 I am going to keep this short and sweet. I do not have any slides, so I'm just going to pull the questions back up, and we will open the floor to discussion. I just had a question about the training. Is it focused on how to work up the case, or has there been a focus on how to follow the patient after a diagnosis or after not having a diagnosis? So there's a couple of different settings for the training that we're doing, at least in the UDP program. One of them, as Ron mentioned, is having people rotate through our program, and that's very much on management and work up while people are there. We encourage people that are rotating to come to some of our other meetings where we discuss things that are going on after a person leaves the program. But I think that there may be a gap there that includes some of the things you're talking about that we're not doing yet. And then other parts of our training program focus more on the technical aspects of a UDP, for instance, the bioinformatics that you would use for a UDP type of patient. So there may be places for us to go that we're not covering yet, especially in follow-up. Yes? So it's possible that some of this was covered in the session that I missed, because I came late this morning, but it also relates to training. And that is, does the network have a sort of systematic process evaluation and improvement sort of arm? Are you looking, in other words, at the diagnoses that did get made and asking the question, the next time around, how should this be approached so that that diagnosis gets made more efficiently? I would think that the system should be learning as to how to do this well. And so when it comes to teaching, it's not just teaching how to analyze genomic data, which is sort of the obvious thing you do well, and a lot of places could use that knowledge. But I would think that you ought to be able to find ways to more efficiently answer these questions and help disseminate that information out to the community. Yes, Wendy? So it's obvious that there's synergy with the Centers for Mendelian Disorders. How does it actually work in terms of being able to aggregate the data and perhaps do case matching in terms of seeing rare variants across cases? Is this easier? Do you have to go through DBGAP and be able to get access to each one of those studies, which seems quite laborious? So I can take that. So the data for the Centers for Mendelian Genomics is all being also fed into the Matchmaker Exchange just through a different node. So all of our data that's going into Phenom Central will be able to match with the data from the Centers for Mendelian Genomics and anyone else who feeds into the Matchmaker Exchange. But it does mean that the person analyzing the data has to recognize that variance and push it out to the Matchmaker Exchange, right? I mean, it's. It does require someone to put the data in a database somewhere first. So I think this is what we do. We're connected with the CMG. And every time you submit a case, we go to all the databases, including the CMG database, and have been actually already able to exclude cases or find cases where we found the second case. So this is done systematically. Judy? I'm wondering if there's going to be a new genetic specialty of interpretation of what you get back from the lab. In other words, some of the labs interpret a little bit or say we don't know what this means. But don't bother to go to all the databases to find that there was ever anything reported before. And it seems to me that some thought should be given to training such people. So there are such a person at tertiary care centers. I mean, I don't think clinicians are going to be able to do this. I really don't. You're going to depend on the lab or somebody who has the time to do the rest of the work. So I actually think there may need to be a new specialty. So I can speak a bit to that. So we are in, and I agree with you, we are developing a training program really for a variant curation. So we all talk about curation. But this is a really specialized field where there have to be rules that are followed. And the more universally they're followed, the better. So we're developing a training program. It'll be more of a certificate, probably, for individuals with PhDs. These may be individuals in their postdocs and genetic counselors as well. At the American College of Medical Genetics and Genomics has begun thinking about that sort of thing as well. And actually creating a certification pathway that would be analogous to medical biochemical genetics, like a one-year fellowship you would do. OK, question back there. So also with regard to more general training, you can have a subspecialty certificate. But that means you need some fundamental educational goals in the training of medical genesis as well. I don't think any of us is going to pretend that we're going to become the expert curators unless we have additional training. But we have to have some strategy for making sure that young people in training now at least know what they need to do to get the information. And the other thing that I was intrigued by the whole concept of people rotating is that is there a defined curriculum that could be established in other centers where even if you weren't trying to be the undiseased disease center, you could at least set up a paradigm or protocol that could be emulated and taught so that other people could become more effective in getting things started for you. In some ways it's the outfall of exactly what this program is trying to do, of get you to the researcher who's working on it as well. And if it was curated well, then you get your totally unique patient to the really right person. So two things. One, I don't think that