12:01:46 Welcome, everybody. I'm gonna go ahead and get started. I'm so happy to welcome everyone to the second ELSI Journal Club. I'm Josephine Johnston. I'm associate professor at the University of Otago's bioethics center. I'm also a fellow of the Hastings Center and a member of the CERA, the Center for ELSI Resources and Analysis, funded by the National Human Genome Research Institute, which provides resources through the website ELSIhub and we sponsor the ELSI journal club.
12:01:46 So I'm delighted that you've joined us for the second journal club. Today we are featuring the article called: Parents' Perceptions of the Utility of Genetic Testing in the NICU. Which is published in the journal Genetics in Medicine. And Genetics in Medicine is a CERA partner.
12:02:07 So a few housekeeping notes. We're dropping some logistical information about closed captioning in the chat. So we're gonna use the chat function for that information.
12:02:20 And we really welcome questions from you at any time. You can put them in the Q and A, which is a different function, the Q and A box. So please pop your questions in there whenever you have them, and we'll come to them in the Q and A part of the session.
12:02:35 So the first thing I want to do is introduce Stacey Pereira, associate professor in the Baylor College of Medicine Center for Medical Ethics and Health Policy and an ELSI section editor of Genetics in Medicine. She's gonna share some information about our collaboration with the journal and a publication opportunity related to today's session.
12:02:59 >> Thank you, Josie. So Genetics in Medicine is pleased to collaborate with CERA on the session today and future ELSI journal club sessions, which will feature newly published articles in the journal. In support of this initiative, Genetics in Medicine is inviting authors of our featured article to contribute a GenePod podcast to our series, which will be archived both on the journal website and ELSIhub.
12:03:24 The journal is also inviting a short response to today's featured manuscript for publication in the journal. And you can find information and instructions for proposing a response article in the chat.
12:03:36 And I look forward to seeing your submissions.
12:03:40 >> Thanks, Stacey. So I'm the moderator today, for this session. And it's my real pleasure to introduce our featured author and our discussant. We're going to put full bios in the chat. But I'll just do a quick introduction. So...
12:03:56 Dr. Katharine Press Callahan is an attending physician in the division of neonatology at children's hospital of Philadelphia and assistant professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Welcome, Katharine.
12:04:15 And Dr. Jessica Ezzell Hunter is the director of the genomics, ethics, and translational research program at RTI international.
12:04:23 She is a genetic epidemiologist whose work focuses on the impact of genomic variation on health outcomes. And the plan for today is we will first hear a brief overview of the article from Dr. Callahan.
12:04:38 And then Dr. Hunter will share her discussion and reflections with us for about 15 minutes, and then we will have a moderated Q and A. So now I'm just very happy to hand off to you, Dr. Callahan.
12:04:51 >> Thank you. And thank you for having me today. So first I wanted to just take a step back and think about how I even got to write this article, or do this work. And I have spent most of the past decade, throughout my pediatrics and neonatology training, kind of in parallel, thinking about how we use genetic information.
12:05:12 So I certainly had my ear to the ground for this. But how I got to this particular work was: In the NICU, I just noticed that the more I talked to parents, mostly of patients I had taken care of, about their experiences with genetic information, the stories were very complex.
12:05:29 And at first, one of the things I noticed was that some parents actually declined genetic testing. Which resulted in a separate study that I conducted of why parents declined genetic testing. But even beyond just some negative feelings, parents had complicated explanations for kind of how they fit genetic information and the idea of a diagnosis in general into their own child's complex course.
12:05:59 And their own ability to cope with that experience and try and make sense of it. And when I read the literature about parents' perspectives on neonatal genomic medicine, it mostly talks about medical impacts. And of course, most parents will do whatever they can, even if there's a small chance of improving their children's medical outcome.
12:06:24 But it seemed to me that there was more to this story, and some of it was missed. And then as a researcher, I had observed that some of the questionnaires were designed to focus on medical impact. And I think that has been the focus for a lot of genomic medicine.
12:06:39 And at the same time, most of them also only included parents who had consented to genomic research, which to me is a very particular subset. So I tried in this project to kind of think about... Well, what is going on with parents' sort of more global perception of whether this information is quote-unquote "useful" to them?
12:06:59 Like, in what realms are they kind of evaluating utility? I didn't call it utility to parents -- or actually even in the initial draft of this paper. But I do agree that it is a form of utility. Or many forms of utility. And how could we kind of conceptualize utility more broadly for parents? And then take that forward to think about what that means for our own practice and our own research.
12:07:26 So I came to this sort of broad questioning of parents and then a model of kind of the many problem solving contexts in which they're trying to slot this genetic information. As part of a larger experience.
12:07:40 And that's all I'll say for now. I'll let Jessica take the stage.
12:07:51 >> Let me share my screen.
12:07:58 So... In reading through this manuscript, it really made me think about just the bigger picture concept of utility. And historically how we've thought about this domain.
12:08:12 Historically, to kind of start, there were two themes that emerged as I was thinking about the concept of utility. One is the emerging scope, and what-all we now consider as part of the concept of utility.
12:08:27 And how we can measure it in order to inform implementation of future genomic medicine initiatives. As well as in the clinic and in research how can we adapt pre- and posttest discussions to account for this diverse range of perspectives, of individuals and parents?
