Low Burden Wearable Sensor System for Diagnosing Obstructive Sleep Apnea Over Multiple Nights: Diagnostic Agreement With Home Sleep Testing
Phase: NA
Conditions: Obstructive Sleep Apnea of Adult
Sponsor: Northwestern University

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PROTOCOL TITLE: Low Burden Wearable Sensor System for Diagnosing Obstructive Sleep 
Apnea Over Multiple Nights: Diagnostic Agreement with Home Sleep Testing 
 
PRINCIPAL INVESTIGATOR: 
Phyllis Zee MD PhD 
Chief of Sleep Medicine 
Northwestern Memorial Hospital 
Professor of Neurology 
Northwestern University Feinberg School of Medicine  
P: 312-503-4409 
Email: p-zee@northwestern.edu 
676 N St Clair St Arkes Pavilion, Ste 7-701, Chicago, IL 60611 
 
Sponsor:   
National Heart, Lung, and Blood Institute 
 
Sponsoring company:   
Sibel Inc 
Representative: Peter Xu., MD, PhD. 
6650 W Touhy Ave 
Niles, IL 60714 
P:  224-251-8859 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The information in this document contains information that is privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable laws and regulations. In any 
event, persons to whom the information is disclosed must be informed that the information is 
privileged or confidential and may not be further disclosed by them. These restrictions on 
disclosure will apply equally to all future information supplied to you, which is indicated as 
privileged or confidential. 
 
 
 
 
 
 
 
 
 
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Signature Pages 
 
Principal Investigator(s): 
 
 
                 
 
Name: Phyllis Zee MD PhD  
 
 
        Date: 
Title: Chief of Sleep Medicine 
Northwestern Memorial Hospital 
Professor of Neurology 
Northwestern University Feinberg School of Medicine  
P: 312-503-4409 
Email: p-zee@northwestern.edu 
676 N St Clair St Arkes Pavilion, Ste 7-701, Chicago, IL 60611 
 
 
Sponsor Company: 
 
 
 
 
      
 
Name: Peter Xu, MD, PhD 
 
 
 
        Date: 
Title: Sibel Health’s Chief Operating Officer 
6650 W Touhy Ave 
Niles, IL 60714 
P:  224-251-8859 
Email: peter.xu@sibelhealth.com 
 
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PROTOCOL SUMMARY 
Protocol Title (Long 
Title) 
Low Burden Wearable Sensor System for Diagnosing Obstructive 
Sleep Apnea  
Protocol Number 
v.1 
Study Duration 
4 to 6 months  
Setting 
 
Northwestern University and  Participant’s Homes  
 
Sample Size 
A total of approximately 100 subjects may be recruited to achieve at 
least 30 subjects to complete the study (Home Sleep Testing portion). 
 
 
Main Inclusion 
Criteria 
• 
Age >22 years old or older 
• 
Subjects with suspected or confirmed OSA based on history 
 Persons with a previous diagnosis of OSA 
 Subjects with self-reported symptoms of OSA 
 Willingness to give consent and comply with study procedures 
Objectives: 
Analysis of diagnostic yield from multiple nights with ANNE Sleep  
• 
Analysis of agreement for diagnosis of moderate to severe 
OSA by determining a patient’s Apnea-Hypopnea Index (AHI) 
wearing the ANNE Sleep system and WatchPAT ONE over 
one (1) night worn concurrently 
• 
Assessment of usability compared to current HST in the 
intended population 
Investigational 
Product and Planned 
Use 
ANNETM Sleep System 
Commercial 
Available HST Device 
WatchPAT ONE 
Statistical Analysis 
Three subsequent nights will be with the ANNE Sleep system alone. 
Patient preference will be elicited via psychometric surveys for comfort 
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and usability comparing ANNE and a commercially available Home 
Sleep Test (HST). We expect completion of this aim in 6 months. 
The apnea-hypopnea index (AHI) will be calculated in ranges of 15 – 
30 apnea/hypopnea events per hour for moderate OSA and ≥30 
apnea/hypopnea events per hour for severe OSA. The oxygen 
desaturation index (ODI), the hourly average number of desaturation 
episodes, will also be calculated. With a sample size of at least 30, the 
large amount of within-person data provides high statistical power for 
all planned analyses, allowing this data set to answer all proposed 
questions while minimizing study costs and any risk to patients.  
1. LIST OF ABBREVIATIONS 
 
AASM   
American Academy of Sleep Medicine 
AHI    
Apnea-Hypopnea Index  
ECG 
 
Electrocardiogram 
EDF   
European Data Format 
EDW    
Electronic Data Warehouse 
EHR    
Electronic Health Record 
EMG  
Electromyography 
GCP 
 
Good Clinical Practice 
HIPAA  
Health Insurance Portability and Accountability Act of 1996 
HR 
 
Heart Rate 
HST   
Home Sleep Test 
ICF   
 
Informed Consent Form 
ICH-GCP 
International Conference on Harmonization Good Clinical Practice 
IRB    
Institutional Review Board 
MRN    
Medical Record Number 
NMH    
Northwestern Memorial Hospital 
NPV    
Negative Predictive Value 
OSA    
Obstructive Sleep Apnea  
ODI    
Oxygen Desaturation Index 
PAP 
 
Positive Airway Pressure 
PAT 
 
Peripheral Arterial Tonometry 
PHI 
 
Protected Health Information 
PI 
 
Principal Investigator 
PPV    
Positive Predictive Value 
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PSG 
  
Polysomnography 
RPSGT 
Registered Polysomnography Technicians 
RR 
 
Respiratory Rate 
SDB 
 
Sleep Disordered Breathing 
SL 
 
Sleep Latency 
SoC 
 
System-on-Chip 
TST 
 
Total Sleep Time 
 
2. OBJECTIVES: 
The main objective of this study are as follows: 
 
• 
Analysis of diagnostic yield from multiple nights with ANNE Sleep 
• 
Analysis of agreement of diagnosis of moderate to severe OSA by determining a 
patient’s Apnea-Hypopnea Index (AHI) wearing the ANNE Sleep system and WatchPAT 
ONE over one (1) night worn concurrently 
• 
Assessment of usability compared to current HST in the intended population 
 
