 So actually we'll segue now with Lisa Parker playing the role of Jeff Ginsburg. All right, thank you. So since my two fellow panelists both mapped out many of the issues, and actually Wendy had given us such a good introduction to the terrain of issues raised by return of results, I will focus in this summary just to highlight a couple of particular opportunities that I think Emerge presents in this regard. Our morning discussion certainly highlighted that Emerge is engaged in and poised to continue the research on the clinical implementation, this middle ground before we actually get to clinical implementation broadly and fully, that Emerge has the opportunity to ask the questions about what we should be doing with regard to all of the normative issues and preferences and educational needs that were recently discussed. I think that with the opportunity to continue doing site-specific as well as network-wide projects, we have an opportunity for innovative pilot studies around return of research results as well as comparative studies, and indeed capitalizing on the non-uniform healthcare system that we have and differences across institutions and their electronic health record systems. And indeed the fact that some of our Emerge sites, the healthcare system is also involved in ensuring lives, and so that we do have an opportunity for some of the economic and broader policy examination that's been raised. That we can do this across time and in two senses, both longitudinal study querying deep diverse phenotypes and also across the lifespan that we do have pediatric patients, we have much older patients, and that I would suggest that at least some say, despite the ACMG recommendations, that the age of the person in whom the result is identified may indeed matter, whether this is an elderly person for whom that disease risk may not be likely to be manifesting or you're talking about a newborn or a pediatric patient. And so I think very briefly in the summary, so we do have time for discussion, both with Gail and Susan and then everyone, I just want to emphasize that what I have found Emerge to have most particularly in contrast to any other research setting or research network is that there's an integrated infrastructure for conducting the empirical LC research. And that return of research results is a key topic for this integration. There are certainly practical logistical issues, but that those are so intimately intertwined with the ethical, the legal, the economic, the social aspects, social risks, if you will, of returning results and that Emerge has proved through two phases thus far that really more than than more than elsewhere and perhaps more than the LC seers to some extent, there's a real integration of empirical ethics researchers, policy researchers into the science. And therefore, there's a real opportunity here, I think, to examine both what I'll call the individual participant level issues as well as now system-wide issues of economics, the impact on health care costs, quality assurance issues, data security and participant privacy issues at a systemic level as well as looking at the clinician preparedness and needs, the decision support and participant responses including as we go forward and consider the implications for families who may be outside of the given health care system or beyond the electronic health record, implications for them, liability issues and just sheer family member responses. So I think Emerge is well positioned to continue to try to address the issues raised by return of results. And I will stop. Would you like to kind of lead the polling of the other? Oh, I will, yes, absolutely. I had intended in fact to turn on now Gail if you wanted to weigh in on this discussion and then we'll have Susan and then open it up. Yes, and I think, you know, one of the things we talked a lot, we had several calls and our panelists did a great job of, you know, being prepared and, you know, the quote, let's say we're prepared. We talked a lot about how, you know, what kind of balance of discovery and implementation work that where you're getting results that you can return to people that have value to them. And but also there are good LT questions, there are good discovery questions and that's actually sort of how we kind of honed in on this, you know, more penetrant gene idea. And I'm very much in favor of that. And I like pharmacogenetics. There are a lot of people working in that state. I mean, we have some good pharmacogenetic data. But I think as far as returning things to actual people and learning how to do that, that the highly penetrant stuff is more, you know, critically demanded and that there is a really lot we could learn, not just about which variants are pathogenic, but about which variants aren't pathogenic and issues like penetrance and other things, a lot of questions in that state. So as we kind of went over, well, what do we want to learn? What are our unique strengths? I mean, that idea of more highly penetrant conditions jumped out more and more. That's what I'm saying. Susan, did you want to chime in? Sure. I want to go back to the question of what unique opportunities eMERGE may have in the return of results space. And I've got a couple thoughts on that. First of all, I think eMERGE probably needs to, as well as can, test and go beyond the ACNG statement on return of results, return of incidental findings, actually, in clinical sequencing. Because, of course, that was about clinical sequencing and Greenedale is agnostic on its implications, at least in the text, for research, but eMERGE is already facing these issues, as we know, in the research sphere. So an ACNG in that statement was modest appropriately in saying this is a first pass. We need a better evidence base. So I think eMERGE can really play a leadership role there including on the specific question of the role of participant and patient preference on what to look for and what to return. As everyone knows, they're contested questions. Another domain, I think, where eMERGE has unique capability is digging in on some of the consent questions. And Iftacar had on his slide some of the cutting-edge ones like consent to include genomic data in the EHR. Others are consent to share with kin, consent for posthumous use. So there are really some emerging important issues. Third, I think, at least I'd like to put a proposal out there to be innovative and take a hard look at how we are defining actionability. Because I was very interested in Heidi's slide about developing a scoring scale on actionability but overwhelmingly the dialogue on actionability has been driven by investigator and clinician views of actionability and has largely ignored, I think, participant and patient views on what do they see as actionable in their lives. What about reproductive views? I understand that would open up Pandora's box but what are