Non-inferiority randomized controlled trial of digital therapeutics for children with attention-deficit/hyperactivity disorder

CAI Yuanhao; ZHAO Xi; HAO Wenbi; WANG Yujiao; YUAN Jing; CAI Tengguang; QIAN Yan; XU Tong; ZHOU Lin; LEI Lei

doi:10.11852/zgetbjzz2025-1017

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Chinese Journal of Child Health Care ›› 2026, Vol. 34 ›› Issue (6) : 594-600. DOI: 10.11852/zgetbjzz2025-1017

Special Column on Attention-Dificit/Hyperactivity Disorder

Non-inferiority randomized controlled trial of digital therapeutics for children with attention-deficit/hyperactivity disorder

CAI Yuanhao¹, ZHAO Xi², HAO Wenbi¹, WANG Yujiao³, YUAN Jing¹, CAI Tengguang¹, QIAN Yan¹, XU Tong³, ZHOU Lin¹, LEI Lei¹

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Abstract

Objective To evaluate whether a digital therapy based on non-invasive brain-computer interface is non-inferior to pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD), so as to provide a new non-pharmacological intervention option for ADHD. Methods A non-inferiority randomized controlled trial was conducted.Children diagnosed with ADHD at the pediatric outpatient clinic of Shanghai Changhai Hospital and Shanghai Changzheng Hospital between February 2023 and February 2025 were enrolled and randomly assigned to either a digital therapeutics group or a medication group.The digital therapeutics group completed 30 home-based training sessions over 8 weeks, while the medication group received sustained-release methylphenidate hydrochloride for 8 weeks.The primary outcome was the change in SNAP-Ⅳ total score from baseline to the eighth week (non-inferiority margin Δ=4).Secondary outcomes included changes in the Behavior Rating Inventory of Executive Function (BRIEF), Digital Cancellation Test (DCT), and Questionnaire-Children with Difficulties (QCD). Results A total of 122 participants were enrolled, with 99 completing follow-up (50 in the digital therapeutics group, 49 in the medication group).Analysis of covariance showed that in the full analysis set, the between-group difference in the change of SNAP-Ⅳ total score was 0.26 (95%CI: -1.58 to 2.10), and the lower bound of the 95% confidence interval (-1.58) was above the non-inferiority margin (-4), indicating that digital therapeutics was non-inferior to pharmacological treatment in improving core symptoms of ADHD.Results were consistent in the per-protocol set, with a between-group difference of -0.59 (95%CI: -2.93 to 1.76).No statistically significant differences were observed in secondary outcomes(P＞0.05). Conclusion The digital therapeutics is non-inferior to conventional pharmacological treatment in improving core symptoms of ADHD, with a good compliance and safety profile, and may serve as a potential non-pharmacological intervention or complementary treatment option for ADHD.

Key words

attention-deficit/hyperactivity disorder / digital therapeutics / non-inferiority / neurofeedback / executive function / randomized controlled trial

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CAI Yuanhao, ZHAO Xi, HAO Wenbi, WANG Yujiao, YUAN Jing, CAI Tengguang, QIAN Yan, XU Tong, ZHOU Lin, LEI Lei. Non-inferiority randomized controlled trial of digital therapeutics for children with attention-deficit/hyperactivity disorder[J]. Chinese Journal of Child Health Care. 2026, 34(6): 594-600 https://doi.org/10.11852/zgetbjzz2025-1017