3. INTRODUCTION  
Sleep disordered breathing (SDB) is an increasingly common disorder characterized by a 
pathological increase in upper airway resistance experienced during sleep that ranges from 
benign snoring to its most severe form of obstructive sleep apnea (OSA). OSA is characterized 
by recurrent episodes of cessation of breathing and physiological stress as a result of 
intermittent periods of hypoxemia, and arousals. Studies have demonstrated that OSA leads to 
profound sleep fragmentation, disturbance of the autonomic nervous system, insulin resistance, 
increased systemic inflammation, oxidative stress, and subsequent vascular endothelial 
dysfunction. These physiologic changes cause significant morbidity; OSA is an independent risk 
factor for wide ranging adverse health outcomes including cardiovascular disease 
(hypertension, stroke, myocardial infarction), metabolic disorders (insulin insensitivity, diabetes), 
neurological (dementia), motor vehicle accidents, and mood disorders.1-5  
 
The ANNETM Sleep system has been validated as a diagnostic aid for moderate to severe OSA 
in a multi-center, open-label clinical study with n=225 subjects. Subjects wore PSG and ANNE 
Sleep concurrently for one supervised night at a sleep center. Both PSG and ANNE Sleep data 
were manually scored by 3 blinded registered polysomnography technicians. If AHI values 
determined by the 3 scorers exhibited great than 15% variation, a board-certified Sleep 
Medicine physician reviewed the raw data independently per AASM guidelines to account for 
interscorer variability. The results of the study indicate that ANNE Sleep is sufficiently accurate 
as an aid to diagnosis of moderate to severe OSA with sensitivity and specificity of 90% and 
98% respectively. 
 
 
4. STUDY ENDPOINTS: 
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4.1 Primary Outcome Measures 
• 
Analysis of variation between nights of AHI derived from ANNE Sleep system across 
multiple sleep nights at home 
• 
Analysis of agreement for diagnosis of moderate to severe OSA by determining a 
patient’s Apnea-Hypopnea Index (AHI) wearing the ANNE Sleep system and WatchPAT 
ONE over one (1) night worn concurrently 
• 
Patient responses on psychometric surveys for comfort and usability comparing ANNE 
Sleep and WatchPAT ONE 
 
 
• 
 
 
5. RECRUITMENT METHODS 
 
5.1 INCLUSION AND EXCLUSION CRITERIA 
 
Eligible participants will be recruited using electronic medical records from Northwestern Medicine 
Enterprise Data Warehouse (NMEDW) using the below inclusion/exclusion criteria for search 
criteria.  No special populations will be targeted for the enrollment in this study. Additional patient 
referrals will be made by the physicians who are participating as investigators on this study. The 
referring physicians of patients to the study will make an assessment if a potential study subject 
can provide informed consent and will not refer patients unlikely to understand what is being 
asked of them. All potential subjects will be evaluated by research staff to match them to the 
inclusion and exclusion criteria that has been established. 
5.1.1 Inclusion Criteria 
1. ≥22 years old 
2. Subjects with suspected OSA based on history and physical. Subjects with self-reported 
symptoms of OSA based on the STOP-Bang questionnaire indicating affirmative answers 
to any of the following: snoring, daytime fatigue/sleepiness/tiredness, partners who have 
observed the subject stopping breathing or choking/gasping during sleep. Persons with a 
previous diagnosis of OSA are also eligible. 
3. Willingness to give written consent and comply with study procedures 
5.1.2 Exclusion Criteria 
1)  An unstable medical condition, acute or chronic, that in the opinion of the investigator puts 
the subject at health risks related to this trial or interferes with the clinical trial and data 
collection based on the opinion of the investigator, this includes but is not limited to:  
A. Significant cardiorespiratory disease: patients that are oxygen dependent, previous 
hospitalization for cardiorespiratory issues, or left ventricular ejection fraction ≤ to 40% 
B. Respiratory muscle weakness due to a neuromuscular condition  
C. Awake hypoventilation or suspicion of sleep related hypoventilation  
D. Chronic opioid medication use 
E. History of stroke  
F. History of severe insomnia 
2)  Inability to understand instructions 
3)  Has a skin abnormality that precludes assessment 
4)  Has a history of dementia 
5)  Patients with implanted pacemakers or defibrillators 
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5.2 RECRUITMENT METHODS 
 
Identifying potential participants will be through the Electronic Data Warehouse (EDW) and 
through the use of study flyers and recruitment materials. The EDW at Northwestern is updated 
daily. An algorithm can be set up based on the eligibility criteria of the trial to identify potential 
participants that have met enrollment criteria. Data gathered in the EDW request will include 
Name, contact information (address, email and/or phone), Date of Birth, MRN, hospitalization 
date(s), and if applicable, date that a HST or PSGG is ordered. The EDW request may exclude 
people based on the exclusion criteria. The use of the EDW will be used exclusively for 
recruitment purposes and no data from the warehouse will be added to the study data set for 
research analysis. The use of study flyers or advertisements will also be shared with potential 
study subjects who will be given contact information to follow up with the study team. 
 
6. STUDY INVESTIGATIONAL DEVICE:  
ANNE™ Sleep system 
Sibel’s ANNE™ Sleep system includes two skin-mounted, bio-integrated sensors to record vital 
signs, a wireless charger, a wireless charger adaptor, single-use chest adhesives, single-use 
finger adhesives, and a mobile device with a mobile software application that enables data 
recording for download for further analysis.  
 
