 So, I'm Julie Sap and Danielle. We are going to spend a little bit of time talking about some work that we actually collaborated on together. So, I'll start off and kind of set the stage and then Danielle will jump in and talk more about our results and our findings. So, we conducted this study of trying to understand the attitudes and the underlying values and beliefs of parents who are undergoing exome sequencing because their children are undiagnosed. So, when we started the study in 2011, this was a relatively new idea. I understand this is much more common now. So, all of our participants came from a research protocol here at the NIH called Whole Genome Medical Sequencing for Gene Discovery and the two broad goals of the protocol were of course to determine the underlying genetic etiology for rare disorders and then we also had some social and behavioral goals of this project that are ongoing to develop best practice approaches for the return of results to our participants and so that's what we're going to focus on today. So I wonder if this, I'm just going to take a bet that this will not be the last time the theory of reasoned action is invoked or mentioned at some point. So our goal is really to understand our participants' values and beliefs that underlie or that build upon their attitudes about what kind of choices they make about receipt of genetic testing results, exome sequencing results for their children. So again, the participants in this protocol are parents who are making decisions on their child's behalf and our main questions were whether or not parents' attitudes and, to assess parents' attitudes and preferences about a variety of categories of results and see whether or not their attitudes are stable or change over time and then what's currently ongoing right now is trying to develop an understanding of how our participants, how our parents are using these results after they've been returned. So we'll focus mostly on the first part of, again, our ongoing social and behavioral research projects that are associated with this protocol. So, oh, actually I think that's when I'm going to turn it over to you. Yeah, exactly. Very good. Just a pointer. Can I do this? Yeah. Yeah. All right. So our, let's switch places. Oh, sorry. There we go. Our research was a qualitative study for this first part. So we had 25 parents of 13 minor participants who were interviewed prior to consent and I think that that's an important part of what we're going to talk about in our talk today because it was specifically designed so that our participants and the people that were interviewed were a bit naive to what they were going to get into. So this was really, we were doing a pre-test conversation, then the participants came to the NIH and the full consent happened and then testing and then post-testing interviews were after. Again, it was a structured interview that we went through and the two main highlights of what we talked about, what we went through, what the sequencing technology was, what is whole genome sequencing, why is your child going to have it, why are you going to have it as a part of our protocol and then what was their interest in receiving four different categories of specific results that you could get. So again, the primary variant being the reason why that child was there. That child had an undiagnosed condition with an unknown genetic etiology. They could receive the primary variant as one of the results and then the three others that we have up here were they could receive secondary variants for disorders that were actionable in childhood, something they could do something about and the example that we used in the interviews was something like FAP, something you could actually treat in childhood. The third category were the variants for disorders that are not actionable in childhood, something like Alzheimer's or an adult onset cancer and then we had carrier status for a number of autosomal recessive disorders for which the example was talking about cystic fibrosis and then we had variants of uncertain clinical significance and we're not really going to talk very much about this today. This is a part of our ongoing research and I actually think is something we just wanted to highlight here because it was something that emerged during the interviews that we were doing. Something we added in during the interview process and I think shows how important it is that you're learning in this qualitative study and then adding in things that where you might find something interesting later on so we really like that part of this. So here is one of our punchlines at the end of what came out of the research is that really parents attitudes vary and it was across the range of action ability and what can happen with those results. So the first two that we have over here on the side, the primary variants, again the reason the genetic etiology for that child's underlying condition, uniformly all 25 parents wanted to learn about, not a surprise because that was one of the goals of the research and then secondly also the treatable or preventable in childhood secondary variants, that was something that all 25 parents wanted to learn about. And what we'll talk a little bit more that was really interesting were the carrier status and then what was any variants for not treatable or preventable in childhood conditions. So we have two slides about these two. So the variants of the genetic variants that were not actionable in childhood, we had a pretty broad range and we thought this was one of the most interesting things that came out of the research. We had 10 participants who absolutely wanted to learn these variants. We had three conditional yeses, we had six parents that had six answers that were ambivalent and six noes. These do not add up to 25 because parents can hold more than one of these attitudes at the same time. So we had reasons across the board and that I think is again a really important finding of all of this. The two that were again so of the positive yeses is going over that there were genetic variants that you cannot do anything about in childhood and 10 of the parents said but there are still things that can be done and measures that can be taken. So that this shows that the parents' perception of what the genetic variant was was it was something useful. It was useful to them and wanting to know that they could do something about it. And then secondly that parents also, the ones that answered positively yes they'd want