July 17, 2021 @ 12:00 pm – 1:00 pm EDT

Dr. Thomas Frazier of JCU presents “Improving the assessment of SYNGAP1 and related genetic conditions by creating online measures for parents and patients.”

Parents are encouraged to join to learn about a chance to participate in Dr. Frazier’s study which is partially supported by SRF. To learn about the grant see syngapresearchfund.org/post/srffrazier

See Dr. Fraizer on the Today show talking about Autism.

Here are our introductory comments:

Hello everyone and welcome to today’s session. My name is Jess Duggan I’m a the parent of a little girl with SYNGAP1 and part of the Syngap Research Fund.

We are very excited to continue the SRF Syngap research fund webinar series. The goal of the series is to empower your communications with clinicians as you get more clear knowledge of SYNGAP.

We also want to give a plug for our next presentation “Interpretation of variants in SYNGAP1” which will take place on August 19, 2021 10:00 AM in pacific time with Dr. Eduardo Perez Palma.

Our talk for today is “Improving the assessment of SYNGAP1 and related genetic conditions by creating online measures for parents and patients”

I have the pleasure to introduce today’s speaker, Dr. Thomas Frazier. As a clinical psychologist, Dr. Frazier has focused his career on improving autism identification; developing and studying new treatment approaches; creating and refining measures for tracking autism symptoms and quality of life in individuals and families affected by autism. He was the director of the Cleveland Clinic Center for Autism and the chief science officer at Autism Speaks. Currently he is professor of Psychology at John Carroll University.

Today Dr. Frazier will introduce to us a study trying to develop and validate an online neurobehavioral evaluation tool on SYNGAP and other neurodevelopmental genetic syndromes. This study is in part possible with a grant funded by SRF.

A recorded version of this webinar will be available on the SRF website under Webinars on the Family menu.

By the end of this presentation, you will have the opportunity to get the answer to your questions. We’d love to hear from you – please write your question in the Q&A.

For those of you just joining us, welcome, and again our speaker is Dr. Thomas Frazier and his talk is “Improving the assessment of SYNGAP1 and related genetic conditions by creating online measures for parents and patients ”. It is now my pleasure to turn things over to Dr. Thomas Frazier.

Welcome Dr. Frazier

THIS IS FOR TRANSCRIPT ONLY:

0:05Hello everyone and welcome to today’s webinar my name is Jessica Duggan and I’m the parent

0:11of a little girl with SYNGAP1 disorder. We’re very excited to continue this SynGAP Research

0:18Fund webinar series. The goal of the series is to empower your communications with clinicians,

0:24as you get more clear knowledge of Syngap. We also wanted to give a plug for our next presentation

0:30which is interpretation of variants in SYNGAP1 and that will take place on August 19th at 10

0:37a.m pacific time with Dr Eduardo Perez Palma. Our talk today is improving the assessment of SYNGAP1

0:44and related genetic conditions by creating online measures for parents and patients

0:50and I have the great pleasure today to introduce today’s speaker Dr Thomas Frazier. As a clinical

0:56psychologist Dr Frazier has focused his career on improving autism identification

1:01developing and studying new treatment approaches creating and refining measures for tracking autism symptoms and the quality of life in individuals and families affected by autism.

1:12He was the director of the Cleveland clinic center for autism and the chief science officer at Autism Speaks. Currently he’s a professor of psychology at John Carroll university.

1:23Today Dr Frazier will introduce us to a study which is trying to develop and validate an

1:29online Neurobehavioural Evaluation Tool on SYNGAP1 and other neurodevelopmental genetic syndromes.

1:37This study is in part possible with a grant funded by SRF and I want to remind you a recorded version of this webinar will be available on the SRF website

1:46under webinars. By the end of the presentation you’ll have the opportunity to get answers to your

1:52questions and we’d love to hear from you so please write your questions in the Q&A and for those of

1:57you who are just joining us welcome again and our speaker is Dr Thomas Frazier and his talk is

2:03″Improving the assessment of SYNGAP1 and related genetic conditions by creating online measures for

2:09parents and patients” and it’s now my pleasure to turn things over to Dr Frazier thank you.

2:16Thanks Jessica. I appreciate it. Is it okay if I share my screen now? Yes, yes please.Background

2:25Thank you for that great introduction. I really appreciate it. As Jessica mentioned

2:32over the last really now 12 years, 13 years I’ve been interested in genetic syndromes

2:39associated with neurodevelopmental disorders including autism and ADHD but really more

2:45broadly genetic syndromes that influence neural development and a little bit before the pandemic

2:52I started to study different methods that we could use to improve the assessment of genetic syndromes

2:59and neurodevelopmental disorders and so this project that I’m going to describe to you today is

3:06really about how we can do a better job of making sure that we have the right assessment tools,

3:13that those tools are easier to use for patients and informants and parents and family members

3:19and that ultimately those tools help us to track change in outcomes in patients

3:27so that when we institute any kind of intervention or if we just are following patients over time we

3:33can better understand what’s happening with them and how they’re improving. So this project is What is neural behavior

3:39funded by several different organizations but i just want to call out SRF, SynGAP Research Fund,

3:44for its funding for this project. It’s really fantastic. When i first contacted Mike as he just

3:52really understood what I was trying to accomplish and how it would benefit SYNGAP1 patients and families and so I’m very grateful for this support and I hope you’ll also see that what we’re doing

4:04can be useful for the community. We’re developing something called a Neurobehavioral Evaluation

4:11Tool or a ‘NET’ for short. And obviously a reasonable question to ask me is “What is a NET?”

