Sex Differences in Attention Improvements Across Two Clinical Trials of AKL-T01, A Novel Digital Therapeutic for Inattentive Symptoms in Children and Adolescents with ADHD

Objectives Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed and undertreated in girls. One important contributor is the predominance of inattentive symptoms in girls relative to boys. Though less “visible,” inattentive symptoms represent a key driver of impairment, often persisting into adulthood. EndeavorRx (AKL-T01) is a game-based, FDA-authorized digital therapeutic directly targeting inattention. This analysis sought to examine potential sex differences in the efficacy of AKL-T01. Methods We conducted a secondary analysis of clinical outcomes by sex in 326 children and adolescents from two trials of AKL-T01 ( n1 = 180 children; 30.6% female, M age = 9.71; n2 = 146 adolescents; 41.1% female, M age = 14.34). All participants had high inattention per a baseline score ≤ -1.8 on the Test of Variables of Attention (TOVA), a computerized, FDA-cleared continuous performance task objectively measuring attention. Participants used AKL-T01 for 25 minutes/day over 4 weeks. Primary outcomes included change in attention on the TOVA Attention Comparison Score (ACS) and sub-metrics, and change in symptoms on clinician-rated ADHD Rating Scale (ADHD-RS). To evaluate study hypotheses, we conducted a series of t-tests of TOVA and ADHD-RS change scores by sex. Results Across the pooled sample, girls using AKL-T01 demonstrated significantly greater improvements in attention on the TOVA ACS ( M Δ = 2.44) compared to boys ( M Δ = 1.32; t [211.77]) = 2.62, d = .31, p = .009), as well as TOVA reaction time standard score (girls’ M Δ = 13.22; boys’ M Δ = 3.54; t [229.12] = 3.93, d = .46, p <.001). We did not observe sex differences in the 2 other TOVA sub-metrics, nor in ADHD-RS ( p s >.05). There were sex differences in compliance ( t [207.99] = 2.17, d = .26, p = .031), with girls completing more sessions on average ( M = 90.22) compared to boys ( M = 80.19). Conclusions Results suggest that AKL-T01 may be associated with particularly strong improvements to attentional functioning in girls relative to boys. That there were no significant sex differences in ADHD symptom change over the course of treatment in either sex underscores the specificity of these effects to inattention processes rather than broad ADHD symptoms. Limitations include categorization based on binary sex, which may not capture nuances of gender identity. Funding Akili Interactive