Heart rate (HR), snore, chest movement, and body position are recorded from the ANNE™ Chest 
sensor. Blood oxygenation (SpO2), peripheral arterial tonometry (PAT), and pulse rate are 
recorded from the ANNE™ Limb sensor. PAT is indicative of vasoconstriction, which can serve 
as a proxy for respiratory disturbances and accepted by the American Academy of Sleep Medicine 
for use as a component of home sleep testing.  
 
The first sensor (chest unit) located on the chest contains a 3-axis gyroscope and 3-axis 
accelerometer, Bluetooth Low Energy System-on-Chip (SoC), a Lithium-Polymer battery, power 
management 
component, 
an 
analog 
front-end 
component, 
passive 
electrodes 
for 
electrocardiogram (ECG). 
 
The second sensor (limb unit) located on the finger of a patient contains Bluetooth Low Energy 
SoC, a Lithium-Polymer battery, power management solution, low-power microcontroller, an 
analog front-end component, pulse oximeter (SpO2). 
 
The chest sensor is placed on the body via a single-use chest adhesive. Both adhesives will be 
removed and discarded after one use. The limb sensor is held in place by a single-use finger 
adhesive, which is removed and discarded after one use, then replaced with a new finger 
adhesive. 
 
 
Chest Unit 
Limb Unit 
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Multi-Use 
 
 
 
Figure 1.  The ANNE™ Sleep consists of 2 sensors, a chest unit worn on the thorax and a limb 
unit that folds over the index finger.  
 
6. PREPARATION OF ANNE™ SLEEP SYSTEM 
6.1 Standard study supply kit 
The study sponsor company will ship ANNE™ Sleep system (study supply kit) to Northwestern. 
 
Study supply kit list 
● 
Cardboard mailer box 
● 
Wearable study sensors 
● 
Study devices (Tablet(s) or smart phone(s) with sensor application pre-loaded).  
● 
Wireless charger(s), charger adaptors 
● 
Device accessories; chest adhesives, finger adhesives 
● 
Printed instructions or other study materials 
 
The research coordinator from the sponsor will document tracking records of each device. All 
adhesives are single use with new ones provided to each new subject.  
6.2 Study Kit Cleaning 
 
Participants will return study supply kits in person by meeting a member of the research team or 
by mailing them back using pre-paid shipping labels. Study sensors are reusable after completion 
of study procedures and data collection.  
 
The detailed sanitation instructions for the study kit are attached as APPENDIX D. 
 
7. PREPARATION OF WatchPAT ONE 
 
The WatchPAT ONE is a commercialized HST system, which received FDA 510(k) clearance 
(KK183559).  The WatchPAT ONE will be prepared by following its operation manual. 
 
The study coordinator will provide study participants a case with everything needed for a 
WatchPAT ONE. The case will include: 
 
 
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• 
An WatchPAT ONE device. This is a rectangular device that will keep track of body 
position (information such as whether a person is lying on their back, side, or stomach). It 
will also store all the information from the system. 
• 
A pulse oximeter. This is a wire with a gray rubber sensor placed on the finger. It will 
measure pulse, blood flow, and the amount of oxygen in the blood. The pulse oximeter 
should already be attached to the device. 
• 
A chest sensor. The Chest Sensor monitors snoring, movement, and body position. The 
chest sensor should already be attached to WatchPAT ONE. 
• 
AA batteries. This will only use these if the batteries inside the HST device stop working. 
 
8.  STUDY PROCEDURES 
 
8.1 Sleep Study Procedures   
 
8.1.1 Consent form 
 
To protect participant confidentiality, we will conduct all research-related discussions and 
informed consent procedures in a private setting. The consent process will be completed either 
in person or remotely by using an electronic consent document and collection of an electronic 
signature with REDCap or other electronic signature service like Adobe DocuSign. The study 
coordinator will review the Informed Consent in person, by phone or in Zoom during the remote 
informed consent discussion.  
 
The study procedures, risks, and benefits will be discussed and the study team will answer all 
questions prior to obtaining consent. The person performing the Informed Consent process, will 
ask questions of the study subject to confirm understanding and comprehension of the study. All 
versions of the consent forms will be approved by the relevant ethics committees prior to study 
initiation.  
 
Eligible participants who do not wish to participate in this study will continue to receive care 
according to local clinical standards.   
 
Informed Consent will be reviewed and signed electronically using REDCap.  
 
8.1.2 Initial Visit Day: Screening/Enrollment  
 
The subject will have the option to discuss with the study coordinator over the phone or by a 
Zoom teleconference from the subject’s personal device. If Zoom communication is selected a 
unique meeting number and password known only to the subject will be provided. The study 
coordinator will monitor the number of attendees in the meeting and restrict meetings to IRB 
approved researchers on this study, the study subject, and additional people at the subject's 
discretion. Researchers will host the Zoom sessions and will utilize the waiting room feature to 
ensure that only the appropriate participants are included on the call. 
 
The study coordinator will cover following topics associated with the study during the 
Screening/Enrollment visit: 
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(1) Informed Consent will be reviewed and signed electronically using REDCap.  
(2) The qualified subject will be asked to schedule a study date to participate at home. The 
nights of sensor wear do not need to be consecutive. Subjects will be instructed to set-up 
both devices on Night One of sleep testing and then only the ANNE device on Nights 2-4.  
One Night = HST and ANNE Sleep 
3 Additional Nights = ANNE Sleep only   
The target time frame will be to complete the sleep nights within 8 weeks of enrollment.  
 
(3) Subjects will be advised to avoid alcohol and sleep medication use such as antihistamine 
(OTC) or prescribed medicines for sleep support on the testing night. Any use of these 
substances on the night of monitoring sleep will be asked to be recorded in the diary. 
 
(4) Subjects will be informed how to complete the Demographic, Medical History and Sleep 
Survey sleep diary and usability survey (Appendix A-C). The surveys should be available 
to complete via an email link through REDCap or printed out forms. 
 
