ECG App Algorithms Clinical Validation Study
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Apple Inc.

 
 
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ECG app 2.0 Algorithms Clinical Validation Study 
 
Sponsor: 
Apple Inc. 
Protocol Number 
013 
Version and date: 
– 5 December 2019 
Compliance Statement: 
This study will be conducted in accordance 
with this protocol, the Declaration of 
Helsinki, and ICH GCP Guidelines, and the 
applicable regulatory requirements (21 CFR 
Parts 50, 54, 56, and 812). The conduct of the 
study will be approved by the US Food and 
Drug Administration (FDA) and appropriate 
Institutional Review Board (IRB) of the 
respective Investigational site.  Safety 
assessments (adverse events) for this study 
will be conducted in accordance with ISO 
14155-1 (2011).  
 
 

 
 
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INVESTIGATOR APPROVAL PROTOCOL SIGNATURE PAGE 
 
Protocol: 
 
Title: 
ECG app 2.0 Algorithms Clinical Validation Study 
 
Amendment: 
 
 
 
 
I confirm that I have read and understood this trial protocol and attached appendices and will 
conduct this study in compliance with the protocol, all statements regarding confidentiality, 
local regulations, International Council for Harmonization Good Clinical Practice E6 (ICH-GCP), 
and United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (21 CFR 
Parts 50 [protection of human subjects], 54 [financial disclosure by clinical investigators], 56 
[informed consent and Institutional Review Board (IRB) requirements], 812 [Investigational 
Device Exemptions]).  
With my signature, I agree to: 
(i) Conduct the investigation in accordance with the agreement, the investigational 
plan, applicable provisions of 21 CFR Part 812 and other Food and Drug Administration (FDA) 
regulations, and conditions of approval imposed by the reviewing IRB or FDA;  
(ii) Supervise all testing of the device involving human subjects; and  
(iii) Ensure that the requirements for obtaining informed consent are met. 
 
Reviewed and Approved by: 
 
 
[TO BE SIGNED WHEN PROTOCOL IS FINALIZED] 
  
Investigator’s Signature 
 
 
Date 
 
 
 
Name/Title 
 
 

 
 
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SYNOPSIS 
Study Title 
ECG app 2.0 Algorithms Clinical Validation Study 
Protocol Version 
 
Protocol Date 
5 December 2019 
Study Design 
Prospective, multi-center, non-significant risk study. 
Key Inclusion 
Criteria 
All cohorts:  
• Age 22 or older 
• Resides in the United States (US) and will remain in the US for 
the duration of the study 
• Able to read and understand a written ICF 
• Wrist circumference between 130 mm and 245 mm 
Cohort 1: No known history of atrial fibrillation (AF) and in normal 
sinus rhythm at the time of screening 
Cohort 2: Known persistent or permanent or chronic AF, and be in AF 
at the time of screening 
Key Exclusion 
Criteria 
All cohorts:  
• Physical disability that precludes safe and adequate testing  
• Physical or medical impairments that preclude exercise testing such 
as musculoskeletal back pain, arthritis, leg claudication, etc. 
• Mental impairment that in the opinion of the Investigator would not 
allow subject to complete the trial  
• Pregnant women at the time of the screening visit 
• Subjects with any Medical History, Physical exam, vital sign or any 
other study procedure finding/assessment that in the opinion of the 
investigator could compromise subject safety during study 
participation or interfere with the study integrity and/or the accurate 
assessment of the study objectives.  This includes patients with 
known untreated medical conditions that are considered clinically 
significant by the Investigator, such as but not limited to significant 
anemia, important electrolyte imbalance and untreated or 
uncontrolled thyroid disease.  Physical exam limitations include but 

 
 
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Endpoints  
Co-Primary Endpoints: 
1a. Correct classification of subjects with normal sinus rhythm (HR 
50-150) on simultaneous 12-lead ECG as “Sinus Rhythm” or “High 
Heart rate” on a readable and classifiable ECG app strip. 
[Specificity] 
1b. Correct classification of subjects with AF (HR 50-150) on 
simultaneous 12-lead ECG as “AF” on a readable and classifiable 
ECG app strip. [Sensitivity] 
Secondary Endpoints: 
2a. Correct classification of subjects with normal sinus rhythm (HR 
50-99, sinus rhythm (SR) on simultaneous 12-lead ECG) as “Sinus 
Rhythm” on a readable and classifiable ECG app strip 
2b. Correct classification of subjects with AF (HR 50-99, AF on 
simultaneous 12-lead ECG) as “AF” on a readable and classifiable 
ECG app strip 
2c. Correct classification of subjects with sinus tachycardia (HR 
100-150, SR on simultaneous 12-lead ECG) as “High Heart Rate” 
on a readable and classifiable ECG app strip 
2d. Correct classification of subjects with AF with high heart rate 
(HR 100-150, AF on simultaneous 12-lead ECG) as “AF (high 
heart rate)” on a readable and classifiable ECG app strip 
2e. Equivalence of the ECG app waveform to Lead I from a 12-lead 
ECG as measured by acceptable morphology of PQRST complexes 
2f. Equivalence of the ECG app waveform to Lead I from a 12-lead 
ECG as measured by R-Wave amplitude agreement 
Test Device 
Investigational ECG app 2.0 algorithms 
Study App 
ECG App for Data Collection 
Reference Device 
12-lead ECG (GE Healthcare Cardiosoft Systems (K031561)) 
Study Procedures 
Subjects will wear an Apple Watch and record a single lead ECG using 
the ECG sensor on Apple Watch and a simultaneous 12-lead ECG. 
Subjects will exercise to target a HR of at least 85% of predicted max 
heart rate (not to exceed 150 bpm), then record a 30- second single lead 
ECG using the ECG sensor on Apple Watch and a simultaneous 12-
lead ECG. After data collection, the investigational ECG app 

 
 
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algorithms will be run on the sensor data collected from subjects to 
generate waveforms and rhythm classifications. 12-lead ECGs will be 
adjudicated for rhythm diagnosis by 2 independent US Board Certified 
Cardiologists (with a 3rd reviewer in the event of discrepancy). 
Waveform comparison will be adjudicated by 2 independent cardiac 
technicians (with a 3rd reviewer in the event of discrepancy). 
Duration of Study 
Participation 
Approximately 4 hours 
Total Number of 
Study Subjects 
Enrolled  
Approximately 568 subjects total, including approximately 168 with 
sinus rhythm and approximately 400 with AF. 

