Evaluation of the Reliability of Effect of Rimegepant for the Acute Treatment of Migraine Across Multiple Attacks
Conditions: Migraine Disorders
Sponsor: Pfizer

Rimegepant
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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Evaluation of the reliability of effect of rimegepant or 
triptans for the acute treatment of migraine across 
multiple attacks 
Protocol number
C4951066
Protocol version identifier
Final, V2.0 (amendment 1)
Date
23 April 2024
Active substance
Analgesics, calcitonin gene-related peptide (CGRP) 
antagonists. ATC code: N02CD06
Medicinal product
Rimegepant (Nurtec 75mg ODT)
Research question and 
objectives
The objectives of this study are to 1) explore reliability 
of effect with acute use of rimegepant or triptans; 2) 
evaluate satisfaction with rimegepant or triptans; 3)
evaluate willingness to continue using rimegepant or
triptans; 4) explore proportion optimized on treatment 
with rimegepant or triptans.
Research questions:
1. What is the reliability of effect of rimegepant or
triptans in the real world over multiple migraine
attacks when taken PRN?
2. How satisfied are patients with rimegepant ortriptans
to treat their migraine attacks?
3. How willing are patients to continue taking
rimegepant or triptans to treat their migraine attacks?
4. What proportion of those treating acutely with
rimegepant or triptans are adequately responding and
well managed?
5. When do patients administer rimegepant or triptans
when treating an acute attack?
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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................3
2. LIST OF ABBREVIATIONS................................................................................................5
3. RESPONSIBLE PARTIES....................................................................................................7
4. ABSTRACT...........................................................................................................................8
AMENDMENTS AND UPDATES...........................................................................................9
5. MILESTONES.....................................................................................................................10
6. RATIONALE AND BACKGROUND................................................................................11
7. RESEARCH QUESTION AND OBJECTIVES .................................................................12
8. RESEARCH METHODS ....................................................................................................13
8.1. Study Design ...........................................................................................................13
8.2. Setting......................................................................................................................13
8.2.1. Inclusion Criteria ........................................................................................15
8.2.2. Exclusion Criteria.......................................................................................15
8.3. Variables..................................................................................................................15
8.4. Data Sources............................................................................................................22
8.5. Study Size................................................................................................................22
8.6. Data Analysis ..........................................................................................................22
8.6.1. Analysis Plan for Describing Patients with Migraine Receiving 
Rimegepant or Triptans PRN...........................................................................23
8.6.2. Analysis Plan for Objective 1.....................................................................27
8.6.3. Analysis for Objective 2 .............................................................................28
8.6.4. Analysis for Objective 3.............................................................................29
8.6.5. Analysis for Objective 4.............................................................................30
8.7. Quality Control........................................................................................................30
8.8. Limitations of the Research Methods......................................................................30
8.9. Other Aspects ..........................................................................................................31
9. PROTECTION OF HUMAN PARTICIPANTS .................................................................32
9.1. Patient Information and Consent.............................................................................32
9.2. Ethical Conduct of the Study ..................................................................................32
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10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................32
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........33
12. REFERENCES ..................................................................................................................34
13. LIST OF TABLES.............................................................................................................36
14. LIST OF FIGURES ...........................................................................................................36
ANNEX 1. LIST OF STANDALONE DOCUMENTS ..........................................................36
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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
Adverse Event
AIDS/HIV
Acquired Immunodeficiency Syndrome/Human 
Immunodeficiency Virus
ARW
Adelphi Real World
BMI
Body Mass Index
CGRP
Calcitonin Gene-related Peptide
CM
Chronic Migraine
COVID-19
Coronavirus Disease 2019
CV
Cardiovascular
DSP
Disease Specific Programme™
EC
Ethics Committee
ED
Emergency Department
EM
Episodic Migraine
EMA
European Medicines Agency
EphMRA
European Pharmaceutical Market Research 
Association
GI
Gastrointestinal
IBM
International Business Machines Corporation
IBS
Irritable Bowel Syndrome
ICJME
International Committee of Medical Journal Editors
ICSR
Individual Case Safety Reports
IRB
Institutional Review Board
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Abbreviation
Definition
MHD
Monthly Headache Day
MMD
Monthly Migraine Day
m-TOQ6
Migraine Treatment Optimization Questionnaire
NASH
Nonalcoholic Steatohepatitis
NSAIDs
Non-steroidal Anti-inflammatory Drugs
ODT
Orally Disintegrating Tablet
PCP
Primary Care Physician
PRF
Patient Record Form
PRN
Pro Re Nata
PRO
Patient-reported Outcome
PSC
Patient Self Completion
QoL
Quality of Life
RWD
Real World Data
Rx
Prescription
SAP
Statistical Analysis Plan
SD
Standard Deviation
SPSS
Statistical Package for the Social Sciences
SUNCT
Short-lasting, Unilateral, Neuralgiform headache 
attacks with Conjunctival injection and Tearing
TIA
Transient Ischemic Attack
US
United States of America
YLD
Years Lived with Disability
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Ri me ge pa nt
C 4 9 5 1 0 6 6 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
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3. R E S P O N SI B L E P A R TI E S
Pri nci p al I n vesti g at or (s) of t he Pr ot oc o l
N a m e, D e gree(s)
J o b Title
Affili ati o n
A d dress
0 9 0 1 7 7 e 1 a 0 8 d 5 d df\ A p pr o v e d\ A p pr o v e d O n: 1 0- M a y- 2 0 2 4 1 4: 3 2 ( G M T)
P P D

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4. ABSTRACT
Stand alone document.
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AMENDMENTS AND UPDATES
Amendment 1
This amendment is to add a descriptive analysis of triptans compared to rimegepant for the 
acute treatment of migraine attacks.
Version 
Identifier
Date
Amendment Type 
(substantial or 
administrative)
Protocol Section(s) 
Changed
Summary of 
Amendment(s)
Reason
Version 2.0
23 April 
2024
Administrative
3. Responsible 
parties
PIs updated
Clinical 
scientist 
joined the 
team, and 
changes to 
vendor
team
Version 2.0
23 April 
2024
Administrative
6. Milestones
Timelines for 
additional analyses 
& reporting added
Provide 
data for 
China 
NRDL 
submission
Version 2.0
23 April 
2024
Substantial
8 – Research 
Objectives
9.2 Setting
9.2.1 Inclusion 
criteria
9.2.2 Exclusion 
criteria
9.3 Variables
9.6 Data analysis
9.6.1 Analysis Plan
9.6.2 Analysis Plan
for Objective 1
9.6.3 Analysis Plan
for Objective 2
9.6.4 Analysis Plan
for Objective 3
9.6.5 Analysis Plan
for Objective 4
Addition of triptans 
as treatment of 
interest.  For
descriptive analysis 
only.