Any subject’s questions or concerns associated with the study will also be addressed. 
 
At least 24 hours prior to the subject’s sleep nights, the study coordinator will contact the 
participant by phone to confirm their planned sleep study nights at home. 
 
The below sections describe the procedures for setting up the ANNE and HST devices, 
respectively.  
8.1.3 ANNETM Sleep procedures 
The ANNE™ Sleep sensors will be applied by the study subjects themselves. 
 
1) 
The PI or study coordinator will ensure the ANNE™ Sleep sensors are functional 
and collecting data properly prior to providing to subjects.  The study coordinator 
will provide instructions for use of the ANNE™ Sleep system in the subject study 
kit.  
 
2) 
Sensor placement (to be completed by the subject): 
 
 
a) 
Using IPA alcohol wipes, the subject will wipe down the areas of the skin 
where the sensors will be placed thoroughly to remove any dirt, oils, etc. 
IPA alcohol wipes will also be used to clean the surface of the sensors 
before placement. If necessary, the subject may need to shave their chest 
to provide better adhesion and comfort of the sensor.   
b) 
The subject will apply a single use adhesive to the chest sensor and place 
it on their chest at the suprasternal notch (see Figure 2). The subject will 
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attach the limb sensor to their finger using a single-use adhesive (see 
Figure 2). 
 
 
 
 
Figure 2.  Placement of the ANNETM chest and limb sensors 
 
 
3) Setting up a mobile device with an ANNE Sleep application 
 
a) 
The subject will pair the ANNE™ Chest and ANNE™ Limb sensors with 
the ANNE Sleep mobile application by following the instructions on mobile 
device 
b)  
After checking that the sensors are placed correctly and the signal quality 
is adequate, subjects will then proceed to sleep.  
 
4)  Data collection and storage 
 
a) 
After a full night of data collection, data will be collected through the ANNE 
Sleep application. The subject will download the data from the sensor 
through Bluetooth. 
b) 
The data will be uploaded automatically to ANNE™ Hub, a secure data 
repository from the application, and will be associated with the subject ID. 
c) 
The data will be stored in an EDF data format for further analysis. 
 
8.1.4    WatchPAT One Procedures  
 
The device along with a user manual and quick start guide will be provided to the 
participant.  Participants will be instructed to follow the safety instructions in the user 
manual.  
 
The procedures for the WatchPAT ONE are as follows (to be completed by the subject):  
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1. Subject will download the WatchPAT One mobile application on their mobile device. 
2. Subject will strap the WatchPAT device to their non-dominant hand.  
3. Subject will place the chest sensor 
a. Subject will thread the chest sensor through the sleeve of their shirt. 
b. Subject will peel the liner from the adhesive and attach the chest sensor to the chest 
under the sternal notch. 
4. Subject will place the finger probe 
a. Subject will insert a finger on the non-dominant hand into the Finger Probe until 
they feel the tip of the probe 
5. Subject will press the START button on the application to begin data collection. 
6. After a night of sleep, the subject will press the END RECORDING button on the 
application. 
 
• 
 
 
8.2    COMPLETION OF THE STUDY 
(1) 
After completing data collection, subjects will be given surveys (Appendix C) to 
complete in print material or by email link via a secure online platform managed by 
Northwestern University (i.e. REDCap). 
(2) 
Once the surveys and sleep nights are complete, the study coordinator will let the 
subject know that their participation is complete. The study coordinator will have a 
phone call with the subject to confirm testing was successful and address any 
issues if needed.  
(3) 
Subjects will be instructed to arrange for a time to return the study kit to the 
research team in person or will be provided with a pre-paid shipping label. A 
compensation gift card will then be mailed to the subject’s home address or given 
to them in-person (if they return the study kits in person to the research team). 
 
7.1.4    Checklist for scheduled events 
             The study coordinator should review the schedule of events, summarized below: 
 
Initial Visit Day: Screening/ 
Enrollment 
ANNETM and HST 
Night One  
ANNETM ONLY 
      Night Two,   
Three, and Four  
 
End of Study* 
Eligibility 
X 
 
 
 
Consent 
X 
 
 
 
Demographics, 
Medical Hx, 
STOP-BANG 
Questionnaire  
X 
 
 
 
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ANNETM Sleep 
 
X 
X 
 
HST Sleep 
 
X 
 
 
Sleep Diary 
 
X 
X 
 
Phone follow-up 
(which may occur 
up to 1 week after 
the study) 
 
 
 
X 
Usability Survey 
 
 
 
X 
Adverse Events 
 
X 
 
X 
 
 
9. SCORING 
 
9.1 ANNETM Sleep Scoring 
The data from ANNETM will be reviewed and scored for respiratory events by three (3) 
registered polysomnography technicians (RPSGT) who are blinded to the scoring of the HST, 
and represent scorers in clinical practice in AASM accredited sleep disorder centers. An 
average will be taken of the three scores. In order to minimize interscorer variability, the 
technicians will have >85% concordance. To ensure quality and reproducibility, a board certified 
sleep medicine physician who is blinded to the experimental condition will review all raw HST 
data. If AHI determined from ANNETM Sleep exhibits greater than 15% difference between three 
RPSGTs, a board-certified sleep medicine physician will provide the final determination of the 
AHI for ANNE Sleep. 
 
Scoring of ANNETM Sleep data will follow guidelines established by the American Academy of 
Sleep Medicine Manual for the Scoring of Sleep and Associated Events (v2.6)6. Sleep scoring 
includes the following variables: total sleep time (TST= the total amount of sleep time scored 
during the total recording time in minutes). The scoring of respiratory events to evaluate for 
sleep disordered breathing will also follow AASM scoring rules.  
 
