Challenges in designing an FDA approved video game for therapeutic purposes

Episode summary:

We discuss the early challenges in designing a video game for therapeutic purposes. The designers found that having scientific constraints actually helped unleash their creativity and forced them to create new game mechanics. They also had to build a diverse team from different industries and teach each other about design. To ensure alignment with FDA approval, they defined different buckets within the game and tested changes in those areas separately. They are also working towards using machine learning and AI to test new features more quickly. The game is currently indicated for pediatric ADHD, but they have plans to expand it to adolescents and adults with ADHD, as well as explore other disease populations such as depression, MS, traumatic brain injury, and Alzheimer's.

Pfizer approached the company to see if their technology could detect the difference between individuals likely to develop Alzheimer's and those who were not, even when both groups performed equally on cognitive tests. The game was able to distinguish between the two groups in just seven minutes of gameplay. The data collected by the company is used solely for improving the medicine and making it better for everyone. The accelerometer data gathered during gameplay provides insights into engagement levels and how someone is performing in the game. The goal is to integrate assessments and diagnostics seamlessly into people's daily lives through gaming, allowing for early detection of potential issues. This approach could lead to earlier check-ups and interventions, potentially preventing more serious diseases later on.

Matt discusses the future of digital therapeutics and the importance of cognition in improving overall health. He believes that cognitive health should be given as much attention as physical health, and that collecting data on biometric sensors will help create a common platform for measuring and improving cognitive health. Matt also talks about how doctors are becoming more receptive to prescribing digital products, such as gamified therapies, especially when there is solid data and a good safety profile. He envisions a future where these therapies are accessible to all levels of society.

Outline:

• Chapter 1: Introduction to Health Points
  • 00:06 - Ben and Pete welcome listeners to another episode of Health Points
• Chapter 2: Introduction of Guest - Matt
  • 00:17 - Matt is introduced as the guest for the episode
  • 01:25 - Ben compliments Matt's background and expertise
  • 01:37 - Matt expresses his passion for finding people who use games to promote health and well-being
• Chapter 3: Matt's Journey into Games
  • 02:22 - Ben asks Matt about how he got into games
  • 03:46 - Matt acknowledges the question but does not provide an answer
• Chapter 4: The Beginnings of Endeavorx
  • 05:35 - Pete asks about the beginnings of Endeavorx
  • 05:49 - Matt starts explaining the partnership with Dr. Ghazali's lab at UCSF and the creation of neuroracer
• Chapter 5: Neuroracer and Cognitive Decline
  • 07:36 - Matt describes the creation of neuroracer and its potential to measure cognitive decline
  • 09:47 - Matt emphasizes the importance of neuroracer's ability to assess cognitive decline
• Chapter 6: Transferable Benefits of Games
  • 14:23 - Pete mentions the transferable benefits of games into real-world actions and behaviors
  • 15:39 - Matt agrees and highlights the ecological validity of games as interventions
• Chapter 7: Games as Measurement Instruments
  • 18:38 - Pete asks about the role of games as measurement instruments for clinical assessments
  • 19:17 - Matt believes measurements and assessments are a significant part of the future of the industry
• Chapter 8: Data Collection in Endeavorx
  • 21:36 - Matt discusses the extensive data collection in Endeavorx, including accelerometer data and other metrics
  • 23:50 - Pete asks about how engagement is measured in the game
• Chapter 9: Design Process in Endeavorx
  • 23:52 - Pete inquires about the design process in Endeavorx
  • 24:10 - Matt explains the challenges faced during the design process and the importance of collaboration and testing
• Chapter 10: Aligning Research and FDA Approval
  • 29:56 - Pete asks how Endeavorx stays aligned with research and FDA approval while adapting to different populations
  • 30:38 - Matt explains the need to define different areas within the game and conduct virtual patient trials
• Chapter 11: Results and Future Goals
  • 34:22 - Matt discusses the positive results of Endeavorx in adults with ADHD
  • 35:02 - Matt expresses the plan to expand availability beyond the US and reach everyone in the ADHD realm
• Chapter 12: The Future of Gamified Digital Therapeutics
  • 36:35 - Ben and Matt discuss the potential of gamified digital therapeutics and the convergence of different areas within the field
  • 37:46 - Matt emphasizes the importance of focusing on cognition and fast-forwarding progress
• Chapter 13: Accessible and Safe Games for All
  • 43:33 - Matt envisions a future where gamified digital therapeutics are accessible and available at different levels
  • 43:45 - Ben concludes the show, expressing gratitude to Matt for his insights and contributions

Episode Transcript:

Ben
Hey everyone, and welcome to another episode of Health Points where we talk about anything and everything. Gamification, health. I'm Ben and here with me is my co host Pete.

Pete
Good to be with you again.