4:18and you know the first place to start in answering that question is what is neurobehavior?

4:24So neurobehavior really is just a fancy word that is represents all of the different brain processes

4:30and brain functions that help us to thrive in our world and there are many different examples

4:35of these but I’ll just give a few positive and a few negative examples. So positive examples would be like attention. We allocate our attention to things that we want to understand, that we want

4:46to process, that we want to take in, that we want to remember and so attention is really a

4:51very very important cognitive function because it allows us to understand our world. Another example

4:58is executive function. You might have heard of executive functioning or executive functions.

5:03This includes a whole bunch of different cognitive processes but the most common ones are things

5:08like planning, organizing, inhibiting, sequencing, these are all the kinds of things we have to do to

5:15be successful because if we don’t plan things we can’t figure out what we need to do with our day,

5:20we can’t manage our behavior. If we can’t inhibit our impulses we might do something that we regret later that isn’t productive. So these are just some examples of different

5:30aspects of neurobehavior that we’re going to want to measure with our NET. And then dysfunctional

5:35examples or negative examples would be things like anxiety, right? If we aren’t doing a good job of

5:41managing our emotions or regulating our affect we can sometimes experience anxiety or extreme fear.

5:48Another example would be challenging behavior. Challenging behavior is very common in individuals with neurodevelopmental disorders. It can range from things like oppositional behavior

5:58to aggression, self-injury, elopement, property destruction, and certainly not everybody with

6:04neurodevelopmental disorder has challenging behavior but when folks do have challenging behavior it’s really important to measure it and track it because you obviously want to make a

6:14difference there and challenging behavior is the number one reducer of quality of life in families. Why do we need a new tool

6:21So we’re building the evaluation tool to assess these different brain processes and we had a

6:28number of different motivations for this. You know, somebody who’s involved in this field might look at me and say well, Dr Frazier I appreciate your effort here but we have a lot of existing

6:37tools here. Why do we need a new one? Well, first of all the existing tools are not specifically

6:44designed for neurodevelopmental genetic syndromes like SYNGAP1, like PTEN, like ADNP, like some of

6:50the other neurodevelopmental genetic syndromes that we’re studying and so we need to actually

6:56make measures that are more appropriate for these patient populations and to do that we’re including

7:02clinician scientists, experts, caregivers and patients in the development process.

7:10We also know that many of the items on existing tools are kind of irrelevant or maybe not the best way to phrase or frame something

7:20for the cognitively impaired or non-verbal or minimally verbal patients that are often

7:26a part of these communities and so I had a lot of parents that would come up to me for example after

7:31we’d have them fill out these existing tools and would be like “well, I only filled out about half of it” and, you know, when I would talk to them about it I realized well, they filled out half

7:40of it because other half of it wasn’t really relevant to their child or their situation. So we have to be much more careful about that when we develop tools. We need to collect data

7:49repeatedly as well, right? We need to be able to do this in a way that is easy as possible on the patient and the family and so this is even before the pandemic I realized, you know,

7:59we need to do this online and at home as much as possible. So our measures are going to be online

8:04measures that can be collected from home really in the safety and leisure of the home environment.

8:12Make it easier on patients and families. And then we want to have a bunch of different

8:17measurements here, right? So we need to measure all kinds of different aspects of neural behavior

8:22and we need to have those measurements be normed at the same time so that we can get a really accurate profile of the patient’s strengths and weaknesses. We can compare

8:33that profile not only within that patient over time but also to other patients in that community

8:41and if we institute an intervention we of course want to be able to track that over time.

8:47And there are two basic ways we’re thinking about (in terms of our project) to collect neural behavior. The first one is kind of obvious. It’s a survey or set of questionnaire scales, right?

8:59And for this one we’ll be asking a parent or another informant to fill out these surveys

9:04that ask about the child’s strengths and weaknesses, behavior problems daily living skills, etc. And surveys are really important because obviously the informant or the

9:15parent or the other caregiver that fills it out oftentimes has a lot of information about the

9:21patient’s behavior and so we need that sort of really detailed look at the patient’s behavior.

9:28But we also want to collect data directly from the patient and we can do that now using webcams.

9:35Most people, not everybody unfortunately, but most people have a webcam and for this study even if you don’t have a webcam but you have a computer we’ll send you

9:44a webcam. We can also use tablets for this study as well because tablets have a webcam

9:50but webcams allow us to collect data directly from the patient and I’ll show you just now sort of… this is a little bit of a busy slide but I’ll just Webcam measures

9:58sort of walk you through some of the different ways we can collect this kind of data. So webcam

10:04measures allow us to get a video of the patient as they’re watching the screen and from that video

10:10we can do two big things. One is we can track where the patient is looking on the screen

10:15and two is we can track their facial expressions, their reaction, their engagement with the screen.

10:22And so using those measures and changing what we show on the screen

10:27we can collect information about different cognitive and emotional processes.

