, management, prevention, et cetera, and counseling to promote informed choices and adaptation to risks or condition. And in some sense, that's what we ask of our genetics professionals in our broader clinician workforce, but we can't rely on that workforce because of the challenges that face us. There just isn't enough, and so we need tools to make that possible. Some of the specific challenges include the scale of the issue as genomic medicine or genetic medicine moves out from specialty settings into the general medical setting. The workforce demands are just going to be overwhelmed. Secondly, the scope of genomic medicine as we move from targeted to much more broad sequencing or genomic testing, the potential findings that may come back become so broad that it becomes very challenging with our traditional models of education and counseling and decision support to address them. And finally, of course, the issues of science and genetics literacy. We've been talking over the last hour about this from the perspectives of clinicians. We all realize this is a challenge from the perspectives of patients and families and the public as well. So if you think about the functions of patient-facing tools, this is crude, but I want to break it down into pre-test and post-test settings. I think there are three broad ones, one of which is education of patients and families. The second is risk assessment and the third is decision support. And the education may be education that's related for the indication that we are considering doing this particular test, and then some preemptive education related to the possibility of incidental or secondary findings. Risk assessment is going to relate to phenotype and personal as well as family history, and decision support includes things like whether to test, and then possibly, and I put a question mark here because I don't think our community has settled on how we're going to deal with this issue, but possibly the question of preferences for the return of incidental or secondary findings. In the post-test setting, again, we have challenges related to education, risk assessment, and decision support. For education, there is, of course, education related to the primary result that comes back. Education related to any secondary or incidental findings that come back, particularly educational challenges related to variants of uncertain significance, if and when those are reported back. And something we actually haven't talked a lot about over the course of this meeting, but the challenges of negative tests and what those mean, particularly when you're talking about broad sequencing. Risk assessment again becomes a problem, particularly in the setting of secondary or incidental findings. Hopefully you've done a good risk assessment up front for the thing that's relevant to the indication for your test, but you certainly haven't or are unlikely to have done a complete risk assessment for one of the thousands of possible secondary findings that might come back. And so now at the time of that finding coming back is the time to do that risk assessment. And then, again, decision support, both with respect to any diagnostic therapeutic or preventive interventions that might be related to the results. And then, of course, what are we going to do about family members who might be implicated as well? So just to sort of set the stage, and then I'll turn it over to Janet. There is a clear need, I think, for effective, safe, and efficient needs for... There are things that we need in order to be able to effectively, safely and efficiently implement genomic medicine, and that includes a whole suite of patient-facing tools, strategically designed suite of tools that are directed at patients. And many of these tools are really going to be designed to support and extend clinicians who are practicing genomic medicine, including both genetic and genomic specialists, non-genetic specialists in my own world of oncology. The general... There's a subset of oncologists who really are experts in high-risk or inherited cancer syndromes. So most oncologists really are not truly expert in those things, and for them it's a significant challenge, and I think this is true across most areas of medical specialization, and then, of course, primary care clinicians. So with that, let me turn it over to Janet. You're welcome to come on up, Janet, and run the slides from here. And it is this one. So my task in our work group, our panel, was to take a look at some of the tools out there that are designed for patients and that provide them with education or with the means to understand genomics. And although a bit tongue-in-cheek, one of the things that I wanted to do was to just kind of take a look at where would patients go to find information, and in talking with patients that, you know, the place they go is to the internet, and if you're just trying to find out information about what is genomics, what does it mean, I didn't evaluate every one of these, but it is pretty daunting to just get an explanation of what's involved. In looking at the funded projects that are represented here in the room, again, I did some perusing mainly on websites, had a little bit of background information about resources that have been published, and there's much more out there than I could show here, but some of the top items that are referenced in terms of patient education or patient resources include, I think, first and foremost, genetics home reference, which has played a large role, I think, in providing patient-oriented information. I think that many of the oncology folks are well familiar with the cancer genetics PDQ out of NCI, and that's been very helpful also in providing background information for clinicians as well as for patients. The new resource Genome Connect is looking to be a great source of information for the new types of genome findings that are coming out, although they also are, will likely be one of those resources that are connected to many of our projects. Genetic Alliance is mentioned many times. Medline Plus is mentioned, and then, of course, the National Rare Diseases Group is mentioned, and then ARFANAT, which is really more a European site that's available. So these are resources that patients can go to when they're looking primarily for specific information on a specific disease. It's less oriented towards providing resources or tools for patients to understand if they want to do genome sequencing or how that might benefit their family, how they might understand genome sequencing or genome information, and then also how they might communicate information with their families. A couple of these tools, which are