 All right. Hello, everyone. I'm Sarah and I am a project manager and tonight counselor at Brigham and Women's Hospital in Boston I'll be talking today about the baby seek project, which is a randomized trial exploring the use of genome sequencing in both healthy and sick newborns But before I describe our plans for the baby seek project I wanted to first introduce some of our pilot data that got us to the point of being funded for the baby seek project So we started with a simple question, which is our parents even interested in genome screening for their newborns So we approached over 1,300 parents in the well newborn nursery at Brigham and Women's Hospital within 72 hours after they give birth and We after consenting them we randomized each family to receive one of two versions of a survey The difference between the surveys was that one version included a five-minute overview of genetics and genome screening and Then we asked parents to rate their interest in genome screening for their newborn If it were available as part of a research study for free And they were asked to rate their interest on a five-point Likert scale which ranged from one not at all interested to five extremely interested and the reason for this randomization is because we wanted to address concerns that even Discussing genome screening or newborn screening with parents would raise their Awareness of the state mandated newborn screening that goes on and would lead them to question or refuse newborn screening So then we followed up with parents Several months later with another survey also asking them about their interests and Some of these parents in the follow-up survey received mock results that gave them a better sense of what they could learn from genome screening I'm actually not going to focus on the follow-up survey data, but stay tuned for that. It will be published soon I'm going to primarily focus on our baseline data So when we asked parents in the hospital how interested they would be in this test for their baby We saw generally a high level of interest So over 82 percent of parents were at least somewhat interested in genome screening for their baby And we also checked with the clinical staff on the while newborn nursery And they reported that over the two-year period that we conducted the survey not a single parent questioned or refused state mandated newborn screening So then our question was can we find any Associations between demographic characteristics of our sample and level of interest in genome screening So those analyses are shown here. So in the second column, you see the summary statistics So our sample was 33 years old was the mean age two-thirds of the parents who responded were the mothers Some ethnic and racial diversity although largely white population 80 percent were married Very educated population. So 50 percent had at least some graduate school training For half of parents. This was their first biological child and these last two family history of genetic disease and infant health concerns These questions were a bit vague in their self-reported data. So Particularly for the infant health concerns that these were all parents of well newborns And so it was really their perception that there was some some potential health concern with their newborn So six percent of parents said yes We ran a logistic regression to see if there were associations between any of these variables and interest in genome screening for that analysis we dichotomized interest into Not interested which was those parents who said not at all or a little versus Interested which was those who said somewhat very or extremely and we saw that of these variables Parents who were married were slightly less likely to be interested in genome screening and those who had some health concerns about their infant were less likely And we can talk about in a discussion why that might be there's some interesting hypotheses We also were interested in how closely mothers and fathers would agree. So among our 514 parents who who were asked this interest question 168 of those were couples and We defined having a similar level of interest as being within one point on the five-point Likert scale So 127 or about three quarters of parents were in that category where they generally agreed with our interest level and About 25% were discordant in their level of interest and concordance was more likely for couples who were married So some limitations of our pilot survey were that it was a simple survey just asking about hypothetical interest parents didn't Actually have to make a choice about whether they want a genome screening Mothers and fathers in general were asked at the same time and generally in the same room And we did explicitly ask them not to collaborate on their answers, but in some cases it happened anyway And while we did check with the clinical staff to make sure that no parents had refused newborns state newborn screening We didn't track whether there was increased anxiety or confusion or questions about states state screening But despite these limitations our data did suggest that parents can be asked about genome screening in The immediate postpartum period without threatening compliance on state newborn screening and that there's a high level of interest among parents So with these data and other data we applied for and were awarded funding for the baby seat project Which is a randomized trial that will explore the benefits and risks of Genomes genome sequencing in both healthy and sick newborns Our study was one of four that were funded by the NIH last year to look at this the question of genome Sequencing in newborns in different ways and among those four projects ours is the only one that will be offering sequencing to healthy newborns So pending IRB approval