10:33And we do this primarily by showing static slides or more often we show videos and those videos are

10:42pulling for different kinds of neurobehavioral processes or cognitive processes. So for example

10:49in the top left here you can see we show a slide that has different pictures on it and what we’ll do is when we show those pictures we’ll say “look at the person

10:57kicking” and that’s an example of a slide that’s pulling for receptive vocabulary, receptive

11:04language and by tracking where the person looks after we give the direction then we can see

11:11that we can look at their receptive vocabulary. We also do things like just showing people’s faces and asking people to look at certain faces like “look at the happy face”

11:22and that on the top right here you can see that we track where people look and because of that we can track to see if they’re looking at the happy face. But even then, even if they’re not looking at

11:31the happy face, we can also track whether or not their facial expressions have changed, right. Are they showing a more positive or a more negative facial expression? On the bottom left you can see

11:41we show some stimuli that have like a social half and then a non-social or an abstract half

11:48and on those stimuli we can track social attention because we all have this general preference for looking at social information but that preference differs across people and over time and

11:58we can measure that preference and track it over time. And then lastly, but this isn’t the only…

12:04these aren’t the only stimuli we show but I’m just giving you examples, the last example here is a joke stimulus where a young child is telling a joke, just a funny sort of “dad joke” and we can

12:17again track where they look in their facial expressions to these things. So these are just some examples of different stimuli we can use to better understand cognitive functions using the webcam. Study goals

12:28So in terms of the specific goals of the study: we’re going to use a data collection here from

12:35SYNGAP1 patients as well as other patients and controls and we’re going to use that

12:41data collection to evaluate the ability of our survey measures and our webcam measures

12:48to track changes in behavior and functioning over time. So I’ll describe a little bit more how we’re

12:54going to do that but that’s the main goal of the study and by doing that we’re going to be able to validate these measures for people with SYNGAP1 and other genetic syndromes as well

13:04as people with neurodevelopmental conditions that don’t have an identified genetic syndrome.Study participants

13:11So for this study we’ll be recruiting patients with SYNGAP1, obviously that’s why we’re doing

13:17the webinar. We’ll also recruit patients with PTEN mutations, ADNP mutations, SCN2A, STXBP1,

13:26NFIX or Malan syndrome, and also Autism Spectrum Disorder and we’ll also have healthy controls

13:31including sibling controls which we’re always looking for and unrelated healthy controls as

13:39well. And the controls are just to help us to understand how the measures are functioning in people that don’t have a genetic syndrome or a neurodevelopmental condition.

13:49In terms of eligibility for this study our primary participants the patients will be ages 3 to 45. We Eligibility

13:58unfortunately we can’t go above 45 right now and I know that’s been frustrating for some families, for some patients, but for right now the FDA kind of wants us to keep it to a narrower age range

14:09but but it’s still a pretty broad age range. You have to be diagnosed with a genetic syndrome

14:15and or Autism Spectrum Disorder. They have to have a willing supporting participant like a parent

14:20or another family member or some kind of close informant that knows their behavior and they have to be willing to come to complete or at least attempt to complete

14:32the supporting participant must be an individual who is knowledgeable of the of the primary participants behavior and functioning and they’re going to be the person that completes the survey

14:41measures both participants have to have a reliable internet connection and they have

14:47access to a tablet with a stand or a laptop or a computer like I said we can provide a webcam if

14:53the webcam is broke or not working or just don’t have a webcam but we need to have that computer

14:59so for the survey portion the supporting participants are going to complete a survey Survey

15:05that helps measure behavior and functioning of the primary participant and they’re going to be asked

15:12to complete that survey at three different time points the initial or baseline one month later

15:19and then four months after baseline so three months after the first follow-up but four months after the baseline the survey links will be sent by the research coordinator who happens to be on

15:31this webinar names katie hubba and she’ll send the the links so to by email to make it easy on people

15:38to complete and we estimate that each survey will take about 20 to 30 minutes to complete

15:43and the webcam measures can take anywhere from sort of 15 minutes to 20 minutes to completeWebcam

15:53so for the webcam portion the primary participants are going to be asked to watch several videos

15:58the videos like i showed you earlier are going to measure different cognitive functions or thinking skills like language attention processing speed or the time it takes to complete a task things

16:10like word recognition the videos do not require a verbal or a physical response that’s intended

16:17to make it easier because some patients are not to are non-verbal or minimally verbal or non-speaking

16:23i should say and or may not have the ability to generate a physical response the videos are going

16:30to be approximately 60 seconds long we try to keep the videos pretty short because before each

16:36video we have to calibrate gaze and we don’t want the videos to be too long because we might lose

16:41the person’s gaze and also we you know people lose attention and we wanted to keep these videos short so even young kids or people that have trouble paying attention might be able to do

16:50the videos so again the same three time points are going to be used for the webcam

16:56as for the survey measures and baseline one month follow-up four-month follow-up and

17:02again our research coordinator katie hubba will send the links to the videos by email

17:08and like i said the webcam measures take 15 to 20 minutes to complete you can do the videos

17:15in chunks that’s really important because some people might say hey we can’t you know

17:20my son or daughter are not going to be able to do these videos in 15 minutes you know they’re just

17:25not going to be able to keep their attention well guess what you can do each of the videos in really short chunks so you can do one or two or three minutes and then take a break and come back to it

17:37later and do the next two or three minutes until you’re all the way through the video so we’re trying to make it as easy as possible on folks to do these we will be compensating participants Amazon gift cards

17:48there’s a $30 amazon gift card per survey completed and then there’s a $30 amazon gift card per webcam

17:55measurement completed so across the whole study because we have multiple we have three time points

