 And first is Deborah Leonard from the College of American Pathologists. Well, thank you for inviting us to participate in this conference. We're very excited. And I was a little daunted when I got this list of topics that we were supposed to cover. So I will try to, I targeted my talk simply to address the questions that were asked. And so we will look at the first two together. Member needs assessments completed or planned in state of genomic science and practiced by members. We are at toward the end of a five-year process of what we call the pathology transformation process, which was driven by changing pathologist demographics as well as healthcare delivery reform and genomics. Those were kind of the three major driving forces of this. In 2010, we did a member survey of genetic genomic knowledge, and we were rather pleased to find that, you know, 61 percent of people, pathologists, practicing pathologists, and this was a thousand of our 17,000 practicing pathologists, were familiar with whole genome sequencing or analysis, which we were very surprised to find. Now, we did not test them, so we don't know what they mean by familiar, but, and then we also asked about gene panel tests and single gene tests, and of course the familiarity went up. So from 2009 to 2012, we basically defined the pathology transformation strategy, which I think any practice subspecialty, you could take this and just change pathology to pediatrics or medicine or whatever, enable our members to control their professional economic destinies, focus our support on pathology practices because, classically, the College of American Pathologists had been focused on the individual pathologist, so it's just a technical point, and help them create greater value, especially in embedding new genomics and informatics capabilities in their work, get paid for this in the context of coordinated care. So it's a very simple strategy, and we are going to implement a multi-year series of initiatives starting this year and moving forward, and one of the aspects is to take the analysis that we've already done, and develop a specific genomics strategy or genomic medicine strategy of what initiatives are going to have the greatest impact in helping pathologists move toward the practice of genomic medicine. So we were next asked to talk about the short and long-term pace of change in genomics use, so in pathology practice we are currently, standardly, doing single or few mutation or single-genar pathogen detections or a few genes, but we are moving to incorporating next-gen sequencing, basically, or genomic analysis into our practices, doing, predominantly, gene panels or exome sequencing, right now, research, this slide may be rapidly becoming dated, but genome and transcriptome sequencing, we are beginning to think about doing clinically, but pretty much remain in the realm of research, and we feel like all of the research will build back flow to help us understand the clinical usefulness of the sequencing that we are doing over time. So this is what we call genomic analysis by next-gen sequencing. So what you need to understand about pathology or molecular pathology tests is that not all molecular pathology tests can move over into next-gen sequencing platforms. So we do a lot of tests, HIV viral loads, CMV, EBV viral loads, bone marrow and graphene analysis, those will have to stay on their current platforms and can't really be done by next-gen sequencing, but there are a lot of genetic and cancer-related tests that are better done by next-gen sequencing either as gene panels, and that would be for cancer or specific inherited disorders where you know the sets of genes used for that or causative of that disease, or exome sequencing, also for cancer or for unidentified inherited disorders, exome or genome. So we, in the process of doing this transformative strategy investigation, looked at the early adopters of genome exome sequencing or gene panels, next-gen sequencing technology in clinical laboratories, and there was quite a rise in the number of laboratories doing this, and this is in 2011 just when the MySeq and Ion Torrent smaller instruments became available, which are really the game-changers. So I will go very rapidly through this, that the first genome was done on ABI sequencers, which cost a lot of money, moving into next-gen sequencing mostly in research, but it was an instrument that cost $750,000, and it had a one-week data processing time, I mean data generation time, but the MySeq and Ion Torrent basically are in a clinically relevant price range and a clinically relevant turnaround time, so this is what is the game-changer for us, and we're moving on to an Ion Proton and other instruments that will have clinically relevant costs and turnaround time, so we are seeing much, much greater adoption of next-gen sequencing technologies, predominantly for gene panels in clinical laboratories. So the current plans to address genomic literacy by the college, and I'm going to talk about different categories of initiatives, and one is assuring the quality of the genomic tests that are being performed because the college also is an accrediting body for clinical laboratories with deem status under CLEA, and so we have developed an NGS inspection checklist series of questions that address both the wet bench aspects of generating the data as well as the bioinformatics pipeline, and it focused prominently on proper validation and documentation and applies to any instruments or tests being done by next-gen sequencing technology, and those became available in July 2012, and