References

[1] Salari N, Ghasemi H, Abdoli N, et al.The global prevalence of ADHD in children and adolescents: A systematic review and meta-analysis[J].Ital J Pediatr, 2023, 49(1):48.
[2] Allan CC, DeShazer M, Staggs VS, et al.Accidental injuries in preschoolers: Are we missing an opportunity for early assessment and intervention?[J].J Pediatr Psychol, 2021, 46(7):835-843.
[3] S Alamri A.Genetic diversity of attention-deficit/hyperactivity disorder[J].Pak J Biol Sci, 2021, 24(8):913-919.
[4] Arnold LE, Hodgkins P, Kahle J, et al.Long-term outcomes of ADHD: Academic achievement and performance[J].J Atten Disord, 2020, 24(1):73-85.
[5] Gagnon M, Sasseville M, Leblanc A.Classification of digital mental health interventions: A rapid review and framework proposal[J].Stud Health Technol Inform, 2022, 294:629-633.
[6] Reynard S, Dias J, Mitic M, et al.Digital interventions for emotion regulation in children and early adolescents: Systematic review and meta-analysis[J].JMIR Serious Games, 2022, 10(3):e31456.
[7] Hollis C, Falconer CJ, Martin JL, et al.Annual research review: Digital health interventions for children and young people with mental health problems -a systematic and meta-review[J].Child Psychol Psychiatry, 2017, 58(4):474-503.
[8] Kollins SH, DeLoss DJ, Cañadas E, et al.A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): A randomised controlled trial[J].Lancet Digit Health, 2020, 2(4):e168-e178.
[9] Pandian GSB, Jain A, Raza Q, et al.Digital health interventions (DHI) for the treatment of attention deficit hyperactivity disorder (ADHD) in children -a comparative review of literature among various treatment and DHI[J].Psychiatry Res, 2021, 297:113742.
[10] Liu X, Yang Y, Ye Z, et al.The effect of digital interventions on attention deficit hyperactivity disorder (ADHD): A meta-analysis of randomized controlled trials[J].Journal Affect Disord, 2024, 365:563-577.
[11] Schulz KF, Altman DG, Moher D.CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials[J].BMJ, 2010, 340:c332.
[12] Storebø OJ, Storm MRO, Pereira Ribeiro J, et al.Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)[J].Cochrane Data Syst Revi, 2023, 3(3):CD009885.
[13] Riggs PD, Winhusen T, Davies RD, et al.Randomized controlled trial of osmotic-release methylphenidate with cognitive-behavioral therapy in adolescents with attention-deficit/hyperactivity disorder and substance use disorders[J].J Am Acad Child Adolesc Psychiatry, 2011, 50(9):903-914.
[14] 国家药品监督管理局药审中心.药物临床试验非劣效设计指导原则[EB/OL].(2020-07-28)[2025-09-02].https://www.cde.org.cn/main/news/viewInfoCommon/322593ac8e690e63730fc63acd1ecba4?sessionid=.
[15] Zhang S, Faries DE, Vowles M, et al.ADHD rating scale Ⅳ: Psychometric properties from a multinational study as clinician-administered instrument[J].Int J Methods Psychiatr Res, 2005, 14(4):186-201.
[16] 赵泽慧, 胡思源, 蔡秋晗, 等.基于选择健康测量工具共识标准评价SNAP-Ⅳ量表测量属性的系统评价[J].中国循证儿科杂志, 2023, 18(3):215-220.
Zhao ZH, Hu SY, Cai QH, et al.Systematic review of SNAP-Ⅳ measurement properties based on COSMIN [J].Chin J Evid Based Pediatr, 2023, 18(3): 215-220.(in Chinese)
[17] Hall CL, Guo B, Valentine AZ, et al.The validity of the SNAP-Ⅳ in children displaying ADHD symptoms[J].Assessment, 2020, 27(6):1258-1271.
[18] 上海数治耀智能科技有限公司.脑乐乐[EB/OL].[移动应用].Apple App Store.[2025-06-08].https://apps.apple.com/hk/app/脑乐乐 /id1615566834.
[19] Pan L, Ru M, Huang Y, et al.Psychometric validation of the SNAP-Ⅳ rating scale in amblyopic children at high AD/HD risk: Structural validity and measurement invariance[J].Front Psychiatry, 2025, 16:1655548.
[20] Tallberg P, Vahlström R, Martí Valls C, et al.Psychometric properties of the Swedish version of the SNAP-Ⅳ rating scale parent form in a birth cohort of 11-year-old children[J].Nord J Psychiatry, 2025, 79(7):503-514.
[21] Pasotti F, Aiello EN, Bollani A, et al.The single-matrix digit cancellation test, a screener for selective attention deficits: Standardization in an Italian population sample and clinical usability in acute stroke patients[J].Cerebrovasc Dis, 2024, 53(1):62-68.
[22] Skogan AH, Zeiner P, Egeland J, et al.Parent ratings of executive function in young preschool children with symptoms of attention-deficit/-hyperactivity disorder[J].Behav Brain Funct, 2015, 11(1):16.
[23] Usami M, Sasayama D, Sugiyama N, et al.The reliability and validity of the Questionnaire-children with/difficulties (QCD)[J].Child Adolesc Psychiatry Ment Health, 2013, 7(1):11.
[24] White IR, Carpenter J, Horton NJ.Including all individuals is not enough: Lessons for intention-to-treat analysis[J].Clin Trials, 2012, 9(4):396-407.
[25] Kofler MJ, Wells EL, Singh LJ, et al.A randomized controlled trial of central executive training (CET) versus inhibitory control training (ICT) for ADHD[J].J Consult Clin Psychol, 2020, 88(8):738-756.
[26] Purper Ouakil D, Blasco Fontecilla H, Ros T, et al.Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial[J].J Child Psychol Psychiatr, 2022, 63(2):187-198.
[27] Van Vyve L, Dierckx B, Lim CG, et al.Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines[J].Eur J Pediatr, 2024, 183(3):1047-1056.
[28] Attention deficit hyperactivity disorder: Diagnosis and management[M].London: National Institute for Health and Care Excellence (NICE), 2019.
[29] Schein J, Cloutier M, Gauthier-Loiselle M, et al.Reasons for treatment changes in children and adolescents with attention-deficit/hyperactivity disorder: A chart review study[J].Adv Ther, 2022, 39(12):5487-5503.
[30] Sibley MH, Bruton AM, Zhao X, et al.Non-pharmacological interventions for attention-deficit hyperactivity disorder in children and adolescents[J].Lancet Child Adolesc Health, 2023, 7(6):415-428.