This week, we’re diving into the innovative world of digital therapeutics with Dr. Scott Kollins, exploring the potential of a unique game-based treatment for ADHD.
Dr. Kollins works for a company called Akili that has been developing a video game that is designed to help treat the symptoms of ADHD. The game EndevorOTC was only available for iOS, but they also just recently launched an Android version.
In our conversation today, we discuss the challenges, successes, and future of this pioneering approach to managing ADHD.
Check out Endeavor OTC
William Curb: Could you tell me a little bit about Akili and your work with creating this really cool game for ADHD?
Scott Kollins: Yeah, sure. So I'm the Chief Medical Officer for Akili, and I'm a clinical psychologist. I've been at the company since December full-time, but I've actually been working with and known about the company for a lot longer than that. So actually, more than 10 years now.
So I spent most of my career starting in the year 2000 up until 2021. In my faculty researcher role at Duke, we were approached by this new company at the time in 2013, Achilles. And Akili had recently been founded by licensing technology out of the University of California, San Francisco; a neurologist and neuroscientist there named Adam Ghazali had been researching a kind of game for health in a lot of different ways for a number of years. And he had published a study where they used what is effectively a prototype of our current product of endeavor in older adults and found using that prototype for about a month results in really substantial cognitive improvements. They were associated with changes in the brain and the areas that you would expect them to be associated with and the effects are really durable.
So they saw improvements even six months after the research participants had stopped treatment. That was the formation of the company. And then when I got involved, they came and said, because company was formed, they've got this cool technology. And they said, okay, we've got a product here that was built from the ground up to help attentional control.
What is what's the best target for that product? And they decided that ADHD, given everything that's known about the primary challenges that people with ADHD face, that would be a good starting point. So they came to us and said, we have this product, and we would like to do a small-scale study proof of concept, see if this thing works in kids with ADHD.
They had actually taken the initial prototype and turned it much more into a kind of a user-friendly game at that point for kids. So as researchers, we said, sure, we would be happy to do this. Let's see if there's a there there. So we did a small-scale study about we had 40 or 50 kids enrolled, and it was positive. And we showed that after four weeks of using this treatment, we saw improvements in their attentional functioning. And that that for the company at the time, that was their kind of go-no-go decision to say, all right, we want to invest in really developing this product as a medical product. What that means is that they wanted to put investment into conducting large-scale controlled clinical studies with the goal of then using those clinical studies to go to the FDA to get approval as an actual medical device. So that's what they did. And I worked with them closely on that journey.
We designed two what are called pivotal studies. The first one had about 350 kids. The second one had a little over 200. So upwards of 600 kids total multi-site studies, all the bells and whistles that you need to have a rigorous and properly controlled study. So we did those studies. They were positive.
We published both of them. And that was the basis of submitting to the FDA to say, we would like you to regulate us so that we can say that this is actually a medical treatment for ADHD. We did that the treatment, and the product was approved in June of 2020. There was a lot going on in the world in June of 2020, a few months into COVID. So for a variety of reasons, the decision was made at the company at the time that we're not going to go whole hog into launching and getting a sales force together and all that because the world's in the midst of a pandemic. So the product was released and there was use, but it wasn't until last summer, so 2022, that Achilles started to get really serious about commercializing the product and building awareness, getting a sales team out there to educate providers.
Because this is new and different, no pediatrician and most psychiatrists have never heard of this. And so this is part of the thing that we've been working on. And then I had left you back in June of 2021, started another small startup company and then joined Achilles back in December, having been really familiar with product evolution with the clinical research that we've done so far. So here we are. And we're really excited about the direction that we're headed.
William Curb: Yeah. I mean, I remember I had initially heard about when the FDA approval process and I was like, oh man, this is going to be, I'm going to hear so much about this.
And then pandemic stuff was going on. And I'm like, in there on my radar, I'm like, I should really look into that again because that sounded really neat. And so then when you guys emailed me, I was like, this is something I actually really want to look into. So I was really excited about it. And it was really cool that you guys sent me the code to try the game out the Endeavor OTC, which has been harder than I was expecting it.
