China Headache and Vertigo Registry Study

Migraine attack is defined as any consistent migraine attacks or the use of specific migraine drugs. If a migraine attack is interrupted by sleep, or temporarily relieved, and then relapses within 48 hours, it is considered an attack. In addition, migraine attacks that were successfully treated with drugs but relapsed within 48 hours and lasted for more than 48 hours were counted as one attack.

The response rate is calculated as the percentage reduction in the frequency of migraine attacks (or days of migraine, or days of moderate or severe headache) compared with the baseline during each treatment period. The response rate is traditionally defined as a reduction of at least 50% from the baseline, but other percentage reductions (for example: 30%, 75%, 100%) may be used.

Four-point rating scale was used to evaluate the headache intensity of each migraine day--painless, mild, moderate, or severe. Migraine intensity is not recommended as the main outcome measure alone, but it is important to record the decrease in migraine intensity as an indicator of disability reduction.

Depending on the design of the trial, subjects should be asked to record the intensity of each migraine. In addition, the 11 point visual rating scale (VAS) can be used instead or in combination with the 4-level classification rating scale. The use of VAS in clinical trials may increase the likelihood of showing differences in severity.

The cumulative number of hours of moderate / severe pain calculated by electronic headache diaries. If an attack occurs before going to bed and when you wake up, the amount of sleep also counts as the number of headache hours.

Defined as the number of days without aura, prodromal symptoms, headaches, pain and subsequent symptoms. It needs to be determined by headache diary.

The number of days without headache also includes the number of days without related symptoms directly caused by migraine (including physical function, cognitive or emotional disorders).

Subjects should record the maximum intensity of daily headaches and any medication used. An 11-point digital rating scale can be used instead of or in conjunction with a 4-level classified rating scale.

An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The allowed medications include the following categories of drugs: triptans, ergots, opioids, analgesics (including acetaminophen), NSAIDs (including aspirin), and antiemetics.

The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment. Participants are asked to rate the level of difficulty experienced in the past 24 hours with performance of daily activities (ie, difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities) and physical impairment (ie, difficulty walking, moving body, bending forward, moving head) using a 6-point rating scale

Four items based on a 24-hour recall will be administered daily using Headache and Non-Headache versions as additional health outcome measures and for evaluation of the AIM-D.

The first item will be used to assess difficulty in concentrating with 6 responses ranging from "Not difficult at all" to "Extremely difficult" and an option of "I could not do it at all." The second item will be used to assess difficulty in thinking clearly with 6 responses ranging from "Not difficult at all" to "Extremely difficult" and an option of "I could not do it at all." The third item will be used to assess activity level within the past 24 hours with a 5-level response ranging from "No activity - Spent all day lying down" to "Exercised - Brisk walk, running, jogging, biking or other activity for 30 or more minutes." The fourth item will be used to evaluate activity limitation with a 5-level response ranging from "Not at all limited - I could do everything" to "Extremely limited."

The HIT-6 is a 6-question assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home, and in social situations. It assesses the effect that headaches have on normal daily life and the participant's ability to function.

Responses are based on frequency using a 5-point scale ranging from "never" to "always." The HIT-6 total score, which ranges from 36 to 78, is the sum of the responses - each of which is assigned a score ranging from 6 points (never) to 13 points (always).

The MIDAS is a 7-item questionnaire designed to quantify headache-related disability over a 3- month period. The MIDAS score is the sum of missed work or school days, days at work or school plus days of household work where productivity was reduced by half or more, missed household work days, and missed non-work activity days due to headaches in the last 3 months.

The PGIC is a single item questionnaire used to measure the participant's impression of overall change in migraine since the first dose of study medication. The measure uses a 7-point rating scale with responses ranging from "very much better" to "very much worse."

The WPAI:MIGRAINE will be used to assess work productivity specific to migraine. The measure uses a 1-week recall and contains 6 questions related to work productivity. The WPAI measures both presenteeism and absenteeism. The measure yields four scores expressed as impairment percentages ranging from 0 to 100%: Percent work time missed, percent impairment while working, percent overall work impairment, and percent activity impairment due to migraine.

EQ-5D-5L is a generic instrument for use as a measure of health status. The EQ-5D-5L consists of 2 components - the EQ-5D descriptive system and the EQ VAS. The descriptive system comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.

