Electronically Signing Child Medical Consent Made Easy

Electronically signing child medical consent

i'm going to be talking today about the baby seek project which some of you may have heard a little bit about before and i'll be sure to cover some of the background as well as some of the results from the study but what i really want to focus on today are some of the special considerations we have for this project in terms of enrollment and consent of participants so this quote from francis collins back in 2012 and said whether you like it or not a complete sequencing of a new of newborns is not far away um and you know that being over eight years ago now um it's still something that we don't see fully um but it's really something that's been coming um coming along in terms of research as well as just being in the news and having a lot of public exposure and in 2014 the nhgri and nichd put out an rfa to put together a consortium examining the clinical utility and the impact of genomic sequencing in newborns and so that's how the baby seek project came to be led by pis robert greene at genomes to people at the brigham as well as alan beggs at boston children's with leadership from heidi reem at the time at the laboratory for molecular medicine as well as the broad and some of our colleagues at baylor college of medicine including amy mcguire and the babysit project was looking at specifically at the impact of sequencing both in healthy and in sick newborns i mean it was a first of its kind study and i'll go into a lot more detail about it but really the overarching goal was to look at the medical behavioral and economic impact of doing this type of sequencing in the unique population of newborns so how does this impact their medical care now and in the future how do parents and physicians react to this information and how do they utilize it and what are the economic impacts so what is the cost on the health care system right away and as as these children grow so baby seek was set up as a randomized clinical trial of whole exome sequencing as i mentioned both in healthy and in sick infants so our icu newborns were recruited from boston children's hospital as well as the brigham and mass general and then we also had the other half of our cohort being the healthy newborns which were recruited from the the brigham well baby nursery and so for both of those cohorts when infants were enrolled they were randomized into our two study arms we had our control arm which was standard of care newborn screening so that's the blood spot that every newborn in massachusetts gets as well as some version of it every newborn in the united states um looking at a panel of um conditions where there's some type of treatment or actionability in the newborn period many of which are genetic as well as a family history from a genetic counselor and then our experimental or sequencing arm was that same standard of care plus a genomic sequencing report and those reports were then disclosed back to the families and with a study physician as well as genetic counselor and then the results were also passed along to the infant's pediatrician or their treating neonatologist or physician if they were an inpatient and after the results um were returned there was our kind of outcomes measures so those children were followed just by medical record review as well as a series a whole series of surveys for parents as well as those physicians to capture many of those different um economic as well as you know medical and behavioral outcomes that i discussed previously so this was not only a first of its kind study in terms of exploring doing sequencing in this very very early period looking at not just the presentation of health issues say in the icu but also just screening in general looking for future health risks for these children that may impact them um in the newborn period but also all the way throughout childhood and life so it was exciting in terms of being new and being a territory that really hadn't been explored but it was also quite complex in terms of the actual study logistics and how we would be able to go about doing this um so here's just a quick study timeline on top we have our parents um in blue and so the infants were enrolled typically right after birth up to about six weeks of age at which time they would have a sample collected um and they would have a baseline survey and be randomized to either sequencing or the control arm results were then disclosed about um a few months after that um the sequencing was actually done here at the broad um and the uh data was then interpreted and reported by the lmm and then those families were followed by an immediate post-disclosure survey as well as surveys at three months and 10 months post-disclosure at the same time we were exploring the impact on physicians via the pediatricians or neonatologists so when one of their infants were enrolled in the study they had the option of participating as well in completing a baseline survey and then they would have additional post-disclosure surveys with every infant that they had enrolled some physicians may have just had one infant others may have had several during the course of the study physicians also had the option to order what we called an indication-based analysis so on top of the initial whole exome if a child were to develop new symptoms as a sick infant or even one of the healthy infants developing some type of potentially genetic condition they could then ask for that data to be reanalyzed with a particular focus on whatever that condition may be and the physicians were then given a survey at the very end of the study that was linked to the baseline survey to kind of complete their participation so the actual sequencing itself we called the newborn genomic sequencing report um this was a little bit different than your classic whole exome sequencing report being that for many of these infants this was a more of a screening type of test we weren't looking particularly to explain any um presenting health conditions because these were essentially healthy newborns in many of the cases and what those reports were looking to report were three different