Scott Kollins: I want to hear about the experience, but just to comment on that, because we actually have two products in the market now. So the initial product that was approved by the FDA is a prescription-only product for kids. That product is approved for kids eight to 12 with ADHD. We have another application into the FDA now that they're reviewing to extend that up to age 17, which will also be a prescription product. And we submitted that adolescent application because we did another study with adolescents that was really positive.
And so we said, OK, we're going to kind of go the normal channels to get our approval to say, OK, now we can market this to kids up to age 17. But in the meantime, so back in the spring, we got our final study results in from another study that we'd done with adults. We did another clinical trial about 220 adults with ADHD. And what we saw was actually results that were even more positive than what we'd seen either in the adolescent or in the kid study. So we said, wow, this is, I mean, and it was really robust. And so we as a company thought, man, we want to get this into the hands of adults as quickly as we can.
Every other week, there's an article somewhere about age 17. ADHD in adults and rising diagnosis rates. There's a massive stimulant medication shortage, you know, the frontline treatment for ADHD that is affecting a lot of people's ability to get access to care.
We thought this is just a good moment for us. So we decided we were gonna launch this directly to adults over the counter, no prescription required. The way we've been able to do that since we launched is that ironically there's some guidance from the FDA that is in place that started at the beginning of COVID. At the beginning of COVID, the FDA said, we're in a public health emergency and if you are a company and you have a product, it's for mental health and it's safe and it's digital, market it however you want. We're not gonna regulate because we just need options, we need things out, which is great. That was actually part of the reason that we decided to slow down a launch because in essence, we had gone through all the proper steps of doing the research to get FDA approval and now all of a sudden the FDA was saying, you don't need our approval to market a product. So it wasn't a good time for us, but now fortunately the public health emergency has ended and it's called enforcement discretion expiring towards the end of the year, but we still have this window to say, we can still market our product under this enforcement discretion.
This is what we wanna do. There's just too much of a crisis going on with adults with ADHD. So that's what we did when we launched the OTC version.
We do intend in the next month or so, month or two, to submit to the FDA to continue to market the product after this regulation ends, but it's been exciting to see the uptake. Your feedback or your initial reaction is not surprising. I've talked to a lot of people in our clinical trials. The most, even though side effects and what we call adverse events in clinical trials were really infrequent,
like single digit percentages. The ones that we did see, a lot of times had to do with getting frustrated and frustration tolerance, even in adults. I saw this, I had my son go through a couple months of endeavor and I saw firsthand what that frustration looked like. I don't have ADHD, but I have used the OTC product myself just to be familiar with it and I understand where that comes from.
William Curb: I do play a lot of video games. I'm like, oh, that'll just translate to here. And in some respects, it did. In other respects, I feel like it made it harder for me because I was higher on my skill level, but low on my focus level. And so I was like, I can physically do this, but my brain is not following through with what I want it to do.
Scott Kollins: Are you talking about your focus score?
William Curb: Well, just my like ability to focus on the game and then eventually the focus score. Like where I'm like, I should be doing better.
Scott Kollins: Yeah, that's really interesting because we've gotten that feedback and especially now that we have a more direct consumer facing product, the OTC, we get app reviews and we get social media messages. And we hear that, we hear people saying, gosh, this is a good idea, but I'm really frustrated and I feel bad that I'm not progressing. And the feedback that we try to give people is that that is actually, it is almost by design, is that it is hard and you can't think of it like a video game that is designed solely for entertainment purposes.
This is not an entertainment product. This is a medical product that is sort of disguised as a video game. And so it's funny what I talked to my son about. I was like, do you like it every time you have to go to therapy to see psychologists for behavioral studies? Well, no, you're not going to like this every time. But the cumulative effects is what kind of keep that in the back of your mind.
William Curb: Yeah, I had to kind of refocus how I was looking at the game, too, because then it's on my phone and I typically have phone games that I do when I'm like, I got five minutes here, 10 minutes here. That is not what this is for. And then my kids would come interrupt me. I'm like, there isn't a pause. I have to like go out of the.