12:08:49 But to take a step back for the concept of utility, we've historically -- in the context of medical genomics -- only thought about clinical utility. Most broadly defined as the usefulness of an intervention for or in clinical practice.
12:09:07 But definitions of utility can vary, based on who takes the action. Is it a clinician? Is it an individual for themselves? Is it a parent for their child? Who receives the benefits? The individual? The individual's family? Society?
12:09:22 As well as what kind of benefits are considered. Are you looking for a diagnosis? Are you looking to improve health outcomes? Is it to guide reproductive decision making? And it can also include consideration of the balance of risks and benefits of getting testing.
12:09:41 Whether you're considering some sort of alternate to inform comparative utility, as well as whether aspects of program implementation are considered, such as availability of testing, equitable access, and the financial costs related to testing.
12:10:01 I would be remiss, as the lead of the actionability work of ClinGen, to not connect this to the concept of actionability. They are very related terms, in many ways overlapping. But I tend to -- most of the time -- work in the space of actionability, which is very similar.
12:10:21 We tend to think of actionability as very related to utility, including clinical and non-clinical actions. Actionability can take into account the different people who take the action, who receive the benefits, and how the benefits can differ, as noted in the previous slide.
12:10:39 And we tend to think of actionability at the individual level. What's the usefulness of an intervention from an individual's perspective. And utility more at the system level.
12:10:49 What's the usefulness of an intervention from a clinical systems perspective.
12:10:57 And if you were on the prior journal club, this figure will look very familiar to you. This is how we generally perceive the range of actionability and what's all considered, including the who, from the person to society, and the context, from clinical to non-clinical implications and contexts.
12:11:22 One important aspect of defining these aspects of utility is capturing outcomes. And so measures have been developed, like the personal utility scale, to capture personal utility. There's an adult version of this. And it was recently adapted for the parent context, in order to capture benefits to the child, including helping with child life planning.
12:11:47 Helping to better understand the child's health. It captures effective apparent benefits, such as just gaining information, and it captures control, such as helping the parent feel more in control of the child's life. But there's a lot more utility beyond personal utility. And can include concepts of dysutility, both positive and negative aspects, related to genetic testing.
12:12:15 And it's important, as emphasized by this paper, to take into account these different perspectives, given that they can be very subjective and very dynamic, even within the same person.
12:12:27 Utility can include a whole range of things, from gaining knowledge, the psychosocial impacts, behavioral changes, other non-clinical actions, as well as more negative things, such as concern about discrimination and concerns about privacy.
12:12:41 They can be dynamic and impacted by a range of factors across and even within individuals. From the clinical context, such as: Are we talking about the person making the decision for themselves or their child? Are they healthy? Are they looking for a diagnosis? As well as the clinical versus research setting. And I think this article really adds to the literature, to help them form the perspectives for more clinical perspectives.
12:13:11 Also perceived understanding. Both how much does the person feel that they understand what the genetic tests can tell them and what the results mean.
12:13:22  They can change by feelings of responsibility, changes in identity, timing, as well as societal shifts. Perspectives of science and medicine can change at a societal level over time. That can impact perspectives.
12:13:39 So we did a study as part of the Caesar Consortium, funded by NHGRI, looking at some of the outcomes for parents who were making decisions about genetic testing for their children. And we looked at perceived understanding of the results, as well as the parent perspectives of their personal utility and their test-related distress.
12:14:01 And though we found overall high perceived understanding of the child's result and personal utility and low tests related to stress, we did find that these perspectives differed, based on the finding. So parents of children with a pathogenic or likely pathogenic variant endorsed higher personal utility, but also higher test-related distress.
12:14:23 So both positive and negative reactions to the test result. And so this, along with articles like the one we're talking about today, support the idea of tailored support for disclosure discussions.
12:14:38 Of course, there's a lot more to be considered beyond personal utility, test-related distress, and Hadley Stevens Smith as part of the Caesar Consortium, published a really lovely assessment of the bigger concept of perceived utility. And noted that limiting parent assessment to personal utility alone may not capture all the full range of health and non-health-related impacts that patients and families experience.
12:15:08 And there's this really lovely figure to outline the different domains that emerge from this model, related to clinical utility, cognitive utility, behavioral, emotional, and social utility.
12:15:21 And all of this is to guide future assessments, to help capture some of these outcomes. In parents and individuals, to help us guide future implementation of genomic medicine to account for these different factors.
12:15:36 And indeed, there is... I think there's an adult version as well. But the pediatric version of the GENE-U, to capture some of the bigger picture versions of the utility assessments beyond the current assessments that exist, are an attempt to do that.
12:15:59 And this article we're discussing today adds to that body of literature, of what are parents experiencing and how are they perceiving the results, both in a potentially helpful and harmful way, in order to help us better define and better consider the breadth and scope of the concept of utility, in order to guide the generation of measures to help capture these outcomes and guide genomic medicine implementation and informed consent.
12:16:29 And so, then, taking a step back in how we can approach informed consent and counseling, it's really important to acknowledge the emotional complexity of these decisions and receiving the results.