 
 
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TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................3 
LIST OF ABBREVIATIONS ...................................................................................................9 
1. 
INTRODUCTION .......................................................................................................... 10 
1.1. Background ................................................................................................................. 10 
1.2. Device Description ...................................................................................................... 10 
This clinical study is being conducted to support investigational ECG app 2.0 
algorithms (test device) for the Apple ECG app which expand the 
classification heart range, introduce new classification results, and 
introduce minor, non-user-facing algorithm updates. ............ Error! Bookmark not 
defined. 
1.3. Study Rationale ........................................................................................................... 11 
1.4. Risk/Benefit Assessment ............................................................................................. 11 
2. 
STUDY OBJECTIVES, ENDPOINTS, AND HYPOTHESES .................................... 12 
2.1. Study Objective ........................................................................................................... 12 
2.2. Study Endpoints .......................................................................................................... 12 
2.3. Study Hypotheses ........................................................................................................ 12 
3. 
STUDY DESIGN ............................................................................................................ 15 
3.1. Overview ..................................................................................................................... 15 
3.2. Required Equipment .................................................................................................... 15 
3.2.1. Sponsor-Provided ............................................................................................ 15 
3.2.2. Storage and Handling Procedure ...................................................................... 15 
3.2.3. Accountability ................................................................................................. 15 
3.2.4. Investigational Study Site-Provided ................................................................. 16 
3.3. Qualification Criteria for US Board-Certified Cardiologists ......................................... 16 
3.4. Randomization and Blinding ....................................................................................... 16 
3.5. Duration of Subject Participation ................................................................................. 16 
4. 
STUDY POPULATION ................................................................................................. 17 
4.1. Subject Recruitment .................................................................................................... 17 
4.2. Study Cohorts and Target Population........................................................................... 17 
4.3. Inclusion Criteria ......................................................................................................... 17 
4.4. Exclusion Criteria ........................................................................................................ 18 
4.5. Subject Discontinuation ............................................................................................... 19 
4.6. Subject Follow-up ....................................................................................................... 19 
5. 
STUDY PROCEDURES ................................................................................................ 20 
5.1. Screening .................................................................................................................... 20 
5.2. Study Day 1................................................................................................................. 21 
5.2.1. Study Procedures ............................................................................................. 21 
5.2.1.1. Data Collection Study Equipment Set up ................................................ 21 
5.2.1.2. Data Collection – Rest ECG ................................................................... 22 
5.2.1.3. Exercise 22 

 
 
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5.2.2. Apple Watch Data Processing .......................................................................... 23 
5.2.3. Adjudication of ECG Data ............................................................................... 23 
5.2.3.1. 12-lead ECG ........................................................................................... 23 
5.2.3.2. ECG Strip Overlay.................................................................................. 24 
6. 
STATISTICAL ANALYSIS .......................................................................................... 26 
6.1. Dataset Generation ...................................................................................................... 26 
6.2. Statistical Methodology ............................................................................................... 26 
6.2.1. Primary Endpoint Analysis .............................................................................. 26 
6.2.2. Secondary Endpoint Analyses .......................................................................... 27 
6.2.3. Safety Analyses ............................................................................................... 30 
6.2.4. Additional Analyses ......................................................................................... 30 
6.3. Sample Size Determination ......................................................................................... 31 
6.4. Significance Level ....................................................................................................... 32 
6.5. Missing Data ............................................................................................................... 32 
6.6. Subgroup Analyses ...................................................................................................... 32 
6.7. Interim Analyses ......................................................................................................... 32 
6.8. Analysis Sets ............................................................................................................... 32 
7. 
SAFETY PARAMETERS AND ASSESSMENT .......................................................... 34 
7.1. Adverse Events............................................................................................................ 34 
7.1.1. AE/SAE Collection .......................................................................................... 34 
7.1.2. SAE Reporting ................................................................................................. 35 
7.1.3. Reporting of all other Study Adverse Events .................................................... 35 
7.2. Safety Plan .................................................................................................................. 36 
7.3. Overview of study suspension and termination criteria ................................................ 36 
8. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS ............................................................................................ 37 
8.1. Institutional Review Board .......................................................................................... 37 
8.2. Informed Consent ........................................................................................................ 37 
8.3. Ethical Conduct of Study ............................................... Error! Bookmark not defined. 
8.4. Confidentiality and Privacy ......................................................................................... 38 
8.5. Protocol Adherence ..................................................................................................... 38 
8.6. Collection and Management Responsibilities ............................................................... 38 
8.7. Study Monitoring ........................................................................................................ 38 
8.8. Data Quality Assurance and Quality Control  .............................................................. 39 
8.9. Use of Information ...................................................................................................... 39 
8.10. 
Study Record Retention ........................................................................................ 40 
8.11. 
Study Termination and Site Closure...................................................................... 40 
8.12. 
Completion of the Study ....................................................................................... 40 
9. 
REFERENCES............................................................................................................... 41 
 

 
 
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LIST OF ABBREVIATIONS 
The following abbreviations are used in this study protocol. 
Abbreviation  
Explanation 
ADE 
Adverse device effect 
AE 
Adverse event 
AF 
Atrial fibrillation  
AFL 
Atrial flutter 
BMI 
Body mass index 
CFR 
Code of Federal Regulations 
CRO 
Contract research organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HR 
Heart Rate 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
IRB 
Institutional Review Board 
NA 
Not applicable 
PAF 
Paroxysmal atrial fibrillation 
QC 
Quality control 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SR 
Sinus rhythm 
SVT 
Supraventricular tachycardia 
UADE 
Unexpected adverse device effect 
US 
United States 

 
 
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1. 
INTRODUCTION 
1.1. 
Background 
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and when left untreated, is a 
leading cause of morbidity and mortality from stroke, heart failure and myocardial infarctioni,ii. 
Data from the Framingham Heart Study indicates that by age 40 years, lifetime risk for 
developing AF is 1 in 4iii. AF is also a growing public health problem with prevalence projected 
to triple between 2010 and 2050, with an estimated 12.1 million diagnosed cases in 2030 in the 
United States (US) aloneiv.  
Early detection and treatment of patients with AF minimizes the risk of sequelae of 
thromboembolism including >60% reduced risk of strokeii,v. However, atrial fibrillation is 
commonly underdiagnosed; many people with AF are asymptomatic or experience mild 
nonspecific symptoms for which they do not seek medical attention or screening.ii. As a result, 
asymptomatic patients are 3 times as likely to have sustained an ischemic stroke prior to 
diagnosis than those with symptomsi,vi. These findings raise concerns and have prompted several 
variations of screening programs to detect patients with asymptomatic AF to prevent an embolic 
eventi,ii. While systematic and opportunistic screening programs have demonstrated increased 
rates of detection when compared to detection during routine clinical practice, such screening 
programs are not yet widely implementedii. Additionally, AF may be paroxysmal (PAF or 
intermittent AF) and therefore missed by recording a single in-clinic electrocardiogram (ECG). 
This is especially true for those patients with intermittent symptoms. Holter devices are 
commonly used for ambulatory 24-hour ECG monitoring in at-risk patients, but have limited 
sensitivity for the detection of new AFvii. Given that mobile ECG devices permit an on-demand 
assessment by a user, our hypothesis is that use of the ECG app on Apple Watch can facilitate 
identification of AF. 
1.2. 
Device Description 
 
The ECG app software is comprised of a pair of mobile medical apps—one on Apple Watch and 
the other on the iPhone. 
 