categories first was our kind of classic monogenic disease risk so a genetic change putting the infant at a high likelihood for developing some type of health condition we also were reporting on carrier status so just having a single heterozygous variant in a gene known to cause a recessive condition um so that would really have no impact on the child's health but be important information for family planning much further down the line but then also maybe more immediately family planning for their parents um many of which would be going on to have additional kids then the last category was our pharmacogenomic variants so there was a small selection of those genes related to pharmacogenetic risks in childhood and the genes themselves were carefully analyzed to kind of bend them into different categories and this was led by osgay bersoy at the lmm and about a thousand or so genes were split into these categories so we would have some guidance in terms of what would be reported back first would be childhood onset strong evidence of the gene to disease association and high penetrance so a high likelihood that the child would actually go on to develop that condition then the next category kind of softened some of those thresholds a little bit um particularly the uh the evidence and the penetrance could be more moderate if there was some type of clinical action ability for that condition or gene in childhood what initially wasn't reported were things like adult onset limited evidence or low penetrance genes a very small number of those highly actionable well-established adult onset conditions were added to the protocol shortly after it started mainly the brca and lynch syndrome genes but otherwise genes with with no actionability in adulthood or limited evidence were not included in these reports on the variant level we're reporting pathogenic or likely pathogenic changes um so not recording benign are likely benign and we were able to report variants of uncertain significance only on those indication-based reports so if there was a vus in a gene um that had a high likelihood of being associated with the child's presenting condition then that could be reported but otherwise on the more screening results the us's were not included so with this type of study you may think great we have the technology let's go ahead and do this there's a lot of interest here why aren't we sequencing newborns and those are certainly um the thoughts of of many people particularly maybe in our field or or here at the broad but there was also a lot of pushback from the community particularly in 2015 when we started this but even now in you know 2021 there's still a lot of controversy surrounding doing this type of screening particularly in the healthy infants and these are just a few of the ethical and irb considerations that our team had to tackle while we were working to develop this protocol and figuring out how we would run this study so i wanted to take some time to go through these just to give you a little bit of background in terms of how we kind of worked through them um as well as um you know how it impacted how we ran this study the first that we heard a lot about and we continue um the argument often is when we think of healthy screening in infants is child autonomy so by doing this type of sequencing and consenting to a study a parent is taking away the child's future decision making in terms of their ability to decide whether or not they may want to participate in learning about a health risk or genetic health risk and this is something that's fairly more pertinent in the healthy population when we think of the critically ill nicu infants it's generally more acceptable to be able to do this type of testing because the benefit the potential benefits of finding a diagnosis for a child's presenting condition generally outweigh the loss of autonomy that might come with that but prior to that we didn't really have that balance when we're thinking of healthy newborns or just screening for unrelated conditions her familial impacts we all know that genetics doesn't occur in a vacuum for these infants we weren't just going to be learning about them we were going to be learning about their parents maybe their siblings their future siblings and also extended family members we did collect samples from mom and dad as part of this study they weren't getting wholexome this was done as pro-band only not trio but we did have samples in order to confirm particular variants found in the child um particularly there was a health risk associated with them we could then go back and see if the variant was inherited from mom or dad or was de novo uh incidental and secondary findings is always a buzzword with the irb and consent forms when we're thinking about any type of genetic testing for this study really almost all of what we were planning to report was going to be quote unquote incidental or secondary that wasn't felt to explain a child's condition maybe in some aspects within nicu children but it would go well beyond that so there's the question of um you know are these going to be actionable results maybe in some cases but we were also going far beyond that in terms of childhood onset conditions um and would be reporting things that were regardless of actionability parental response to results is something we hear a lot about and it's kind of at this point was a theoretical risk there was a lot of concern that learning about a child's future health risk would be detrimental to a parent that they would have increased anxiety or distress or would treat their child differently um you may have heard of something like vulnerable child syndrome and so that was a real concern for the irb and the community in general some more logistical things we were talking about documenting things here in the electronic health record so this was not just research testing this was clinical testing where a child would get a clia certified result back and it would be put into the medical record and once something is in the medical record that's something that cannot really be taken out so there's an aspect of privacy that goes along with this as well genetic discrimination