Ben
And joining us today we have Matt. We with over 20 years experience in the game industry, Matty's cofounder and chief creative officer at Akili Interactive, the creators of the world's first and only FDA approved doctor prescribed video game in history, EndeavorRX. Working with leading cognitive neuroscientists, they are developing the world's first truly therapeutic mobile games to treat cognitive illnesses such as adhd, depression, autism, Alzheimer's, MS, as well as a range of additional patient populations. He has a background as executive art director and creative director at studios including DreamWorks Electronic Arts, Lucas Arts and Microsoft. He has worked on over 20 games, including multiple Star wars and Medal of Honor titles. He has also taught computer graphics at the Academy of Art University and Art Institute of San Francisco, and authored the book creating the Art of the Game.

Ben
Matt has recently begun consulting and advising for the digital health industry more widely and is passionate on games for good. Matt, that is quite the bio. Thank you very much for coming to the show.

Matt
Thank you both for having me. I'm extremely grateful for the collection that you have been bringing together. I've listened to every episode at this point and not only the guests, the content, the focus, everything that I'm learning in the results of you guys pulling everyone together. So I'm super grateful and love what you're doing. So extremely happy to be here.

Pete
Thanks for that.

Ben
Yeah, huge thanks for that. It's been a passion project of mine and Pete's to go out and find all the people on the planet who are using games or game mechanics or the principles of behavior change in games to create health and well being. So no, glad that it's getting out there and people are seeing it. More importantly, looking at the titles you've worked on, Star wars and medal of honors, I know I've played quite a few of the games you've worked on, which is amazingly exciting for me too. So let's jump into it. Can you tell us, I mean, the bio I just read out says a lot about your background, but kind of how did you start to even to get into games? How did you start to get into DreamWorks and Lucas art? What was your journey to get there?

Ben
Or what was the things you experienced in your adolescent childhood, adulthood that made you realize this was the industry for you?

Matt
Absolutely a circuitous route for sure. As I'm getting to know myself over the years, I'm seeing one very distinct pattern, which is I tend to chase down unknown, unsolved, problem type things. I tend to run towards them instead of away from them for some reason, for better or for worse. So as I look back at kind of your question, that's one thing that I'm starting to see emerge about myself. And I think it started. I've always grew up as an artist, absolutely. Since I was very young and became very quickly obsessed with computers and games. As soon as those became part of my ecosystem, and had always had this kind of like sub hobby about the brain, too. And I think just because it was such an unknown, it was like Sci-Fi to me in the same way.

Matt
And so I kind of grew up with that bundle, that package. And there was a tipping point, I think, for me. I saw the music video by dire straits, money for nothing. If anybody remembers that, it was 1984 or five, and I'm like, what is that, this computer graphics concept? I need to do that. I need to find out what that's all about. And so over the years, I chased that down. And so I ended up going to university at a school that was at the time, the only one that I could find that had a degree in computer animation. And so that's what I kind of targeted and went after heavily because it combined a lot of things I was interested in. Yet it was a very new industry at the time.

Matt
So after graduating, I went, like many of my fellow students, went into film and games, which is great, and started working in that area, even did some medical animations on the side, which was kind of cool and kind of a little bit foreshadowing down the road, and I love doing that. But I was young in my career, and I started knocking on the door of a game studio in Chicago at the time. And I was really intrigued by making games and by the idea of them. And so I kept knocking on their door and I'm like, can I just work for you part time, nights and weekends? And they eventually let me and they eventually caved.

Matt
And the moment I started to look under the hood at games and what it takes to make them, how hard they are to make, especially 3d games, were just coming into play at this point in time. And it was one thing to work on tv and film, which I love, but that's passive entertainment. You can do anything you want one frame, but when you have to make something look good and be lit and beautiful and feel right from 360 degrees, and it has to be fun. And it has to run on the process. Like all these complications of making games came together and I was like, oh dear, I think this is for me even more so. And so at that point, I really moved into making games full time as my career.

Matt
And so I'll pause there, but I think that's a good kind of the short story. Believe it or not, that kind of led me to that point.

Ben
It's amazing what happens when you tap on doors. Sometimes they say, I really want to spend more time. I'm really curious and passionate. Sometimes that's the way to get through and break through. Amazing. So endeavorx, what was the beginnings was there moment, this light bulb to go? I believe that games can change people's health and well being. Where did Endeavor Rx start?

Matt
Sure. So I mentioned earlier my kind of sub hobby and interest in the brain socially. I met, and this was probably 1617 years ago, I think I met Dr. Adam Gozali, who's one of our co founders. He's our co founding neuroscientist. And I met him socially initially and we started to just kind of chat. And it's like, wait, you work at UCSF and you're a neuroscientist and he's like, wait, you make video games? He's always a gamer growing up. And we immediately started to pick each other's brains and very quickly started to feel that there was something there. There was some kind of collaboration that was going to happen. And at the same time, there were actually some other neuroscientists were starting to look at off the shelf video games.

Matt
This was during the time when there was a lot of press about how evil games are. And I think Noah talked about this a bit, but there were some neuroscientists that said, wait, there might be something else going on here. And they started to look at different games to see if there were some positive benefits. And surprise, there were. Specifically, I think, of Dr. Daphne Bavalier, who's just absolutely amazing. And she happened to be looking at Medal of Honor at the time, which I had long since worked on. But she has an amazing TED talk if anyone wants to track her down. She's incredible.

