Clinical Decision Support for Patient Migraine Management
Phase: NA
Conditions: Migraine
Sponsor: Albert Einstein College of Medicine

Official Title: Clinical Decision Support for Patient Migraine Management 
NCT Number: NCT03706794 
IRB Number: 2015-5743 
IRB Approval Date: 06/30/2021   
Statistical Analysis Plan: 06/30/2021    

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CDST IRB Protocol – September 2020May 2021
SYNOPSIS 
Little is known about who adheres to migraine management strategies, and circumstances that enhance 
adherence. This knowledge is required to develop patient-level interventions to improve adherence to migraine 
management strategies. This type of intervention is novel, long overdue, and a major step forward in the 
clinical care of people with migraine. The proposed project will develop and pilot the first patient level 
intervention designed to improve adherence to preventive and acute migraine management strategies. We 
plan to identify people most at risk for non-adherence to migraine management strategies. We will randomly 
assign the subjects to one of two groups; for one group we will develop an individually tailored clinical decision 
support tool (CDST) (study group), for the other we will provide general headache education (control group).
PRIMARY OBJECTIVE 
The primary objective of this study is to describe and analyze how individual differences and circumstances 
influence adherence to preventive and acute migraine management strategies.  Mobile electronic headache 
diaries will be used to 1) assess the roles of individual differences and conditions in adherence to preventive 
and acute migraine management strategies, and 2) develop and pilot a tailored clinical decision support tool 
(CDST) to improve adherence to preventive and acute migraine management strategies.
PRIMARY OUTCOME VARIABLES 
The primary outcome variables will be adherence to acute and preventive migraine management 
strategies. All primary outcome variables will be assessed through an electronic headache diary. 
STUDY DURATION 
The study will last for approximately 5 years. Phase 1 of the project began in April 2016 under the approved 
Einstein IRB protocol # 2015-5743. We anticipate completing data collection in 2019, and initial data analysis 
in 2020. 
STUDY DESIGN 
This study has three phases: 
1) The first phase is an iterative qualitative design with the purpose of developing and refining the 
CDST app for use in people with episodic migraine. 
2) The second phase is a prospective observational design with the purpose of evaluating the roles of 
individual differences and conditions in adherence to preventive and acute migraine management 
strategies. 
3) The third phase is a pilot randomized clinical trial with the purpose of evaluating the CDST app 
compared to a Headache Education app to improve adherence to acute and preventive migraine 
management strategies. 
STUDY POPULATION 
Phase 1 (A & B): 
Participants will be included if they 1) have an International Classification of Headache Disorders – 3 beta 
diagnosis of migraine, 2) self-report between 6 to 14 headache days per month, 3) are currently prescribed a 
triptan for acute migraine management, 4) are between the ages of 18 and 65, and 5) self-report at least one 
problem with adherence to preventive and acute migraine management strategies.
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Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, and 3) are pregnant or are planning to 
become pregnant during study involvement (as triptans are Category C medications).
Phase 2: 
Participants will be included if they 1) have an International Classification of Headache Disorders – 3 beta 
diagnosis of migraine, 2) self-report and diary-confirmed 6 to 14 headache days per month, 3) are currently 
using one of the following treatments for acute migraine management: triptans, ditans, gepants, NSAIDs, or 
acetaminophen, 4) are stable on current preventive and acute treatment regimen for migraine, 5) are between 
the ages of 18 and 65, 6) read English, 7) have capacity to consent, and 8) complete 80% of diary recordings 
in the first 30 days of monitoring.
Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, 3) are pregnant or are planning to become 
pregnant during study involvement (as triptans are Category C medications), 4) psychiatric illness or cognitive 
difficulties that would interfere with participation in the study, and 4) participated in Phase 1 of the Clinical 
Decision Support for Patient Migraine Management protocol. 
Phase 3: 
Participants will be included if they 1) completed Phase 2 of the study, 2) completed at least 80% of diary 
recordings throughout Phase 2 of the study, and 3) demonstrated poor (<50%) adherence to at least one acute 
migraine management strategy and at least one preventive behavioral migraine management strategy during 
study Phase 2.
Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, 3) are pregnant or are planning to become 
pregnant during study involvement, 4) psychiatric illness or cognitive difficulties that would interfere with 
participation in the study. 
NUMBER OF PARTICIPANTS
There will be a total of 394 participants.
NUMBER OF STUDY SITES 
The study will be conducted at: 
The Seng (Headache & Adherence) Lab, Van Etten Building, 1225 Morris Park Ave, Bronx, NY 10461.
The Montefiore Headache Clinic, Hutchinson Tower #2,1250 Waters Pl, Bronx, NY 10461.
STUDY FLOW CHART
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1.INTRODUCTION 
1.1 Introductory Statement  
This document is a protocol for a human research study. This proposal will use mobile electronic headache 
diaries to 1) assess the roles of individual differences and conditions in adherence to preventive and acute 
migraine headache management strategies, and 2) develop a tailored Clinical Decision Support Tool to 
improve adherence to preventive and acute migraine management strategies. The purpose of this protocol is 
to ensure that this study is to be conducted according to ICH GCP guidelines (CRF 21 Part 312), applicable 
government regulations and Institutional research policies and procedures
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2. BACKGROUND 
2.1 Background/Prevalence of Research Topic 
Migraine is a chronic, painful condition with episodic attacks of head pain, nausea/vomiting, and sensitivity to 
light/sound (1). Migraine is common, affecting 1 in 7 Americans annually (2). Migraine is the most disabling 
neurological disease worldwide (3), and costs the U.S. healthcare system $4.3 billion annually (4). Patient 
adherence to migraine treatment recommendations is problematic (5-7) and can lead to increased migraine 
symptoms, burden, and economic cost (5, 8-10). Some people with migraine use preventive migraine 
management to reduce migraine frequency, and virtually all people with migraine use acute migraine 
management to reduce the impact of migraine attacks (11-14). Adherence to preventive migraine management 
strategies involves consistent use of behavioral strategies (regulating stress, sleep, and diet) (15, 16) and 
sometimes medication (often beta-blockers or antiepileptics). For acute migraine management, triptans, ditans 
and gepants are the first-line strategy for moderate-severe migraines, and non-steroidal anti-inflammatories 
(NSAIDs) or acetaminophen are the first-line strategy for mild-moderate migraines (14, 17-19). Acute migraine 
medications are most effective if taken early during a migraine episode, when head pain is still mild (11, 20-
22). Most acute migraine medication use should be limited to avoid medication overuse headache, a 
secondary headache caused by regular overuse of acute headache medication (Triptans ≥ 10 days/ month; 
NSAIDs and acetaminophen ≥ 15 days/month). Thus, adherence to acute migraine management requires in-
the-moment decision-making (11, 23).  Little is known about who adheres to preventive and acute migraine 
management strategies (individual differences) and when patients adhere to these strategies (circumstances). 
Certain individual differences (age, gender, education, psychiatric comorbidity and patient beliefs) have been 
associated with retrospective reports of adherence and pharmacy refill in isolated studies (5, 8, 24-28). 
Changes in treatment conditions (time of day, weekly migraine frequency, variations in stress and sleep) may 
be implicated in adherence to acute migraine management strategies (8), but have not been empirically 
examined. Understanding individual variability in adherence is the foundation to targeting vulnerable 
populations with adherence interventions.
3. RATIONALE/SIGNIFICANCE 
3.1 PROBLEM STATEMENT 
Migraine is a common (29), disabling (30), and costly (31) disorder characterized by episodic, painful 
symptoms. Preventive treatments can reduce migraine frequency (12, 15, 16, 32, 33), and acute treatments 
can reduce (or eliminate) symptoms of an ongoing migraine episode (11, 14, 17). Efficacy of these treatments 
relies on patient adherence. Patient adherence to migraine treatment recommendations is problematic (5-8) 
and can lead to increased migraine symptoms, burden, and economic cost (5, 8, 9). Development of 
interventions to improve adherence to migraine management strategies could reduce migraine symptoms and 
the personal, economic, and societal burden associated with migraine(5, 8, 9). Understanding factors 
associated with adherence to migraine management strategies is the foundation of improving patient 
adherence.
3.2 PURPOSE OF STUDY/POTENTIAL IMPACT 
A clinical decision support tool (CDST) for people with migraine would build upon commonly used daily 
headache diaries and offer clinical decision support to the people making clinical decisions in their daily lives: 
patients. Mobile electronic devices are potentially powerful tools to improve adherence to preventive and acute 
migraine management strategies. Electronic headache diaries are common in clinical treatment of migraine 
and have high adherence rates (6). Migraine is most prevalent mid-life (34), when the majority of Americans 
