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Cited by 385Attention Deficit Hyperactivity DisorderDigital Mental Health InterventionsAutism Spectrum Disorder Research

A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial

Open access
Kollins, Scott H, DeLoss, Denton J, Cañadas, Elena, Lutz, Jacqueline, Findling, Robert L, Keefe, Richard S E, Epstein, Jeffery N, Cutler, Andrew J +1 more·2020·The Lancet Digital Health
DOI 10.1016/s2589-7500(20)30017-0
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Abstract

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. METHODS: The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. FINDINGS: Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). INTERPRETATION: Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. FUNDING: Sponsored by Akili Interactive Labs.

AI snapshot

Written from the paper’s full text.

TL;DR

In the STARS-ADHD randomised controlled trial, the AKL-T01 digital therapeutic improved an objective measure of attention (TOVA API) versus a digital control in children aged 8–12 years with ADHD. It did not significantly outperform control on most secondary symptom and impairment measures, but was well tolerated with mild adverse events.

Key findings

  • The primary outcome, mean change in TOVA API, favoured AKL-T01: adjusted p=0·0060; Hodges-Lehmann median change 0·88 (95% CI 0·24–1·49); mean (SD) change was 0·93 (3·15) with AKL-T01 versus 0·03 (3·16) with control.
  • More AKL-T01 patients were TOVA API responders: improvement >1·4 points in 79/169 (47%) versus 51/160 (32%), p=0·0058; post-intervention API ≥0 in 18/170 (11%) versus 7/160 (4%), p=0·033; normative range on at least one objective attention measure in 36% versus 21%, p=0·0027.
  • There were no intervention-group differences for secondary measures including IRS, ADHD-RS, ADHD-RS-I, ADHD-RS-H, BRIEF-Parent Inhibit and Working Memory, BRIEF Metacognition, and CGI-I. IRS responder rates were higher with AKL-T01 (82/171 [48%] vs 60/161 [37%], p=0·049), and parent-reported attention improvement was higher (97/173 [56%] vs 71/162 [44%], p=0·025); child-reported improvement was not significant (126/172 [73%] vs 107/162 [66%], p=0·15).
  • Intervention-related adverse events occurred in 12/180 (7%) with AKL-T01 versus 3/168 (2%) with control; there were no serious adverse events or discontinuations. Common AKL-T01-related events were frustration (5/180 [3%]) and headache (3/180 [2%]). AKL-T01 compliance was a mean of 83·2 of 100 sessions (83%; SD 29·2); control use was 480·7 of 500 min (96%).

Methods

  • Randomised, double-blind, parallel-group, controlled trial at 20 US research institutions; 857 children were screened and 348 were randomly assigned 1:1 to AKL-T01 (n=180) or control (n=168). Eligible patients were aged 8–12 years with confirmed ADHD, TOVA API ≤ -1·8, ADHD-RS-IV ≥28, IQ ≥80, and no disorder-related medications; randomisation was stratified by stimulant medication status.
  • AKL-T01 was an investigational digital therapeutic delivered via iPad mini 2, targeting attention and cognitive control through a video game-like interface, instructed for about 25 min/day, 5 days/week for 4 weeks. The control was a digital word game matched for expectancy, engagement, and time on task.
  • Primary outcome was mean change in TOVA API from pre- to post-intervention, analysed in the intention-to-treat population using Wilcoxon rank-sum tests, Hodges-Lehmann estimate, O’Brien-Fleming alpha adjustment, and Cui-Hung-Wang method. Secondary outcomes included IRS, ADHD-RS-IV, CGI-I, and BRIEF.

Limitations

  • The paper states that inclusion required TOVA API ≤ -1·8, excluding many patients with a clinical ADHD diagnosis; children could not take ADHD medication and could not have significant psychiatric comorbidity, limiting generalisability. It also states the 28-day intervention and approximately 25-min daily sessions leave unclear whether other regimens or longer durations would show benefit, that no power calculations were done for secondary or post-hoc outcomes, and that no EEG or mechanistic data were collected.
  • The paper states that results are not sufficient to suggest AKL-T01 should replace established and recommended ADHD treatments, and that transfer to real-world settings, full clinical meaningfulness, and mechanisms require further study.
  • Evident from the text: the control was an active, engaging digital word game, and both groups improved on secondary endpoints; the authors note that expectation of benefit may have contributed to improvements in both groups, and most secondary symptom/impairment comparisons did not differentiate AKL-T01 from control.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s2589-7500(20)30017-0

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The mean (SD) change from baseline on the TOVA API was 0.93 (3.15) in the AKL-T01 group and 0.03 (3.16) in the control group.