The ECG Watch app analyzes data collected by the integrated electrical sensors on a compatible 
Apple Watch to generate an ECG waveform similar to a Lead I, calculate average heart rate, and 
provide a rhythm classification to the user for a given 30 second session. When a user opens the 
ECG Watch app while wearing the Watch on one wrist and places the finger of the opposite hand 
on the digital crown, they are completing the circuit across the heart which begins a recording 
session.  
 
Once the recording session is complete, the ECG Watch app performs signal processing, feature 
extraction and rhythm classification to generate a session result.  
 

 
 
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1.3. 
Study Rationale 
This clinical study is being conducted to support investigational ECG app 2.0 algorithms (test 
device) for the Apple ECG app which expand the classification heart range, introduce new 
classification results, and introduce minor, non-user-facing algorithm updates, and evaluate the 
performance of the test device.  
1.4. 
Risk/Benefit Assessment 
No significant risks or permanent side effects are anticipated. However, subjects may experience 
temporary discomforts or have risks while or as a result of participating in this study.  
• Subjects may experience slight to moderate discomfort associated with attachment 
and removal of adhesive electrodes used for ECGs. The risk will be minimized by 
using medical-grade disposable electrodes and by leaving them attached to the skin 
only for the limited study duration.  Even with these precautions, temporary skin 
irritation may still occur.   
• Subjects may experience slight to moderate discomfort associated with wearing the 
Apple Watch.  
• Exercising on a treadmill or stationary bike may cause temporary discomfort due to 
exertion. This risk will be minimized by asking subjects to self-select exercise 
intensity, so subjects may choose to reduce the workload at any time if necessary.  
• Subjects participating in exercise may feel other symptoms, including but not limited 
to dizziness, heart palpitations, anxiety, and shortness of breath. 
• Rarely, people with atrial fibrillation (AF) may experience an abnormal heart rhythm 
that may be life-threatening and/or require further treatment. If this happens, subject 
participation in the study may be terminated. 

 
 
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3. 
STUDY DESIGN 
3.1. 
Overview 
This is a prospective, non-significant risk study. The study protocol will undergo review and 
approval by an Institutional Review Board (IRB) prior to enrolling study subjects.  
Written, informed consent will be obtained from all subjects before any protocol-directed 
procedures are performed. All potential subjects will participate in a screening visit, and if 
eligibility is confirmed, subjects may begin study participation at the same visit.  
The investigational ECG app 2.0 algorithms (test device) will be run post-hoc on the sensor 
dataset to generate ECG app waveforms and classifications. The performance of the test device 
will be determined based upon adjudication of concurrent data from the reference device.  
3.2. 
Required Equipment 
3.2.1. 
Sponsor-Provided 
The Sponsor will provide the study sites with sufficient Apple Watch Series 4 and 5 to complete 
the study. iPhones will also be provided to study sites, but subjects will not be expected to 
interact with these iPhones (for clinical research staff to upload data to study sponsor only).  
Sponsor will provide 12-lead ECG monitor: GE Healthcare CardioSoft Systems. CardioSoft is an 
FDA cleared ECG device (K031561). All study equipment will be returned to the Sponsor at the 
end of the study. All study equipment will be pre-labelled and supplied to the Investigational Site 
by Sponsor. 
No specific packaging of the study equipment is required, as this study is non-interventional and 
will temporarily dispense study equipment to subjects. 
 
3.2.2. 
Storage and Handling Procedure 
All study equipment and reference devices (the “study equipment”) will be stored in normal 
room temperature/humidity/pressure conditions with no exposure to direct sunlight or heat 
source throughout the study. The storage area should be secure with restricted access. 
 
3.2.3. 
Accountability 
Test and reference device ID numbers used for each subject will be recorded in the source 
documents. All study equipment will be returned to the Sponsor at the end of the study. 
 

 
 
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3.2.4. 
Investigational Study Site-Provided 
• Space to screen subjects 
• Space to conduct testing and regular examination room/office equipment 
• Treadmill 
• Stationary bike 
• Equipment to record vital signs  
• Appropriate safe and storage area for study equipment 
3.3. 
Qualification Criteria for US Board-Certified Cardiologists 
Reviewers of 12-lead ECG data must be US board-certified medical doctors specialized in 
cardiology.  
Reviewers of ECG waveforms will be Certified Cardiographic Technicians. 
Curriculum vitae and medical license will be collected for each US board-certified medical 
doctors specialized in cardiology. 
3.4. 
Randomization and Blinding 
Subjects in this study will not be randomized to any treatment regimens.   
Approximately 100 subjects (50 SR; 50 AF) will be randomly selected to assess waveform 
equivalence of the ECG app to Lead 1 from a 12-Lead ECG.  Subjects will be randomly selected 
using a systematic sampling approach. A number between 1 and 6 will be randomly selected for 
the AF cohort and then every 6th consecutively enrolled AF subject will be selected at random 
within each site. Likewise, a number between 1 and 3 will be randomly selected for the SR 
cohort and then every 3rd consecutively enrolled SR subject will be selected at random within 
each site. 
US board-certified cardiologists will be blinded to the subjects’ past medical history, stage 
(resting or exercise) and ECG app classifications during the assessment and adjudication of ECG 
data. 
Cardiac technicians will be blinded to the subjects’ past medical history, ECG app 
classifications, stage (resting or exercise) and origin (ECG app or 12-lead ECG) of the waveform 
being reviewed during the assessment and adjudication of ECG data. 
Adjudicators will be instructed to review ECGs independently and separately of each other and 
not to confer about diagnoses. 
3.5. 
Duration of Subject Participation 
Subjects will participate in a screening visit and, if eligible, participate in the study for 1 day 
(study procedures will last approximately 4 hours) within a window of 30 days after screening 
visit. 