to know about these variants is that they could keep abreast of the research, they could curate the literature and understand better than not knowing, better than just a researcher having that information. So these were really important attitudes of why that parent wanted to know and again was that one of the beliefs that they had that underlined why they wanted to know about this information. The conditional yeses again also the parents wanted to know but they wanted to wait until the program wasn't an appropriate age. They really wanted to know the information but we're going to wait at some point to know that so they could discuss it with their child. And then the neutral ambivalent they were really unsure during that interview process whether they wanted this information and then there were four absolutely not I do not want to know that. So for the carrier variants again so this took away the no categories so there were 13 absolutely yes I'd want to know any carrier variants and then a conditional, five conditional yeses and seven ambivalents. So again this was a little more skewed toward wanting to know the information where we had no absolutely positive noes here. So again parents want to know their children's results along this continuum of action ability and these five beliefs underneath were again some of the foundations of why these parents were making these decisions that were really interesting that came out of this so parents having want some responsibility they wanted some control over those results as well as having a preference for knowledge again these are I think important themes and that sometimes that they wanted them because of faith-based decision faith-based beliefs and altruistic beliefs as well so where we are right now is that this is this component of our protocols of our of our study is complete but we're still interviewing parents and in an ongoing fashion so we're continuing to return results and we validate any primary variants and then so Danielle interviewed all of these people immediately before they consented and then she's interviewing them again at the time that we have results available so we call them we let them know that we have results available and then they complete another structured interview where we're making it a little bit more concrete and they're declaring their actual results preferences that will use in returning results to folks so even though people have some nuanced opinions so far I haven't had anybody say anything other than if you know anything you can possibly tell me including this idea of variants of uncertain clinical significance which is something that we introduced kind of halfway through the process because people were were were asking about this kind of after the consent process and so that those interviews are in progress and then we also interview participants again six months after the return of results and again this is just anecdotal data but the findings of of those we've done eight of those interviews and so far people have absolutely no recollection of anything that we've told them other than the primary variant we haven't delivered any particularly I would call them high impact variants to people but I think one of the participants that you most recently interviewed said did I even get results for myself did we even talk about anything else other than the cause for my child's condition so so far people are not really remembering those conversations very well and they're not utilizing this information and they're not disseminating it throughout the family so we'll just see how that goes and then another kind of corollary project that's going on right now again emerged from Danielle's initial interviews where we're specifically focusing on the rationale that parents bring to the table when they're thinking about whether or not they want variants of uncertain clinical significance and again the idea that we're in this protocol it's structured in such a way that they are actually getting choices so that they can make decisions and they can distinguish between different categories of results that they want to receive so that's also something that's going on those interviews are conducted by my research assistant and so and actually Sam you're you know you know the data much better than I do so we'll have something to report about that sometime soon so we of course like to thank all of our participants and the people that we work with the research assistants who coded the data the people who supervise the research assistants who coded the data and that's us in 2005 we're doing questions at the end collectively right so we should move okay did everybody hear Barb's question you it you want me to repeat it again for okay so I think Barb's question was in our cohort this this idea of what sticks with people how much of that is related to the the fact that they have been on this long diagnostic odyssey I think it's absolutely related I think they have their eye on this very particular prize and everything else is secondary until it's not right so we like I said we haven't delivered anything else that would require any sort of action ability thus far with one exception that hasn't been six months yet so you haven't interviewed them so well you know so we'll see but I think that I think it's absolutely related do you want to yeah no I absolutely agree and again just thinking back to anecdotally the actual interviews that was I would give the participants a chance to talk at the beginning just tell me and every one of them started with here's my child this is what we've been through this is the testing I've had you're gonna help me so that I think that was the start of the conversation and it continues through absolutely because I'm not really good at restating questions I'm not sure if I missed this but I guess I'm just surprised that none of the parents said that they didn't want to know the results because they didn't want to take away their child's autonomy and like their decision to want that information so that was that was actually a rationale for underlying positive values about receiving information not more people talked about I'd like the information but I will I will hold on to it I will keep it I will curate it and then I will share it with my child at the appropriate time then they talked about wanting to preserve their their child's autonomy we I think we did have one or two people say that but it didn't make it into kind of our major themes yeah great thanks