Page 100 - Demo

Chapter 498EEG data will be processed offline using the Neurophysiological Biomarker Toolbox,81 an open-source MATLAB toolbox for the computation and integration of neurophysiological biomarkers. With this toolbox, a wide array of resting state parameters can be evaluated including power spectra and coherence and has been applied to neurological clinical studies. The data processing will be performed using MATLAB 7.12.0 software.82DiscussionWith the proposed series of randomized, double-blind N-of-1 trials with open-label extension phase, the effectiveness of CBD on severe behavioral manifestations in TSC, MPS III and FXS will be evaluated. TSC, MPS III and FXS are distinct RGNDs with unique clinical features. They share similarities in terms of their neurological involvement, ID, and behavioral challenges. However, they differ in terms of the underlying genetic variants, disease mechanisms, physical manifestations, and prevalence. It is crucial to note that each condition exhibits a wide range of symptoms and severity. Using a single study protocol for multiple disorders offers advantages such as increased efficiency, larger samples sizes, and comparative analysis opportunities, and can be considered a basket trial.83,84 Especially in rare, complex, and heterogeneous disorders such as these, series of N-of-1 trials enable determination of the treatment effects in individual patients as well as at the group level. In this way, structured and evidence-based treatment decisions can be made for an individual patient at risk for trial and error approach, and cross-over disease comparison together with medical, indepth and mechanistic information will produce generalizable knowledge that can be applied to future patients with RGNDs. N-of-1 studies are recommended in rare genetic disorders when the intervention has a predictable duration of effect and low recruitment rate is expected, like this proposed trial.44 An explanation about the suitability of N-of-1 studies in RGNDs in terms of heterogeneity, personalization, design, outcome measures, and the analyses was provided in a recently published N-of-1 study protocol.44 The N-of-1 approach to estimating population effects may come with a caveat regarding generalizability of the results. To tackle Annelieke Muller sHL.indd 98 14-11-2023 09:07