own a smartphone (35). This study will use mobile electronic headache diaries to 1) assess the roles of 
individual differences and conditions in adherence to preventive and acute migraine management strategies, 
and 2) develop a tailored CDST to improve adherence to preventive and acute migraine management 
strategies. 
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3.3 POTENTIAL RISKS AND BENEFITS 
Study risks are minimal. Participants may feel uncomfortable answering questions about their headaches or 
changing lifestyle factors associated with migraine. These outweighed by the potential gains both for study 
participants and for people with migraine broadly. 
3.3.1 POTENTIAL BENEFITS 
Individual study participants, may experience improved knowledge about their own adherence to migraine 
management strategies, as well as daily variations in headache symptoms, stress and sleep. Participants may 
experience improvements in their adherence to migraine management strategies, and potentially experience 
improvements in their migraine management.  Regarding societal benefits, this study will identify patterns of 
individual differences and circumstances associated with migraine management adherence. This will allow for 
tailored interventions to improve migraine management adherence in the patients who experience the most 
difficulty with adherence. This study will also test the feasibility and obtain initial effect sizes for a novel tailored 
intervention to improve patient adherence to migraine management strategies. If successful, this intervention 
could improve adherence to migraine management strategies, and potentially improve the effectiveness of 
migraine treatments.  
3.3.1 POTENTIAL RISKS 
The randomization process inhibits therapeutic choice of participants. It is possible that taking a headache 
diary will elicit psychological discomfort as it draws attention to each participant’s headache activity and 
associated disability. It is also possible that participants will experience discomfort when provided with 
education about how their lifestyle impacts their migraine. Finally, there is a risk that a data breach could reveal 
private information collected as part of the study.
Protections Against Risk - If participants choose to initiate a new migraine medication during the study, they 
will be removed from the study, but will be offered both the CDST and Headache Education following their 
participation in the study. Participants randomized to receive Headache Education will be offered the CDST 
following their participation in the study. Participants randomized to receive the CDST will be offered Headache 
Education following their participation in the study. Participants will be given a random study identification 
number. Participants data will either be collected on paper and stored in a locked lab file cabinet, or through 
REDCap, a secure online data capture software, through the headache diary application.  Data will be de-
identified and converted to electronic databases and stored in password-protected files on a password-
protected computer in the locked lab. The list linking participant names to identification numbers will be kept on 
paper in a locked file drawer, and destroyed immediately after the last participant information is entered in a 
de-identified database, no more than 6 months after the last day of data collection. The research assistant will 
call participants at least once per month throughout the study to assess for adverse events. The PI will also 
monitor each participant’s recorded headache diaries monthly to assess for adverse events. If either of these 
procedures identify a potential adverse event, the PI will call the participant to assess the potential adverse 
event. If the event meets adverse event criteria, the PI will immediately inform the IRB and the NIH. If the 
adverse event requires medical or professional intervention, the PI will immediately contact the participant’s 
primary clinician at the MHC and develop an intervention plan. 
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4. STUDY OBJECTIVES 
4.1 HYPOTHESIS 
Primary: We hypothesize that higher education, income and outcome expectancies, female gender, and lower 
rates of psychiatric comorbidities, will be associated with improved adherence to preventive and acute 
migraine management strategies. 
Secondary: We hypothesize that the use of the CDST will increase adherence to preventive and acute 
migraine management strategies compared to Headache Education. 
4.2 PRIMARY OBJECTIVE 
The primary objective of this study is to describe and analyze how 1) individual differences and 2) 
circumstances influence adherence to preventive and acute migraine management strategies. 
4.3 SECONDARY OBJECTIVEs (if applicable)
The secondary objective of this study is to develop and pilot a tailored clinical decision support tool (CDST) to 
improve adherence to preventive and acute migraine management strategies.
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5. STUDY DESIGN
5.1 GENERAL DESIGN
5.1.1 STUDY DURATION 
The study will last for approximately 5 years. Phase 1 of the project began in April 2016 under the approved 
Einstein IRB protocol # 2015-5743. We anticipate completing data collection in 2019, and initial data analysis 
in 2020. 
4/1/2016 – 2/1/2018
Develop CDST app
Pilot test CDST app with up to 24 people with 
migraine
Set up recruitment procedures for remainder of study
2/1/2018-10/1/2019
Recruit and run up to 120 people with migraine for 
the 3-6 months of the study period
10/1/2019-12/1/2019
Clean data
12/1/2019-4/1/2020
Conduct primary analyses and planned secondary 
analyses
4/1/2020-12/31/2020
Submit primary analyses and planned secondary 
analyses for publication
5.1.2 NUMBER OF STUDY SITES
The study will be conducted at: 
1) The Seng (Headache & Adherence) Lab, Van Etten Building, 1225 Morris Park Ave, Bronx, NY 10461.
2) The Montefiore Headache Clinic, Hutchinson Tower #2,1250 Waters Pl, Bronx, NY 10461.
5.2 OUTCOME VARIABLES 
5.2.1 PRIMARY OUTCOME VARIABLES 
The primary outcome variables will be adherence to acute and preventive migraine management 
strategies. All primary outcome variables will be assessed through an electronic headache diary. 
Adherence to Acute Migraine Management Strategies.
a) Treat Early: When participants record headache activity, they will record type, timing, and current 
pain level for each acute medication dose taken. Treating early is operationalized as taking acute 
medication while the pain is mild. 
b) Avoid Overuse: Avoiding overuse is operationalized as taking fewer than 10 triptans and 15 non-
specific pain medications (NSAIDs and acetaminophen) per month. 
Adherence to Preventive Migraine Management Strategies: 
a) Adherence to Preventive Behavioral Strategies: Each participant will record information related to a 
single strategy: stress management, sleep management, or consistent eating. Participants will record 
either 1) whether they used a stress management strategy today (assessed each evening; Yes = 
adherent, No = non-adherent), or 2) when they got in and rose out of bed (consistent bedtime and rise-
time; assessed each morning; Within 1 hour of median = Adherent, outside of 1 hr of median = Non-
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Adherent), or 3) whether they ate at least three times that day (consistent eating, assessed each 
evening; Yes = Adherent, No = Non-adherent). 
b) Adherence to Preventive Medication: If a participant is taking a preventive medication, they will 
record whether they took preventive medication each day. Taking preventive medication = Adherent, 
Not taking preventive medication = Not-adherent. 
5.2.2 SECONDARY OUTCOME VARIABLES 
Migraine Symptoms
a) Headache days per 30 days as assessed by daily headache diary.
b) Average head pain severity as assessed by daily headache diary.
Distress and Disability
a) Migraine-Related Disability as assessed by the Migraine Disability Assessment (MIDAS) (36).
b) Migraine-Specific Quality of Life as assessed by the Migraine-Specific Quality of Life Questionnaire 
(37). 
c)
Pain Interference as assessed by the PROMIS-Pain Interference (38).
d) Depression symptoms as assessed by the PROMIS-Depression Short Form (39, 40).
e) Anxious symptoms as assessed by the PROMIS-Anxiety Short Form (39, 40).
Psychological Factors
a) Stress as assessed by:
a.
The Perceived Stress Scale (41).
b.
The Daily Stress Inventory (42).
c.
Daily ratings of perceived stress on a 0-10 numeric rating scale. 
b) Sleep as assessed by:
a.
The PROMIS Sleep Disturbance (43).
b.
A daily rating of sleep quality on a 5-point Likert-type scale ranging from “Very Poor” to “Very 
Good.”
c.
A daily rating of sleep hours.
c)
Headache Management Self-Efficacy as assessed by the Headache Management Self-Efficacy 
(HMSE) scale (44) 
d) Acute Medication Self-Efficacy as assessed with the Acute Medication Self-Efficacy – Headache 
(AMSE-H) (45)
e) Study-Specific Self-Efficacy as assessed by items based on the HMSE and AMSE-H, assessing self-
efficacy for study-specific lifestyle and preventive medication adherence. 
f)
Outcome Expectancies as assessed by items based on items used in other studies (46) to assess 
each preventive and acute migraine management strategy.
g) Catastrophizing as assessed by the Pain Catastrophizing Scale (47, 48).
h) Locus of Control as assessed by the Headache-Specific Locus of Control Scale (49).
i)
Mindfulness as assessed by the Five Factor Mindfulness Questionnaire (50).
j)
Acceptance as assessed by the Chronic Pain Acceptance Questionnaire (51).
Feasibility and Acceptability
a) Patient Satisfaction as assessed by the Client Satisfaction Questionnaire (52).
b) Perceived effectiveness of intervention as assessed by the Program Evaluation Survey (based on the 
program evaluation survey used in the Treatment of Severe Migraine Trial (33)).
c)
Adverse Events as assessed by the adverse events check-ins. 
d) Adherence Rates to the diary as assessed by proportion of entries completed.
e) Education Utilization as assessed by rates of participant viewing each education module.