we plan to enroll 244 240 healthy newborns at Brigham and women's and 240 babies in the NICU at Boston Children's as well as their parents and physicians and This is an overview of what our study our study design So we have built in a pre-enrollment genetic counseling session Which is basically a consent session. That's very detailed and structured and will outline the potential benefits and risks and limitations of genome sequencing and The study designed the fact that it's a randomized design and parents may not actually receive genome sequencing for their baby Parents who are then interested will be consented will draw blood from the infant and both parents and the genetic counselor will gather a detailed family history Then the infants in both groups will be randomized So all the infants will receive the standard of care state mandated newborn screening the family history that the genetic counselor gathers And half of babies in each arm will receive a genome report So what that will include will be any pathogenic variants that are related to childhood onset conditions carrier status for any childhood onset conditions and a limited number of pharmacogenomic variants that could be useful in the childhood period for those infants that have a phenotype so Primarily the infants in the NICU their physicians will have the option of ordering an indication-based report Which is basically a targeted query of genes that are known to be associated with the infants phenotype The disclosure will be led by the study genetic counselor and study physician and we're really structuring this to model clinical care as much as possible So we want it to look like a clinical genetics consult So the results disclosure led by the genetic counselor and study physician and the outcome or the summary of that disclosure as well as any recommendations and Reports from the study will be sent to the infants pediatrician and to any other Physicians who have been involved in that infant's care and though that consult letter will be placed in the medical record At ten months after the disclosure session the infant and parents will return for another Visit that mimics a clinical visit with a study physician and genetic counselor and again the consult letter will be sent to the infants physicians We'll be doing a medical record review to look at health care utilization tests and procedures that were ordered for these infants And then throughout we'll be gathering outcomes, which I'll talk about in a minute so we'll be administering surveys to both parents and physicians and We also will have study physicians and genetic counselors available throughout the course of this study to answer questions from any parents or any Physicians who are part of this study So now focusing in on what the experience will be for infants and parents so for infants born at Brigham or admitted to the Children's NICU. They'll be approached by an RA to give parents information about the study if parents are interested They'll have the pre-enrollment genetic counseling session and consent We'll survey them there and then from that point forward They have the option of contacting study physicians and genetic counselors at any point to ask questions We have the results disclosure led by the the GC and the study physician The genetic counselor will also call parents one week after the results disclosure We see that primarily as a safety check-in To make sure that parents aren't distressed, but it's also an opportunity for collecting data So we'll be administering measures of anxiety and postpartum depression And at three months they will receive a another survey by mail or by email and then at ten months They have their follow-up visit with the physician and genetic counselor and we'll be surveying them at that point, too So for physicians, we're going to try to survey as many physicians who might interact with these babies as possible up front So that will include attending neonatologists specialists who consult in the in the NICU and Community pediatricians who tend to see a lot of infants that are born at Brigham or Children's admitted to children's and we'll be sending them a baseline survey Which is primarily to gather their attitudes about genome sequencing and their Justouts of the perceived utility of the test. We're not going to be formally consenting them But rather they're completing the survey will serve as their consent For each physician they may end up not having any patients enroll in the study They may have patients enroll and by chance all those patients are randomized to the standard of care arm Or they may have at least one one infant in under their care who is randomized to receive genome sequencing So at the point that any of their patients enroll they can contact a study physician or genetic counselor to ask questions about the study or about interpretation of results Once one of their patients enroll and we're prepared to return that Patients results to the family. We will remind the physician to please complete the baseline surveys So hopefully we'll have that data before they receive any results then after the results disclosure session to the family the Physicians will receive the consult letters from our study staff and For any of the physicians who receive a genome report each time they receive a genome report from the study We will send them a utilization a post disclosure survey that Asks them how they have used that information in the infant's care how they plan to use that information in the infant's care And again, we won't be formally consenting them, but their completion serves as their consent at the end of the study We will be surveying all of the physicians again In a survey similar to the baseline survey that it gets at their attitudes and their perception