um is another category that we certainly talk a lot about in consent forms and just with genetic testing in general many of you are probably familiar with some of the protections that we do have the federal law gina protects against genetic discrimination by health insurers and employers but that is not something that extends to life insurance long-term care and disability insurance when we're doing testing for a child who has a condition and we're looking to explain it this really doesn't come into play as much because they already are presenting with this condition the genetic testing is really just explaining what's going on but this really is something that comes to the forefront when we're talking about future risk and learning about a potential health risk for a healthy individual we were also asking to follow these children long term so the active participation in the study if you want to call it that was more like one or two years where we would be sequencing actively following up with parents with surveys interviews speaking with them but we wanted to continue our study out or have the ability to continue it out well beyond then with medical record review or the potential to follow up with new surveys so we could really take hold of this really important and novel cohort and follow it long term and there's always extra considerations when you're thinking of doing something like that and certainly not the last issue but another important one to talk about is the vulnerable enrollment period so we were seeking to enroll patients directly after birth so for healthy patients this means in the immediate postpartum period and for those of you who are not parents um who are not familiar with kind of the the postpartum period generally a healthy newborn and parents are in the hospital for about 48 hours after birth before they're discharged home um maybe a few days more if there's a c-section so it's a very short period of time parents are understandably sleep-deprived mom may be on particular pain medications there's a lot of excitement and hustle and bustle in terms of families visiting pediatricians needing to see the patient ob is needing to see the mom there's a lot going on in a very short period of time and there's also just a lot of emotions and stress in that time period at the same time in the nicu you're taking all of that and then you're heightening it with a critically ill child so there are really a lot of environmental things that we had to take into account when we're thinking about approaching families for research during this period all right so we're taking all those ethical considerations we have them in mind now we need to figure out how to address them in order to make a study protocol that was acceptable to the irb and also acceptable to the study staff we wanted to make sure that we were you know putting out a responsible well thought out study where we're not introducing an excess of risk so it was really important that we addressed all of these different categories child autonomy is a tricky one and i think you know you do your best to address that and how our protocol is written how the consent form is written but that's always a risk that's going to have to maintain be maintained throughout the study and people may disagree with in order to combat that a little bit um it was a requirement that both parents agreed to the child's participation so they both had to sign the consent form if one parent did not agree then the child became ineligible to participate and we also have language in there about assenting the child when they're 13 years old so getting permission from them to continue participation in the study if we're still actively collecting information at that point in time and this goes hand in hand with the familial implications so we were not only just consenting the parents for their child's participation but each parent had to sign their own consent form and enroll themselves of subjects because we were collecting a sample from them and very well could learn about a health risk for them maybe a health risk that was more immediate to them than it even was to their child we also created something that we called our genomic resource center which is staffed by our study geneticists neonatologists and genetic counselors and that was created for families and pediatricians to really assist with results follow-up so not only answer questions about the results but also help to further disseminate that information so if a parent learned about a risk for cardiomyopathy in their child that they themselves also were found to have the same variant for we were there to be able to help in terms of directing them to a particular cardiology specialist or in terms of speaking with their own pcp to help make that process a little bit smoother we also in some instances helped with communication to a larger number of family members outside of that immediate family all right so the incidental and secondary findings as i mentioned the vast majority of what we had the potential to report was going to be you know unanticipated for these families so our consent form and our consent conversation with these families required a really extensive review of the potential result types so not only was this listed in the consent but we also created an educational aid that had example vignettes of the different conditions so um anything from you know talking about a condition like rett syndrome where a child could be born healthy and eventually after a couple years of age start to lose symptoms lose milestones and develop neurological symptoms and it's a condition that right now we don't have a good treatment or cure for so we had to talk to parents about that make sure they understood the types of results they could um get from this type of study and that they were comfortable with that and that they could try to you know encourage them to think through how they might react to that type of information and then we also defined those result return thresholds that i shared with you earlier so no variance of uncertain significance um penetrance limits et cetera looking taking a really careful look at actionability