Comparing Patient-Reported Outcomes Between Rimegepant and Triptan Users With Migraine in the United States
Conditions: Migraine
Sponsor: Pfizer

Rimegepant
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL
V1.0, 04 October 2024
PFIZER CONFIDENTIAL
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study 
Page 1 of 20
NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study information
Title
Comparing Patient-Reported Outcomes Between Rimegepant and 
Triptan Users with Migraine in the United States
Protocol number
C4951076
Protocol version 
identifier
1.0
Date
04 October 2024
Active substance
Analgesics, calcitonin gene-related peptide (CGRP) antagonists. 
ATC code: N02CD06
Medicinal product
Rimegepant (Nurtec 75mg ODT)
Research question 
and objectives
The goal of this research is to assess patient-reported outcomes 
(PROs), specifically treatment satisfaction, healthcare resource use 
(HCRU), quality of life (QoL), work productivity loss, and migraine-
specific disability of Rimegepant users, relative to triptan users, 
among US adults diagnosed with migraine.
Secondarily, a sensitivity analysis will be conducted, applying a 
more restrictive definition for the Rimegepant acute user cohort, to 
corroborate the initial set of results. Findings from these analyses 
may be used to inform communications with payers regarding 
reimbursement of Rimegepant.
Country of study
United States (US)
Author
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and 
not copy or disclose it to others (except where required by applicable law) or use it for unauthorized 
purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be promptly 
notified.
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)
PPD

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 2 of 20 
1. TABLE OF CONTENTS 
 
1. TABLE OF CONTENTS .......................................................................................................2 
2. LIST OF ABBREVIATIONS ................................................................................................4 
3. RESPONSIBLE PARTIES ....................................................................................................6 
4. ABSTRACT ...........................................................................................................................7 
5. AMENDMENTS AND UPDATES .......................................................................................8 
6. MILESTONES .......................................................................................................................9 
7. RATIONALE AND BACKGROUND ..................................................................................9 
8. RESEARCH QUESTION AND OBJECTIVES .................................................................10 
9. RESEARCH METHODS ....................................................................................................10 
9.1. Study Design ...........................................................................................................10 
9.2. Setting ......................................................................................................................10 
9.2.1. Inclusion Criteria ........................................................................................10 
9.2.2. Exclusion Criteria .......................................................................................11 
9.3. Variables ..................................................................................................................11 
9.4. Data Sources ............................................................................................................14 
9.5. Study Size ................................................................................................................14 
9.6. Data Management ...................................................................................................15 
9.7. Data Analysis ..........................................................................................................15 
9.8. Quality Control ........................................................................................................16 
9.9. Limitations of the Research Methods ......................................................................17 
9.10. Other Aspects ........................................................................................................17 
10. PROTECTION OF HUMAN PARTICIPANTS ...............................................................17 
10.1. Patient Information ................................................................................................17 
10.2. Patient Consent ......................................................................................................17 
10.3. Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) ...........17 
10.4. Ethical Conduct of the Study ................................................................................17 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................18 
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS .......18 
13. REFERENCES ..................................................................................................................18 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 3 of 20 
14. LIST OF TABLES .............................................................................................................20 
15. LIST OF FIGURES ...........................................................................................................20 
ANNEX 1. LIST OF STANDALONE DOCUMENTS ..........................................................20 
ANNEX 2. ADDITIONAL INFORMATION .........................................................................20 
 
 
 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 4 of 20 
2. LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AAN 
American Academy of Neurology 
AE 
Adverse event 
ATT 
Average treatment effect of treated 
CGRP 
Calcitonin gene-related peptide 
ER 
Emergency room 
FDA 
Food and Drug Administration 
GCS 
Global composite score 
HCRU 
Health care resource use 
HRQoL 
Health related quality of life 
IEC 
Independent ethics committee 
IP 
Internet Protocol 
IPTW 
Inverse probability of treatment weighting 
IRB 
Institutional review board 
mAb 
Monoclonal Antibody 
MCS 
Mental composite score 
MIDAS 
Migraine Disability Assessment Scale 
NHWS 
National Health and Wellness Survey 
NSAID 
Non-steroidal anti-inflammatory drugs 
OLS 
Oracle Life Sciences 
OTC 
Over the counter 
PCS 
Physical composite score 
PRO 
Patient-reported outcome 
QoL 
Quality of life 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 5 of 20 
US 
United States of America 
WPAI-GH 
Work Productivity and Activity Impairment – General Health 
 