The ANNETM Sleep will be scored similarly with the system’s onboard sensors as an alternative 
hypopnea and apnea sensor via PAT. The definition of mild, moderate, or severe obstructive 
sleep apnea is based on AHI. 
 AHI < 5: Normal  
 AHI ≥ 5 – <15: Mild  
 AHI ≥15 – <30: Moderate  
 AHI ≥ 30: Severe 
 
The AHI calculated from ANNETM Sleep will be considered an estimation of AHI, coined as AHI. 
 
An apnea event is defined as:  
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 A drop in peak signal excursion by ≥ 90% of pre-event baseline for ≥ 10 seconds using an 
oronasal thermal signal, PAP device flow, or an alternative apnea sensor.  
 No requirement for a desaturation or an arousal 
 
Hypopnea will be defined by: 
 The peak signal excursions drop by ≥30% of pre-event baseline using nasal pressure 
(diagnostic study), PAP device flow (titration study), or an alternative hypopnea sensor 
(diagnostic study) 
 The duration of the ≥30% drop in signal excursion is ≥10 seconds 
 There is a ≥4% oxygen desaturation from pre-event baseline and/or the event is 
associated with an arousal 
 
The scoring of respiratory events to evaluate for sleep disordered breathing will also follow 
AASM scoring rules. Apnea-hypopnea index will be used to determine the presence and 
severity of sleep apnea (AHI= apneas + hypopneas *60/TRT).  
 
The accuracy (sum of the number of true positives and true negatives divided by the sum of the 
number of true positives, true negatives, false positives, and false negatives), sensitivity, 
specificity, positive predictive value, and negative predictive value of the ANNE™ Sleep to detect 
moderate to severe obstructive sleep apnea will be compared to outputs from WatchPAT ONE. 
A Bland-Altman plot will be gerenated with 95% confidence to intervals to assess agreement. 
 
9.2 WatchPAT ONE Scoring 
 
The scoring method will be produced in accordance with the device operating manual. 
 
 
10. STATISTICAL ANALYSIS 
 
10.1  Sample size 
 
With a sample size of at least 30, the large amount of within-person data provides high 
statistical power for all planned analyses, allowing this data set to answer all proposed 
questions while minimizing study costs and any risk to patients.  
 
10.2 
Apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) 
 
1. AHI will be calculated in ranges of 15 – 30 apnea/hypopnea events per hour for moderate 
OSA and ≥30 apnea/hypopnea events per hour for severe OSA. Continuous variables of 
AHIs during threefour-night study will be summarized using tables of descriptive 
statistics.  The AHIs with variables will be summarized using counts and percentages. 
Descriptive statistics will be presented by diagnosis.  
2. Diagnostic outcomes will be tabulated and compared for ANNE Sleep vs WatchPAT ONE. 
3. Patient preference will be elicited via psychometric surveys for comfort and usability 
comparing ANNE and WatchPAT ONE. 
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4. The oxygen desaturation index (ODI), the hourly average number of desaturation 
episodes, will also be calculated. 
 
10.3  Exploratory measurements for research purposes 
 
Additional statistical analyses will be performed to compare outputs of AHI between the 
different systems. Specifically, these analyses include: 
 
 
1. Linear regression to establish correlation between AHI determined by ANNE Sleep vs 
WatchPAT ONE on the same night.   Bland-Altman plots will be created to establish bias 
and 95% confidence intervals of agreement between AHI determined by ANNE Sleep and 
WatchPAT ONE. 
2. Summary statistics of the sensitivity, specificity and accuracy of the classification of the 
severity of OSA (normal, mild, moderate, and severe OSA) determined by AHI between 
ANNE Sleep and WatchPAT ONE. 
3. Accuracy analysis between AHI determined by ANNE Sleep vs AHI determined by 
WatchPAT ONE on the same night. 
4. Descriptive analysis of patients’ characteristics and assessments (e.g. sleep diary) before 
and after study procedures. Patient characteristics include age, gender, ethnicity, race, 
height, weight, baseline vital signs, relevant medical and surgical co-morbidities will be 
abstracted from the medical record or by direct survey of the participants. 
5. The listings, specifically adverse events and major protocol deviations, will be ordered by 
subject. 
      
11. COMPENSATION FOR PARTICIPATION IN RESEARCH ACTIVITIES 
 
Subjects who complete the at home testing will receive $100 in gift cards for their time and effort 
for completing all 4 nights with corresponding surveys. If subjects complete one night with the 
HST and ANNE and one night with ANNE only, they will receive $50 in gift cards for their time 
and effort for completing these 2 nights with corresponding surveys. 
 
Compensation will be given to participants directly or mailed to the participant’s home within 4-6 
weeks after study completion. 
 
12. WITHDRAWAL OF PARTICIPANTS 
 
Participants may end their participation at any time during the study. The study investigators may 
choose to withdraw a study subject if he or she is unable to use the devices or complete the study 
procedures. The study investigators may withdraw a patient if they develop skin sensitivity or have 
a medical complication that precludes wearing of the sensors on the suprasternal notch.  
 
If a subject is withdrawn from the study, they will be asked to return the study kit that is given to 
them at the start of the study. Unless specifically requested in writing, researchers will maintain 
and use data from patients that end their participation early.  
 
 
13. RISKS TO PARTICIPANTS 
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Risk category: minimal 
 
Potential risk: There is a risk of skin irritation, rash, possible injury upon removal of the sensor, or 
allergic reaction to the ANNE™ Sleep sensors adhesive.  The devices will be placed on skin 
epidermis without conductive gel, thereby minimizing the risk of any skin irritation or allergic 
reaction. In addition, there will be no skin preparation except the use of a sterile alcohol pad 
(provided) to gently exfoliate the dead skin cells or dirt on epidermis. The adhesives are silicone 
based and have passed both biocompatibility, skin sensitization and cytotoxicity testing. 
 
There is a risk of Protected Health Information (PHI) disclosure. Subject data will be de-identified 
and stored securely to prevent PHI disclosure. 
 
