 So thanks for the invitation to speak. My day job now is at Geisinger Medical Center, where I made a recent move from Brigham and Women's Hospital and Harvard Medical School. But today, as was said, I'm representing the American College of Physicians. John Tuquer has been involved in preparing this presentation along with me, but unfortunately, he couldn't make it today due to family reasons. So the ACP, the American College of Physicians, is very interested in this area and very dedicated to building collaborative efforts and meeting the needs of their membership. So with that, I'll say that for my talk, I want to just show you a few introductory slides and then talk about the description of the ACP and some of the educational tools that has developed, not specific area of genetics and genomics, but more broadly. And then in response to Jean's questions in preparation for this, we started conversations within the ACP about what was known in answer to those questions. And we've realized that while we had many opinions, we had very little data. And so the ACP actually commissioned a survey specifically getting at some of these questions, which I'll share with you. As I said, when we were preparing the survey, we had to be a little cautious for internists, practicing internists, asking them what they need as far as genetics education, or genomics education, would have been a little bit like asking one of us in the late 80s as to what we would want out of our email accounts as we start to prepare to start doing email. So most internists have not been thrown into this pool yet, but I think it's coming soon. And I always like to show this during talks that I give. So the number of genomes that have been sequenced, Nicholas Wade in the New York Times just a couple of years ago, pointed out that only seven human genomes had been fully sequenced at that point in time. Francis Collins, speaking to us at the Brigham in late 2011, pointed out that by the end of 2012, so a time point that we've already passed now by a month, the NIH alone would have completed about 73,000 genomes. That's exomes plus whole genomes. And I don't know if that number played out accurately or not, but it gives you an idea of the uptick here. And then there are people making predictions. And whether it's exactly true or not, I think it's a reasonable ballpark estimate that sometime in 2014, the one millionth person will have had their genome sequenced. So it's difficult to pin down such a number since some of this is being done in the private sector. Some of it's being done by research organizations other than the NIH. But it gives you a sense of where we're going here. And I think that when I talk to clinicians, particularly practicing internists, and they point out that we don't think this is coming that quickly, I think it's hard. It's going to be hard to keep these one million people out of the health care arena where they're going to be asking their providers to put their whole genomes or their whole exomes in context. So we had done some educational work with the ACP when I was at the Brigham. This was one of the courses that we put on. And the audience have participated as faculty. And in 2009, we got the ACP to join in this. This was a standard sort of three day event. You come to a hotel. You pay probably too much money. And you get talked to by a number of experts in the field. These were two and a half day courses. We were always struggling to get an audience. We generally got 100 to 200 practicing clinicians to sign up for these. And when the ACP joined us in 2009, Steve Weinberger, who's one of the vice presidents of the ACP, pointed out to me, well, you know, it is a spinach course. And I didn't know what that meant. So he pointed out that genetics and genomics, for internists, when that's offered, most people will choose something else from the menu. A small percentage of people will take it because they think it's good for them. And only a very small percent will actually take it because they like it. So I think that it played out that way. We struggled for six years to really make this a break-even course. And it went on permanent sabbatical in 2011. But I want to tell you a little bit about a course we're developing, and we're test driving right now. And this is being organized in the context of Robert Green's CSER awards. That's the clinical sequencing awards from the NHGRI. So in that grant, we have 20 providers who have signed up to enroll their patients to be randomized to whole genome sequencing or standard care. And those 20 providers are 10 academic internists at Brigham and Women's Hospital and 10 cardiologists. And we designed a primary care course in genomics for those 20 providers. And the way that we've designed it is that there is a live lecture, book ending, four hours of self-study. And these cases are really designed to emphasize competencies, as has been mentioned by many of the speakers. So we're not trying to teach content. We're not trying to make people experts in pharmacogenetics or in genomics, but rather giving them situations where they will be getting data back that they have to put in the context of care. So we should have the first run-through of this done in a week or two. Our hope is to publish our experience out of the U01. And then within three to six months, our hope is to have a derivation of this on Geisinger's website for wide access for providers who are getting into this area. So the American College of Physicians are familiar. It's the organization for internal medicine physicians or internists. And then, of course, they have to go on and explain who the internist