there's a curriculum for our inpatient rotation, but I think it's a great idea, something for us to think about. And then to the second point, a huge part of our time at this point is spent trying to accomplish a transition of people that we have seen into some sort of research or find an expert. So if we don't diagnose 75% of our patients and we have an ongoing relationship with that group, you can imagine that after having seen 1,000 patients, most of the people that we deal with on a day-to-day basis administratively are people that we are following that process for. So it's really become a major undertaking of what we're doing. So David, so should we then, as UDN, develop such a curriculum? All the sites contribute to it? Because I think that would be very useful. And we have kind of done a little bit of it in our Masters of Clinical Science program. And we take our, these are physicians who are going through getting their masters in clinical science. And we have a two-month rotation that they get to analyze sequence data, figure out how do you figure out which variant may be a disease-causing versus non-disease causing, work with our internal model organism cores and stuff like that. But I think, going back to Susan's point at your point, it may be useful if we, maybe that'll, that'll involve making another working group, which would not be good. But I think it'll be very useful, because all of the sites would have useful things that they can contribute to that core curriculum. And then that can be implemented not only to the internal side, but to any other site that want to take part in that. Well, I think it's a wonderful idea, of course. I think it's just a matter of finding the people who to put in the time and answer the usual fundamental questions, which are, who are the target people? What are the goals? What's going to be the product of this? Is it practical information about how to address variants? Or is it for a physician or someone else who's designing a follow-up program for somebody who's come through a program? There's lots of different things you could do. You know, because I think, if you think in terms of long-term, eight years down the road, I mean, one of our goals could be actually train as many physicians as we can. We cannot make them geneticists. They may not be able to go through the training that American College of Medical Genetics is proposing to do, but maybe in each institution we could have X number of people, maybe they're cardiologists, maybe they're pulmonologists, have gone through, gotten some experience. So they can be starting point for guiding other physicians how to kind of approach that. And that is something that we could do without going through an extensive sort of. I would go one step further than this. I mean, isn't the fundamental pathway here defining mechanistic medicine? It's getting from syndromic pattern recognition to causation and a subset of disorders. And that's essentially all of medicine, ultimately. And you can, the fact is we can only do it in a very limited subset of disease at the moment. As information accrues, it's gonna be all of medicine. So I thought, I actually have to say, I thought integrating Rachel's comments with Bruce's comments. This is something that has to be so clearly aligned with the way that all of medicine is practiced, all of training is integrated, that there should be some effort to try and bring in organizations that are actually responsible for all of those components of the infrastructure to make it a generalizable theme. It's not gonna happen overnight, but we need to be able to begin to include all of the training organizations in medicine, all of the training, all of the organizations that build the infrastructure for the practice of medicine. I mean, if you think about it, pattern recognition, this is the sort of thing, as I said at the start, and I actually do have more than one thing to say, but I always say the same thing. If there was a uniform phenotype, you'd just be able to basically work out which classification that phenotype dropped into, and then you would understand the pathways and the biology that you might need to. At the moment, we're literally at the level of saying, epilepsy, which fine is a great classification scheme, but it's one that was invented in biblical times, and we haven't really moved beyond it. Perhaps thinking about the model of the North American Metabolic Academy, so an intensive one week type of course, granted it wouldn't reach everyone, but you could open it up to a wider audience and address really all of the things you were talking about, whether it's how to work up the patients with undiagnosed disorders, how to do variant curation, how to think about modeling, something like that might be extremely useful. Any more comments as far as training? So what about the international collaboration? So one of the things that we are tasked with in this session is looking beyond the UDN and sustainability. So there already have been workshops in Budapest and Vienna and other places, Anastasia can probably expand more, to already start these connections with international UDN collaboration, so international and domestic collaboration. So are there any comments as far as those? Or suggestions or questions? Yes, David? Just in answer to a question earlier about what do the sites get out of being a member of the part of the UDN, for instance. I don't think it's been established really as far as the UDN itself, that's something we're working on in terms of the international group, it's very much been, at least in my opinion, feeling like a meeting of equals where everybody gets together and says, we all have a collection of our own patients locally, what are