and age of onset and things of that nature the parental response to results now this was a tricky one um we wanted to make sure that we were measuring a parental distress to see if in fact the concern about parents not being able to handle this type of information was really grounded in an actual risk and so we needed to measure things like postpartum distress at all of our survey points and we did that from some of our established scales as well as additional questions looking at parent and child bonding and vulnerability however because we were asking those questions we also had to have particular safety measures in place so the irb wanted to make sure that we had a plan that if you're asking a question about distress what are you going to do if a parent does say you know their responses do indicate that they are having some level of distress and so we had a study staff psychologist susan weisbrin who was fantastic and was able to help us follow up with all of the individuals who may have been flagged and this was in both our control and our sequencing group um the neonatal period as everyone knows is a really stressful time so it wasn't um it wasn't unheard of for us to have individuals who did kind of cross our threshold for being uh needing to have someone check in with them and then we also did something that was a first for me in terms of working with consensus protocols and that was administering consent understanding questions so this was something that the irb wanted in order to ensure that parents were really on board that they were listening during the consent session particularly during this vulnerable period and so there were 18 questions true or false that we went through after completing the verbal consent process to make sure that a parent actually fully understood what we were um asking them to consent to for ehr documentation um this was a little bit easier you know it's kind of a cut and dry thing when you have a clinical report it goes into the medical record so we did establish several time points for study withdrawal prior to results return where parents knew that if they changed their mind they could leave the study and there would be nothing in terms of results documented in the medical record however once they chose to actually listen to the results at that point forward things had to be documented and privacy was also listed as a risk in the informed consent form for genetic discrimination similarly it was uh there was a thorough review of that as a risk in our informed consent um and we were providing families with an educational aid that reviewed what gina covered and what it didn't and were able to answer questions about that for them in terms of long-term follow-up a family was paired with a single research assistant and genetic counselor to try to maintain continuity of steady contact throughout the study so this was to try to limit confusion for families with all of these follow-up steps make them feel comfortable and that they had someone that they could go to with questions about the study so the research assistant who initially approached them and helped arrange their consent session was the one who would then be following up to remind them about their disclosure visits their surveys um asking for you know updates about the child's pediatric care etc and same goes for the genetic counselor the one who performed their consent but also be the one who'd be present at their results disclosure and i've touched a little bit already on the the vulnerable enrollment period but a few other things that were unique to this study is that we were um asked and agreed to not approach families until about 24 hours post birth so that even shrunk our window of opportunity even smaller to only 24 hours in some instances um but it was important in order to reduce the risks of um you know obtaining consent from someone who truly shouldn't be providing consent um uh you know if mom was heavily medicated or exhausted for all of those reasons we were bumped out for about 24 hours and we also involved the nicu physicians and the well-baby nursery charge nurses in our approach process so once a research assistant had looked at the census they would be reviewing all of their eligible babies with either the nicu attending or the well-baby nursery charge nurse to make sure they didn't have any objections whether that be social issues or particular health problems or really anything happening in that time period where the clinical staff felt like it wasn't appropriate to approach a family so their permission was obtained first before we went any further and then something that was also unique about the study was this two-week delay um when families were enrolled they signed their consent forms they actually weren't considered officially enrolled in the study until they actually completed their baseline survey which could be done anywhere between that point in time and two weeks later it was once that baseline survey was completed by at least one parent that the study randomization would happen if a family didn't complete that survey they were considered passively withdrawn so this just gave them a chance to go home look through things again think about it and if they had any issues or concerns they could reach out or choose not to participate all right so in addition to some of those logistical uh ethical barriers we had a lot of logistical barriers as well um and just a few of them are listed here so that immediate postpartum period as well as the icu environment can be very stressful there's not a lot of opportunity for um an hour to sit down with a genetic counselor to review a study consent form and that proved to be quite difficult in terms of getting these families all the way through enrollment before they were just discharged from the hospital um the consent time commitment again it was not just a hey sign here sign here sign here um this is a 19 page consent form and require that a genetic counselor review the full thing with the families and review it twice if mom and dad weren't together they each had to sit through that conversation and that typically took at least an hour we were asking for