5.3 STUDY POPULATION 
The study population will include adult patients enrolled in the Montefiore Medical System for at least 
one year who have been prescribed a triptan within one year. Potentially eligible patients will be 
identified using Clinical Looking Glass. 
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Patients who have been prescribed a triptan, ditan or gepant, or who have taken NSAIDs or 
acetaminophen in the past year will be identified using Clinical Looking Glass. The research 
coordinator will email appropriate patients (see “Introductory email to participants” attached). There is 
an opt-out option included in the email and only patients who have not opted out will be called. Those 
who meet eligibility criteria will be consented and enrolled into the study over the phone for Phase 1 
(See “CDST stamped Oral Consent Form”, previously approved) and using the REDCap HIPAA-compliant 
data capture system for Phase 2 and 3. (Informed consent document previously approved).
Potential participants will also be recruited via internet resources such as Twitter, Facebook, and online 
postings (see “CDST Online Recruitment” and “CDST Online Recruitment - for Twitter” attached). The material 
directs potential participants to contact the study coordinator by email who will then pre-screen them.
Sampling will be stratified by gender [male = 30%; female = 70%; modeled after population migraine 
demographics (34)] to permit tests of the association of gender and adherence. 
5.3.1 NUMBER OF PARTICIPANTS 
There will be a total of 394 participants in this study. It will be necessary to screen 900 potential participants to 
meet this goal. This is a feasible goal: in the 8/2016-8/2017 period over 3,500 unique patients were prescribed 
a triptan across all providers in the Montefiore system.
5.3.2 ELIGIBILITY CRITERIA 
Eligibility will be determined by a phone screen provided by a research assistant, supervised by the PI. 
Inclusion/Exclusion Criteria Phase 1 (A & B): 
Participants will be included if they 1) have an International Classification of Headache Disorders – 3 beta 
diagnosis of migraine, 2) self-report between 6 to 14 headache days per month, 3) are currently prescribed a 
triptan for acute migraine management, 4) are between the ages of 18 and 65, and 5) self-report at least one 
problem with adherence to preventive and acute migraine management strategies.
Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, and 3) are pregnant or are planning to 
become pregnant during study involvement (as triptans are Category C medications). 
Inclusion/Exclusion Criteria Phase 2: 
Participants will be included if they 1) have an International Classification of Headache Disorders – 3 beta 
diagnosis of migraine, 2) self-report and diary-confirmed 6 to 14 headache days per month, 3) are currently 
using one of the following treatments for acute migraine management: triptans, ditans, gepants, NSAIDs, or 
acetaminophen, 4) are stable on current preventive and acute treatment regimen for migraine, 5) are between 
the ages of 18 and 65, 6) reads English, 7) has capacity to consent, and 8) complete 80% of diary recordings 
in the first 30 days of monitoring.
Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, 3) are pregnant or are planning to become 
pregnant during study involvement (as triptans are Category C medications), 4) psychiatric illness or cognitive 
difficulties that would interfere with participation in the study, and 4) participated in Phase 1 of the Clinical 
Decision Support for Patient Migraine Management protocol. 
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Inclusion/Exclusion Criteria Phase 3: 
Participants will be included if they 1) completed Phase 2 of the study, 2) completed at least 80% of diary 
recordings throughout Phase 2 of the study, and 3) demonstrated poor (<50%) adherence to at least one acute 
migraine management strategy and at least one preventive behavioral migraine management strategy during 
study Phase 2.
Exclusion criteria are 1) probable or confirmed medication overuse headache, 2) a plan to change, or changing 
preventive or acute migraine medication during study participation, 3) are pregnant or are planning to become 
pregnant during study involvement, 4) psychiatric illness or cognitive difficulties that would interfere with 
participation in the study. 
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6. METHODS 
6.1 INTERVENTION 
6.1.1 DESCRIPTION OF INTERVENTION 
Intervention occurs only in Phase 3 of the study. All data collection will occur in REDCap (Research Electronic 
Data Capture), a secure, HIPAA-compliant electronic data capture system hosted by the Research Informatics 
Core at Einstein (53). Survey collection will occur in the participant’s browser. Daily diary collection will occur 
using an app (Status/Post) developed for this study to connect participants seamlessly to REDCap using an 
Apple device. Participants who do not have an Apple device will be provided with a study iPod. Interventions 
will be delivered through the Status/Post app. 
Participants will be randomized to receive either the 1) CDST or 2) Headache Education version of the 
Status/Post App. 
1) The Clinical Decision Support Tool (CDST) version of the Status/Post app will include several 
education modules with companion reminders. Education modules are individualized websites linked to 
the app that provide a consistent source of information about migraine management. Reminders are 
just-in-time notifications the participant receives in response to their adherence behaviors throughout 
the study that briefly remind participants about the education they received in response to their 
behaviors.
All participants will receive the Medication module, designed to provide information regarding 
appropriate use of acute and preventive migraine medication. Participants will be assigned to one of 
three behavioral management education module based on their individual adherence to that behavioral 
management strategy during the Phase 2 of the study.  The three behavioral management education 
modules are: Stress Management, Sleep Management, and Consistent Eating/Hydration. Each is 
designed to provide education about why the behavioral strategy is important for migraine 
management, and provide specific tools to help patients improve their behavioral migraine 
management adherence. 
2) The Headache Education version of the Status/Post app will include several education modules 
available in the app designed to increase general knowledge about migraine, including 1) diagnostic 
criteria of migraine and other common headaches, 2) pathophysiology of migraine, and 3) common 
comorbidities of migraine and other headaches. 
6.1.2 METHOD OF ASSIGNMENT/RANDOMIZATION
A research assistant will randomize 60 people (n = 30 per group) to either the CDST Group or Headache 
Education Control Group, using block randomization with random size blocks using a computerized random 
number generator. Randomization will be stratified by gender. This research assistant will have no contact with 
any participant after he or she is randomized.
6.1.3 Selection Of Instruments/Outcome Measures 
All measures were selected using materials from the National Institutes of Neurologic Disorders and Stroke 
(NINDS) Common Data Elements (CDE) initiative. When possible, measures from the National Institutes of 
Health Patient Reported Outcome Measurement System (PROMIS) were selected. Primary outcomes were 
selected based on previous studies evaluating adherence to migraine management (5, 20, 27, 54, 55). 
Surveys
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All surveys to be used have been uploaded via the iRIS website.
Demographics 
NINDS CDEs will be used to evaluate: Age; Gender; Ethnicity; Race; Sexual Orientation; Education 
Level; Marital/Partner Status; Employment Status; Household and Income; Overall Health; Medical History; 
Height and Weight. 
Migraine Symptoms
American Migraine Study/American Migraine Prevalence and Prevention (AMS/AMPP) 
Diagnostic Module. The AMS/AMPP Diagnostic Module (34, 56) is a survey based on the ICHD-2 criteria for 
migraine; migraine criteria remain unchanged in the updated ICHD-3b (1). The sensitivity and specificity for 
migraine are 100% and 82% respectively (56).
Allodynia Symptom Checklist (ACS). The ACS is a 12-item survey designed to assess cutaneous 
allodynia in people with migraine (57). Items assess frequency of allodynia symptoms, with response options 
ranging from none to ≥ 50% of the time. Scale development identified here factors: thermal, mechanical static, 
and mechanical dynamic. Initial development indicated good psychometric qualities (57).
Medications
Preventive. Preventive medication name, dose, frequency and timing of administration, route of 
administration, and start date will be evaluated using the NINDS CDE for medications taken on a regular basis.
Acute. Acute medication name, dose, frequency, route of administration, and start date will be 
evaluated using the NINDS CDE for medications taken on an as-needed basis.
Literacy
Newest Vital Sign. The Newest Vital Sign is a 6-item survey that measures health literacy (58). 
Participants respond to open-ended questions about a nutrition label, which are coded as correct or incorrect. 
It has demonstrated reliability and validity in primary care and electronic health settings (58, 59) 
eHEALS. The eHEALS is an 8-item survey measure of eHealth literacy designed to evaluate 
knowledge, comfort, and participant self-evaluation of skills at finding, evaluating and applying electronic health 
information (60). The measure has demonstrated reliability and validity (60, 61)
Disability/Quality of Life
Migraine Specific Quality of Life Questionnaire (MSQL) v 2.1. The MSQL (37) is a commonly-used 
14-item survey measuring quality of life in people with migraine. Items comprise three subscales (Role 
Restriction, Role Prevention, and Emotion Function) which have demonstrated adequate reliability and validity 
in a number of studies with migraine (37, 62).