we are updating those this year in 2013. CAP also has a proficiency testing program that we offer to laboratories, and so we are looking at how you do proficiency testing for next-gen sequencing-based tests. We are going to use highly characterized genomes, and I can go into detail about how we're characterizing those, and then each laboratory would perform their test on those A characterized genome or more sent to them, and it will assess both the sequence data generation and bioinformatics processes. We also have developed what we call resource guides, and we actually have four resource guides. There are two related to genomics. There's a genomic analysis resource guide and a molecular diagnosis resource guide, so some pathologists need to get up to speed with the now routine molecular testing, but then there's also one for genomic analysis, and here you can see the table of contents. You can read through it of the genomic analysis resource guide, but there are pearls from early adopters, there's technology information, we do it by, we have information for different types of testing being done, standards and accreditation, and in 2013 we're going to be adding a bioinformatics section to this resource guide, so many pathologists have given us very positive feedback that these are very, very useful to them. In education realm, we had 37 molecular or genomic courses at CAP 12. I know relative to ASHG, every single one of their courses is related to genetics or genomics, but this is a big change for the college, and there's a range of topics, some involving next gen sequencing, but others molecular testing, molecular heme path, molecular microbiology, so we have to consider the molecular and genomics of all kinds of applications from inherited disorders to cancers to infectious diseases and pharmacogenetics. We also have three pharmacogenomics online courses and other, you know, a total of 16 online courses that pathologists can use for CME or SAMS. SAMS is what we, it's the continuing education for re-accreditation at the 10-year period. And out of the committee that I run, we also have a webinar series that's been going on for three years, and it focuses in three areas. Genomic testing, around next gen sequencing of panel sex homes or genomes, molecular pathology testing, so, you know, not next gen, and then organ-based molecular pathology, which predominantly focuses on cancer. And these webinars have reached more than 4,500 CAP members, have attended one or more webinars, and so we're having a pretty significant impact in reaching pathologists with the webinar series. And these are some of the upcoming topics, molecular microbiology and community-based practice, pathologist role in breast cancer diagnosis, you can see many of them are, we always have a talk on DNA day that is available nationally, but it's done at the College of American Pathologists headquarters in Chicago. And we are also providing tools for practice pathologists. We call these specs, don't ask how that happened, but they're short presentations on emerging concepts, and what they are are short PowerPoint presentations of five to ten slides that can be used to describe testing that is relevant and impacts patient care directly now. And they are not branded with CAP logos or anything, they are to be used by the practicing pathologist, and we also provide key references because some practicing pathologists actually do not have easy access to PubMed, believe it or not. And so they can customize these for their local conferences, tumor boards, or to talk with their hospital administrators, and we are tracking the use and we are providing updated materials. So when you download you have to register that you are getting this, and then as we update the information we would push out the updated information to anyone who's already downloaded previous versions of these. And so we have five of these in existence, our plan is to develop two more and update these, one on the work up of colorectal cancer, so that's somatic mutations, and then inherited colorectal cancer, metastatic melanoma, BRAF testing in thyroid cancer, and work up of polycythemia and thrombocytosis jack two. So what's the process for genomics practice guidelines development for diagnosis and treatment? We have what we call the CAP pathology and laboratory quality center to ensure that they're, so basically this is our area of the college that develops guidelines, uses evidence to support development of practice guidelines and protocols, and we usually are doing that development in the context of a multidisciplinary approach working with either specialists from other subspecialty areas or other professional organizations. And it facilitates the coordination of consensus activities in the absence of evidence-based practice guidelines. And so this is the process, ideas for guidelines that are needed are submitted and we select the ones we're going to work on, and so we develop the scope and form the work group, do the research and literature review, solicit and develop the guidelines, solicit public comments, complete recommendations, review and approve, publish and implement, and then we haven't yet quite figured out the process for maintaining, well, actually we do, I mean, because we have some guidelines that are out. So there are two guidelines developed in collaboration with ASCO around breast cancer testing. We have one in-press around the selection of lung cancer patients for EGFR and Alk tyrosine kinase inhibitors and two more that are in development around acute leukemia and colorectal