18:01it’s possible that people will earn a total of $180 dollars in amazon gift cards even though it’s not

18:09a long study we we do know that there’s you know it’s people have to take their time their energy

18:15to do this and the supporting participants are oftentimes going to have to help the primary participant do the webcam measures so we just wanted to make sure we’re appropriately

18:24compensating people for their time you know, if if you feel like this might be a challenge for Research Coordinator

18:31you to participate the research coordinator is available to assist you they can jump on a zoom

18:36or a google hangout and try to help you through a part of the process or give you tips and tricks

18:42for how to make this easier on the primary participant you can always withdraw from the study at any time there is a third opportunity for participation and that’s if siblings would

18:53like to participate i mentioned that we would like healthy control siblings ages 3 to 45

18:59of the primary participant that do not have a genetic syndrome or neurodevelopmental condition

19:05could also participate we just want to make sure you’re aware if they do participate then the supporting participant will have to fill out surveys for them as well

19:13so they’ll be doing two sets of surveys one for the primary participant and one for the siblingWhy does this matter

19:22I did want to sort of end on just you know I went through a lot of the logistics and thanks for bearing with me but why does this really matter for SYNGAP1 or for other genetic syndromes and

19:32you know the the big deal here is is that we have an opportunity to improve clinical

19:38practice and these new NET measures if we develop them and validate them in the way that we hope to

19:43could really improve clinical practice by making it easier on the clinician and the patient and family by having some measurements that are collected ahead of time they can track

19:52function and behavior and the clinician can just use those you don’t have to fill them out in the waiting area you don’t have to fill out a bunch of paper forms which can be quite tedious to fill

20:01out trust me I’ve done it for my son many times so this is a way for us to improve clinical practice

20:08our new measures here the NET could also be used to track progress in future longitudinal studies

20:14and natural history studies we need to learn a lot more about SYGNAP1 in order to be able to come up with the best ways to help patients and so these kinds of longitudinal studies can

20:24be really important and then lastly and probably the thing that’s oftentimes most on people’s minds

20:29is are there going to be future clinical trials and I hope the answer and I’m pretty sure the answer to that is going to be ‘yes’ there are but the NET is a way for us to improve and have

20:39better outcome measures for those clinical trials one of the reasons why some clinical trials in the

20:45past have not been successful we think is because the measures themselves were not appropriately

20:51capturing change and so these new NET measures we think are going to be much more effective

20:57and useful for future clinical trials this is the investigative team obviously myself Investigative team

21:02and Katie who I have introduced we also have Mirko Ulijarevic who is a senior research fellow

21:08at the University of Melbourne he’s a psychiatrist he’s been helping us with developing the measures

21:15and then Antonio Hardan is a child and adolescent psychiatrist at Stanford University and he’s the

21:21director of the division of child adolescent psychiatry there long-standing interest in neurodevelopmental disorders and he is also closely involved in helping us with the project

21:30and then we have several teams of experts that are also engaged with us on developing the measures so Questions

21:39I’ll end here and just I’d love to take any questions that people have or any

21:46issues comments concerns people have we’re really hopeful that the project is going to make a

21:52difference and you know but we need your support we need your help we need you to participate

21:58we think it’s we’re trying to make the participation as easy as possible on you but we do know that it does require time and effort so thank you for considering this thank you for

22:08watching our talk and it’s usually more fun to do questions if people have them

22:13anyway so I’d love to stop here if that’s okay.Age limit

22:22Thank you so much Dr Frazier that’s amazing. So I’m looking in the Q&A and in the chat and I’m

22:29not not seeing anything yet so I’ll just start off hopefully people will write in some things

22:35well actually yeah already there is some so Genoveva writes Dr Frazier thank you for the

22:42interesting talk for the survey because it’s filled out by the primary participant is their

22:48age limit so I think that might be a certain age limit sorry I understand the primary participant

22:56is the patient with neurodevelopmental disorder genetic syndrome so the SYNGAP1 patient in this case is the primary participant and there is an age limit on that that’s three to forty five

23:05but for the supporting participant the person who would actually fill out the survey there is no age limit for that person so as long as they have a really good understanding

23:15of the primary behavior as wrong as long as they really understand that person that

23:20that person with SYNGAP1 then there is no age limit for them obviously most of these folks

23:26are going to be parents oftentimes moms who fill out the surveys but we don’t have an age limitTablet or webcam

23:34that’s great thank you so I had a couple questions as you were going through one is

23:42they’re pretty you know specific to the setup so with the tablet or computer with the webcam

23:50need to be on a stand you know like I know my son sits on his bed and watches his iPad

23:58looking kind of down on it sitting on the bed so I’m kind of wondering if what the physics of

24:06everything is for this good question yeah the webcam has to be stable so we can’t have the

24:11child holding the tablet because obviously that’ll move a lot so we need to have the tablet like on a stand or sitting up in a stable position and then the calibration process allows

24:23the supporting participant and the primary product to sort of see where their head needs to be

24:30luckily there’s some wiggle room there like they don’t have to stay perfectly stay straight

24:35the whole time they can move around they can they can their eyes can even go off screen for

24:40a little bit and we can usually recapture them back but the tablet itself needs to stay stable

24:49we usually if you have an option between a tablet and a webcam we usually prefer the webcam in

24:55general I’ll say in general because generally speaking those are going to stay more stable

25:01regardless of the situation and oftentimes the screens are a little larger because the larger