a blood draw from an infant who may not have needed any type of draw this is a venous draw not a not a heel stick which was typically used for our estate newborn screening we were asking for multiple follow-up steps steps and return visit to the hospital for kids in the nicu that may not have been as problematic they may have still been in the nicu at results return or they may be frequently coming to the hospital for follow-ups but for many families that pediatric care was going to be at their community physician and there wouldn't be a typical normal plan to come back to the hospital and then also a continuity of care once we returned to these results these kids were no longer in the care of the the hospital they were typically under the care of their pediatricians out in the community so to combat some of those issues we really tried our best to educate and engage the nicu and nursery staff we wanted to make sure that they knew who we were and what our study was so they felt like they could answer questions for their patients or they could um you know know who to contact if there was an issue and just feel like they were on board with the type of work we were doing we also created that uh grc that i spoke about earlier and had that two-week enrollment checkpoint which is definitely a novel thing for most research you typically sign the consent form and complete your verbal consent and you're ready to go so this is an extra step and we also tried to collect excess clinical sample or tack on to a clinical draw whenever possible just to reduce the number of research-only blood draws to try to put parents at ease a little bit but generally particularly healthy population that wasn't usually an option and there had to be just a research only draw and as we started this process it was difficult and we found that there were a lot of hiccups and barriers along the way that made it difficult for families to enroll and so we had to go back and revise our protocol over time that's an important thing to know when you're working on a study that what you lay out in the beginning particularly when you haven't had any experience with this type of enrollment environment you want to be able to you feel like you can go back and reassess and change things so we were able to to do that several times over um we extended eligibility criteria to six weeks of age prior to that it was a much shorter time um we allowed for a enrollment of one parent so if um mom and dad weren't together at the bedside we were able to consent one in person and consent the other by a phone call um we offered delayed enrollment so they could enroll post discharge um if a family was introduced to the study but wanted to think about it further we allow them to go home and complete their enrollment at a later date should they want um and we also added remote disclosure visits nowadays we're doing so many things remote but this is pretty novel back then the ability to return results over the phone or by video call all right but despite all that enrollment was not a very smooth process we approached a pretty huge number of patients and ended up with quite a low overall percentage of enrollment so in the healthy cohort we approached upwards of 4 000 babies and families only about 10 percent of those agreed to sit down with a genetic counselor and go through the consent session um of those about two-thirds actually ultimately decided to enroll in the study um but still that led to about a six percent uptake rate in the well-baby nursery um and just slightly higher at 10 um in the nicu uh so when we saw these numbers we were we were quite you know perplexed we weren't sure um exactly you know what we could do to change this you know with the irb and with the ethical situation of the study you had to you know talk about all of these risks it was important that the consent session covered everything so it was going to be long we we had chosen to use the the newborn period and there were some barriers that you just couldn't wipe away and so we wanted to really take a close look at why families were actually deciding not to participate in the hopes that that would really educate us on future studies as to why this was something that fewer parents were interested in than we thought i think many people on our study thought we are offering state-of-the-art really exciting sequencing for free to families to learn about these potential health risks that you know maybe could be life-saving for their child you know why wouldn't you want to enroll and what we learned is there's a lot of reasons why parents maybe weren't interested but the first thing to note is that of those 4 000 babies the vast majority i shouldn't say vast majority but 60 were just simply not interested in research they may not have even heard of what our study was it could have simply been a research assistant knocking on the door saying hi i'm here to talk to you about research can i come in and the family's saying no thank you we're not interested in research so that was a quite a large chunk of those families who ultimately didn't want to sit down with a genetic counselor so i think that really doesn't have anything to do with genetics or someone's disinterest in screening it was more about you know this kind of special time period where they were likely overwhelmed or just didn't really want to deal with another person coming into their room but for the 30 of those individuals where we did have a reason um we looked into that further to see exactly why they didn't want to enroll a pretty large chunk a little over 40 percent it was mostly about the study design or logistics they didn't want to commit to coming back or being followed for an extensive period of time they didn't want to do a blood draw or they didn't have time to sit for an hour or so and go through the consent paperwork but then there's also a smattering of other reasons more directly related to the study content itself like concerns with return of results or being uncomfortable with genomic sequencing being uncomfortable with privacy or the potential for discrimination or being overwhelmed and there was a difference here in those who