cancer. What you can see from this is that for pathologists, the reality is we make our money around surgical pathology practice. And so the cancer genomics is much more important and sellable to practicing pathologists than is inherited disorders that we don't have a lot of familiarity with, but we are trying to impact that. So activities by associated specialty boards to include genomics and certification processes. Our residency training program requirements currently require one to three months of training in molecular pathology, not necessarily specifying genomics. So those areas, those centers that have training programs that are incorporating next-gen sequencing and genomic testing into their molecular pathology laboratories are providing that as part of their training. Others that don't have it are not. So there aren't any specific requirements for genomics per se. The American Board of Pathology includes molecular knowledge. We refer to as molecular pathology knowledge. Seven to nine percent of the AP exam is based on molecular pathology and 10 to 15 percent of the CP. So that's anatomic pathology and clinical pathology. We are the only specialty that has two primary board certifications. Sub-specialty board certification in molecular genetic pathology is jointly by the American Board of Pathology and the American Board of Medical Genetics. That has not yet incorporated genomics into their requirements, but again, most of the places that have MGP fellowships are at academic medical centers. That's also where the next-gen sequencing is being adopted mostly. So many of the molecular genetic pathology fellows are being trained in next-gen sequencing technologies. And then the college and the association of pathology chairs have actually developed a memorandum of understanding to work together on pathology residency training issues, including genomics residency education, both at the residency and the fellowship levels. And then finally, and this is my last slide, there is Richard Haspel is at Beth Israel Deaconess, Harvard, and he has been leading an inter-society initiative, inter-pathology society initiative to develop a national curriculum in cancer genomics for pathology residents. We called it TRIG. Actually, it's not just pathology because the National Society for Genetic Counselors and other organizations have also been involved in this. And so, Rich just got an NCIR-25 to support a five-year project in implementing a curriculum that we have already begun to develop, but we are going to fill it out a little bit more with three aims, is to develop the curriculum, evaluate that, and my university of Vermont will be one of the four training sites where this will be tried and then promote the national implementation of this curriculum. The goal is greater than 90 percent of pathology residency training programs nationwide. So I think I answered the questions. Great. Thank you very much, Deborah. Yeah, that was a tour to force through the many questions that we sent you. Thank you. So we have Mark Retain, Jean, let's see, Bill, sorry, and then Mark. So, Deborah, I appreciate that Pharmacogenomics is one of the areas in which CAF is interested, and I note on your website that you have a number of learning opportunities, and I'm just wondering, are you partnering with any clinical pharmacology organizations to develop these, or is just something CAF is doing on its own? We have toxicology expertise, and because we run toxicology laboratories, and so I think it goes along with the pharmacognetics testing that we do, and it's growing, so it's a collaboration between toxicology, which is within pathology, but not necessarily clinical pharmacology. Yeah, because I don't think the lab medicine types are very involved in cutting-edge work that is going on, and so I would encourage you to think about working with organizations such as American Society for Clinical Pharmacology and Therapeutics as one example. Well, we clearly are highly collaborative anyway, so that's a good suggestion. Jean? Thank you for really a nice summary, Deborah. A couple of questions. One is, in 2008, you or someone said about putting this all together and you've got a wonderful product. Can you tell us a little bit about how you did that? Painfully. It really was the vision of the president of the College of American Pathologists at the time, as well as several of our board members who really felt like we needed a process to move pathology toward what we were then calling personalized medicine. We're now transitioning that term because personalized healthcare, personalized medicine is offensive to many physicians because we don't go out into the waiting room and say, okay, everybody with pneumonia, come into my office now. You know, it's really, we personalize the care that we do now. So we prefer the term genomic medicine or precision medicine, but genomic medicine really ties it to the genomic information. But all that was happening and a big uproar within the college in 2008 because many pathologists were not incorporating genomics and even reticent around molecular pathology, which is the single gene testing. Genomics was kind of like the future at that point. The future is now. So there was some resistance to change, I guess. Yeah, but it became overwhelming to change. And then I actually chaired, there were four modules that did a two-year process of looking at the economics, the demographics of pathologists. I was doing the Emerging Technologies, which included not only genomics, but also in vivo microscopy and digital pathology, and then the service