Protection against risks: The sleep sensors can be removed if associated with significant 
discomfort or rash.   
 
SURVEY/DIARY: Some questions may make subjects uncomfortable or upset. Subjects do not 
have to answer these questions if they do not want to. 
14.  ADVERSE EVENTS 
The PI will determine whether adverse events are related to the study or unrelated to the study. 
The length of the study will be 4 nights. All serious adverse events – even if not deemed to be 
study-related – will be reported to the IRB. This includes a participant’s death, life-threatening 
condition, hospitalization, or disability. All study-related adverse events determined by the PI as 
serious will be recorded and reported to the IRB and the sponsor within 1 business day. Serious 
study-related adverse events are defined as adverse skin effects that warrant prescription medical 
therapy, skin tears leading to bleeding or an open wound, or skin burns. Study-related adverse 
events will be recorded on the adverse event form. If participation is discontinued, the timing of 
this will be recorded.  
15.  DATA MANAGEMENT AND PARTICIPANT CONFIDENTIALITY 
Subject identifiable medical information obtained as a result of this study is considered 
confidential and disclosure to third parties other than the PI and the study team is prohibited. All 
reports and communications relating to subjects in this study will refer to each subject only by 
their study identification number. Data generated as a result of this study are available for 
inspection on request by Food and Drug Administration or other government regulatory agency 
auditors, Sibel business partners specifically HealthCore, Inc. and the Institutional Review Board 
(IRB). 
 
Subject identity will be protected through use of a coded list of identifiers which will be maintained 
separately from the data set. Any paper source documents, questionnaires, and CRFs are kept 
in a secured area (in a locked cabinet in a locked room) and all electronic data is password 
protected on a secure NU research server so that only authorized personnel can have access. 
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Only authorized research personnel listed on the IRB protocol will have direct access to this data 
set, although there may be collaborative exchange of de-identified data with other research 
institutions for assistance in the analysis of raw data. 
 
Data will be capture using NU REDCap, a secure research database. Data stored and used for 
future research will be de-identified. Data will not be used for future research outside of the scope 
of this study.  
 
PROTECTED HEALTH INFORMATION (PHI AND HIPAA) 
The following PHI will be collected, and is also listed on the consent form for study enrollment: 
• 
Demographic data including name, birthdate, address and phone number 
• 
Results of physical examinations 
• 
Medical history 
• 
Lab tests, or certain health information indicating or relating to a condition as well diaries and 
questionnaires 
• 
Records about study medication or drugs 
• 
Records about study devices 
Entry of any data into a study site clinical record during the duration of the research study is also 
PHI that may be collected and listed in the consent form. PHI from the above categories may be 
obtained from the respective study sites and affiliated entities listed as study locations.   
Any research information shared with outside entities during the study will not contain the name, 
address, telephone or social security number or any other personal identifier unless disclosure of 
the identifier is necessary for review by such parties or is required by law or study site policy 
except that such information may be viewed by the Study sponsor and its partners or contractors 
at the Principal Investigator’s office. 
 
 
18.  PROTOCOL DEVIATIONS 
Any deviation from this protocol will be reported to the IRB. 
 
19. CONSENT PROCESS 
To protect participant confidentiality, we will conduct all research-related discussions and 
informed consent procedures in a private setting. The consent process will be completed either 
in person or remotely by using an electronic consent document and collection of an electronic 
signature with REDCap or other electronic signature service like Adobe DocuSign. The study 
coordinator will review the Informed Consent in person, by phone or in Zoom during the remote 
informed consent discussion.  
 
The study procedures, risks, and benefits will be discussed and the study team will answer all 
questions prior to obtaining consent. The person performing the Informed Consent process, will 
ask questions of the study subject to confirm understanding and comprehension of the study. All 
versions of the consent forms will be approved by the relevant ethics committees prior to study 
initiation.  
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Eligible participants who do not wish to participate in this study will continue to receive care 
according to local clinical standards.   
 
20. NON-ENGLISH-SPEAKING PARTICIPANTS 
 
Non-English-speaking participants may be enrolled if the study team acquires an official 
translation of the approved informed consent form or performs consent with a translator and 
completes the accompanying short form in the participant’s native language.  
 
The research team will only enroll non-English speaking participants if a member of the study 
team is a fluent or native speaker of their language and assigned to them specifically. This is to 
ensure that continued support, clear communication and study training is possible for all study 
participants.  
 
21.  GOOD CLINICAL PRACTICE 
The current study will be conducted in compliance with the protocol, International Conference on 
Harmonization Good Clinical Practice (ICH-GCP), and the applicable regulatory requirements. 
Study personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective task(s) in accordance with GCP. 
 
22.  INSTITUTIONAL REVIEW BOARD (IRB) 
All relevant documents for this study will be submitted to an appropriate Institutional Review Board 
(IRB) for review. A signed and dated letter documenting IRB approval must be obtained prior to 
entering participants at the site. IRBs must be constituted and their authority delegated through 
the institution's normal process of governance according to applicable regulatory requirements 
for each participating site. Each participating institution must provide for the review and approval 
of this protocol and the associated informed consent documents and relevant participant materials 
by an appropriate IRB. For each participating site, the protocol and associated informed consent 
and relevant participant materials will be submitted for approval to the local IRB, as per site local 
regulatory policies and procedures. The study will not commence at any site until initial approval 
is obtained from the designated IRB and an approval to enroll notification is released to the site. 
 
The investigators must obtain approval from the IRB for all protocol amendments and, when 
warranted, changes to the informed consent document and/or participant materials. Protocol and 
informed consent form amendments can be made only with the prior approval from the PI. The 
investigator may not implement any protocol deviation except where necessary to eliminate an 
immediate hazard to study participants, or when change(s) involve only logistical or administrative 
aspects of the trial, i.e., change of monitor(s) or telephone number(s) (ICH 4.5.2). The investigator 
shall notify the IRB of deviations from the protocol or serious adverse events occurring at the site. 
      