The scoring range of the EQ-5D descriptive system is typically from 0 (dead) to 1 (full health).

The EQ VAS records the respondent's self-rated health on a vertical, VAS where the endpoints are labelled "Best imaginable health state" and "Worst imaginable health state." The scoring range of the EQ VAS is from 0 (worst imaginable health) to 100 (best imaginable health).

The PGI-S is a single item questionnaire used to measure the participant's impression of severity in relation to migraine symptoms overall at the time of administration of the measure. The measure uses a 5-point rating scale with responses ranging from "none" to "very severe."

The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality-of-life impairments attributed to migraine in the past 4 weeks. It is divided into 3 domains: Role Function Restrictive assesses how migraines limit one's daily social and work-related activities; Role Function Preventive assesses how migraines prevent these activities; and the Emotional Function domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale ranging from "none of the time" to "all of the time." Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life.

The PROMIS-PI measures self-reported interference of pain on relevant aspects of daily life (ie, social, cognitive, emotional, physical, recreational) over the past 7 days. A 5-level response scale for all six items ranges from "Not at all" to "Very much." Scores range from 6 to 30, with higher scores indicating greater pain interference.

Suicidal ideation should be monitored in trials of central action drugs, higher scores mean a worse outcome.

Many migraine clinical trials used the Columbia suicide severity scale (C SSRS).The C-SSRS consists of a maximum of 20 items. C-SSRS will be administered in study subjects at each study visit to assess possible suicidal ideation and behavior. Reports of suicidal ideation with intent to act (endorse item 4 or 5) and reports of actual, aborted, or interrupted suicide attempts or a behavior preparatory for making an attempt indicate subjects at high risk for suicide.

GAD-7 is a proven, self-administered and concise tool for screening and diagnosing mental health disorders, which has been tested in the field in office practice. The screening scale is easy to use and can be completed in a short time, which improves the recognition rate of anxiety disorders and facilitates diagnosis and treatment. The main statistical index of this scale is the total score, that is, the sum of item scores. The total score range of GAD-7 is 0: 21 and that of GAD-2 is 0: 6. The score of GAD-7 can be used to evaluate the severity of anxiety symptoms: 0: 4: no clinical significance: anxiety: 5: 9: mild; 10: 14: moderate; > 15: severe. When used as an assistant diagnosis of anxiety symptoms, the cut-off value of GAD-7 is greater than or equal to 10.

Functional impairment scale (FIS) is a 4-point scale to evaluate the functional status and injury intensity in daily activities. It can be used in conjunction with the four-point pain intensity scale, usually done daily and summarized within four weeks.

Migraine physiological function influence diary (MPFID) assessed the effect of migraine time during and between attacks on daily behavior and work.

Blood samples will be collected from all participants who consent to participate in the substudy, for the purposes for future biomedical research, such as biomarkers of primary headache, such as inflammatory cytokines, neuropeptides and proteins.

Subjective AEs will be collected from the time of consent through the last visit. For all AEs, the investigator must provide an assessment of the severity, causal relationship to the investigational product, start and stop date, and seriousness of the event (eg, SAE), document all actions taken with regard to the investigational product, and detail any other treatment measures taken for the AE. For events noted as SAEs, Allergan must be notified immediately to meet their reporting obligations to appropriate regulatory authorities. Number of participants with treatment-related adverse events are assessed by CTCAE v4.0

A complete physical examination (PE) per standard of care (including neurological exam) will be performed on all subjects. Any clinically significant anomalies noted during the initial screening phase are to be detailed in the Medical History CRF. Investigators are to check for any findings that would constitute study exclusion.

A review of medical and medication history will be performed at initial screening to confirm subject eligibility. Targeted medical history is to be recorded in the Neurologic Medical History CRF and Cardiovascular Medical History CRF, and other medical history is to be recorded in the General Medical History CRF. Source notes for subjects referred to the research site must include all of the above information.

The following measurements are to be performed: height (initial screening only) and weight. Height and weight are to be measured without shoes. Body Mass Index (BMI) should be calculated using the following formula: BMI (kg/m2

• = weight (kg)/[height (cm)/100]2

All measurements are to be recorded on the Physical Measurements CRF.

Blood samples will be collected from all participants who consent to participate in the substudy, for the purposes for genetic analysis of familial headache and vertigo.disease.