is for the general public. So essentially, it's an adult care provider. The ACP has 130,000 members. It's the second largest after the AMA. And it's, of course, focused just on one specialty. And of course, they advocate and give information to their members. Interestingly, they have many tools in their toolbox for providing CME and for getting information out to their constituency. So internal medicine is their annual meeting, which is held in the spring, 260 presentations. Unfortunately, in the past, there's been very few of them on genetics and genomics. But hopefully, that's going to change in response to what we tell them after this meeting. They have what's known as MIXAP, which is the self-assessment program that is available to internists, practicing internists, as well as trainees. They have something that is called peer, so physician information and educational resource. And this is a web-based decision support tool. As you can see, there are many not modules already in place with plans to continue to expand this. And there are various resources that are available to providers on their mobile devices that take some of this information as well as create other new information. Additional CME opportunities within ACP, some relevant to genetics and genomics, of course. There are ethics cases, which cover a broad variety of clinical ethics. Touch on genetics and genomics also. There's a review course for board certification, which, of course, motivates lots of practitioners. And then there are statewide chapter meetings, which also have scientific programs and CME attached. A little bit about what ACP does in general. Regarding clinical recommendations. So they develop, through their infrastructure, three different types of clinical recommendations. Clinical practice guidelines. Clinical guidance statements and best practice advice. So this is available on your smartphone if you're an ACP member or if you sign up. But the guidelines, of course, are systematic review of the literature, evidence-based. You're familiar with these from multiple organizations that generate these. There's guidance statements, of course, regarding guidelines. And then I think this is an interesting product, which they have, which is best practice advice. So this is really trying to get into that space where there may not be current guidelines or enough evidence-based to generate clear guidance statements, but the providers are looking for information on how to take care of their patients. And I think right now in the genomic space, I could see some things moving right into that area. So the best practice advice tool, you can see here some of the best practice advice documents that they've already developed. So along with John and Arlene Weissman, who's the director of the survey group at ACP, we decided to survey some internists about genetics and genomics. This took place in November and December, so just a couple months ago, in preparation for this meeting. So the objectives were, and you can see the questions from Jean sort of paraphrased in this. We were interested in gaps in knowledge, gaps in skills related to genetics. We wanted to survey them about the changes in the volume of genetic testing taking place. We wanted to ask them about barriers that they saw when they tried to incorporate genetic testing into practice. And we wanted to ask them about their interest in educational programs. So the ACP has a very powerful survey infrastructure. A survey was designed and sent out to 806 participants from the ACP. And unlike myself, who gets surveys and seems to delete the emails in many cases, these docs are very responsive. And as you can see here, we got a 60% survey response to this survey sent out in November and December. And this is the breakdown of the respondent. So you can see it's across a broad range of practice experience, so from trainees and recent trainees throughout the lifespan of a clinician here, under 40 and over 55, as well as in between. A broad range of practice settings, most commonly the private practice, which is where most internists are. And it included both the internal medicine specialist, who is a generalist, if you follow me, and the internal medicine subspecialist, which includes all the theologists of adult care. So is their knowledge adequate? You can see here the response of those 400 to 500 individuals. So the percentage reporting adequate knowledge in, and they could answer affirmatively to as many of these as they so chose. So interestingly, 60% felt that their basic genetics knowledge was adequate. I don't know if that's been tested recently, or if an independent group would agree, but maybe they're telling us they don't want any more basic genetic teaching, or perhaps they are, in fact, up to speed on genetic principles. We didn't dive any deeper on that. Only a quarter or so felt that they had adequate knowledge in the indications for genetic and genomic testing and intervention. You can see that 3 fourths were worried about not being adequate as far as LC, ethical, legal, and social implications for genetics and genomics. And the numbers go down from there. So understanding and explaining results, when to test individuals, what to do with the results. They didn't have a good working knowledge in general about the performance and the validity of the tests, or which specific tests to order for a clinical disorder. And only 6% felt that they understood when insurance would cover the genetics test. And I can tell you that we do this all the time, and I don't understand that. So I'm interested in learning from these 6%. And we put here at the bottom some of the