Page 307 - Demo

Summary / samenvatting30510Millions of people worldwide are affected by a rare genetic neurodevelopmental disorder (RGND). Although individually rare, together these are collectively common, affecting 1-3% of the population. RGNDs are often characterized by complex, multiorgan comorbidity, with neuropsychiatric manifestations and intellectual disability (ID) posing the greatest burden. The lifelong need for care presents challenges for health care professionals when it comes to delivering optimal personalized care, which is the implementation of etiology-driven health monitoring and treatments. This necessitates further research on evidence-based care to improve quality of life of these vulnerable individuals. Advances in translational research has resulted in emerging development of (targeted) therapies, varying from diets, drug-repurposing, to enzyme and gene therapy. Throughout life, many interventions may be applied in individuals with RGNDs and ID, with risk for over- and/or undertreatment. However, evidence for efficacy is often low due to methodological and statistical challenges in these populations, resulting in affected individuals missing out on possibly effective (targeted) treatments.Interventional research is challenging due to the rarity and heterogeneity of the patient populations, but these difficulties are not insurmountable. The N-of-1 design provides a powerful alternative for conventional parallel group randomized controlled trials (RCTs), providing the highest level of evidence. In an N-of-1 study, which is in fact a double-blind RCT requiring less participants, an individual receives multiple blocks of treatment alternated with a comparator (e.g., placebo). This type of research enables investigation of effectiveness of treatments, and addresses the question of inter-individual variability in treatment response.The ultimate goal is to realize evidence-based care for individuals with RGNDs and ID. This requires a methodological framework for trial designs as well as selection of outcome measures that are (clinically) relevant and measure what matters. This thesis discusses the importance and challenges of evidence-based interventions for RGNDs. Part I focusses on N-of-1 studies in RGNDs, starting with providing a methodological framework and recommendations, followed by two study protocols as examples of Annelieke Muller sHL.indd 305 14-11-2023 09:08