Provide 
data for 
China 
NRDL 
submission
Version 2.0
23 April 
2024
Substantial
9.5 Study size
Sample size 
updated to include 
triptan population.
Provide 
data for 
China 
NRDL 
submission
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5. MILESTONES
Milestone
Planned Date
Protocol/SAP (Version 1.0)
7 Dec 2023
Data collection started (Version 1.0)
2 Jan 2024
Data collection completed (Version 1.0)
3 Jan 2024
Final study tables (Version 1.0)
29 Jan 2024
Protocol/SAP (amendment V.1.)
23 Apr 2024
Final study tables (Phase V1.1)
30 April 2024
Final report
02 Dec 2024
Abstract 1
17 Feb 2024
Abstract 2
17 May 2024
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6. RATIONALE AND BACKGROUND
Migraine is a common, often disabling neurologic disease characterized by recurrent attacks 
of head pain that are typically unilateral, throbbing, and associated with a range of symptoms 
that may include photophobia, phonophobia, nausea, and vomiting.1-3 Migraine can be 
classified as episodic or chronic based on the frequency of the migraine or headache: 
episodic migraine (EM) is characterized by one to 14 monthly headache days (MHDs) or 
monthly migraine days (MMDs), while chronic migraine (CM) is characterized by 15 or 
more MHDs for at least three months, with at least eight days a month on which the 
headaches and associated symptoms meet diagnostic criteria for migraine.1,3,4 Migraine is a 
clinically complex disorder, and in addition to its direct clinical burden, patients experience a 
greater number of comorbidities compared to those without migraine.5
In 2019, an estimated 1.1 billion people in the world suffered from migraine, causing 
42.1 million years lived with disability (YLD).6 Women are two to three times more likely 
than men to be affected by migraine.7-9 The global age-standardized prevalence of migraine 
was 14.1% in 2019, which is an increase of 1.7% since 1990. There were 87.6 million 
incident cases of migraine globally in 2019, resulting in an incidence of 11.4%, which was an 
increase of 2.1% since 1990.6
In the US, migraine accounted for $36 billion in both direct and indirect costs in 2016.10 The 
three most common locations for migraine care are primary care, neurologist, and emergency 
department (ED) settings, with approximately 1.2 million ED visits in the US annually due to 
migraine attacks.11 Indirect costs related to work productivity impairment are commonly 
incurred in patients with migraine, with presenteeism accounting for the majority of work-
related productivity loss.12,13 Annual costs due to migraine-related lost productivity in the US 
were estimated at $2.1 million for the manufacturing sector and $2.9 million for the service 
sector (per 10,000 individuals).14 Patients with refractory migraine have higher mean annual 
frequency of outpatient visits, ED visits and admissions, and a higher intensity of care vs. 
patients with migraine and those without migraine.15
While treatment goals vary by region, guidelines from both the US and France (the most 
recently published treatment goals in Europe) for acute migraine treatment suggest these are 
rapid and sustained freedom from pain, improvement in other migraine symptoms, and 
minimal or no adverse events (AEs).16,17 There is significant need for effective and tolerable 
treatments for migraine sufferers, especially those who experience at least four migraine days 
per month. In these patients, preventive treatment is recommended to reduce migraine-related 
disability and the overuse of acute therapies and rescue medication.16 Both US and European 
guidelines note the importance of reduced attack frequency, reduction or maintenance (no 
escalation) of acute treatment use, and an improvement in quality of life (QoL).16,17 Current 
migraine treatments leave millions of people who have migraine with unmet needs due to 
lack of and/or insufficient efficacy, AEs, and contraindications.18,19
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Rimegepant (VYDURA®/NURTEC® ODT), a next-generation, small molecule oral 
selective and potent calcitonin gene-related peptide (CGRP) receptor antagonist, is the first 
and only migraine treatment approved for both the acute treatment of migraine with or 
without aura in adults and for the preventive treatment of EM in adults who have at least four 
migraine attacks per month. Prior to rimegepant, there was no single medication proven to be 
safe and effective for both acute and preventive treatment of migraine. Rimegepant was 
approved in the US for the acute treatment of migraine in February 2020, and for preventive 
treatment of episodic migraine in adults who have at least 4 migraine attacks per month in 
May 2021. It was approved by the EMA for both indications in April 2022.
The Adelphi Real World (ARW) Migraine Disease Specific Programme™ (DSP) 2022 
surveys provide an opportunity to examine physician and patient perspectives for rimegepant 
in the US. This protocol describes the analysis of ARW Migraine VII DSP™ as a secondary 
real-world data (RWD) source to address the research questions.  
7. RESEARCH QUESTION AND OBJECTIVES
The objectives of this study are to 1) explore reliability of effect with acute use of rimegepant
or triptans; 2) evaluate satisfaction with rimegepant or triptans; 3) evaluate willingness to 
continue using rimegepant or triptans; 4) explore proportion optimized on treatment with 
rimegepant or triptans. 
Research questions:
1. What is the reliability of effect of rimegepant or triptans in the real world over 
multiple migraine attacks when taken PRN?
2. How satisfied are patients with rimegepant or triptans to treat their migraine attacks?
3. How willing are patients to continue taking rimegepant or triptans to treat their 
migraine attacks?
4. What proportion of those treating acutely with rimegepant or triptans are adequately 
responding and well managed?
5. When do patients administer rimegepant or triptans when treating an acute attack?
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8. RESEARCH METHODS 
8.1. Study Design
A cross-sectional study design using physician and patient survey data drawn from the ARW
Migraine VII DSP will be employed to assess the acute use of, satisfaction with, willingness 
to continue use and treatment optimization of rimegepant or triptans in patients with 
migraine. Participants were recruited into the Migraine VII DSP in the US between May 
2022 and November 2022. This study comprises a secondary data analysis of DSP data.
The full DSP methodology has been published and validated and the illustration below 
outlines the main phases of the DSP].20,21,22 The DSP was conducted across a number of 
countries including the EU5 and US. Given the timing of the data collection, only data from 
the US will be utilized as rimegepant was available on the US market at the time of 
administration, unlike for other countries. 
The ARW DSP™are made available to subscribers upon the strict condition that all 
information remains the intellectual property of ARW and should not be divulged to any 
third party except with the written prior permission of ARW. Pfizer has subscribed to access 
the ARW Migraine VII DSP and so cannot be considered as the Study Sponsor.
8.2. Setting
ARW works with field partners across the US with the same principle of physician-based 
recruitment for all DSPs. Both physician-level and patient-level data are available for 
analyses of the migraine DSP (see Figure 1). 
The study population will comprise of consulting patients included in the Migraine VII DSP 
between May 2022 and November 2022; namely, consulting adult patients diagnosed with 
migraine and prescribed rimegepant or triptans as an acute treatment for their migraine in the 
US.
DSP physician participants for the migraine DSP in the US were neurologists and general 
physicians identified from public lists of healthcare professionals and meeting the following 
criteria:
!