    “The mean (SD) change from baseline on the TOVA API was 0•93 (3•15) in the AKL-T01 group and 0•03 (3•16) in the control group”
    Quote in the paperSubstantial claim
  • Findingown data

    Sensitivity analyses showed no evidence that site, baseline TOVA API, age, or sex attenuated the intervention effect.

    “Sensitivity analyses showed no evidence that site, baseline TOVA API, age, or sex attenuated the intervention effect.”
    Quote in the paperNot a substantial claim
  • Findingown data

    IRS responder rates were significantly higher after AKL-T01 versus control (82 [48%] of 171 vs 60 [37%] of 161, p=0.049).

    “IRS responder rates were significantly higher after AKL-T01 versus control (82 [48%] of 171 vs 60 [37%] of 161, p=0•049).”
    Quote in the paperSubstantial claim
  • Findingown data

    AKL-T01 significantly improved performance on the primary outcome measure, the TOVA Attention Performance Index (API), in paediatric patients with ADHD compared with the control condition.

    “In this randomised controlled clinical trial of a digital intervention for ADHD, the active intervention AKL-T01 significantly improved performance on the primary outcome measure-an objective measure of attention (TOVA API) in paediatric patients with ADHD compared with the control condition.”
    • Also stated in: § Table 3: Summary of intervention-emergent adverse events (intentionto-treat population) · boosted
      “It showed that compared to the control condition, AKL-T01 significantly improved objective measures of attention, as measured by the TOVA.”
    Quote in the paperSubstantial claim
  • Findingown data

    AKL-T01 is safe.

    “AKL-T01 is a safe and easy-to-access intervention”
    Quote in the paperSubstantial claim
  • May combine two claims. 39
  • Classified as probably not a substantial claim. 33

  • May combine two claims.

    Findingown data

    Both AKL-T01 and patients in the control group showed significant within-group improvements in all secondary endpoints.

    “Both AKL-T01 and patients in the control group showed significant within-group improvements in all secondary endpoints”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In post-hoc within-group analyses, change in TOVA API score from pre-intervention to post-intervention significantly improved with AKL-T01 (p<0.0001) but not with control (p=0.67).

    “In post-hoc within-group analyses, change in TOVA API score from pre-intervention to post-intervention significantly improved with AKL-T01 (p<0•0001) but not with control (p=0•67).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no intervention-group differences for secondary measures: IRS, ADHD-RS, ADHD-RS-I, ADHD-RS-H, BRIEF-Parent Inhibit and Working Memory and Metacognition (post hoc) from pre-intervention to post-intervention or mean CGI-I score at post-intervention.

    “There were no intervention-group differences for secondary measures: IRS, ADHD-RS, ADHD-RS-I, ADHD-RS-H, BRIEF-Parent Inhibit and Working Memory and Metacognition (post hoc) from pre-intervention to post-intervention or mean CGI-I score at post-intervention”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a significant difference between intervention groups on the primary efficacy endpoint (adjusted p=0.0060); non-parametric estimate of the population median change (Hodges-Lehmann estimate) was 0.88 (95% CI 0.24-1.49).

    “There was a significant difference between intervention groups on the primary efficacy endpoint (adjusted p=0•0060); non-parametric estimate of the population median change (Hodges-Lehmann estimate) was 0•88 (95% CI 0•24-1•49).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All post-hoc t tests were in agreement with corresponding non-parametric Wilcoxon tests with respect to significance for all results reported.

    “All such tests were in agreement with corresponding non-parametric Wilcoxon tests with respect to significance for all results reported.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Of 857 children screened for eligibility, 348 patients were randomly assigned to receive AKL-T01 (n=180) or control (n=168) between July 15, 2016, and Nov 30, 2017.

    “Of 857 children screened for eligibility, 348 patients were randomly assigned to receive AKL-T01 (n=180) or control (n=168) between July 15, 2016, and Nov 30, 2017”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no serious intervention-related AEs or discontinuations due to AEs in either group.