 
 
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4. 
STUDY POPULATION 
4.1. 
Subject Recruitment 
Subject recruitment can be accomplished in any appropriate fashion, within the guidelines of the 
IRB and the investigational site(s). Recruitment will continue until enrollment requirements are 
met, including reaching the targeted number of subjects completing the study procedure. 
Investigators should keep a record, i.e. subjects screening log, of subjects who are entered into 
the study.  Each subject must meet all of the inclusion criteria and none of the exclusion criteria 
for this study at the time of screening and study participation. The sponsor must approve any 
changes to the target distribution of subjects in writing prior to enrollment. 
4.2. 
Study Cohorts and Target Population 
The study will include two cohorts of subjects:  
• Cohort 1 will include subjects with no known history of AF and are in normal sinus 
rhythm at time of screening  
• Cohort 2 will include subjects with known persistent or permanent or chronic AF who are 
in AF at the time of screening 
The following age, gender, and race/ethnicity enrollment targets will be adhered to during 
subject recruitment: 
• A minimum of 20% of subjects in both cohorts will be enrolled in each of the age 
categories of 55 to 64, and ≥65 years, and a minimum of 10% of subjects in both cohorts 
in the age category of <55 years..  
• At least 40% of subjects in Cohort 1 will be female. At least 20% of subjects in Cohort 2 
will be female. 
• At least 30% of subjects in Cohort 1 will be either American Indian or Alaska Native, 
Asian, Black or African American, Native Hawaiian or Other Pacific Islander.  
• In Cohort 2, at least 15% of subjects will be either American Indian or Alaska Native, 
Asian, Black or African American, Native Hawaiian or Other Pacific Islander 
The incidence of AF is known to increase with age, male gender, and White raceviii. These 
recruitment targets are also consistent with the subject population observed in the Apple Heart 
Studyix, which is representative of the intended use population.  
 
4.3. 
Inclusion Criteria 
Subjects must meet all the following inclusion criteria to be enrolled: 
1. Able to read, understand, and provide written informed consent 
2. Willing and able to participate in the study procedures as described in the consent form 
3. Individuals who are 22 years of age and older at time of screening 

 
 
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4. Able to communicate effectively with and follow instructions from the study staff 
5. Have a wrist circumference between 130 mm and 245 mm (Measured at “band center” on 
the preferred wrist).  
 
6. Subjects enrolled into Cohort 1 must have no known medical history of AF and in normal 
sinus rhythm at the time of screening.  
7. Subjects enrolled into Cohort 2 must have a known diagnosis of persistent or permanent 
or chronic AF and be in AF at the time of screening.  
4.4. 
Exclusion Criteria 
Subjects must meet none of the following criteria to be enrolled: 
1. Physical disability that precludes safe and adequate testing  
2. Physical or medical impairments that preclude exercise testing such as musculoskeletal 
back pain, arthritis, leg claudication, etc. 
3. Mental impairment as determined by the Investigator 
4. Pregnant women at the time of the screening visit. 
5. Subjects with any Medical History, Physical exam, vital sign or any other study 
procedure finding/assessment that in the opinion of the investigator could compromise 
subject safety during study participation or interfere with the study integrity and/or the 
accurate assessment of the study objectives.  This includes patients with known untreated 
medical conditions that are considered clinically significant by the Investigator, such as 
but not limited to significant anemia, important electrolyte imbalance and untreated or 
uncontrolled thyroid disease.  Physical exam limitations include but not limited to open 
wound(s) on the wrist and forearm where the subject will be wearing the watch. 
6. Any history of wrist surgery with scarring in the area of the sensor location on the wrist 
where the subject will be wearing the watch 
7. Vital signs measurement, medical history, or physical exam finding that makes the 
subject inappropriate for participation according to the Investigator. 
8. Tattoos or moles in the area of the sensor location on the wrist where the subject will be 
wearing the watch. 
9. Skin conditions on either wrist that would preclude subject from wearing watch on either 
wrist. Severe symptomatic (or active) overly dry/injured skin, skin disorders, or allergic 
skin reactions such as eczema, rosacea, impetigo, dermatomyositis or allergic contact 
dermatitis on wrist and locations where the electrodes will be placed (e.g. chest, 
forearms, stomach), as determined by the investigator. 
10. Known allergy or significant sensitivity to medical adhesives, isopropyl alcohol, or ECG 
patch 

 
 
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11. Known allergy or sensitivity to fluorocarbon-based synthetic rubber, such as 
fluoroelastomer bands primarily used in the wrist worn fitness devices. 
12. Clinically significant hand tremors as judged by the Investigator. 
 
14. Subjects with implantable pacemaker devices or an automated Implantable Cardioverter – 
Defibrillator devices 
 
4.5. 
Subject Discontinuation and Replacement  
Each enrolled subject shall remain in the study until completion. However, subject participating 
in the study is voluntary and the subject has the right to withdraw at any time. Some example of 
possible subject discontinuation may be:  
• 
Subject Death 
• 
Subject voluntary withdrawal 
• 
Subject withdrawal by an investigator 
• 
Subject early termination by Sponsor 
The sponsor must be notified of the reason(s) for subject discontinuation. The site will provide 
the information to the Sponsor. Site Investigators must also report this to their respective IRB as 
defined per their IRB procedures.  
Subject Replacement:  
Subjects who discontinued from the study will be replaced as determined by Sponsor.  
4.6. 
Subject Follow-up 
No subject follow-up will be performed.  

 
 
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5. 
STUDY PROCEDURES 
5.1. 
Screening 
Informed consent will be obtained before any study protocol-directed procedures are performed. 
After the signing of informed consent, the subject will be evaluated for eligibility according to 
the study inclusion/exclusion criteria (Section 4.3 and Section 4.4).  
During screening, the following should be obtained on each subject: 
• 
Age 
• 
Gender 
• 
Race and ethnicity 
• 
Diagnosed medical conditions such as: past surgical history, illness, previous 
diagnoses 
• 
Prior and Concomitant Medications 
• 
Allergies 
• 
Tobacco and Nicotine history 
• 
Alcohol use (self-reported) 
• 
Recreational drug use (self-reported) 
• 
Physical examination (will include at a minimum general appearance, lungs, chest, 
heart, head and neck, abdomen, musculoskeletal/extremities, lymph nodes, skin and 
neurological assessment) 
• 
Height and weight 
• 
Body mass index (BMI) 
• 
Vital signs will be collected after sitting for at least 5 minutes. Vital signs collected 
may include blood pressure, heart rate, and body temperature  
• 
Urine pregnancy testing for women of childbearing potential 
• 
Caffeine intake 
• 
Exercise habits 
• 
Dominant hand 
• 
Wrist circumference of wrist wearing the Watch 
• 
Skin fold thickness of wrist wearing the Watch 
• 
Wrist hairiness of wrist wearing the Watch 
• 
Assessment of tattoos, moles, scars on wrist of wrist wearing the Watch  
• 
12-lead ECG will be collected supine after lying for at least 5 minutes 