Physicians identified as a PCP or neurologist.
!
PCPs must make treatment decisions for at least 10 patients with migraine and 
neurologists must make treatment decisions for at least 20 patients with migraine.
Candidate respondents were screened online and those who met the predefined eligibility 
criteria were invited to participate (see Section 8.2.1 and Section 8.2.2). 
Each participating physician was asked to provide patient data for up 8 patients with
migraine. Patient data for the migraine DSP was based on patients aged 18 years or older 
with a diagnosis of migraine and not involved in a clinical trial. 
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As described in Figure 1, during the US survey period (May–November 2022), physicians 
involved in the management of migraine patients were recruited to complete an online survey 
(Physician Survey) of their attitudes and behaviors regarding the treatment of migraine. Each 
physician then completed an electronic Patient Record Forms (PRFs) on 8 consecutive 
consulting patients with migraine, regardless of the reason for the visit. The consecutive 
approach to recruitment was stressed to each participating physician to remove the element 
of selection bias. A generic copy of the data collection forms for Physicians is included in 
APPENDIX 2. COPIES OF PATIENT RECORD FORM (PRF), PATIENT SELF 
COMPLETION (PSC) QUESTIONNAIRES and PHYSICIAN SURVEY 
QUESTIONNAIRES: ENGLISH LANGUAGE VERSION.
The patients were then asked if they would be willing to complete a pen-and-paper Patient 
Self-Completion (PSC) questionnaire about their experiences of having migraine. This 
allows a unique view of the disease from both the patient and physician perspective. 
Completion of the PSC by the patient was voluntary.
Figure 1.
Migraine DSP Data Collection Methodology
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8.2.1. Inclusion Criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
final study population for analysis:
1. Patients who have episodic and/or chronic migraine 
2. Patients age >18
3. Currently prescribed rimegepant OR triptans for the acute treatment of migraine
8.2.2. Exclusion Criteria
Patients meeting any of the following exclusion criteria will not be included in the study
population for analysis:
1. Currently prescribed rimegepant for prevention of migraine or for both the acute 
treatment & prevention of migraine
2. Rimegepant group: currently prescribed an acute treatment for migraine other than 
rimegepant
3. Triptan Group: currently prescribed an acute treatment for migraine other than 
triptans
8.3. Variables
The variables of interested captured in the data collection forms are summarized in Table 1:
Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Physician provided Patient Report Form (PRF)
Patient age
Patient biological sex
Patient BMI
Patient ethnicity
Patient 
demographics
PRF AQ1
PRF AQ2
PRF AQ3/4
PRF AQ6
Male, Female, Intersex
White / African American / 
Native American / Asian 
(Indian subcontinent) / South-
East Asian / Asian (other) / 
Hispanic / Middle Eastern / 
Other
Working fulltime / part-time / 
retirement / student / 
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Employment Status
Insurance Type
PRF AQ8
PRF AQ9
PRF AQ10
PRF AQ14
unemployed / long-term sick / 
home maker / don’t know
Part-time / retirement / student / 
unemployed / long-term sick 
due to migraine: yes/no
Days off work due to migraine
Medicaid / medicare /
commercial / exchange plan / 
cobra / non-medicare retired 
benefit / tricare/veterans / other / 
no insurance / don’t know
Migraine diagnosis- chronic?
Number of migraine related 
headache days in last 3 months
Severity of attacks over last 3 
months
Current migraine 
symptoms/most bothersome 
symptom
Duration of attack without 
treatment
Patient clinical 
characteristics
PRF CQ5
PRF CQ4bi
PRF CQ7a
PRF CQ6a/6b
PRF CQ10
PRF CQ3
Yes / No
Very mild / Mild / Moderate / 
Severe  / Very Severe
Pain on one side of the head / 
Pain that moves from one side 
of the head to another/ Pain on 
both sides of the head at the 
same time / Pulsating/throbbing 
pain / Pain worsened by activity 
/ Photophobia / Sensitivity to 
smell / Visual aura / Light-
headedness / Speech changes / 
Sensory aura / Nausea / 
Vomiting / Allodynia / 
Watery/swollen/red eyes / 
Facial swelling / Runny 
nose/nasal congestion / Ear 
congestion / Kinesiophobia / 
Muscle weakness / Mood 
changes / Changes in appetite / 
Other / Unknown
Hours/days
Tension type headache / 
Medication overuse headache / 
Cluster headache / SUNCT / 
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Other headache conditions 
Current comorbidities 
PRF KQ2/LQ1
Hemicrania continua / New 
daily persistent headache / 
Primary stabbing headache / 
Primary exercise headache / 
Primary thunderclap headache / 
Hypnic headache / Secondary 
headaches / Other headache 
conditions / None
Myocardial infarction / 
Ischaemic stroke / 
Haemorrhagic stroke / TIA / 
Cerebrovascular disease /
Hypertension / Hypotension / 
Ischaemic heart disease / 
Congestive heart failure / Atrial 
fibrillation / Arrhythmia / 
Angina / Deep vein thrombosis / 
Cardiomyopathy / Coronary 
artery disease / Peripheral 
vascular disease / Mitral valve 
disease / Reynaud’s disease / 
Type 1 diabetes (with and 
without complications / Type 2 
diabetes (with and without 
complications) / Obesity / 
Thyroid disease / 
Hyperlipidaemia / 
Dyslipidaemia / 
Mild/Moderate/Severe renal 
disease / Mild/Moderate/Severe 
liver disease / NASH/ 
Depression / Anxiety / Stress / 
Vascular dementia / 
Alzheimer’s disease / Other 
dementia / Epilepsy / 
Parkinson’s disease / Obsessive 
compulsive disorder / Panic 
disorder / Sleeping disorders / 
Seizures / Vertigo / Chronic 
pulmonary disease / Asthma / 
Chronic sinusitis / Connective 
tissue disease / 
Hemiplegia/Paraplegia / 
Rheumatologic disease / 
Arthritis / Neuropathic pain / 
Osteoporosis / Neck pain / Back 
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
pain / Fibromyalgia / 
Trigeminal neuralgia / Muscle 
weakness / Any malignancy / 
Metastatic solid tumour / 
Tumour without metastases / 
Gastrointestinal problems / 
Peptic ulcer disease / Lupus / 
Anorexia / Alcoholism / 
Menstrual disorders / IBS / 
Glaucoma / AIDS/HIV / 
Erectile dysfunction / Long term 
effects of COVID-19 / Other / 
None
Patient received prior acute 
treatment(s)
Time spent on Rimegepant or 
triptans (currently receiving)
Patient current & 
prior acute 
treatments
PRF DQ10
PRF DQ2a
Triptan(s) including 
combinations / NSAID(s) 
including combinations /  Anti-
CGRP gepants / Opioid 
analgesics including 
combinations / Non-opioid 
analgesics including 
combinations / Ergotamines and 
Derivatives / Serotonin 5-HTIF
agonist (ditan) / Other / No drug 
treatment 
Days / Don’t know
Patient current preventive 
treatment(s)
Patient prior prevention 
treatment(s)
Patient current & 