specific comments from the survey respondents. So adequate skills related to genetics and genomics. Again, these are those reporting adequate skills, so these are the affirmative. The finding the recommendations and guidelines for when to test, a quarter felt they could do that, and I think that's a skill that they probably apply in many areas of clinical medicine. Incorporating genetics into practice, you can see we're falling behind below 20% in all of these categories. When to test to confirm a diagnosis, when to test to confirm risk, and again confirming a suspected diagnosis using genetic biomarkers, and which tests to use to evaluate risk of developing disease. So there's a little bit of overlap here in some of the concepts, but you get the picture here. Certainly less than a quarter of these respondents felt that they were adequately prepared for most of these. So this is one that I didn't expect much action on, but this is the survey response that we got. So almost half being subspecialists versus generalists. 7% of the respondents said that they'd seen an uptick, substantial uptick in the volume of genetic tests. 42% increased somewhat, and 37% saying it stayed the same. We didn't again dive deep in this initial survey into what the same was, whether it was zero or a few, but none performed was 13%. Barriers to incorporation, the cost and the reimbursement issue again comes up large here and not understanding how to get around that tank. Charity with the tests themselves, lack of evidence about effectiveness, questions about validity. Again, ethical, legal, social issues related to genetic testing, anxiety or a barrier around whether the patients can understand the results about a quarter. And we looked into this just as many people have looking at patients obtaining testing outside of the medical system through direct to consumers and then bringing that to them about 10 to 15%. So when we asked them interestingly how much time would you be willing to spend in this area, you can see that we're gonna have a very limited amount of time for busy practicing internal medicine docs and internal medicine subspecialists. So we have one to two hours to teach all of genetics and genomics competencies for a large percentage of the respondents and then going down from there with 3% telling us to go away. The most preferred format, these categories are a little fuzzy around the edges, but you can see that people still like books and journals as a way to get their CME or their improved knowledge. A quarter still like the old-fashioned presenter in front of the room, self-assessment modules. We didn't specifically ask how these would be delivered, but in the ACP structure, many are delivered through the internet. Case discussions, workshops, discussions with experts or leaders and discussions with peers. As you can see, it goes down from there. And sorry, I'm not sure whether that's 37 or 47, I don't have the original data with me and I noticed that this morning. So most people in this survey wanted to get their education delivered online, some by print and then going down from there to other techniques. And one of the problems has been, of course, in getting people to participate is that some of the things that motivate providers most to participate in CME are not currently there for practicing internist. So it's not showing up on their board examinations. To a large extent, their patients are not coming in and asking them to interpret results or get genetic tests for them. So I think that those are about to change. I hope that some of them are. But you can see here that the things that would drive them to participate more would be CME credit, a big driver, maintenance of certification, of course, extra reimbursement, never a bad idea. And with that, I think that ends the survey data that I have to share with you. John Tucker has been a big advocate for this work within ACP, Steve Weinberger, Patrick Alguire and Arlene Weissman helped to prepare the survey and the data that I presented to you. And with that, I think we have time for questions, comments, et cetera. So we have Bruce, Rex, and Gene and Erwin. So Mike, with what you've presented and what Bob presented a few minutes ago with surveys, it's pretty obvious that at least these two groups feel ill-prepared. I honestly worry sometimes, though, that there has been a kind of almost, well, a negative perception in the community that this is just so dazzlingly difficult that it's a Mount Everest to climb. And actually don't think that that's a good message for people to get, if you'll forgive me. The evolution we're talking about, we have the opportunity for it to be intelligently designed also in the, I guess my hope would be to make it clear to people that you can dock what's new to what they already know. That physicians have a lot of experience, for example, dealing with ambiguity and making decisions about clinical validity. And largely the same is true here. I think we have, again, the ability to embed things in point of care decision support and we have partners whom they can work with. And so I hope that as these various surveys are interpreted that we try to put a positive spin on things that, yes, this is a lot is new, but it really has to be docked to what is familiar. And I think that should not be so hard to do. I think that's a great point. And in the genomics course that we're developing, we're really trying to use cases where the providers will be doing a lot of what they're familiar with, putting in complex information into context for the patient is what they do all the time. And though they may be a little bit intimidated