    “There were no serious intervention-related AEs or discontinuations due to AEs in either group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across several secondary outcomes, including parent and clinician ratings of ADHD symptoms and functional impairment, AKL-T01 significantly improved outcomes from pre-intervention to post-intervention, but not to a significantly greater degree than the control condition.

    “Across several secondary outcomes, including parent and clinician ratings of ADHD symptoms and functional impairment, AKL-T01 significantly improved outcomes from pre-intervention to post-intervention, but not to a significantly greater degree than the control condition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All AEs associated with AKL-T01 were classified as mild or moderate in severity and resolved after study discontinuation.

    “All AEs associated with AKL-T01 were classified as mild or moderate in severity and resolved after study discontinuation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no serious adverse events or discontinuations.

    “There were no serious adverse events or discontinuations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this randomised controlled trial, AKL-T01 increased attentional functioning in an objective measure of attention to a significant degree in paediatric patients with ADHD, as well as patient-reported and parent-reported attentional functioning.

    “In this randomised controlled trial, AKL-T01 (an investigational digital therapeutic) increased attentional functioning in an objective measure of attention to a significant degree in paediatric patients with ADHD, as well as patient-reported and parent-reported attentional functioning.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180).

    “Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most common intervention-related AEs associated with AKL-T01 were frustration (5 [3%] of 180) and headache (3 [2%] of 180).

    “The most common interventionrelated AEs associated with AKL-T01 were frustration (5 [3%] of 180) and headache (3 [2%] of 180).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The control was designed to match AKL-T01 on expectancy, engagement, and time on task in the form of a challenging and engaging digital word game, targeting cognitive domains not targeted by the AKL-T01 intervention and not primarily associated with ADHD.

    “The control was designed to match AKL-T01 on expectancy, engagement, and time on task in the form of a challenging and engaging digital word game, targeting cognitive domains not targeted by the AKL-T01 intervention and not primarily associated with ADHD.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Hardy, 2015, Enhancing cognitive abilities with comprehensive training: a large, online, randomized, active-controlled trial, PLoS One source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    A single interim analysis for sample-size re-estimation was prespecified to occur after half of the initial sample size was collected, and done by separate unmasked statistical staff in order to minimise any bias in the conduct of the study.

    “A single interim analysis for sample-size re-estimation was prespecified to occur after half of the initial sample size was collected, and done by separate unmasked statistical staff in order to minimise any bias in the conduct of the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The α criterion for the final analysis of the primary outcome was reduced by means of the O'Brien-Fleming alpha-spending method to 0.0412.

    “The α criterion for the final analysis of the primary outcome was reduced by means of the O'Brien-Fleming alpha-spending method to 0•0412.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Existing treatments have side-effects that limit their acceptability, are only effective when administered, and may not be as effective for reducing daily impairments versus ADHD symptoms.

    “Existing treatments have side-effects that limit their acceptability, 6 are only effective when administered, and may not be as effective for reducing daily impairments versus ADHD symptoms.7”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Toomey, 2012, Why do children with ADHD discontinue their medication?, Clin Pediatr (Phila) source

      Not checked in the free run.

    • cites [7] Weiss, 2018, Relationship between symptomatic and functional improvement and remission in a treatment response to stimulant trial, J Child Adolesc Psychopharmacol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Front-line intervention for ADHD includes pharmacological and non-pharmacological interventions, which have shown short-term efficacy.

    “Front-line intervention for ADHD includes pharmacological and non-pharmacological interventions, which have shown short-term efficacy.[3][4][5]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3][4][5]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Because missing data did not exceed the prespecified limit, sensitivity analyses for missing data were not done.

    “Because missing data did not exceed the prespecified limit, sensitivity analyses for missing data were not done.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The digital intervention described by Anguera and colleagues improved cognitive performance and these changes were associated with functional electroencephalogram (EEG) changes in the prefrontal cortex.

    “The digital intervention improved cognitive performance and these changes were associated with functional electroen cephalogram (EEG) changes in the prefrontal cortex.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Anguera, 2013, Video game training enhances cognitive control in older adults, Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study was done in accordance with the International Conference on Harmonisation Regulations, and was approved by each site's institutional review board.