 
 
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* For women of child-bearing potential only. A woman will be considered not of child-bearing 
potential if they are surgically sterile and have provided documentation, or they are >55 and have 
not had a cycle for >2 years. 
All subjects will undergo a 12-lead ECG. The 12-lead ECG will be reviewed and interpreted by 
the investigator. If subjects were not previously aware of any abnormal findings on ECG, the 
investigator will inform the subject of the findings; any further medical care will be at the 
discretion of the subject’s non-study medical provider. Non-AF subjects must be in normal sinus 
rhythm at the time of the 12-lead ECG at screening in order to be assigned to Cohort 1.  AF 
subjects must be in AF at the time of the 12-lead ECG at screening in order to be assigned to 
Cohort 2. AF subjects that do not present AF at time of screening may come back another day 
within 7 days to determine their eligibility for Cohort 2 at a maximum of one repeat time.  
If any of the study staff believe the vital signs or screening 12-lead ECG are of poor quality, they 
may repeat the measurements. 
5.2. 
Study Day 1 
Subjects will report to the clinic for the Day 1 visit at their scheduled date and time. No special 
preparation for this visit is required.  If eligibility is confirmed after completion of all screening 
procedures, subjects may begin study participation following the screening.  
Subjects will be asked to remove jewelry and any underwire bras during 12-lead ECG data 
collection. NOTE: Non-underwire bras are acceptable during data collection 
5.2.1. 
Study Procedures  
5.2.1.1. 
Data Collection Study Equipment Set up 
The following procedures will be performed for each study subject at study participation:  
Assign an Apple Watch and the paired iPhone to each subject and document the Apple Watch 
and paired iPhone numbers and the version of Study App. The Watch configurations were 
selected at random from the total set of Watch configurations. The random assignment of 
watches to subjects is based on a pre-determined randomization schedule stratified by site, age 
group and cohort 
1. Instruct the subject to choose his/her preferred wrist to wear the Apple Watch. The Apple 
Watch can be worn on whichever side the subject prefers unless there is a skin condition 
on one wrist as noted above in the exclusion criteria, in which case, the Apple Watch 
must be worn on the non-affected wrist. Record the chosen wrist. If the subject does not 
have a side preference or skin condition on one wrist, the device will be placed on the left 
wrist. 
2. The subject will be asked to put the Apple Watch on his/her wrist (as indicated in 1). The 
Apple Watch should be fitted tightly enough that it does not move when the hand/wrist is 
shaken.  
3. Check band tightness for a snug fit and adjust as needed. 

 
 
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5.2.3.1.2. Rhythm Diagnoses 
The following rhythm diagnoses will be adjudicated to the 12-lead ECG data (Section Error! 
Reference source not found.) for each 12-lead ECG: 
1. Sinus Rhythm (will include sinus bradycardia, normal sinus rhythm, and sinus 
tachycardia) 
2. Atrial Fibrillation  
3. Supraventricular tachycardia (SVT) with regular beat-to-beat intervals (e.g., AVNRT, 
AVRT, Atrial Tachycardia with HR over 100 beats per minute) 
4. Other Abnormal Rhythm 
a. Frequent Premature Atrial Contractions (>3 in 30 seconds) 
b. Frequent Premature Ventricular Contractions (>3 in 30 seconds) 
c. Atrial flutter 
d. Ventricular tachycardia 
e. Ventricular fibrillation 
f. Second degree AV block, Type I 
g. Second degree AV block, Type II 
h. Third degree AV block 
i. Other 
5. Uninterpretable 
5.2.3.1.3. Combining Heart Rate and Rhythm Diagnoses on 12-lead ECG 
Heart Rate 
Rhythm on 12-lead ECG 
 
Sinus 
Rhythm 
Atrial 
Fibrillation 
SVT with 
regular intervals 
Other 
Uninterpretable 
<50 
HR<50 
HR<50 
N/A 
HR<50 
Uninterpretable 
50-99 
SR 50-99 
AF 50-99 
N/A 
Other 50-99 
Uninterpretable 
100-150 
SR 100-150 
AF 100-150 
SVT 100-150 
Other 100-150 
Uninterpretable 
>150 
HR>150 
HR>150 
HR>150 
HR>150 
Uninterpretable 
 
5.2.3.2. 
ECG Strip Overlay 
1. Strip preparation 

 
 
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a. The Sponsor will prepare one paired set of rest ECG strips and one paired set of 
exercise ECG strips from 100 randomly selected subjects (50 AF; 50 SR). Each 
set of rest and exercise ECG strips will be comprised of the Apple Watch ECG 
and lead 1 ECG from the 12-lead. 
2. Cardiac Core Lab review: 
a. Three blinded, independent cardiac technicians or cardiologists will review each 
paired sets of strips on 25mm/s, 10 mm/mV standard. 
b. One reviewer will identify the first six consecutive distinct readable PQRST 
complexes without artifact that match between the subject device strip and 
reference device strip for evaluation. For example, if the reference strip has an 
artifact in beats 2 and 5 but all other beats are good and the strip from the test 
device has artifact in beats 1 and 6 but all other beats are good, the six 
consecutive beats to be used will begin at beat 7 of both strips. The strips will be 
excluded if six consecutive beats cannot be found. The six PQRST complexes 
identified by the initial reviewer will be used by the 2 other reviewers. 
c. The strips will be rendered semi-transparent through the use of back lighting and 
overlaid to visually assess for morphological similarity. 
d. Each reviewer will assign a pass/fail to the strips by visually assessing all 6 
PQRST complexes. A “pass” is given when the morphology of the PQRST 
complexes appears to overlay to the unaided eye. 
e. Measure R amplitude from the isoelectric baseline of the PR segment at the onset 
of the QRS complex to the highest vertical deflection of the R-wave. Measure to 
the nearest 0.5 millimeter for the first QRS complex of the six consecutive distinct 
readable PQRST complexes in both the reference strip and test device strip. The 
reviewers will be blinded to the identity of the reference strip and test device strip. 
 

