Page 64 - Demo

Chapter 362As the population with ID often presents with atypical side effects, a standardized checklist of side effects of MPH40 together with an open interview to capture possible atypical side effects will be used to determine (the number of) side effects including sleeping problems.Study populationThe study population consists of children or adults from the Netherlands with SMS and an ADHD diagnosis established by a multidisciplinary team. Inclusion criteria are a minimum of six years old, a genetically confirmed diagnosis of SMS, and the availability of a caregiver for proxy-reports. Baseline characteristics will be recorded in detail, including age, gender, genetic test results, comorbidity, and medication. Exclusion criteria include presence of a contra-indication for MPH, planned general anesthesia, pregnancy, breastfeeding, current treatment with biologically interfering drugs, substance or alcohol abuse, and incapacity to swallow tablets. The latter may however bias the sample toward a higher functioning segment of SMS. We aim to conduct a patient-centered trial, allowing for a natural setting and flexibility, including the continuation of concurrent therapies such as (for example) sleep medication. Use of concurrent therapies will be recorded.Sample sizeThe sample size calculation was based on a summary measures analysis of the treatment effect as measured with the primary outcome SDQ.41 The difference between the mean SDQ hyperactivity/inattention ratings in MPH periods and placebo periods was used as a summary measure for the treatment effect in an individual subject. The estimated standard deviation (SD) of 2.3 points for single ratings was used based on a reported standard error for the parent-rated SDQ subscale.42 Using a test–retest intraclass correlation coefficient (ICC) of 0.84,43 we decomposed a SD into a withinsubject SD of 0.92 and a between-subject SD of 2.11. Assuming an SD of 1 point for the treatment effect, 95% of the subject-specific treatment effects roughly falls within a range of 4 points. Based on the estimate assuming three cycles with seven daily SDQ ratings within each period, a total of 6 subjects will yield 80% power to detect a mean difference of 1.5 points Annelieke Muller sHL.indd 62 14-11-2023 09:07