Statistical analysis
migraine, RS
REGRESSION, DISEASE, MIGRAINE
The presence of a carry-over effect of treatment was tested, before proceeding with any analysis, by performing two-sample t tests on clinical variables and RS FC maps from all study subjects. Since the results of these analyses suggested the presence of a carry-over effect in the ereneumab/placebo sequence (supplementary results), all analyses were limited to data collected during the first 12-week treatment period, using a parallel group-like design.Between-group differences in clinical changes from baseline to week 12 were assessed using the Chi-square or Fisher exact test for categorical variables and ANCOVA models, including baseline value and treatment as covariates, for continuous variables (SAS, version 9.4). The difference in least square mean values was extracted as the measure of treatment effect along with corresponding two-sided 95% Confidence Interval (CI).A propensity score to be used as an independent covariate for statistical analysis of RS FC was created by entering in a logistic regression age, sex, migraine frequency in the 3 months preceding study entry, disease duration and number of previous preventives tried. Average maps of positive RS FC were obtained using scanner-adjusted one-sample t tests, including all time points from all study subjects. Longitudinal RS FC changes within study groups and comparisons of RS FC changes between erenumab and placebo, as well as between responders and non-responders were obtained using propensity score- and scanner-adjusted full factorial models. Results were masked with average maps of positive RS FC within each network. Correlation analyses of longitudinal RS FC changes with patients’ clinical response were run in all migraine patients, and in erenumab and placebo patients, separately, using propensity score- and scanner-adjusted multiple regression models. Results were masked with between-group differences of RS FC changes in the erenumab Average baseline RS FC Z-scores within the main effects of interest of each network were extracted using REX (Primary outcomes were analysed on the full analysis set (FAS), i.e., all patients randomized for study treatment, and on the per-protocol set (PPS), i.e., all patients who completed at least the first 3 months of double-blind treatment with no major protocol violation. Secondary outcomes were analysed only on the PPS population.The analysis protocol of this study was pre-registered with ClinicalTrials.gov, number NCT03977649.