by genetics and genomics, it's just a different kind of data that they're gonna be doing the same things with. Great, thanks, Rex. So the survey data is really, really interesting, but I wanna go back to something you talked about at the beginning of your talk in terms of the fact that ACP does a lot of work in the clinical guideline space. And one of the topics that's come up it's, I think virtually every one of the previous genomic medicine meetings is the fact that there are relatively few clinical practice guidelines for any areas of genomic medicine. And A, is it just too early for that to be, for any of them to be really solidly validated or how should we be thinking about that from your perspective? So that's a great question. And I thought it was interesting that a lot of the Vox felt that they can incorporate the guidelines because there aren't any, or very few. I think that ACP has a very well organized infrastructure for generating guidelines. And it has a lot of requirements about an evidence base. And most of clinical genetics and genomics does not meet the rules for evidence-based clinical guidelines. And so we're stuck in the position of not being able to write guidelines that would meet the expectations of the evidence-based medicine group. And so that's why I was particularly interested in ACP's other kind of less rigorous types of guidelines to help with practice. And I can't speak for how to play out with an ACP, but I'm hopeful that we would be able to find instances where we could get sort of that intermediary ACP behind certain best practices until we get to the point where we can write the hard guidelines, but... Can I just follow up on that a little bit? So what process, if any, could NHGRI or the broader genomic medicine scientific community be doing to advance things in your category of I guess it would be best practice guidelines maybe, which was sort of I think the lowest bar of evidence? One of the problems we face is that for some of these things, the evidence base will forever be small because we're just not gonna have a lot of examples and we're certainly not gonna be able to do randomized clinical trials on a particular variant. So is it just inevitably we'll just be at that lowest level of clinical practice guideline or best practice? Well, I think maybe an idea for a future genomic medicine meeting would really be to get those practice guideline experts in the room together with us and start thinking about that. I mean, it's almost for a while and on many topics, we're gonna have expert opinion driving best practice and I'm not sure without the real guidelines gurus in the room, whether we can sort of lay out the intermediary steps, but I think it's a great question. I don't know if anyone else in the room has experience or ideas about that. I know that cardiologists do a lot of guidelines. So maybe asking to speak to this specific thing because we have other folks. So we had Bill first and then Donna. I think this is a great discussion here because this is the way we're gonna be able to drive some of this uncertainty of where does this field lie for the practitioner? Forget about the academic practitioner. It is the majority are in practice and they need some guide within the guidelines. Now, addressing the guidelines, obviously the OAM came in with even more rigorous criteria, if you will, particularly from a review process. And for our guidelines, actually, Donna is here, she's president of the American Heart Association and our guidelines are done jointly, American College of Cardiology, American Heart Association. Where it comes is the rigor of the scientific background and the, if you will, transparency and lack of conflict there. However, if you look at our guidelines, the vast majority are not randomized clinical trials. A lot of them are expert consensus opinion. And I think this is, so within that, we're really not that limited provided that we have clinical outcome as opposed to just testing and whether testing does really change the outcome in individuals or the way you treat them. So I think this is very important for us to address and going back to at least my opinion and we'll share that with you this afternoon is we would like to embed this in the disease process. So instead of putting guidelines for genetics, it will be if we're talking about coronary disease, if we're talking about hypertrophic cardiomyopathy, Marfan, whatever it is, where does genetic testing fit? What should you do? If particularly and consider different clinical scenarios and this is where we came about with beyond guidelines is appropriateness use of where should you in all these different clinical scenarios, where would it be appropriate to order such a test and when? So I think there's a mechanism through the guideline process to do this. And I think this is very timely. Okay, so focusing again on guidelines, we have a whole list of folks who weren't talking about guidelines. And let me just, Joan, yours is about guidelines too. Okay, so we'll do guidelines, Donna. Just to build on Bill's comments, we really don't at this moment have the evidence base in cardiovascular diseases to really develop a guideline using RCT experience. So we would be in the realm of using appropriate use criteria. So I think being that's the realm, that's where we should start and that will drive practice ultimately. Great, okay, so and Ned is about guidelines too, but I'm not calling on you, so because I think we had Alan, were you gonna talk about guidelines? No, okay. So the guideline folks who were, let's see, Mary, Joan, and someone else here, and I'm sorry, Catherine, and then Ray