    “The study was done in accordance with the International Conference on Harmonisation Regulations, and was approved by each site's institutional review board”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Patients in the control group used their intervention 480.7 min of 500 min (96% instructed use).

    “Patients in the control group used their intervention 480•7 min of 500 min (96% instructed use).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    These protocol changes are not expected to have any effect on study outcomes.

    “These changes are not expected to have any effect on study outcomes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ADHD is one of the most commonly diagnosed paediatric mental health disorders, with a prevalence estimated to be 5% worldwide.

    “ADHD is one of the most commonly diagnosed paediatric mental health disorders, with a prevalence estimated to be 5% worldwide, 1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Polanczyk, 2014, ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis, Int J Epidemiol source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Eligible patients were randomly assigned 1:1 to receive AKL-T01 or a control.

    “Eligible patients were randomly assigned 1:1 to receive AKL-T01 or a control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    The TOVA is a validated, computerised, continuous performance test that objectively measures attention and inhibitory control, normalised by age and sex.

    “The TOVA is a validated, computerised, continuous performance test that objectively measures attention and inhibitory control, normalised by age and sex.22”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Leark, 2018

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    STARS-ADHD was a randomised, double-blind, parallel-group, controlled trial done at 20 research institutions in the USA from July 15, 2016, to Nov 30, 2017.

    “STARS-ADHD was a randomised, double-blind, parallelgroup, controlled trial done at 20 research institutions (appendix p 3) in the USA from July 15, 2016, to Nov 30, 2017.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    VeraSci Trials reviewed data for select cognitive and clinical measures to determine quality and consistency within and between measures.

    “VeraSci Trials (formerly NeuroCog Trials) reviewed data for select cognitive and clinical measures to determine quality and consistency within and between measures.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A recent meta-review concluded that a range of digital interventions, including working memory training and neurofeedback, could not be recommended for treatment of ADHD owing to inconsistent findings and generally minimal effects on outcomes provided by independent unmasked observers.

    “a recent meta-review concluded that a range of digital interventions, including working memory training and neurofeedback, could not be recommended for treatment of ADHD owing to inconsistent findings and generally minimal effects on outcomes provided by independent unmasked observers.14”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Hollis, 2017, Annual research review: digital health interventions for children and young people with mental health problems—a systematic and meta-review, J Child Psychol Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    To minimise bias, parents and patients were informed that the study was evaluating the effect of two different investigational interventions for ADHD.

    “To minimise bias, parents and patients were informed that the study was evaluating the effect of two different investigational interventions for ADHD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A prespecified analysis plan governed all analyses, unless identified as post hoc.

    “A prespecified analysis plan governed all analyses, unless identified as post hoc.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The proportions of responders at the end of treatment phase for primary and secondary endpoints were prespecified on the basis of previous studies.

    “The proportions of responders at the end of treatment phase for primary and secondary endpoints were prespecified on the basis of previous studies, 20,24”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Davis, 2018, Proof-of-concept study of an at-home, engaging, digital intervention for pediatric ADHD, PLoS One source

      Not checked in the free run.

    • cites [24] Gordon, 2015, Clinically significant symptom reduction in children with attention-deficit/hyperactivity disorder treated with micronutrients: an open-label reversal design study, J Child Adolesc Psychopharmacol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Prespecified sensitivity analyses of the primary and key secondary endpoints were designed to assess the effects of: cohort, site, age, sex, missing data (if >10% of outcome data were missing), and parent expectancy (secondary endpoints only).

    “Prespecified sensitivity analyses of the primary and key secondary endpoints were designed to assess the effects of: cohort, site, age, sex, missing data (if >10% of outcome data were missing), and parent expectancy (secondary endpoints only).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ADHD exerts a substantial burden on families and society.

    “exerts a substantial burden on families and society. 2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Gupte-Singh, 2017, Economic burden of attention-deficit/hyperactivity disorder among pediatric patients in the United States, Value Health source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All outcomes were analysed in all randomly assigned patients by means of an intention-to-treat methodology.

    “All outcomes were analysed in all randomly assigned patients by means of an intention-to-treat methodology.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Randomisation was stratified by stimulant medication status at screening.

    “Randomisation was stratified by stimulant medication status at screening.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The randomisation scheme was generated by Duke Clinical Research Institute statistics by means of validated computer software-generated pseudorandom numbers.