prior preventive 
treatment (s)
PRF EQ1
PRF EQ3
PRF EQ10
Yes / No but previously / Never
Failure to achieve pain freedom 
within 2 hours post dose
(physician perspective)
Outcome-
Objective 1
PRF DQ18
Yes / No / Unknown
Reason for choice of current 
acute treatment- ‘consistency of 
response after repeated use’ 
(physician perspective)
Outcome-
Objective 1
PRF FQ1a
Complete pain freedom after 2 
hours /  Pain relief after 2 hours 
/ Relieves most bothersome 
migraine symptom / Fast onset 
of action / Relieves even the 
most severe migraine attacks / 
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Prolonged pain relief/long 
duration of action / Avoids the 
need for a second dose or rescue 
treatment / Low headache 
recurrence (within 24 hours of 
attack) / Tends to work across 
all patients / Consistency of 
response after repeated use / 
Dual use treatment- a single 
drug to achieve acute and 
preventive treatment effects / 
Ability to prescribe a stronger 
initial dose, rather than multiple 
additional doses / Ability to take 
additional doses for non/partial 
response / Available as a 
table/capsule / Available as a 
melt / Available as a patch / 
Available via nasal 
administration / Available as an 
injection / Ability to prescribe 
for consecutive days (eg, for 
menstrual migraine and other 
trigger events / Allows repaid 
return to function / Patient can 
continue activities and honour 
commitments / Patient can 
enjoy recreational/leisure 
activities / Reduces number of 
days missed from school/work / 
Improves patient’s quality of 
sleep / Patient can maintain 
relationships / Low risk of 
medication overuse headaches 
with repeated use / Lower risk 
of  paraesthesia (abnormal 
sensation(s) of the skin) / Lower 
risk of  palpitations/flushing / 
Lower risk of  other CV side 
effects / Lower risk of  
nausea/vomiting / Lower risk of  
other GI side effects / Lower 
risk of  memory/concentration 
problems / Lower risk of  
drowsiness/sedation / Lower 
risk of dizziness / Lower risk of  
fatigue / Lower risk of  liver 
damage / Lower risk of  weight 
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Final V2.0 Amendment 1, 23 April 2024
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
problems / Lower risk of  
depression / Lower risk of  
allergic reaction / Lower risk of  
breathing difficulties / Lower/no 
risk of injection site reaction / 
Lower risk of   addiction/abuse / 
Suitable for adjunctive/add-on 
therapy / Lack of interaction 
with other drugs / Safe for long 
term use / Efficacious in 
patients who have failed prior 
acute migraine treatments / 
Suitable for patients with 
moderate/high CV risk / Safe in 
patients with cardiac/circulatory 
disorders / Suitable for 
vomiting/nauseous patients / 
Suitable for patients with 
menstrual migraine / Suitable 
for women of child bearing age 
/ Suitable for women of child 
bearing age / Suitable for 
physically active patients / 
Suitable for use in career 
orientated professionals / 
Approved for migraine / Good 
patient adherence / Patient 
convenience / Patient 
request/preference for therapy / 
Cost effective treatment / 
Persona; experience prescribing 
this drug / On local/national 
formulary / Clinical 
trial/publication evidence / 
Other selected for rimegepant or 
triptans
Satisfaction with current acute 
treatment (physician 
perspective)
Outcome-
Objective 2
PRF IQ1a
Extremely satisfied / Satisfied / 
Slightly Satisfied / Neither 
satisfied nor dissatisfied /
Slightly dissatisfied / 
Dissatisfied / Extremely 
dissatisfied
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Drivers for lack of satisfaction 
with current acute treatment 
(physician perspective)
Outcome-
Objective 2
PRF IQ1b
Lack of efficacy / Slow onset of 
action / Efficacy diminished 
over time / Number of side 
effects experienced / Severity of 
side effects experienced / Mode 
of administration / Complicated 
dosing regimen / The number of 
prescribed acute treatments / 
The treatment is costly for the 
patient / Other
Patient Self-Completion Form (PSC)
Number of migraine attacks 
acute treatment achieves pain 
freedom within 2 hours post 
dose (patient perspective)
Outcome-
Objective 1
PSC HQ6
0 out of every 5 attacks / 1 out 
of every 5 attacks / 2 out of
every 5 attacks / 3 out of every 
5 attacks / 4 out of every 5 
attacks / 5 out of every 5 attacks
Satisfaction with current acute 
treatment (patient perspective)
Outcome-
Objective 2
PSC HQ18a
Extremely satisfied / Satisfied / 
Slightly Satisfied / Neither
satisfied nor dissatisfied / 
Slightly dissatisfied / 
Dissatisfied / Extremely 
dissatisfied
Drivers for lack of satisfaction 
with current acute treatment 
(patient perspective)
Outcome-
Objective 2
PSC HQ18b
It only reduces my migraine 
pain by half / IT reduces my 
migraine pain by less than half / 
It does not work quickly enough 
/ It does not work as well as it 
used to / The number of side
effects I experience / The 
severity of the side effects I 
experience / I am not happy 
with the way I have to take it / I 
find it difficult to know when to 
take it / I have too many 
different acute treatments to 
take / I worry about becoming 
dependent on it / It costs me too 
much money / Other
Patient willingness to continue use 
of acute treatment (patient 
perspective)
Outcome-
Objective 3
PSC HQ18c
Definitely yes / Probably yes / 
Do not know / Probably note / 
Definitely not
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Table 1.
Variables
Variable
Purpose
Data Source(s)
Operational Definition
Migraine Treatment Optimization 
Questionnaire (m-TOQ6)
Outcome-
Objective 4
PSC Section I- m-TOQ6
Reported by item and total score.
When patient takes acute Rx 
treatment
Outcome –
Objective 5
PSC HQ3
Before any sign of a migraine 
attack, but in anticipation of one 
starting / At the first sign of a 
migraine attack (before the pain 
starts) / When the pain starts / 
After the pain has started and I have 
an idea of how severe it is
How many days per month patient 
takes acute Rx treatment
Outcome –
Objective 5
PSC HQ4a
8.4. Data Sources
Data will be drawn from the Adelphi Migraine DSP, fielding in the US between May and 
November 2022.
8.5. Study Size
Given the primary research objective is purely descriptive in nature (i.e., no a priori 
hypotheses specified), the available sample size is fixed by the DSP data collection 
methodology and simply impacts the precision of any estimates. Therefore, formal sample 
size calculations are not applicable and have not been performed. All patients who meet the 
eligibility criteria will be included in the study. For this study, the sample size is 
528 (91 Rimegepant, 437 Triptans) for the physician-reported outcomes, and 
143 (29 Rimegepant, 113 Triptans) for the patient-reported outcomes. Data Management 
Pseudoanonymised data are taken from the Migraine VII DSP, which is owned and managed 
by ARW.