actually tools that help to explain results for patients include lab tests online, which is a very generic sort of tool, but it includes genetic results. You heard about the CIRC project on my results formulated by John Connolly, a CHOP, with input from the CIRC members of eMERGE, is another patient resource place to enter genome information and have support that comes back. There's webresourceyourgenome.org that again is patient facing. I wanted to highlight the Mi-46 out of the University of Washington only because it really is a more total tool for patients. It does enable you to upload your results, to have information about what was found in those results. It will help support you in terms of any single gene testing, genome sequencing, or whole genome sequencing. It does offer the process of dynamic consent, something I'll talk about in just a minute, but it also then facilitates researchers to be able to again look at how patients select the results that they wish to receive and how the results can be managed and how patients might use that information that they learned from this tool. I will say that in addition, Genome Connect is also offering that resource to researchers as a means to link patients and researchers. One of the things I wanted to lift up was again the work we've been doing with regard to our whole genome sequencing project, which is looking at tying patient results to clinician results within the electronic health record and providing an interface for these tools to be available both for patients and clinicians at the same time. In terms of our patient qualitative work, I think it's important to recognize the themes that at least the patients within our whole genome sequencing project identified, and that is that patients who have a child with an undiagnosed disease do embark on this ongoing continual search for valid information and resources. They do that now through the Internet and see that as both a blessing and a curse. That prior reports on genetic results are not adequate and are not helpful to patients, and of course they weren't designed to be patient directed, but parents expressed a need for a report that they could understand, and they emphasize that a report that was designed for them would be something that they could use for communication, both with their other providers. Many of these children tend to have multiple providers because they have multiple health conditions and their chronic utilizers of the healthcare system, but they also described how they would use a genome report with explaining the findings and the diagnosis to family, to friends, to their schools in the context of an individualized educational program assessment, and then again with other physicians as well. And they outlined the things that they were looking for in a genome report designed for patients, and that is of course understandable language, a logical flow, some visual appeal, information on what to expect in the future, what's the prognosis that's associated with this genome finding, and then what are the next steps that should be taken, and finally that they would love to see the option for different ways of receiving that report. We are proposing it through the patient portal in MyGuySinger, but our patients do have some connectivity issues in central Pennsylvania and suggested that perhaps they could also receive it on a thumb drive or a phone app or something that enabled them to have that information that wasn't necessarily tied to internet connectivity. I wanted to highlight the CSER project in terms of the work that they're doing on genetic counseling and specifically evaluating genetics counselors' work with patients in the space on returning genome results, but also in the work that they're doing on developing patient-facing educational materials and the publications. I think they'll be an important group to continue to watch. I thought it was also interesting, as I was looking at different options for patient education, that one of the things that the Genetic Alliance in the U.K. has done is to develop a patient charter and that they outlined, again, the support that patients that they found their patients had for genetic counseling, that they recommend actually through this genetic alliance in the U.K. that all patients should be able to access a dedicated genetic counselor before they have their genome sequenced and that there should be more support given to the training of genetic counselors as the need for their services increases. And I couldn't support that more being a genetic counselor, but I'd also like to announce that there are at least 10 new genetic counseling programs currently in development that should be online again within the next year or two. Again, out of this patient charter that was actually established in February of this year, they noted how patients do welcome the sharing of their genomic data for research purposes. I think that's encouraging for all of us in the room, and that they encourage researchers then to engage with the patient community in order to develop accurate and comprehensive information regarding genome sequencing and that we need to make an effort within our research studies and in delivering our clinical care in order to involve in genome sequencing to more closely reflect what patients experience with that information in terms of how we communicate the information. Finally, I wanted to just briefly touch on the issues of counseling and consent. I think that there's been quite a bit of work done in the realm of consent within research. We don't have standards that are accepted for consent for genome sequencing, but I think that the process of taking that from a research setting into consent in the clinical setting is even more onerous. We talk about clinicians not having time to evaluate the results that come back. They also don't have time to spend in the consent process ahead of time. So we need to think critically about how do we accomplish this in the setting of clinical care. Within the Genome Alliance, the UK, as they talked over with their genome researchers, actually this was out of the Hastings Center report, but it was also alerted to in the Genome Alliance, Genomic Alliance UK, that routine approaches to consent for genome sequencing are probably not effective and that it will require innovative approaches to ensure decisions that are informed and meaningful. And this is where the issue of dynamic consent and the idea of revisiting consent as the context for the individual changes. And that context may then influence what an individual patient or a family may want to know. And I believe that's all that I'm going to be talking about. I