12:16:42 It's important to discuss the multiple dimensions of utility that exist. As well as to clarify the scope and limits of testing in order to set realistic expectations.
12:16:54 Addressing psychosocial impact on parents and their decision making -- they may experience decisional regret after having genetic testing. And so how can their journey and genetic testing be supported, to help them navigate these complex emotions?
12:17:11 How can informed consent support ongoing and dynamic perspectives and reactions, and tailor the communication based on parent goals and preferences? So I will pose for discussion a few points of how can healthcare providers incorporate these broader definitions of utility into practice, what approaches to informed consent and disclosure can be done to ensure the processes adequately address diverse perspectives and experiences,
12:17:45  and what resources can be made available to help parents cope with the psychosocial harm or decisional regret related to complex or uncertain results?
12:17:54 So with that, I am looking forward to discussion.
12:17:59 >> Thank you so much, Jessica.
12:18:02 So as I said at the beginning, it would be great if people would pop their questions for Jessica and for KP, the authors of this paper, in the Q and A, which is one of the functions there on Zoom.
12:18:17 And while people are thinking about what to ask, we can pick up one of the questions that Jessica posed, and Katharine, it's just so great that you're a practicing clinician in this area. What has changed for you, in terms of how you think about parental decision making in the NICU, and how you counsel parents or how you work with parents, following this work that you've just -- that we've just been hearing about, that you've published?
12:18:47 >> Sure. I think... What this really confirmed or established for me is that it seems obvious now, but I think a lot of the time, we don't recognize this -- that whether something is useful to you depends what problem you're trying to solve.
12:19:02 And I think a lot of times we as neonatologists go into a room thinking about a particular problem, and we don't always establish that parents are actually thinking about the same problem. And this extends far beyond genetics.
12:19:18 But if you take a step back, and think like... I mean... We're taught to do this somewhat. Like, you sort of start out the meeting by saying: What is it you want to talk about today?
12:19:28 But then even when we're internalizing that, we're thinking... Oh, if this meeting is about genetics, they want to talk about the medical impact of this genetic change, and it might actually be something totally different.
12:19:39 And that is true, for example, also -- I think of all complex information. Like... Neuroimaging or other -- especially when things have to do with prognosis. Parents usually have some sort of context into which they're fitting the information.
12:19:53 And I think to me, it's just made me pause and think... Okay. Well, whether this is gonna be helpful to you depends what problem you're trying to solve. And we need to have more overt, clear ways of establishing a shared mental model for the problem, before I can even really talk to someone about whether something will be helpful.
12:20:19 >> Thank you. So just a reminder for people to look for the Q and A there, along the bottom. But I'll pose another question in the mean time. So...
12:20:32 Can we talk a little bit about the NICU as the context for this study? So that's quite a particular environment. And I just wanted to ask you to reflect, both of you, on that environment, and then how... What you think might translate to other environments... Where we're testing what might happen and how we might be specific about the NICU as a place.
12:20:57 Maybe we can start with you, KP, and then go to Jess.
12:21:01 >> Sure. I think the NICU is just one of the most stressful places. I think even if situations are equally dire and have gone on for longer, parents kind of equilibrate to that reality. Like... At CHOP in the NICU, we keep patients for up to a year.
12:21:16 So we even see that process starting. But I think even down the line, it happens more. People get used to whatever situation they're in. But because they're in a difficult situation, I think parents are particularly predisposed to search for any information that they think might be helpful to the problems that they see.
12:21:34 And at the same time, they're not in the best position to kind of sort through their own thinking about that information. Because they're just in a crisis mode. So I feel like it's a particular obligation of clinicians to help them think about the different impacts that this information might have.
12:21:55 Or their own ability to define their own problem. That maybe if you met with a parent later, and they had a child with intellectual disability that had gone undiagnosed for many years, they would have already framed some of that for themselves.
12:22:14 Does that make sense? Okay.
12:22:18 >> Yeah. I mean, my response was gonna be very similar. And I think this is what I was getting at, of how perspectives can change, based on the clinical contexts. And I think the NICU is a very unique clinical context. And at least in my experience and other clinical contexts, this gets at where perceptions can really vary from person to person and over time, and in the moment and in that situation, it may just be... Yes. Give me as much information as you can. Right now.
12:22:50 To help inform my care. And for someone else, it may just be... I can't think about one more thing. And I'm barely digesting what's happening now. Don't give me one more thing to think about.
12:23:01 And so it can really vary, and for those that can't handle that one more thing, it may just not be right now. But it may be a week from now. It may be two weeks from now. It may be a year from now. It's just a matter of timing and the context and that person's particular perception of an experience.
12:23:22 >> I have one more thought. Which is... In the NICU, we're taking care of babies. And babies can't do much of anything. But like... All babies can't do much of anything. And they don't have prior lives or prior existences outside of the hospital.
12:23:36 So I do think medical information in general takes on a particular weight in the NICU, because it's not being stacked on top of a child that the family has known for years, and a whole medical history before. And their other experience. It's just... You just were pregnant and this child emerged and they were just a baby who couldn't do much.
12:23:56 And then you have this information that I think can become bigger, as a result of that.