    “The randomisation scheme was generated by Duke Clinical Research Institute statistics by means of validated computer software-generated pseudorandom numbers.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In general, the quality of digital intervention studies is low, and many do not include a control group.

    “In general, the quality of the studies is low, and many do not include a control group.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Catalá-López, 2017, The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: a systematic review with network meta-analyses of randomised trials, PLoS One source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    TOVA has been cleared by the US Food and Drug Administration (FDA) to facilitate assessment of attention deficits and to evaluate the effects of interventions in ADHD.

    “TOVA has been cleared by the US Food and Drug Administration (FDA) to facilitate assessment of attention deficits and to evaluate the effects of interventions in ADHD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Leark, 2018

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Reported effect sizes for digital interventions are generally small but differ widely with respect to interventions and study designs.

    “Reported effect sizes are generally small but differ widely with respect to interventions and study designs.13”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Cortese, 2015, Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Given these limitations, the results of the current trial are not sufficient to suggest that AKL-T01 should be used as an alternative to established and recommended treatments for ADHD.

    “Given these limitations, the results of the current trial are not sufficient to suggest that AKL-T01 should be used as an alternative to established and recommended treatments for ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Although future research is needed, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events.

    “Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The TOVA is an FDA-cleared device for the objective assessment of attention and inhibitory control as part of an ADHD diagnosis or for monitoring intervention outcomes and has been widely used in both clinical practice and research studies.

    “The TOVA is an FDA-cleared device 23 for the objective assessment of attention and inhibitory control as part of an ADHD diagnosis or for monitoring intervention outcomes and has been widely used in both clinical practice and research studies.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Forbes, 1998, Clinical utility of the Test of Variables of Attention (TOVA) in the diagnosis of attention-deficit/hyperactivity disorder, J Clin Psychol source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    The inclusion criteria required that patients have a TOVA API up to -1.8, thus showing an objective baseline deficit in attentional function.

    “First, the inclusion criteria required that patients have a TOVA API up to -1•8, thus showing an objective baseline deficit in attentional function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The intervention was well tolerated, and this risk-benefit ratio suggests that AKL-T01 could be a novel addition to the range of intervention options for ADHD.

    “The intervention was well tolerated, and this risk-benefit ratio suggests that AKL-T01 could be a novel addition to the range of intervention options for ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In the current trial, despite few group differences on the ADHD-RS, significantly more children in the AKL-T01 group were responders on the IRS, suggesting that this intervention, like other non-pharmacological interventions, may differentially affect impairment versus symptoms.

    “In the current trial, despite there being few group differences on the ADHD-RS, significantly more children in the AKL-T01 group were responders on the IRS, suggesting that this intervention, like other non-pharmacological interventions, may differentially affect impairment versus symptoms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Diagnostic methods modelled after pharmacological randomised controlled trials were used to establish eligibility for the study.

    “Diagnostic methods modelled after pharmacological randomised controlled trials were used to establish eligibility for the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Power analyses were calculated for the primary outcome to power the trial, but no power calculations were done for any of the secondary outcomes or post-hoc analyses.

    “Fourth, power analyses were calculated for our primary outcome to power our trial, but no power calculations were done for any of our secondary outcomes or post-hoc analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Digital interventions have been cited as possible ways to improve otherwise poor access to mental health services.

    “Digital interventions have been cited as possible ways to improve otherwise poor access to mental health services.14”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Hollis, 2017, Annual research review: digital health interventions for children and young people with mental health problems—a systematic and meta-review, J Child Psychol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The study evaluated a 28-day intervention period with approximately 25-min daily sessions; it is unclear if the benefits in attentional functioning might have been observed with a different regimen.

    “Third, the study evaluated a 28-day intervention period with approximately 25-min daily sessions; it is unclear if the benefits in attentional functioning might have been observed with a different regimen.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Attentional processes are specifically linked to relevant clinical outcomes and symptom-based measures (eg, ADHD-RS) do not always correlate highly with measures of functional impairment.

    “We also selected the IRS as a targeted measure of ADHD-related impairment because, as noted previously, attentional processes are specifically linked to relevant clinical outcomes and symptom-based measures (eg, ADHD-RS) and do not always correlate highly with measures of functional impairment.5”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Kollins, 2018, Moving beyond symptom remission to optimize long-term treatment of attention-deficit/hyperactivity disorder, JAMA Pediatr source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Children could not be taking medication for ADHD during the trial and could not have significant psychiatric comorbidity.