think I'm next going to turn it over now to Bill and talking about PCORI. Thank you. I'm going to sort of present a view from an outsider and I wanted to start with just a brief roughly two minute explanation of PCORI as I'm not sure how many people here are familiar with them. I'll try and actually keep that literal on the two minutes. But just a little overview first, the purpose of our institute, the Patient-Centered Outcomes Research Institute, is to assist patients, clinicians, purchasers and policymakers in making informed health decisions basically through the provision of evidence and evidence synthesis. So not only are we talking about providing primary research but talking about providing that research in context through systematic reviews, things like that, so synthesizing across the evidence. And so our big interest is trying to help people make decisions about their care. We put this within a space bar, right? Oh boy. We put this within the context of comparative effectiveness research, essentially comparing what your options are available or what your options are available at any particular decision point and actually comparing the benefits and harms of them. And part of that is actually making sure that we're disseminating research findings to clinicians, to patients, and to other stakeholders. Just a brief thing on who we are on the science side. We have five science programs, the Assessment of Prevention Diagnosis and Treatment Options, which is informally known as our Comparative Effectiveness Research Group. These are the folks who, if you're thinking about actually comparing two different approaches to testing, various interventions that you're probably going to be looking at, our Improving Health Care Systems Group looks at different systems approaches to helping patient care. So thinking about trying to put things within the context of a plan, different types of care management approaches, things like that. The Communication Dissemination Research Group, of which I'm a part, is actually interested in looking at different ways of disseminating information to patients so that we can actually improve decision making. We also have an Addressing Disparities Group looking at how do we improve care for vulnerable populations. And then finally, our Methodologic Research Group, which funds basic methodologic studies in comparative effectiveness research. And it's also our Data Infrastructure Group that sponsors PCORnet, which has both clinical and patient-oriented research organizations, which I believe some of you are members of. Spacebar, spacebar. I will remember spacebar. So part of our mandate here is talking about how do we get information out to patients to actually improve their decision making. And again, that's sort of in my group. And our basic tenet is that producing information is not enough. We've got to get it out to all audiences. And in general, the information itself is of little use unless it reaches those who need it, and it's clear and comprehensible to those who are receiving it. And so with that, I just wanted to give a few thoughts from other areas in which we've done decision making work, and hopefully this might be useful at thinking going forward with your programs. So moving towards the development of decision-making tools, and I put content in here too. Counseling, genetic counseling is a very important approach, but it's also important to understand what that content is in the counseling. So I want to make the comments both on sort of tools, both patient-facing tools and on counseling. So the content basically, number one, the way we look at it, is it's based upon the evidence linking choices to patient relevant outcomes. So in thinking about it, what we are looking for is information. If you're doing the test or thinking about doing the test, does actually doing that improve someone's health, longevity, some other sort of patient-relevant outcome? We're looking for methodologically rigorous studies, probably the most relevant group in thinking about this for helping patients to make decisions is the International Patient Decision Aid Standards Group, and that may be one resource to look to. Involve patients and clinicians throughout the process of developing and evaluating the tools. And one of the things that I will try to harp upon is stakeholder engagement writ large. People should be involved in the research at the start of the research. Don't bring them in at the end to say, how do you help disseminate this? It should be accessible to patients, which I have, there are two forms of accessible. Number one, it should be available. If they can't find it, it's useless. And it's got to be understandable. And here there are big issues in terms of health literacy and health numeracy. I was at a decision science meeting last week where an investigator presented data that she surveyed a group of patients out of clinic and started with the question that John was supposed to take his pills on empty stomach but ate lunch. And the directions say, well, you can take it two hours after the meal. When should he take his pills? 40% of people couldn't answer that question. So things to be thinking about as you move forward, making sure that it's accessible to a wide range of patients. It should be responsive to patients' needs and preferences. So basically, helping to inform choices based upon preferences as opposed to dictating what you want them to do. And then finally, evaluate it. Does it actually work? So just a couple of thoughts moving past development. And PCORI doesn't really fund development of decision-making tools and such. But we are interested once you have some basic efficacy data on actually comparing them in real world situations. And that may be one way we can talk about interface between NHR, GI, and PCORI. But with translation into the real world settings, I'm a primary care doc. How are you going to get me to use this? And are my patients going to understand it? Will it get used? Do you have buy-in from the relevant stakeholders? Again, if I don't know to use it as a primary care doc, then chances are my patients aren't going to use it. For the decision tools, who maintains them? We've talked a little bit within the group about doing repositories of the tools and such. This is a rapidly evolving field. And there's a lot of impetus to developing the tools. But when things change, there's not a whole lot of impetus to update the tools. So who maintains them? And then finally, do the tools actually improve decision-making? And does it improve patient outcomes, which is really what we're looking for? And are there general points here? All right. Do you want to?