Statistical analysis plan for the feasibility trial assessing external trigeminal nerve stimulation versus sham stimulation for ADHD in children and adolescents aged 7 to 17 years (the eTNS4ADHD trial)

Abstract Background: External trigeminal nerve stimulation (eTNS) is a non-invasive intervention being investigated as a potential treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. The eTNS4ADHD trial aims to assess the feasibility of conducting a larger randomised clinical trial comparing active eTNS with sham stimulation. This paper presents the prespecified statistical analysis plan for the trial. Methods: The eTNS4ADHD trial is a multicentre, parallel-group, randomised pilot and feasibility trial involving children and adolescents aged 7 to 17 years with ADHD. Participants are allocated to four weeks of active eTNS or sham stimulation. Feasibility outcomes include recruitment, treatment compliance, acceptability, follow-up completion, and concomitant treatment use. Exploratory clinical outcomes include ADHD symptoms, school absence, emotional lability, functional impairment, quality of life, sleep quality, and adverse events. All analyses will follow the intention-to-treat principle. Feasibility outcomes will primarily be assessed using proportions with 95% confidence intervals, while exploratory clinical outcomes will be analysed using regression models or non-parametric methods, as appropriate. Two independent statisticians blinded to treatment allocation will conduct the analyses, and blinded conclusions will be prepared before unblinding. Discussion: This statistical analysis plan was finalised before unblinding to promote transparency and minimise the risk of selective analyses and reporting. Given the feasibility design and limited statistical power, exploratory clinical findings will be considered hypothesis-generating rather than confirmatory. The results will inform the feasibility, outcome selection, sample size estimation, and statistical methodology of a future definitive randomised clinical trial evaluating eTNS for ADHD in children and adolescents. Trial registration: ClinicalTrials.gov, NCT06655610 .