 
 
 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 6 of 20 
3. RESPONSIBLE PARTIES 
Principal Investigator(s) of the Protocol 
Name, Degree(s) 
Job Title 
Affiliation 
Address 
Simon Dagenais, PhD 
Evidence Generation 
Innovation Lead 
Pfizer Inc 
1 Portland St, Cambridge, MA 
02139 
Martine C. Maculaitis, 
PhD, MA 
Sr. Evidence Generation 
Lead, Real World 
Evidence 
Oracle Life Sciences 
2300 Oracle Way Austin, TX 
78741 USA 
 
Additional Investigator(s) of the Protocol 
Name, Degree(s) 
Job Title 
Affiliation 
Address 
 
Pfizer Inc  
66 Hudson Blvd E, Fl 20, New 
York, NY 10001 USA 
 
Pfizer Inc 
1 Portland St, Cambridge, MA 
02139 
, MPH, 
PhD 
Oracle Life Sciences 
2300 Oracle Way Austin, TX 
78741 USA 
 
Oracle Life Sciences 
2300 Oracle Way Austin, TX 
78741 USA 
 
 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)
PPD
PPD
PPD
PPD
PPD

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 7 of 20 
4. ABSTRACT 
None. 
 
 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 8 of 20 
5. AMENDMENTS AND UPDATES 
None. 
 
 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 9 of 20 
6. MILESTONES 
Minimum requirements: 
Milestone 
Planned Date 
Initiation of data analysis 
05 October 2024 
First draft of abstract 
10 October 2024 
Final abstract 
15 October 2024 
Completion of data analysis 
20 November 2024 
First draft of poster content 
01 March 2025 
Final poster content 
15 March 2025 
 
7. RATIONALE AND BACKGROUND 
Triptans, also known as serotonin receptor agonists, are considered as a standard treatment 
for acute migraine and have been widely prescribed in the United States 1. A systematic 
review showed that standard dose (taken orally or intranasally) of triptans alleviated pain 
within 2 hours in 42 to 76% of patients and provided sustainable headache relief at 24 hours 
in 29% to 50% of patients 2. However, triptans are not for preventing migraine and are 
associated with numerous adverse events including nausea, dizziness, and coronary 
vasoconstriction 3. 
Rimegepant, an oral medication which works by blocking the calcitonin gene-related peptide 
(CGRP) receptors, was approved by the Food and Drugs Administration (FDA) in February 
2020, as an alternative method for the acute treatment of migraine in adults 4. Rimegepant 
relieves pain as well as incommodious symptoms and can prevent migraine when given the 
proper dose 5. However, nausea, urinary tract infection, and dizziness were adverse events 
reported for Rimegepant 6. 
Both triptans and Rimegepant are commonly prescribed for acute migraine but have different 
efficacy and side effects. Triptans showed better pain relief compared to gepants, whereas 
gepants were associated with fewer adverse events compared with triptans 1. Recent research 
also showed Rimegepant being more effective in the acute treatment of migraine in adults 
with a history of insufficient response to 1 or ≥2 triptans among and in current triptan users 7. 
As patients with migraine tend to experience worse health status, reduced health-related, 
reduced work productivity, the impact of treatment in improving patient reported outcomes is 
critical 8,9. Among triptan users, the HRQoL and work productivity were significantly 
impacted in those with insufficient response to triptans 10. In addition to the reduction in 
migraine frequency, Rimegapant was associated with improvement in HRQoL over time 11. 
However, few studies have comprehensively examined patient reported outcomes among 
Rimegepant users compared with triptan users. As such, the purpose of this study was to 
assess patient-reported outcomes (PROs) including treatment satisfaction, healthcare 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 10 of 20 
resource use (HCRU), quality of life (QoL), work productivity loss, and migraine-specific 
disability of Rimegepant users, relative to triptan users. 
8. RESEARCH QUESTION AND OBJECTIVES 
The primary aim of this analysis is to assess PROs, specifically treatment satisfaction, 
HCRU, QoL, work productivity loss, and migraine-specific disability of Rimegepant users, 
relative to triptan users, among US adults diagnosed with migraine.  
Secondarily, a sensitivity analysis will be conducted, applying a more restrictive definition 
for the Rimegepant user cohort, to corroborate the initial set of results. Findings from these 
analyses may be used to inform communications with payers regarding reimbursement of 
Rimegepant.  
9. RESEARCH METHODS  
9.1. Study Design  
This is a cross-sectional study using the 2023 US (N=75,007) National Health and Wellness 
Survey (NHWS) data. People who use Rimegepant will be compared with those who use 
triptan on treatment satisfaction, HCRU, QoL, work productivity loss, and migraine-specific 
disability outcomes. The cross-sectional design allows us to compare the Rimegepant vs. 
triptan users on multiple outcomes in a relatively quick and inexpensive way.  
9.2. Setting 
All data from the NHWS are reported by the respondent. NHWS participants are recruited 
through an existing, general-purpose (i.e., not health care-specific) web-based consumer 
panel via opt-in e-mails, co-registration with panel partners, e-newsletter campaigns, banner 
placements, and affiliate networks. All panelists explicitly agree to be a panel member, 
register with the panel through a unique e-mail address, and complete an in-depth 
demographic registration profile. A stratified random sampling procedure is implemented to 
ensure that the demographic composition of the final NHWS sample is representative of the 
general adult population in the US. In each year the NHWS is fielded, data from the 
International Database of the US Census Bureau are used to identify the relative proportions 
of adults by age, race/ethnicity, and gender; these proportions are then mimicked during the 
recruiting of panel members. 
9.2.1. Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study: 
1. Patients who have consented to the anonymous use of their data for research purpose. 
2. Aged 18 or older. 
3. Self-reported a diagnosis of migraine by physician. 
4. Currently on Rimegepant or triptan (via oral route) use at time of survey. 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 11 of 20 
5. In addition, patients to be included in the sensitivity analysis need to meet the following 
criteria: 
• Currently on acute Rimegepant use (<12 days using Rimegepant per month), or 
triptan (via oral route) use at time of survey.  
9.2.2. Exclusion Criteria 
Patients meeting the following criteria will not be included in the study: 
1. Currently on both Rimegepant and triptan use at time of survey. 
 
