 Okay, so I work on the ClinSeq project here at the NIH, and I'm going to present a little bit of data that we're just starting to collect on qualitative interviews we did with participants, some of our first participants who've gotten results back through our project. So I thought I would start with just a little bit of background literature. So obviously, as the number of people having sequencing grows, there's so much debate going on about whether and how to return results, how these results are going to impact people both in terms of sort of emotional or psychological reactions, and in terms of medical care, whether these are actually going to be used as you've already sort of heard about today. And so some of the arguments that have been pointed out in favor of returning more results are that, you know, maybe we need to be sharing these results out of respect for participants, or we should share them to maximize benefits if we can show that the risks of sharing these results are low, that it would make sense to share more. On the other hand, a lot of people talk about not sharing results in order to sort of minimize harms until we know exactly what's going on, or to avoid minimizing burden on the medical system, so not overwhelming people with lots of follow-up testing that they would need to have done based on genetic susceptibility. And so several studies have started to look at both the general population and participants in research studies and sort of their preferences around getting results back. And I think generally what we've seen is that people are wildly enthusiastic about getting their results back, and then when probed in more detail, tend to discriminate a little bit more between different result types, and so they tend to want, similar to what Daniel and Julie were reporting on, tend to be most favorable about actionable results and carrier results, and then their attitudes, if they're going to have a negative attitude, it tends to be around those non-preventable things. There's also been a lot of studies done about motivations for wanting results, and similar to what was already presented today, I think there's these ideas about having enough as much information as possible, both in terms of implementing screening and following medical recommendations, but also just in terms of sort of being vigilant yourself or curating information on your own, rather than relying on somebody else. Also making diet and lifestyle changes, personal planning decisions like purchasing insurance, but also just this general belief in the value of information, even when it's uninterpretable. People really just value the information and would like to have it in their own hands. The other thing that's come up quite often in the debate about what to return and what's valuable is the difference of clinical utility and personal utility, and so clinical utility is exactly what you think it is. It's changing somebody's clinical care, it's something that medically, we would say, would be actionable, and it's often been used as the standard for thinking through return of results that something as clinical utility, it seems pretty clear cut that we should share it with people. Even though it's unclear to what degree any of these results actually impact an individual's clinical care. There's also this concept of personal utility, so value people may gain from results because of their impact on how they perceive themselves, their relationships, other factors, and it's been sort of an amorphous concept, this idea that probably people have some personal value of these results, but it hasn't really been articulated what that might be and then how much weight that would deserve in deciding what to return to people. And so we wanted to do a project where we were going to look at a couple of the issues that this background literature brings up, so one is just describing the experience of participants in our project who have received individual genetic testing results back so far. And so we wanted to, I think the first aim is really sort of a practical or boring aim of like how did you like the process, how did you like the experience, what worked and what didn't work. The second part was looking at the psychological and emotional impact of these results as well as the impact on things like communication with health care providers and family members. And then lastly exploring this concept of personal utility with participants and seeing how they're really valuing this beyond some of the things that we might imagine as health care providers. So we did this within the ClinSeq population and I'm just going to do a quick description for those of you who don't know about it. ClinSeq is a study of over a thousand people in the D.C. area who've all elected to come in and have pretty broad consent for either exome or whole genome sequencing. Most of our study participants are healthy. We do recruit about a quarter of them to have heart disease. It was initially sort of focused on heart disease and has moved away from that now and is more presented as a broad based genetic test to look for genetic susceptibility. Our participants are 45 to 65 years old when they consent and we know from previous surveys that they are highly educated, mostly Caucasian. We have a good breakdown of males and females and they've been consented since 2007 so one of the things I get called about all the time is all the people who've been in the study for seven years and have gotten no results back yet. So lots of these people wait a long time before they actually get these results back. Our return of result process is something that's always in flux but what we've been doing most recently is when we find a variant I call the participant and I tell them that we have something for them but I don't tell them what it is. I don't usually tell them what category it fits into. I just say we have a result. Talk to me about what your preferences are, what you want to know, what you don't want to know and if we have something that falls into a category that you want to know about then we'll validate it and return to you. The exception are the variants on the ACMG list which we consider of such importance that we return them whether or not participants want them. Then people if they want the result they come in, they have an in-person disclosure session with a geneticist and a genetic counselor and they get a follow-up report from us and generally a phone check-in from me and counseling over the phone if they would like it. So for this qualitative interview project we recruited people who were enrolled in ClinSeq and had gotten back one genetic testing result so far who'd not been in previous social behavioral studies and were willing to complete a 30-minute phone interview. And so we had about 50 or 60 people who were eligible and they were all contacted several times via phone and written letter to participate in the study. We ended up having about half of the participants about 31 complete interviews, 29 of the interviews were recorded transcribed and coded and just to give you a sense of the types of results people got back so many of them were sort of off that ACMG list and considered to be highly actionable so hereditary cancer, cardiomyopathy, hypercholesterolemia, but also lots of people who had sort of more mild results so spherocytosis, protein S deficiency and things like that and these results were returned over about a six-month period to the participants. So the experience receiving results, most participants were really satisfied with the process they really felt like yes there were some nagging negative parts of the process for me but generally it was more positive than negative and that sort of outweighed in the experience for them. The negative parts for most people were either the waiting from the time when I call them to when they get to come in which makes sense or feeling like the session sort of overemphasized the results either by making them come in in person they felt like that put too much emphasis on the result or by offering counseling they felt like that often ever emphasized the results which is always tricky for me because I think I just struggle with feeling like somebody who gets for example this guy a BRCA result back have in my mind that that's going