declined the study at first approach versus those who declined to study after sitting down with a genetic counselor and going through things further i don't think i have time today to really dive into those but we do have a publication out that talks about that in much greater detail all right so the results um for this study we found that of the 159 babies in the sequencing arm 11 were found to have a monogenic disease risk so found to have some type of kind of concrete disease risk on their newborn sequencing uh report the 89 who were not found to have an mdr they weren't just blank reports they the vast majority of those and i think upwards of 90 did have um at least a single carrier status variant or perhaps a pharmacogenomic risk um so this 11 was pretty substantial and we now know that it's pretty on par with some of the other uh screening healthy screening sequencing studies that are done like the med seek or real seek projects where you find um you know a decent number of individuals with an unanticipated risk so the i'll go into the details about these results but the majority of these were completely unanticipated so not explaining why a child is sick or in the nicu but talking about a future risk so we found 18 of those cases um and the genes that we reported on are listed here and there's a big range of the types of conditions themselves um from kbg syndrome which is an intellectual disability um and uh congenital malformation syndrome to things like cardiomyopathy familial cancer like the brca or lynch syndromes to g6pd so there was really a great variety in the types of results we were finding which for me as a genetic counselor speaking to these families and returning the results it really made me appreciate all of the time and planning and conversations that went into developing the consent form because these families were prepared for the types of results they were getting back um due to that really in-depth consent process that was at times really tedious but you felt as though they knew what they were signing up for and that's certainly important as you can see with the breakdown of these conditions we had some where once we found the con result itself we were able to go back and actually see that the patient themselves did have some phenotypic evidence whether that was either subclinical or not appreciated previously we found that in four cases in another uh almost nine cases i believe we were able to identify some family history whether that be hearing loss or parents or grandparents with heart conditions that were likely to be cardiomyopathy or a history of cancer within the family and the last kind of group were cases where it was completely unanticipated and there were no there was no family history or no current uh presentation but represented a future risk so we really kind of found conditions um and had cases are all the way across the spectrum right so another really important aspect here is going back to that parental response we said we were going to be reporting on how parents handle this information um and actually giving hard data to those questions about you know can parents handle this information and that theoret theoretical risk that a lot of people talked about when we started this study so this is a bit of a busy slide but what's important to notice here is that across all of these time points baseline post disclosure three month 10 month there was really no significant difference in the different groups we have displayed here we have the control group our sequencing group and then broken out of that sequencing group we have our individuals who had a monogenic disease risk finding so those 18 families and so you know here we have the different cutoffs for things like parental depression or anxiety these are established cut ups where if scores are higher than that there's concern for for clinical anxiety or depression and really we didn't see that in any of our groups and there were no significant differences between the groups or between time points we also looked at things like parental self-blame or the perception of the parent-child relationship so parent bonding vulnerability really any dysfunction in that there's a lot of really excellent work done by our colleagues at baylor college of medicine to both develop these outcome measures and then analyze them as well so there's some exciting uh publications that are out and and that are in preparation um that will go into this in far greater detail but the really the take home messages we were able to execute this study and see how parents responded and we didn't find any significant concerns here in terms of how parents were able to react to and and work with this type of information all right now another important thing to talk about here are the demographics of our enrolled participants so this was as we talked about um a really exciting study but it was a lot that we were presenting to families and our participants tended to be early adopters and those early adopters were the vast majority white non-hispanic and socio-economically and educationally privileged we really did not have a population that was representative of the general population in our area and this represents a major limitation in our study and a major kind of disparity that we have in research particularly genetic research and so we wanted to really be able to tackle that in our in our future directions and try to expand this and make it more generalizable while we got a lot of really important information and we're continuing to to analyze and get important information from this cohort there's a lot that we're missing as well by looking at this very specific demographic cohort of patients so for our future directions and we actually have baby seek two in the works um and it excitingly just received a a fundable score from the nih um and this study is going to specifically look at a much more ethnically racially and socio-economically diverse group of infants we're going to move slightly out of that kind of crazy newborn period and focus more on the one to six month range working with community physicians and community health centers for enrollment sites