Page 39 - Demo

N-of-1 studies in rare genetic neurodevelopmental disorders372demarcations in targeting the possibly underlying mechanisms. Concurrent therapies were mentioned in 7 studies.Methodological CharacteristicsThere was a wide variety of methodological approaches in the reviewed studies with great variation in number of periods and trial conditions and duration of the interventional period (Table 3). Only 1 study included a washout period, and 1 study a run-in. Randomization was applied in 7 studies. None of those that did randomize explicitly specified the method of randomization. Seven studies were double blinded, 2 single blinded, and 4 were not blinded. The main comparator used was placebo followed by no intervention, with some studies applying a combination of several comparators. Graphical or tabular analyses were most often used to assess treatment effects. In 4 studies, (non)parametric statistical analyses were performed.Outcome Measures and Evaluation MethodsIn 9 studies, a primary outcome measure was present and predefined, although only 3 studies explicitly used the term primary outcome measure. Generally, outcome measures were targeted at behavioral and cognitive improvements (Table 2). The evaluation methods used were diverse, varying from validated questionnaires to self-designed scoring lists. Only in myoclonus-dystonia syndrome, condition-specific rating scales were used.29 Once, a quality of life assessment was used.28 In 4 studies, biological plasma measurements were assessed to confirm an appropriate blood level of either the supplement or diet. None of the studies included generalization measures. Mostly, outcomes were assessed by caregivers and to a lesser degree by investigators.Main Results and Adverse EventsNeither the supplement nor diet interventions revealed significant positive results, whereas results of drug interventions varied and nondrug interventional studies all reported positive effects, though not substantiated with statistical analysis. One study had to be prematurely discontinued due to unexpected adverse events to the study drug (ecopipam)30; the authors concluded that a run-in period would probably have prevented this.Annelieke Muller sHL.indd 37 14-11-2023 09:07