In EndeavorRx, designed for iPhones and iPads, children guide an avatar surfing through molten lava and an icy river, dodging fires and icebergs while grabbing flying objects. The game is not yet available for purchase, nor has a price been released, but its Boston-based developer, Akili Interactive Labs, may now feature its unique status in ads and pursue coverage by insurance plans. No trip to the pharmacy is needed: Doctors and nurses will be able to prescribe the game by giving parents a code to download an app.
Barkley and three other ADHD experts who reviewed Akili’s research said the firm was overpromising by implying that EndeavorRx can provide meaningful help for children struggling in school and at home with the sometimes-debilitating neurodevelopmental disorder, whose symptoms include distraction, forgetfulness and impulsivity.
“I’m a little shocked and more perplexed about why the FDA would approve this and allow it to be paid for by insurance,” said Mark Rapport, head of the Children’s Learning Clinic at the University of Central Florida, who has published extensive research on other brain-training programs making similar claims. “I abhor seeing desperate parents spend money based on empty promises. . . . On moral grounds, I think it’s wrong to tell people to get their doctors to prescribe this when it does nothing of real-world importance.”
In an email, Akili chief executive Eddie Martucci said the company sought the FDA approval “to give families and doctors full confidence in our product.” He called the criticisms “inaccurate and a misunderstanding of the FDA process,” adding: “We’re excited about this FDA labeling that clearly shows EndeavorRx is a low-risk, targeted treatment for a cognitive issue.”
In dispute is the real-world value of what is being “targeted.”
Akili’s strongest evidence of EndeavorRx’s potential benefits is children’s performance on a 21.6 minute-long, continuous-performance test known as TOVA (Test of Variables of Attention). The test, described by the Tova Co. as “long and boring,” requires participants to push a button intermittently after seeing a certain geometric shape.
Akili’s leading study in support of its FDA clearance, which the company paid for and which was published last February in The Lancet Digital Health, a peer-reviewed journal, found that 36 percent of children who had played its game for 25 minutes a day, five days a week, for a month, no longer had a deficit of attention as measured by the TOVA. But the critics questioned whether the change was likely to affect their schoolwork or behavior.
“The effects just don’t generalize,” Barkley said. “You get better at playing the game and anything similar to playing the game.”
Martucci countered that EndeavorRx is specifically designed to help children with ADHD who struggle with specific attention issues. “Even though inattention is often less recognized than overt symptoms like hyperactivity, we’ve heard from numerous families and physicians that they are seeking new options to specifically help children living with the day-to-day challenges caused by attention issues,” he said.
The FDA cleared EndeavorRx as a Class II medical device (a category that includes powered wheelchairs and some pregnancy kits) through a regulatory review process that is less rigorous than the one required for new medications. Now that EndeavorRX has been cleared, future developers will only need to show a “substantial equivalence” to the approved game.
EndeavorRx is based on software invented in the lab of Adam Gazzaley, a neuroscientist at the University of California at San Francisco. He is now a board member of Akili. The firm began its pursuit of the FDA approval in 2013, submitting data from five studies involving a total of more than 600 children.
Four of the five studies, one of which is still unpublished, were wholly or partially funded by Akili, according to the company. The Lancet Digital Health report said the lead author of that study was a paid consultant with stock options in the firm and three other authors were Akili employees. It’s not rare for companies to pay for such research, but peer-reviewed journals require such relationships to be disclosed as potential conflicts of interest.
The authors of the Lancet study warned that their results weren’t sufficient to suggest that the game substitute for more established treatments for ADHD. Among the limitations of their study, they noted that they had excluded children taking ADHD medication or who had an additional “significant” psychiatric problem, leaving in question whether even the TOVA improvement would apply to those groups.
The authors also disclosed that they found no difference between parents’ assessments of children in the EndeavorRx group and a control group who played a computerized word game. Both groups of parents reported improvements, suggesting there may have been a placebo effect, and leading the authors to speculate that “any intervention that requires the patient to engage in a regular, structured setting that may include repeated failure or repetitiveness can be seen as a potential intervention for ADHD.”
The case of EndeavorRx revives a broad and long-simmering controversy over the benefits and risks of computerized “brain-training,” part of a global industry projected to be worth more than $8 billion by 2021.
For several years, researchers and industry leaders have debated whether playing “brain games” can meaningfully improve memory and other cognitive skills, or whether the money and time they require might be better spent on more evidence-based activities such as physical exercise or cultivating friendships.
Although Akili’s Lancet study said it found “no serious adverse effects” from playing the game, the authors disclosed that about 7 percent of trial participants experienced “mild or moderate” problems including frustration, headaches, dizziness, nausea and aggression.
Yet critics say they’re less worried about these potential issues than the risk that parents will waste time and money on what Rapport called “a delightful distraction that has no effect on school performance or learning,” when those scarce resources might be better spent on tutoring or other educational activities.
Such parents constitute a large and lucrative market, given that some 6.1 million U.S. children ages 2 to 17 have been diagnosed with ADHD, which can lead to school failure, social ostracism and defiance at home. Surveys show 62 percent of these children take medication, most commonly stimulants. Yet the pills are widely stigmatized, don’t always help, and can involve severe side-effects, leaving ever-hopeful parents vulnerable to a cottage industry of controversial and often-hyped alternatives, such as elaborate exercise regimes, computer games, nutritional supplements and fidget-spinners.
“It is so hard to see your child struggle to fit in a world where they fail to meet expectations, not because there is anything wrong with them but because it is easier and more cost-effective to cater to just one type of kid,” said Elisa Castillo, a hardware engineer and mother of two in Fremont, Calif.
Wary of starting medication with her son, now 12, who was kicked out of his first-grade after-school program for misbehavior, Castillo has spent hundreds of hours investigating and trying non-pharmaceutical approaches, including Omega-3 supplements and blood tests to check for mineral deficiencies, and signing up for a clinical trial of a computer game (not EndeavorRx) in Gazzaley’s lab, which required her to drive her son for 80 miles round trip to San Francisco for 10 two-hour sessions.
After failing to see any improvements, she has crossed computer games of all types off her list, she said.
“I actually think my son’s video game addiction is a more serious problem than his ADHD,” she said. “I have to do everything I can think of so he isn’t playing every minute.”