had a comment on, oh, and Ned. Okay, oh my goodness. So, yeah, really, now I've forgotten where I was. Mary, yeah, Mary, go ahead. So I think one of the things that's making genetic testing guidelines different than other guidelines that we're used to using in medical practice is this pressure that whole exome and whole genome and other array-based tests are being performed. So take out all of that soul searching about whether to test. And that changes the question a lot, and that's what I run CPIC, Clinical Pharmacogenetics Implementation Consortium with the firm GKB, and we are specifically aimed at pretend you already have the genetic information. What are you obligated to act upon for patient care? And that takes very practical clinical decisions. How serious is the disease? How serious are the adverse effects? What are the alternatives? If there's good alternatives, your threshold for creating an action plan based on genetic testing is completely different than if there aren't. So I think a lot of guidelines are bogged down in the whether to test, and we need to get away from that because it's going to be how should you act upon the information once you already have it. Okay, so guideline folks, I think Catherine, Ned, Joan, and possibly Ray. Okay, I just wanted to act quickly. Anybody who's been in a room with Mewing Curry is this is his favorite topic, I think, of evidence and how much evidence we really need. And we've spent a lot of time on the IOM Roundtable talking about this. One thing I think he's doing, and maybe somebody else knows more about this in the room, is convening a meeting in February with all of the players in evidence guideline development to talk about this very issue about how much we really need to do. We're not gonna have randomized control trials and what kind of things we need to do to gather the evidence to move forward. Great point, yeah. Let's see, so Ned. So that's a great segue. So I think what we may face is the fact that the methods will vary on the clinical scenario. And so a lot of work for EGAP and other groups has been based on the screening scenario and the tumor profile and the clinical scenarios that are being discussed around the table have a different imperative day-to-day clinical care. So I wanna follow up. The reality is we have the information. We're going to have to incorporate guidelines before the evidence is available. My plea is that we don't stop there as we have often in the history of medicine and not fill in the gaps of evidence and let these guidelines be evidence-based as we fill that information over time. That I think is the kind of moral imperative of evidence-based guidelines that we have to do something with the information we have now because the patient and the test are in front of us. But we need to fill in those evidence gaps and have that discipline to change those guidelines over time. Now that's an excellent point, Ned. And one of the things I think we find on the research side is we don't really know where are the areas that you need evidence and what kind of evidence do you need. And then we have to match that with our resources and being able to produce it. But somehow we need to make that link a little bit tighter in producing it. Okay, so Joan? Yeah, my comment is really a question directed to the different healthcare provider organizations who are represented here. And I realize there's a lot who are missing because usually when it gets down to the actual practice levels, practitioners look to their own societies for their own practice guidelines. And that's often a barrier, particularly in an area like this, in that every organization has its old standards, its own methods, which are often several years in making to come up with the guidelines. So I wonder if this is an opportunity for various practitioners and through different organizations to be working together around the generation of practice guidelines for genomics, as opposed to every provider organization doing their own. No, again, an excellent point. I think one of the reason we have everyone in the room, and I'm sorry, we don't have a longer lunch period so that we can be addressing it, but it will be addressed, I think, later this afternoon. So I did see you, but let me see. Anyone else about guidelines? Just one second, Mira. Ray, was your point covered? As a cardiologist, both a fellow of the AHA and the American Collegiate Cardiology, I have authored guidelines for the cardiomyopathies, genetic cardiomyopathies for the Heart Failure Society of America in 2009. It's very important. We actually discussed this issue of, of course, being a cardiologist, we expect the highest level of real evidence and we just won't have that. So I think this topic is really key if we can make headway on what the most appropriate evidence is, whether it's called the guideline or not. I do think there is intense interest in the cardiovascular community for this, and particularly as we move into whole genome and strategies for, even the Mendelian diseases, a lot of interest, and we have to address this. Ray, so I think this will be the last guideline comment. Mira, for the moment, at least, Mira. I'd actually just like to second the comment about collecting outcome data, because I think as, and embedding it within the disease process, because if whatever the healthcare system of the future turns out to be, we're gonna have to show value. And if value is outcome over cost, if we can actually show that the outcomes are better over the lifetime of a disease by doing this testing, we're gonna not have to deal as much with the cost issue. Excellent point. Okay, so I