Matt
So even with Medal of Honor first person shooters, they were finding not just increases in reaction time and peripheral vision, but they were starting to show that maybe these things aren't all evil, maybe they're not the devil's instrument, because I heard a doctor call them once in the early days of Achilles that these could actually beneficial. And I'd always had a strong reaction to the stigma of video games, even growing up, and always suspected them to be something greater. And I always thought of them actually more as interactive experiences. And so seeing this kind of glimmer that, okay, there is a future where these things aren't going to be painted as just evil, and they could be really beneficial. I partnered with Dr. Ghazali while still working at Lucas Arts at the time. I brought over Eric Johnston, who's a brilliant engineer.

Matt
That's when we brought in Noah Falstein as well. And we started to work nights and weekends at Dr. Ghazali's lab at UCSF to create the very first, I guess, the initiating technology that led to Achilles called neuroracer. And so that partnership and that concept is where it really began for me. So my obsession with the brain was able to kind of come full circle and was able to know, take me to UCSF, scan my brain. And Adam wanted to come to LucasArts and see how games were made. And so, really, that spark is a lot what led me down this path.

Ben
Finding people with diverse skills, diverse specialisms and expertise, but shared, that's where. That's where the magic can happen, that's where the spark can come from. In that case, talk through to the listeners. What does it feel like as a player in Endeavor RX? For anyone taking it personally for the first time?

Matt
Yeah. So Endeavorrx looks and feels and behaves like a high quality consumer mobile game. And I could talk more about the decisions there and the design process, of course. But one thing to note is that even though it looks and feels familiar, if I were to compare it to anything in its kind of style, it's got a little bit of a Nintendo esque approachability to it, and that's very much by design. I've always admired Nintendo's ability to be probably the most universally appealing game company. Right? They're able to just cross age gaps and culture gaps and just bring together this sense of joy and sense of wonder that almost everyone on earth can tap into. And that's not easily done. That just doesn't happen by accident.

Matt
And so, looking at inspiration, realizing were about to introduce the world to the very first prescription video game, the very first FDA approved and ce marked video game, it had to be familiar. And so if you were to pick up Endeavor RX and start to jump into it would feel not od or intimidating or strange or out there. It would feel like something you kind of expect to experience. And then when you get into it. One of the things you would notice right away is it's hard. This is a really important part here. In order for Endeavor Arc to do what it does, which is actually change the neural network of the brain, it has to push on it has to hurt a little.

Matt
And thankfully, games happen to be one of the greatest things we've created as a species, to be able to control experiences and to be able to create loops of reward and challenge. And so that challenge, the difficulty that exists in endeavor Rx, is equally paired with the appropriate amount of reward, right, as all good games do. But experiencing it, you feel it. When you're done, you actually feel like you had a mini personal trainer in your brain pushing just the right spot for you. And so in order to change that neural network, similar to like a physical exercise, it's not a perfect analogy, right? But you need to tear that muscle, you need to have a targeted approach. You need to push in the area that needs development.

Matt
And so as you play the game, you're having fun, you're experiencing this, you're going through a lot of things that are very familiar from really good games, but you feel it in a way that you don't feel with other games.

Pete
I've seen this mentioned in other research under neuroplasticity, and how games get you in this state of neuroplasticity if it's immersive and hard enough so that you can change habits. That's how I came across it. Because traditionally it would take the research says, like, 66 days to form a new habit, or you can go and get it neuroplastic and do it faster. So what you're saying is this is how you've approached this problem?

Matt
Yeah. I'm glad you brought up neuroplasticity, Pete, because this is a really important part of, I think, this entire industry and where this is all going and why it started in the first place, is that for the longest time, we and neuroscience thought our brain just kind of declined right as we got older, and there was really nothing we could do about it. In fact, the very first study that we put together at UCS with Dr. Ghazali was designed to do two things. One is he believed that a video game built from the ground up could be sensitive enough to detect cognitive decline as we age, which really hadn't been measured before. Just, we all feel it. We all knew. So that alone is super cool. Wow.

Matt
Could a video game be sensitive enough to be able to see the difference between people in their twenty s thirty s, forty s, fifty s, all the way up to their ninety s. The answer there was true. Absolutely, it could, which is super cool. And that trajectory, as you imagine, was just what we expect. In fact, it started a little earlier. I think it was like 27 is when some of the decline started, which was a little surprise finding. So that was the first thing that he set out to do with the study. And the second, which is even cooler, was, okay, if we can detect that, can we improve it? And not just getting someone better at the game, right? Can we actually have transfer of benefit to the real world? And the answer there was also yes.

