Page 287 - Demo

General discussion2859Single-case experimental designs in clinical practiceDespite the urgent call for personalized medicine and the challenges the field of rare disorders is facing with regard to novel treatment options and repurposed medicine, SCEDs have not yet been extensively used in either research or clinical practice.25,26 Researchers might encounter barriers when conducting SCEDs.27 Recently, a formal International Collaborative Network for N-of-1 Trials and Single-Case Designs (ICN) was established to facilitate wider adoption of SCEDs.25 In Chapter 2, the limited use of N-of-1 studies in RGNDs is described with recommendations to enhance methodological quality and generalizability, feasibility, and personalization, which is underlined by an editorial published in the specific journal in which it was published (Neurology).28 For example, sample size calculations for N-of-1 trials are recommended for generalizability purposes, and statistical analyses could properly address inter- and intra-individual variability.29 The use of patient registries, (deep) phenotyping, and longitudinal monitoring could help clarify treatment response, natural course and identify possible biomarkers. Future use of the methodological framework should assist clinicians and researchers to realize the sorely needed personalized evidence-based therapies in both care and research settings. Measuring what matters The importance of outcome measuresEqually important as the study designs are the outcome measures of choice. By selecting outcome measures, both the patient perspective (including relevancy and burden) and methodological perspectives should be thoroughly considered. The question has frequently been raised whether an intervention is truly inferior to a comparator or whether the selected outcome measurement instrument was inappropriately chosen.30 This last issue could be related to relevance, feasibility, acceptability, sensitivity in that specific patient population, and other psychometric properties, such as reliability, validity and responsiveness to change. For example in Fragile X syndrome research, substantial efforts were made to evaluate efficacy of promising targeted treatments, but (human) trials did not demonstrate significant benefits based on the primary outcome measure.31 Despite some promising results on secondary endpoints, these trials were Annelieke Muller sHL.indd 285 14-11-2023 09:08