 
 
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24. REFERENCES 
 
1) Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in 
the general population: a systematic review. Sleep Med Rev 2017;34:70-81.  
 
2) Peppard, PE, Young T, Palta M, Skatrud J. Prospective study of the association 
between sleep disordered breathing and hypertension. New Eng J Med 2000;342:1378-
84.  
 
3) Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in 
men with obstructive sleep apnoea-hypopnoea with or without treatment with 
continuous positive airway pressure: an observational study. Lancet 
2005;365(9464):1046-53.  
 
4) Peppard PE, Szklo-Coxe M, Hla KM, Young T. Longitudinal association of sleep-
related breathing disorder and depression. Arch Intern Med 2006;66(16):1709-15.  
 
5) Mulgrew AT, Nasvadi G, Butt A, Cheema R, Fox N, Fleetham JA, Ryan CF, Cooper 
P, Ayas NT. Risk and severity of motor vehicle crashes in patients with obstructive 
sleep apnoea/hypopnoea. Thorax 2008;63(6):536-41.  
 
6) The AASM Manual for the Scoring of Sleep and Associated Events: Rules, 
Terminology and Technical Specifications, Version 2.6. www.aasmnet.org, Darien, 
Illinois: American Academy of Sleep Medicine, 2020 
 
7) Sleep-related breathing disorders in adults: recommendations for syndrome definition 
and measurement techniques in clinical research. The Report of an American Academy 
of Sleep Medicine Task Force, Sleep, 1999, vol. 22 (pg. 667-89) 
 
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8) Cleaning and Disinfecting Your Facility. Centers for Disease Control and Prevention. 
January 5, 2021. https://www.cdc.gov/coronavirus/2019-ncov/community/disinfecting-
building-facility.html 
 
9) Obuchowski NA et al. Prospective studies of diagnostic test accuracy when disease 
prevalence is low. Biostatistics, Volume 3, No. 4, pages 477-492. 
10) Li J et al. On sample size for sensitivity and specificity in prospective diagnostic 
accuracy studies. Statistics in Medicine, Volume 23, pages 2537-2550. 
 
11) Machin D et al. Sample Size Tables for Clinical Studies, Third Edition. Wiley-
Blackwell, Chichester, United Kingdom. 
 
12) Zhou XH et al. Statistical Methods in Diagnostic Medicine. Wiley-Interscience, New 
York. 
 
 
 
 
 
 
 
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APPENDIX A - SLEEP DIARY 
                                  
 
 
            
           ID/NAME:  
 
 
 
 
 
 
 
 
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APPENDIX B – 
APNEAS ANNE Sleep Sensor Survey 
Subject #: _________ 
 
 
 
 
 Date: ____/_____/_____ 
 
Thank you for participating in wearing the ANNE Sleep system. This survey helps researchers 
better understand your experience with wearing sensors and helps develop and improve them 
for future patients. Please provide one answer to each of the following questions. You can skip 
any questions you do not know the answer to or do not want to answer.  
 
1. Overall, all of the the sleep study sensors were comfortable for me to sleep with: 
 
 
Strongly 
Agree 
 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagree 
 
Strongly 
Disagree 
 
 
 
2. Overall, ANNE Sleep sensors were comfortable for me to sleep with: 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
3. How quickly you fell asleep comparing to typical nights for you  
 
 
Much 
Slower 
 
Slower 
 
About 
the 
same 
 
Faster 
 
Much 
Faster 
 
 
 
4. The ANNE Sleep Sensors would be more comfortable to other sleep sensors 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
5. The application of the ANNE Sleep Sensors was easy and comfortable. 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
6. The removal of the ANNE Sleep Sensors was easy and comfortable. 
 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
7. Using wireless ANNE Sleep Sensors would be easy to do at home.  
 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
8. Please describe how the wireless Chest sensor felt while sleeping. 
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Very 
uncomfortable 
 
Uncomfortable 
 
No 
change 
 
Comfortable  
 
Very 
comfortable 
 
9. Please describe how the wireless Limb sensor felt on your finger while sleeping. 
 
 
Very 
uncomfortable 
 
Uncomfortable 
 
No 
change 
 
Comfortable  
 
Very 
comfortable 
10. Please indicate if you experienced the following while wearing the wireless sensors: 
 
 
Redness 
 
Irritation 
 
Both 
 
None 
11. Having my sleep data collected at home and sent to my doctor would be more convenient 
for me. 
 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
12. I could see myself using ANNE Sleep at home to monitor my breathing while I sleep.  
 
 
 
Strongl
y Agree 
 
Agree 
 
Neither 
agree or 
disagree 
 
Disagre
e 
 
Strongly 
Disagree 
 
 
 
13. Please provide any other thoughts about the concerns or benefits of wireless monitoring:   
 
 
 
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APPENDIX C – DEMOGRAPHIC, MEDICAL HISTORY AND SLEEP DIARY 
 
Field Label 
Choices, Calculations, OR Slider Labels 
In order to ensure that this research serves all people living in the U.S., we need to ask you 
how identify your ethnic and racial background. This information will remain confidential, and 
will not affect your participation in the study in any way. It will only be used for reporting 
general demographics or statistics. 
 