25:07the screen the more accurate the gaze capture is but katie can tell you we recently had a patient

25:13we’ve been doing a lot of initial testing on this and we recently had a patient completed on a

25:2010 inch or maybe a slightly smaller than 10 inch tablet and it worked so we recommend tablets that are larger in size than that but but we were pretty

25:33impressed that we actually got pretty good data from a smaller tablet we we don’t want people to use smaller tablets unless they absolutely have to but but we recommend a larger tablet auditory commands

25:43okay that’s great it sounds like maybe at least the setup I’m thinking of might be a a laptop

25:49might be best as it has its own kind of sort of a stiff a stiff laptop would be great okay

25:58so I have two more questions is so you were saying that you can have you can ask the

26:09to look at various things are these auditory commands embedded in the video I know like

26:17for my child he he doesn’t get auditory commands that well but he does paired with pictures so I’m

26:25wondering if there’s if if I’m just wondering what the commands are to look and what if you’ve kind

26:31of thought about that kind of approach totally yeah you know we know that a fair number of the

26:36patients that we’re trying to evaluate are going to have some receptive language challenges or some

26:42difficulties with following particular directives so we have four basic paradigms and I’ll just sort

26:49of walk you through them since you asked one is a social attention paradigm that does not have

26:56many it has a few but not many specific directives in it okay the only specific directives in that

27:03paradigm are look at the happy face look at the sad face look at the mad face otherwise

27:09that paradigm we we don’t really have directives there the second paradigm is a receptive language

27:15paradigm for that we do have auditory directives look at the person kicking look at the ball look

27:22at the person drinking etc etc we know that there are some individuals that will have will struggle

27:28with that in our experience so we we actually already have a published study on that paradigm

27:36and that paradigm we were able to get about 90 to 95 of individuals including some

27:44very significantly impaired individuals who are two and three years old to complete the paradigm

27:56but that doesn’t mean everybody can complete it and there are certainly some kids that just can’t find the directives the good news here is is the we ask you to try the first one minute video

28:08and if it really looks like to you that that the child or or whoever is trying attempting to do the

28:15the task if that person is not able to do the task you do not have to persist through the remaining

28:21videos so for example if it’s obvious to you that this is just not a paradigm that works

28:27for your child then it’s perfectly fine to actually skip those remaining videos for that

28:32paradigm and go on to the next because we don’t want to torture people like we want to make it

28:38you know, really difficult for people so the third paradigm we have is a single word reading paradigm

28:44the Simon’s foundation asked us to add that paradigm so we’re going to put that one last because we know that there’s a fair number of individuals that don’t read

28:53and so we understand that we get it it was a request from a funder we’re going to put that

28:58at the end people don’t want to even try that that’s okay by us it’s fine and then the third

29:04paradigm I think almost everyone can the fourth paradigm which we’re gonna put third in order

29:11is I think almost everyone can do it it’s a it’s it’s meant to just be a way to track

29:17the person’s gaze on the screen there is a directive but the directive is not too bad

29:23which is sort of just look at a particular object so like look at this object and even

29:30if the child doesn’t do well with auditory the supporting participant can point at the object

29:36on the initial screen and say look at that object right and so there’s a practice slide ahead of

29:42time and and we’re sort of orienting the person to look at this particular thing so let’s say it’s a

29:48red balloon they will look at the screen and we’ll show them this is a red balloon look at all the

29:54red balloons and then on the next screen they’ll be red balloons mixed with other things and we just want the person to look at the red balloons so we think on those paradigms we can get a pretty

30:04good maybe not a hundred percent but close to 100 percent of people will be able to do those tasks Auditory vs visual instruction

30:12does that answer your question or yeah it mostly does I’m gonna just dive just a tiny bit deeper

30:17because i think there’s one nuance that i didn’t get across in my question which is

30:23it’s about a difference between taking in directions auditorily versus visually

30:28so if you wanted someone to look at someone kicking a ball you could do like a quick

30:34video of a ball being kicked and then go to a still of two things and one was a foot about to

30:40kick a ball and one was like a swimmer right and then they might be able to like look at

30:46the foot about to kick the ball sort of showing that they understood that was what it was

30:51it’s that kind of thing just sort of visual versus auditory instruction without reading you know

30:57although i i will say that i think for Syngap i think kids have a very good visual memory and i

31:04think sight words are very common for some guy kids that’s something we’ll definitely consider

31:10i think one of the trade-offs we’re trying to deal with in this paradigm is we only have 60 seconds

31:16to capture gays before we have to go on and we need a certain number of items in order to make

31:22useful tasks so we have to be very careful about how much practice we can do ahead of time but

31:27that’s definitely a cool idea and i think maybe we could even start katie and i can start thinking

31:33about how we can make versions of that to help certain participants be able to understand those

31:39skills I think that’s a cool idea so definitely katie i know katie’s taking notes so

31:46let’s get back together on that and see if there’s a way for us to implement something like that

31:52yeah okay cool so there’s another there’s a there are a few more questions here in the Q&A same

32:01person before Dr Frazier do you take into account any various treatments for the genetic syndrome

32:06or neurodevelopmental disorder the participants may have and how they will influence the results

32:11from the survey and webcam yes before each survey we asked the supporting participant to complete a

32:18questionnaire that asks about treatments and any other environmental changes that the patient is

32:25experiencing we asked for a little bit of detail around that so yes in our analyses we’ll be able

