Using N-of-1 Experiments to Answer Patient Generated Research Questions
Phase: NA
Conditions: Atrial Fibrillation Paroxysmal
Sponsor: University of California, San Francisco

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INDIVIDUALIZED STUDIES OF TRIGGERS OF 
PAROXYSMAL ATRIAL FIBRILLATION (I-STOP-AFIB) 
Principal Investigator: 
Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS 
Sponsor: 
University of California, San Francisco 
Funding Source: 
The Patient Centered Outcomes Research Institute 
Data and Site Coordinating Center: 
University of California, San Francisco 
NCT03323099

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TABLE OF CONTENTS 
Aim 2: I-STOP-AFib Study 
2 
1.1 Background 
3 
1.1.1 Paroxysmal Atrial Fibrillation (AF) 
3 
1.1.2 A Critical Research Gap 
3 
1.1.3 Potential for the study to improve health care and outcomes 
4 
1.1.4 Study Setting 
4 
1.2 Study Objective 
4 
1.3 Technology Platform 
4 
1.3.1 Technology Platform Configuration 
5 
1.4 Study Design 
6 
1.4.1 Interventions and Comparators 
7 
1.5 Study Procedures 
7 
1.5.1 Outcome Measures 
9 
1.6 Participant Selection and Withdrawal 
9 
1.6.1 Inclusion Criteria 
9 
1.6.2 Exclusion Criteria 
9 
1.6.3 Participant Pre-screening and Recruitment 
10 
1.6.4 Early Withdrawal of Participants 
10 
1.7 Statistical Plan 
10 
1.7.1 Sample Size Determination 
10 
1.7.2 Statistical Methods 
11 
1.8 Safety and Adverse Events (AE) 
12 
1.8.1 Adverse Event Reporting 
12 
1.8.2 Data and Safety Monitoring Board 
13 
1.9 Data Handling and Record Keeping 
13 
1.9.1 Confidentiality 
13 
1.10 Technology Platform - Eureka 
13 
1.10.1 Short Description of Eureka 
13 
1.10.2 Registration, Consents, Eligibility 
14 
1.10.3 Eureka Risks 
14 
1.10.4 Eureka Efforts to Minimize Risk 
14 
1.10.5 Confidentiality Measures 
15 
1.10.6 Data Storage 
15 
1.10.7 Data Security 
15 
1.10.8 Records Retention 
15 
1.11 Ethical Considerations 
15 

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1.11.1 Conflict of Interest 
16 
1.12 Stakeholder Involvement 
16 
1.12.1 Initial Study Development: 
16 
1.12.2 Study Execution: 
16 
1.12.3 Disseminating the study results: 
17 
1.12.4 Alliance Patient engagement principles: 
18 
1.12.5 Study Participant & Patient Stakeholder Compensation 
18 
1.13 References 
19 
1.14 Appendixes 
20 
Appendix A: AFEQT Survey 
20 
Appendix B: Consent Form 
26 
Appendix C: DSMB Charter 
30 
Appendix D: Eureka Privacy Policy 
37 
Appendix E: Trigger Survey 
39 

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1 
I-STOP-AFib Study 
This study aims to (1) help patients randomized to N-of-1 trials determine the individual 
effectiveness of trigger modification in reducing AF severity and frequency, and (2) determine 
the comparative effectiveness of N-of-1 trial designs vs. symptom surveillance alone in reducing 
AF severity and frequency. 
 
 
1.1 
Background 
 
 
1.1.1 
Paroxysmal Atrial Fibrillation (AF) 
Paroxysmal AF is a common arrhythmia that impairs the lives of otherwise healthy, 
high-functioning individuals. AF is the most common arrhythmia, has a lifetime risk of 1 in 4, and 
is expected to affect 16 million Americans in 2050.1 Each year, AF is responsible for >100,000 
strokes, >400,000 hospitalizations, and >$6 billion in direct health care expenditures.1-5 
Paroxysmal AF patients have a similar or worse quality of life than patients with heart failure or 
myocardial infarctions.6 To help alleviate the related debilitating symptoms, the American Heart 
Association (AHA) and other cardiology societies recommend potentially lethal drugs and 
invasive procedures to reduce AF episodes.7 Prevention and treatment strategies that are lower 
risk, lower cost, and more directly under patient-control are needed. 
 
Studies have identified risk factors for new onset AF; however, triggers for discrete episodes 
have been largely ignored. Behaviors or exposures that may trigger AF episodes have not been 
studied systematically, but clinical experience, anecdote, and patient reports suggest that 
personal behaviors (e.g., sleeplessness, stress, caffeine) may trigger AF. Several studies 
suggest that alcohol may be an acute trigger for AF episodes.8,9 If triggers could be identified, 
they might be avoided, providing a strategy to effectively prevent AF. To our knowledge, no 
previous study has examined if triggers affect AF episodes, demonstrating the profound 
disconnect between previous research and the interests of the patients suffering from AF. If AF 
episodes can be manipulated based on personal decisions, a new, inherently patient-centered 
paradigm in the treatment and prevention of AF may be achieved. 
 
1.1.2 
A Critical Research Gap 
Identification of AF triggers (the “trigger wars”) is a top priority among AF patients. Patients 
participating in online forums and focus groups frequently discuss what particular factors trigger 
AF episodes. Mellanie True Hills, CEO of StopAfib.org, refers to these common online 
discussion as the “trigger wars”. It is thus not surprising that identifying factors that trigger AF 
episodes in particular individuals using single subject study designs emerged as a key research 

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priority at the 2014 HeH Patient-Powered Research Summit, a research brainstorming session 
attended by nearly 100 patients, researchers, clinicians and other stakeholders. During this 
conference, an exercise allowed patients to communicate what they believed to be the most 
important issue in their disease. Common themes were identified and patients were divided into 
interest groups – one organically formed around AF. Members of the AF interest group identified 
individual-level triggers for the AF episodes as their highest research priority, After learning 
about the concept of mobile technology enabled N-of-1 trials, the AF interest group worked with 
content and clinical research experts to develop a study idea to test if an N-of-1 approach to 
identifying and elimination of AF triggers would improve AF outcomes. 
 
1.1.3 
Potential for the study to improve health care and outcomes 
Using N-of-1 methods to help AF patients identify the best treatment will shift the clinical 
paradigm towards a more personalized and patient-centric approach to this important disease 
and provide patients with individualized data about the effectiveness of trigger modification in 
controlling symptoms. Rigorously applied trials will convince the evidence- focused cardiology 
community that triggers of AF differ between individuals and carry value. Modern technology 
and devices that are now so ubiquitous allow implementation of personalized N-of-1 studies in 
large populations with AF. This extremely common arrhythmia, that has few effective treatment 
options and yet might be readily manipulated by patients themselves, is ripe for this novel 
approach. 
 
1.1.4 
Study Setting 
The study will take place remotely using an internet-based system produced at the University of 
California, San Francisco within the Health eHeart Alliance Patient Powered Research Network 
and will leverage the resources available in the Health eHeart Study, a web-based 
cardiovascular cohort study that enables remote consent, electronic data capture system 
(Eureka--please see technology platform configuration 1.3.1), and integration with devices and 
apps. To date, the Health eHeart Study has enrolled > 91,000 individuals from around the world, 
with >4,700 participants with atrial fibrillation. 
 
 
1.2 
Study Objective 
 
Test the comparative effectiveness of N-of-1 trials versus data tracking alone to identify and 
eliminate individual- level triggers and reduce AF frequency and severity. 
 
 
1.3 
Technology Platform 

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1.3.1 
Technology Platform Configuration 
Eureka: The Eureka Research Platform is a digital research platform developed at the University 
of California San Francisco as part of a cooperative agreement with the NIH. The purpose of the 
platform is to facilitate mobile health research for any interested investigator. The Eureka 
platform includes a participant-facing “front end,” an investigator portal, a secure “back end” for 
data storage and analyses. The platform is designed as an all-inclusive, configurable, 
easily-scalable research platform, inclusive of all aspects of research—from participant 
enrollment, onboarding and consent, to multi-modal data collection, study 
administration/management and data extraction. The platform’s front end can be customized by 
individual investigators to implement their specific research project. Existing functionality 
includes the ability to obtain remote consent (although in-person consent can also be used), 
deploy participant surveys, message participants via push notifications, texts, or emails, 
integrate with external apps, sensors, and Bluetooth enabled devices, and capture data 
collected from smartphones (such as HealthKit data, geolocation data, accelerometer/ activity 
data). The investigator portal provides a secure website wherein investigators, coordinators or 
other individuals with appropriate permissions can visualize relevant participants’ data and study 
status. The back end of the Eureka platform is a multi-tenant system that enables data 
collection, management and storage derived from multiple sources and from studies of various 
forms. This architecture rests on a secure and HIPAA-compliant AWS cloud with the capacity to 
curate dense data from more than 1 million participants. In addition to providing data as needed 
to investigators, the infrastructure houses a de-identified data repository that is publically 
available to help fulfill the general mission of advancing science and wellness. 
 
Eureka will configure a study-specific version of the platform to collect data required to execute 
the research proposed in this study. Study participants will use the Eureka N-of-1 platform 
(website and mobile app) to collect outcome data, track intervention/exposure status, and 
review collected data in real time. Upon trial completion, Eureka will present N-of-1 results to 
patients randomized to N-of-1 trials with easy-to-understand graphics that include probabilistic 
assessments of the benefits of the intervention. 
 
As part of design sessions held prior to enrollment, members of the research team, including 
patients and clinicians, provided input regarding the study-specific configurations of the Eureka 
platform. Study specific configurations will include: (1) trial specific onboarding page, (2) study 
library to generate and perform analyses of trials based on a trial-specific template, (3) server 
workflow that automates execution of the personal trials, and (4) customization of the user 
interface for prompts, reminders, forms, surveys, and visualizations. Final configurations will 
depend on input from key stakeholders. Technology modifications will be done via iterative, 
rapid development and testing cycles with a firm completion deadline by month 6 of this study, 
prior to patient enrollment. 

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AliveCor: AliveCor is a mobile electrocardiogram (ECG) monitoring app that pairs with a 
smartphone case to enable single lead ECG recordings. To date, >1,000 HeH participants have 
successfully downloaded this app and fitted the smartphone case, and all have done so 
remotely using the same work-flows that would be used for the current proposal. The AliveCor 
device includes an FDA-approved, patient-facing algorithm to detect AF episodes. A 
connectivity wizard already developed for the Eureka portal will enable linking the AliveCor 
monitoring to study data.This Eureka integration will allow the study to receive data from the 
AliveCor device and can be used as validation of atrial fibrillation episodes. 
 
 
1.4 
Study Design 
This is a randomized controlled trial that examines the comparative effectiveness of N-of-1 
study protocols vs. symptom surveillance (data tracking alone) for reducing AF episode 
frequency and severity (Figure 1). Throughout the duration of the study, all study participants 
will use the Eureka mobile app to self-report daily mood and sleep quality, AF episode duration 
(in minutes) and severity, and will use the AliveCor mobile electrocardiogram (ECG) to record 
ECG tracings. Participants will be instructed to take ECG tracings at least once per day as well 
as any time they think they are having an AF episode. Participants will be able to visualize their 
data in real time and will receive weekly summaries of their AF frequency and severity via 
Eureka. Due to the rapid growth and availability of mobile apps and devices that can monitor AF 
episodes, we believe the symptom surveillance condition is a realistic and appropriate 
comparison group. 
 