9.3. Variables 
The NHWS includes self-reported data on demographics, health characteristics, disease 
history, and health outcomes. The Table 1 below provides further details on the specific 
variables that will be assessed in the study. 
Table 1. 
Study Variables 
Variable 
Role 
Operational Definition 
Rimegepant vs. triptan 
use 
Exposure 
Current Rimegepant users (for sensitivity analysis 
restricted to acute Rimegepant users with <12 days use per 
month) vs. triptan users (no OTC, oral route only). 
Outcomes: Migraine treatment use and treatment satisfaction 
Migraine medication 
type (drug or OTC) 
Outcome 
Defined as drug only, OTC only and both drug and OTC, 
based on current use of migraine medication classes 
Migraine treatment type 
(acute or prevention) 
Outcome 
Defined as acute only, prevention only and both acute and 
prevention, based on current use of migraine medication 
classes 
Total number of acute 
migraine agent drug 
(continuous) 
Outcome 
Total number of acute agent classes (both drug and OTC) 
used 
Total number of acute 
migraine agent drug 
(categorical) 
Outcome 
Including 1 drug class, 2 or more drug classes, and 3 or 
more drug classes based on the total number of acute 
agent (both drug and OTC) classes used 
Total number of 
prevention migraine 
agent drug (continuous) 
Outcome 
Total number of prevention agent classes (only drug) used  
Total number of 
prevention migraine 
agent drug (categorical) 
Outcome 
Including 1 drug class, 2 or more drug classes, and 3 or 
more drug classes based on the total number prevention 
agent classes (only drug) used 
Current migraine 
treatments (drugs) 
Outcome 
Defined as yes or no for current migraine treatments on 
drug classes including: Rimegepant, triptans, NSAIDs, 
opioids, barbiturates, ergots, gepants (acute, including 
Rimegepant), ditan, combination analgesics, other acute 
drugs, anticonvulsants, beta-blocker, antidepressant, 
CGRP mAb, botox, and gepant (prevention, including 
Rimegepant) 
Treatment satisfaction 
(drugs) 
Outcome 
Treatment satisfaction of drug classes of: Rimegepant, all 
acute agents, triptans, NSAIDs, opioids, barbiturates, 
ergots, gepants (acute), ditans, combination analgesics, 
other acute treatment, all prevention agents, 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 12 of 20 
anticonvulsants, beta-blockers, antidepressants, CGRPs 
mAb, botox, and gepant (prevention) 
Categorized into 7 categories: extremely dissatisfied, very 
dissatisfied, somewhat dissatisfied, neither dissatisfied nor 
satisfied, somewhat satisfied, very satisfied, extremely 
satisfied 
Current migraine 
treatments (OTC) 
Outcome 
Defined as yes or no for current migraine treatments on 
OTC classes of analgesics (acetaminophen only), 
analgesics (combinations), NSAIDs, other OTCs 
Treatment satisfaction-
analgesics 
(acetaminophen only) 
Outcome 
Treatment satisfaction of OTC classes of analgesics 
(acetaminophen only), analgesics (combinations), 
NSAIDs, and other OTCs 
Categorized into 7 categories: extremely dissatisfied, very 
dissatisfied, somewhat dissatisfied, neither dissatisfied nor 
satisfied, somewhat satisfied, very satisfied, extremely 
satisfied 
Outcomes: HRQoL 
RAND-36 
Outcome 
PCS, MCS, and GCS index scores of the RAND-36 12 
EQ-5D-5L 
Outcome 
Health state utilities and the EuroQoL Visual Analog 
Scale (EQ-VAS) 13 
WPAI-GH 
Outcome 
Absenteeism (% of work time missed because of one's 
health in the past 7 days), presenteeism (% impairment 
experienced while at work in the past 7 days because of 
one's health), overall work impairment (combination of 
absenteeism and presenteeism), and activity impairment 
(% impairment in daily activities because of one's health 
in the past 7 days) among total population, employed, 
unemployed, and disabled 14 
MIDAS 
Outcome 
Total score, categorical (grade I-IV), and item scores (1-7) 
of MIDAS 15 
Outcomes: HCRU 
ER visits 
Outcome 
Visited ER in past 6 months (yes or no); number of ER 
visits in past 6 months among total population and 
participants with ER visits 
Hospitalizations 
Outcome 
Was hospitalized in past 6 months (yes or no); number of 
hospitalizations in past 6 months among total population 
and participants with hospitalizations 
General 
practitioner/family 
practitioner visits 
Outcome 
Visited general practitioner/family practitioner in past 6 
months (yes or no); number of general practitioner/family 
practitioner visits in past 6 months among total population 