32:30to look at whether or not and the treatments are impacting the measurements that we’re taking Followup

32:37so yeah and i guess the follow-up of this is i i think that what you said at the outset is this initial study is to look at these measures like the study is to look at the

32:49measures not to look at the participants really in in some sense yes yeah we want

32:55to understand what the participants look like on the measures but but you’re right the main

33:00thrust of the study is really to develop measures that are useful for the SYNGAP1 patient population

33:07and other neurodevelopmental neurogenetic conditions so we’re not so much focused on

33:12saying hey does this treatment work we won’t be able to answer those kinds of questions what we will be able to say at the end of this hopefully is these measures look appropriate and

33:22useful for the vast majority of the SYNGAP1 population that’s what we’re hoping for Video content

33:30yeah that is that’ll be such a great day okay so in the chat from jess a few questions here so

33:42is the video content varied or the same over the evaluation sessions

33:48yeah so the the video content for the webcam will be the same across the evaluation sessions

33:54and the reason for that is there’s some technical reasons for that but

33:59we do know that people might get annoyed or bored with it but remember we’re putting one month and then three months in between administrations and so in general when we’ve done this in the past

34:12we don’t see major differences as a result of repeating the information and we have ways of

34:18adjusting for that when we do see them so we are going to show the same content over time

34:24the other nice thing about not varying the content or the paradigms too much is that

34:30we do want to see how much people might improve just due to practice effects because that’ll give

34:36us a sense in the future of whether or not it’s useful to actually do sort of an initial practice

34:43before let’s say we were to implement these measures in a clinical trial then if we learned that practice really mattered then we’d actually want to administer the measures

34:53a couple of times before the treatment started in order to make sure that we were measuring

34:58change and not just practice on the measures so we’re gonna use the same kinds of video content

35:04over time some people have told us after the third or fourth time they see it like yeah i was ready for the you know whatever that particular stimulus was i was ready for that

35:16but it turns out that it doesn’t change their days a whole lot and it doesn’t

35:21really change their responses overall a whole lot so far anyway thank you and i’ve been a a poor Improvements over time

35:31host to not ask you to stop sharing your screen so we can all see each other oh yeah sorry okay

35:41and then Jess also asked can you speak about how you would expect improvements to look over time

35:51yeah so we’re measuring different processes here different thinking skills

36:00and other kinds of problems that people might experience and so if we have a good measurement

36:06at time one and we repeat that measurement say a month later or three months later then what we

36:12can do is we can sort of see how much the score on each of these measures changed and if the measures

36:19are reliable and that’s our goal is to develop really reliable useful measures if the measures are reliable then hopefully even small changes in the patient will show up on the measures whether

36:31they’re the survey measures or the webcam measures they’ll show up and what i mean by that is the

36:36score will change over time and that score will show us what improvements people are experiencing

36:42so for example in general people with any kind of neurological condition

36:50if they improve with a treatment one of the first things that improves is their attention

36:56so this is true in many many different neurologic problems neurogenetic conditions etc

37:03and so by measuring attention and by the way we’re measuring attention in two different

37:08ways we’re gonna ask the parent and we’re gonna measure attention through the webcam by measuring attention we should be able to see if there’s any improvement from time

37:17one to time two to time three does that address the question or am i missing it

37:25yeah that does thank youVariation

37:31i guess a follow-up to that question will be how about kind of variation you know how how do you

37:41think this will i guess within each trial if you have 15 to 20 minutes you’ll see some variation in

37:49that in that time is that is that the main way you’re going to look at variation or oh you’re

37:54saying variation within the short time period that we collect the measures yeah well like i let’s see

38:02i guess I’m just trying to imagine what the data looks like I’m imagining graphs and standard deviations and points and three values and yeah i just i don’t quite understand

38:13yeah so for each measurement let’s just take one one of the measures we’ll collect from the webcam is a measure of sustained attention how long can the person keep

38:22their attention to the screen it’s a very basic measure right very simple measure

38:28and it really is just going to have to do with how long was their gaze detected on the screen

38:33okay across all of the different things that they tried to look at and it comes as a proportion it

38:38turns out it’s from zero to a hundred a hundred means you looked all the time and zero means you didn’t look at all right and so we’ll use that measure to compare that individual over time

38:52and also across patients right so different SYNGAP1 patient so we can understand things like

38:57if you’re a SYNGAP1 patient that has a particular other problem do we see that also manifest in

39:05sustained attention or not right and so we’ll be able to look at those measures each individual

39:12measure and sort of compare that them within each patient and across patients and then of course

39:18if we implement these in clinical trials then we’ll be able to see is the clin is the treatment really improving this person’s sustained attention and we’re going to collect

39:29you know the webcam itself will probably allow us to collect at least 15 to 20 of these types

39:35of measures and then the survey measures will also collect roughly 10 to 15 different scores

39:47okay that’s great get complicated as you get into all of it but yeah yeah of course well i’m also thinking you know sir you’re talking about certain 100 and i’m assuming that

39:56typical cognition would not be a hundred no no typically yeah

40:05yeah so there’s going to be some kind of you know there could be staring that isn’t engagement or Q A

40:11you know anyway it’s it’s a it’s a very interesting interesting topic you have

40:16here okay we have a question in the Q&A from Nancy hi thank you so much for developing these

40:22measures question my question is is about assessor directions and prompts how will this influence