 
Figure 1: Study Design 
 
 
In addition to tracking mood, sleep and AF data, participants in the N-of-1 trial arm of the study 
will also test their triggers and track their trigger exposure. N-of-1 trials will be conducted using a 

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citizen health-scientist approach where patients are empowered and supported in independent 
experimentation. Together with the HeH Alliance Patient Advisory Board (PAB), the study team 
designed a menu of triggers that participants will select from to test in their personal AF triggers 
in a rigorous testing environment. These N-of-1 trials will consist of 6 randomly assigned  
periods of exposure (trigger exposure/trigger “on”) and elimination (avoiding trigger/trigger “off”). 
 
1.4.1 
Interventions and Comparators 
 
N-of-1 Trial arm: Participants will use the Eureka mobile application and AliveCor device to 
execute at least one N-of-1 trial with the goal of identifying and better controlling their AF 
triggers. Each N-of-1 trial will last a total of 6 weeks and will include up to 3 periods of trigger 
exposure and 3 periods of trigger elimination with each exposure/elimination period lasting 1 
week. Participants will be randomly assigned to start their trial with a period of either trigger 
exposure or elimination. During each N-of-1 trial, participants will track daily AF duration and 
severity, daily mood and sleep quality, daily AliveCor tracings and daily trigger exposure. At the 
end of each trial, participants will be able to review their trial results which will include 
visualizations of their daily AF symptom and trigger tracking over time. After completing a trial, 
participants will be instructed to implement any lifestyle changes they deem appropriate based 
on what they learned from the results of their trial. Participants will implement these changes for 
a period of 4 weeks during which they will continue to track AF episode duration and severity via 
the app. At the end of the 4-week lifestyle change period, participants will complete the Atrial 
Fibrillation Effect on QualiTy of Life survey (AFEQT) (Appendix A) and will then have the option 
of testing another trigger or ending their study participation. 
 
Symptom Surveillance arm: Participants will use the Eureka app and AliveCor device to record 
daily AF duration and severity, daily AliveCor readings and daily mood and sleep quality for a 
period of 10 weeks. Participants will be able to visualize their AF, sleep and mood data in real 
time and will receive a weekly summary of their data via the Eureka app.At the end of the 
10-week data tracking period, participants will complete the AFEQT survey and will then have 
the option of either ending their study participation or crossing over to the N-of-1 trial arm to test 
their triggers. 
 
 
 
1.5 
Study Procedures 
Randomization/Baseline evaluation: Potential participants will be identified via the Health eHeart 
Study and the StopAfib.org patient advocacy organization and reached out to via email 
campaigns. Of note, invitations will be extended broadly to include friends family and 
acquaintances of those participants. Patients may also be recruited directly from UCSF clinics 
or other web-based sources of potentially interested atrial fibrillation patients. The study email 
campaign will contain an overview of the study. If the patient is interested in participating in the 
study there will be a link for the participant that will take them to the mobile app store to 

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download the Eureka app. Potential participants will be prompted to register an account and will 
complete an inclusion/ exclusion criteria survey within the Eureka app. If eligible, they will 
continue on to the study consent form (Appendix B). Upon completion of the electronic study 
consent, Eureka will randomize participants to either the N-of-1 or the symptom surveillance arm 
of the study with a 1:1 allocation ratio. 
 
Participants will then be asked to complete baseline data collection which will include basic 
demographics, medical history, and current atrial fibrillation medications. After baseline data 
collection, the study team will ship AliveCor devices to study participants over a period of two 
weeks. At the end of this two week period, participant will be prompted to visit the Eureka 
application to complete a device consent and then will be instructed to download the AliveCor 
app and link their AliveCor device to their Eureka account. All participants will then complete the 
Atrial Fibrillation Effect on QualiTy of Life survey (AFEQT) (Appendix A). Once they complete 
the survey, the app will show participants which study arm they have been randomized to and 
prompt them to begin the appropriate study activities. 
 
Experimental arm: Participants randomized to the N-of-1 study arm will test AF trigger(s) (ie. 
diet, exercise, sleep, alcohol, smoking, certain exercises, etc). Using a menu of options in 
Eureka, participants will select a trigger to test and then will be randomly assigned to start with a 
period of trigger exposure or elimination. Each exposure/elimination period will last 1 week and 
each trigger will be tested for a total of 6 periods with 3 weeks of trigger exposure and 3 weeks 
of trigger elimination. During each testing period, the Eureka app will send participants daily 
reminders of the behavior that is required, specifying quantity and type of trigger 
exposure/elimination when appropriate. For example, if the trigger is alcohol consumption, this 
might include a daily alert that reads: 
 
Elimination week: “This week, AVOID your trigger: ALCOHOL. Avoid drinking any 
alcohol. 3 more days left of AVOIDING alcohol this week.” 
 
Or, alternatively: 
 
Exposure Week: “This week, TEST your trigger: ALCOHOL. Go ahead and consume 
alcohol this week. 3 more days left to TEST your trigger this week.” 
 
During the testing period, participants will also receive daily reminders prompting them to go to 
into the Eureka app to complete study activities. Participants will be asked daily about the 
estimated total duration and severity of their AF episode(s), mood and sleep quality and trigger 
exposure (e.g. “How many alcoholic drinks did you have yesterday?”). They will also be 
prompted to take daily AliveCor readings. Participants will be instructed to take ECG tracings at 
least once per day as well as any time they are experiencing AF symptoms. Following the 
completion of their N-of-1 trial, participants will be able to view their trial results and 
interpretations on the Eureka app. Once their N-of-1 trial is complete, participants will stop 
receiving reminders about trigger exposure/elimination and trigger tracking but will be prompted 

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to continue to track their AF frequency and severity for 4 more weeks. During this 4 week 
period, participants will be able to implement any lifestyle changes they deem appropriate based 
on what they learned from their N of 1 trial. Following the completion of the 4 week “lifestyle 
change” period, participants will complete the AFEQT survey and will then have the option of 
either testing another AF trigger or concluding their study participation. Participants that choose 
to test additional triggers will have up to one week to start their next N-of-1 trial that will follow 
the same trigger testing protocol as the first. Participants will have the option of testing up to 5 
triggers following this protocol. 
 
Symptom Surveillance: Participants randomized to the symptom surveillance arm will engage in 
data tracking for a period of 10 weeks and receive daily reminders to complete study activities. 
Participants will be asked daily about the estimated total duration and severity of AF episode(s) 
and daily mood and sleep quality. They will also be asked to take AliveCor readings at least 
once per day and anytime they are experiencing AF symptoms. Participants will be able to 
visualize their AF data in real time and will receive a monthly summary of their AF frequency 
and severity via the Eureka app. At the end of the 10-week tracking period, participants will 
complete the AFEQT survey. Then, participants will have the option to cross over to engage in 
trigger testing. Participants that choose to test their triggers will be able to test up to 4 triggers, 
one trigger at a time, following the N-of-1 trial protocol described above. 
 
 
1.5.1 
Outcome Measures 
 
The primary study outcome is change in quality of life, measured by the AFEQT, between those 
randomized to N-of-1 experiments versus those that tracking their data alone. Secondary 
outcomes will include results of individual-level N-of-1 trials. 
 
 
1.6 
Participant Selection and Withdrawal 
At least 478 AF patients will be recruited to participate remotely in the RCT. 
 
1.6.1 
Inclusion Criteria 
(1) symptomatic paroxysmal AF 
(2) a smartphone 
 
1.6.2 
Exclusion Criteria 
1. Non-English speakers 
2. Children (age < 18 years) 
3. Patients with plans to substantially change AF management (such as with ablation or 
change in antiarrhythmic drugs) over the ensuing 6 months 
4. Unwillingness to test AF triggers. 
5. Patients who have had an AV node or AV Junction ablation 

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1.6.3 
Participant Pre-screening and Recruitment 
 
Participants will be recruited primarily from two sources: (1) the Health eHeart Study, which has 
>4,000 well-characterized AF participants who have consented to be contacted via the internet 
about other studies and which recruits >1,500 new participants (58 AF patients) per month; and 
(2) StopAfib.org, a patient-run website with 765,000 unique visitors, 2.2 million pageviews in 
2014 and a mailing list of 13,000 engaged AF patients. Those participants will also be recruited 
as “ambassadors for the study by inviting others they know that might be interested. Patients 
may also be recruited directly from UCSF clinics or other web-based sources of potentially 
interested atrial fibrillation patients. Participants recruited directly from the Health eHeart Study 
will be emailed by the Health eHeart study team.We will plan to email the Health eHeart Study 
participants who have indicated they have AF. Participants recruited from StopAfib.org will 
receive a similar email with a link to the mobile app store. Potential participants will then be 
prompted to register an account, consent for the study then complete an inclusion/ exclusion 
criteria survey within the Eureka app. 
 
 
1.6.4 
Early Withdrawal of Participants 
 
Study participants can opt out of testing a trigger or withdraw from the study at any time of their 
choosing without penalty. 
 
1.7 
Statistical Plan 
 
 
1.7.1 
Sample Size Determination 
 
We conservatively estimate that the available pool will include 10,000 engaged individuals 
meeting the inclusion and exclusion criteria. Given that we estimate that 478 participants will be 
needed, we need to consent only 5% of eligible patients. Strategies to overcome barriers to 
enrollment include continuing aggressive efforts to recruit large numbers of HeH participants (in 
collaboration with the HeH Alliance and partners such as the AHA) and ongoing messaging 
from the CEO and other leadership encouraging enrollment to StopAfib.org participants and 
visitors (Std PC-2). In order to achieve at least 478 patients that complete the 6 month study, we 
will aim to initiate at least 600 patients. 
 
Sample Size & Power Calculations: As those with at least moderate AF severity have an 
AFEQT score of 58 ± 1958 and the most modest of therapies typically improves this score by a 
mean of 5-10, we have powered this study conservatively to detect an improvement of 5 points 
in the AFEQT. We estimate 239 patients in each group would provide 80% power to detect this 
small, yet still clinically meaningful difference. Given the enthusiasm of >1000 AF patients 
already engaged by the investigators, we believe enrollment will not pose a challenge. 

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1.7.2 
Statistical Methods 
 
Analysis of Individual N-of-1 Trials: At the end of each person’s N-of-1 trial, statistical analysis 
will be performed to compare results on the two treatments. Each N-of-1 trial requires a 
separate analysis which is automated to run in the background once each trial is completed. 
The analysis consists of running Bayesian models that make different assumptions about the 
nature of the data (e.g., data with and without correlation over time, with and without carryover 
across interventions). Models will incorporate the appropriate scales for the outcomes (e.g. 
normal distributions for continuous variables, multinomial distributions for categorical variables) 
and the appropriate representation of the function linking the expected outcome to the 
predictors (e.g., cumulative logit link for ordinal outcomes).The results of these models will be 
automatically compared to determine which best fits the data and the simplest model that 
accurately fits the data will be chosen using appropriate model selection criteria such as the 
deviance information criterion. Each patient will be provided with an estimate of the (1) 
treatment difference, and (2) probability (or likelihood) that each treatment is the best for a 
particular outcome. Results will be portrayed numerically and graphically. We will develop 
educational materials to aid patients in interpretation. Posterior probabilities of outcomes will be 
calculated using an interface that incorporates open-source R software interfacing through 
Rjags with open-source JAGS software.55 The R code creates the Bayesian model, loads the 
stored data and chooses intelligent starting values that are then fed into JAGS to return the 
Markov chain Monte Carlo (MCMC) simulations of the joint posterior distribution. The R package 
will accept input from Orchestra to construct models. The statistical methods used are being 
applied currently in another N-of-1 study and will be adapted as necessary to create a 
connection between the R code and Eureka.. 
 
