Sample size estimation
migraine, RS
MIGRAINE
At the time of the study design, no data were available to estimate the effect size for the primary endpoints of the study. Moreover, there were no data regarding a possible carryover effect and its duration upon discontinuation of erenumab (or placebo) on RS FC changes after 3 months of treatment. The sample size calculation for this study was therefore based on the conservative assumption that a relevant carry-over effect was present. As described in literature [Based on these scenarios, the sample size of 100 evaluable patients, 50 per treatment group, was chosen as the one which allowed solid results in each subgroup analysis. Considering observing at least a 15% of non-evaluable patients (i.e., fMRI not evaluable or dropout patient), 120 randomized are needed to obtain 100 evaluable patients. The target sample size for this study was therefore 120 patients randomized. In order to obtain 120 randomized patients, about 140 patients were to be screened.However, due to the COVID-19 pandemic, the study was interrupted balancing the number of available enrolled patients. In fact, the number of 60 randomized patients, 30 per group, guarantees a sufficient level of precision. In detail, considering the evaluation of the difference between treatment groups, about 25 patients are needed to detect a difference between treatment groups of 0.5%, with an intrasubject variability σW of 0.75%, a between-patient variability σB of 0.5%, a power of 90% and an alpha level of 0.002.With regards to the evaluation of whether the changes of the endpoint are different between the two groups of clinical response within treatment groups: (a) in the erenumab group, considering a percentage of clinical responders of about 30% in migraine patients with previous treatment failure [