12:24:04 >> I was gonna ask you a question about ambivalence. Because you characterized that in some sense... You characterized the findings as a whole as kind of showing a picture of ambivalence. And I was wondering if you thought... How that intersected with the context that people have higher expectations for... Maybe higher expectations for what the testing is gonna tell them.
12:24:29 And then is the ambivalence... How do you understand the ambivalence as a kind of overall reaction? Do you think it would be different in different contexts? Would there be less ambivalence or more? Because I think that's quite a striking thing that comes out of the study.
12:24:46 >> Ambivalence, I believe, comes from thinking about information in many different ways. So maybe it's helpful in one way but not helpful in another. I think there is ambivalence even within a medical context. Because let's say a parent thought this test was gonna help and then it wasn't as helpful for their child's care as they expected.
12:25:02 Or the reverse. Could have impacted the management more. But most of the time, I think ambivalence results from feeling torn between different dimensions. Like... I need to do this, because there's a small chance it will result in an improved treatment.
12:25:15 But it's really hard for me to process this information. Or I need to do this, because I feel like a good parent would say yes to all technology. But I'm not sure how... If it's going to be... Make my experience be feel more meaningful, and kind of feeling torn. And that by no means is unique to genetics. I think parents are often kind of torn in those ways about like...
12:25:38 There are different obligations that they feel to a child.
12:25:47 >> As well as the reaction to the findings can vary. A negative or an uncertain finding can be disappointing for some. But informative in a way to others. Of... Well, now we know what it's likely not.
12:26:01 So that can be highly variable as well.
12:26:06 >> Right. We have got some questions now in the Q and A. So thanks for popping those in. And people should just continue to do that. I was gonna ask... There are a couple of questions about the interviews themselves.
12:26:17 So someone asked: I'm curious about the didactic interviews with both parents of the same child. Could you speak to the dynamics of these interviews? Was each parent's data analyzed separately? And I noticed another person had also asked -- I think a similar question -- which is about: Any differences between fathers' versus mothers' perception of the testing? I would love to hear from you, Katharine.
12:26:44 >> The interviews I did separately for the most part -- like, physically separately with each parent, unless they requested to do them together. Which a few parents did. And I actually really liked the ones that we did as three people. Me and two parents. Because I think you could sort of see that sometimes parents were even thinking about these different contexts of the information. Both regarding genetics and more generally.
12:27:11 And it was interesting to see how that played out in their joint assessment of whether something was useful. I don't think I have enough data to say really whether mothers versus fathers felt any particular way.
12:27:26 >> But parents didn't always feel the same way as each other?
12:27:30 >> Yeah. Parents didn't... It seemed like... In most cases, they had sort of come to a shared understanding. But maybe by thinking about different problems and then converging...
12:27:46 >> So... Someone here is also asking: I'm interested in conceptualizing utility of genomic medicine and dimensions. Can you speak to where this research might go further?
12:28:01 It would be interesting, KP, where you think things are heading.
12:28:10 >> Do you want to go first, Jessica? Or me? I'll go.
12:28:14 >> You can go.
12:28:15 >> Okay. From a very direct standpoint, I think the obvious implications are both measuring utility and figuring out how to measure all these complex ideas -- about which there's a lot of work being done, mostly not by me, by many thoughtful researchers, such as Hadley, whose papers you highlighted.
12:28:34 And then I am working on rethinking models of consent and actually what information would be most useful for preparing parents to think about the different contexts, which they are then processing afterward.
12:28:47 I also think this work has led me to realize that utility of genetic medicine is probably not something we're ever going to be able to entirely measure in a NICU context. Because most of these contexts and most of what parents talk about is the sort of thing that actually plays out over years or decades, after they leave.
12:29:06 And if... In cases where genetic medicine is impacting something acutely in the NICU and we change a treatment and that improves an outcome, that's easy to measure. But in most cases, we don't have a targeted treatment like that.
12:29:20 And so then we're kind of becoming part of this longer narrative and story. And that sort of utility, I believe, requires more longitudinal study to be able to actually assess how useful was this to someone. So that's something that I am hoping to do in the future. Actually, along with a few people that are on this meeting. Including Nancy Spinner, who I see on here.
12:29:48 >> And I will say for me... I feel like my focus over the past year or so has been moving more towards preventative testing, like population screening. Which is becoming more and more popular. And thinking about utility and actionability in that context, these programs are only gonna be successful in improving health outcomes if people act on them and we have positive outcomes.
12:30:16 And so thinking about implementing such programs, where we don't have as much information on unselected populations for some of these conditions... Most of our information is based on populations that present based on the findings. Right?
12:30:34 So I imagine our perspectives of things like penetrance will change over time, as we start to have more unselected genetic testing. And so... How does implementation of population screening programs both change outcomes and perceptions of these test results, moving forward?
12:30:55 Slightly different perspectives.
12:31:00 >> So I've got a couple more sets of questions coming up. But I'll go with the ones... Some people had more questions just about the study itself.
12:31:08 So someone asked... Who did the consenting for the families in the study? Was it the genetics or the neonatology teams or people... I'll ask that question first, maybe, Katharine.
12:31:26 >> It was first my research coordinator, who I suppose was indirectly part of the neonatology team.
12:31:32 >> And then... Were parents concerned about loopholes in gena or were they not aware of these issues? Did that come up at all as part of your study?