Meta-Analysis of N-of-1 Trials: The collection of individual N-of-1 trials can be thought of as a 
set of studies whose results can be combined as in a meta-analysis. The data can be 
considered as a multilevel structure in which a set of patients is studied with each patient having 
a set of measurements. Standard multilevel mixed model methods will be used to estimate the 
average effect and variance within and across patients. Across patient values estimate the 
average effect in the population of patients studied, while the within-patient estimates describe 
an improved estimate of each patient’s true effect assuming exchangeability across patients. 
We will fit these models using a Bayesian multilevel model with non-informative priors in order to 
obtain posterior distributions of the within and between effect sizes. We will then compare the 
multilevel patient estimates with those from the patient’s data alone in order to determine how 
much the effects change and how much additional precision these estimates gain. 
 
Analysis of Comparative Effectiveness: The experimental design is a simple two-arm 
randomized trial comparing N-of-1 vs. symptom surveillance. The primary outcome is the 
change in the AFEQT scale from baseline to 12 weeks. The mean change in each treatment 
group will be compared by a t-test. The average frequency and severity of AF episodes per 
week during the final month of each participant’s enrollment will be the secondary 

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outcomes.Their group means will also be compared with a t-test. We will check for balance in 
covariates across the randomized groups and will adjust for any imbalances by including those 
covariates in regression analyses and reporting the adjusted treatment effect as a secondary 
analysis. 
 
Missing Data: A major purpose of this aim is to determine the feasibility and usability of N-of-1 
studies for actual application in clinical practice. Therefore, carefully documenting adherence 
and completion rates and predictors of each will be an important aspect of this study. Within the 
HeH study, we have found that >90 % of all AF HeH study participants complete all AF-related 
surveys, including the AFEQT. The primary analysis will be intent-to-treat which uses all 
participants as randomized. When no endpoint is available, we will assume no change. Further 
analyses will employ multiple imputation to fill in missing values, particularly in 
covariate-adjusted models (Std MD-2, MD-3). 
 
Heterogeneity of Treatment Effects (Std HT-1 through 4): HTE between individuals with AF is a 
major issue that is of particular interest to patients. In secondary analyses, we will test for 
interactions between treatment and covariates that describe potential pre-specified HTE 
hypotheses. Predetermined interaction analyses will include testing for effect modification by 
“lone” AF (age <65 years of age without any cardiovascular risk factor) vs. not, sex, and race 
(non-Hispanic white race vs. not). Additional post hoc interaction analyses examining currently 
unrecognized moderators will be planned based on input from patients over the course of the 
study. These are likely to include testing for effect modification by particular triggers (e.g., 
setting an early bedtime works well whereas avoiding morning endurance exercise does not). 
Statistical significance for interaction analyses will use a p-value cut off of ≤0.01. 
 
 
1.8 
Safety and Adverse Events (AE) 
 
1.8.1 
Adverse Event Reporting 
 
Participants will receive monthly prompts via the application about the following things: 
hospitalizations (AF, emergency department, cerebrovascular event, myocardial infarction or 
heart failure), antiarrhythmic medication changes and ablation plans. 
 
We will share reports with the DSMB outlining the results of the above survey. 
 
1.8.2 
Data and Safety Monitoring Board 
 
Although randomization to N-of-1 trials versus symptom surveillance (data tracking) is low risk, 
we will form a DSMB to ensure the safety of participants. This board will be comprised of a 
patient, a cardiac electrophysiologist, and a statistician from outside the research groups or 
institutions of the study personnel otherwise involved in the project. They will meet prior to 

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implementation of the study to review the safety of a near-final AF-specific N-of-1 platform. They 
will meet again after 100 patients are enrolled and again after 350 patients are enrolled. 
An analyst will prepare summary statistics of results collected prior to the second and 
third meetings. The DSMB will review study progress and any adverse events that have been 
reported by patients. The DSMB will also discuss trouble around retention, compliance, protocol 
violation and recruitment issues. The DSMB will have the authority to stop the study for safety 
reasons or to alter it if needed. Because the study is expected to be low risk, patients may 
actually benefit from study participation, and specific subgroups (e.g., those in whom N-of-1 
studies identify a trigger), may yield important results, the DSMB will not perform any interim 
analyses for efficacy or consider stopping the study early for futility. In addition, all potential 
participant data obtained by the study investigators will be monitored on an ongoing basis to 
ensure compliance, to provide quality assurance (QA), and to obtain metrics for quality 
improvement. 
 
See Appendix C for DSMB Charter 
 
1.9 
Data Handling and Record Keeping 
 
1.9.1 
Confidentiality 
 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those 
regulations require a signed subject authorization informing the subject of the following: 
 
● 
What protected health information (PHI) will be collected from subjects in this study 
● 
Who will have access to that information and why 
● 
Who will use or disclose that information 
● 
The rights of a research subject to revoke their authorization for use of their PHI. 
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) 
at the end of their scheduled study period. 
 
1.10 
Technology Platform - Eureka 
 
1.10.1 Short Description of Eureka 
 
The Eureka mHealth Research Platform Resource is a mobilized cohort and infrastructure to 
carry out clinical research studies using mobile and digital technology. Patients will submit their 
data via SMS text messages, via mobile applications, via secure websites, or upload their data 

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from other services they may authorize. Simple, non-PHI carrying messages are sent by the 
system, and typically unidentifiable numeric responses are returned. The only PHI involved in 
the transaction is the phone number or unique ID used to identify the patient’s phone. This data 
is then stored on the study platform as previously described. 
 
Eureka Goal: The goal for the Eureka mHealth Research Platform is to provide an infrastructure 
for efficient data collection, storage, and sharing that can be configured to support Internet- or 
mobile phone app-based research studies. 
 
1.10.2 Registration, Consents, Eligibility 
 
Eureka will support a registration procedure that will allow registration with identifying 
information that will generally include name, date of birth, and mobile phone number. 
 
In registering for our study, Eureka will provide a consenting process for participants within the 
onboarding flow. In this process, the study informed consent as well as the Eureka Privacy 
Policy and Data Security Measures (Appendix D) will be presented to eligible participants. 
 
1.10.3 Eureka Risks 
 
The risk of loss of privacy in our study hosted by the Eureka Research Platform will be present 
for all persons participating. Loss of privacy could occur by compromise of the Eureka technical 
system, or if Eureka is required by law to disclose data to authorities, e.g. to prevent serious 
harm to the participant or others. This is the primary reason for the Eureka Privacy Policy and 
Data Security Measures. 
 
1.10.4 Eureka Efforts to Minimize Risk 
 
To minimize risk of loss of privacy, Eureka takes the following steps: 
 
Technical system security: Information will be transmitted and stored using state-of-the-art 
security systems similar to those that protect websites used by banks and electronic health 
record systems. Specifically, the Eureka Platform is hosted on Amazon Web Services (AWS), a 
cloud-based server system and computing services that are HIPAA compliant, and Eureka 
follows security guidelines of the U.S. Health Insurance Portability and Accountability Act of 
1996 (HIPAA). Specifically, all research data are stored behind a secure firewall, guarded by 
intrusion detection software, and encrypted at rest and in transit in our Amazon Virtual Private 
Cloud. 
 
Inform patients: As described above, we will include the Eureka Privacy Policy and Data 
Security Measures that will be referenced in study onboarding and viewable at any time. The 
statement will inform patients of the risks of loss of privacy, including via technical compromise 

Version: 1.0, September 20, 2017 
Page 15 
 
or legal requirements. We will also make them aware that they are responsible for keeping their 
login credentials secure. 
 
1.10.5 Confidentiality Measures 
 
Identifying information (name and email address) will be stored in separate (but linked) data 
tables so that health-related data can be viewed by approved staff as needed without 
inadvertent association with identifiers when such linkage is not required. 
 
In the event of a data break, the Eureka Research Platform Team will notify all Study Teams 
and Study Participants in accordance with UCSF guidelines. 
 
1.10.6 Data Storage 
 
Data is stored on Amazon Web Services (AWS or Amazon Cloud) 
 
1.10.7 Data Security 
 
Data are coded; data key is kept separately and securely. Electronic data are protected with a 
password. Data are stored on a secure network 
 
1.10.8 Records Retention 
 
The investigator must retain all study records and source documents for the maximum period 
required by their institution or as required by local and national governing regulations, whichever 
is longer. Study records include consent forms and source documentation. The investigator 
must contact the sponsor prior to destroying any records associated with the study. 
 
 
1.11 
Ethical Considerations 
 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 50, part 56 and ICH guidelines), applicable government regulations 
and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a centralized, properly constituted 
independent Ethics Committee (EC) or IRB, for formal approval of the study conduct. The 
decision of the EC/IRB concerning the conduct of the study will be made in writing to the 
investigator and a copy of this decision will be provided to the sponsor before commencement 
of this study. The sponsor and investigator will maintain a list of the central EC/IRB members 
and their affiliates in their files. 

Version: 1.0, September 20, 2017 
Page 16 
 
All subjects (and/or the subject’s legally authorized representative) for this study will be provided 
a consent form describing this study and providing sufficient information for subjects (and/or 
their legally authorized representative) to make an informed decision about their participation in 
this study. The sponsor will provide the investigator with appropriate sample informed consent 
forms. The formal consent of a subject (and/or the subject’s legally authorized representative), 
using the EC/IRB-approved consent form, must be obtained before that subject undergoes any 
study procedure. 
 
1.11.1 Conflict of Interest 
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the conflict 
reviewed by a properly constituted Conflict of Interest Committee with a Committee-sanctioned 
study specific conflict management plan that has been reviewed and approved by the IRB 
providing oversight for that investigator prior to participation in this study. This information shall 
also be made available to the study sponsor upon request or as required under any separately 
executed agreement between the sponsor and study site. 
 
 
1.12 
Stakeholder Involvement 
 
1.12.1 Initial Study Development: 
 
Research Prioritization Process: As a patient-powered research study, patients have been and 
will continue to be integral in shaping each stage of this study’s development. The research 
question and initial study design emerged out of the 2014 HeH Patient-Powered Research 
Summit, a research brainstorming session attended by nearly 100 patients, researchers, 
clinicians and other stakeholders. Members of the Atrial Fibrillation (AF) interest group named 
identifying individual-level triggers for their AF episodes as their highest research priority. After 
learning about the concept of mobile technology enabled N-of-1 trials, the AF interest group 
worked with clinical research experts to develop a study idea that would test if an N-of-1 
approach to identifying and eliminating AF triggers would improve AF outcomes (the stimulus for 
this study). 
Designation as an “Alliance Sanctioned” Study: As an “Alliance-sanctioned study,” this study 
was designed to meet the following criteria: there will be (1) at least one HeH Alliance member 
is participating as a patient-leader in a decision-making role and receiving compensation for that 
role; (2) accountability reporting on study progress and results back to the HeH Alliance 
Community and the Steering Committee; (3) co-authorship for at least one Alliance 
patient-leader on the final results paper; and (4) acknowledgement of the HeH Alliance in the 
final results paper. 
 