Migraine Disability Assessment (MIDAS). The MIDAS (36, 63) is a commonly-used 5-item survey 
measuring disruption experienced due to migraine. Items target role functioning and ask about lost days of 
house-work, job-work, and non-work activities. Each item is an open question, allowing entry of number of 
days lost over 90 days). Total scores are categorized into four, graded levels of disability severity. Several 
studies have shown the test to have good internal consistency, reliability and construct validity (63, 64).
PROMIS Pain Interference – Short Form (PROMIS-PI). The PROMIS-PI (38) is an 8-item survey 
selected from a 41-item bank developed using Item Response Theory to evaluate the amount pain interfered 
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with daily activities and enjoyment of life in the past 7 days using a normative sample. Response options range 
from 1 (Not at all) to 5 (Very Much). The measure is commonly used to evaluate pain interference and has 
demonstrated reliability and validity in a number of studies (65).
Sleep
Pittsburgh Sleep Quality Index (PSQI). The PSQI (66) is a commonly-used, reliable and valid 
measure of sleep quality that includes 19 self-rated items and 5 items rated by one’s bed partner; the first four 
self-rated items evaluate self-reported bed time, time to sleep onset, rise time, and hours of sleep per night, 
and are used in this study to evaluate sleep behavior.  
Berlin Questionnaire (Berlin). The Berlin (67) is a 10-item survey evaluating risk factors for sleep 
apnea, including snoring (Category 1), waketime sleepiness and/or fatigue (Category 2), and the presence of 
obesity and hypertension (Category 3). Qualifying as “high risk” in two of the three categories is considered 
“high risk” for sleep apnea. Items within categories demonstrated good internal consistency, and adequate 
sensitivity and specificity across categories of sleep apnea severity (67).
PROMIS Sleep Disturbance – Short Form (PROMIS – SD). The PROMIS-SD is an 8-item survey (43) 
selected from a 27-item bank (68) developed using Item Response Theory to evaluate sleep disturbance using 
a normative sample. The first item assesses perceived sleep quality, with response options on a 5-point Likert 
scale ranging from very poor to very good; the remainder of the items evaluate the extent to which participants 
endorse problems with sleep, with response options on a 5-point Likert scale ranging from not at all to very 
much. It has demonstrated validity related to other measures of sleep disturbance, including actigraphy (43, 
68).
Stress
Perceived Stress Scale (PSS). The PSS (41, 69) is a 10-item survey evaluating frequency of 
perceptions of stress (feeling life is unpredictable, uncontrollable, or overloaded) in the past month, with 
response options on a 5-point Likert scale ranging from never to very often. The PSS is the most commonly 
used survey of stress, has normative data from the United States, and has demonstrated reliability and validity 
for a two-factor model in numerous patient samples (70, 71).
Daily Stress Inventory (DSI). The DSI (42) is a 53-item survey evaluating whether 53 common daily 
hassles (e.g., performed poorly at task, ignored by others) occurred (Response options: Yes/No), and the 
extent to which hassles that occurred were appraised as stressors, with response options  on a 7-point Likert 
Type scale ranging from “occurred but was not stressful” to “caused me to panic.” The scale has demonstrated 
concurrent and construct validity (42), and has been associated with headache onset in people with chronic 
migraine and chronic tension-type headache (15).
Psychiatric Symptoms
PROMIS Depression Short-Form (PROMIS-D). The PROMIS-D (39) is an 8-item survey selected 
from a 28-item bank assessing severity of depression symptoms in a normative sample. Items assess 
frequency of depression symptoms (“I felt worthless”) in the past 7 days with response options on a 5-point 
Likert scale ranging from “never” to “always.” The PROMIS-D has demonstrated validity and increased utility in 
providing information about depression symptoms compared to other self-report measures (39, 40, 65)
PROMIS Anxiety Short-Form (PROMIS-A). The PROMIS-A (39) is an 8-item survey selected from a 
29-item bank assessing severity of anxiety symptoms in a normative sample. Items assess frequency of 
anxiety symptoms (“I felt nervous”) in the past 7 days with response options on a 5-point Likert scale ranging 
from “never” to “always.” The PROMIS-D has demonstrated validity and increased utility in providing 
information about depression symptoms compared to other self-report measures (39, 40, 65).
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Psychological Variables
Pain Catastrophizing Scale (PCS). The PCS (47) is a 13-item survey designed to assess the extent to 
which a participant utilizes maladaptive, catastrophic cognitive styles in response to painful experiences.  Items 
comprise three subscales (Rumination, Magnification, and Helplessness) with response options on a 5-point 
Likert scale ranging from “not at all” to “all the time.” The current study utilizes the headache version, which has 
demonstrated reliability and validity in people with headache (48).
Headache Management Self-Efficacy (HMSE). The HMSE (44) is a 25-item survey designed assess 
the extent to which a person with headache is confident in their ability to change their behavior to manage 
headache episodes. Response options are on a 7-point Likert scale ranging from “strongly disagree” to 
“strongly agree.” The HMSE has demonstrated excellent internal consistency and validity in samples with 
headache and migraine (44, 72). 
Acute-Medication Self-Efficacy – Headache (AMSE-H). The AMSE-H (45) is a 7-item survey 
designed to assess the extent to which a person with headache is confident they can take his or her acute 
headache medication optimally. Response options are on an 8-point Likert scale and range from “strongly 
disagree” to “strongly agree.” The AMSE-H has demonstrated adequate internal consistency and construct 
validity (45). 
Study-Specific Self-Efficacy. The study-specific self-efficacy survey includes three items that evaluate 
confident to adhere to each behavioral self-management strategy evaluated in this study (manage stress, 
sleep consistently, and eat and drink consistently), with response options on a 7-point Likert scale and range 
from “strongly disagree” to “strongly agree.” Items were developed using guidelines recommended by Bandura 
for self-efficacy scale development (46).
Outcome Expectancies. The study-specific outcome expectancies survey includes 7 items that 
evaluate the extent to which a participant believes that adhering to the specific migraine management 
strategies evaluated in this study will lead to a reduction in headache symptoms. Items were developed using 
guidelines recommended by Bandura (46) and items developed for other studies evaluating outcome 
expectancies for treatments for migraine and osteoporosis (45, 73)
Headache-Specific Locus of Control (HSLC). The HSLC (49) is a 33-item survey designed to assess 
the extent to which individuals with recurrent headache expect the occurrence, worsening, and improvement of 
their headaches are influenced primarily by their own behavior, by chance or fate, or by the actions of medical 
professionals. Items are coded on a 5-point Likert-type scale ranging from “strongly disagree” to “strongly 
agree.” It contains three subscales, which include Internal, Chance, and Medical Professionals. Each subscale 
demonstrated good internal consistency (s = 0.80-0.89) and adequate 3-week test-retest reliability (rs = 0.72-
0.78). Subscales also demonstrated significant expected relationships with related measures (49).
Five Factor Mindfulness Questionnaire (FFMQ). The FFMQ (50) is a 39-item survey designed to 
evaluate the extent to which participants engage in mindfulness. Items comprise five subscales: Observing, 
Describing, Acting with Awareness, Non-Judging of Inner Experience, and Non-Reactivity to Inner Experience 
and are rated on a 5-point Likert scale ranging from “never or rarely true” to “very often or always true.” The 
FFMQ has demonstrated adequate internal consistency and construct validity (50). 
Chronic Pain Acceptance Questionnaire (CPAQ). The CPAQ (51) is a 20-item survey designed to 
assess pain-related acceptance that was developed with patients suffering from chronic pain. Items comprise 
two subscales (Pain Willingness and Activity Engagement) and are rated on a 7-point Likert scale ranging from 
“never true” to “always true.” The current study uses the headache version. The CPAQ has demonstrated 
acceptable internal consistency ( = 0.78–0.82) and construct validity in pain and migraine samples (51, 74)
Patient Satisfaction
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Client Satisfaction Questionnaire (CSQ). The CSQ (52) is an 9-item survey designed to measure 
users’ general satisfaction with human service programs. The CSQ is commonly used in treatment and 
program evaluation and has demonstrated excellent internal consistency (52). 
Program Evaluation. The Program Evaluation survey is an 8-item, study-specific survey that evaluates 
the extent to which participants deemed the app to be effective (with response options on a 5-point Likert scale 
ranging from “not at all effective” to “very effective”) and the extent to which participants are likely to 
recommend the app to a friend with migraine (with response options on a 5-point Likert scale ranging from “not 
at all likely” to “very likely”). Items were based on the program evaluation survey from a previous clinical trial 
evaluating preventive medication and behavioral migraine treatments (33). 
Daily Diary
Morning. The morning diary will include measures assessing a) Menstruation, b) Headache 
Symptoms using ICHD-3b migraine criteria (1), c) Acute Medication Usage with items used in other 
headache medication adherence studies (54), and d) Sleep Behavior, using selected items from the 
Consensus Sleep Diary (75).
 