12:31:43 >> Yeah. People did talk about misuse as kind of a general category. I actually wrote a paper that was in Genetics in Medicine Open last year, about why people declined. And I talked about it more in that paper.
12:31:56 But... Concerns about misuse, both by forces outside of medicine, but also by doctors and how they would be... What would be available to a patient and how doctors would sort of perceive the patient... Were reasons that people cited for declining testing. I wonder, too, if I did it now...
12:32:20 Like, two years or a year and a half later... If people would have more concerns about those issues. Maybe.
12:32:28 >> Did insurance specifically come up? Was it part of what people were specifically mentioning?
12:32:32 >> Life experience. Yeah. They did. I'm picturing one set of parents who did talk a lot about... There was one set of parents that... They were Black. And the dad said to me... I think I put this quote in the decline. He was like... He's already gonna face discrimination from being Black. He doesn't need to have more discrimination.
12:32:53 And they had declined testing. Which I thought was kind of interesting. That he aligned those two. Like... Obvious sources of potential bias.
12:33:07 >> So we have another question here. Someone... Lots of people said thank you to you both when they asked the questions. Someone says... I have a question regarding the concept of utility you presented, which is very broad.
12:33:22 Even the actionability discussion is also quite broad. I wonder if during the interview you have seen parents' immediate perception of utility, which might be narrower, and then that somehow conflicts with other benefits that they've been... That have been included in the broader concept.
12:33:39 So it was the kind of movement and that understanding.
12:33:47 >> I tried to start very broadly, as I said at the beginning -- I didn't actually include the word utility. Because parents don't really know what that means anyway. I didn't really start with a medical framework.
12:34:00 I really just began by asking parents... What they had hoped for, from the testing. If they consented to it, or their reasons or concerns if they had declined it. And afterward, similar questions. About like... Well, in what ways was it helpful to you?
12:34:18 And they came up with all these -- people had already decided whether it was helpful. I think I had to encourage people -- this is what I've learned. As just part of qualitative work in general -- encourage people to keep going down those directions.
12:34:34 Because I think in particular, because I did about half the interviews and they knew I was a neonatologist, they thought I wanted to hear about things they imagined a neonatologist would be interested in.
12:34:45 So I sort of encouraged them to tell me about their lives and families and spiritual ideas, et cetera.
12:34:57 >> Do you have anything you want to add on that narrowness versus broad kind of utility stuff, Jess?
12:35:04 >> No. I mean... I think kind of just leveraging what KP said, I imagine the broadness would just vary from person to person. And how they're thinking about and which aspects they're considering, and at what time. You know, pretesting versus posttesting.
12:35:22 >> We have a specific question here about whether you noticed any differences in the way parents approached the utility of panel versus exome or genome testing.
12:35:32 >> Again... I don't think I have the data to answer it, because we do almost... There is a very large genome-based panel that has become standard of care for most patients in our NICU.
12:35:45 And so most patients had that. And a few had additional testing as well. But I don't think I have enough data to say for sure. My suspicion is no. Like... I think the type of test actually matters a lot less than doctors think. Or researchers think.
12:36:05 I don't think parents really register much about the test mechanism. Maybe there are different kinds of concerns that come up, for example, with secondary or incidental findings, which obviously are different risks in different tests.
12:36:22 >> So someone has also asked sort of about... Within your particular group, clinical group, how you've tried to act on the paper's findings. And how receptive other clinicians have been to having the more nuanced conversations that your paper calls for or suggests would be helpful.
12:36:45 >> Yeah. That's a good question. I mean... I hope that they've sort of in general ways incorporated them, but I think I need to figure out more concrete suggestions before I can expect the work to actually be useful to people.
12:36:57 And as I said, I'm working on a study of consent models that I hope might be easier... Have a more direct impact. Yeah. We have had a few discussions in our division recently about whether parents want prognostic information. So I can only hope that I've informed that somewhat.
12:37:24 We recently had a discussion about whether we should be getting brain MRIs on all preterm babies. Which is an area of controversy in neonatology in general.
12:37:35 And I think carries similar kinds of promise and risks, in like... It might give you information about the future. But it might be really uncertain, and people aren't sure if that's... Necessarily useful to them. And it's certainly individualized. So I hope that it's impacted conversations like that. But I can't say for sure.
12:37:59 >> But it's changed the way you counsel? Yourself?
12:38:06 >> I always was a little bit open about my own... I try to be really clear with parents about... If we're recommending genetic testing, what I think it will do and what it might not do. So that they can then slot that information into... What they were hoping for.
12:38:26 >> I have a question to follow up on that. Of how do you navigate conversations where you might see utility and the parents don't?
12:38:34 >> Yeah. That's a good question. That happens all the time. I mean... With genetic testing and with other kinds of interventions. And I guess it just somewhat... Figuring out if it really is a difference of value or something of understanding, you can convey the information and try and see if it changes people's minds.
12:38:54 But I think unless it's outside of a zone of reasonable parent decision making, sometimes we just have to defer to what a parent sees as the right decision.
12:39:08 Actually, there are... One of the things I've thought about is that: There probably should be different types of consents in different clinical scenarios. Because in some cases, you really believe a genetic test is gonna impact NICU decision making in an important way.