 
1.12.2 Study Execution: 

Version: 1.0, September 20, 2017 
Page 17 
 
To maintain the patient-centeredness of the study, patients will be involved throughout the entire 
process, including in planning, implementation, tracking progress and disseminating results. 
The study team will work closely with the Patient PI and Patient Advisory Board: The study’s Pt- 
PI is an AF patient and HeH Alliance Steering Committee member (Kathi Sigona). She will take 
part in all planning discussions and study design meetings with the study PI (Greg Marcus) and 
the Alliance Project Director (Madelaine Faulkner) and she will chair quarterly meetings of the 
Patient Advisory Board (PAB). These meetings will provide an opportunity to discuss progress, 
milestones, challenges to implementation and modify plans in an iterative fashion with a broader 
group of patients. Patients will take an active role in identifying potential triggers for testing and 
in the design and testing of the Eureka N-of-1 and symptom tracking apps. The study team 
solicited feedback from all HeH Study AF patients and StopAfib.org visitors around atrial 
fibrillation triggers via a survey delivered via email (Appendix E).  We also  engaged a group of 
4 UCSF AF patients in focus group activities for the initial study design process. In this way, 
patients were directly involved in the finalizing the study design, including the identifying the 
potential triggers to be studied, the adaptation of the Eureka platform to accommodate the 
description of those triggers, and beta-testing of the product before it is finalized. 
 
 
1.12.3 Disseminating the study results: 
 
Under the leadership of Kathi Sigona (patient PI) and together with the PAB, HeH patients will 
play an active role in all dissemination activities. In addition to the many existing HeH 
dissemination channels, we plan on working with the PAB to find the additional methods for 
dissemination, including atypical arenas to reach a broader population. This may include posting 
updates via HeH Study communication channels, social media updates, advocacy groups such 
as Stopafib.org, or other opportunities reported as valuable by our patient population. 
 
 
1.12.4 Alliance Patient engagement principles: 
 
Reciprocal Relationships: The two study co-PIs for HeH (Marcus & Sigona) along with the leads 
of the patient engagement and PPRN integration teams, will lead decision making for Aim 2. 
Our goal is to ensure that patients, clinician, and other stakeholders have a primary voice in key 
decisions and that the investigator team works in service of implementing their goals while 
ensuring methodologic rigor. Kathi Sigona (patient co-PI) will lead efforts to more broadly 
engage patients through both the PAB and study focus group. She will play a critical role in 
ensuring that the patient voice is represented in investigator team meetings and in HeH specific 
study meetings. 
Co-learning: Within the HeH Alliance, there is an established process for ensuring good 
communication between researchers and patients. The communication principles developed by 
the HeH Alliance will be incorporated throughout the study to ensure we are using language that 
is understandable to patient and researcher stakeholders. Engaging Kathi Sigona (patient co-PI) 
as a facilitator in meetings where multiple stakeholder groups are represented will also help to 
alleviate any communication concerns. 
Partnership: Patients play a crucial role in studying AF triggers. AF triggers are inherently 

Version: 1.0, September 20, 2017 
Page 18 
 
patient-centric as they are personalized and patient-defined. We developed the Aim 2 focus 
group plan and compensation strategy after discussion with AF patients and advocates in order 
to ensure that participation is worthwhile. We plan to utilize the internet and email as much as 
possible to facilitate participant convenience and will minimize in-person meetings. 
Trust, Transparency, Honesty: The HeH Alliance has rules governing interaction with patients 
and one of the main principles is radical transparency. HeH believes that involving patients in all 
processes helps keep the work truly patient- centered. HeH has a system of shared notes and 
decision tracking so that patient leaders and PRB members have full transparency as to how 
decisions are made. In addition, all members of the study team will adopt the broader HeH 
Alliance list of working values (i.e., Trust & Partnership, Respect & Listening, Empowering 
Solutions) that are meant to encourage meaningful and honest communication with patient 
partners in research. 
 
 
1.12.5 Study Participant & Patient Stakeholder Compensation 
 
Patient Advisory Board members will be compensated in a show of appreciation for their time 
and expertise and will be paid annually at $75/ hour. We plan to hold quarterly meetings with 
PAB members to track study progress, results dissemination and troubleshoot other potential 
study concerns. Our PAB members will be involved with the study team for all three years of 
the grant and will be supported by the Health eHeart Alliance PPRN. 
Focus group members who are not on the PAB will be engaged for a total of 8 hours in year one 
and will be invited to be included on study updates through the life of the study.  These 
members will be compensated at $75/ hour. 
Finally a patient will be included on the 3-person, Aim 2 DSMB; for which they will be 
compensated $500/meeting. We anticipate there will be three meetings during the life of the 
study. 

Version: 1.0, September 20, 2017 
Page 19 
 
1.13 
References 
 
1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update: a 
report from the American Heart Association. Circulation. 2012;125(1):e2-e220. 
 
2. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the 
Framingham Heart Study. Circulation. 2004;110(9):1042-1046. 
 
3. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in 
Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future 
prevalence. Circulation. 2006;114(2):119-125. 
 
4. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, Zimetbaum P. Assessing the 
direct costs of treating nonvalvular atrial fibrillation in the United States. Value in health : the 
journal of the International Society for Pharmacoeconomics and Outcomes Research. 
2006;9(5):348-356. 
 
5. Kozak LJ, Lees KA, DeFrances CJ. National Hospital Discharge Survey: 2003 annual 
summary with detailed diagnosis and procedure data. Vital and health statistics. Series 13, Data 
from the National Health Survey. 2006(160):1-206. 
 
6. Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients 
with intermittent atrial fibrillation: implications for the assessment of investigational therapy. 
Journal of the American College of Cardiology. 2000;36(4):1303-1309. 
 
7. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of 
patients with atrial fibrillation: a report of the American College of Cardiology/American Heart 
Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 
2014;130(23):e199-267. 
 
8. Mandyam MC, Vedantham V, Scheinman MM, et al. Alcohol and vagal tone as triggers for 
paroxysmal atrial fibrillation. The American journal of cardiology. 2012;110(3):364-368. 
 
9. Mukamal KJ, Tolstrup JS, Friberg J, Jensen G, Gronbaek M. Alcohol consumption and risk of 
atrial fibrillation in men and women: the Copenhagen City Heart Study. Circulation. 
2005;112(12):1736-1742. 

Version: 1.0, September 20, 2017 
Page 20 
 
1.14 
Appendixes 
 
Appendix A: AFEQT 
 
Atrial Fibrillation Effect on Quality of Life 
Survey Number: 1-17c 
 
This survey is triggered from 1-06 Medical Conditions,[afib] = ‘1’. 
 
Everyone who does this survey will also do 1-17a Atrial Fibrillation and 1-17b AF Severity 
Scale. All 3 are triggered from 1-06 Medical Conditions, [afib] = ‘1’. 
 
Question? 
Popup Language Title 
Popup Language Body 
variable name 
field type 
branching logic 
required/not required 
1, Option #1 
2, Option #2 
 
Text Validation 
Triggering Between Survey 
 
Note - questions that are triggered have a blue “fill” 
 
Are you currently in atrial fibrillation? 
Atrial Fibrillation 
Atrial Fibrillation (also called AFib or AF) is a quivering 
or irregular heartbeat (arrhythmia) that can lead to 
blood clots, stroke, heart failure and other heart-related 
complications. Some people refer to AF as a quivering 
heart. 
current_af 
yesno 
none 
required 
1, Yes 
0, No 
When was the last time you were aware of having 
had an episode of atrial fibrillation? Please check 
one answer which best describes your situation. 
last_time 
radio 
[current_af] = ‘0’ 
required 
1, Earlier today 
2, Within the past week 
3, Within the past month 
4, 1 month to 1 year ago 
5, More than 1 year ago 
6, I was never aware of having atrial fibrillation 
 

Version: 1.0, September 20, 2017 
Page 21 
 
The following questions refer to how atrial 
fibrillation affects your quality of life. 
On a scale of 1 to 7, over the past 4 weeks, as a 
result of your atrial fibrillation, how much were 
you bothered by: 
Please choose one number which best describes 
your situation. 
section_2 
descriptive 
none 
not applicable 
Not a question 
Palpitations: Heart fluttering, skipping or racing 
palpitations_heart_flutter 
radio 
none 
required 
1, 1 – Not at all bothered Or I did not have this 
symptom 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Irregular heart beat 
irregular_heart_beat 
radio 
none 
required 
1, 1 – Not at all bothered Or I did not have this 
symptom 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
A pause in heart activity 
pause 
radio 
none 
required 
1, 1 – Not at all bothered Or I did not have this 
symptom 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Lightheadedness or dizziness 
lightheadedness 
radio 
none 
required 
1, 1 – Not at all bothered Or I did not have this 
symptom 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 

Version: 1.0, September 20, 2017 
Page 22 
 
 
On a scale of 1 to 7, over the past 4 weeks, have 
you been limited by your atrial fibrillation in your: 
Please choose one number which best describes 
your situation. 
limited 
descriptive 
none 
not applicable 
Not a question 
Ability to have recreational pastimes, sports, and 
hobbies 
pastimes 
radio 
none 
required 
1, 1 – Not at all limited 
2, 2 – Hardly limited 
3, 3 – A little limited 
4, 4 – Moderately limited 
5, 5 – Quite a bit limited 
6, 6 – Very limited 
7, 7 – Extremely limited 
Ability to have a relationship and do things with 
friends and family 
relationship 
radio 
none 
required 
1, 1 – Not at all limited 
2, 2 – Hardly limited 
3, 3 – A little limited 
4, 4 – Moderately limited 
5, 5 – Quite a bit limited 
6, 6 – Very limited 
7, 7 – Extremely limited 
 
On a scale of 1 to 7, over the past 4 weeks, as a 
result of your atrial fibrillation, how much 
difficulty have you had in: 
Please choose one number which best describes 
your situation. 
difficulty 
descriptive 
none 
not applicable 
Not a question 
Doing any activity because you felt tired, fatigued, 
or low on energy 
activity 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 

Version: 1.0, September 20, 2017 
Page 23 
 
7, 7 – Extreme difficulty 
Doing physical activity because of shortness of 
breath 
short_breath 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 
7, 7 – Extreme difficulty 
Exercising 
exercising 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 
7, 7 – Extreme difficulty 
Walking briskly 
walking_briskly 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 
7, 7 – Extreme difficulty 
Walking briskly uphill or carrying groceries or 
other items, up a flight of stairs without stopping 
walking_briskly_uphill 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 
7, 7 – Extreme difficulty 
Doing vigorous activities such as lifting or moving 
heavy furniture, running, or participating in 
strenuous sports like tennis or racquetball 
vigorous 
radio 
none 
required 
1, 1 – No difficulty at all 
2, 2 – Hardly any difficulty 
3, 3 – A little difficulty 
4, 4 – Moderate difficulty 
5, 5 – Quite a bit of difficulty 
6, 6 – A lot of difficulty 
7, 7 – Extreme difficulty 
 
On a scale of 1 to 7, over the past 4 weeks as a 
result of your atrial fibrillation, how much did the 
feelings below bother you? 
Please choose one number which best describes 
your situation. 
Not a question 

Version: 1.0, September 20, 2017 
Page 24 
 
feelings 
descriptive 
none 
not applicable 
 
Feeling worried or anxious that your atrial 
fibrillation can start anytime 
worry_af_start 
radio 
none 
required 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Feeling worried that atrial fibrillation may worsen 
other medical conditions in the long run 
worry_af_worsen 
radio 
none 
required 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
 
On a scale of 1 to 7, over the past 4 weeks, as a 
result of your atrial fibrillation treatment, how 
much were you bothered by: 
Please choose one number which best describes 
your situation. 
treatment 
descriptive 
none 
not applicable 
Not a question 
Worrying about the treatment side effects from 
medications 
side_effects 
radio 
none 
required 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Worrying about complications or side effects from 
procedures like catheter ablation, surgery, or 
pacemakers therapy 
complications 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 