of genome sequencing and its utility overall There's some specifics about our plans for surveying parents and physicians these survey domains are subject to change But in general you can see here that the physician surveys are indicated in orange and the parents in black so for Physicians they'll be surveyed at baseline and end of study about their attitudes perceived utility and Plans or actual utilization of genome sequencing results And they'll also be surveyed once after every time that they receive a genome report for parents They'll be surveyed at baseline immediately post disclosure three months and ten months later And in addition to getting their attitudes perceived utility and health care utilization will also be assessing their health behaviors and health intentions And intentions and we're really interested in family dynamics. So parent-child bonding partner relationships and parents distressed So this is the combined work of over 40 different investigators and wanted to acknowledge and thank them all Thank you to Danielle Bach who contributed some of these slides This is I've presented our plans and we are really hoping that this will become a reality and we'll actually start implementing the study in late fall or early winter so stay tuned for more data and Thank you all for your time. I have a question. Is this on? so this is an incredibly detailed design and having been involved in some of the ClinSeq studies as well where we're trying to Mimic clinical care as much as we can in a research setting you're more in a clinical environment than we are and Take good care of patients. So your side arrow about having the availability of physicians and genetic counselors throughout How do you balance? It's not even balanced. How do you account for what might change your outcome? So if you find a subset or even a majority of people who have more negative attitudes in the end and are more distressed What do we attribute that to? I mean, how do you go back and say it was the information they received it was how they received it? It was what the people in the and ICU said to them. How do you how do you tease that apart? That's a good question. I Think we have I suppose we have to think about what we can gather from our surveys or from interviews and There's a limited amount that we can ask in the surveys We may end up with some satisfaction questions, which may or may not get at your at your point, but We're hoping to build an option of interviewing parents, too. Otherwise. I think it's really hard to tease out Yeah, we're trying to take advantage of as many Places where we can gather data as possible. So any time that parents contact a student and accounts are a physician We want to gather data on the content of that conversation And and we don't yet have a structured Way of we haven't quite decided how we'll analyze all that or what the content, you know What form we'll use to gather that data and That's something that definitely something to think about I'm dead So I'm really interested in this and I understand the focus on how the parents are responding and you're It occurred to me that and I know that you're going to have some survey data of the Clinicians the physicians that receive these letters of result. I thought It an interesting question occurred to me, and I'm sure it occurred to you guys And I'm wondering if you could give us a sense of that discussion of the how The clinicians value the not just getting a report or having their patients receive these results But getting the additional information to them from the genetic counselor Describing or explaining what the results are as part of your letter so the question that occurred to me is what is the added value to the pediatricians and others that are treating these patients that They're attributing to these letters within the context that we all think that you know clearly The focal point Around genetics information is spreading to non-genetic counselors and clinicians and certainly primary care physicians We're gonna have to help patients with this kind of information without You know letters from the genetic counselors to tell me what you guys thought about that and where you think That question fits in this study Yeah, I think that's that's a great question as well so we originally had envisioned this study to be more hands-off and to return we would return results to the family But we would be much more hands-off in sending that information to the pediatrician So we had talked about we'll just send the results to pediatrician without that a really a detailed accompanying letter and we'll see what they do with it and I think we came around to Acknowledging that IRBs and others think that this is this study is really rocking the boat is really really far out there and that we want to be sensitive to those concerns and and study and what we are more what we Value more is studying how this information could be used in infants care and whether we have a more active hand in that I think that's something that we just Decided would be okay that we can take a more active hand and and still Draw conclusions about the utility of this information So it will be the way we have a design where all physicians will get that detailed letter We we won't be able to tease out. What's the added value of that those detailed recommendations? We could look at Which physicians choose to have an in-person or phone conversation with a genetic counselor and physician? and You know the content of those conversations might give us some additional information We could look at how physicians interact with the study physicians and genetic counselors ad hoc by you know inquiries and But I think we ultimately decided that it would be more pragmatic I think to to take a more hands-on approach