40:30these results will the family members receive directions and or practice prior to administering

40:37yes absolutely Nancy great question thank you i couldn’t I didn’t pay you to ask the question but

40:45the this is a really great question because the answer to all of these is is is yes we will

40:52be giving you directions we will be showing you we have both videos and katie can actually jump

41:01on a call with you to walk you through how to do this the assessor directions and prompts could

41:07influence the results but what we’re trying to do is we’re trying to get the best performance here right we don’t want to hamstring the person with SYGNAP1 by saying hey you figure it

41:18out we actually want to get that person to the optimal performance possible for them

41:24and so we want the supporting participant to help them as much as possible without

41:31giving away answers or telling them where to look right so we’re going to actually katie

41:37like i said we have some video methods and we also have a lot of instructions for you

41:43we’re going to be trying to train you up on the best way to get the best performance possible

41:48from the person that we’re administering the task to without cheating right without without actually

41:55doing it for them and so there’s all kinds of different ways we can do that including practice

42:00administrations including having katie give you tips and techniques and walk you through it and we

42:06have a lot of different ways to help you with that so as long as you’re willing to work with us on it

42:11we’re totally up for working with you on it and in fact we expect that probably somewhere around 20

42:18of individuals will not be able to validly complete some of the videos the first time through

42:26and that’s okay because we’re willing to work with you to actually try it again if you’re willing to

42:32work with us we’ll try it again and in fact in our pilot testing what we’ve seen is for some

42:37individuals they’ll do it the first time and it’s sort of borderline maybe it’s not really valid and

42:45then we go back and we try it again and it looks great and we want that optimal performance we’re

42:51not trying to hamstring you know people here we want we want them to do the best they possibly can

43:03great thank you well i don’t see any more questions right now in the chat or the q a

43:10but i have kind of a you know a question it’s not really fair to you but i was wondering about even

43:19sort of broader measures when i first was thinking webcam i was thinking you know

43:26you know you could have something overnight and sort of show nighttime behaviors or you know you

43:32could you could have like much more constant you know something more like a wearable where

43:38you’re really constantly collecting data so it surprised me i didn’t i didn’t i’m excited

43:43to hear what you’re doing and this sounds amazing so i don’t want to detract anything from it but i but something that was a little bit surprising to me was that these are three

43:52fairly short moments of time over a few months and i think you’re gonna get

43:58great data from it but i i’m always wondering how can we how can we tell what’s happening

44:04with our kids especially when they can be so angelic and then they can be so so unhappy

44:11well i have a good friend named matt goodwin who’s working a lot on wearables for kids with neurodevelopmental syndromes and i think wearables are a fantastic other way that we can do a lot of

44:22this stuff and even like webcam behavioral observation stuff is really cool as well

44:29there are some tricks right now there’s a lot of work that needs to be done in ai and machine learning to sort of make sure we can extract that data efficiently but matt goodwin’s doing

44:39really great stuff with wearables like watches that you can wear on the wrist or even the ankle and you can get really good autonomic data we were more going for cognitive data like

44:49thinking processes but autonomic data you can get from the wearables and actually

44:54i’m working with the company to try to get them to collect some data on the pupil as well

45:01we’re not going to be doing this the first time through but for those of you that aren’t aware like the pupil is a really interesting window into our autonomic nervous system and you can

45:11learn a lot about sympathetic activation and also sort of parasympathetic calming of of the of our

45:20of our autonomic nervous system through the pupil and so we would ultimately also like to

45:28collect pupil data we’re not going to have that the first time because there’s a lot of tricks in how to do that but that’s another way we can gather information but i totally agree there’s

45:38all kinds of these different opportunities out there right now we’re only taking advantage of one small corner of this space but we would love to include other stuff in the future

45:51that’s really great just i just want to ask do any of the other panelists have questions or does katie have anything she wants to add because i’d love to hear from katie if she had something all

46:01right looks like kansas is on meeting let’s hear hans yeah thank you catherine thanks everybody

46:06and dr frazier for the webinar in the past when i’ve done surveys with my son i’ve developed a

46:12degree of frustration because he’s non-verbal and a lot of times the question and answer components

46:19of the survey is is frustrating to try to you know find the right answer and and there

46:25is some significant heterogeneity to this to the subjects you’re looking at between PTEN and ADNP

46:31and Syngap STX and so forth can you expand on that please and do you stratify your analysis based

46:38on verbal or non-verbal is it an adaptive survey yeah so we aren’t able to start with an adaptive

46:46survey but you’ve anticipated we do want to move to adaptive surveys in the future so with a more

46:53traditional looking survey but as we gather more and more data we think it can become more adaptive

47:01to your verbal non-verbal point my son is also non-verbal and i’m very sensitive to this issue

47:08because i’ve had the exact same experience that you just described and I can’t say that every item

47:14we’ve developed is going to make you excited about the survey but i can tell you that through my own

47:20experience and through a lot of our experts we are eliminating many many many of the traditional

47:25verbal items that you would see on these measures and so what we’re doing is we’re focusing on other

47:31ways to get at the same constructs without asking verbal questions questions that involve a verbal

47:38component to it we’re also going to be offering people the ability to choose a response so we want

47:46people to sort of take a guess but then we’re also going to be offering people for each item the option to say you know i wasn’t sure i didn’t think this item was super applicable to my child

47:58and so hopefully that gets rid of some of the frustration that people experience