and participants with general practitioner/family 
practitioner visits 
Cardiologist visits 
Outcome 
Visited cardiologist in past 6 months (yes or no); number 
of cardiologist visits in past 6 months among total 
population and participants with cardiologist visits 
Neurologist visits 
Outcome 
Visited neurologist in past 6 months (yes or no); number 
of neurologist visits in past 6 months among total 
population and participants with neurologist visits 
Traditional healthcare 
provider visits 
Outcome 
Visited traditional healthcare provider in past 6 months 
(yes or no); number of traditional healthcare provider 
visits in past 6 months among total population and 
participants with traditional healthcare provider visits 
Covariates adjusted through IPTW 
Age (continuous) 
Potential confounder 
Age of participants in years 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 13 of 20 
Sex 
Potential confounder 
Male vs. female 
Race 
Potential confounder 
Categorized as black, white, and other 
Hispanic/Latino 
Potential confounder 
Yes vs. no 
Marital status 
Potential confounder 
Single/ not living with partner vs. married/ living with 
partner 
Health insurance 
Potential confounder 
Categorized as private insurance, public insurance, no 
insurance, and unsure 
University education 
Potential confounder 
Less than university education vs. university education or 
higher 
Annual household 
income 
Potential confounder 
Categorized as below median income (<50,000), median 
income ($50,000-$74,999), above median income 
(≥$75,000), and decline to answer 
Employed 
Potential confounder 
Yes (full-time/ part-time/ self-employed) vs. no 
Charlson comorbidity 
index 
Potential confounder 
Charlson comorbidity index scores with and without 
patients of score 0 and categories based on scores: 0, 1, 2, 
3, and 4+ 
Body mass index 
Potential confounder 
Body mass index in kg/m2 
Alcohol use  
Potential confounder 
Currently drink alcohol vs. currently do not drink alcohol 
Smoking status 
Potential confounder 
Categorized as current smoker, former smoker, and never 
smoked 
Exercise 
Potential confounder 
Number of days exercise per months 
Contraindications 
Potential confounder 
Ever experienced each of contraindications (angina, 
arrythmia, atrial fibrillation, congestive heart failure, heart 
attack, left ventricular hypertrophy, mini-stroke/transient 
ischemia attack, peripheral arterial disease /poor 
circulation, Peripheral vascular disease, stroke, and 
unstable angina/chest pains) 
Cardiovascular risk 
factors 
Potential confounder 
Ever experienced each of cardiovascular risks (high blood 
pressure, high cholesterol, current smoker, type 2 
Diabetes, and obesity) 
Any contraindications 
Potential confounder 
Ever experienced any contraindications listed above 
Any cardiovascular risk 
factors 
Potential confounder 
Ever experienced any cardiovascular risks factors listed 
above 
Any contraindications or 
cardiovascular risk 
factors 
Potential confounder 
Ever experienced any contraindications or cardiovascular 
risks factors listed above 
Time since migraine 
diagnosis 
Potential confounder 
Time since migraine diagnosis in years 
Monthly migraine days 
(continuous) 
Potential confounder 
Number of days experienced migraine in past 30 days 
Monthly headache days 
(continuous) 
Potential confounder 
Number of days experienced headache in the past 30 days 
Medication overuse 
(migraine only) 
Potential confounder 
Yes or no, for migraine-specific medications only 
Other covariates that will be evaluated for balance between exposure groups  
Age (categorical)* 
Potential confounder 
Categorized based on age of participants in years: 18-29, 
30-39, 40-49, 50-59, 60-69, 70-79, 80-89 
Monthly migraine days 
(categorical)* 
Potential confounder 
Categorized based on number of days experienced 
migraine in past 30 days: <4, 4-9, 10-14, and ≥15 
Monthly headache days 
(categorical)* 
Potential confounder 
Categorized based on number of days experienced 
headache in past 30 days: <4, 4-9, 10-14, and ≥15 
Experience migraines 
related to menstrual 
cycle 
Potential confounder 
Yes vs. no, female participants only 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 14 of 20 
*Categorical age, monthly migraine days, and monthly headache days will be included in inverse probability of 
treatment weighting (IPTW) adjustment if their distributions are not balanced (standardized mean difference 
>0.1) after IPTW. 
 
