Page 43 - Demo

N-of-1 studies in rare genetic neurodevelopmental disorders412Reporting of the N-of-1 Trials Against CENT 2015 CriteriaNone of the studies provided a registration number, name of trial registry, nor information about accessibility of the full trial protocol. Two studies identified the study as (a series of) N-of-1 trials in the title.21,28 The rationale for using an N-of-1 approach was not clarified in any of the studies. Other omissions included the description and measurement properties including validity and reliability of outcome assessment tools, determination of sample size or requirement of the number of periods in a single N-of1 study, and randomization and sequence allocation with a rationale or method. Carryover effects were not addressed, nor were period effects. As for the series, quantitative synthesis of individual data, including subgroup and sensitivity analyses, adjusted analyses, and analyses to determine heterogeneity between participants, were not reported. Moreover, (group) estimated effect sizes and its precision for each primary and secondary outcome were only reported in 2 studies.27,31Strengths of the N-of-1 Studies IdentifiedThe main strengths reported by the studies’ authors included individualcentered evidence-based interventions and the intent to measure personalized and clinically relevant outcomes. Other assets were independence of assessors, control for day-to-day variation in symptoms, and use of subjective as well as objective and biological measures of treatment. Reviewers identified additional strengths that were encountered in some but not all studies: proof of concept in relatively small studies, individual-centered, multiple assessors, inclusion of baseline conditions, (clinically) relevant outcome measures, inclusion of control participants to determine whether effect is specific to the genetic disorder, and the systematic approach.Limitations of the N-of-1 Studies IdentifiedThe authors of the conducted N-of-1 studies reported difficulty with identifying appropriate and validated outcome measures, especially for specific genetic heterogeneous conditions for which outcome measures were often subjective. Reviewers additionally identified unclear measurement properties as a limitation, involving reliability, validity, and responsiveness. Psychological interventions and outcome assessment were vulnerable to bias because of subjectivity, task engagement, and personal attention or interaction. In 1 study, indications for a strong negative caretaker bias of a seemingly already Annelieke Muller sHL.indd 41 14-11-2023 09:07