 
 
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The following primary endpoint hypothesis will be tested using a one-sided type I error of 0.025: 
 
 
Using the cross-classified data from Table 1, the sensitivity and specificity for the primary 
endpoint hypothesis will be estimated as follows: 
Sensitivity estimate = n22/(n12 + n22) 
Specificity estimate = n11/(n11 + n21) 
 
Each subject may contribute up to 2 paired ECG app and Adjudicated 12-Lead ECG results for 
analysis; one at rest (first trial run) and the other after exercise (first trial run).     
Because data will be collected from the same subjects at rest and after exercise, a bootstrap 
approach will be implemented to obtain two-sided 95% confidence intervals for the sensitivity 
and specificity to account for potential within-subject correlation.  Subjects with at least one 
adjudicated result of AF (for sensitivity), SR (for specificity) and with a classifiable algorithm 
result (i.e., SR or AF) will be selected at random with replacement and the 2.5th and 97.5th 
percentiles of the distribution of bootstrap estimates will represent the two-sided 95% confidence 
bounds.  If the lower confidence bounds for both sensitivity and specificity exceeds the pre-
established performance goal associated with these performance metrics, the null hypothesis will 
be rejected in favor of the alternative hypothesis. 
As an additional analysis associated with the primary endpoint, the sensitivity and specificity 
will also be estimated and reported along with their corresponding bootstrap two-sided 95% 
confidence intervals by including the Inconclusive algorithm classification category in the 
calculation.  More specifically, the sensitivity and specificity for the additional analysis will be 
estimated as follows: 
Sensitivity estimate (additional analysis) = n22/(n12 + n22+n32) 
Specificity estimate (additional analysis) = n11/(n11 + n21+n31) 
 
6.2.2. 
Secondary Endpoint Analyses 
The following truth table will be generated to cross-classify data collected from enrolled subjects 
according to the ECG app device and adjudicated ECG data from the 12-lead ECG for secondary 
endpoint analyses as presented below 
Table 2: Cross-classification truth table for secondary endpoint analyses 
 
Ground Truth via Adjudicated 12-lead ECG  
HR 
<50 
50-99 
50-99 
100-
150 
100-
150 
>150 
50-150 
 
 

 
 
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ECG app 
Device 
Output 
Rhythm 
Any 
SR 
AF 
SR 
AF 
Any 
SVT or 
Other 
Uninter
pretable 
Total 
Low HR (<50) 
n11 
n12 
n13 
n14 
n15 
n16 
n17 
n18 
N1D 
SR (50-99) 
n21 
n22 
n23 
n24 
n25 
n26 
n27 
n28 
N2D 
AF (50-99) 
n31 
n32 
n33 
n34 
n35 
n36 
n37 
n38 
N3D 
High HR (100-150) 
with no AF 
n41 
n42 
n43 
n44 
n45 
n46 
n47 
n48 
N4D 
AF (100-150) 
n51 
n52 
n53 
n54 
n55 
n56 
n57 
n58 
N5D 
HR >150 
n61 
n62 
n63 
n64 
n65 
n66 
n67 
n68 
N6D 
Inconclusive 
n71 
n72 
n73 
n74 
n75 
n76 
n77 
n78 
N7D 
Poor Recording 
n81 
n82 
n83 
n84 
n85 
n86 
n87 
n88 
N8D 
Total 
N1 
N2 
N3 
N4 
N5 
N6 
N7 
N8 
N 
Note: Bold indicates data values used for the secondary endpoint analyses.  
 
The following four secondary endpoint hypotheses will be tested: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Using the cross-classified data from Table 2, the percent correct for each of the four secondary 
endpoint hypotheses will be estimated as follows: 
Hypothesis 2a:  Percent Correct = n22/(n22+n32+n42+n52) 
Hypothesis 2b:  Percent Correct = n33/(n23+n33+n43+n53) 
Hypothesis 2c:  Percent Correct = n44/(n24+n34+n44+n54) 
Hypothesis 2d:  Percent Correct = n55/(n25+n35+n45+n55) 
 
Each subject may contribute up to 2 paired ECG app and Adjudicated 12-Lead ECG results for 
analysis; one will be at rest (first trial) and the other after exercise (first trial).     
Because data will be collected from the same subjects at rest and after exercise, a bootstrap 
approach will be implemented to obtain two-sided 95% confidence intervals for the percent 
correct associated with each of the four secondary endpoint hypotheses to account for potential 
within-subject correlation.  Subjects with at least one adjudicated result of SR (HR 50-99) 
[hypothesis 2a], AF (HR 50-99) [hypothesis 2b], SR (HR 100-150) [hypothesis 2c], AF (HR 
100-150) [hypothesis 2d] and with a classifiable algorithm result will be selected at random with 
replacement and the 2.5th and 97.5th percentiles of the distribution of bootstrap estimates will 
represent the two-sided 95% confidence bounds.  If the lower confidence bound of the percent 
correct equals or exceeds the pre-established performance goal associated with the associated 
secondary endpoint hypotheses, the null hypotheses will be rejected in favor of the alternative 
hypotheses.     
Additional secondary endpoint analyses will be performed similarly by including the HR < 50, 
HR >150, and Inconclusive algorithm results in the computations of percent correct.    
  
Two hypotheses associated with secondary objective to demonstrate that the ECG app produces 
a waveform that provides clinically equivalent information to Lead 1 of the 12-Lead ECG will be 
tested.  
The first hypothesis is aimed at demonstrating that the proportion of subjects with a morphology 
pass rating based on the visual assessment of 6 consecutive readable PQRST complexes is at 
least 
. The majority result from the pass/fail readings of the 3 independent, certified cardiac 
technicians will be used for analysis. The hypothesis for this objective is stated as follows: 
 
 
The second hypothesis will be based on the results of the quantitative analysis of the R-wave 
amplitudes as measured by each of 3 independent, certified cardiac technicians on the paired 
ECG app and Lead 1 from the 12-Lead ECG reference strips. The majority result from the three 

 
 
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technicians (i.e., if at least two technicians measured the difference in amplitudes between the 
SUT and reference strips to be ≤2 mm then the paired strips for a given subject were deemed 
≤2 mm) was used for
 
 
 
For each subject, the QRS complex from the 12-lead ECG with the largest R amplitude (out of 
the two QRS complexes with R-wave amplitude measurements) will be used for purposes of 
determining the majority result. 
Data from the first trial run of the randomly selected subjects while the subject is at rest and after 
exercise will be used to test the two waveform assessment hypotheses using a bootstrap sampling 
approach.  If the 2.5th percentile of the bootstrap distribution for the Morphology Pass Rating 
Proportion 
 the null hypothesis H0_2e will be rejected.  
 