12:39:23 But those cases are a minority. And in many more cases, it's reasonable for a parent to say they would prefer not to have it at that time. Or that they're gonna have it, but they're gonna think about it in a different way that we're thinking about it.
12:39:36 And I think making sense of that for ourselves as clinicians is useful, to kind of be... Split those bins.
12:39:49 >> This is a connected question. We have one here. Someone says: I'm intrigued by the idea that perceptions of utility may be a foregone conclusion. Perhaps as a motivator for agreeing to test, rather than an outcome.
12:40:02 This person is curious if you could say more about your findings, related to this, and how it might come into play in your longitudinal work and/or implications for informed consent.
12:40:12 >> I'm not totally sure I understand the question. I think you're saying... Like... If a lot of the work sort of takes for granted that people...
12:40:25 Can the person explain it? Or no?
12:40:28 >> Yeah. We can ask a little bit more.
12:40:31 On that. I'll see what pops up.
12:40:36 >> Okay. Unless somebody else understands it better than me.
12:40:40 Okay. We'll come back to it.
12:40:43 >> Yeah. So here's another question. Based on the models of perceived utility that have been published -- so, for example, in Hadley's paper -- do you think these should be applicable to offering genomic testing in different NICUs across the US? Are these models sufficient? Have they been evaluated in multiple NICU locations?
12:41:04 >> I mean... Models don't determine whether testing is offered. Models just are our own way of conceptualizing whether it's useful. I think... I do think that there should be a more thoughtful process, maybe even shorter and more thoughtful process, about what parents actually want from decidings whether to have testing. And that's what I'm trying to work on, in my consent project.
12:41:31 Because, for example, I don't think people really care about chromosomes or the workings of genes or how one genetic test compares to another. Which is what we spend most of genetic consents talking about.
12:41:41 But I think they might want to hear about: What  are the other parents' experience, having a genetic test. So I think there's room to move forward from a consent standpoint. But this collective body of work that all the papers just cited and many more... Are pointing to that: Genomic medicine kind of started with this implication that it was going to change management.
12:42:11 And that was the primary focus. And that was kind of where it ended. And I think there's growing recognition that... Changing management in many cases might not even be the purpose of the test. Like... Or might not even be appropriate. Nevertheless, it might still be useful.
12:42:26 And trying to broaden our conception of that.
12:42:36 >> I was actually... We were wondering about that, as related to this idea that people can feel distress. So that actually some negative outcomes can happen. If the orientation is initially... That it's gonna be useful for actually changing treatment, then the idea of distress might feel like quite a distant possibility.
12:42:59 So... Could you say a little bit more about those sort of more negative reactions? And how to think about those, in terms of counseling people at the beginning?
12:43:11 >> I think we should be very up front with people. I mean, it's hard to predict whether a test will change management. Because if we knew what it would show, we wouldn't have to do the test in the first place. But as a neonatologist, I think usually I do have a sense of what I anticipate are the range of possibilities of how a test would change an outcome.
12:43:31 And I think as a neonatologist, I'm also the best situated to do that. A genetic counselor -- it's not really fair to ask a genetic counselor to come into a situation of a complex ICU patient and then talk about how management would change. That's not their realm.
12:43:45 They're not ICU doctors. And so I feel that they often do sort of a more standardized consent about genetics. Which makes sense. But I think that it's... It probably needs to be neonatologists or the analogous doctor that provides information about what you actually expect this to do from a medical standpoint.
12:44:07 And I think that dictates to a large extent how much the other domains matter. If you really think this is gonna lead to a targeted gene editing treatment, then... It might be hard for parents to cope with, but maybe that's just the right thing to do. And probably most parents won't care if it's hard for them to cope with.
12:44:29 Those realms become more important when treatment isn't as likely to be directly impacted. So I think it's up to us to kind of help people through that. And often I think parents don't even think that their own experience matters in making this decision.
12:44:49 And sort of being honest about... We don't expect this to change what we're doing today. It would really more be providing prognostic information to you. And if that's valuable to you... Maybe even helps them have space to think about other realms.
12:45:08 >> So I got a follow-up from Hadley Smith about that question before. So: She says if parents arrive to the consent for testing with specific perceptions of the harm/benefits of the test in mind, do you think that these perceptions of the harms and benefits change between pre- and posttesting? Or do people frame the outcomes according to their pretest ideas?
12:45:32 >> I love that question. That is really interesting. I think everything is kind of framed according to the mental model you created for it. And one of the things that I think sometimes... Even my own colleagues are like... Well, you're against genetic testing.
12:45:48 No, that's not at all my purpose. I actually think people would find testing more useful if we set it up for them, in terms of what we really expected it to do. And that then they have a mental model. Like... Oh, I was expecting this to give me information about the future. And rather than being frustrated by that, for example, you would be anticipating it.
12:46:10 So I do think the two things are very much linked. Of course, there are surprises. Like... Genetic results are somewhat inherently a surprise. We don't know them a priori. Or at least, we don't have a confirmation of them in advance.
12:46:24 But there's a meshing of like... The expectations we set up and then how useful people think a result is.
12:46:31 >> I imagine that posttest perception also changes over time. And kind of the perception immediately after, versus months down the road, may differ.
