Page 47 - Demo

N-of-1 studies in rare genetic neurodevelopmental disorders452overall enduring effect on the personal course, including (multiple) baseline, placebo, and follow-up measurements. In this way, disease-modifying treatment options can be investigated, theoretically expecting a more enduring effect on the individual’s natural course for disease-modifying drugs vs a temporary effect for symptomatic drug treatments.Clarify:- Disorder and diagnostic criteria- Baseline characteristics- Target symptom(s)- Eligibility- Concurrent therapies- Comorbid conditionsHeterogeneityConsider to add:- Baseline period- Dose titration period- Run-in period (to ensure blinding, add to comparator period too)- Washout period considering biological and psychological effects- Follow-up measurementDesired number of:- Participants- Periods- Frequency of measurementsChoose several levels of measurement, such as personalized, disorder-specific,biological, or neuropsychologicalDescribe measurement properties, explicitly responsiveness to change, andapplicabilityMinimize burden for (proxy) ratersAcquire multiple data points per periodConsider assessment by multiple raters, in relevant settingsDesignValidityPerform power analysisOutcomemeasuresSubstantiate duration of period based on pharmacokinetics and -dynamicsConsider a measure for generalizationPopulationMethodologyAppropriate number of crossover periods and valid off-periodsTake natural course into accountEnsure optimal engagement with intervention and outcome measures InterventionRationalePerform:- (Non-)parametric analysis- Ancillary analyses- If possible, interim analyses to minimize burden to patient AnalysisComplianceInferenceReliabilityDistinguish disease-modifying and symptomatic interventionElaborate on setting and locationChallenges RecommendationsElaborate on validity regarding the population (including disorder, intellectualdisability, age)Appropriate randomization and sequences ensuring optimal blinding; deliberate onmethods to use for randomizationFigure 4. Challenges and Recommendations for Conducting and Reporting N-of-1 Studies in Rare Genetic Neurodevelopmental Disorders.Annelieke Muller sHL.indd 45 14-11-2023 09:07