All data analysis will be conducted using Stata 17 software, version 17.0 (StataCorp, College 
Station, Texas) / IBM® SPSS® Data Collection Survey Reporter v7.5 or the latest available 
version at time of analysis. All programming code/ syntax written to conduct the required
analysis will be logged for transparency and replicability.
8.6. Data Analysis
Analyses will be based on patients receiving rimegepant or triptans only as an acute 
treatment currently for their migraine. 
Data will be stratified by time spent on rimegepant or triptans and number of migraine 
related headache days. 
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Analysis will be descriptive. The mean, standard deviation (SD), median, 25th and 75th
percentiles and minimum and maximum values will be reported for numeric variables, whilst 
relative frequencies and percentages will be reported for categorical variables.
The real-world nature of the DSP means many variables will contain missing data. We would 
expect the base of patients to vary from variable to variable due to imperfect physician 
knowledge, physicians not wishing to answer the question, etc. The base relevant to each 
analysis will be reported in any data tables provided. There will be no imputation of missing 
data. Where missing values are found in a particular variable, any patients with missing 
values will be removed from all pieces of analysis where that variable is used. However,
patients removed from one piece of analysis are still eligible for inclusion in other analyses. 
In the derivation of PRO variables, the handling of missing data will follow the official 
instructions as provided by the author/owner of the PRO questionnaire.
Detailed methodology for summary and statistical analyses of data collected in this study is
documented in a statistical analysis plan (SAP) below:
8.6.1. Analysis Plan for Describing Patients with Migraine Receiving Rimegepant or 
Triptans PRN
Variable
Data Source(s)
Analysis Plan
Patient age
Patient biological sex
Patient BMI
Patient ethnicity
Employment status
Insurance type
PRF AQ1
PRF AQ2
PRF AQ3/4
PRF AQ6
PRF AQ8
PRF AQ9
PRF AQ10
PRF AQ14
Mean, Median, SD, Q1, Q3, Min, Max to be displayed
Proportion of responses to: Male, Female, Intersex
Mean, Median, SD, Q1, Q3, Min, Max to be displayed
Proportion of responses to: White / African American / Native 
American / Asian (Indian subcontinent)  / South-East Asian / 
Asian (other) / Hispanic / Middle Eastern / Other
Proportion of responses to:  Working full time / Working part-
time / Retirement / Student / Unemployed / Long-term sick / 
Home maker 
Responses of “Don’t know” will be omitted from analysis.
Proportion of responses to: Yes / No
Responses of “Don’t know” will be omitted from analysis.
Number of days taken off work/studies in last 3 months due to 
migraine presented as Mean, Median, SD, Q1, Q3, Min, Max 
to be displayed. 
Responses of “Don’t know” will be omitted from analysis.
Proportion of responses to: Medicaid / Medicare / Commercial 
/ Exchange plan / Cobra / Non-medicare retired benefit / 
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Variable
Data Source(s)
Analysis Plan
Tricare/veterans / Other / No insurance 
Responses of “Don’t know” will be omitted from analysis.
Migraine diagnosis-
chronic?
Number of migraine related 
headache days in last 3 
months
Severity of attacks over last 
3 months
Current migraine symptoms
Most bothersome migraine 
symptoms
Duration of attack without 
acute treatment (hours or 
days)
Other headache conditions 
PRF CQ5
PRF CQ4bi
PRF CQ7a
PRF CQ6a
PRF CQ6b
PRF CQ10
PRF CQ3
Proportion of responses to: Yes / No
Mean, Median, SD, Q1, Q3, Min, Max to be displayed
Proportion of responses to: Very mild / Mild / Moderate / 
Severe  / Very Severe
Proportion of responses to: Pain on one side of the head / Pain 
that moves from one side of the head to another/ Pain on both 
sides of the head at the same time / Pulsating/throbbing pain / 
Pain worsened by activity / Photophobia / Sensitivity to smell / 
Visual aura / Light-headedness / Speech changes / Sensory 
aura / Nausea / Vomiting / Allodynia / Watery/swollen/red 
eyes / Facial swelling / Runny nose/nasal congestion / Ear 
congestion / Kinesiophobia / Muscle weakness / Mood 
changes / Changes in appetite / Other / Unknown
Responses of “Don’t know” will be omitted from analysis.
Proportion of responses to: Pain on one side of the head / Pain 
that moves from one side of the head to another/ Pain on both 
sides of the head at the same time / Pulsating/throbbing pain / 
Pain worsened by activity / Photophobia / Sensitivity to smell / 
Visual aura / Light-headedness / Speech changes / Sensory 
aura / Nausea / Vomiting / Allodynia / Watery/swollen/red 
eyes / Facial swelling / Runny nose/nasal congestion / Ear 
congestion / Kinesiophobia / Muscle weakness / Mood 
changes / Changes in appetite / Other / Unknown
Responses of “Don’t know” will be omitted from analysis.
Mean, Median, SD, Q1, Q3, Min, Max to be displayed. 
Responses will be calculated into one unit of choice- hours or 
days.
Responses of “Don’t know” will be omitted from analysis.
Proportion of responses to: Tension type headache / 
Medication overuse headache / Cluster headache / SUNCT / 
Hemicrania continua / New daily persistent headache / 
Primary stabbing headache / Primary exercise headache / 
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Variable
Data Source(s)
Analysis Plan
Current comorbidities
PRF KQ2/LQ1
Primary thunderclap headache / Hypnic headache / Secondary 
headaches / Other headache conditions / None
Responses of “None” will be omitted from analysis.
Proportion of responses to: Myocardial infarction / Ischaemic 
stroke / Haemorrhagic stroke / TIA / Cerebrovascular disease / 
Hypertension / Hypotension / Ischaemic heart disease / 
Congestive heart failure / Atrial fibrillation / Arrhythmia / 
Angina / Deep vein thrombosis / Cardiomyopathy / Coronary 
artery disease / Peripheral vascular disease / Mitral valve 
disease / Reynaud’s disease / Type 1 diabetes (with and 
without complications / Type 2 diabetes (with and without 
complications) / Obesity / Thyroid disease / Hyperlipidaemia / 
Dyslipidaemia / Mild/Moderate/Severe renal disease / 
Mild/Moderate/Severe liver disease / NASH/ Depression / 
Anxiety / Stress / Vascular dementia / Alzheimer’s disease / 
Other dementia / Epilepsy / Parkinson’s disease / Obsessive 
compulsive disorder / Panic disorder / Sleeping disorders / 
Seizures / Vertigo / Chronic pulmonary disease / Asthma / 
Chronic sinusitis / Connective tissue disease / 
Hemiplegia/Paraplegia / Rheumatologic disease / Arthritis / 
Neuropathic pain / Osteoporosis / Neck pain / Back pain / 
Fibromyalgia / Trigeminal neuralgia / Muscle weakness / Any 
malignancy / Metastatic solid tumour / Tumour without 
metastases / Gastrointestinal problems / Peptic ulcer disease / 
Lupus / Anorexia / Alcoholism / Menstrual disorders / IBS / 
Glaucoma / AIDS/HIV / Erectile dysfunction / Long term 
effects of COVID-19 / Other / None
Responses of “None” will be omitted from analysis.