    “Second, children could not be taking medication for ADHD during the trial and could not have significant psychiatric comorbidity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The TOVA setting has been described as mimicking one component of the classroom situation in which children are required to remain seated and engaged in a tedious, repetitive task, suggesting ecological validity of the TOVA test for real-world settings in which children with ADHD often struggle.

    “Finally, the TOVA setting has been described as mimicking”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Teicher, 1996, Objective measurement of hyperactivity and attentional problems in ADHD, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    In this study, parents of patients in both groups believed that their child received a novel intervention for ADHD; thus, the expectation of intervention effect can be assumed for both interventions.

    “In our study, parents of patients in both groups believed that their child received a novel intervention for ADHD; thus, the expectation of intervention effect can be assumed for both interventions, and may partially explain improvements in both groups.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The expectation of intervention effect can be assumed for both interventions.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The current study represents a single intervention of 1-month duration, which is quite short.

    “The current study represents a single intervention of 1-month duration, which is quite short.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    AKL-T01's risk-benefit profile is favourable, as only 12 (7%) of 180 patients assigned to AKL-T01 had AEs, compared with rates of 40-60% in trials of commonly used stimulant medications.

    “First, its risk-benefit profile is favourable, as only 12 (7%) of 180 patients assigned to AKL-T01 had AEs, compared with rates of 40-60% in trials of commonly used stimulant medications.26”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Wolraich, 2001, Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder, Pediatrics source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    These steps included having masked raters and clear procedures for minimising discussion between parents and study staff about intervention assignment, and instructing parents and children in both groups who believed that they were receiving an investigational intervention for ADHD.

    “These included having masked raters and clear procedures for minimising discussion between parents and study staff about intervention assignment, and instructing parents and children in both groups who believed that they were receiving an investigational intervention for ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Expectations of efficacy have been shown to moderate intervention effects in general, and also for digital interventions.

    “Second, expectations of efficacy have been shown to moderate intervention effects in general, and also for digital interventions.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Boot, 2013, The pervasive problem with placebos in psychology: why active control groups are not sufficient to rule out placebo effects, Perspect Psychol Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    The digital nature of the intervention could help to increase access for populations who might not otherwise be able to find nonpharmacological interventions.

    “The digital nature of the intervention could help to increase access for populations who might not otherwise be able to find non-pharma cological interventions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Attention performance metrics such as RT mean, RT variability, and ex-Gaussian tau are well-characterised indicators of attention-relevant cognitive processes, and are associated with clinically relevant outcomes including academic behaviour and inattention and social problems.

    “attention performance metrics such as RT mean, RT variability, and ex-Gaussian tau are well characterised indicators of attention-relevant cognitive processes, and are associated with clinically relevant outcomes including academic behaviour 29 and inattention and social problems.30”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] Antonini, 2013, Behavioral correlates of reaction time variability in children with and without ADHD, Neuropsychology source

      Not checked in the free run.

    • cites [30] Abdel-Kader, 2016, Continuous performance task in attention deficit hyperactivity disorder children, Egypt J Neurol Psychiat Neurosurg source

      Not checked in the free run.

60 of 60

  • The paper relies on this without support.

    Pharmacotherapy may not be suitable for some patients due to caregiver preferences or concerns about abuse, misuse, and diversion.

    “Pharmacotherapy may not be suitable for some patients due to caregiver preferences or concerns about abuse, misuse, and diversion.”

  • The paper relies on this without support.

    Digital therapeutics for ADHD may address limitations of existing treatments with improved access, minimal side-effects, and low potential for abuse.

    “Digital therapeutics for ADHD may address these limitations with improved access, minimal side-effects, and low potential for abuse.”

  • The paper relies on this without support.

    Meta-analyses conclude that interventions more broadly targeting cognitive functions generally show larger effects.

    “Nevertheless, meta-analyses conclude that interventions more broadly targeting cognitive functions generally show larger effects.”

  • The paper relies on this without support.

    AKL-T01 is easy-to-access.

    “AKL-T01 is a safe and easy-to-access intervention”

  • The paper relies on this without support.