their priorities? What about life significance even if the clinicians can't fix the disease or the risk factor? So I think actionability needs a lot of work. And the last thing I would throw in is the description of the rich diversity in the emerged populations including diversity by ancestry opens a really important opportunity. So much work on return of results and ELSI work more broadly suffers from a lack of diverse populations in which to ask the question, are there differences in view on what people want to have happen? I think that's a really important domain that it sounds like a merge can uniquely contribute to. I want to clarify, this is Gail, that I am not endorsing any of the opinions of the ACMG statement with regard to mandatory return or return to minors when I say that the list, the actual list of genes is a good starting place for us to look at for what is, you know, agreeable to many people as actionable. I think there are more actionable genes. There are a couple that I'm dicey about on the list. I might have got the 57th one thrown off. But the list of genes I think people have generally a positive review of whereas what to do with that, those variants, I think is a wonderful research stage for a merge. What do people actually want? Not just what does the ACMG station happen, but what do people, what do patients want, what do providers want? I think that's a good point. I think this is a really high profile issue as one of the authors on the paper first of all said, Gail, you only get one gene off, all right? You're... No, I'm not writing the other two. I'm okay with them. All right, good. Glad to hear that. But I think, you know, one of the things that we faced in creating the statement on the list is that as everyone here knows, there's been almost no research in this area at all. And so while we gave it our best effort based on what we thought was a reasonable way to proceed, I think the whole process would dramatically welcome actual formative research about how do people feel about this, what's really the best way to do it and develop a research agenda around these types of questions. Now, I don't know if Heidi's still on the call or not, but I know she's leading the ongoing process that's being developed relating at least to the list. And so you may have some insights in terms of your perspective on that type of research. Heidi, how are you? I think Heidi got off. Okay. I saw her step off. But I just want to acknowledge that the paper was very clear that an evidence base needed to be developed. Yes. And I think, you know, the paper that Wiley Burke led on opportunistic screening and the need for real evidence around the fact that these people are coming in and largely asymptomatic as to the 56, so what do we know about... Do we have enough evidence in that context? That's a really important set of questions that we can address and emerge, absolutely. So as a non-specialist in this area, but having the benefit that when you're a grandparent, you get to see digital natives, the millennials, and I think, well, what would they think of this entire discussion? And they would think this was laced with nothing but degrees of paternalism. There was no option at one end that sounded like no paternalism, which is, can I just have all my results? And why are you withholding them from me? So I guess it seems to me at least some recognition that this space has moved a lot in just the amount of time since eMERGE was created, the public expectation of, well, you accept the risks of just telling it like it is, but I want everything about me. It doesn't seem to have been in this discussion of incidental findings. I slid over that slide. I actually think that has been in the debate. I think that was part of the original impetus for even a decade ago raising the idea that participants in research and patients might want their incidental findings or even their research results. I mean, I see the trend moving toward providing choice so that some people might indeed say, I want a ton. I mean, in fact, I define actionability much more broadly than you do. Some people might even say, actionable or not, give it to me now. Whether you understand it or not, give it to me now because it's mine. And some people might be much more cautious. I don't think we know yet about what frequencies are attached to those attitudinal positions. We need to know, but ultimately, I suspect, we need to have a range of options that people can avail themselves of. And is it any more moral to ignore that view and give me all my data now? It's my data. Then it is to say, no, I don't want that data. Don't return that for me or I don't want that result. We all agree that we need to do that. But what about the person on the other side? And we just saw data for the pharmacogenome except the error rate is down there one percent or less. Why is this really something that we shouldn't return? Are we hiding behind these constructs that we've created? Research was designed because you didn't know the answer. And now we're getting findings that are true. This data should not be, even if we can't interpret the data, can we give the data to the participants? I think we're back to the clear discussion. Maybe or not. I mean, we could write a research protocol that said, and we will take the genetic information and give it to the participants. Actually, there is one like that. It's called multiple studies. Yeah, and it was done with specific candidate genes. But we could do it with GWAS, or what is close to GWAS. It overlaps the implementation conundrum that perfect is the enemy of useful. I'm not forgiving people their data, and I'm probably at one of the few places that would let us give back non-clear data. But my impression from my peers is that many places cannot be excited. Well, but so is there. Yeah, just to extend that, right? So I think in the 21st century, that's saying knowledge is power, and the people that have the power want to keep it. Millennials, how much is liability? It also is about intellectual power. It also suggests that eMERGE is in a good position to study the next step, and not just the next day or next month, or even six months out, responsive individuals to having received their results, but in fact, over a certain amount. More time, what they actually do with it and what the effect on demand for healthcare services is, how that links up to clinical practice guidelines for actually responding to the level of disease risk or preventive interventions or whatever that are recommended. Do people come in and ask for more because they're now more concerned? Does it actually inspire them to follow a clinical practice guideline that's recommended? And eMERGE is especially well suited, structured to be able to ask those questions and address them. EMERGE is also a really important position to deal with the fact that more and more people