Abbreviations: OTC: over the counter; NSAID: non-steroidal anti-inflammatory drugs; CGRPs mAb: 
calcitonin gene-related peptide antibodies monoclonal antibodies; HRQoL: health related quality of life; PCS: 
physical composite score; MCS: mental composite score; GCS: global composite score; WPAI-GH: the Work 
Productivity and Activity Impairment – General Health; MIDAS: Migraine Disability Assessment Scale; 
HCRU: health care resource utilization; ER: emergency room; IPTW: inverse probability of treatment 
weighting 
9.4. Data Sources  
This study will use self-reported data sourced from the NHWS. The NHWS is an annual, 
cross-sectional, internet-based survey of adults conducted across several countries annually. 
The current study will use data from the 2023 US (N =75,007) NHWS.  
9.5. Study Size 
Sample size estimates, based upon preliminary feasibility, are provided below, in Table 2. 
The sample size for this study is fixed by the number of patients in the NHWS database who 
meet the imposed criteria.  
Table 2. 
Estimated Sample Sizes 
Patient Cohorts 
n 
Overall NHWS sample 
75,007 
Diagnosed with migraine 
8,439 
Triptan users (oral route only, no OTC) without Rimegepant use 
1,340 
Rimegepant users without triptan use 
144 
Rimegepant users (acute only) without triptan use* 
112 
*For sensitivity analysis. 
 