Afternoon. The afternoon diary will include measures assessing a) Headache Symptoms using ICHD-
3b migraine criteria (1), and b) Acute Medication Usage with items used in other headache medication 
adherence studies (54).
Evening. The evening diary will include measures assessing a) Preventive Medication Usage with an 
item used in other headache medication adherence studies (54), b) Headache Symptoms using ICHD-3b 
migraine criteria (1), c) Acute Medication Usage with items used in other headache medication adherence 
studies (54), d) Eating and Hydration Behavior using one item asking participants to check off each hour 
during which they consumed food in the past 24 hours, and one item asking participants how many glasses of 
liquids they consumed in the past 24 hours, e) Stress Level and Management using a 0-10 Visual Analog 
Scale to rate stress level and a single item assessing stress management, and d) Migraine Disability using an 
abbreviated daily version of the MIDAS (36).
6.1.4 Intervention Administration
During Phase 1, the CDST or Headache Education version of the app will be administered to participants for 
one week. During Phase 3, the CDST or Headache Education version of the app will be administered to 
participants for 3 months. In both Phases, participants will download the app to their personal Apple device, or 
to a study-provided Apple device. Participants will receive a series of education modules (Figure 6.1.4), and for 
participants in the CDST group, notifications in the app tailored based on diary entries, which occur three times 
daily. 
Figure 6.1.4
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Treatment fidelity is conceptualized as the app providing the education and reminders at the allocated times. 
The app will monitor this information internally during both Phase 1 and 3. 
6.1.4 Reaction Management 
The expected risk of the CDST intervention is increased headache activity due to inhibition of therapeutic 
choice of participants. This risk is considered minimal. Participants may reach out to the research coordinator 
at any time if they experience discomfort or distress related to the study. The research coordinator will 
proactively assess participant reactions to the study in bi-weekly check-ins. The unblinded research assistant 
will also monitor participant’s headache diary recordings to evaluate reactions to the study. Participants who 
report, or are suspected to have, clinically significant discomfort or distress during the study will immediately be 
reported to the PI, Dr. Elizabeth Seng, Ph.D., clinical psychologist. Dr. Seng will assess the reaction and 
determine whether further action is warranted, such as an intervention plan or referral for treatment. If Dr. Seng 
is unavailable, or if her role as PI would interfere with her ability to assess and intervene with participant 
distress, Dr. Elizabeth Hirky, Ph.D., clinical psychology and Director of Clinical Training at Ferkauf Graduate 
School of Psychology, Yeshiva University (anne.hirky@mail.yu.edu) will assess and determine the best course 
of action in the case of participant distress.
6.2 Assessments
6.2.1 Efficacy 
The primary outcome variables will be adherence to acute and preventive migraine management 
strategies. All primary outcome variables will be assessed through the daily electronic headache diary, 
collected through the Status/Post app and captured by the REDCap system. 
Adherence to Acute Migraine Management Strategies.
When 
assessed
Question asked
Indication of 
adherence
Indication of
non-adherence
Stress
each 
evening
whether they used a stress 
management strategy today
Yes
No
Sleep
each 
morning
when they got in and rose out of bed
Within one hour of 
median
Outside of one hour 
of median
Eating
each 
evening
whether they ate at least three times 
that day
Yes
No
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Treat Early: When participants record headache activity, they will record type, timing, and current 
pain level for each acute medication dose taken. Treating early is operationalized as taking acute 
medication while the pain is mild. 
Avoid Overuse: Avoiding overuse is operationalized as taking fewer than 10 triptans and 15 
NSAIDS/acetaminophen per month. 
Adherence to Preventive Migraine Management Strategies: 
Adherence to Preventive Behavioral Strategies: Each participant will record information related to a 
single strategy: stress management, sleep management, or consistent eating. Participants will record 
either 1) whether they used a stress management strategy today (assessed each evening; Yes = 
adherent, No = non-adherent), or 2) when they got in and rose out of bed (consistent bedtime and rise-
time; assessed each morning; Within 1 hour of median = Adherent, outside of 1 hr of median = Non-
Adherent), or 3) whether they ate at least three times that day (consistent eating, assessed each 
evening; Yes = Adherent, No = Non-adherent). 
Adherence to Preventive Medication: If a participant is taking a preventive medication, they will 
record whether they took preventive medication each day. Taking preventive medication = Adherent, 
Not taking preventive medication = Not-adherent. 
6.2.1 Safety 
Safety will be evaluated by:
1)  Tracking adverse events reported by participants, and collected proactively in bi-weekly check-ins 
conducted by the research coordinator, as described below; and,
2) The unblinded research assistant will monitor symptoms recorded in participant’s headache diaries for 
any unexpected changes in symptoms. Potential adverse events or any other situation requiring 
reaction management will immediately be reported to the PI. If Dr. Seng is unavailable, or if her role as 
PI would interfere with her ability to assess and intervene with participant distress, Dr. Elizabeth Hirky, 
Ph.D., clinical psychology and Director of Clinical Training at Ferkauf Graduate School of Psychology, 
Yeshiva University (anne.hirky@mail.yu.edu) will assess and determine the best course of action in the 
case of participant distress.
The unblinded research assistant will collate data regarding adverse events and changes in symptoms by 
group and provide these data to the Data Safety Monitoring Committee monthly. 
6.2.1.2 Adverse Events Definition And Reporting 
An adverse event (AE) is any troublesome medical occurrence in a subject during participation in the clinical 
study. An AE can include a sign, symptom, abnormal assessment, or any combination of these. A serious 
adverse event (SAE) is any AE that results in one or more of the following outcomes: death, a life-threatening 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, a congenital anomaly or birth defect, or an important medical event based upon 
appropriate medical judgment. We will use the HHS/NIH/NCI Common Terminology Criteria for Adverse 
Events (Version 4.0) grading scale; for reference, we have provided the criteria for headache AEs (Grades 1-
3): Grade 1: Mild (mild headache pain); Grade 2: Moderate (moderate headache pain that limits instrumental 
activities of daily living); Grade 3: Severe or medically significant but not immediately life threatening (severe 
headache pain that limits self-care activities of daily living); Grade 4: Life-threatening consequences; Grade 5: 
death related to AE. When present, each AE will be categorized according to the likelihood that they are 
related to the CDST on a 4-point scale, ranging from definitely unrelated, possibly related, probably related, to 
definitely related.  The expected risk of the CDST intervention is increased headache activity due to inhibition 
of therapeutic choice of participants. This risk is considered minimal.  
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The research coordinator will assess adverse events in bi-weekly check-ins with participants. The unblinded 
research assistant will assess headache activity bi-weekly and provide reports to the Data Safety Monitoring 
Committee (DSMC) at minimum every 6 months.  The research assistant will call participants at least once per 
month throughout the study to assess for adverse events. The PI will also monitor each participant’s recorded 
headache diaries monthly to assess for adverse events. 
If any of these procedures identify a potential adverse event, the participant will be called immediately to 
assess the potential adverse event. Participants who disclose potential adverse events to any study staff at 
any point during the study will immediately be reported to the PI, Dr. Elizabeth Seng, Ph.D., clinical 
psychologist. If Dr. Seng is unavailable, Dr. Elizabeth Hirky, Ph.D., clinical psychology and Director of Clinical 
Training at Ferkauf Graduate School of Psychology, Yeshiva University (anne.hirky@mail.yu.edu) will assess 
and determine the best course of action in the case of immediate participant distress. If the adverse event 
requires medical or professional intervention, the PI or Dr. Hirky will immediately contact the participant’s 
primary clinician at the MHC and develop an intervention plan and referral if necessary. If a participant 
experiences an adverse event, he or she will be given an opportunity to leave the study. Any SAEs that are 
possibly related to the study intervention will be reported to the IRB and NIH within 7 days. All AEs will be 
compiled and reported to the Einstein IRB and NIH in accordance with the Einstein IRB requirements.
The Data Safety Monitoring Committee (DSMC) will consist of Drs. Andrea Weinberger, Ph.D., Assistant 
Professor of Psychology, and Frederick Foley, Ph.D., Professor of Psychology, at Ferkauf Graduate School of 
Psychology, Yeshiva University. The DSMC has final authority regarding making decisions regarding 
continuation, revision or discontinuation of the research project. The DSMC will meet every six months. The 
unblinded research assistant will provide reports of adverse events and diary-recorded symptoms by group to 
the DSMC at minimum every six months. The DSMC will provide minutes of each meeting to the PI, including 
attendance, summary of the discussion, and any findings. The PI will be responsible for implementation of this 
Data Safety Monitoring Plan and will report directly to the Einstein IRB and the NIH. 
6.3 Study Procedures
6.3.1 Study Schedule 
Phase 1A
Screening and Enrollment: Up to 50 potential participants will be screened to identify 24 participants eligible 
and interested in the study. Potential participants will be contacted by phone or email by the research 
coordinator to be screened for inclusion criteria. If participants meet inclusion criteria and are interested in 
study participation, the research coordinator will provide informed consent over the phone (see “CDST 
stamped Oral Consent Form”, previously approved). 
Study Procedures: Participants will then receive an email from the research coordinator (see “CDST - App 