things that our local governments and our local institutions will allow us to share and then work on equal peer data sharing as a place to start. So I think that that's been a central focus of the international meetings so far. Yes, Judy? I like collaborations a lot, I think they make you think about things you wouldn't think about it, elsewise. Has the network thought about bringing in a healthcare provider to start to get the healthcare provider to actually think about how it would do this? Because ultimately, you know, 10 years, maybe 15 years, the healthcare provider should be doing this. And if you brought them in at this stage, maybe just as an observer or whatever, they might help you think about, okay, we're Kaiser, and if we spent more than $10,000 trying to make a diagnosis, we'll now go into plan B, rather than spend any more money trying to make a diagnosis, something like that. But to get one of the big healthcare providers like starting to listen and starting to understand who these people are and what's involved. I think it has to be more than one, I think ideally it should be a consortium of parents that are actually observing and understanding how this is implemented, otherwise it's not gonna be worthwhile. I think Howard has had experience dealing with Blue Cross, Blue Shield, and others. And I don't know what your thoughts are, but I think building a broad consortium and having them understand how this will impact care delivery in the next three to five years is critical. And the other thing about it is it's very well aligned with PMI, with ongoing efforts in care redesign. I mean, everybody is trying to do all of these things in their own different ways in different parts of the healthcare system, but nobody's talking to each other. And the healthcare payers are at least one place where it all sits. One of the challenges with the payers having just moved states, I can tell you that they're all state driven. And so you have a big difference of problem sets with the different Blue Crosses and Blue Shield. Blue Cross, Blue Shield of Alabama just last week said they would start paying for any genetic testing. So I think one of the challenges is, it might be coincidental that we're there, that there's a lot of pressure that has to go on in this. And I think the challenge with the payers is that they keep looking for what the study designs are to prove this. And I have to tell you, I have found no one who's told me what the answer is and so our solution has been really very simple. So I will give you our secret sauce. You find if they'll pay for a gene test, you say, I will do this gene test. And then when that fails, I will do this gene test. And then when that fails, I will do this panel. And then when that fails, I will do the exome. And when that fails, I'll go to whole genome. And so when we were in Wisconsin, we got over 80% of the time we were getting reimbursement because we had done that. So they knew that it was more economical. So I think that's not about the clinical utility. I think it's about showing that it's more economical for them. And so it's not an easy road, but it is nothing but appeal after appeal after appeal. And then building that with the institutions to a point where it becomes recognizable. And the other part that I'm doing that I would encourage all of you to do, in fact, I will tell you right now, your institutions also don't pay for genetic testing. Your plans don't pay for genetic testing. So have your plans start driving, will you pay for genetic testing? And that's the other way to do this. So getting companies starting to demand this. The insurance companies only deliver on the policy for which the payer pays. So they're just managing it. So again, push your institutions, push those people you're talking to when people say, what can I do? Demand your employer pay for genetic testing and I guarantee you that will change it. I think getting the payers together, we've tried this, I'm just not optimistic. So just a message from a universal healthcare provider as in Canada, when you show how much money you spent on the Odyssey, they get it. No, not in our system because they're only on the system for 18 months, right? The average time someone is on one of our plans is 18 months. So it's a little bit of a challenge. The idea is is the old, get them out of my emergency room mentality. Let's just get them out the door as quick as we can. It's a problem, it's a problem. And I have to say, Judith, it might be different in British Columbia, but in Ontario, I'm still trying to convince them about the economics of this. It's not that straightforward. We want to of course be the leaders for Canada. So again, I think we're talking about value or outcomes related to cost, but you mentioned that clinical utility wasn't in the equation when you made the argument. So I'm a little bit, I'm not quite, I'm hearing around the table that trying to demonstrate the utility or usefulness of the information and patient management, I would guess, is important. So clinical utility is really easy to say. It's really hard to prove because who is defining the boundary that you're jumping over? How many cases are we talking about? Are we talking about a million cases? Are we talking about how many variants? And it's a really hard problem of getting somebody to say, this is the bar you jump over. If we knew what the bar was, we could design something around it. But I've yet to have an executive, a chief medical officer, or anybody else in the insurance industry tell me what clinical utility means for us to be able to meet. So a lot of times it means improved health, net health outcomes. So that's pretty vague. But maybe one of the roles that this group could