Abbreviations: NHWS: National Health and Wellness Survey; OTC: over the counter 
 
A sample size of 1) 130 and 2) 100 in each group (1:1 allocation) will have 80% power to 
detect an effect size of at least 1) 0.35 standard deviation (SD) units (indicative of at least a 
“small-to-medium” effect) and 2) 0.4 SD units (indicative of a medium effect), respectively, 
using a 2-group t-test with a 5% 2-sided significance level. We will have a sample size much 
greater than 130 in one of our groups, resulting in higher statistical power compared to the 
1:1 allocation mentioned above. A total sample size of 100 will have 80% power to detect an 
effect size from a chi-square distribution of at least 0.33 (indicative of at least a “small-to-
medium” effect) using a chi-square test with a 5% 2-sided significance level and 3 degrees of 
freedom. There will be sufficient power to detect a “small-to-medium” effect of Rimegepant 
user vs. triptan use on the outcomes in the main analysis, and sufficient power to detect a 
medium effect in the sensitivity analysis with acute Rimegepant users only.  
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 15 of 20 
9.6. Data Management  
This study will use previously collected data that have been deidentified, processed, and 
cleaned. Prior to initiating the study programming, procedures were implemented to assess 
the quality of responses including, but not limited to, response ranges, consistency, and skip 
patterns. Data entry was completed instantaneously as the respondent answered the survey 
questions. Therefore, there are no paper surveys to house or destroy, and no manual data 
entry is required. The database that houses the questionnaire responses allows for direct 
exportation into statistical software. Identifying information about panel members will not be 
released other than a single panel identification number. Therefore, the working data files 
contain no identifying information, apart from the panel identification number. Specifically, 
the dataset does not include names, addresses, or any other information that can personally 
identify the respondents.  
Quality checks were implemented on the dataset before it became final. These checks 
included Internet Protocol (IP) address checks (i.e., ensuring the respondent resided within 
the country stated and that a single IP address was not associated with multiple panel 
accounts), completion times (ensuring a respondent did not complete the survey in a 
timeframe that was too short, implying inattentiveness), illogical/inconsistent data responses, 
etc. At the discretion of the data management team, respondents who failed these checks 
were excluded from the final dataset. 
The statistical software package that will be used for the study is R 4.3.1 (R Project for 
Statistical Computing).    
9.7. Data Analysis  
The average treatment effect of treated (ATT) will be measured to evaluate the effects of 
Rimegepant vs. triptan among current Rimegepant users.  
Based on clinical relevance, we will prespecify a list of variables to adjust for the 
comparison.  
Inverse probability of treatment weighting (IPTW) will be conducted to adjust for 
confounding by the covariates. The propensity score for each participant will be estimated by 
logistic regression and by including the prespecified list of variables to adjust for. Weights 
for ATT will be calculated for both exposed (Rimegepant users) and unexposed group 
(triptan users) 16. Stabilized weights will be used to address extreme weight values.  
To confirm that the IPTW procedure is successful, the weighted Rimegepant users and 
triptan users will be compared on the covariates using standardized mean difference (SMD) 
to ensure both groups are adequately balanced across all weighting criteria. While there is no 
definitive cut-off for identifying imbalance in IPTW, as a rule of thumb, a standardized mean 
difference (SMD) that is >0.10 is indicative of imbalance 17. This threshold will be applied to 
determine the quality of the weighting.  
Once the weighting is confirmed to be successful, bivariate analyses will be conducted to 
compare the weighted cohorts on treatment satisfaction, HCRU, QoL, migraine-specific 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 16 of 20 
disability, and work productivity loss. Specifically, categorical variables will be analyzed 
using chi-square tests or Fisher’s exact tests for small samples; continuous variables will be 
analyzed using 2-sample t-tests. Non-parametric tests may be considered for comparisons on 
skewed variables (e.g., HCRU) when the sample size is small (e.g., <30). For bivariate 
comparisons, p-values <0.05, 2-tailed, will be considered statistically significant. If there are 
covariates that are unbalanced after weighting (i.e., SMD >0.1), those covariates will be 
adjusted for in the regression analysis of outcomes. Generalized linear models will be fit 
depending on the distributions of outcomes. 
As a sensitivity analysis, the aforementioned IPTW and bivariate comparisons will be 
replicated after restricting the Rimegepant user cohort to the subset of those presumed to be 
acute treatment users (<12 days using Rimegepant). 
