Page 49 - Demo

N-of-1 studies in rare genetic neurodevelopmental disorders472of frequent recording of data points enabling multiple measurements, and the number of periods and duration of the trial, increasing treatment adherence should be prioritized. To foster treatment and trial adherence, patient involvement on the intervention, design, and outcome measures appears to greatly contribute to the experienced relevancy and enthusiasm of participants.43 However, this might strengthen potential placebo effects. As participants with ID can often not report on their clinical condition, this places a demand on parents and caregivers. Proxy-friendly assessment tools are required to ensure trial compliance.Targeting behavioral outcomes in patients with rare disorders and varying levels of cognitive functioning is complex as appropriate outcome measures are limited and often lack validity.44 Hence, interpretation of efficacy is hampered leading to disappointing results of disorder-specific interventional studies. This underlines the need for more sensitive and disorder-specific evaluation strategies, such as the phenylketonuria–quality of life (PKU-QOL) questionnaire.45 For outcomes, the property responsiveness to change is essential in measuring the effectiveness of interventions but is often unknown. Of the included studies that used existing rating scales, responsiveness to change was discussed for Dementia Care Mapping, the Vineland Adaptive Behavior Scale, and the Behavior Problems Inventory.46–48 Of interest to heterogeneous populations with ID is the recently introduced NIH battery of neuropsychological assessments, which is increasingly validated.49As patients with rare genetic neurodevelopmental disorders comprise a vulnerable patient group often affected by severe comorbidity and complex environmental factors, there is a great need for personalized and disorderspecific outcome measures. This was also indicated by the frequent use of self-designed outcome measures in the included studies. Instruments such as patient-reported outcome measures,44,50 Goal Attainment Scaling,51 or experience-sampling methods52 may be considered, enabling quantitative expression of meaningful subjective patient experiences while translating these into evidence.43 As personalized outcome measures may compromise generalizability, inclusion of generalization measures can provide information on transfer effects of the intervention to other Annelieke Muller sHL.indd 47 14-11-2023 09:07