Page 115 - Demo

Outcomes and outcome measurement instruments1135outcomes (PerfOs), well-defined and reliable assessments of affected individuals’ symptoms, overall mental state, or how they function.4,17,18Knowledge about the genetic etiology of GNDs rapidly increases and offers disorder-specific treatment options which can be targeted to the gene, protein, or downstream biological pathway.19 It allows for personalized care, which is the implementation of etiology-drive health monitoring and treatments.20 For neuropsychiatric manifestations, targeted treatments are underway21–24 and guidelines are increasingly available.25However, interventional research in GNDs and ID is challenging. This is due to the rarity, complexity and variability of health manifestations, even among individuals with the same disorder, as well as the heterogeneity in treatment response.26 Other hurdles in these populations include varying cognitive and adaptive abilities, environmental factors, high rate of behavioral and emotional disturbances, a lack of stability, practice effects, and lack of consensus on the best measures within a particular construct.27 Many outcomes have been measured in the past, but assessments of disease severity using clinical rating scales omitted patient perspectives about issues of relevance to their health. Deciding upon an appropriate outcome measure can be a daunting task, taking into account the acceptability and feasibility, and important measurement properties, such as validity, reliability, and responsiveness to change. Noticeably, selection of outcome measures for a study has far-reaching implications. Previous trials that did not demonstrate significant clinical benefits based on the primary endpoints have been deemed ‘negative’ or ‘failed’ even though improvement on secondary endpoints or in clinical subgroups may be present,27 as happened for clinical trials investigating the effects of Arbaclofen in Fragile X syndrome.28,29 As such, inappropriate outcomes or outcome measurement instruments can result in negative results about the effectiveness of interventions, potentially meaning that truly effective treatments do not become available to patients and their families.19,30Annelieke Muller sHL.indd 113 14-11-2023 09:07