and we're working not just in boston but also um at the mount sinai in new york city and university of alabama and with the hope of enrolling 500 healthy uh infants for whole genome sequencing this time and similar to baby seek one we're going to be looking at a lot of those same outcome measures we want to evaluate the impact of genomic sequencing on their health care on their behavior and on that the health care economy but we also want to do this in a responsible way with a diverse group of stakeholders and input from parents in the community to really figure out how we can create a recruitment retention enrollment strategy that can help us succeed in a much more uh ethnically and racially and socio-economically diverse group of infants so that was a bit of a whirlwind of all of babyseek all the ethical considerations and where we want to go in the future but it's really just the tip of the iceberg for this study so i'm happy to answer any questions for you i want to give a big kudos to our very large group of babysik team members this is just some of them here who are working with the study as well as all of the different organizations including the broad that we worked with to make this study happen great thank you so much casey for that really thoughtful um presentation of what was such a huge undertaking um if anyone in the audience has any questions please feel free to type them in the q a or raise your hands um but one of the things i was wondering about casey is how you feel about kind of ongoing um review of results um and uh how you will do re-analysis sorry there's a fire engine um how you will do re-analysis as new genomic data come up that's a great question um and it's something we thought a lot about as part of this study and have actually considered seeking additional funding for re-visible reporting and being able to more regularly go back and re-analyze cases at this point in time we aren't regularly going back to all cases and doing a full reanalysis mostly due to funding restrictions but what we do have in place is when any variant that was reported for a child changes in terms of its uh you know whether it moves from a likely pathogenic down to a vus or something like that um the lm is able to alert us and make a new report that we're able to give to our family members and then we also have the op continued option for uh the indication based reports so if any infants who have been enrolled in our study develop some type of symptoms or maybe the ill infants if their symptoms change or a doctor wants another look we're able to go back um in those cases and do a re-analysis that's great thank you i think monica wojcik has a uh a question oh yeah thank you so much casey oh that was a great talk as you were as you were speaking about the psych you know re-contact for parents who flagged high for anxiety i was actually just thinking i was recruiting a family to one of my cities in the nicu the other day and the dad was like so wait a minute if i do this sermon you're not going to have like some psychologist call me if i answer the questions wrong right you know he's like i did a survey for the nicu it wasn't yours i did the service right there in the queue you know i said i was stressed and next thing i know i had the social worker checking in and i felt a little bit trapped and like it just it did seem a little sneaky and i imagine that i think i don't know what study he had enrolled in elsewhere that you know i imagine you with your lengthy consent process and everything you know maybe there's better understanding among the baby seek participants but it definitely gave me pause about you know putting in some of these scales that will formally diagnose anxiety or depression and then have a psychologist reach out and then the families might feel you know potentially a little bit entrapped by that they that they hadn't been wanting to invite you know a psych consult on themselves so just to hear i mean obviously we need to be safe but just to hear your thoughts about how to do that respectfully and honestly yeah absolutely thanks monica that's a great question and it's definitely something that we really harped on in our consent sessions particularly as time went on so it was something that we did have in the consent form that a social worker that could be part of their clinical team or someone who is part of our research team may re reach out to families based on their study responses but i would say in the very beginning of our our study consent conversations it wasn't something that i spent a lot of time talking to parents about but that definitely shifted very early on in the study as we saw how many families were actually crossing that threshold just at their baseline survey so likely having nothing to do with the actual sequencing or study participation but just being it the newborn period and so we made sure to really actually give them the heads up about that in the study consent for that very reason you don't want families thinking that you are kind of going behind their back or talking about them um in a way that they that they you know would be uncomfortable with definitely something to think about for future studies do you think it might be interesting this i don't know if the responses vary at all when you tell it when you try to hammer that point home i think that's the downside is that you want people to answer honestly and not worry that they're gonna say something that will trigger psych involvement but you know it seems like it wasn't as big of a problem for your population no we found and i thought about that too um you know you don't want to you want people to answer those questions as truthfully as possible um and i was actually quite um impressed by how open and honest a lot of people were with their responses um we had a lot of you know people who didn't seem to be holding back in terms of of how they were answering those questions which is great um i don't know if that's something that's that's generalizable and i'm sure it wasn't the case all the way through the whole all of our study participants but there were many people who seemed to be quite honest in their responses you