Matt
And that's why this landed on the COVID of nature, which I didn't appreciate at the time, but that's apparently like the Academy Award for neuroscience, is beyond the COVID of nature. And so that's why this was such a big deal. It not only showed that a video game could be this sensitive, but that we could actually train and improve. And so that opened the door to so much, including, I think, a lot of this new kind of digital therapeutics industry. And. Sorry. The point I wanted to come back to on the neuroplasticity is we now know that our brain is just like most of the muscles in our body. They can be changed, they can be developed, and our brains, even when we're in our, can still be improved in some of these areas. So that's a massively cool finding.

Matt
And it also opens up, again a whole new world through that approach. And like, okay, well, what does that mean? So that's where I think we are today. What I would like to point out about endeavor RX and about this core technology. To your point, Pete, with plasticity, is the not so secret sauce of why this works so well and actually changes the brain is this closed loop system. And Dr. Ghazali would be the first to say that a closed loop system is the best way to change anything, whether it's behavior, whether it's physical, it's being able to get a measurement of an ability or a strength or a weakness, train it, get really frequent feedback, adapt the training very quickly, run that cycle again, get the feedback, measure it again, and do that over and over again.

Matt
That is the best way to make change happen. And turns out video games are an awesome way to be able to do that. Not only do we have great data collection, but we collect data at 60 frames per second. Endeavor Rx. Right. And it's adapting at that rate to each individual. Not to mention we're able to make improvements to the game and make different versions of the games for different groups. So there's a lot there. I can talk about that closed loop concept forever, but it really is one of the most powerful parts of what makes this work.

Ben
I have many things I want to start unpacking now. So I think the analogy about neuroplasticity and physical activity and exercise is a really good one. So to improve muscular strength, it's going to result in micro tears at a protein filament level within the muscle. But that damage has to happen for remodeling to occur, for that change to occur as well. So I think, actually, the idea being that games should be hard in the way that training is probably going to be hard if you want to develop strength and muscle, is a really good analogy. Actually, I think we should talk more about games being challenging rather than gamification, is just making it fun, because I think also that just devalues it from the wider medical community.

Ben
We just go, oh, it's just a bit of fun, where actually no games are challenging and hard, and that's where the change happens. What I think is also really interesting is around the idea, the transferable benefits from the game itself into real world actions and behaviors and reaction times, or whatever it is, emotions and everything else. It gives this ecological validity of it as an intervention, resulting not just someone getting better at a game, but at having a direct influence in their day to day lives. Was that the key element within the FDA approval process? Was that the key element within the research to demonstrate that it should be prescribed? This is something that was a medical intervention and not a game.

Matt
Great question, and the answer is that and more. I think the philosophy to go that route in the first place was based on this is like the intent was, can we truly improve people's lives? Can we help patients? And transfer of benefit into the real world is what really matters in the end. And so the original intent and the decision for us as a company to actually invest in this massive undertaking of going down the route for FDA approval and becoming a prescribed product and running all these massive, large, expensive, long clinical trials, was based on that. What we recognized early days, when we started to see the data come out of neuroaser and out of UCSF, was like, this was not brain training, brain fitness, this was a brand new category of medicine.

Matt
This was something really important that we knew the world needed to understand it as such. And it could have easily, had we done, I think a different approach could have been maybe lost in the shuffle with some other things that are just no data backing them up, but just say, this is good for your brain. We knew that this was really important and had to be brought into the world in the appropriate way. And we knew no one else on the planet was probably going to do it at that time because it is hard and it is long and expensive. But that was the originating decision that we made to go this giant route, and we're super glad that we did, and it took a long time.

Matt
We could talk about the FDA process and we could talk about going through all that, but the clinical rigor that we applied from the inception of the company, we often say there was two pillars that hold up achilles. One is the clinical rigor and validation, and the other is the quality of the experience. Right. It's the design with the capital D, and we invested equally and heavily in those because we know they are so dependent one another, and they're both so critical to having an effective product, because if it is working perfectly under the hood, the science is nailed. But it's not engaging or immersive, and no one wants to pick it up. Doesn't do you any good, or vice versa. So we started with that philosophy.

Matt
As you point out, the scientific validation of this and the validation of this as a new category of medicine to the world was incredibly important.

Ben
The other one I want to pick up on is, I think, the fact that what was teased out of some of the data, was it possible to measure cognitive decline from people playing the game? So, within the world that I work in, around rehabilitation and musculoskeletal care, one of the big things is about measurement of change. Ideally, objective measurement of change. Not someone telling you they're feeling better, but actually a measurement which no one can't talk about how they're feeling, but actually a measurement of physical function is always a pain. And historically, when trying to run clinical trials, I had people terrible at reporting it if they had to self report and complete the measure themselves, or didn't want to, because it was just a test, it was boring. People don't want to fill in forms or complete tests.

Ben
What do you think the role of games could be as a measurement instrument for clinical assessments more generally?