12:46:47 >> Yeah. I recently got an email from a parent about a genetic test result that... They had initially been sort of grateful for. Although it was very uncertain. And the uncertainty has lived on and on. And they've had subsequent testing and it's still uncertain. And they've become incredibly frustrated with it. So that's one example.
12:47:07 I think more commonly it goes in a different trajectory. Where their own emotional response kind of dissipates and maybe they think it's more useful as that goes on. I totally agree. So that's why I think there needs to be a lot more longitudinal work.
12:47:20 >> Yeah.
12:47:21 >> Here's a hard question, I think. And it would be for both of you, I'm pretty sure. Given the harms that some parents perceived, do you think there are sufficient ways to help families navigate concerns once they leave the NICU?
12:47:42 >> I guess once they live the NICU is a tricky question. Because every place has different available services. In a lot of cases, parents have actually already left the NICU, even, when they receive results.
12:47:59 All I can say is I think that should be part of the consideration of... Like, being able to mitigate harms, potentially -- I guess that's just adequate psychosocial support. And access to genetics. And maybe that's part of our obligation as a healthcare system in offering testing, is to have people be supported in a longer term way.
12:48:22 >> Yeah. I think... Some of the barriers that we've captured in the past is concerns around discrimination and privacy. And to some degree, we can help clarify that. As came up in the Q and A earlier... Are people even aware of things like GENA, that exist, to potentially protect to a certain extent. And so providing some information about that, as well as... Where we don't have as good information, kind of where the protections of something like GENA may stop...
12:49:00 And where that may vary, geographically, as well, I think to a certain extent, there are resources that can be provided, to help mitigate some of those harms. But others are a bit more... Murky.
12:49:18 >> I was wondering if... So people might end up just bringing these questions to their pediatrician and everyday providers. Do you think there are sufficient resources to help in that transition from specialist care to their primary care? And where they can go -- where people can get more help on that? Actually looking after people on an ongoing basis?
12:49:51 >> I think Hadley wrote a paper about this that was in pediatrics. And from what I remember, parents are often in a position of kind of informing clinicians about their own results. But she can comment if there's more. That doesn't surprise me.
12:50:08 I think the reality is, though, for most results, we don't always know what it means for patients' future. Which is part of what we should be honest about, it's not like... Oh, in some metabolic conditions, you need to remember that if you go to the emergency room, you need to tell the doctors to start dextrose right away, because otherwise there will be a metabolic crisis. That's kind of straightforward.
12:50:34 But in many case it's not as straightforward. We know this child is at risk for developmental problems. It's not a concrete change in the medical management.
12:50:48 >> Perhaps we can think a little bit as well about sort of future research that people might do to build on this work. Incorporating -- I was wondering, Jessica, if you had reflections about that, coming out of your ClinGen Working Group role on clinical actionability. What do you think needs to be on the research agenda? In this area?
12:51:11 >> Most of my work on ClinGen has been the assessment of how actionable conditions are. Mainly from the clinical perspective, in order to help guide what findings a population screening program may return. So not so much how you set up a population screening program, but if there is a population screening program, how do you consider what condition you are or are not going to return as part of that program.
12:51:41 Historically, most of our work has been around secondary findings. So if you're already doing genomic screening, how do you identify other findings to return, based on actionability? So most of the work on ClinGen has been based mostly in clinical actionability.
12:51:57 But I also have a strong interest in kind of the broader concept of actionability, that we don't necessarily consider as part of ClinGen. Such as just the value of the information, and the benefit to family members that may not be directly related to the person getting genetic testing in the first place. And how do we start to incorporate that into our models?
12:52:23 As well as kind of capturing individual and family perspectives of those things. You know, I think we as... Researchers and clinicians can think about what's important, but making sure that we're actually capturing those perspectives and considering those, and figuring out how we can adapt our implementation processes, to address all that variability, I think, is really important.
12:52:51 >> I'll add one more general idea, which is... Obviously this is an ELSI forum and I myself am quite invested in doing ELSI work. But I do think there is growing momentum to think about... What are patients in the NICU setting... And parents... Thinking about, in terms of what's important to them. And how we can make that not just sort of a side goal of research, but actually integrate it into the primary way we do research.
12:53:21 Like, what outcomes do people want to improve? And how can we focus on those? Which in so many ways... Medicine has evolved to be a system of prioritizing how doctors and researchers see things. And I think for example... That is sort of a silent underlying assumption, is that genetics is gonna impact medical management, and that's the primary goal.
12:53:46 But in many other fields, the same sort of assumptions exist. So this is just a tiny piece of a bigger change, I think, that's happening. And I would encourage people in all different fields to think about... Okay. You're making a difference. In what? What outcomes do people actually want you to be making a difference in?
12:54:13 >> And what might be some candidates for that?
12:54:18 >> Well, I'm doing a project on what parents care about with respiratory morbidity, related to prematurity, with Anij Jambier, who researched this more than anybody in a clinical context. We tend to measure respiratory morbidities with a tracheostomy, three hospitalizations. There are set things we measure.
12:54:41 But there are all kinds of potential complications of respiratory disease. From changes in your voice to... Ability to go to day care. And kind of thinking through what people actually want to change, but there must be many examples, beyond my little NICU sphere, of... You know... All kinds of research.