Version: 1.0, September 20, 2017 
Page 25 
 
radio 
none 
required 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Worrying about side effects of blood thinners such 
as nosebleeds, bleeding gums when brushing 
teeth, heavy bleeding from cuts, or bruising. 
blood_thinners 
radio 
none 
required 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
Worrying or feeling anxious that your treatment 
interferes with your daily activities 
daily_activities 
radio 
none 
required 
1, 1 – Not at all bothered 
2, 2 – Hardly bothered 
3, 3 – A little bothered 
4, 4 – Moderately bothered 
5, 5 – Quite a bit bothered 
6, 6 – Very bothered 
7, 7 – Extremely bothered 
 
On a scale of 1 to 7, overall, how satisfied are you 
at the present time with: 
Please choose one number which best describes 
your situation. 
overall_satisfaction 
descriptive 
none 
not applicable 
Not a question 
How well your current treatment controls your 
atrial fibrillation? 
treatment_control 
radio 
none 
required 
1, 1 – Extremely satisfied 
2, 2 – Very satisfied 
3, 3 – Somewhat satisfied 
4, 4 – Mixed with satisfied and dissatisfied 
5, 5 – Somewhat dissatisfied 
6, 6 – Very dissatisfied 
7, 7 – Extremely dissatisfied 
The extent to which treatment has relieved your 
symptoms of atrial fibrillation? 
treatment_relieved 
radio 
none 
required 
1, 1 – Extremely satisfied 
2, 2 – Very satisfied 
3, 3 – Somewhat satisfied 
4, 4 – Mixed with satisfied and dissatisfied 
5, 5 – Somewhat dissatisfied 
6, 6 – Very dissatisfied 
7, 7 – Extremely dissatisfied 

Version: 1.0, September 20, 2017 
Page 26 
 
 
Appendix B: Consent Form 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
I-STOP-AFib Study 
 
SUMMARY 
 
I- STOP-AFib Study, led by Dr. Greg Marcus from UCSF, is designed to test the comparative effectiveness 
of studies that allow you to test your personal afib triggers versus daily recording of your AF frequency 
and severity. This Atrial Fibrillation Study is an internet-based mobile platform-enabled study supported 
by the Eureka Research Platform. 
 
Research studies include only people who choose to take part. Please take your time to read this 
consent form thoroughly to make your decision about being a part of this study. 
 
STUDY PURPOSE and GENERAL INFORMATION 
 
Why is this study being done? 
 
The purpose of this study is to compare the ability to test your individual afib triggers vs tracking your 
afib severity and duration in order to improve quality of life for afib patients. 
 
Who is paying for the study? 
 
Patient Centered Outcomes Research Institute is paying for the conduct of this study, and AliveCor is 
providing devices at no cost to the researchers or research participants. The investigators do not have 
any financial or proprietary interests. 
 
Am I eligible? 
 
You are eligible if you have: 
 
(1) Symptomatic atrial fibrillation that comes and goes with potential triggers for your episodes 
(e.g. lack of sleep, caffeine or exercise), and 
(2) An Android or iOS smartphone with reliable Internet and/or Wi-Fi 
How many people will take part in the study? 
About 480 people will take part in this study. 
Can I decide not to participate? 
Taking part in a research study is your choice. You may choose to either take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No matter what 
decision you make, there will be no penalty to you. 

Version: 1.0, September 20, 2017 
Page 27 
 
PROCEDURES 
 
What will happen if I take part in this research study? 
 
● If you are randomized to test your personal triggers: The study duration will be at least 3 months 
but could be up to a year, depending on how many triggers you choose to test. At the start of 
the study, you will select one trigger to test for a period of 6 weeks using a menu of options in 
the app. For example, if the trigger is coffee consumption, this might include a daily alert to 
“avoid coffee today” or “drink coffee today”. You will receive daily reminders to record trigger 
exposure, AF frequency and severity, and to perform a tracing with your AliveCor device. It is 
important to note that you will be identifying your personal triggers and will not be engaging 
in any activities you would not otherwise, if not enrolled in the study. Once your first trigger 
study is complete, you can view your study results and interpretations in the app. Then you will 
have 4 weeks to implement any lifestyle changes from what you learned from the 6 weeks of 
testing your trigger. During this period, you will continue to track AF frequency and severity via 
the app. At the end of the 4-week lifestyle change period, you will have the option to test 
another trigger or end your study participation. If you choose to test another trigger, you will 
follow the same protocol to test up to 5 other AF trigger(s) (i.e. diet, exercise, sleep, alcohol, 
smoking, certain exercises, etc.) using the app. 
● Afib Tracking Arm: If you are randomized to this arm you will collect daily AF episode frequency 
and severity using the app and a daily ECG tracing using your AliveCor device, for 10 weeks. You 
will be able to visualize your afib data in real time on the app and receive a monthly summary of 
your AF frequency and severity via the app. At the end of the 10-weeks you will have the option 
to test your triggers. You will have up to 9 months to test your AF trigger(s) (i.e. diet, exercise, 
sleep, alcohol, smoking, certain exercises, etc.) using the app and the trigger testing protocol 
described above. 
● Follow-up Evaluation: At the end of the 3-month enrollment period, you will complete a 
follow-up assessment of your AF severity and quality of life via the app. 
 
How long will I be in the study? What if I want to stop participating? 
 
The I-STOP-AFib Study will take 3 months to 1 year to complete (depending on how many triggers you 
choose to test). You can decide to stop participating at any time.  We won’t delete the information 
about you that we’ve already collected, but the study will stop collecting any new information about you 
and stop contacting you. 
 
What are the costs of taking part in this study? 
 
There will be no costs to take part in this study. Depending on your situation, there may be some 
indirect costs to you from participating in this study, including incurring extra mobile data plan charges. 
 
Will I be paid for taking part in this study? 
 
You will not be paid for taking part in this study. By participating, each participant will be able to keep 
their AliveCor device after they have completed their participation in the study. 

Version: 1.0, September 20, 2017 
Page 28 
 
BENEFITS/RISKS 
What side effects or risks can I expect from being in the study? 
Participation in the study should not result in any increased physical risk. 
 
Although we will do our best to protect your study information, there is still a very small risk of loss of 
privacy. 
 
Taking part in a mobile-based study may also lead to incurring additional data charges due to increased 
interaction with your smartphone. 
 
If you have additional questions about the risks and side effects of this study, please contact the study 
researchers (see contact information below). 
 
Are there benefits to taking part in the study? 
You may not benefit from participating in this study. Testing triggers may help you identify the role of 
trigger modification in controlling your AF symptoms. We hope that study participation will lead to a 
better understanding of the triggers for AF and optimal means to manipulate those triggers to enhance 
the health of AF patients. We hope that society may benefit from your participation in research. 
 
Will I get advice about my health from the study? 
 
No. While you will have access to the results of your N-of-1 trials and AliveCor readings, we will not 
provide you with information about your health or clinical interpretations of your data from the study. 
Participation in this study does not in any way substitute for professional medical advice, diagnosis, or 
treatment that your doctor or other healthcare provider may give you. Always ask the advice of your 
healthcare provider if you have any questions about a medical condition. Do not disregard professional 
medical advice or delay in seeking care because of something you have read as part of this study. If you 
think you may have a medical emergency, call your doctor or dial 911 immediately. 
 
PRIVACY & SECURITY 
 
You are participating in a research project supported by the Eureka Research Platform, which maintains 
a Privacy Policy and Data Security Measures. You will be notified of any changes in this policy. Here is the 
Policy: 
 
<<Clickable link to “Eureka Privacy Policy and Data Security Measures”>> 
 
Who can answer my questions about the study? 
Please contact Madelaine Faulkner at madelaine.faulkner@ucsf.edu or 415-476-3393 for questions 
about this study. 
If you wish to ask questions about the study or your rights as a research participant to someone other 
than the researchers or if you wish to voice any problems or concerns you may have about the study, 
please contact the UCSF Human Research Protection Program at (415) 502-1814 or IRB@ucsf.edu. 

Version: 1.0, September 20, 2017 
Page 29 
 
CONSENT 
 
You can access and download a copy of this consent form from your N-of-1 Study Settings page. 
 
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to participate or to withdraw 
at any point in this study network without penalty or loss of benefits to which you are otherwise 
entitled. 
 
The Experimental Subject’s Bill of Rights can be found here: 
http://www.research.ucsf.edu/chr/Recruit/English.pdf. 
 
Clicking the button below indicates that you have read and understood the information in this 
consent form. You freely consent to be in this research study and authorize the use and disclosure of 
your unnamed and coded data to electronic database(s) to be broadly shared for future research 
studies. 
 
<<AGREE>>   <<NO THANKS>> 

Version: 1.0, September 20, 2017 
Page 30 
 
Appendix C: DSMB Charter 
 
Data and Safety Monitoring Plan 
 
Although randomization to N-of-1 trials versus symptom surveillance (data tracking) is low risk, we will 
form a DSMB to ensure the safety of participants. This board will be comprised of a patient, a cardiac 
electrophysiologist, and a statistician from outside the research groups or institutions of the study 
personnel otherwise involved in the project. They will meet prior to implementation of the study to 
review the safety of a near-final AF-specific N-of-1 platform. They will meet again after 100 patients are 
enrolled and again after 350 patients are enrolled. 
An analyst will prepare summary statistics of results collected prior to the second and third 
meetings. The DSMB will review study progress and any adverse events that have been reported by 
patients. The DSMB will also discuss trouble around retention, compliance, protocol violation and 
recruitment issues. The DSMB will have the authority to stop the study for safety reasons or to alter it if 
needed. Because the study is expected to be low risk, patients may actually benefit from study 
participation, and specific subgroups (e.g., those in whom N-of-1 studies identify a trigger), may yield 
important results, the DSMB will not perform any interim analyses for efficacy or consider stopping the 
study early for futility. In addition, all potential participant data obtained by the study investigators will 
be monitored on an ongoing basis to ensure compliance, to provide quality assurance (QA), and to 
obtain metrics for quality improvement. 
 
 
DATA AND SAFETY MONITORING BOARD (DSMB) CHARTER 
PRIVILEGED AND CONFIDENTIAL 
 
I-STOP-AFib 
 
1.0 
Overview 
 
This Charter summarizes the roles and responsibilities of the Data and Safety Monitoring Board (DSMB) 
for the investigator-initiated study protocol titled “I-STOP-AFib” 
 
The DSMB is an autonomous body in charge of reviewing safety data and providing advice to Gregory M. 
Marcus, MD, Principal Investigator, throughout the conduct of the study. DSMB administration and 
coordination of all activities during the trial will be conducted by the University of California, San 
Francisco Coordinating Center (UCSF CC). The Charter is intended to be a living document. The DSMB 
may review it at regular intervals to determine whether any changes in procedure are needed (see 
section 8.0). 
 
2.0 
Responsibilities of the DSMB 
 
The DSMB is responsible for safeguarding the interests of study participants, assessing the safety and 
validity of study procedures, and for monitoring the overall conduct of the study and outcomes data. 