Matt
Yeah, great question. I'm glad you brought that up. Measurements and assessments and diagnostics, frankly, I think, are a big part of the future of this industry. We ran a really interesting study with Pfizer in early days, which I still am fascinated by, and I have to remind myself of how cool this is. But Pfizer approached us because they were looking into Alzheimer's, and they believed that something like our technology, this is what they came to us with, might be sensitive enough also to detect the difference between someone who is likely to develop Alzheimer's down the road and someone who is not, even when they have all passed the cognitive battery of tests equally. Right? So we ran this big trial with Pfizer, and, I mean, hundreds of patients, I don't remember exactly how many.

Matt
And they did all the work up front, where they actually did the ct scans to detect amyloid plaque in a whole bunch of individuals, and then divided two groups. So there was folks who had detection of amyloid plaque in their brains, and some that did not. Again, all of them behaved the same cognitively. They all scored the same on these batteries. So a version, early version, of what became in Deborah Rx, was able to tell the difference between those two groups in seven minutes of gameplay. And so that concept alone, like that idea alone, hopefully can answer your question that even just what we have is more powerful as a detection device and as an assessment and potentially a diagnostic down the road than I think we all give credit for today. So, to answer your question, yes, I do.

Matt
I think that these will be really important measurement tools. And what I want to see is I want to see them happening sometimes through fun and joy and experiencing like a game, but more importantly, invisibly, I just want to see them happening to us as we go about our daily life, doing the things that we want to do. And so I think that's the ultimate goal.

Pete
I think what's really interesting in the seven minutes when you're playing a game, if I'm right, you're gathering thousands of data points. Whereas if I answer a series of survey questions, I might answer seven or eight in that seven minutes. Whereas you might have. How many thousand data points are you picking up and tracking?

Matt
Yeah. As I mentioned before, Deverx, in this case, 60 frames per second, and it's gathering a tremendous amount of data. And one of the things that I love to talk about is the data that we collect as a company. We're not collecting data like a normal tech company or anyone else. We're not collecting it for advertising or anything. We're collecting it to make the medicine better. That's it, period. Right? It's part of that closed loop, if you really think about it, as we get more data, both from clinical trials, but now, out in the real world, that is just feeding that loop to make the medicine better and better for everyone. So some simple things, Pete, like as simple as the accelerometer data that's coming out at 60 frames per second as someone.

Matt
Because when you're using endeavor RX, you're tilting the iPad to control the character. This is a key part of activating that part of the brain is this continual motor task that is unpredictable that you have to be doing, which keeps this part busy while we are feeding you these other challenges. But just that accelerometer data alone is incredibly insightful into how someone's doing. We can tell how engaged someone is. Are they really trying in the game versus just kind of phoning it in? It's pretty deep how we can go scientifically looking at the medicine and peeling apart, is this helping this person, and can we predictively guess how much it's going to help them? That's the wish here.

Ben
It's pretty cool to build on that. I think the idea people hate tests, one because they hate completing tests two because they're anxious what the result of that test may be. So people don't do tests and they're not assessed, or they don't go for checkups. What if in the world where people's day to day interaction with things they do, such as a high proportion of the planet, are now using their mobile phone to play some form of game at some time, it's no longer the minority of the population of planet that play games. It's now the majority of the population, mostly through mobile gaming. What if just our daily lives could detect, actually, do you know what? Maybe you should go for a further test.

Ben
Or maybe you should go and speak to someone about that so it doesn't become anxiety driving event in life. It's just, oh, yeah, there is a change. Maybe actually it's time to go and have a chat with someone. Imagine all those earlier checkups, imagine all those earlier follow ups, what that could mean for the prevention of worst disease later on.

Matt
Yeah, love that.

Ben
Ben, I need to move to San Francisco and start tapping on your.

Matt
Sure, sure, absolutely. Come on out. Come on out.

Ben
So what I want to ask into next is what is your design process in Endeavorx? Because like all tech companies is all about kind of what are we doing next? Next features, next functions? How are we going to adapt to this population? How do you approach that as a design team?

Matt
Yeah, I think it's great to talk about some of the early challenges that we had when were faced with that initial question, like, okay, how do we design this? And I could take this back to the neuroracer days, but even more specifically, Achilles. So Neuroracer had wrapped. That trial was such a wonderful outcome that there was the nature cover and we knew were founding a company. We have to start with, which population do we want to begin with? So there's a whole bundle there of reasons that we chose ADHD, pediatric ADHD, to be specific.

Matt
But to your question on design process, one of the first questions that I think is really scary for a lot of game designers right away is when you're given some pretty heavy scientific constraints, that can be intimidating or maybe even deflating of like, oh, it has to do that. That's not fun. We got over that pretty quickly and we realized that this was actually kind of a gift. And this is something that I've realized in working with creative people now over the years, too, is that we love a box. If you just give us a blank canvas, we're just going to crumble, we're going to fall apart and be like, make me something cool.