12:55:03 Like... What patients and caregivers... I read an interesting article recently that was 30 years old, from JAMA. It's about how many studies in diabetes use HbA1c as an endpoint. Whereas... No one goes around feeling good because their HbA1c is low. They go around feeling good because they have energy and can eat normally and can go out for dinner or whatever.
12:55:32 And the article was a systematic review where it talked about how many papers actually used an endpoint that would be even potentially meaningful to a patient. And I thought that was an interesting model.
12:55:44 If we did that in every field, what would the ratios look like?
12:55:53 >> I'm thinking about studies on the impact of different interventions for ADHD, and I did see one study that was talking about... That parents were less interested -- not just interested in seeing symptom reduction in all the different symptoms, but also just seeing better interactions between teachers and the kid, for instance.
12:56:21 The lived experience type of outcomes versus the more sort of scale measurable things.
12:56:26 >> I love that! I read an article about ADHD recently where they said... Well, it isn't really effective in long-term school outcomes. And I was like... Well, that is important. But what if it makes the parents' life easier? As the parent of a 2 and 4-year-old, it's important to me to make my life feasible.
12:56:42 So you know... I think there's all kinds of things that might or might not be important to people. And different ways to think about it in different fields.
12:56:52 >> Yeah. And I've seen that in the rare disease world as well. Of like... Developing outcome measures for clinical trials that are beyond kind of the... Does this cause a clinically relevant change, versus does it increase quality of life? For the individual or family.
12:57:11 And a much broader perspective of the outcomes that we're considering in clinical trials. Which is really encouraging.
12:57:19 >> So I think we just have time for maybe one or two more questions. There is a question in the chat about whether people are declining testing or are concerned about testing, if they are immigrants. And worried about whether or not the data might be used to identify or track them as immigrants.
12:57:42 And somebody add that they had a family agree to genome testing only if the lab agreed to destroy the sample after results. Those are very real world implications, that someone might be carrying with them. As their kind of measure for whether they go ahead. Have you had any that encountered any of that, any of you?
12:58:00 >> I have never heard those specific concerns. Although I can certainly imagine how they come up. And... They seem like valid concerns to me.
12:58:14 >> I don't have any personal experience of that.
12:58:16 >> So maybe I'll just ask one quick more question about... If you have anything you want to add about where we should be taking this research, especially as an ELSI community. Or what you hope that people might take away from the paper or from this area of research.
12:58:38 Final thoughts.
12:58:43 >> My whole stance is: I think we need to be very honest and realistic both with families but also with ourselves about the quantity of cases in which we're really changing medical outcomes, versus where we're providing information, which may be very valuable, but is largely dependent on who is receiving the information.
12:59:03  And that sort of reframes the whole narrative. Because we publish these cases of... You find the gene, and this is real. This happened at CHOP with the gene editing case recently. Where you find something, and there's a dramatic solution. And who cares about the coping context? The child is much better.
12:59:21 But... We need to be clear about the proportion of cases in which that happens. And when that's not really... I think it's far more common that there are these complex gains of knowing about the future, albeit with uncertainty. And then we can start thinking about how to dive into those realms that are a little bit more complicated.
12:59:44 Rather than trying to simplify it. And I think miss some of that story.
12:59:49 >> Jess, do you have any other final thoughts?
12:59:53 >> Just to jump off of that, I mostly think about how we measure those things and how we capture that. And how we look at associations in order to help personalize those conversations and assessments.
13:00:07 And so I think what I'm hoping that studies like this and others will help inform is the development of those measures, so we can start capturing those outcomes and informing future genomic medicine initiatives.
13:00:22 >> So thank you both. So we're right at the hour now. And I just want to say a big thank you to you, KP, and Jessica, for this really rich discussion, and to our audience for these really fantastic questions. And it's really great to see people even engaging in answering each other's questions.
13:00:40 So thank you very, very much. Before we leave, I just want to highlight that CERA does lots of different kinds of events. And so we have our monthly ELSI Friday Forum on rigor, reproducibility, and responsibility: ELSI questions in population data practices. And that's gonna be on the 13th of June.
13:00:59 The link to register for that session is in the chat. And then CERA is excited to launch a positive fun new feature, I think, called CERA Shoutouts. This is gonna be on ELSIhub. And this is a chance to celebrate an achievement within the ELSI field. It might be a new book or an award or a well earned retirement. The founding of a new center. Some kind of... Or a noteworthy trainee placement.
13:01:25 So if you have something exciting happening, that's happening to you, or to one of your colleagues, or friends, help us recognize and honor those milestones by nominating these people for a CERA shoutout. And the link to submit an achievement is in the chat.
13:01:41 And then I just want to finally say that we'll put up a postevent survey. And I have never seen a group who take surveys as seriously as CERA does. So please do fill in this survey, and let us know what you thought of how the session went today.
13:01:57 If you have any comments or suggestions for technical or content, we will gladly receive them. So with that, I would like to thank our speakers again.
13:02:09 Thank you so much and thanks to everyone for coming, and we will see you at a future ELSI event. CERA event. Thanks a lot!
13:02:16 >> Thank you.