to the evaluation of the R-Wave Amplitude Agreement Proportion. 
6.2.3. 
Safety Analyses 
All adverse events will be recorded throughout the entire study period, whether they are 
considered to be related to the study procedures or not. Signs and symptoms of each AE will be 
described in detail: date of event, description of event, severity, relationship to study procedures, 
action taken and outcome. Adverse events will be collected as spontaneously reported by the 
subjects. 
The number of any adverse events and the number and percentage of subjects reporting each 
type of adverse event will be presented by Preferred Term. Multiple occurrences of the same 
event reported by the same subject will be counted only once. 
6.2.4. 
Additional Analyses 
The following additional analyses will be performed. 
• Percent correct associated with the Other abnormal rhythm truth category will be 
estimated as n77/(N7 - n87).   
• Percent correct associated with the HR under 50 (HR<50 on simultaneous 12-lead ECG) 
truth category will be estimated as n11/(N1-n81). 
• Percent correct associated with the HR over 150 (HR >150 on simultaneous 12-lead 
ECG) truth category will be estimated as n66/(N6-n86). 
• Percent correct associated with the AF rhythm classification for adjudicated heart rate 
values between 50-120.  The numerator of this percent correct calculation will be the 
number of test device classifications of AF and test device heart rate between 50-120 
with an adjudicated AF rhythm classification and adjudicated heart rate value between 
50-120. The denominator will include all classifiable test device results with an 
adjudicated AF rhythm classification and adjudicated heart rate between 50-120.  

 
 
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Classifiable Analysis Set (CAS): All subjects with readable paired ECG app and 12-Lead ECG 
adjudicated results.  This analysis set will be used to analyze data for the co-primary endpoints 
(1a, 1b), the four secondary endpoints (2a, 2b, 2c, and 2d) and the additional analyses. 
Waveform Assessment Analysis Set (WAAS): Randomly selected subjects with readable paired 
strips from the ECG app and Lead 1 of the 12-Lead ECG. If 6 consecutive beats for analysis 
cannot be found in these strips, they will be excluded from analysis. This analysis set will be 
used for assessing the clinical waveform accuracy associated with secondary endpoints 2e and 
2f. 

 
 
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7. 
SAFETY PARAMETERS AND ASSESSMENT 
7.1. 
Adverse Events  
The definition of adverse events are as follows: 
Term 
Definition 
Reference 
Adverse 
Event (AE) 
Any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in 
subjects, users or other persons, whether or not 
related to the device. 
ISO 
14155: 
2011 
Serious 
Adverse 
Event (SAE) 
Adverse event that 
a) Led to death, 
b) Led to serious deterioration in the health 
of the subject, that either resulted in 
1) A life-threatening illness or 
injury, or 
2) A permanent impairment of a 
body structure or a body 
function, or 
3) In-patient or prolonged 
hospitalization, or 
4) Medical or surgical intervention 
to prevent life-threatening 
illness or injury or permanent 
impairment to a body structure 
or a body function, 
c) Led to fetal distress, fetal death or a 
congenital abnormality or birth defect 
ISO 
14155: 
2011 
 
7.1.1. 
AE/SAE Collection  
An adverse event is defined as any untoward medical occurrence (clinical symptom, sign, or 
significant laboratory finding, for example) in a clinical investigation subject which does not 
necessarily have to have a causal relationship with the study procedures. 
Any abnormal laboratory findings, abnormal safety assessments, or anticipated day-to-day 
fluctuations which are associated with a pre-existing disease or condition, are not considered an 
Adverse Event unless judged by the investigator to be worsening or more severe than expected. 
All adverse events must be fully recorded throughout the entire study period, whether they are 
considered to be related to the study procedures or not. Adverse events will be collected as 
spontaneously reported by the subjects.  
 

 
 
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Adverse events should be followed until they are resolved or stabilized (returns to baseline for a 
pre-existing condition) and followed by a private MD, or the subject is lost to follow-up. In the 
event of a subject not returning to the clinical unit, the outcome of this event will be recorded as 
lost at follow up. 
Possible AEs include the following: 
 
● Skin rash on wrist due to wearing the Apple Watch;  
● Pressure artifacts on wrist due to wearing the Apple Watch; 
The following occurrences are not to be regarded as AEs: 
 
● Underlying (pre-existing) symptoms or diseases, unless there is an increase in severity 
or frequency during the course of the investigation; 
● Detection of atrial fibrillation or other irregular heartbeat; 
● Complaint about iPhone or Apple Watch functionality;  
● Study app or ECG app functionality issues that do not allege an adverse event 
 
7.1.2. 
SAE Reporting  
 
The Site Investigator should report all SAEs to the Sponsor as soon as possible but no later than 
24 hours of becoming aware of the event. The Site Investigator should also report the SAEs to 
their IRB according to their IRB reporting requirements.   On the date the Site Staff became aware 
that the event met the SAE definition as per provided in this protocol, the investigator will be 
requested to complete a separate SAE reporting form in addition to the information on the source 
documentation. The Investigator will conduct further investigation of these events regarding 
determination of event as a serious adverse event and determination of relatedness of the event to 
the study. The investigation of these events will be completed and reported to the Sponsor within 
15 days of initial report to Sponsor. 
 
7.1.3. 
Reporting of all other Study Adverse Events 
Possible adverse events (non-serious) related to the study will be reported to the Sponsor within 
14 business days of being reviewed by the Investigator. The Investigator will conduct further 
investigation of these events regarding determination of event as a serious adverse event and 
determination of relatedness of the event to the study. The investigation of these events will be 
completed and reported to the Sponsor within 30 days of initial report to the Sponsor. 
 
Any technical issues / complaints related to the ECG app should be referred to AppleCare, 1-
800-275-2273. 
 

 
 
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7.2. 
Safety Plan  
The clinical staff is responsible for the ongoing safety and well-being of the subjects during 
study participation. Management of all medical complications arising during the course of the 
research study will be managed by the investigator as deemed appropriate. A medical monitor 
will be available for consultation related to subject safety and adverse events.  All incidental 
findings identified during screening will be referred at the investigator’s discretion to the 
appropriate additional care in accordance with current standard of care. This can include removal 
of the study associated devices, as well as other measures as required. Even if a study device is 
removed prior to the specified duration, data may be used if of suitable quality. Replacement of 
the study subject who has had the device removed prematurely will be as deemed appropriate, 
following review of the data.  
7.3. 
Overview of study suspension and termination criteria 
 
The research study will be completed as planned unless one or more of the following criteria are 
satisfied that require temporary suspension or early termination of the study: 
 
• 
New information regarding the safety or performance of the study becomes available in such 
a way that the research study is deemed unsafe or ineffective; 
• 
Significant violation of Good Clinical Practice (GCP) that compromises the ability to achieve 
the primary study objectives or compromises subject safety; 
• 
Failure to meet expected enrollment goals; 
• 
Administrative reasons. 
 