Matt
Okay, but when you're given a box, when you're given something to work, constraints like this to work in, it actually unleashes your creativity and say, okay, well, I know where the boundaries are. So now let me just stay in here and get crazy. And so what we found is it forced us to not reach into our old bag of game design tricks and say, let's pull out solution one, two, five, a. But instead, we had to create new game mechanics, new game designs, new in many cases. A lot of times we're using really obvious, awesome stuff that we know works where it makes sense, but when we're in that box, we have to get really thoughtful and spend a lot of time in the design process to figure out how to make that work. And it was super rewarding. Super rewarding.

Matt
So it went from really intimidating and kind of scary to really one of the most creatively rewarding moments of my life is trying to figure those things out. And the cool thing is they're still not perfect, but we get to iterate. It's one of the wonderful things about a video game is we can iterate on it indefinitely and continue to make it better. So the design process started there, which was, okay, let's get over the scary part and let's focus on trying to take what we have and make it as fun as possible. The other part that came around that same time was how do we build the teams, how do we build a company? And we recognize that were combining two, if not four, really different industries for the first time.

Matt
You've got not just healthcare, but you've got specifically pharma, you've got biomed, you've got entertainment, you've got game, you've got tech. And were mashing up these two industries in a big way, and they are very different, no doubt. So when we knew from early days that diversity would be our greatest power, but also our greatest challenge, so went into that open eyed, which I think was really great, and we really focused on hiring people who are hungry and lifelong learners and who are creative, no matter which industry you come from, creative meaning they just will be willing to solve problems from a different angle. And so filtering for that and starting to combine these folks and then teaching each other back and forth was a huge part of the design process. And in many cases, we actually have to teach what design is.

Matt
I think for many folks who aren't in the tech or the games or industry, who haven't worked in that, when they hear design, they're like, oh, that's the person who makes the pixels at the end or something along that line. That's the person that makes the type look nice. But as we all know, design really is so much bigger. It's a way of solving problems. It's a human centered focus on how you solve problems, which lines up exactly in Achilles case with our very patient centric attitude. Right. Everything we do is focused on what's right for the patient. So that overlapped beautifully with the classic design process.

Matt
So we really spent a lot of time kind of cross pollinating and training and learning from each other and being hungry so that were in a good place to be able to move forward and not block horns all the time, which would have easily happened, and I've seen it happen at other places. So that was a lot. But I think that foundational part of the design process was by far the most important. The rest of it looks a little bit more traditional, like we had seen. Then we try new features, we test them, we iterate them, improve them. But that beginning stuff was the really challenging and I think most critical part of the design process.

Pete
Those constraints and making you more creative seems to be a theme running through your early career and what you were drawn towards all the way through, doesn't it?

Matt
I guess so.

Ben
Within the design process, the thing about creating digital products which are consumer facing, and a lot of it is about making sure they are continually changing and adapting and engaging and interesting. And I think one of the things you mentioned earlier about, the great thing about a closed loop approach is that actually what you want to be doing is repeat a pattern to the point they improve, create the neural connection. So actually you get that neural change. It's a similar thing in rehab as well. Actually, the best thing that someone could do is just do the same exercise for quite a lot of repetitions, because that's going to get the greatest tissue change. But humans don't enjoy that. Actually, what they want is variety. They want it to be interesting.

Ben
So when you're designing these elements of endeavorx to make sure the features and functions actually explore the passions of people so they can go and find it engaging, because you want that repeat engagement. How far can you move away from what was tested and submitted in clinical trials and FDA approved before suddenly is no longer the intervention that has the approval. It's a lot easier. Things like penicillin or morphine. Because penicillin is penicillin, morphine is morphine. It doesn't really deviate, but as an interactive therapeutic intervention that will adapt and look different every month to every year, how do you make sure you stay aligned to the research and the kitemark FDA approval?

Matt
Thanks, Ben. I love this question. And we've gotten a version of it over the years, which is wonderful, even from when we first posed this idea of, like, we want to bring the first FDA approved video game into the world here, not only were there raised eyebrows, but that question comes up like, wait a minute, what happens when you change it? Right? Because the drug is a drug. Drug takes could be ten years and a billion dollars. You get the molecule, right, and then you manufacture it and you market it. That's simple. You're not changing each pill to be custom colored and taste for each individual, all these type of things. It was a question that has been with us for a very long time.

Matt
And there was part of us, I think, that was hoping that someone out there would have the answer to this. Like, maybe someone has figured this out. Maybe it's FDA. Nope. It's another one of these unsolved problems, which so immediately we're like, okay, let's dig in. And we realized that there was answer. We had to find a proposal, a way to do this. And there was a couple of things that we've done. One of the first and kind of most obvious is that we had to define the different buckets that existed within the game. There's a bucket that is that core medicine. That is the core constraint, the algorithm. In the case of Endeavor Rx, it's called the SSME, the selective stimulus management engine, and it's very focused on a specific part of the brain and activating a very specific neural network.