48:03like i said i don’t think we’re gonna solve that problem entirely but i am very sensitive to it so

48:09i’m and we by the way we will collect whether or not people are verbal or non-verbal and we will also collect some other clinical information that will help us to stratify the analysis yes

48:21and then i was going to ask in terms of you know it’s great to hear about gaze tracking and

48:28attention you know if if there’s a tennis racket on the screen you’re unlikely to get attention

48:34from my little boy if there’s a garbage truck he’s going to lock eyes with that garbage truck and and

48:39not blink so is there a is there an ability to personalize what will provoke attention in the

48:47subject we don’t have the ability to personalize the provoking of attention but we we do have on

48:55the background on the analytic side we have the ability to look and see okay if we presented

49:01something that the person was really engaged with maybe it’s just by happenstance we presented it

49:08then and for that stimuli what does their cognitive processing look like there versus one

49:16where they were not as interested not as engaged so we do have the ability on the back end to look

49:22at that and that is something i’m also pretty sensitive to because my son has a similar it’s not garbage trucks for him but it’s he has similar things that interest him visually

49:30unfortunately on the front end we have to be more standardized with the presentation and so

49:36we can’t like assess what’s interesting to them and then put those into the

49:42into the task we we thought about that initially but it became too challenging it becomes too

49:48challenging to make sure that the difficulty is relatively matched if that makes sense

49:55and then one last question has has the fda shared any insight into their thinking in terms of

50:02maybe the angelman’s aso pre-ind meeting or any guidance documentation that’s come out

50:09the fda as i’m sure you probably know has their patient-focused drug development process processes that they’ve been put in place and through the p10 research

50:19foundation we are engaging the fda on these measures and so we’ve already had one preliminary

50:26meeting as we’re developing the measures and the fda gave us input in that meeting including

50:31adding some additional steps for us to go through in the measure development process once we’re done

50:37with that initial measure development process the FDA has asked us to come back and have another meeting and so we’ll have another meeting probably somewhere in the september october time frame

50:48at which point we’ll be asking for their blessing on moving forward with the what we’re calling

50:54phase two but for for this group is really the the major data collection we’ll be moving forward

51:00as soon as the fda gives us their blessing on the measure development process and then

51:06of course after we’ve collected the major set of data we’ll be bringing it back to the FDA

51:12again for their review of the data what things look like in terms of reliability validity

51:18and we’ll be asking for their blessing then for the measures for future work

51:28that’s great thanks so much I did miss one question from jess how are you recruiting for this study for people with asd

51:38we have some local clinics and then i obviously have a connection to autism speaks we’re probably going to do some national recruitment through them but we’re always open for referrals right

51:49so if there’s just a family that participates that is associated with singap1 and they know

51:54a family that has idiopathic asd we’d be happy to have them refer to the study as well so meet

52:00inclusion exclusion criteria great great thank you and katie did you want to say anything

52:12hi everyone yeah i just wanted to say hello and as dr fraser mentioned i will be here

52:18to help you and assist you in any way possible to make this as easy as possible for you guys

52:24during the surveys and the performance measures and how we can work together over zoom or google meets to you know make it as easy as possible to to get as best data as we

52:34can so and just from some things that we’ve seen so far we’ve been able to get some really great

52:45with you know just results even with some patients who parents thought you know it wasn’t

52:52gonna be a possibility to to gather that we’ve been able to do that and that’s just with a small pool that we’ve been working with so far so i’m really

52:59hopeful and excited to work with you guys during this project so i look forward to it

53:07thank you and then before i end i just want to say thank you so much

53:12Dr Frazier and Katie and your whole team this is such an essential crucial

53:19point that we need measures good measures and i i’ve clearly been thinking very deeply about this

53:27and we just you know couldn’t couldn’t ask for anything more so that’s it for me and i

53:33don’t know if marta or jaisal i just want to give you thank you and i mean i this work is just can

53:40change life for our kids in the schools in in you know i still remember when my daughter when she

53:47was little getting evaluated in the school and she couldn’t do anything and then there was no measure

53:53possible because she was not verbal and and we know a lot of these kids the expressive

53:59understanding is zero but they they i mean they cannot express but they understand a lot then

54:06this is this is great for the future of all these kids with these disabilities of being unable to

54:13express themselves thank you so much thank you for having me and i just do want to put in a plug that

54:20we do expect to start recruitment in a month or so but we’ll obviously work through the foundation

54:25at that point and let folks know when we’re ready but just thanks for everybody who watched this and

54:30appreciate all your time and and appreciate the the foundation’s desire to do this with us and

54:36just thanks so much oh dr fresher you can mention the international recruitment we were talking

54:43informally initially but i think that’s very important for yeah yeah we’re also able to take so

54:50one of our inclusion criteria is just that people have to be fluent english speakers that is a

54:55unfortunately that is a limitation but as long as they’re fluent in english speakers we can

55:01include people internationally we’ve already had interest from folks in Australia, Canada the UK

55:07we’ve had folks across other parts of Europe that are fluent english speakers that have also

55:13you know wanted to participate so we we definitely encourage international participation

55:18we’re working with several people in Europe and Australia i have connections in Canada as well so you know definitely we’re open we’re excited we we want people that are excited about

55:29participating we need that kind of energy because you know anytime you participate in research it’s

55:36you know it’s it takes time and effort so please do consider it thank you so much

55:45thank you okay bye