 

 
 
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8. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
8.1. 
Institutional Review Board 
IRB approval for the protocol, ICF and any subject facing materials will be obtained by the Site 
Investigator at each Investigational sites prior to participation in the study. The IRB approval 
letter must be received at the Investigational site prior to starting the study, and a copy must be 
provided to the Sponsor. No changes will be made to the Protocol, ICF or subject facing 
materials without appropriate approvals, including the IRB, and Sponsor’s approval.  
Until study completion, the site Investigator will inform/advise his IRB of the study progress, per 
their IRB requirements. Further, any amendments to the protocol, as well as the associated ICF, 
and subject facing materials will be submitted to IRB and written approval obtained prior to 
implementation in the study. 
 
The submitted documents will include but are not limited to: 
 
  a.The final protocol 
  b.IRB application forms 
  c.Informed Consent Form (ICF) 
 
The study will not begin unless the IRB gives a favorable opinion of the study. 
 
8.2. 
Informed Consent 
All information about the study, including the subject information and the informed consent form 
(ICF), is prepared and used for the protection of the human rights of the subject according to 
International Council for Harmonisation (ICH) GCP guidelines and the Declaration of Helsinki. 
It is the responsibility of the Investigator to obtain signed ICFs from each subject participating in 
this study after adequate explanation of the aims, methods, and objectives of the study and before 
undertaking any study-related procedures. 
The ICF, prepared by the Investigator with the assistance of the Sponsor, must be approved 
along with the study protocol by the IRB and be acceptable to the Sponsor. 
The subject must be provided with the subject information and ICF consistent with the study 
protocol version used and approved by the relevant IRB. The ICF must be in a language fully 
comprehensible to the prospective subject. Subjects must be given sufficient time and 
opportunity to inquire about the details of the study and to discuss and decide on their 
participation in the study with the Investigator concerned. The subject and the person explaining 
about the study and with whom they discuss the informed consent will sign and date the ICF. A 
copy of the signed and dated ICF will be retained by the subject and the original will be filed in 
the Investigator file unless otherwise agreed. New information will be provided in written form 
to the subject. 

 
 
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8.3. 
Record Keeping 
This study will be conducted in accordance with GCP guidelines. Trial documents should be 
retained until at least 2 years after the last approval of marketing application in an ICH region 
and until there are no pending or contemplated-marketing applications in an ICH region. If there 
are no local laws, sites should retain filed for 5 years after completion of the study. Records 
include informed consent, protocols, and electronic case report forms (eCRFs).  
8.4. 
Confidentiality and Privacy 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
the Sponsor and its agents. The study protocol, documentation, data and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the Sponsor. 
Compliant with Health Insurance Portability and Accountability Act of 1996 (HIPAA) 
guidelines, only certified copies of coded data will be sent from the study site to the cardiology 
reviewers. Under no circumstances, except when legally compelled, will any healthcare provider 
of any enrolled subject be allowed to receive specific outcome data for that subject. 
8.5. 
Protocol Adherence 
The protocol must be read thoroughly in its entirety and instructions followed exactly.  Any 
deviations should be agreed on by Sponsor and the Investigator and reported to IRB as per their 
reporting guidelines, with the appropriate written and approved protocol amendments made to 
reflect the agreed upon changes.  Where the deviation occurs for the well-being of the subject, 
the Sponsor must be informed of the action taken. Actions taken for the well-being of a subject 
may occur before the sponsor is notified. 
8.6. 
Collection and Management Responsibilities  
Data will be collected using eCRFs in a validated system. The Sponsor or designee will supply 
the eCRFs. All eCRFs should be completed by designated, trained personnel, as appropriate. All 
changes or corrections to the eCRF will be documented via a data correction form (query) with 
an audit trail and adequate explanation for the revision is required. eCRFs will be signed and 
dated by the Principal Investigator or designee.  
The investigator(s) will permit trial-related monitoring, audits, IRB review and regulatory 
inspections(s), providing access to data documents. Members of the investigational site team and 
their designated authorization(s) will be identified in a log. 
Access to data collection devices will be controlled and the devices will be used only in the 
clinical investigation and according to the clinical investigation plan. The investigator or 
authorized designee will keep records documenting the receipt, use and return of the study-
related data collection devices. 
8.7. 
Study Monitoring 
On behalf of the Sponsor, a CRO monitor will contact and visit the investigator(s) at the study 
site(s) before the entry of the first subject and at predetermined appropriate intervals during the 

 
 
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This confidential information shall remain the sole property of the Sponsor and shall not be 
disclosed to others without the written consent of the Sponsor and shall not be used except in the 
performance of this study. 
8.10. 
Study Record Retention 
All data collected or derived from this research study will remain the property of the Sponsor.  
Any and all correspondence relating to this research study, for example with the Sponsor or the 
IRB, should be kept in the appropriate file folders at the CRO. Records of research study 
subjects’ source documents which pertain to the research study must be kept on file at the CRO.   
Records must be maintained according to the guidelines of the International Conference on 
Harmonization (ICH) and Good Clinical Practice (GCP). 
8.11. 
Study Termination and Site Closure 
The Sponsor and the investigators reserve the right to terminate the study or participation in the 
study, respectively, at any time. Both parties will arrange discontinuation procedures. In 
terminating the study, the Sponsor and the investigators will assure that adequate consideration is 
given to the protection of the subjects’ interests. 
The Sponsor reserves the right to discontinue the study at any time for medical or administrative 
reasons. When feasible, a 30-day written notification will be given. 
The entire study will be stopped if: 
• Evidence has emerged that, in the opinion of the Sponsor or the investigator(s), makes the 
continuation of the study unnecessary or unethical; 
• The stated objectives of the study are achieved; 
• The development of the study device is discontinued. 
Regardless of the reason for termination, all data available for subjects at the time of 
discontinuation of follow up must be recorded on the eCRF. All reasons for discontinuation of 
treatment must be documented.  
8.12. 
Completion of the Study 
The investigator(s) agree to provide financial disclosure forms and to complete this study in 
satisfactory compliance with the protocol and all applicable regulatory requirements within the 
timeframe allotted in the financial contract. Delays in the completion and/or reporting of the 
study beyond this time must be mutually agreed upon in writing by both the investigator and the 
Sponsor. 

 
 
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Detach 12-lead ECG 
  
X 
Remove wrist device 
  
X 
Transfer data from wrist device to paired 
smartphones 
  
X 
Record Adverse and/or Serious Adverse Events  
 
X 
Disposition Status Assessment 
 
X 
 
1For women of child-bearing potential only. A woman will be considered not of child-bearing 
potential if they are surgically sterile and have provided documentation, or they are >55 and 
have not had a cycle for >2 years.  
 
2Only needed if study day is different from screening day 
 
3 Study Day can be on the same day or different day than the Screening Day.