download email” attached) with instructions to download the study app. Participants will download the study 
app onto their device and will receive either the CDST or Headache Education version of the app. Participants 
will use the app, including three daily diary entries, for one week. After one week, the PI will have conduct a 
focus group interview with each participant (see “Focus Group Seed Questions 11.10.15” previously approved. 
Once the focus group is completed, the research coordinator will send the participant a thank you email (see 
“CDST - Thank you emails “attached) with an attached gift card compensation ($30).
Phase 1B
Screening and Enrollment: Up to 500 potential participants will be screened to identify 250 participants 
eligible and interested in the study. Potential participants may be contacted by phone or email by the research 
coordinator to be screened for inclusion criteria. If participants meet inclusion criteria and are interested in 
study participation, they will provide informed consent via the REDCap app. 
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Study Procedures: Participants will then receive an email from the research coordinator (see “CDST - App 
download email” attached) with instructions to download the study app. Participants will download the study 
app onto their device. Participants will use the app, making one daily diary entry, for one month. After one 
month, the PI may conduct a focus group interview with each participant (see “Focus Group Seed Questions 
11.10.15” previously approved). Once participation completed, the participant will be entered in a raffle for one 
of three $200 gift cards as compensation. 
Phase 2 and 3
Figure 6.3.1. Phase 2 and 3 Study Schedule
Screening: Up to 350 participants will be screened to identify 120 participants who may be eligible to 
participate in Phase 2 of the study. The research coordinator will identify participants who may be eligible using 
Clinical Looking Glass. The PI will obtain permission from providers with numerous potentially eligible patients 
to send a letter from the provider informing them of their eligibility for the study and providing them study 
contact information to opt-out of further communication, or express interest in enrollment (see “CDST 
Recruitment Potential Participant Letter’ previously approved). Participants will then be contacted by phone or 
email (see” CDST - Introductory email to participants” attached) by the research coordinator to set up phone 
screens with a research assistant, who will be supervised by the PI (see “Phase 2-3 Screening Checklist 
1.8.18” attached). 
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Phase 2: Participants who are interested in study participation and self-report meeting eligibility criteria during 
the phone screen will be send a REDCap link to provide informed consent and complete baseline surveys (see 
Figure 6.3.1). Participants who provide informed consent and complete all Month 0 surveys will be sent 
instructions to initialize the study app for daily diary data collection ONLY (e.g., no CDST or Headache 
Education intervention). Participants will complete one month of daily diary collection during the Baseline 
Evaluation Period to assess eligibility criteria that require diary confirmation. If participants continue to meet 
criteria for the study, they will be invited to complete monthly and midpoint assessments and continue with the 
daily diary until Month 3.
The research coordinator will email each participant bi-weekly and provide feedback on diary days completed, 
offer troubleshooting for the application, and assess for adverse events (see “CDST - Bi-weekly email” 
attached). Participants will receive an additional contact from the research coordinator if they fail to record data 
for 2 days in a row (see “CDST - Missed entries email” attached). After the conclusion of Phase 2, the research 
coordinator will thank participants for their study participation (see “CDST - Thank you emails” attached) and 
provide a compensation gift card ($20 for Month 0 and 3 surveys, $10 for Months 1 and 2 surveys, and $0.50 
for each diary entry, with total possible compensation of $105).  
Phase 3: At the end of Phase 2, a research assistant supervised by the PI will evaluate each participant’s diary 
data to determine eligibility criteria for Phase 3. The research coordinator will reach out to each participant and 
inform them of their eligibility determination for Phase 3, and assess interest in continuing in the study. 
Participants who are eligible and interested in participating in Phase 3 will be randomized by an unblinded 
research assistant, who will have no contact with participants after randomization. The rest of the study staff 
will be unaware of each participant’s randomization status. 
After randomization, the participant will be sent instructions for initialization of the intervention study app from 
the research coordinator. Participants will use the intervention version of the app for three months. During this 
time, participants will continue to complete the headache diary three times daily and complete monthly and 
endpoint surveys (see Figure 6.3.1). 
The research coordinator will continue to email each participant bi-weekly and provide feedback on diary days 
completed, offer troubleshooting for the application, and assess for adverse events, and reach out if the 
participant fails to record data for 2 days in a row. After the conclusion of Phase 3, the research coordinator will 
thank participants for their study participation and provide a compensation gift card ($20 for Month 6 surveys, 
$10 for Months 4 and 5 surveys, and $0.50 for each diary entry, with total possible compensation of $85).  
6.3.2 Informed Consent 
Phase 1A
Prior to the screening call, the research coordinator will send the prospective participant an email including a 
copy of the oral consent form (see “CDST - Oral consent preview email” attached). During the screening call, 
the research coordinator will inform prospective participants that the study seeks to develop a tool embedded 
in a headache diary to improve patient decision making regarding migraine management adherence. They will 
be informed that the study will last for one week, during which time they will receive popup notifications in a 
3x/day headache diary. They will also be informed that, at the end of the week, they will participate in a focus 
group with the PI that may last up to an hour. They will be informed about compensation for participation. The 
research coordinator will obtain informed consent over the phone (see “CDST stamped Oral Consent Form”, 
previously approved) and send the participant a confirmation email (see “CDST - Oral consent confirmation 
email” attached).
Phase 1B
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Prospective participants will be informed that the study seeks to develop a tool embedded in a headache diary 
to improve patient decision making regarding migraine management adherence. They will be informed that the 
study will last for one month, during which time they will receive popup notifications in a 1x/day headache 
diary. They will also be informed that, at the end of the month, they may participate in a focus group with the PI 
that may last up to an hour. They will be informed about compensation for participation. The prospective 
participant will electronically sign the consent form on REDCap, a secure web application for building and 
managing online surveys and databases. The research coordinator will send the participant a confirmation 
email after consent is obtained.
Phase 2 and 3
During the screening call, the research assistant supervised by the PI will inform prospective participants that 
the study seeks to understand how people manage their migraines, and what factors impact patient migraine 
management, using monthly surveys and a headache diary that will sound three times per day for three 
months. Prospective participants will also be informed that, if they meet inclusion criteria after three months, 
they will have the opportunity to continue in the study and be randomized to receive one of two kinds of 
education that will pop-up as notifications in their headache diary, with the goal of improving migraine 
management. Prospective participants will be informed that they would continue to take monthly surveys and a 
headache diary that will sound three times a day for an additional three months. Thus, the total potential length 
of study participation is 6 months. Participants will be informed about compensation for participation. If 
interested and eligible, the potential participant will be provided with an opportunity to provide online informed 
consent (“Informed Consent Phase 2.3” uploaded to the informed consent section of iRIS).
6.3.3 Screening 
Phase 1
Participants will be screened for inclusion/exclusion criteria during a scheduled phone call by the Research 
Coordinator (see “CDST Screener Grid” previously approved). This call should take no longer than 20 minutes. 
Phase 2 and 3
Participants will be pre-screened for inclusion/exclusion criteria through Clinical Looking Glass by the 
Research Coordinator (see “Phase 2-3 Screening Checklist 1.8.18” attached). Participants will be screened by 
a research assistant supervised by the PI during a scheduled phone call (see “Phase 2-3 Screening Checklist 
1.8.18” attached). This call should take no longer than 30 minutes. Participants who self-report meeting study 
inclusion criteria will be enrolled in the study and monitored with a headache diary three times daily for 30 
days. After 30 days, a research assistant supervised by the PI will confirm study inclusion criteria. If 
participants do not meet study inclusion criteria at this time, they will be informed and removed from the study 
and provided with appropriate gift card compensation (see “CDST-Thank you emails” attached). 
6.3.4 Enrollment 
Phase 1
After completing the phone informed consent, the research coordinator will enroll the participant in the study 
and assign them a random study identification number.
Phase 2 and 3
After potential subjects have completed the online informed consent document, the research coordinator will 
assign them a random study identification number and register the participant in the study in 
Einstein/Montefiore’s EPIC medical records system.
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6.3.5 On Study Visits 
All study visits occur either over the phone or via scheduled REDCap data capture sessions, which are either 
accessed through the participant’s email on any device, or through the study app on either the participant’s 
personal Apple device or the study-provided Apple device.
Phase 1A & B
Screening