A sensitivity analysis will be conducted by incorporating NHWS sampling weights into the 
IPTW process. Sampling weights will be applied in the logistic regression to predict the 
propensity score, and the final weight will be the product of the propensity score weight and 
the sampling weight. Bivariate comparisons will then be replicated after using these newly 
derived weights for the participants. 
9.8. Quality Control 
This is a non-interventional retrospective study, so issues of quality control at study sites, 
e.g., data queries, do not apply. The following programming specifications will be used: 
• NHWS survey includes single select questions, multi select multiple choice questions, as 
well as open-ended questions (e.g., asking participants to type in the types of over-the-
counter medications they were taking).  
• NHWS data to be used in this study will be downloaded from the Oracle server and saved 
as a separate data file. This data file will be stored in a secure folder on the Oracle server, 
which is backed up in multiple iterations on a regular basis. 
• Programming code will be created for data management. This programming code will 
include the creation of cohort variables or any other derived variables.  
• All analyses will be performed using R 4.3.1 (R Project for Statistical Computing). For 
quality assurance purposes, a second independent researcher will review the 
programming code to be used for analysis.   
• Programming code used for data management and programming code used for analysis 
will be stored on the Oracle server and will be backed up on a regular basis. 
• Data will be reviewed for quality control prior to data analysis by OLS. For example, if a 
respondent entered the same number for most responses, or followed a pattern in their 
responses, they would be considered for removal from analysis. In addition, prior to data 
analysis, all variables are cleaned and checked for outliers and inconsistencies by OLS. 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 17 of 20 
9.9. Limitations of the Research Methods 
The data from the NHWS are self-reported; thus, independent, or clinical verification of 
responses will not be possible. Due to the self-reported nature of the data, recall error or other 
response biases may potentially introduce measurement error. However, many of the 
measures included in the study were developed solely for the purposes of patient self-report 
(RAND-36, EQ-5D-5L, WPAI-GH, MIDAS), and self-report is a valid and appropriate 
methodology for assessing subjective outcomes. Because of the cross-sectional nature of the 
data, causal inferences cannot be drawn, and longitudinal fluctuations in the relationships 
between study variables cannot be determined. While IPTW will be used to control for 
potential confounders, it is possible there are other variables that could not be included in the 
analyses that may at least partially explain any relationships observed in the current study. 
Finally, while the NHWS is designed to reflect the demographic composition of the general 
adult population in each country in which it is fielded, it is possible that the data may not be 
representative of the specific patient subpopulations examined in this study. 
9.10. Other Aspects 
Not applicable. 
10. PROTECTION OF HUMAN PARTICIPANTS 
10.1. Patient Information  
This study involves data that exist in deidentified/anonymized structured format and contain 
no patient personal information.   
10.2. Patient Consent 
As this study involves deidentified/anonymized structured data, which according to 
applicable legal requirements do not contain data subject to privacy laws, obtaining informed 
consent from patients by Pfizer is not required. 
10.3. Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) 
IRB/IEC is not required for this study. However, the protocols and questionnaire associated 
with the original fielding of the 2023 US NHWS were reviewed by Pearl Institutional 
Review Board (Indianapolis, IN; Protocol Number: 2023-0121) and granted exemption from 
expedited or full ethical review. The granted exemption is stored on the Oracle server.  
10.4. 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 
described in Good Practices for Outcomes Research issued by the International Society for 
Pharmacoeconomics and Outcomes Research (ISPOR)18.  
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 18 of 20 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS  
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 
(i.e., identify a potential association between) a particular product and medical event for any 
individual. Thus, the minimum criteria for reporting an adverse event (AE) (i.e., identifiable 
patient, identifiable reporter, a suspect product, and event) cannot be met.  
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
Study results will be disseminated in the form of abstract submissions and poster 
presentations at the American Academy of Neurology (AAN) meeting in May 2025. For all 
publications relating to the study, Pfizer will comply with recognized ethical standards 
concerning publications and authorship.  
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