Version: 1.0, September 20, 2017 
Page 31 
 
The DSMB members are independent consultants to UCSF and are required to provide 
recommendations with regard to: starting, continuing, and stopping the study. In addition, the DSMB is 
asked to make the following recommendations, as appropriate: 
● Effectiveness of the study intervention 
● Benefit/risk ratio of procedures and participant burden 
● Selection, recruitment, and retention of participants 
● Adherence to protocol requirements 
● Completeness, quality, and analysis of measurements 
● Amendments to the study protocol 
● Adequacy of and amendments to consent forms 
● Performance of individual centers and core labs 
● Participant safety 
 
DSMB responsibilities also include: 
1. 
Approval of the initial DSMB Charter and any subsequent revisions, as necessary 
2. 
Reviewing safety and related reports of a pre-specified format and content 
3. 
Based on the review of the reports, making recommendations, as described above 
4. 
Ensure the confidentiality of all reviews and analyses 
 
Although the DSMB may make recommendations to UCSF about changes in the conduct of the study, 
final decisions will be made by the UCSF Principal Investigator, in consultation with the I-STOP-AF 
Investigators. In the case of early termination of the trial, consultation with PCORI and the UCSF 
institutional review board may also be required. 
 
Members of the DSMB will not share any unblinded or partially-blinded information with anyone outside 
of the DSMB. The study investigators will remain fully blinded* to results related to the overall group 
randomized to data tracking versus the group randomized to N-of-1 trials throughout the study unless 
the DSMB recommends changes in the conduct of the study (e.g., early termination due to negative 
safety findings). Note: the investigators will not be blinded to the results of individual-level N-of-1 trials. 
 
3.0 
Membership 
 
The DSMB will be comprised of: an established cardiac electrophysiologist, a patient with atrial, and a 
statistician from outside the research groups or institutions of the study personnel otherwise involved in 
the project. The DSMB will be composed of three voting members, who will serve on the Board for the 
duration of the Afib N-of-1 trial, provided they fulfill the roles and duties in the Charter. 
 
 
3.1 
Membership Selection 
 
The initial Board membership will be chosen by UCSF with a goal of obtaining optimal scientific and 
clinical expertise. 
 
Additional appointments to the DSMB may be made to replace members of the initial membership (e.g., 
in cases of member resignation or necessary removal of a member) or if the DSMB believes that 
additional expertise is required. Any such appointments would be made by UCSF after consultation with 
the members of the DSMB. Nominations for new members will be accepted from all current Board 
members. 

Version: 1.0, September 20, 2017 
Page 32 
 
 
The DSMB is also empowered to seek additional consultancy with prior agreement from UCS, as to the 
identity of the consultant. Consultants will not be voting members of the Board and will only be 
consulted for advice regarding specific issues/situations, as appropriate. 
 
3.2 
Conflicts of interest 
 
DSMB members will not be employed by UCSF. None of the DSMB members should have any financial 
interest that could be substantially affected by the outcome of the study or have any serious conflicts of 
interests that could affect their objectivity. Should the latter statement no longer hold true for any 
reason, DSMB members agree to notify the DSMB members and UCSF. Financial support for DSMB 
members from UCSF beyond the consultation fee specified in their contracts must be disclosed. Any 
other potential conflicts of interest should be declared to the study investigator. 
 
DSMB members will be asked to approve the DSMB Charter, upon their appointment to the DSMB. 
 
 
4.0 
DSMB Meetings 
 
The DSMB meetings will be scheduled as follows, unless more frequent meetings are warranted by 
issues that arise during the conduct of study or if a meeting is requested by the DSMB Chair: 
 
● Meeting #1: Prior to implementation of the study to review the safety of a near-final AF-specific 
N-of-1 platform. 
 
● Meeting #2: after n=100 have been randomized 
 
● Meeting #3   after n=300 have been randomized 
 
Individuals from UCSF, and other experts in the field may be invited to attend individual meetings, as 
needed/appropriate, as non-voting participants. 
 
Each DSMB member will receive an honorarium of $500 per meeting. 
 
They will meet again after 100 patients are enrolled and again after 300 patients are enrolled. An analyst 
will prepare summary statistics of results collected prior to the second and third meetings. They will 
review study progress and any adverse events that have been reported by patients. The DSMB will have 
the authority to stop the study for safety reasons or to alter it if needed. Because the study is expected 
to be low risk, patients may actually benefit from study participation, and specific subgroups (e.g., those 
in whom N-of-1 studies identify a trigger), may yield important results, the DSMB will not perform any 
interim analyses for efficacy or consider stopping the study early for futility. In addition, all potential 
participant data obtained by the study investigators will be monitored on an ongoing basis to ensure 
compliance, to provide quality assurance (QA), and to obtain metrics for quality improvement. 

Version: 1.0, September 20, 2017 
Page 33 
 
 
 
4.1 
Initial Meeting 
 
At the initial meeting of the DSMB will be held to provide the DSMB with an overview of the study, 
establish meeting guidelines, as well as review the Charter and safety report format/content which will 
be used for future DSMB meetings. Additional topics which might be discussed at this meeting include: 
● Frequency of meetings and format of future meetings 
● Key safety and additional variables to be reviewed for decision making 
● Interim analysis planning 
 
4.2 
Subsequent Ad hoc Meetings 
 
Meetings will be scheduled according to the timeline noted in Section 6.0. Subsequent ad hoc meetings 
(by telephone/webinar) may be scheduled at the discretion of the DSMB. UCSF may also request that 
the DSMB hold additional meetings if warranted by study progress. 
 
4.3 
Quorum 
 
DSMB members will make every attempt to attend the meeting by tele/webconference. All three DSMB 
members will be required to attend each meeting. 
 
4.4 
Voting 
 
DSMB members will vote to approve the initial DSMB Charter and amendments, all 
proposals/recommendations to be submitted to UCSF, and protocol revisions (only those changes to the 
protocol required by the DSMB need to be reviewed). 
 
To vote, a DSMB member must be a participant in a meeting held by tele/webconference. Each member 
will have a single vote. Issues will be decided based on a simple majority vote with the following 
exceptions: 
 
● DSMB member with expertise in statistics must vote on all recommendations regarding protocol 
changes that impact sample size or planned analysis. Neither proxies nor designees are 
permitted. 
● Approval of the DSMB Charter and any amendments to the Charter require a unanimous vote 
from all members. 
 
Voting will be conducted verbally at the meetings, but a member may request that a vote be conducted 
by anonymous written ballot instead. The DSMB will attempt to come to a consensus evaluation by the 
end of a meeting. When this is not possible, the different opinions (as well as their rationale) will be 
documented in the meeting minutes and the DSMB will decide how to proceed or follow-up. 

Version: 1.0, September 20, 2017 
Page 34 
 
 
 
5.0 
Confidentiality 
 
Any information and materials that a DSMB member may acquire, during the course of his/her 
membership, with respect to UCSF’s business or the I-STOP-AF study will be maintained in secrecy, and 
each such member will use all reasonable diligence to prevent disclosure of them during the trial. 
 
No obligation of confidentiality shall exist as to information and materials that are in the public domain 
by public use, publication, general knowledge or the like, or contained in the publication of the HOLIDAY 
study results. 
 
6.0 
Meeting Materials 
 
The UCSF study team will draft the DSMB agenda and will produce/distribute all materials to attendees 
prior to the meeting. 
 
 
6.1 
Planned Interim Analyses 
 
AS described above, an interim analysis of the primary effectiveness endpoints will not be performed. 
 
 
6.2 
Request for Unscheduled Interim Analyses 
 
It is acknowledged that a significant safety concern entitles the DSMB to request unscheduled formal 
interim analyses. The DSMB may request unscheduled formal interim analyses of either the primary or 
secondary endpoints. 
 
Provided that the DSMB unscheduled interim analysis involves the review of safety data and no 
effectiveness data, no adjustments will be performed to the α level for the primary endpoint evaluation 
at the end of the study. In the case that a formal unscheduled interim analysis is actually performed 
involving effectiveness data, the test criteria (i.e. critical boundaries) will be amended according to the 
appropriate α-spending function and the study sample size may be amended. 
 
6.3 
Final DSMB Meeting Minutes/Recommendations Review Process 
 
Meeting minutes, which will include the DSMB recommendations and requests, are to be prepared for 
all meetings and distributed to the DSMB members after the meeting for review and approval. 
 
A copy of the open session minutes will be available to the Principal Investigators and the UCSF 
Institutional Review Board (IRB). 

Version: 1.0, September 20, 2017 
Page 35 
 
6.3.1 
DSMB Action Items 
 
Communication of the DSMB recommendations and requests will occur as follows: 
 
● In the event of a safety concern, or other DSMB recommendations/requests should be 
immediately communicated at the end of the meeting to the UCSF. 
 
 
All DSMB recommendations and requests will be considered action items, which will require resolution 
or a response (or update) by the time of the next meeting. Any recommendations of the DSMB 
involving a possible safety risk to participants will be handled by all parties in as expedited a manner, as 
possible. 
 
 
7.0 
Approval of and Amendments to the DSMB Charter 
 
DSMB member approval of this version of the Charter represents the entire understanding of the parties 
with respect to the subject matter hereof and merge and supersede all prior and contemporaneous 
Charters or understandings, oral or written, with respect thereto. The failure of a member to adhere to 
any term of this Charter on any occasion may only be excused by waiver. All waivers must be in writing 
and signed by the party making the waiver (i.e., DSMB chair or UCSF representative). 
 
Amendments to the Charter may be proposed by UCSF or a DSMB member. This Charter shall not be 
modified except by unanimous vote of all DSMB members. 
 
 
DSMB Members: 
 
Jonathan C. Hsu, MD, MAS 
Assistant Professor of Medicine 
Section of Cardiac Electrophysiology, Division of Cardiology 
University of California, San Diego 
 
Dr. Jonathan Hsu is an Assistant Clinical Professor of Medicine at UCSD School of Medicine, Division of 
Cardiology. His primary clinical interest is in cardiac electrophysiology, and he specializes in the medical 
and procedural care of patients with all types of heart rhythm disturbances. 
 
He is a clinical research investigator with formal advanced training (Master’s Degree) in clinical research 
methods and biostatistics. His research focuses on the epidemiology and clinical outcomes in patients 
with all types of cardiac arrhythmias and devices, including reducing the risk of stroke in atrial fibrillation 
patients with oral anticoagulants and reducing complications in implantable-cardioverter defibrillator 
recipients. 
 
Dr. Hsu has a special clinical interest in quality of cardiovascular care improvement and outcomes 
research. He has specific expertise in Registry and large database analyses to improve the medical and 

Version: 1.0, September 20, 2017 
Page 36 
 
procedural care of patients with arrhythmias. 
 
Dr. Hsu completed fellowship training in general cardiology and received additional advanced 
subspecialty training in cardiac electrophysiology at the University of California, San Francisco (UCSF), 
where he also completed his Master’s Degree in Clinical Research (MAS). He completed both his 
internship and residency at Massachusetts General Hospital. He earned his undergraduate and medical 
degree at Northwestern University. 
 
Stephen Belford 
Patient DSMB representative 
 
Stephen Belford is a 72 year old male who is retired from a position of technology management. My 
expertise was program management (including project management) and product usability and the user 
experience. I am active in retirement. I was diagnosed with paroxysmal AFib in early to mid-2000s but 
holter monitor and stress cardio test were unable to detect again. I then went to Dr. Jeff Olgin and was 
diagnosed as having permanent AFib. In fall of 2015, I went for my annual visit with Dr. Olgin, and was 
found not to have AFib. This resulted, I believe, from reduction in alcohol intake.  Using a Kardia 
monitor regularly, I determined that I would enter AFib, only after drinking in excess of 1 glass of wine 
daily. 
 