Research coordinator will assess inclusion/exclusion criteria

Approximately 20 minutes in length
App Testing

Interact with CDST or Headache Education version of app 3 times daily for 7 days (Phase 1A) or 30 
days (Phase 1B).

Each diary entry will take between 1-5 minutes 
Focus Group:

At least one participant per focus group; Focus group led by the PI

Up to 60 minutes in length

Questions will focus on: 1) User Interface; 2) Message Content; 3) Message Delivery and Frequency, 
and 4) Overall Satisfaction
Phase 2 and 3
Screening

Research assistant will assess inclusion/exclusion criteria with the supervision of the PI

Approximately 30 minutes in length
Electronic Data Collection:

App-based

Phase 2: Month 0-Month 3

Phase 3: Month 3-Month 6

See schedule of assessments below
Table 6.1.3. Timing of Measures
Month 0
~20 min.
Demographics
Migraine Symptoms 
Medications
Health literacy (Newest Vital Sign)
E-health literacy (eHEALS)
Pittsburgh Sleep Quality Index (first 4-items)
Berlin Questionnaire
Month 0
Month 3
Month 7
~40 min.
Migraine Disability Assessment
Headache Management Self-Efficacy 
Acute Medication Self-Efficacy - Headache
Study-Specific Self-Efficacy
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Outcome Expectancies
Headache Specific Locus of Control
Pain Catastrophizing Scale
Five Factor Mindfulness Questionnaire
Chronic Pain Acceptance Questionnaire
Monthly
~20 min.
Migraine Specific Quality of Life 2.1
PROMIS Interference
Perceived Stress Scale
PROMIS Anxiety 
PROMIS Depression 
PROMIS Sleep Disturbance
Daily Stress Inventory
Daily 
Morning (~3-5 min.)
-Menstruation
-Headache Symptoms
-Acute Medication Usage 
-Sleep Behavior
Afternoon (~1-2 min.)
-Headache symptoms
-Acute Medication usage 
Evening (~3-5 min.)
-Preventive Medication Usage
-Headache Symptoms
-Acute Medication Usage 
-Eating and Hydration behavior
-Stress Level and Management
-Migraine Disability
Month 7
~7 min.
Client Satisfaction Questionnaire
Program Evaluation
6.3.6 End of Study and Follow-Up 
At Month 7, participants will complete a long battery of surveys they have been completing throughout the 
study; additional surveys are the CSQ and Program Evaluation Surveys. If a participant is randomized to an 
intervention group but discontinues participation in the study for any reason prior to Month 7, they will be asked 
to complete the CSQ and Program Evaluation Surveys. Adverse Events are assessed by research coordinator 
contacts bi-weekly throughout the study. If a participant withdraws from the study early for any reason, we will 
complete this assessment at that time. 
6.3.7 Removal of Subjects
Phase 1: Participants will be removed if they choose to voluntarily withdraw. 
Phase 2 and 3: Participants will be removed if they choose to voluntarily withdraw. Participants will be 
removed if they no longer meet any study inclusion/exclusion criteria (for example, if they do not have diary-
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confirmed migraine, or if they initiate a new migraine medication during the study). Participants who withdraw 
for any reason will be given the option of continuing to use the app if they choose. 
All participants will be provided with a synopsis of their diary data to be used in their routine clinical care 
following the study. 
6.4 Statistical Method
6.4.1 Statistical Design 
Basic descriptive statistics (e.g., means, standard deviations, frequencies) for variables of interest will be 
computed. Graphical approaches will be used to further explore the data where appropriate. The outcomes are 
either 1) repeated measures of binary adherence to each migraine management strategy [coded each day as 0 
(did not adhere) or 1 (adhered)] or total number of non-adherence days for each migraine management 
strategy over the relevant time-frame. Longitudinal binary outcomes will be analyzed using randomized logistic 
models, and number of total non-adherence days will be examined using Poisson regression models. SAS 9.3 
will be used in the analyses. All tests are two-sided using significance level 0.05.
6.4.2 Sample Size Considerations 
Based on n=30 subjects in CDST and Headache Education Control groups, and assumptions of dropout rate 
and correlations as described in the initial phase of the study, we will have 80% power to detect an odds ratio 
of 1.28 in adherence to migraine management strategies between CDST and Headache Education Control. 
For Phase 1b, we would like to estimate satisfaction, usability, and attrition over the course of the month of 
diary use. In our previous daily diary research, approximately 60% of participants do not continue using 
headache diary applications after 3 days, and approximately 30% of people adhere to the daily diary for the 
duration of a 30-day study. Therefore, we hope to obtain information from n=60 people regarding satisfaction 
and usability at the end of the 30-day period. 
For the main phase of the study, based on estimated proportions of 0.37 for stress management, 20% with 
mood disorder and 30% male, cumulative drop-out rate of 0.073, 0.172 and 0.216 at the end of 1, 2, and 3 
month, respectively, from previous studies 1, and assuming correlations of no more than 0.6 among repeated 
daily  migraine management strategies, with n=100 participants, we can detect odds ratios of 1.29 between 
those with and without mood disorder, 1.26 between female and male, and 1.17 corresponding to 1 SD 
difference in continuous predictors, with 80% power.
6.4.3 Planned Analyses 
6.4.3.1 Primary Analyses 
Primary Objective: Describe and analyze how individual differences and conditions influence adherence to 
preventive and acute migraine management strategies. 
Phase 2 diary data will be utilized. Random effects logistic models will be used to examine the effects of 
individual differences (e.g., age and gender) and circumstances (headache days/last 7 days, variations in 
stress) on daily adherence to migraine management strategies during the initial three-month study period. The 
random effects logistic model is a kind of generalized linear mixed effects model which can take account of 
missing data due to drop outs. This type of analysis yields robust estimates even in situations when 
observations are missing both at random, and not at random. The total number of non-adherence days at the 
end of follow-up will also be obtained, and the effect of individual characteristics and conditions on the rate of 
non-adherence will be examined using Poisson regression model with log of length of follow-up as offset. 
 
6.4.3.2 Secondary Objectives Analyses
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Secondary Objective: Develop a tailored CDST to improve preventive and acute migraine management 
strategies. 
Phase 3 diary data will be utilized. As described above, random effects logistic models will be used to examine 
the effects of Group (CDST vs. Headache Education Control), Time, and Group X Time on daily adherence to 
migraine management strategies. Poisson regression model with log of length of follow-up as offset will be 
used to examine differences between the groups on total number of nonadherence days at the end of the 
study.   
6.4.3.3 Safety 
Safety will be evaluated by:
1)  Tracking adverse events reported by participants, and collected proactively in bi-weekly check-ins 
conducted by the research coordinator, as described below; and,
2) The unblinded research assistant will monitor symptoms recorded in participant’s headache diaries for 
any unexpected changes in symptoms. Potential adverse events or any other situation requiring 
reaction management will immediately be reported to the PI. If Dr. Seng is unavailable, or if her role as 
PI would interfere with her ability to assess and intervene with participant distress, Dr. Elizabeth Hirky, 
Ph.D., clinical psychology and Director of Clinical Training at Ferkauf Graduate School of Psychology, 
Yeshiva University (anne.hirky@mail.yu.edu) will assess and determine the best course of action in the 
case of participant distress.
The unblinded research assistant will collate data regarding adverse events and changes in symptoms by 
group and provide these data to the Data Safety Monitoring Committee monthly. Any SAEs that are 
possibly related to the study intervention will be reported to the IRB and NIH within 7 days. All AEs will be 
compiled and reported to the Einstein IRB and NIH in accordance with the Einstein IRB requirements.  
6.4.3.4 Analysis of Subject Characteristics 
Demographics (age, gender, and education) will be assessed in the initial assessment via questionnaire. 
Sampling will be stratified by gender (male n = 30; female n = 70; modeled after population migraine 
demographics) to permit tests of the association between gender and adherence.  Basic descriptive statistics 
(e.g., means, standard deviations, frequencies) for variables of interest will be computed. Graphical 
approaches will be used to further explore the data where appropriate.
6.4.4 Subsets and Covariates 
Although we hope that the randomization procedure will result in relatively equal groups, we recognize that 
with a pilot study with such a small sample, it is possible groups will differ on relevant variables. We will 
evaluate differences between randomized groups on demographics of interest: age, gender, education, and 
race/ethnicity. Because of the relatively low number of men participating in migraine studies, we will stratify 
both recruitment and randomization by gender. We will also evaluate baseline differences between randomized 
groups on adherence outcomes collected during Phase 2, and migraine symptoms (days and severity) 
collected during Phase 2. If any significant differences are found between the groups, we will run unadjusted 
and adjusted primary outcome analyses. 
6.4.5 Handling of Missing Data 
The random effects logistic model is a kind of generalized linear mixed effects model which can take account 
of missing data due to drop outs. This type of analysis yields robust estimates even in situations when 
observations are missing both at random, and not at random.
7. Trial Administration
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7.1 Ethical Considerations  
There is no deception in this study.  All participants will be told that they will receive additional messages in 
their headache diary, and that the purpose of the study is to examine what kinds of messages improve 
adherence to migraine management. Each participant will receive education that could improve migraine 
management sent via the diary app. Some participants will receive a CDST, whereas others will receive more 
general Headache Education. Group assignment will be random. 
Subjects will be made aware that nominal payment will be provided as compensation. Gift Cards will be sent 
after participation Phase 1A ($30), Phase 1B (participants will be entered into a raffle for one of three $200 Gift 
Cards), Phase 2 (up to $105), and Phase 3 (up to $85). 
The proposed research does not target vulnerable populations and will not involve any of the following 
vulnerable populations: fetuses, neonates, children, pregnant women, prisoners, institutionalized individuals. 
Information about patient diagnoses, medications, and health care utilization will be obtained from the MHC 
electronic health record. Participants will provide data through electronic surveys given either semi-monthly, 
monthly, or as part of a diary given 3 times daily. Participant data will be collected via REDCap, a secure online 
data capture software, through the headache diary application. These data, which will not contain identifiable 
information, will be kept in a password protected database on a password-protected file on lab computers. 
Only the PI, Research Coordinator and research assistant will have access to these files. Data will be de-
identified and converted to electronic databases and stored in password-protected files on a password-
protected computer in the locked lab. A list linking participant identification numbers will be kept in a password-
protected file on the password-protected hard drive in Dr. Seng’s lab, and will be destroyed immediately after 
all data has been entered (no more than 6 months after the end of data collection). 
There is always a slight possibility that an unknown condition will be discovered during initial or follow-up 
interviews, or direct communication with the subject. If either of these procedures identify a potential condition, 
the research assistant will immediately inform the PI who will contact the participant. If the condition requires 
medical or professional intervention, the PI will immediately contact the participant’s primary clinician. If the 
discovery of the condition meets adverse event criteria, the PI will immediately inform the IRB and the NIH.
There will be no information added to the subject’s permanent medical file other than their participation in the 
study.
 