competent authority in any area of the world, or if the party responsible for collecting data 
from the participant (i.e., Oracle Life Sciences) 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.   
13. REFERENCES 
1. 
Yang C, Liang C, Chang C, et al. Comparison of New Pharmacologic Agents With 
Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis. JAMA 
Netw Open. 2021;4(10):e2128544. doi:10.1001/jamanetworkopen.2021.28544 
2. 
Cameron C, Kelly S, Hsieh SC, Murphy M, Chen L, Kotb A, Peterson J, Coyle D, 
Skidmore B, Gomes T, Clifford T, Wells G. Triptans in the Acute Treatment of 
Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015 Jul-
Aug;55 Suppl 4:221-35. doi: 10.1111/head.12601. Epub 2015 Jul 14. PMID: 26178694. 
3. 
González-Hernández, A., Marichal-Cancino, B. A., MaassenVanDenBrink, A., & 
Villalón, C. M. (2018). Side effects associated with current and prospective 
antimigraine pharmacotherapies. Expert Opinion on Drug Metabolism & Toxicology, 
14(1), 25–41. https://doi.org/10.1080/17425255.2018.1416097 
4. 
Scott LJ. Rimegepant: First Approval. Drugs. 2020 May;80(7):741-746. doi: 
10.1007/s40265-020-01301-3. PMID: 32270407. 
5. 
Blair HA. Rimegepant: A Review in the Acute Treatment and Preventive Treatment of 
Migraine. CNS Drugs. 2023 Mar;37(3):255-265. doi: 10.1007/s40263-023-00988-8. 
Epub 2023 Feb 4. Erratum in: CNS Drugs. 2023 Jul;37(7):661. PMID: 36739335; 
PMCID: PMC10299922. 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 19 of 20 
6. 
DeFalco AP, Lazim R, Cope NE. Rimegepant Orally Disintegrating Tablet for Acute 
Migraine Treatment: A Review. Annals of Pharmacotherapy. 2021;55(5):650-657. 
doi:10.1177/1060028020954800 
7. 
Lipton RB, Blumenfeld A, Jensen CM, Croop R, Thiry A, L'Italien G, Morris BA, 
Coric V, Goadsby PJ. Efficacy of rimegepant for the acute treatment of migraine based 
on triptan treatment experience: Pooled results from three phase 3 randomized clinical 
trials. Cephalalgia. 2023 Feb;43(2):3331024221141686. doi: 
10.1177/03331024221141686. PMID: 36739511. 
8. 
Buse DC, Rupnow MF, Lipton RB (2009) Assessing and managing all aspects of 
migraine: migraine attacks, migraine-related functional impairment, common 
comorbidities, and quality of life. Mayo Clin Proc 84:422–435 
9. 
Bigal ME, Lipton RB (2009) The epidemiology, burden, and comorbidities of migraine. 
Neurol Clin 27:321–334 
10. Lombard, L., Farrar, M., Ye, W. et al. A global real-world assessment of the impact on 
health-related quality of life and work productivity of migraine in patients with 
insufficient versus good response to triptan medication. J Headache Pain 21, 41 (2020). 
https://doi.org/10.1186/s10194-020-01110-9 
11. L’Italien G, Popoff E, Johnston K, et al. Rimegepant 75 mg for acute treatment of 
migraine is associated with significant reduction in monthly migraine days: Results 
from a long-term, open-label study. Cephalalgia Reports. 2022;5. 
doi:10.1177/25158163221075596 
12. Johnston, K., Harris, L., Powell, L. et al. Monthly migraine days, tablet utilization, and 
quality of life associated with Rimegepant – post hoc results from an open label safety 
study (BHV3000–201). J Headache Pain 23, 10 (2022). https://doi.org/10.1186/s10194-
021-01378-5 
13. Hays RD, Morales LS. The RAND-36 measure of health-related quality of life. Ann Med. 
2001;33(5):350-357. 
14. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new 
five-level version of EQ-5D (EQ-5D-5L). Qua Life Res. 2011;20(10):1727-1736. 
15. Reilly MC, Arthur S. Zbrozek, Ellen M. Dukes. The validity and reproducibility of a 
work productivity and activity impairment instrument. Pharmacoeconomics. 
1993;4(5):353-365. 
16. Stewart, W. F., Lipton, R. B., Dowson, A. J., & Sawyer, J. (2001). Development and 
testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess 
headache-related disability. Neurology, 56(suppl_1), S20-S28. 
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Rimegepant 
C4951076 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 1.0, 04 October 2024  
 
PFIZER CONFIDENTIAL  
CT24-WI-GL02-RF02 6.0 Non-Interventional Study Protocol Template For Secondary Data Collection Study  
Page 20 of 20 
17. Austin, P. C., & Stuart, E. A. (2015). Moving towards best practice when using inverse 
probability of treatment weighting (IPTW) using the propensity score to estimate causal 
treatment effects in observational studies. Statistics in medicine, 34(28), 3661-3679. 
18. ISPOR. (2024). Good Practices Reports & More. Retrieved April 29, 2024, from 
https://www.ispor.org/heor-resources/good-practices. 
 
14. LIST OF TABLES  
Table 1. 
Study Variables .........................................................................................11 
Table 2. 
Estimated Sample Sizes ............................................................................14 
 
15. LIST OF FIGURES 
Not applicable. 
ANNEX 1. LIST OF STANDALONE DOCUMENTS 
None.  
ANNEX 2. ADDITIONAL INFORMATION 
Not applicable.  
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)

Document Approval Record
Document Name:
	
 	



Document Title:
	
 	



Signed By:
Date(GMT)
Signing Capacity
	
""
 	#$$
%& &! '(()&
090177e1a1e2d01f\Approved\Approved On: 10-Oct-2024 13:59 (GMT)
PPD