Patient receiving acute 
treatment(s) previously
Time spent on Rimegepant
or triptans (currently 
PRF DQ10
PRF DQ2a
Proportion of responses to: Triptan(s) including combinations /  
NSAID(s) including combinations /  Anti-CGRP gepants / 
Opioid analgesics including combinations / Non-opioid 
analgesics including combinations / Ergotamines and 
Derivatives / Serotonin 5-HTIF agonist (ditan) / Other / No 
drug treatment 
Responses of “No treatment” will be omitted from analysis.
Responses of ‘Triptan’ and ‘Triptan combinations’ will be 
combined. 
Mean, Median, SD, Q1, Q3, Min, Max to be displayed. 
Responses will be calculated into one unit of choice- days, 
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Variable
Data Source(s)
Analysis Plan
receiving)
Patient current preventive 
treatment(s)
Patient receiving preventive 
treatment(s) previously 
PRF EQ1
PRF EQ3
PRF EQ10
weeks or months.
Responses of “Don’t know” will be omitted from analysis.
Proportion of responses to: Yes / No, but this patient has 
received preventive prescribed treatment(s) for their migraine 
in the past / No, and this patient has never received prescribed
preventive treatment(s) for their migraine
Proportion of responses to: Anti-CGRP mAbs, 
Anticonvulsants, Beta-blockers, Anti-CGRP gepant, 
Antidepressant/Anxiolytics/Benzodiazepines / Calcium 
antagonists / Contraceptive / NSAIDs (including 
combinations), Opioid analgesics (including combinations) 
Neurotoxins / Other / No drug treatment 
Responses of ‘No treatment’ will be omitted from analysis.
Responses of ‘Rimegepant’ will be omitted from analysis. 
Proportion of responses to: Anti-CGRP mAbs, 
Anticonvulsants, Beta-blockers, Anti-CGRP gepant, 
Antidepressant/Anxiolytics/Benzodiazepines / Calcium 
antagonists / Contraceptive / NSAIDs (including 
combinations), Opioid analgesics (including combinations)
Neurotoxins / Other / No drug treatment 
Responses of ‘No treatment’ will be omitted from analysis.
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8.6.2. Analysis Plan for Objective 1
Objective 1 focuses on the reliability of effect of rimegepant or triptans over multiple attacks 
when taken PRN to treat migraine. This will be addressed by describing the following:
Variable
Data Source(s)
Analysis Plan
Failure to achieve pain 
freedom within 2 hours 
post dose (physician 
perspective)
PRF DQ18
Proportion of responses to: Yes / No
Responses of “Don’t know” will be omitted from analysis.
Reason for choice of 
current acute treatment-
‘consistency of response 
after repeated use’ 
(physician perspective)
PRF FQ1a
Proportion of responses to: Complete pain freedom after 2 hours 
/  Pain relief after 2 hours / Relieves most bothersome migraine 
symptom / Fast onset of action / Relieves even the most severe 
migraine attacks / Prolonged pain relief/long duration of action / 
Avoids the need for a second dose or rescue treatment / Low 
headache recurrence (within 24 hours of attack) / Tends to work 
across all patients / Consistency of response after repeated use / 
Dual use treatment- a single drug to achieve acute and 
preventive treatment effects / Ability to prescribe a stronger 
initial dose, rather than multiple additional doses / Ability to 
take additional doses for non/partial response / Available as a 
table/capsule / Available as a melt / Available as a patch / 
Available via nasal administration / Available as an injection / 
Ability to prescribe for consecutive days (eg, for menstrual 
migraine and other trigger events / Allows repaid return to 
function / Patient can continue activities and honour 
commitments / Patient can enjoy recreational/leisure activities / 
Reduces number of days missed from school/work / Improves 
patient’s quality of sleep / Patient can maintain relationships / 
Low risk of medication overuse headaches with repeated use / 
Lower risk of  paraesthesia (abnormal sensation(s) of the skin) / 
Lower risk of  palpitations/flushing / Lower risk of  other CV 
side effects / Lower risk of  nausea/vomiting / Lower risk of  
other GI side effects / Lower risk of  memory/concentration 
problems / Lower risk of  drowsiness/sedation / Lower risk of 
dizziness / Lower risk of  fatigue / Lower risk of  liver damage / 
Lower risk of  weight problems / Lower risk of  depression / 
Lower risk of  allergic reaction / Lower risk of  breathing 
difficulties / Lower/no risk of injection site reaction / Lower risk 
of   addiction/abuse / Suitable for adjunctive/add-on therapy / 
Lack of interaction with other drugs / Safe for long term use / 
Efficacious in patients who have failed prior acute migraine 
treatments / Suitable for patients with moderate/high CV risk / 
Safe in patients with cardiac/circulatory disorders / Suitable for 
vomiting/nauseous patients / Suitable for patients with 
menstrual migraine / Suitable for women of child bearing age / 
Suitable for women of child bearing age / Suitable for 
physically active patients / Suitable for use in career orientated 
professionals / Approved for migraine / Good patient adherence 
/ Patient convenience / Patient request/preference for therapy / 
Cost effective treatment / Persona; experience prescribing this 
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Variable
Data Source(s)
Analysis Plan
drug / On local/national formulary / Clinical trial/publication 
evidence / Other selected for rimegepant or triptans
Number of migraine 
attacks acute treatment 
achieves pain freedom 
within 2 hours post dose 
(patient perspective)
PSC HQ6
Proportion of responses to: 0 out of every 5 attacks / 1 out of 
every 5 attacks / 2 out of every 5 attacks / 3 out of every 
5 attacks / 4 out of every 5 attacks / 5 out of every 5 attacks
Success will be defined as responses to ‘4 out of every 
5 attacks’ or ‘5 out of every 5 attacks’ combined
8.6.3. Analysis for Objective 2
Objective 2 focuses on satisfaction of physicians and patients with rimegepant or triptans to 
treat migraine acutely. This will be addressed by describing the following:
Variable
Data Source(s)
Analysis Plan
Satisfaction with current 
acute treatment (physician 
perspective)
PRF IQ1a
Proportion of responses to: Extremely satisfied / Satisfied / 
Slightly Satisfied / Neither satisfied nor dissatisfied / Slightly 
dissatisfied / Dissatisfied / Extremely dissatisfied
Satisfaction will be defined as responses to: ‘Extremely 
satisfied’ or ‘Satisfied’ or ‘Slightly Satisfied’ combined
Dissatisfaction will be defined as responses to: ‘Neither 
satisfied nor dissatisfied’ or ‘ Slightly dissatisfied’ or 
‘Dissatisfied’ or ‘Extremely dissatisfied’ combined
Data to be matched to PSC equivalent data (PSC HQ18a)
Drivers for lack of 
satisfaction with current 
acute treatment (physician 
perspective) 
PRF IQ1b
Proportion of responses to: Lack of efficacy / Slow onset of 
action / Efficacy diminished over time / Number of side effects 
experienced / Severity of side effects experienced / Mode of 
administration / Complicated dosing regimen / The number of 