7.2 IRB Review 
This study will undergo a complete IRB review by the Albert Einstein College of Medicine IRB.  It will be 
required to have yearly renewal reviews.
7.3 Subject Confidentiality 
Each participant will be given a random study identification number. Only the PI, Research Coordinator and 
research assistant will have access to identifiable private information. Participants data will be collected 
REDCap, a secure online data capture software, through the headache diary application. These data, which 
will not contain identifiable information, will be kept in a password protected database on a password-protected 
file on lab computers. Only the PI, Research Coordinator and research assistant will have access to these files. 
Data will be de-identified and converted to electronic databases and stored in password-protected files on a 
password-protected computer in the locked lab. A list linking participant identification numbers will be kept in a 
password-protected file on the password-protected hard drive in Dr. Seng’s lab, and will be destroyed 
immediately after the last participant information is entered in a de-identified database, no more than 6 months 
after the last day of data collection.
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7.4 Unanticipated Problems 
If there is any medical or psychological problem discovered, the PI will call the participant immediately to 
assess the problem. If the problem requires medical or professional intervention, the PI will immediately 
contact the participant’s primary clinician and develop an intervention plan and referral if necessary. If a 
participant experiences an adverse event, he or she will be given an opportunity to leave the study.
All adverse events, whether anticipated or not, will be compiled and reported to the Einstein IRB and NIH in 
accordance with the Einstein IRB requirements.  Any serious adverse events, whether anticipated or not will be 
reported to the IRB and NIH within 7 days.
7.5 Data Quality Assurance 
7.5.1 Data Collection 
There will be several types of data collected.

Phase 1 focus group data will be collected through direct transcription during focus groups. Transcripts 
will be de-identified and kept in a password protected database on a password protected file on lab 
computers. Only the PI, research coordinator and research assistants will have access to these files.

All Phase 2 and 3 study data will be entered directly by participants into an electronic database on 
participants’ personal devices or study-provided devices.  REDCap is a secure, web-based data 
capture system accessible via home computers and mobile devices. After de-identification, these data, 
will be kept in a password protected database on a password-protected file on lab computers. Only the 
PI, research coordinator and research assistants will have access to these files. 

A list linking participant identification numbers will be kept in a password-protected file on the 
password-protected hard drive in Dr. Seng’s lab.  Only the PI, Research Coordinator and research 
assistant will have access to this list and it will be destroyed immediately after all data has been entered 
(no more than 6 months after the end of data collection).  
7.5.1.1 Access to Source 
Phase 1: De-identified data is held in password-protected Word documents. This allows for exporting the data 
to be analyzed by qualitative software programs. All analyses are planned to be conducted by lab members 
named as key personnel on this protocol. 
Phase 2 and 3: Daily headache data will be entered by the participant through the daily electronic headache 
diary, collected through the Status/Post app and captured by the REDCap system, a secure online data 
capture software. The answers to all survey questions will be entered by the participant using a direct link to 
the REDCap system. The REDCap data capture system allows for transformation of data to a form that can be 
used with data analysis programs.  We will export the data into a de-identified password-protected database 
which will be held on the lab computer. All analyses are planned to be conducted by lab members named as 
key personnel on this protocol.
7.5.1.2 Data Storage/Security 
Phase 1: Focus group transcripts will be de-identified and kept in a password protected Word Doc on a 
password protected file on lab computers. This allows for exporting the data to be analyzed by qualitative 
software programs. All analyses are planned to be conducted by lab members named as key personnel on this 
protocol. 
Phase 2 and 3: The REDCap data capture system allows for transformation of data to a form that can be used 
with data analysis programs.  We will export the data into a de-identified password-protected database which 
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will be held on the lab computer. All analyses are planned to be conducted by lab members named as key 
personnel on this protocol.
7.6 Study Records 
Study Protocols
Screening Documents
Informed Consent Documents
Focus Group Transcripts
REDCap Database
Identifiable Participant List
7.6.1 Retention of Records 
The Identifiable Participant List will be destroyed no more than 6 months after data collection is finished. The 
Screening Documents will be de-identified no more than 6 months after data collection is finished, but the 
information will be retained to comply with reporting standards. The remaining records will be retained as per 
Einstein Guidelines. If permission is needed to move or destroy the records, the PI (Elizabeth Seng) should be 
contacted.  
7.7 Study Monitoring 
The research coordinator will assess adverse events in bi-weekly check-ins with participants. The unblinded 
research assistant will assess headache activity bi-weekly and provide reports to the Data Safety Monitoring 
Committee (DSMC) at minimum every 6 months.  The research assistant will call participants at least once per 
month throughout the study to assess for adverse events. The PI will also monitor each participant’s recorded 
headache diaries monthly to assess for adverse events. 
The Data Safety Monitoring Committee (DSMC) will consist of Drs. Andrea Weinberger, Ph.D., Assistant 
Professor of Psychology, and Frederick Foley, Ph.D., Professor of Psychology, at Ferkauf Graduate School of 
Psychology, Yeshiva University. The DSMC has final authority regarding making decisions regarding 
continuation, revision or discontinuation of the research project. The DSMC will meet every six months. The 
unblinded research assistant will provide reports of adverse events and diary-recorded symptoms by group to 
the DSMC at minimum every six months. The DSMC will provide minutes of each meeting to the PI, including 
attendance, summary of the discussion, and any findings. The PI will be responsible for implementation of this 
Data Safety Monitoring Plan and will report directly to the Einstein IRB and the NIH. 
7.8 Data Safety Monitoring Plan 
An adverse event (AE) is any troublesome medical occurrence in a subject during participation in the clinical 
study. An AE can include a sign, symptom, abnormal assessment, or any combination of these. A serious 
adverse event (SAE) is any AE that results in one or more of the following outcomes: death, a life-threatening 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, a congenital anomaly or birth defect, or an important medical event based upon 
appropriate medical judgment. We will use the HHS/NIH/NCI Common Terminology Criteria for Adverse 
Events (Version 4.0) grading scale; for reference, we have provided the criteria for headache AEs (Grades 1-
3): Grade 1: Mild (mild headache pain); Grade 2: Moderate (moderate headache pain that limits instrumental 
activities of daily living); Grade 3: Severe or medically significant but not immediately life threatening (severe 
headache pain that limits self-care activities of daily living); Grade 4: Life-threatening consequences; Grade 5: 
death related to AE. When present, each AE will be categorized according to the likelihood that they are 
related to the CDST on a 4-point scale, ranging from definitely unrelated, possibly related, probably related, to 
definitely related.  The expected risk of the CDST intervention is increased headache activity due to inhibition 
of therapeutic choice of participants. This risk is considered minimal.  
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If any of the procedures described above identify a potential adverse event for an individual participant, the 
participant will be called immediately to assess the potential adverse event. Participants who disclose potential 
adverse events to any study staff at any point during the study will immediately be reported to the PI, Dr. 
Elizabeth Seng, Ph.D., clinical psychologist. If Dr. Seng is unavailable, Dr. Elizabeth Hirky, Ph.D., clinical 
psychology and Director of Clinical Training at Ferkauf Graduate School of Psychology, Yeshiva University 
(anne.hirky@mail.yu.edu) will assess and determine the best course of action in the case of immediate 
participant distress. If the adverse event requires medical or professional intervention, the PI or Dr. Hirky will 
immediately contact the participant’s primary clinician at the MHC and develop an intervention plan and referral 
if necessary. If a participant experiences an adverse event, he or she will be given an opportunity to leave the 
study. Any SAEs that are possibly related to the study intervention will be reported to the IRB and NIH within 7 
days. All AEs will be compiled and reported to the Einstein IRB and NIH in accordance with the Einstein IRB 
requirements.
The DSMC will meet every six months. The DSMC will provide minutes of each meeting to the PI, including 
attendance, summary of the discussion, and any findings. The PI will be responsible for implementation of this 
Data Safety Monitoring Plan and will report directly to the Einstein IRB and the NIH.
7.9 Study Modification.
Any modifications to the protocol will be submitted as amendments to the Einstein IRB for review.  The change 
will be implemented after approval.
7.10 Study Discontinuation 
The study would be discontinued if the DSMC recommends discontinuation. 
7.11 Study Completion 
We anticipate completing data collection in 2019, and initial data analysis in 2020. We will notify the IRB as 
soon as data collection is completed. 
7.12 Funding Source 
This study is funded by the NINDS (K23 NS093107; PI: Seng). We are currently in a no-cost extension period 
until March 31, 2022.
7.13 Publication plan 
The PI (Elizabeth Seng, Ph.D.) holds primary responsibility for publishing the study results. Study results must 
be reported on clincialtrials.gov immediately following completion of the study according to NIH protocol. 
Primary objective results will also be submitted for publication in a peer-reviewed journal within one year of 
completion of data collection.  
7.2 IRB Review
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