 
Eric Vittinghoff, Ph.D 
Professor at UCSF Department of Epidemiology and Biostatistics 
 
Dr. Vittinghoff is a temporary DSMB member, helping the study team to identify a suitable DSMB 
statistician for this unique N-of-1 trial. He is an experienced BIostatistician at the University of California 
San Francisco. 

Version: 1.0, September 20, 2017 
Page 37 
 
Appendix D: Eureka Privacy Policy 
 
PRIVACY POLICY AND DATA SECURITY MEASURES 
 
You are participating in a research project supported by the Eureka Research Platform, which 
maintains the following privacy policies and data security measures. 
 
Your information will be used for research 
Information about your background, health, behaviors and other factors that might help 
researchers predict, prevent or treat diseases will be collected for research. This information will 
be used in research analyses, and results of these analyses will be presented in scientific 
conferences and published. These presentations and publications will not show information that 
identifies you or any other individual in the study without your explicit permission. 
 
We will contact you when we need you 
We will send you an email, text message (SMS) or app-based notification when we need you, 
for example when one of your studies needs you to do something. You can set your 
preferences for how you want to be notified - remember that, depending on your mobile phone 
plan, you may be charged for text messages you receive from us. 
 
Your identify will not be shared 
We will never sell, rent, or lease your identifying information, or voluntarily share it for any 
reason without your permission. 
 
You decide how to share your data 
We’ll ask if you want to share the data you donate with other research studies that you’re 
participating in (so you don’t have to re-enter data for two different studies), and with other 
qualified researchers without your name or other identifiers (so your data can used to help 
people everywhere). You’ll also have the option of setting your default data sharing preferences 
to “Share all data with studies I join”, so we don’t have to ask you every time. 
 
You are responsible for keeping your login credentials secure 
When you registered for Eureka, you provided an email or phone number and a password. You 
can use this to sign into our system and see some of the health information you've provided to 
us (your height and weight, medication list, etc). You should be very careful not to provide your 
login information to anyone else, or they could sign in as you and be able to see that same 
health information. If you are worried that someone else may be using your login information, 
please let us know immediately, or change your password yourself through the Participant 
Homepage . 
 
If required by law, we may need to disclose information about you 
In accordance with the law, we may be required to take actions to prevent serious harm to 

Version: 1.0, September 20, 2017 
Page 38 
 
yourself or others. This may include divulging information about you to authorities. Otherwise, 
we will do everything we can to keep your study information private, and we will resist any 
demands for information that would identify you. 
 
We keep our data really secure 
While we cannot provide an absolute data security guarantee, your information will be 
transmitted and stored using state-of-the-art security systems similar to those that protect 
websites used by banks and electronic health record systems. Specifically, our platform is 
hosted on Amazon Web Services (AWS), a cloud-based server system and computing 
services.These systems and services are compliant with the U.S. Health Insurance Portability 
and Accountability Act of 1996 (HIPAA). All research data are stored behind a secure firewall, 
guarded by intrusion detection software, and encrypted at rest and in transit in our Amazon 
Virtual Private Cloud. 

Version: 1.0, September 20, 2017 
Page 39 
 
Appendix E: Trigger Survey 
 
 
Atrial Fibrillation Triggers Survey 
Survey Number: 3 - 1 
 
Question? 
Popup Language Title 
Popup Language Body 
variable name 
field type 
branching logic 
required/not required 
1, Option #1 
2, Option #2 
 
Text Validation 
Triggering Between Survey 
 
Note - questions that are triggered have a blue “fill” 
The triggers that start an episode of atrial 
fibrillation are not well understood and appear 
to be highly variable among patients with AF. 
Based on a research idea co-developed with 
atrial fibrillation patients, we have recently 
received funding from the Patient Centered 
Outcomes Research Institute to study this exact 
research question. Specifically, will the 
identification of triggers objectively 
demonstrated to influence atrial fibrillation 
episodes help enhance quality of life among 
those with the disease. We ill randomly assign 
approximately 500 individuals who have 
symptomatic, intermittent atrial fibrillation (at 
least once a month) to either tract their 
exposures, behaviors and atrial fibrillation 
episodes or follow personalized instructions 
from a smartphone-based app to determine if 
certain triggers are indeed significantly 
associated with atrial fibrillation episodes. Our 
goal is to help patients identify triggers with the 
ultimate goal of learning to minimize, eliminate, 
or at some level control triggers fro purposes of 
reducing the number of bothersome atrial 
fibrillation episodes. 
We are no in the first phase of this novel 
experiment and need your help. As a patient 
with atrial fibrillation, we hope you can help us 
understand what you believe to be important 
Not a question. Description before the survey 
questions. 

Version: 1.0, September 20, 2017 
Page 40 
 
exposures or behaviors that might trigger atrial 
fibrillation episodes. To help us with this 
patient-centered research project on atrial 
fibrillation, please complete this survey to the 
best of your ability. If you know others with 
atrial fibrillation that may wish to participate, 
please share the link. 
Ok, let’s get started: 
intro 
none 
[none] 
required 
 
We want to be sure you have atrial fibrillation 
episodes that you feel. In other words, some 
individuals with atrial fibrillation do not feel any 
differently when they are in atrial fibrillation. 
Do you have symptomatic atrial fibrillation (i.e., 
you experience something that tells you when 
you are in atrial fibrillation) that comes and 
goes on its own (also known as paroxysmal 
atrial fibrillation)? 
afib 
radio 
[none] 
required 
1, Yes (include yes even if you feel it sometimes 
and not other times) 
2, No, but I do not feel it or know it when I am in 
atrial fibrillation 
3, No, I am in atrial fibrillation all the time 
4, I am not certain 

Version: 1.0, September 20, 2017 
Page 41 
 
Thank you so much for contributing to our 
survey. We look forward to engaging you 
further in patient powered research. If you are 
interested in helping us combat diseases like 
atrial fibrillation and have not already done so, 
please consider joining the Health eHeart Study 
here {LINK}. 
OR 
Sorry, but you are not eligible to participate in 
this study. Thank you so much for contributing 
to our survey. We will email you in the future 
with any future update opportunities! 
ineligible 
field type 
[afib] = ‘2, 3’ 
required 
Not a question. Participant does not take the 
rest of the survey. 
Why are you not certain if you have atrial 
fibrillation? 
afib_explain 
string 
[afib] = ‘4’ 
required 
Text box 
 
Do you think there are any identifiable things 
you are exposed to (such as something you eat 
or drink or in the environment) or things that 
you do that trigger your atrial fibrillation 
episodes? 
afib_triggers 
radio 
branching logic 
required 
1, Yes, for all of my atrial fibrillation episodes 
2, Yes, but only for some of my atrial fibrillation 
episodes 
3, I’m not sure 
4, No 

Version: 1.0, September 20, 2017 
Page 42 
 
Thank you so much for contributing to our 
survey. We look forward to engaging you 
further in-patient powered research. If you are 
interested in helping us combat diseases like 
atrial fibrillation and have not already done so, 
please consider joining the Health eHeart Study 
here {LINK}. 
OR 
Sorry, but you are not eligible to participate in 
this study. Thank you so much for contributing 
to our survey. We will email you in the future 
with any future update opportunities! 
ineligible2 
field type 
[afib_triggers] = ‘4’ 
required 
Not a question. Participant does not take the 
rest of the survey. 
For things that may trigger your atrial 
fibrillation episodes, can they be modified or 
influenced by you relatively easily? For example, 
weather events or pollution levels are not easily 
modified or influenced by any individual, but 
intake of alcohol or certain types of exercises 
are. 
trigger_control 
radio 
none 
required 
1, Yes, at least one of the triggers I think may be 
important to my atrial fibrillation can be 
modified or influenced by me 
2, No, all of the potential triggers for my atrial 
fibrillation are completely out of my control 
3, I am not sure 
4, Other 
Please explain below. 
control_explain 
string 
[trigger_control] = ‘4’ 
required 
Text Box 
 

Version: 1.0, September 20, 2017 
Page 43 
 
OK, now we’re going to ask you about some 
triggers that some patients have reported. Then, 
we want to now if you have experience other 
triggers that we have failed to mention. 
Importantly, we are going to continue to focus 
on triggers that can be 
changed/modified/influenced by you since 
these are the only types of triggers we can 
feasibly test in our planned study. 
intro2 
none 
[none] 
required 
Not a question. Description before the survey 
questions. 
Does alcohol trigger your atrial fibrillation? 
alcohol_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of alcohol 
on your atrial fibrillation episodes? This would 
mean receiving messages from a mobile app on 
your phone to go ahead and drink alcohol (to a 
level you are comfortable with) on some days 
and then being instructed to avoid all alcohol on 
other days. 
alctest_willingness 
radio 
[alcohol_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never drink alcohol 
3, No – I do not want to drink alcohol because I 
already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 
 
Why are you not sure about testing the effect of 
alcohol on your atrial fibrillation? 
*In Qualtrics, this question does not exist. 
Instead, the answer choice #4 says, in ( ), 
“Please explain below” and then a text box 
that is not required to fill in. Same for all the 
similar questions below. 
alctest_explain 
Text Box 

Version: 1.0, September 20, 2017 
Page 44 
 
string 
[alctest_willingness] = ‘4’ 
not required 
 
Do caffeine-containing beverages or foods (such 
as coffee or chocolate) trigger your atrial 
fibrillation? 
caffeine_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of caffeine 
on your atrial fibrillation episodes? This would 
mean receiving messages from a mobile app on 
your phone to go ahead and consume caffeine 
(to a level you are comfortable with) on some 
days and then being instructed to avoid all 
caffeine on other days. 
cafftest_willingness 
radio 
[caffeine_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never consume anything with caffeine 
in it 
3, No – I do not want to consume anything with 
caffeine because I already know it will trigger an 
episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
caffeine on your atrial fibrillation? 
cafftest_explain 
string 
[cafftest_willingness] = ‘4’ 
not required 
Text Box 
 
Does lack of sleep trigger your atrial fibrillation? 
sleep_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 45 
 
Do you think this is testable? Obviously control 
over quality of sleep can be difficult. 
sleeptest_willingness 
radio 
[sleep_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I could imagine a strict adherence to a 
certain routine (such as an earlier bedtime or 
avoiding some things prior to bedtime) would 
help my sleep 
2, Yes for some reason other than adherence to 
a certain routine before bed 
3, No – while something might help, I would not 
be able to implement them 
4, No – my difficulty with sleeping is not 
sufficiently under my control 
5, No for some other reason 
6, I am not sure 
Why do you not think lack of sleep is testable on 
your atrial fibrillation? 
sleeptest_explain 
string 
[sleeptest_willingness] = ‘2, 5’ 
not required 
Text Box 
Does vigorous exercise trigger your atrial 
fibrillation? 
exercise_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of 
vigorous exercise on your atrial fibrillation 
episodes? This would mean receiving messages 
from a mobile app on your phone to go ahead 
and exercise vigorously (to a level you are 
comfortable with) on some days and then being 
instructed to avoid all vigorous exercise on 
other days. 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never exercise vigorously 
3, No – I do not want to exercise vigorously 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 46 
 
exertest_willingness 
radio 
[exercise_trigger] = ‘1, 2, 3, 4’ 
required 
 
Why are you not sure about testing the effect of 
vigorous exercise on your atrial fibrillation? 
exertest_explain 
string 
[exertest_willingness] = ‘4’ 
not required 
Text Box 
Does lack of exercise trigger your atrial 
fibrillation? 
noexercise_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of a lack 
of exercise on your atrial fibrillation episodes? 
This would mean receiving messages from a 
mobile app on your phone to limit your exercise 
(to a level you are comfortable with) on some 
days and then being instructed to exercise more 
rigorously on other days. 
noexertest_willingness 
radio 
[noexercise_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never stop or limit my exercise 
3, No – I do not want to stop or limit my exercise 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 47 
 
