Page 48 - Demo

Chapter 246To substantiate the duration of the interventional period, pharmacokinetics and dosage should be taken into full consideration. Dosage should be based on factors such as half-life time, age, weight, and daily timing. Both low dosages and high dosages without a run-in period can result in dropout and lack of efficacy.21,30 Multiple dosages might be considered by implementing an ABC design or adjusting dosages after interim analyses.To minimize carryover and side effects, addition of a run-in and/or washout period is preferred.40,41 In addition to biological carryover effects based on half-life time of drugs, psychological carryover effects for the patient as well as proxies should be considered, such as relief of parental stress after a period with an effective intervention. A baseline condition to observe natural behavior without any intervention and a follow-up will add internal validity and information about the effectiveness and tolerability of an intervention.To gauge the robustness of methods chosen for randomization and sequence allocation, this should be thoroughly described, such as steps taken to conceal the sequence, information about who generated the sequence, who enrolled participants, and who assigned them to interventions. Various randomization and implementation methods may be appropriate depending on the condition and design.40 Interpretation of observed effects becomes problematic with randomization when outcomes unexpectedly or progressively deteriorate or improve.6 Counterbalancing can be used to systematically alternate the treatment order (such as ABBA instead of AABA or AABB) so that neither treatment suffers a worse fate than the other.42In terms of personalized care, included studies were commendable by tailoring interventions to patient or caregiver needs, thus ensuring relevance and optimizing treatment adherence. Outcome measures included objective and biological outcomes, validated symptom checklists, neuropsychological assessments, or personalized outcomes. Preferably, all types are included to optimize pathophysiologic insights as well as relevance to the patient. Feasibility of N-of-1 studies in these vulnerable patients was questioned in 4 studies. As an N-of-1 study might be time and effort consuming for several stakeholders involved in the study because Annelieke Muller sHL.indd 46 14-11-2023 09:07