Matt
And it's a set of algorithms and these closed loop feedback that is clearly defined and patentable and protectable and clearly the medicine. Right? And then we have the other buckets that don't touch that. So you can almost think ven diagrams. Many of them overlap, but there are some that don't. Like the costume store, for example, like, as you earn points, the rewards, choosing whether you choose the big crazy unicorn costume or the motorcycle girl that's in a bucket, that is just truly cosmetic and really just rewards. So we had to first define these different areas, say, this is the medicine. These things are not. And we had to test that, of course, as we do at Achilles, very data driven company. And then secondarily, where we moved into was testing these things, right?

Matt
And saying, okay, well, when we make a change like this, what changes? Let's test it. Let's try it. Let's put it through. So starting that progress and then where it's going and where we're taking it, which I think is really exciting, is more down kind of the machine learning and AI route. Right. As we've been in multiple clinical trials and we have been out in the real world, we have tremendous data on what it looks like when this medicine is working well for an individual. And we can essentially create virtual patients. We can create these patients who can play the game, and they're actually not real people, but they represent how real people play the game. Then we can try all kinds of different stuff much more quickly without having to run a big trial or bring a massive focus group together.

Matt
We can start to say, what if we change this to blue? Or what if we add this new game feature? We can run it through this virtual patient trial and get data out, and we can compare that against the real stuff that we have. And so that's not totally in place or fully functional, but that's where it's going, and that's where we're headed. And I think once we and others figure that out, that's going to be another big boost of fuel, I think, to where this is all going.

Pete
That sounds incredibly valuable to anyone doing a digital product if you've got potentially, like, an FDA approved bucket of virtual patients that you can just hire rent, as it were.

Ben
Well said, pete, I guess, is the bucket becoming unity, where unity is in most games? How can that bucket be put into any other game? So, actually, that's the value which can go into anywhere. Where do you see Endeavorx moving next? Where do you see the new populations that will probably be most affected effectively by games like Endeavorrx?

Matt
Yeah. So ADHD, as I mentioned earlier, was our immediate focus. That's been our kind of pioneering first disease population that we wanted to help for a whole variety of reasons. So endeavor Rx is currently labeled and indicated for pediatric ADHD. So, ages eight to twelve. Our immediate effort is to help everyone with ADHD. So we've already run clinical trials and have great data in adolescents and to adult. In fact, just a couple of days ago, we announced the top line results of our adult population, and to give you a little context there, so the wonderful effectiveness that we had with pediatrics that got us FDA approved and is now being out there helping kids, when we tested with adolescents, it effectively was three times as powerful with adolescents. And our top line results of adults, seven x.

Matt
And we added a bunch of quality of life measurements into that adult population that were unique to that population as well. And seeing, I think, generally 80% of the adults in the top reported improvements in their attention, and three quarters of them improved in quality of life. So this has really just came out a few days ago, and we are really excited about that. That has always been the strategy, and the plan is to reach everyone in the ADHD realm and kind of flesh that out and be as accessible and available to everyone, and not just in the US, of course, but beyond. So ADHD is first and foremost, and we're well underway. To be able to help everyone in that population is our goal.

Matt
And then, as I mentioned earlier, we've run over 30 clinical trials at achille over the years across many disease populations. So beyond ADHD, there's depression, Ms, traumatic brain injury, Alzheimer's, the list goes on. And so we really do think of ourselves as a cognition company. We're not an ADHD company. We just began with ADHD, and that's where we want to get it right and sort out the whole system that, again, didn't really exist for. How do you get a digital therapeutic? What does getting a prescription look like? So a lot of what we have also done is really kind of figure out the machine, build the machine with which to bring digital therapeutics out into the world in an accessible way. So that's really where we are today. But moving into these other disease populations is clearly the next phase.

Ben
And where do you see digital therapeutics? Game mechanics and game play within digital therapeutics, going beyond what you're working at, Irvindirex beyond cognitive, where do you think the future is in the next five or ten years?

Matt
Yeah, I do think there's going to be a lot, and it's been so much fun, again, listening to your previous guests and hearing all these different angles. And I think you're feeling a common thread. You're hearing a common thread of how many things are actually going on. And it's really hard to ignore the convergence of those. You can see them all coming together. So I'm talking about all the biometric sensors that are becoming part of our lives, whether it's as simple as the fitbit to glucose monitoring, to measuring someone's gait when they walk. There's, like, so much that we're starting to collect, and it's still early days, right? It's almost kind of like. That's not a fair comparison, but almost like the automated home, right, where there's all these different companies doing different things, but none of them talk to each other.

Matt
They weren't compatible. We're going down this path with all these different measurements of the things that we're doing in our daily lives are going to come together and have a common platform and a common shared goal. And I do believe cognition, for me, is one of the most important parts of this. What we do know now from the science is that our cognitive health is just as important, if not more than our physical health. So there needs to be a future, I think, for us to move forward as a species. Noah talked about evolution. I think we can actually fast forward some of this stuff if we're going to improve in these areas. I think we need to focus on cognition. It needs to be just as important of a part of our life as our physical is.

