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Methylphenidate for ADHD in Smith-Magenis syndrome693interpretation and generalizability. Also, we will elaborate on setting and location as assessments will be in the participant’s natural environment.Regarding this symptomatic pharmacological intervention, we chose to add a baseline period. This period allows us to observe the behavior in a non-clinical trial setting and to take the natural course of ADHD symptoms into account. Moreover, to ensure optimal efficacy, tolerability and hence compliance, the highest dosage without side effects will be chosen based on the dose titration phase.As for the design, the number of participants and crossover periods to detect a clinically relevant treatment effect was selected based on a power analysis, providing the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder.41 These are needed when intending to provide estimates of the treatment effect at a population level. Duration of periods was based on the pharmacokinetics and -dynamics of MPH. Although no washout period would suffice pharmacologically, one-week washouts were chosen to account for prolonged psychological effects and for planning purposes.To pursue optimal generalizability to the entire SMS population, it is of great importance that outcome measures are validated for the patient population and sensitive to change. Multiple data points per period will be acquired to enable estimation of between and within-period variances. To increase the study’s validity, each interventional period includes at least five measurements of the target symptoms, by using the subscale of the SDQ.26,49 Several other domains of measurement were chosen, such as sleep quality and personalized measurements. GAS also allows for capturing goals in reduction of caregiver stress, as reduction in symptoms may have benefit for family as well. The EDI will also serve as a generalization measure to evaluate transfer effects of the intervention to a broader domain of functioning. Generalization measures are dependent variables that are taken in addition to the target behavior that are used to evaluate whether an intervention generalizes to other behaviors or settings.39 A shortened version and a subscale of two outcome measures were selected to minimize assessor’s burden.Annelieke Muller sHL.indd 69 14-11-2023 09:07