to be a pretty impactful result and a lot of people are pretty underwhelmed and feel like offering the counseling and going through that is putting too much emphasis on what this result will mean for them. In terms of emotional impact of these results the most common responses are that these results satisfy my curiosity they're intellectually exciting I find them fascinating I loved talking about them with the researchers they really almost react more like peers or more like scientists getting these results back than somebody who's getting a personal result they it's almost like they have a degree of objectivity about it and they're a little bit distanced from the results when they talk about them. In terms of emotional reaction they're pretty neutral I mean most people sort of say what this female participant said which is you know I was a little surprised or concerned at first but then as I started to think about it I really have a lot of other health concerns that are more pressing to me than this you know regardless of whether their results were about cancer risk or cardiac arrhythmia they're sort of dealing more in the here and now with things that are impacting their health today. About half of our participants got results that were expected based on their personal and family history so they had a family history of the condition whatever it was they generally would say that they found those results helpful but I think sometimes surprising so they hadn't well they knew they had a family history of this they hadn't necessarily put together maybe that there was a genetic risk and they certainly hadn't put together that they were at that risk necessarily so I think you know we hear a lot of people talking like this that maybe getting this information is confirmation that yes I'm at risk to be affected by this thing that I know is running in my family so not totally new information but a new way of thinking about it perhaps. In terms of communicating the results generally people are sharing these results with their families and their health care providers almost everybody reported that they were sharing at least somewhat and we're seeing that that's having some perceived impact on their health care health behaviors so like people going and getting breast exams or people getting medical alert bracelets things like that. The greatest impact though I think that people are reporting on is really this sense of vigilance or self-monitoring that people are really taking this into their own hands and saying well I'm being much more aware now or I'm really following the literature about this now I'm really watching for symptoms and signs of this condition as opposed to my doctor recommended that I have particular screening or testing done. And then we also asked about future results so pretty much everybody still wants to know everything and this guy with the APOB result is pretty pretty typical give me everything you know. There is some discrimination that people make between different result types but this typically requires prompting so typically when we ask the broad question what do you want to know they say everything and then if the person conducting the interview will say what about something that's not preventable what about something that you know has a low chance of actually affecting you then some people do start to back off of that assertion and say well yeah maybe not that but typically it does really require that prompting before you get people saying these sorts of things where they're actually holding back and saying you know the issue is that you know whether people or I want to have the information about things that I can't control and I still struggle with that. There was also some people who wanted our result return process to change so this is pretty typical of our participants that they would really like their results in a file or sent to them via email they would like to have access to everything that we could provide them. So you know our conclusions were still really reacting to this data since it's really newly analyzed but I think a lot of what we feel like we're seeing is that generally participants are reacting pretty well to this disclosure process most people were not distressed we think we had maybe one or two out of the 30 who were distressed so those negative emotional impacts have been really minimal and this probably has a lot to do with our population so we know ClinSeq participants are really optimistic people. I think also their age plays into this so they are you know now they're in their 50s their 60s their 70s and so a lot of them are saying well you know I didn't get cancer yet I mean I'm feeling like maybe I'm out living some of my risk I mean in some cases we would agree with that and then I think there's also this what we're calling the cool factor of these results that people kind of just think it's cool they I don't know that they think about them as pertaining to their personal health as much as they just think it's interesting academically to have this information and we sort of see that with them then maybe not changing a whole lot necessarily about their health they're kind of engaging with the information on a different way I think we also see that the attitudes they have about their results are pretty newly formed and fluid so when they're they're prompted to think more about result types they may want people do tend to change their mind I shouldn't say tend that's the point at which people would change their minds I don't think a lot of people come to the table with well enough formed ideas to articulate preferences about different types of results and then last on this idea of personal utility what we really got from people was that it's derived from this knowledge of your results so knowing something more about yourself understanding something that you didn't understand before and being able to use that information however you see fit so sort of personal advocacy for your health vigilance around surveillance things like that so a big thanks to everybody who's been working on this project and of course our participants as well that's great Katie thank you so one thing I was thinking about during your presentation is just how our paradigm for thinking about predictive genetic information really started with Huntington's disease and hereditary cancer and how that shaped a lot of how the culture in our field and how we all think about these things and then we're starting to get the initial data from folks from like this and it's in such stark contrast right so I wonder what thoughts you have about your data and how that might kind of teach us about our own selves and where we're coming from with that prior paradigm and to what extent it's at all valid in this setting yeah absolutely I think I think about that a lot and it's definitely something that I'm struggling with daily in clinic and I think a lot of people will because you're right our paradigms have just been shaped around people who are coming with a specific question in mind with this maybe legacy of disease or diagnostic Odyssey more like what Julie was talking about and so I think it is going to be a different model of counseling to some extent but I will say it's not dissimilar from other things we do right so I was talking with one of the people who did the interviews on this project and he works in a cancer clinic and he said you know we return BRCA results sometimes though to asymptomatic 70 year old women who are doing this testing for other people in their families and so I think there are instances in which we're having the same sorts of conversations I think it was just originally that we didn't realize that's how it was going to be for these participants we were sort of lumping it together with like the Huntington's disease and these other sorts of unexpected results instead of lumping it together with these you know like I say the older woman who's coming in and getting BRCA testing for other family members but maybe not for personal risk I think it's I think it's partly a question of motivations and if we can find cases where people were coming to genetics clinics for similar reasons that they're seeking out exome sequencing it might help us have a better frame of reference to start from. Does that make sense?