Matt
We need to spend as much attention and energy and time on our cognitive health as we do our physical. So I think that future is coming and think it needs to. We want to fast forward that. As we talked about earlier, the importance of cognition and cognitive health spans across so much as we're learning so many different disease populations. And you brought up kind of prevention, Ben. And I think even when we talk to the really smart insurers and the payers out there, they're starting to recognize that, yeah, cognition could be preventative medicine for a lot of these things that happen to us down earth, as simple as the behavior change stuff, but even more deeply in kind of helping rewire the neural network early on and intervene early on.

Matt
And so I should say, actually, I know, because it's common sense, right, that if we can get that right, quality of life is going to improve downstream significantly. And so what I want to see in the future is in the near future is a lot of these different things coming together. As I mentioned before, I want people to go about their daily lives, doing the things that they love and they enjoy and that are meaningful to them. And then secretly, or right under the hood there, their data is helping them. That closed loop system is happening. That stuff is being collected, it's being fed back, it's being improved, and we're just constantly being. Yeah, we're constantly part of that closed loop. And I don't think right now we are.

Matt
We stop and start, and I think as soon as we can get into that space, we're just going to see quality of life improve. And that's the future that I want to help enable.

Pete
That's a really great, positive future. That's what I like to hear. I've got a big question for you, though, especially considering you mentioned a doctor called the video games the devil's instrument.

Matt
Sure.

Pete
How much persuasion does it take to convince doctors to prescribe a digital product instead of a pill? And how much of this is needed in order to make this beautiful, positive future?

Matt
Actually, yeah. Great. Great. Thanks, Pete. Yeah, earlier days, it was a little bit more eyebrow raising, as you can imagine. We found initially, when we started to approach doctors with this concept, early days, were initially surprised by how many were like, well, yeah, if the data is good and the safety profile is good, then, yeah, were initially surprised by how many doctors were very receptive to the concept of this, particularly when they would call, like, well, if the data is clear and solid and rigorous and validated, and if the safety profile is what I think it would be, which is incredibly good, why would I not try? This was kind of the initial inspiring, and it really just kind of gave us kind of strength and confidence early on.

Matt
But at the same time, we would talk to some doctors, and many of them older school doctors, right. Folks who didn't grow up playing video games. Right. There's an exact kind of number, I don't know where it's at, but, like, 58 years old now, of people, the dividing line of people who grew up with that and didn't. So we definitely saw that divide come into play. But the good news there is, like, every year we're seeing new, wonderful, thoughtful, creative physicians come into space. And again, many older physicians, too, are very receptive. But, yes, definitely, especially early days, a lot of them, like, wait, you're going to what? I'm going to prescribe a video game. That's ridiculous. That'll never happen. You're crazy to go down the FDA path a lot of that early days, but we've seen that disappear over time. Not entirely. Right.

Matt
So at this point, as I mentioned, endeavor RX's early days, we really have only started launching it out the end of this last year, and it's already being prescribed in all 50 states. In the United States, we have over 10,000 prescriptions. So we're seeing physicians be very open to it and very, in many cases, super advocates for it. And again, I credit a lot to the data, again, and all that time and money and energy that we spent to validate this as a legitimate medicine. But the safety profile, which is something that we don't talk about a lot, this is very different than a drug. It's not meant to be the panacea, replacement for drugs or anything like that. In many cases, doctors are pairing it with a drug. And so we're not antidrug company.

Matt
That works well for a lot of different things, but this is a very different approach in many ways. And so seeing doctors be receptive to it. And again, there's not many days that we go about listening to the news and not hearing about how many people are struggling with adhd and adolescence and how that's transferring to anxiety and depression and problems with adults. It's getting tougher. And access to those medicines is becoming more challenging. The pandemic has definitely magnified so much of what's going on here. So I think having something like this that can help people, that all the data is there, the evidence is there, and it's safe, it's pretty important. So I think when doctors understand that, and they do, pretty quickly, they have the attitude of, like, why not?

Matt
And then, Pete, to your question, does that mean that these always have to be prescribed? We've always imagined that there's a future where Achilles other companies, as this industry continues to grow, right. There's all kinds of different products like this helping all different populations, and some will be FDA approved, I think in areas where you have to be very responsible, like, again, early children, and then there's areas that we hope that do not need to be prescribed or would better to just be out there and available. So I think there's a future where that is all true, where these are accessible and available at all different levels. In order for that very positive, optimistic future to come true, I think that has to be the way it goes.

Ben
Matt. It's been absolutely remarkable having you on today's show, from knocking on doors to following passions and finding people with diverse interests and passions to create the foundations of games for health gameplay that's so sensitive it can be used as a measurement of cognitive change with game score improvements that have transferable real world benefits. The twin pillars of clinical data and design on the journey to prescription of gamified digital therapeutics and the importance of defining therapeutic elements, or buckets, within a game versus those buckets that drive engagement but do not undermine therapeutic intervention. Matt, it's been a remarkable show. Thank you so much for your time today.

Matt
Likewise, Ben and Pete, thank you again for everything that you're doing, and I'm looking forward to all future episodes.

Pete
Brilliant. Thanks. Matt, it's been great having you on.