Scott Kollins: Pro tip, there actually is a pause. I don't know which version you're on, but the upper left corner, even though there's not a button, if you tap the upper left corner, it'll pause it. One of the things that I think is unique about this as a treatment is very much unlike if you're going to see a psychologist or doing therapy of some sort. This can really be slotted into people's schedules in whatever way fits for them. So even though I think many people, and I think in our clinical trial, what our recommendation was that do your 25 minutes a day all in one sitting. We saw a lot of people in our studies that didn't use it that way. And I know that a lot of people that are using it out in the world are not using it that way. They might use it 10 minutes here, 10 minutes there.
And just knowing that you can pause and come back to it is important. I will say that we have gotten, we've seen some feedback that people using it, like if they're on a bus or on a train or something. Sometimes that gives a motion sickness or something like that. So I might not recommend that. But to the extent that it fits in, I think it's OK. Just getting the exposure. You know, you're exercising those attentional control networks. And whether it's 10 minutes or 15 or 25 a day, I think anything is better than nothing.
William Curb: It did make me curious, though, with doing this. Is there like an optimal time to be doing it to get the most out of the exercises? Because I had like I had done it, you know, very early in the morning. Like I was like, OK, kids aren't awake yet. I'm going to do this at like 6 a.m. And I'm like, I am doing terribly at this.
Scott Kollins: The short answer is we don't know yet. I would say that trial and error for each individual user is probably the best way to figure out where it fits the best for you. We have seen user feedback where people say, I built this into my routine, I get up, I have my coffee to whatever. And then I do my endeavor. And then, you know, they say this sets me off on a good path for the day. Others are they want to slot it in like we were just talking about a little bit here, a little bit there. The only thing that I might say that I wouldn't recommend is right before bed.
Just number one, you don't want to screen number two. It's going to make you feel and we hear this feedback a lot. It's going to make you feel a little bit mentally tired to the extent that that still might have an impact on sleep. We wouldn't want to recommend that. I do have this idea that we've just never gotten around. to yet is to look in our clinical trial data because we've got over a thousand participants now with ADHD that have gone through our studies and look at time of day and look to see are there any patterns there. In our studies, we tried to mainly just to give people a routine. We tried to tell people look, try to do it at the same time every day. We didn't kick them out if they didn't do that or anything, but I would like to see even if it's just morning versus afternoon use, does that have any impact on outcomes? So it's a really good question, but like I said, trial and error.
William Curb: Because yeah, there is that big aspect of mental fatigue to it because one of the things that was just made so obviously clear to me is like, I know that when I say focus on something that by the end of the time, I'm not going to be as focused. But like if I'm doing writing or working on something, I don't actually really notice it.
I just maybe produce a little less. When I was playing the game, I'd be like 20 minutes in. I'm like, why is this so hard now? I know the game is designed to ramp up difficulty, but I'm like, I am not hitting any of the things I'm supposed to hit. And I'm just flying into walls. I'm like, I can really see the mental fatigue.
Scott Kollins: I would interpret that as good news. I think that means that you are putting in the effort that you need and you are likely pushing that algorithm to increase the difficulty to the point that it is going to be hard. I've had the same experience too in my use with it.
It is interesting. I don't know how long you've been using it, but I got to the point where as you progress through the world, each world gets harder and there's more distractors and it goes faster and there's more things to avoid on the steering. But once you get through the fourth world, you sort of enter this mode where you can do any of them at any time. You don't have to go into sequence. So the first thing that I did once I hit that is I went back to the very first world, which now only has three distractors.
One of them is the target and there's only one thing that you have to run over the power zones. And I felt like a superhero because I've been in the worlds where there was all this stuff going on. So I haven't played enough since we released Focus Score to actually see the number of where I'm at on Focus Score. But that was a good reminder to me. Disclosure, I do not have ADHD. I'm using the product off label, but I can appreciate how hard it was for me when I started and what 25 minutes in world one felt like versus using the product for probably a month or five weeks to work my way through all those worlds.
William Curb: Talking about worlds and stuff and it's just reminding me how much it does feel like just a regular video game. Like when I first like, yes, it's a game. And then like getting into like world two, I was like, there's like a lava level with like fireballs raining down on you. And I'm like, this feels really like a video game now.