prescribed acute treatments / The treatment is costly for the 
patient / Other
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Variable
Data Source(s)
Analysis Plan
Satisfaction with current 
acute treatment (patient 
perspective)
PSC HQ18a
Proportion of responses to: Extremely satisfied / Satisfied / 
Slightly Satisfied / Neither satisfied nor dissatisfied / Slightly 
dissatisfied / Dissatisfied / Extremely dissatisfied
Satisfaction will be defined as responses to: ‘Extremely 
satisfied’ or ‘Satisfied’ or ‘Slightly Satisfied’ combined
Dissatisfaction will be defined as responses to: ‘Neither 
satisfied nor dissatisfied’ or ‘ Slightly dissatisfied’ or 
‘Dissatisfied’ or ‘Extremely dissatisfied’ combined
Data to be matched to PRF equivalent data (PRF IQ1a)
Drivers for lack of 
satisfaction with current 
acute treatment (patient 
perspective)
PSC HQ18b
Proportion of responses to:  It only reduces my migraine pain by 
half / IT reduces my migraine pain by less than half / It does not 
work quickly enough / It does not work as well as it used to / 
The number of side effects I experience / The severity of the 
side effects I experience / I am not happy with the way I have to 
take it / I find it difficult to know when to take it / I have too 
many different acute treatments to take / I worry about 
becoming dependent on it / It costs me too much money / Other
8.6.4. Analysis for Objective 3
Objective 3 focuses on willingness of patients to continue taking rimegepant or triptans to 
treat their migraine attacks. This will be addressed by describing the following: 
Variable
Data Source(s)
Analysis Plan
Patient willingness to 
continue use of acute 
treatment (patient 
perspective)
PSC HQ18c
Proportion of responses to: Definitely yes / Probably yes / Do 
not know / Probably not / Definitely not
Responses of “Don’t know” will be omitted from analysis.
Willingness to continue will be defined as responses to: 
‘Definitely yes’ or ‘Probably yes’ combined
Unwillingness to continue will be defined as responses to 
‘Probably not’ and ‘Definitely not’ combined
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8.6.5. Analysis for Objective 4
Objective 4 focuses on the proportion of those treating acutely with rimegepant or triptans 
that are optimised on their treatment. This will be addressed by describing the following:
Variable
Data Source(s)
Analysis Plan
Migraine Treatment 
Optimization 
Questionnaire (m-TOQ6)
PSC Section I- m-
TOQ6
Reported by proportion of responses per time item and total 
score.
The official m-TOQ6 scoring algorithm will be used to 
calculate total score.
When patient takes acute 
treatment 
PSC HQ3
Proportion of responses to: Before any sign of a migraine 
attack, but in anticipation of one starting / At the first sign of a 
migraine attack (before the pain starts) / When the pain starts / 
After the pain has started and I have an idea of how severe it is
Number of days per month 
patient takes acute 
treatment
PSC HQ4a
Mean, Median, SD, Q1, Q3, Min, Max to be displayed.
8.7. Quality Control
This study will be conducted according to ARW’s standard operating procedures, with the 
results of the analysis checked for validity and consistency. 
8.8. Limitations of the Research Methods
!
Physicians are asked to provide data on consecutively consulting patients who meet 
the eligibility criteria, thus reducing the chance of any selection bias on the consulting 
population by physicians. However, generalisability of the study results to the wider 
patient population will be impacted as follows:
!
Participants from the Migraine VII DSP (from which the study population is 
drawn) do not constitute a true random sample, more a pragmatic (physicians) and 
pseudo-random (patients) sample, and although minimal selection criteria were 
imposed to identify physicians for inclusion, participation is influenced by the 
willingness to complete the record forms.
!
The patient sample may be more severely affected by their disease and/or 
treatment due to their consulting nature (ie, a requirement for inclusion in the
Migraine VII DSP). Furthermore, patients who consult more frequently are more 
likely to be included in the patient sample. However, physicians were asked to 
provide data for a number of consecutively consulting patients meeting the 
Migraine VII DSP inclusion criteria to reduce selection bias.
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!
No patient selection verification procedures were applied to the Migraine VII
DSP, and identification of the participants included was based on physician 
judgement/ perception rather than formal medical coding (eg, diagnostic codes). 
Nevertheless, this process is representative of physicians’ real-world classification 
of their patients.
!
The cross-sectional design of the DSP does not allow for causal relationships; 
however, identification of associations is possible.
!
Physicians and patients were requested to capture patient information retrospectively 
within the PRF and PSC respectively, which may introduce recall bias – a common 
limitation of survey data. However, physicians did have the ability to refer to the 
patients’ medical records while completing the PRF, thus minimising the possibility 
of recall bias. Moreover, most questions within the PSC have a limited recall period 
to further minimise the risk of recall bias.
Study data are self-reported by participants (eg, physicians and patients) as no independent 
verification was possible due to the nature of the ARW DSP methodology.
8.9. Other Aspects
Strengths of this research methods are:
!
Dataset provides the physicians’ actual treatment and prescribing decisions.
!
The DSP is a pseudo-random sample. The methodology used (collecting next n 
consulting patients) aims to reduce the likelihood of selection bias, and the sample 
should be representative of the consulting population.
!
The dataset is an independent data source providing impartiality of data reporting 
with no set hypotheses at design stage.
!
The DSP includes all consulting patients, covering both insured and non-insured 
patients. Each patient is unique and there is no double-representation. 
!
Amongst the variables collected, importantly, the DSP specifically includes, via the 
physician-completed record form, clinical characteristics, the patient’s complete 
treatment history from diagnosis to current day and reasons for prescribing / stopping 
treatment.
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9. PROTECTION OF HUMAN PARTICIPANTS
9.1. Patient Information and Consent
This study is an analysis of secondary data from the Migraine VII DSP. Participating patients 
in the Migraine VII DSP were treated in accordance with usual medical practice; no 
additional assessments or tests were conducted in order to participate. Data were collected 
cross-sectionally at a single point in time and retrospectively for historical information. 
Patients provided their informed consent prior to completion of the PSC and did not provide 
any personally identifiable information.
