Page 19 - Demo

General introduction 171Figure 4. Impact of a rare genetic neurodevelopmental disorder on multiple life domains with different treatment targets and choice of outcome measures, based on the International Classification of Functioning and Disability (ICF) framework (World Health Organization).However, in RGNDs, the choice of outcomes is often more complicated compared to more common diseases due to the small number of patients and the heterogeneity of the patient populations. PROMs commonly used in clinical trials do often not include disease-specific symptoms, may not be responsive enough for individuals with ID, and are often solely available as self-report.66,67 Individuals with ID are often not able to report on their condition, and parents and caregivers are asked to complete assessments. Therefore, proxy-friendly measurement instruments, such as mobile apps, are desirable to ensure trial adherence.68 Furthermore, threshold or ceiling effects may be more common when used in these heterogeneous populations, which limits the already small number of patients who are eligible to participate. Additionally, (adult) proxy-report instruments are often not available for the domains of interest or are too broad in scope to be sensitive enough for specific changes in particular disorders, which eventually might limit treatment adherence and acceptability as well. As such, it is suggested that health problems have been underestimated because of excluding more severely affected individuals.69–71Annelieke Muller sHL.indd 17 14-11-2023 09:07