have access directly to their electronic health record or some version of it. So if it's in the electronic health record, you would think sooner or later it's going to be available to the individual. And what are the implications of that? I mean, for example, ACMG talked about a dialogue ensuing between the clinician who's gotten the 56 back from the lab or whatever came up in the analysis of 56 and the patient. But if the patient has full access to the electronic health record, that's not much of a filter, not much of a screen. It can be a source of education. So I think the trend, including among millennials toward increasing access to the EHR has to be dealt with and eMERGE could really play a leadership role there. Yeah, I think the other point that's worthwhile to note relating to that access issue is that it's Justin at all pointed out in our Crossing the Omics CASM viewpoint article is it's not clear at this point what all is going to be represented in the electronic health record. In other words, would it just be the results that are deemed by someone to be actionable and we don't give any of the other information? I think most of us believe it's not going to be an entire variant file. But that's another type of research question that could be asked is what do our patients think would be a reasonable amount of information to have in there and how would they like to access it with an uppatient portal or a person, tethered personal health record environment? There's a lot of real opportunity here. What I want to remember is that we are having this discussion about return of results in part because of the behavior of generations of previous researchers. Some of whom basically said here's this information and if you have questions talk to your doctor. And so now we have clinical organizations that are conditioned that when a researcher says I want to give a research subject information they are knee jerk is no because my doctors are going to suffer as a result of it. So if we are going to return the information we have to scope it appropriately that we are in a position to answer and analyze the questions that are asked. So just to follow up on that I did a study years ago where we were measuring LPA and we were required to ask every provider if their patients could get their LPA back to what they are directed to their LPA panel and most of the providers said no because they didn't want it they didn't want to know about it they didn't want to explain it to the patients they didn't want to incorporate it into care. And I think to me that emphasizes how important it is to pick something to return that is important in clinical care that the providers will want to know about and will need to learn about it. That often happens because the patients are asking the doctor instead of the patient rather than posing on the patient he thinks they need which is a version of healthcare being mostly for doctors as opposed to for patients. We still have some more time to I find it curious to you say the data wouldn't be deposited in the EMR well it may not be deposited in EPIC because it can't be or in CPRS but isn't it in fact part of the healthcare record regardless if it's a lab test that comes back even if it's faxed in and it's not incorporated it's part of the record. Not necessarily Larry the example that we used is the ancillary system which is there's a system that's tied to the electronic health record but we don't have all of the mild data for the images in the electronic health record. We have a way that you can view the image through the electronic health record but the data does not reside in the EHR and there are specific performance issues where we think the huge volumes of genomic data if stored within what we consider the EHR environment would be great performance to the point that it would become unusable. Granted that it's in a separate platform and in a separate system in a way that for example radiology is in many is not most healthcare systems but if a patient signs a consent and says I want my MRI first to my other doctor it's part of the record in so far as it is transmitted to that other system or if a patient is now under ME2 says I want that data they can get the data. But I think a good example is if you look at lab tests in many places when you order a serum sodium they do a 20 because it's cheaper to just run it through the multiplexer and they throw the other 19 away and you can't have them. Also they run QA samples with lots of tests and if you want to see a disaster see what happens when the QA results start bleeding into the clinical results and everybody gets confused as heck so there are a lot of results that are collected in some ancillary systems which never come across the wire. Yes, but if you run a panel of 56 genes and those are returned to the clinician with a result file and a PDF and you're in the position where you're going to reinterpret VUSs they better be in some ancillary system that's considered legally part of the EMR. I think it's a terminological difference when we say EMR we mean EPIC or its market partners as opposed to the entire clinical digital record. Right, I think there is a distinction even if it's behind the firewall between a research base and a clinical database if you're doing a randomized trial and it happens to be the conservators happen to be on your premises those data are secured data and not accessible to clinicians for routine care in any way certainly there can be a dialogue between a participant in a trial who wants to get access to the data but only with the investigators that are involved in that trial it's not as if he could go into the medical records office sign a form and say I want my randomized trial secure randomized trial data and that the medical records office would be required to give it to them so they are really separate enclaves even though they're maybe contained behind the firewall of a health system. Right, and I think we're talking about only CLIA results ordered for clinical care. That's a difference but we're starting to blur the line between CLIA results for research purposes that will eventually find their way back to a medical record some of which might find their way back some of which might be retained within an enclave a research enclave because they're not ready for primetime consumption so those lines are beginning to blur but not everything that's contained behind a health system is all treated the same and a patient doesn't have the exact same access to all that data at all points in time. This is an excellent preamble to the next topic which will occur after a 15 minute break. Now having shown that we can actually do a 15 minute break you'll see 20 on your schedule but we're actually going to restart in 15 minutes and we could almost pick this up in mid-sentence but we won't. We'll see you at 15 minutes past the hour.