Why are you not sure about testing the effect of 
lack of exercise on your atrial fibrillation? 
noexertest_explain 
string 
[noexertest_willingness] = ‘4’ 
not required 
Text Box 
Do cold beverages trigger your atrial 
fibrillation? 
bev_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of cold 
beverages on your atrial fibrillation episodes? 
This would mean receiving messages from a 
mobile app on your phone to go ahead and 
consume cold beverages (to a level you are 
comfortable with) on some days and then being 
instructed to avoid all cold beverages on other 
days. 
bevtest_willingness 
radio 
[bev_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never drink cold beverages 
3, No – I do not want to drink cold beverages 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
cold beverages on your atrial fibrillation? 
bevtest_explain 
string 
[bevtest_willingness] = ‘4’ 
not required 
Text Box 

Version: 1.0, September 20, 2017 
Page 48 
 
Do cold foods (such as ice cream) trigger your 
atrial fibrillation? 
food_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 
Would you be willing to test the effect of cold 
foods on your atrial fibrillation episodes? This 
would mean receiving messages from a mobile 
app on your phone to go ahead and consume 
cold foods (to a level you are comfortable with) 
on some days and then being instructed to avoid 
all cold foods on other days. 
foodtest_willingness 
radio 
[food_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never consume cold foods 
3, No – I do not want to consume cold foods 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
cold foods on your atrial fibrillation? 
foodtest_explain 
string 
[foodtest_willingness] = ‘4’ 
not required 
Text Box 
Does a high salt diet trigger your atrial 
fibrillation? 
salt_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 49 
 
Would you be willing to test the effect of a high 
salt diet on your atrial fibrillation episodes? This 
would mean receiving messages from a mobile 
app on your phone to go ahead and consume 
high salt levels (to a level you are comfortable 
with) on some days and then being instructed to 
avoid all salt on other days. 
salttest_willingness 
radio 
[salt_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never consume a high salt diet 
3, No – I do not want to consume a high salt diet 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
a high salt diet on your atrial fibrillation? 
salttest_explain 
string 
[salttest_willingness] = ‘4’ 
not required 
Text Box 
Do large meals or over-eating trigger your atrial 
fibrillation? 
meals_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 50 
 
Would you be willing to test the effect of large 
meals or over-eating on your atrial fibrillation 
episodes? This would mean receiving messages 
from a mobile app on your phone to go ahead 
and consume large meals or over-eat (to a level 
you are comfortable with) on some days and 
then being instructed to avoid all over-eating 
and large meals on other days. 
mealstest_willingness 
radio 
[meals_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never consume large meals or over-eat 
3, No – I do not want to consume large meals or 
over-eat because I already know it will trigger 
an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
consuming large meals or over-eating on your 
atrial fibrillation? 
mealstest_explain 
string 
[mealstest_willingness] = ‘4’ 
not required 
Text Box 
Does dehydration (not drinking 6-8 glasses of 
water per day) trigger your atrial fibrillation? 
dehyd_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 51 
 
Would you be willing to test the effect of 
dehydration on your atrial fibrillation episodes? 
This would mean receiving messages from a 
mobile app on your phone to limit your liquid 
consumption (to a level you are comfortable 
with) on some days and then being instructed to 
fully hydrate on other days. 
dehydtest_willingness 
radio 
[dehydrate_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never drink 6-8 glasses of water per 
day 
3, No – I do not want to drink less that 6-8 
glasses of water per day because I already know 
it will trigger an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
dehydration on your atrial fibrillation? 
dehydtest_explain 
string 
[dehydtest_willingness] = ‘4’ 
not required 
Text Box 
Does laying on your left side trigger your atrial 
fibrillation? 
lay_trigger 
radio 
none 
required 
1, Yes, it is responsible for every one of my atrial 
fibrillation episodes 
2, Yes, it triggers some of my atrial fibrillation 
episodes 
3, It might trigger some of my episodes 
4, No, I have not noticed this as a trigger 
5, I am not sure 

Version: 1.0, September 20, 2017 
Page 52 
 
Would you be willing to test the effect of laying 
on your left side on your atrial fibrillation 
episodes? This would mean receiving messages 
from a mobile app on your phone to go ahead 
and lay on your left side (to a level you are 
comfortable with) on some days and then being 
instructed to avoid laying on your left side on 
other days. 
laytest_willingness 
radio 
[lay_trigger] = ‘1, 2, 3, 4’ 
required 
1, Yes – I would not mind and I would be happy 
to follow those instructions as best I could 
2, No – I never lay on my left side 
3, No – I do not want to lay on my left side 
because I already know it will trigger an episode 
4, No for some other reason 
5, I am not sure 
Why are you not sure about testing the effect of 
laying on your left side on your atrial 
fibrillation? 
laytest_explain 
string 
[laytest_willingness] = ‘4’ 
not required 
Text Box 
 
Now we would like to know what other triggers 
might be important to you. 
other_trig 
none 
none 
required 
Not a question. Description before the survey 
questions. 
Please tell us what trigger you think might be 
important for your atrial fibrillation (you will 
have an opportunity to list more than one, so 
let’s just start with one here): 
describe_othertrig 
none 
none 
required 
Not a question. Description before the survey 
questions. 

Version: 1.0, September 20, 2017 
Page 53 
 
What is it? 
trigger_idea 
string 
none 
required 
Text box 
After exposure to this trigger begins, how long 
until atrial fibrillation occurs? 
trigger_exposure 
string 
none 
required 
Text box (hours and minutes) 
How would you propose to test this? On days 
you might want to TEST the trigger, what 
message would you like us to send you?; (i.e., if 
alcohol were the trigger, this might say 
something like “go ahead and drink alcohol to 
your comfort level today”): 
lang_trigtest 
string 
none 
required 
Text box 
On days when you might want to AVOID the 
trigger (i.e., if alcohol was the trigger to be 
tested, this might be something like “avoid all 
alcohol today”): 
lang_trigavoid 
string 
none 
required 
Text box 
Do you have another trigger you can tell us 
about? 
otheridea_trig 
radio 
none 
required 
1, Yes 
2, No 
Continue for 3 total trigger ideas. 
otheridea_trig 
 

Version: 1.0, September 20, 2017 
Page 54 
 
string 
[other_trigidea] = ‘1’ 
required 
 
 
Great – thanks for sharing your thoughts about 
potential triggers. 
great 
none 
none 
required 
Not a question. Description before the survey 
questions. 
 
We’re almost done. Now to make the best use of 
these data as we can and make sure it’s applied 
effectively to our study design, it will be 
important to know a few things about you. 
demo_intro 
none 
none 
required 
Not a question. Description before the survey 
questions. 
How old are you? 
age 
string 
none 
required 
Text box 
What is your biological sex? 
sex 
radio 
none 
required 
1, Male 
2, Female 
3, Prefer not answer 
Are you of Hispanic, Latino or Spanish origin or 
ancestry? 
Ethnicity 
This is a question about ethnicity, rather than race, as 
used in the US Census. For example, someone may be of 
white race and Hispanic ethnicity or black race and 
Hispanic ethnicity. 
hispanic 
radio 
1, No 
2, Yes, Mexican, Mexican American or Chicano 
3, Yes, Puerto Rican 
4, Yes, Cuban 
5, Yes, Other or Mixed Hispanic, Latino or 
Spanish origin 
6, Don’t know 

Version: 1.0, September 20, 2017 
Page 55 
 
none 
required 
 
What is your racial background? Check all that 
apply. 
race 
checkbox 
none 
required 
1, Black or African American 
2, White 
3, Asian (including South Asian and Asian 
Indian) 
4, Native Hawaiian or Pacific Islander 
5, American Indian or Alaska Native 
6, Some other race 
7, Don’t know 
What is your Asian background? 
asian 
radio 
none 
required 
1, Chinese 
2, Filipino 
3, Asian Indian 
4, Japanese 
5, Korean 
6, Vietnamese 
7, Other Asian or Mix 
8, No Asian background 
What is your Pacific Island background? 
pacisland 
radio 
none 
required 
1, Native Hawaiian 
2, Samoan 
3, Guamanian or Chamorro 
4, Other Pacific Islander or Mix 
5, No Pacific Islander background 
Do you have or have you ever been treated for 
high blood pressure? 
hbp 
radio 
none 
required 
1, Yes 
2, No 
3, I don’t know 
Do you have or have you ever been treated for 
diabetes or high blood sugar? 
diabetes 
radio 
none 
required 
1, Yes 
2, No 
3, I don’t know 
Do you have or have you ever been treated for 
heart failure or too much fluid in the lungs? 
heartfailure 
1, Yes 
2, No 
3, I don’t know 

Version: 1.0, September 20, 2017 
Page 56 
 
radio 
none 
required 
 
Do you have or have you ever been treated for 
coronary artery disease or blockages in the 
arteries? 
cad 
radio 
none 
required 
1, Yes 
2, No 
3, I don’t know 
Do you have or have you ever been treated for 
sleep apnea? 
sleepapnea 
radio 
none 
required 
1, Yes 
2, No 
3, I don’t know 
How tall are you? 
height 
radio 
none 
required 
Text box (feet and inches) 
What is your current weight? 
weight 
radio 
none 
required 
Text box (lbs) 
Does anyone in your immediate family also have 
atrial fibrillation (including biologically related 
parents, brothers, sisters, or children)? Note – if 
ONLY more distant relatives had atrial 
fibrillation (such as cousins or grandparents) 
this should be answered no. 
afib_family 
radio 
none 
required 
1, Yes 
2, No 
3, I don’t know 

Version: 1.0, September 20, 2017 
Page 57 
 
Do you drink alcohol? If yes, how many drinks, 
on average, do you have a week? 
alcohol 
radio 
none 
required 
1, Yes, <1 
2, Yes, 1-3 
3, Yes, 4-7 
4, Yes, 8-11 
5, Yes, 12-14 
6, Yes, 15-18 
7, Yes, 19-21 
8, Yes, >21 
9, No 
10, I don’t know 
Have you smoked at least one cigarette in the 
last month? 
cigarettes 
radio 
none 
required 
1, Yes 
2, No – I used to smoke cigarettes, but I quit 
3, No – I have never smoked 
Have you used any electronic cigarettes or 
“vaped” at least once in the last month? 
ecigs 
radio 
none 
required 
1, Yes 
2, No, but I do use them occasionally 
3, No, but I have used them in the past and quit 
4, No, I have never used them 
 

Version: 1.0, September 20, 2017 
Page 58 
 
Thank you for your participation in this survey. 
Your answers are extremely valuable in helping 
us to design this study and ultimately to 
understand more about atrial fibrillation. If you 
are interested in helping us combat diseases like 
atrial fibrillation and have not already done so, 
please consider joining the Health eHeart Study 
here {LINK}. Also, please keep a look out for the 
study invitation when it launches in a few 
months. Thank you! 
Kathi Sigona 
Atrial Fibrillation Patient 
Patient Co-Principal Investigator 
Gregory M Marcus, MD, MAS 
Endowed Professor of Atrial Fibrillation 
Research 
University of California, San Francisco 
Co-Principal Investigator 
thanks 
none 
none 
required