Scott Kollins: I am. And I think we aren't as a company. We're very proud of that. And just to give you kind of a behind the product perspective on that, from the start when the company was
founded and Adam had worked up this really cool prototype in his lab, they immediately got consumer video game designers on staff to really start bringing this thing to life and making it engaging. And the way that that works now, and we still have a team, our head of product has a long history of really successful consumer games that I'm sure you have played or heard of.
He has a team of people that come from the same kind of background, but that team works with people on my team on the clinical side. We have a cognitive scientist, and they're just constantly working together to say, all right, here's the cool thing that we want to do from the video game perspective. And then our cognitive scientist is saying, you can't do it quite like that, or it's going to actually change the cognitive load too much. And so here's how you should do it. So it's this really very innovative back and forth between making sure the experience from the interface is interesting enough, but making sure that it is staying true to the roots of what the product is actually built to do, which is exercise your cognition.
William Curb: And does it really well. So one of the things that I was also interested in while thinking about the game playing through it, and that you mentioned a bit earlier is the durability of the impact of it. Because I remember when I first learned about brain training games and stuff, it was like, oh, yeah, I did that in college. That was just a few years ago. No, that was not a few years ago anymore. There was like a brain age and all these things. And what I had learned from those is that those generally just taught you to be better at the game in the end. But it sounds like that's not the case here.
Scott Kollins: Couple things. So I'll hit the last part of your question first, which is in our clinical studies, the primary outcome measure for us. So any clinical study, you kind of have to have a single measure that you say, that's what I'm going to hang my hat on and decide if the study is successful or not is, do I make a difference on this primary outcome? And the primary outcome in all of our studies, or most of our studies has been an objective measure of attention, because that's what our treatment targets.
So we've used this measure called the TOBA. It's used clinically by itself as an FDA-approved device to measure attention. But a lot of people have raised the question in our clinical trials, like, well, why do I care about the TOBA? I don't go to my doctor to say, hey, my TOBA score is low. You go to the doctor to say, I have these symptoms. It's causing problems for me in day-to-day functioning. And so in all of our studies, we have also measured things like ADHD symptoms, quality of life, impairment in day-to-day functioning. And we see improvements across those in our clinical studies.
So we are having an impact, at least in the short term, on things other than just we're doing more than teaching to the test. You could make an argument. People have made the argument that, oh, the TOBA is really just the game. It is not. There are some pretty important differences. But even beyond that, we can say, look at all these other clinical measures that we are having an impact on. The second thing is that your question about durability, we don't know the answer with our product of how long we can expect these effects to last. We have some data from studies, the study I mentioned with the prototype with the older adults. They did the treatment for a month, saw really good improvements on cognition. And then in that same study, they came back to all those participants six months later, measured their cognition again, and it was still a little bit of a problem improved.
One of our clinical studies in kids, we treated them for a month, took a month off and then treated them for a second month. And what we found in that study was we saw improvements in the first month, second month with no treatment, they kind of leveled off. We didn't see a worsening, which is good, but then the second month of treatment, we saw continued improvement. So that's not quite the same as durability. That's more of a question of, am I just gonna continue to improve forever if I played it? Probably not. You're probably gonna hit some level, but it did give us some confidence that continued use, you can continue to see benefits. But the question of what happens after a few months is still an open one.
And we are committed to try to understand this. We have a registry where any kid that gets a prescription, their parent gets invited to participate in this registry where we have them fill out surveys and questionnaires monthly over time just to see how are they doing, do they continue to get better, if they stop using the product, do you continue to see improvement? Just this week, we actually got approval IRB ethics board approval to do the same thing for adults. So we're gonna be launching that soon. So anybody that downloads Endeavor OTC will be invited to participate in that as well. So we can start to gather data sort of in the real world over time of what the effects are.
William Curb: Yeah, sounds good because it's things that we definitely want to know.