wanna then go back to the other comments that have been patiently waiting, and maybe we can get the rest of them in the lunch period. So I have Jean Pasimani, Irwin, Kate, and Alan. Were there anybody else who was waiting? And Debra, okay, we may not get to all of these, but we'll do our best. So Jean. So here's a quick one. Did you see any contrast between the generalists and the sub-specialists in your survey? So the survey was too small to tease that out, but the plan is to actually, while we're gonna discuss it in the next couple weeks, is to do a larger survey amongst the ACP wider group with the hope of looking at that. Irwin. Yeah, Mike, thanks for the very timely contribution. I was just wondering, you had in your list of genetic testing only the kind of questions that relate to disease risk, disease susceptibility, et cetera, and I was just curious whether you actually also had questions about pharmacogenetics because there may be a little bit of a different perception in pharmacogenetics compared to disease risk and susceptibility genetics. That's a great point, Irwin, and we didn't go after it in this initial survey, but we're gonna take back ideas to hopefully do a larger survey in the next couple months. That's a good point. Thank you. And Kate, I think? So as someone who's an internist and internal medicine department, I think that the uptick in referrals, and Mike, you can comment on this in the past five years, has been immense, and I think that what I find is that if you have a subspecialty in particular where they start seeing one disease, where they're interested in genetics, as soon as you get the one in there, then they start referring everybody for genetics, and that's, I think, partly why cancer was sort of on the front of this, because they sort of had a disease early on, but now we have pulmonary cardiology and decrine. Every subspecialty is consistently referring patients to us, and once you get in one place, you get the rest, and I think that we have more business than we could possibly handle, basically, and I think that what this really speaks to is a really importance of identifying physicians to be trained in internal medicine and in genetics, which is, given the dearth in other areas, is really even worse than certainly in pediatrics and other subspecialties. Excellent points. Alan, I think you're next. Ah, there you go, and Debra, I think you're next. This is not really a question, but it's a comment from the morning's discussions, which is, could I make a plea that we stop using the word whole in front of exome and genome, because I think that's gonna be just another educational hurdle for physicians in that what we do today doesn't actually get you the entire genome or even exome sequence, so we're gonna have to reeducate everybody that, and also that there are holes in the information, even if you have an exome or a genome, it's not getting to certain mutations, repetitive sequences, pseudogenes, those kinds of things, and even technically, when we get to be able to do that, there are changes that are disease significant that won't be detected by a sequence. So I think if we use the term exome sequencing and genome sequencing, it's actually more accurate, and I apologize, but it's become a pet peeve of mine. Yeah, you actually missed our last meeting where Mike actually proposed that we officially call it whole H-O-L-E genome sequencing, and so that is the convention that we use here, so. Great, all right, any other questions or comments on this topic? Oh, okay, so Bill, the last one. Thank you. I wanna make a comment and then make a suggestion. The first comment is that I'm very impressed with the amount of survey data that are out there. I think it's wonderful. We've had two or three presentations and cardiology is gonna add to that, where we've actually surveyed our members and we have data. It really is good and I think it speaks to the fact that we've all sensed holes, excuse me, for using the term, but, and that's the first step. I think that's great. Well, it sounds like a possible publication in the making if the four of you can get together. Well, and actually, Gene and I talked about that. I think that's great. The other thing is that I just wanna bring up a suggestion here that I would like for folks in the room to consider going forward, not for this meeting, but as other thoughts are pulled together and expressed. One of the services that I provided to the college, our college before I came on full-time was to be co-chair of the Medical Professional Liability Working Group. And it occurred to me as I listened to these presentations that we've made huge technological advances in medicine in genetics and genomics and that whenever there are technological advances in medicine going back to the 1850s, there are substantial liability increases. And so let's just think about that and maybe at some point it may be worth us convening a small mini-group to sort of pull together the experience to identify the risks and begin to think about how they can be mitigated because I think those would be helpful activities for our practitioners, for all of our practitioners going forward. It's interesting in the barriers that have been identified, we almost never hear that one. And yet when you talk to people, they say, what do I do with this information? I'm going to be liable for it and it doesn't come up then, very good point. Great, all right, Mike, thank you very much. You stimulated a lot of discussion and thought. This is great. So next we're hearing from Sandra Swain and Bill Powell. I think you're doing a duet from the Society for Clinical Oncology.