    AKL-T01 was designed specifically to target cognitive control and attention.

    “First, because AKL-T01 was designed specifically to target cognitive control and attention, we sought an outcome that would most precisely and validly index these processes.”

  • The paper relies on this without support.

    The TOVA API differs from most pharmacological efficacy trials for ADHD, which typically use parent-rated or clinician-rated symptom measures.

    “The primary outcome measure for this trial-the TOVA API-differs from most pharmacological efficacy trials for ADHD, which typically use parent-rated or clinician-rated symptom measures.”

  • The authors state this as an assumption.

    The expectation of intervention effect can be assumed for both interventions.

    “In our study, parents of patients in both groups believed that their child received a novel intervention for ADHD; thus, the expectation of intervention effect can be assumed for both interventions, and may partially explain improvements in both groups.”

  • The paper relies on this without support.

    The foundational study from which the intervention was developed reported that effects of the AKL-T01 prototype were mediated by EEG changes.

    “The foundational study from which the intervention was developed reported that effects of the AKL-T01 prototype were mediated by EEG changes.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a randomized controlled trial of children diagnosed with ADHD funded by the developer, playing EndeavorRX resulted in improved attention compared to a control puzzle or word game.

    “In a randomized controlled trial of children diagnosed with ADHD funded by the developer, playing EndeavorRX resulted in improved attention compared to those who received the control, which was a puzzle or a word game [62].”

    From Health Benefits of Video Games in Adolescents and Young Adults (2026) · cites this paper as [62]

    The Discussion (page unavailable) reports that AKL-T01 improved an objective measure of attention in children with ADHD compared with the control, and the Procedures describe the control as a digital word game. The paper calls the intervention AKL-T01, not EndeavorRX, so our copy does not establish the branded identification. Its funding-source section describes a funder’s role, and the Acknowledgements identify Akili Interactive Labs as funding editorial support, but these passages do not explicitly establish that Akili funded the trial. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The Endeavor trial found that the treatment separated from the control on the primary, objective measure of attention, but not on clinical measures related to ADHD subjective symptoms.

    “The study found that the treatment separated from the control on the primary, objective measure of attention, but not on clinical measures related to ADHD subjective symptoms (27).”

    From Appropriate controls for digital therapeutic clinical trials: A narrative review of control conditions in clinical trials of digital therapeutics (DTx) deploying psychosocial, cognitive, or behavioral content (2022) · cites this paper as [27]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Medication-washout subgroup is called both prespecified and post hoc

    Major

    The discussion describes the medication-washout subgroup finding as prespecified, but the methods explicitly classify the subgroup analysis as post hoc. This changes how the reported secondary-endpoint findings should be interpreted.

1 of 1

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Authors
Kollins, S. H., DeLoss, D. J., Cañadas, E., Lutz, J., Findling, R. L., Keefe, R. S. E., Epstein, J. N., Cutler, A. J., & Faraone, S. V.
Affiliations
  • Duke University (US)
  • Virginia Commonwealth University (US)
  • Duke Medical Center (US)
  • University of Cincinnati (US)
  • Lake Erie College of Osteopathic Medicine (US)
  • SUNY Upstate Medical University (US)
Corresponding author
Kollins, Scott H
ORCID
Venue
The Lancet Digital Health
Publisher
Elsevier BV
Published
2020-04
Volume
2
Issue
4
Pages
e168-e178
ISSN
2589-7500 (ISSN-L)
DOI
10.1016/s2589-7500(20)30017-0
OpenAlex
W3007209283
Cited by
385
References
31
Citations by year
2026: 69 · 2025: 64 · 2024: 62 · 2023: 81 · 2022: 53 · 2021: 45 · 2020: 11
FWCI
34.65
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Digital Health (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Purdue University
  • Sunovion
  • IXICO
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Applied Psychology › Digital Mental Health Interventions
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
digital therapeutics, video game-based intervention, attentional performance, cognitive control, Test of Variables of Attention, children aged 8-12, safety and tolerability, parent-child conflict
MeSH terms
Digital Technology, Attention, Attention Deficit Disorder with Hyperactivity, Behavior Therapy, Child, Cognition, Double-Blind Method, Female, Humans, Male, Pediatrics, Play and Playthings, Severity of Illness Index, Software, Video Games

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

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