Scott Kollins: Yeah, absolutely. You have intuitively asked two of the most common questions we get, whether it's from patients or health care providers or insurers who are thinking about covering this is how much do you actually need to play to see benefit and how long do the effects last? Those are really, really common questions. The third one that we commonly get, which we do have a good answer to is can you use this if you're using other treatments like medication for ADHD? And the answer to that is yes. So we've done the three studies, one in kids, one in adolescents, one in adults, where people were either on or off medication and it didn't make a difference whether you were, you still saw a benefit.
William Curb: Actually, that was one of the things I'd written down. Is this more of a supplement for traditional treatments or possible replacement? Seems more like a supplement would be a better.
Scott Kollins: It should be part of a good overall treatment program. What we can say from our data is that if you are not taking medication, you still see benefits. We've seen that across age groups. I would never recommend or suggest, oh, you don't need medication. That is not at all what we're saying, but we're saying there's a lot of people that don't want to take medicine. They don't want their kids to take medicine. They can't take it for whatever reason. And we have an option here.
William Curb: Yeah. I mean, I think that's also just having that option is so important for people because is your project available outside the US?
Scott Kollins: Not yet. We're working on it.
William Curb: Because that's going to be really huge for a lot of people because while we do have our shortages here, I get emails from people all the time, very like, hey, my country, we can't even get ADHD medication.
Scott Kollins: Yeah, exactly. Exactly.
William Curb: Awesome. Yeah. Because I think having options is always better for this kind of stuff because there's plenty of reasons not to take medication and plenty of reasons to and plenty of reasons like, yeah, I can't don't want to, etc. That covers most of the questions I have. I'm readest to say fun to play because of the difficulty level, but it is not not enjoyable. I'm having a good time playing it, but it's like, I'm like, fun is not the right word, but it's a lot like exercising.
Scott Kollins: Yeah, that's an analogy we use a lot for multiple reasons, including if you go to the gym one day, you're not going to see effects. You need to stick with a program no matter what your goal is, whether it's to get stronger or lose weight, get in better cardiovascular shape, whatever, you've got to stick with a program. So that's one thing to emphasize. I think the other thing to emphasize too, Will, on that just general frame is and we're still learning the best way to sort of educate and engage with our users about this. But even though it looks and feels and you can get access to it, especially the OTC product now, just like a million other entertainment games, this is a medical product. It's not necessarily supposed to be easy and fun and enjoyable. You are using it to help you.
So I think keeping that frame of reference. So in the way you just described it, as long as it's not aversive and hurting you, that's a good thing because we're at least at neutral for what that experience is. And knowing what the potential benefits are, I think really is when it gets exciting.
William Curb: Yeah, it hasn't ever been something where I'm like, Oh, I don't want to do that today. But it has been like, OK, I'm not going to do that right now because my kids are going to come in in five minutes and that will be unenjoyable. Yes. When I'm trying to focus and they're like, Dad, you need to look at this.
Scott Kollins: Yeah. Or I want to see what you're doing.
William Curb: So is there anything you want to leave the listeners with before we sign off?
Scott Kollins: I think the one thing and you kind of emphasized it a couple of minutes ago. The thing that I am most excited about and really one of the reasons I joined the company, I've been working clinically and doing research on ADHD for pretty much my whole adult life for 25 years. And I have a family member who is affected. My son is affected.
We have used the exact same treatments for decades. And so to have an option, this isn't a silver bullet by any stretch, but it is a new option that we have rigorously studied for years to show that it works, to be able to get it regulated the way it is, especially in this moment in time in the U.S. right now, when one of the existing two available options, many people can't even access it. I think the optionality piece is the thing that I am the most excited about and something to keep in mind.
William Curb: Awesome. Well, thank you so much for coming on. Thank you for being part of developing this, because I think it's really exciting to have this in the marketplace now.
Scott Kollins: It's a pleasure, Will. And I hope you will keep us posted and we invite any and all feedback. We get lots of feedback that is not always positive and we're happy to get that and think about it from our product development side, as well as from our, you know, just give, respond back to users and things like that. So let us know how it goes.
William Curb: So far, so good. And I've only had a few of the reminders like, Hey, you didn't play yesterday. I'm like, Yeah, I know, because I was sick. Thank you for reaching out. Thank you so much for coming on the show.
Scott Kollins: Yeah, thanks, Will.