do is define outcomes that matter to the various stakeholders involved and to push that agenda so that a diagnosis is an outcome. And what is avoided in terms of pain and suffering or quality of life and those types of metrics. So I guess trying to define outcomes, having metrics and having data sources to measure those metrics would be useful. I was thinking about it. I should say something to this. In general, I agree with you. But something which got a little bit almost, in hindsight this morning is my experience, I would say that one of the most humbling experience of my professional career so far has been just making a diagnosis for the last five years and ending the diagnostic odyssey for these families. I will have to admit I almost underestimated all of these years where I couldn't do it. So when you say diagnosis is an outcome, I think that's good. Let's not restrain ourselves too much because I think we need to make that argument to insurance companies. It's very hard to make that argument whether it's insurance companies or in Canada we have to make it to the government. But it's so powerful that this clinical utility discussion, I agree with you, needs to actually disappear or completely reframed before we, because we are up against the wall here. Yes? Let me just say something about the diagnostic odyssey. Like that's low-hanging fruit right now, but in another five years, you're not gonna have that to look forward to as one of your outcomes. So you really do not have to think prospectively of what are gonna be outcomes from genetic evaluations that have impact on patients and families. Think about clinical utility beyond just the patient because despite what payers say about turnover in their covered lives, we eventually are gonna have value-based health systems and there are gonna be health systems with population management and so they are gonna need to have some kind of data about outcome. And you have to start thinking prospectively about constitutes an outcome of a clinical diagnosis and management. I honestly agree with you, but if you wanna get to the point where you're talking about, we need to make the diagnoses first. Right, but I'm just saying. Yeah, but this- Affording the diagnostic odyssey as low-hanging fruit in five years, you're not gonna make that case anymore. So first of all, I'm not sure you're gonna be right about that. That we are, I'm not sure that we have solved all the cases, but in order to get closer and closer to this, we have to get to a point where we actually get to the low-hanging fruit much more efficiently than we are right now. But could I just comment? I wonder how much, is that always true, the statement that was just made, that you always have to get to the molecular level of a diagnosis? Maybe the outcome isn't going, the patient's health, all the other measurements of quality in their life, if it's epilepsy, it's epilepsy, and maybe for them or other, maybe for us it matters. The scientists and the clinicians who wanna know, but does it really matter? Sometimes maybe it does and sometimes it doesn't, but what a genetic evaluation may do could still add value. I think you make an excellent point, Martin. I mean, one of the things working in a field where sort of genetics has gone through this phase, so long QT syndrome, for example, nobody now wants to have genetic diagnosis in long QT syndrome, because they don't care if they have long QT 11 or 19, they just wanna know, are you gonna be able to make it go away or stop my kids dying young? And I think that's actually quite important. It's very, because there's a simple therapy, it's very tough to persuade people that it's worth even thinking about doing diagnosis, genetic diagnosis, even when it does affect therapy. So that's a, I think a backlash if we overstate or understand, I think we have to get it just right in order to make it stick. So this has been a great discussion, but we are now almost out of time, and so to briefly summarize, it sounds like that more training is needed and it should be expanded outside of the UDN. And there was some talk of maybe a new expertise and expanded training. There was a one week course that was discussed in a curriculum also, and whether the UDN should take part in developing this curriculum. And it also sounds like collaborations as far as getting in healthcare providers or consortium of healthcare providers could be extremely beneficial to a next phase or the sustainability of the UDN. So we'd like to close the session and thank you all very much for your participation. Thanks, Mariska. So thanks everyone for staying remarkably well on time. So we are now at 1220 and we'll be breaking for lunch for an hour. Just some points of business. There are food options here in the building up by the lobby, or you can head over to Pike and Rose, which is only about a block away. And there are a number of quick, fast takeout kind of places that you can get food there and bring it back with you. Please note, we will be trying to start on time at 120. So even if you go somewhere, make sure you're back here again so that we can get started for questions five and six. If you need cabs, please talk to the Sandra and Josh over at the table there to make sure that you can have arrangements made. If you were not going to have slides for your talks this afternoon, or if you do have slides that you need to have loaded, please see Casey so that he doesn't keep hounding you in the back. And if you are interested in one of those two open panelist slots, please let me know. We once again have one or two openings that we could potentially fit in, though we seem to have plenty of discussion here. So I'm sure that we will have lots to discuss. Thanks everyone.