In Part I of this blog post I provided an overview of the first prescription video game, EndeavorRx, that has been cleared by the FDA for treating attention deficit hyperactivity disorder (“ADHD”) symptoms in children between the ages of 8 and 12 years, expanding the market for digital therapeutics (“DTx”) to video games. In Part II I will discuss the FDA’s clearance of EndeavorRx. 

The Federal Food, Drug and Cosmetics Act of 1938 (“FFDCA”) gives the FDA authority to regulate the safety and efficacy of medical devices. The Code of Federal Regulations for Food and Drugs (“CFR for Food and Drugs”) provides the standard for medical devices to be considered safe and effective. Section (d)(1) and (e)(1) of the CFR for Food and Drugs states that, if according to scientific evidence, the probable health benefits outweigh any possible risks the device is considered to be safe, and if the use of the device produces clinically significant results in a significant portion of the target population, a device will qualify as being effective.[1] A device is defined by Section 201(h)(1) of the FFDCA as:

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

• intended for use in the diagnosis of disease or other conditions, or the cure, mitigation, treatment, or prevention of disease, in man or other animals

In recognizing the increased role that software plays in healthcare and products relating to healthcare, the FDA decided to follow the International Medical Device Regulators Forum (IMDRF)’s definition relating to software as medical devices (“SaMD”) and defines SaMD as “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device”.[2] DTx, which consists of software programs that treat, manage or prevent a disorder or disease, which can perform its function without a specific hardware device, will therefore fall into the SaMD category regulated by the FDA.

Akili International Labs Inc (“Akili”) applied for a de novo classification of EndeavorRx as a low-moderate risk device of a new type since no predicate device existed. Their de novo classification request for their video game as a Class II device was approved on 15 June 2020.[3] The de novo classification request described EndeavorRx as a “digital therapeutic device for Attention Deficit Hyperactivity Disorder (ADHD) which is a software intended to provide therapy for ADHD or any of its individual symptoms as an adjunct to clinician supervised treatment”.[4] EndeavorRx’s software is a closed-loop system with adaptive algorithms automatically adjusting the difficulty level to provide a personal treatment experience to the patient.[5] EndeavorRx is therefore software that can perform its medical function without a hardware medical device, bringing it under the definition of SaMD. 

Akili submitted their clinical trial results in order to support their claim that the device is safe and effective. They conducted clinical trials with EndeavorRx in over 600 children with ADHD and the results of the studies demonstrated a favorable benefit over risk profile, reflecting the safety of the device.[6]  Their trials also showed that EndeavorRx had a significant treatment effect for improving inattention in a significant portion of the target population, passing the effectiveness standard. 

Section 520(o)(1)(b) of the FFDCA, however, excludes software that is used “for maintaining or encouraging a healthy lifestyle and is unrelated to the diagnosis, cure, mitigation, prevention or treatment of a disease or condition” from the definition of a device. Therefore software programs that are only aimed at promoting the general wellness of patients will be excluded from the FDA’s regulation. The general wellness software exclusion of Section 520(o)(1)(b) does not apply in this case because EndeavorRx aims to treat ADHD, a specific medical disorder, and it is not just for encouraging a healthy lifestyle. EndeavorRx should therefore be distinguished from other video games which only aim to provide brain training or promote players’ focus in general, which will fall under the general wellness exclusion. 

According to the FDA’s press release on the approval of EndeavorRx, a new regulatory classification was established through EndeavorRx’s de novo classification application. The implication of the new regulatory classification is that devices of the same type with the same intended use can obtain FDA clearance through the Section 510(k) process only, instead of the de novo classification path, by demonstrating that the device is substantially equivalent to EndeavorRx.

In order to determine if FDA approval is required for video games with a health component it is important to distinguish between games that aim to only contribute to the general wellness of players and games that aim to diagnose, cure, mitigate, treat or prevent a disorder or disease. In response to the growing market of medical mobile applications and medical software programs which aim to promote a healthy lifestyle, the FDA released guidelines in 2019 to clarify the regulation of low-risk general wellness products.[7]  General wellness products are defined as products that are only intended for general wellness use and which present a low risk to the safety of users. General wellness video games usually aim to promote mental and physical wellness through physical exercise, brain training, stress reduction and mindfulness. General wellness video games will be exempted from FDA regulation as they will fall under the general wellness exception. On the other hand, video games that claim to have a specific medical purpose that it performs, i.e. diagnosing, curing, mitigating, treating or preventing a disorder or disease, will be classified as game-based DTx and will have to obtain FDA approval as being safe and effective before they can be marketed and sold to the public. Video game developers will have to keep the distinction between general wellness video games and game-based DTx in mind when bringing new video games with a health component to the market.

The FDA’s approval of EndeavorRx as a game-based DTx increases the credibility of game-based DTx as a treatment method within the medical community and from health insurance companies and consumers’ perspectives. The FDA’s approval of a game-based DTx shows their intention to take video games as a form of treatment seriously. Classifying it as a Class II prescription device indicates that from a regulatory perspective, the FDA recognizes the potential harm that game-based DTx can hold if not proven safe and effective. However, at the same time, by classifying it as a device, and not just scolding it off as some game for entertainment purposes, the FDA recognizes the potential of this emerging treatment approach which can have a significant influence on how healthcare is provided. 

Since EndeavorRx was the first and is to date the only game-based DTx approved by the FDA, it is difficult to predict the effect of the FDA’s regulation on the game-based DTx market. The increased regulation in the video game industry may deter video game developers from bringing new game-based DTx products to the market given the additional processes they will have to go through to obtain clearance. On the other hand, the FDA’s oversight might encourage investors to invest more in the development of game-based DTx to obtain FDA clearance for the devices in order for them to be marketed and prescribed as reliable therapies for patients. Analysts predict that EndeavorRx’s sales in the US will peak at USD300 million, and Akili reported a 166% growth of their EndeavorRx sales from 2021 to 2022.[8] If this growth trend continues in the game-based DTx market, we might see a new leading industry within both the healthcare and video game industries in the next couple of years.

It would seem like game-based DTx is here to stay and soon we will say “a little bit of gaming a day keeps the doctor away”!

[1] 21 CFR Chapter I Subchapter H — Medical Devices, https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H.

[2] Center for Devices and Radiological Health, Software as a Medical Device (SaMD), FDA (2020), https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd.

[3] Office of the Commissioner, FDA Permits Marketing of First Game-Based Digital Therapeutic to Improve Attention Function in Children with ADHD, FDA (2020), https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-game-based-digital-therapeutic-improve-attention-function-children-adhd.

[4] Akili Interactive Labs Inc., De Novo Classification Request for EndeavorRx, (2020), https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN200026.pdf.

[5] Tristin Brynn Hooker & Martha Sue Karnes, More than serious: Medicine, games, and care, 65 Computers and Composition 102727 (2022).

[6] Scott H. Kollins et al., A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial, 2 The Lancet Digital Health e168 (2020).

[7] Center for Devices and Radiological Health, General Wellness: Policy for Low Risk Devices, U.S. Food and Drug Administration (2019), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-wellness-policy-low-risk-devices.

[8] Akili’s therapeutic computer game snares world-first approval, Evaluate.com (2020), https://www.evaluate.com/vantage/articles/news/snippets/akilis-therapeutic-computer-game-snares-world-first-approval; Akili Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Update, (2023), https://www.businesswire.com/news/home/20230307005504/en/Akili-Reports-Fourth-Quarter-and-Full-Year-2022-Financial-Results-and-Provides-Business-Update.