Page 72 - Demo

Chapter 370Personalized outcome measures such as GAS and the PQ were chosen to appraise subjective experiences in daily life, enabling quantitative expression of meaningful subjective patient experiences while translating these into evidence.50 Trials tailored to participants by using personalized outcomes may improve treatment adherence as well. Although GAS has not yet been validated and performed in N-of-1 designs nor as an outcome measure in rare genetic disorders with ID, it may be a valuable tool in a complex and heterogeneous population such as SMS. This study will introduce GAS in the N-of-1 design and might be a step towards validation of this personalized outcome measure in rare disorders.Regarding the analysis, a mixed model analysis was selected to analyze the effectiveness of the intervention at the population level, accounting for between-subjects heterogeneity. Ancillary analyses will be performed to evaluate period effects and intrasubject correlation.Limited burden is expected and maximal relevance and treatment adherence is ensured, as an N-of-1 study provides the unique opportunity to tailor interventions and outcomes to individual patients. To optimize compliance, daily questionnaires will be filled out using a user-friendly app and contact moments will mainly take place via digital or telephone calls. Caregivers may experience some burden because of longer withholding of active medication due to one-week washouts to account for eventual psychological effects; this was also the main aberrance from clinical care, necessitating institutional review board (IRB)-approval. On the other hand, every participant is exposed to the active treatment condition and the effect of the individual treatment will be assessed in the best available way, minimizing placebo effects, observer effects, and confirmation biases. After the N-of-1 trial, participants and their representative(s) will be fully informed on the effectiveness of the intervention, allowing shared decision making on future treatment. Participants might thus be particularly motivated to participate in an N-of-1 study due to the existing paucity of evidence and the fact that all subjects will receive an evidence-based assessment of their individual treatment effect.Annelieke Muller sHL.indd 70 14-11-2023 09:07