models for pathologists. And those four groups then provided information and then that became the work of the integration team to put all that together into what we now call pathways for transformation. We have a document that pathologists are actually reading and embracing because it ties in with the ACO changes and the coordinated care models of practice in that pathologists have to be out there. We can't sit in our laboratories. It's becoming really personal now. Sorry. So it ties into a lot of different aspects of how pathology practice has to change, and genomics is just one of those. And your regulatory burden or need helps you get this out to people of all pathologists who are practicing. How many do you think you've actually gotten to with all of this educational stuff? I don't know. I do know that one of my new faculty at UVM went to a leadership conference led by the college and came back drinking the Kool-Aid. And I am absolutely delighted because he's going to lead in changing pathology practice at UVM to be more the transformed model that we are looking to become. Thanks, Bill. Yes, thank you. That was really an excellent presentation. I'm a cardiologist who is full-time with the American College of Cardiology, Senior Vice President for Science and Quality. And I have a question that I think my colleague who directs our Lifelong Learning Division would ask but she wasn't able to be here. And it's a little bit of a nuisance. You mentioned that 4,500 of your CAP members had attended the webinars over a period of several years. We think that... That was actually just in 2011. Oh, just in 2011, even more impressive. We think that webinars are important and promising ways to provide information to our members but have not had success in those numbers ever. And so my question is just basically how many members, how many CAP members are there? I kind of like to get an idea what the denominators... I know that there are supposedly around 17,000 practicing pathologists in the US but I don't know how many are CAP members. And one thing I didn't mention about those webinars, they are not CME because we can't be nimble enough and do CME. I hate to say that with the head of ACCME sitting. But it's very hard to do that. And we also archive those webinars so that you can go online. So you can go on to the CAP website and view any of those webinars over the past three years. They do become dated because they are on pretty hot topics usually. Well, that they're not CME is even more impressive that you have those numbers of attendees. I think that's great. I'd like to just chat offline about how you're so successful in that. My contact information for the next seven weeks is in the bulletin. If you call that number or email me, hopefully it'll be forwarded or my assistant will say where I've communicated. Okay, thank you. Mark? Yeah, it is very impressive because most of us have had the experience that Bill related, which we... if you build it, they won't come. So maybe it says something about the amount of free time that pathologists have. I don't know. So my question is a little... The occasional energy that we have. Okay, fine. Well, you say tomato, I say tomato. So you've obviously been tracking the use, which I think is great, and that's a very useful process metric, but I was wondering if there's been discussion or any efforts in terms of actually measuring the impact on practice. Have you been able to take a look and see how is this really fundamentally changing how our members are practicing? It's much harder to do, and I'm just curious if there's been discussions or attempts. Not in a systematic way. I don't know if the college has plans to repeat the kind of survey that we did in 2010 to see if the kinds of things that we were asking about have changed, but I showed one slide from the survey of the pathologists, but we actually did a survey of other subspecialties, patients, many other people don't know anything about pathologists and it just confirmed that they don't know anything about pathologists and we basically hide in a hole. And so that's part of what we're also trying to... I don't know the way to measure that. We have gotten verbal, I mean, email and other comments back of how individuals would incorporate this information into their practice, but not any systematic way across all of them. Great. Well, maybe while Robert Saul is heading up to the podium for the next talk, I might ask Debra, I noticed your meeting topics were, you know, legion, I think, and it looked like you had a very strong emphasis, as you said, 30-some seminars on genetics. I'm curious, I don't know that a lot of the investigators that NHGRI supports or even some of the other institutes who do molecular genetic type work necessarily submit to your meeting and recognize that, you know, you don't want to commit the college right now or the program committee, would there be interest in having the Cancer Genome Atlas or the Clinical Sequencing Exploratory Research Centers or other things that are supported in this space presenting abstracts or posters at your meetings? The more that pathologists become aware of the other initiatives going on and the college does try to interact with other societies that are appropriate to whatever projects we're working on. So, yes, our meetings are in September, usually, and so I don't know when abstracts are due, but sometime in early summer, and you can go on the CAP website and find that out, www.cap.org, it's very easy. Great, thank you very much. All right, Dr. Saul for the American Academy of Pediatrics.