9.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices. 
The DSP was performed in compliance with the EphMRA Code of Conduct and ARW 
standard operating procedures.
The Migraine VII DSP was submitted to the Pearl IRB in the US (IRB number: 22-ADRW-
143). All data were deidentified and pseudoanonymised. 
All study results will be in tabular form and aggregate analyses. As this is an analysis of 
secondary data, additional informed consent, ethics committee or IRB approval are not 
required. Any publications and reports will not include subject identifiers.
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
This is a database analysis study based on secondary use of data collected for other purposes.
No administration of any therapeutic or prophylactic agent was required in this protocol. No 
reporting of individual case safety reports (ICSRs) ie, adverse events or product quality 
complaints, to regulatory agencies are required for this database study, as there is no access 
to individual patient/subject records, it is not possible to assess the causality.
This study involves data that exist as structured data by the time of study start.
In these data sources, individual patient data are not retrieved or validated, and it is not 
possible to link (ie, identify a potential association between) a particular product and medical 
event for any individual. Thus, the minimum criteria for reporting an adverse event (AE) (ie, 
identifiable patient, identifiable reporter, a suspect product, and event) cannot be met.
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11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
A final study report will be prepared describing methods, results, and interpretation of results 
upon completion of the study (anticipated Q1 2024).
Study results are also intended to be submitted for consideration at a scientific congress and 
published in a peer-reviewed journal (target congress and journal to be determined). 
Authorship of any publications resulting from this study will be determined on the basis of 
the International Committee of Medical Journal Editors (ICJME) Recommendations for the 
Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals.23
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
competent authority in any area of the world, or if the party responsible for collecting data 
from the participant is aware of any new information which might influence the evaluation of 
the benefits and risks of a Pfizer product, Pfizer should be informed immediately. 
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12. REFERENCES
1.
Headache Classification Committee of the International Headache Society (IHS). The 
International Classification of Headache Disorders, 3rd edition. Cephalalgia. 
2018;38(1):1-211.
2.
Mayans L, Walling A. Acute Migraine Headache: Treatment Strategies. American 
Family Physician. 2018;97(4):243-251.
3.
Ailani j, Burch R, Robbins M, Directors ABo. The American Headache Society 
Consensus Statement: Update on Integrating New Migraine Treatments Into Clinical 
Practice. Headache: The Journal of Head and Face Pain. 2021;61(7):1021-1039.
4.
Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between 
episodic migraine and chronic migraine. Curr Pain Headache Rep. 2012;16(1):86-92.
5.
Bonafede M, Cai Q, Cappell K, et al. Factors associated with direct health care costs 
among patients with Migraine. Journal of Managed Care and Specialty Pharmacy. 
2017;23(11):1169-1176.
6.
Safiri S, Pourfathi H, Eagan A, et al. Global, regional, and national burden of migraine 
in 204 countries and territories, 1990 to 2019. Pain. 2022;163(2):e293-e309.
7.
Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of 
migraine in the United States: data from the American Migraine Study II. Headache: 
The Journal of Head and Face Pain. 2001;41(7):646-657.
8.
Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine 
prevalence, disease burden, and the need for preventive therapy. Neurology. 
2007;68(5):343-349.
9.
Burch R, Loder S, Loder E, et al. The prevalence and burden of migraine and severe 
headache in the United States: updated statistics from government health surveillance 
studies. Headache: The Journal of Head and Face Pain. 2015;55(1):21-34.
10.
Research America. Migraine. 2018.
11.
Lipton RB, Araujo AB, Nicholson RA, et al. Patterns of Diagnosis, Consultation, and 
Treatment of Migraine in the US: Results of the OVERCOME Study (Abstract FHM1). 
Headache: The Journal of Head and Face Pain. 2019;59(S1):2-3.
12.
Munjal S, Singh P, Bensimon L, et al. Impact of Monthly Headache Day Frequency on 
Work Productivity and Impairment in Non-Work Activities among Persons with 
Migraine: Results from the Migraine in America Symptoms and Treatment Study 
(Abstract P255LB). Headache: The Journal of Head and Face Pain. 2019;59(S1):190-
191.
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13.
Stewart W, Wood G, Manack A, et al. Employment and Work Impact of Chronic 
Migraine and Episodic Migraine. Journal of Occupational and Environmental Medicine. 
2010;52(1):8-14.
14.
Stewart WF, Bruce C, Manack A, Buse DC, Varon SF, Lipton RB. A case study for 
calculating employer costs for lost productive time in episodic migraine and chronic 
migraine: results of the American Migraine Prevalence and Prevention Study. Journal of 
Occupational and Environmental Medicine. 2011;53(10):1161-1171.
15.
Tang C, Chen Y, Ng K, Wang S. A Retrospective Matched Case–Control Study on 
Medical Costs of Refractory Migraine in Taiwan. Headache: The Journal of Head and 
Face Pain. 2013;53(3):526-539.
16.
Ailani j, Burch R, Robbins M, Directors ABo. The American Headache Society 
Consensus Statement: Update on Integrating New Migraine Treatments Into Clinical 
Practice. Headache: The Journal of Head and Face Pain. 2021;61(7):1021-1039.
17.
Ducros A, de Gaalon S, Roos C, et al. Revised guidelines of the French headache 
society for the diagnosis and management of migraine in adults. Part 2: 
Pharmacological treatment. Revue neurologique. 2021;177(7):734-752.
18.
Marmura MJ, Silberstein SD, Schwedt TJ. The Acute Treatment of Migraine in Adults: 
The A merican H eadache Society Evidence Assessment of Migraine 
Pharmacotherapies. Headache: The Journal of Head and Face Pain. 2015;55(1):3-20.
19.
Moreno-Ajona D, Chan C, Villar-Martínez MD, Goadsby PJ. Targeting CGRP and 5-
HT(1F) Receptors for the Acute Therapy of Migraine: A Literature Review. Headache: 
The Journal of Head and Face Pain. 2019;59 (Suppl 2):3-19.
20.
Anderson et al. Real-world physician and patient behaviour across countries: Disease-
Specific Programmes- a means to understand. Current medical research and opinion. 
2008;24(11):3063-72.
21.
Babineaux et al. Evidence for validity of a national physician and patient-reported, 
cross-sectional survey in China and UK: the Disease Specific Programme. BMJ Open.
2016;16;6(8):e010352. 
22.
Higgins et al. Trends in medication use in patients with type 2 diabetes mellitus: a long-
term view of real-world treatment between 2000 and 2015. Diabetes, Metabolic 
Syndrome and Obesity. 2016:9(9):371-380. 
23.
Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly 
Work in Medication Journals, 2019.
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13. LIST OF TABLES 
Table 1.
Variables
14. LIST OF FIGURES
Figure 1.
Migraine DSP Data Collection Methodology
ANNEX 1. LIST OF STANDALONE DOCUMENTS
None.
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