New Methods for Evaluating Preventive Migraine Treatment

Headache intensity rated on a 11-point Numerical Rating Scale (0=no pain; 10=worst pain intensity) measured 28 days before and after each treatment administration.

Total number of moderate/severe headache days will be measured 28 days before and after each treatment administration. Moderate/severe headache days will be recorded by the presence of headache (yes/no), peak pain intensity (mild/moderate/severe), and duration (< 4h or ≥ 4h), as well as acute medication intake and treatment response.

Occurrence of adverse events in each treatment condition recorded by the presence of adverse events ascribed to the treatment, measured using free recall and prompting. For each prompted symptom, participants respond "yes" or "no" and indicate whether they believe the symptom is related to the medication, the migraine attack, or another cause.

Total number of migraine days will be measured 28 days before and after each treatment condition.

The use of acute migraine medication will be recorded, including the specific drug used, number of days and dose.

PANAS will be used to measure positive and negative emotions or feelings pre- and post-treatment of each treatment condition. Positive affectivity refers to positive emotions and expressions. Negative affectivity, on the other hand, refers to negative emotions and expressions. This scale consists of words that describe different emotions and is scored on a Likert Scale ranging from 1 to 5 (1= very slightly or not at all, 2 = little, 3 = moderately, 4 = quite a bit and 5 = extremely).

It is a 14-item measure designed to assess anxiety and depression symptoms. It is rated on a 4-point Likert scale. It will be measured pre- and post-treatment of each treatment condition.

Short-form-12 (SF-12) is a self-reported outcome measure assessing the impact of health on an individual's everyday life. It consists of two components- physical (PCS-12) and mental (MCS-12). The summary scores are scored using norm-based scoring, where means of 50 and standard deviations of 10 are achieved.

Headache impact test (HIT-6) measures the impact that headache has on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It consists of 6 questions. Each question can be answered with 5 responses (never, rarely, sometimes, very often, or always), which has the following numerical values (6, 8, 10, 11, and 13, respectively).

Intensity of the experienced adverse events will be measured on a 11-point Numerical Rating Scale (e.g., "To what extent have you been feeling fatigue/dizziness?"; 0=not at all; 10=worst imaginable)

At the end of each treatment condition, participants indicate which treatment they believe to have received (fremanezumab or placebo), how certain they are on an 11-point NRS (0 = not at all certain, 10 = completely certain), and the reasons for this response (e.g., adverse events, symptom relief, characteristics of the injection, or other reasons). After completion of all four treatment conditions, participants complete a single, retrospective assessment indicating which treatment they preferred overall. Participants are also asked to briefly describe the reasons for their preference.

This parameter is measured as a predictor using four 11-point NRS scales: expected headache intensity ("How intense do you expect your headache to be during the coming week?"; 0 = no pain, 10 = worst imaginable), expected improvement (0 = none, 10 = greatest possible), expected worsening (0 = none, 10 = greatest possible), and expected adverse events ("To what extent do you expect symptoms/adverse effects?"; 0 = not at all, 10 = greatest possible).

Pre-treatment ratings reflect general expectations for the next 7 days. Post-treatment ratings use the same items but refer to expectations as a result of the received treatment. Immediately after each treatment, expectations are also assessed with the same four scales, focusing on the coming 28 days in relation to that treatment.

This parameter is measured as a predictor. Desire for headache relief is assessed using an 11-point ("How strong is your desire for headache relief from the treatment"; 0 = no desire, 10 = strongest possible desire).