The following questions are about your demographic background: 
Gender 
1, Male | 2, Female 
Race: 
1, American Indian or Alaska Native | 2, Asian | 3, Native Hawaiian or Pacific 
Islander | 4, Black or African American | 5, White | 6, More than once race | 
7, Choose not to answer 
Ethnicity: 
1, Hispanic or Latino | 2, Non-Hispanic or Latino | 3, Choose not to answer 
Highest 
Education 
Level 
completed: 
1, Never attended school or only attended kindergarten | 2, Grades 1 through 
8 (Elementary) | 3, Grades 9 through 11 (Some high school) | 4, Grade 12 or 
GED (High school graduate) | 5, College 1 year to 3 years (Some college or 
technical school) | 6, College 4 years of more (College graduate) 
Current 
Marital 
Status: 
1, Married | 2, Single | 3, Widowed | 4, Divorced/Separated | 5, Domestic 
partner 
 
 
Current 
Employment 
Status: 
1, Employed | 2, Unemployed | 3, Retired | 4, Retired due to disability 
The following questions are about your Health: 
Date of last 
medical 
exam: 
 
Sleep 
Provider: 
 
Location: 
1, Northwestern Memorial Hospital (Downtown) | 3, Central DuPage Hospital 
(CDH) | 4, Northwestern Medical Group (NMG) 
Height: 
 
Weight: 
 
Are you currently diagnosed or do you have a history of any cardiovascular disorders?  
Please select 
all that apply: 
1, Hypertension (high blood pressure) | 2, Congenital heart disease 
(malformations of heart structure existing at birth) | 3, Arrhythmia (abnormal 
heart rhythm) | 4, Coronary artery disease (narrowing of the arteries) | 5, 
Deep vein thrombosis (blood clot in lower extremities) | 6, Pulmonary 
embolism (blood clot in the lungs) | 7, Heart attack | 8, Heart failure | 9, 
Cardiomyopathy (heart muscle disease) | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
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Are you currently diagnosed or do you have a history of any pulmonary or respiratory system 
disorders?  
Please select 
all that apply: 
1, Asthma | 2, Chronic Obstructive Pulmonary Disease (COPD) | 3, Chronic 
Bronchitis | 4, Lung Cancer | 5, Pneumonia | 6, Emphysema | 7, COVID-19 | 
8, Pleural Effusion (collection of fluid between the lung and chest wall) | 10, 
Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any gastrointestinal (GI) disorders?  
Please select 
all that apply: 
1, Acid reflux | 2, Heartburn | 3, GERD | 4, Crohn's disease | 5, Ulcerative 
colitis | 6, Irritable Bowel Syndrome (IBS) | 7, Peritonitis | 8, Fibrosis and 
cirrhosis of liver | 9, Cholecystitis | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any endocrine system disorders?  
Please select 
all that apply: 
1, Hyperthyroidism | 2, Hypothyroidism | 3, Thyrotoxicosis | 4, 
Hypoparathyroidism | 5, Type I Diabetes | 6, Type II Diabetes | 7, Adrenal 
disorder | 8, Cushing's syndrome | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any neurological disorders?  
Please select 
all that apply: 
1, Dementia | 2, Huntington's Disease | 3, Parkinson's Disease | 4, 
Alzheimer's Disease | 5, Bell's Palsy | 6, Cerebral Aneurysm | 7, Epilepsy or 
Seizures | 8, Fibromyalgia | 9, Amyotrophic Lateral Sclerosis (ALS) | 10, 
Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any sleep disorders?  
Please select 
all that apply: 
1, Insomnia | 2, Restless Leg Syndrome | 3, Parasomnia | 4, Sleep Apnea 
(confirmed diagnosis) | 5, Narcolepsy | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
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Are you currently diagnosed or do you have a history of any psychiatric or psychological 
disorders?  
Please select 
all that apply: 
1, Bipolar disorders | 2, Depression | 3, Anxiety | 4, Post-traumatic stress 
disorder (PTSD) | 5, Schizophrenia | 6, Personality disorders | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any lymphatic or hematologic 
disorders?  
Please select 
all that apply: 
1, Lymphedema | 2, Hodgkin's Lymphoma | 3, Non-Hodgkin's Lymphoma | 4, 
Anemia | 5, Sickle cell | 6, Leukemia | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any skin or dermatological disorders?  
Please select 
all that apply: 
1, Acne | 2, Hives | 3, Rosacea | 4, Eczema | 5, Psoriasis | 6, Melanoma | 10, 
Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Are you currently diagnosed or do you have a history of any musculoskeletal disorders?  
Please select 
all that apply: 
1, Carpal tunnel | 2, Arthritis | 3, Osteoporosis | 4, Tension Neck Syndrome | 
5, Tendonitis | 6, Broken bone | 7, Tendon or Ligament Sprain | 8, Torn 
Rotator Cuff | 9, Ruptured or Herniated Disc | 10, Other 
If other, 
please 
explain: 
 
If you selected any of the above disorders, please include dates of diagnosis and current 
status (ongoing or resolved). If resolved, please include end date: 
Do you have a history of any allergies? This can include seasonal, skin, food, or 
drug/medicine allergies. 
Please list allergies here, including start dates and current status (ongoing or resolved). If 
resolved, please include end date: 
Do you have a history of any other medical illness?  
 
 
 
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SLEEP DIARY 
The following questions are about your sleep last night (before study visit). 
Please list all other medical illnesses here, including start dates and current status (ongoing 
or resolved). If resolved, please include end date: 
2. Did you wear CPAP Device last night? 
If yes, level of 
titration: 
 
3. What time did you go into bed? {time_in_bed}  
4. What time did you try to go to sleep? {time_sleep} {ampm} 
 
 
 
1, AM | 2, PM 
5. How long did it take you to fall asleep? 
6a. How many times did you wake up, not counting your final awakening? 
6b. In total, how long did these awakenings last?  
7a. What time was your final awakening?  
7b. After your final awakening, how long did you spend in bed trying to fall back asleep? 
7c. Did you wake up earlier than you planned? 
7d. If yes, 
how much 
earlier? 
 
8. What time did you get out of bed for the day? {time_up} {am_and_pm} 
9. In total, how long did you sleep? 
10. How 
would you 
rate the 
quality of your 
sleep? 
1, Very poor | 2, Poor | 3, Fair | 4, Good | 5, Very good 
11. How 
rested or 
refreshed did 
you feel when 
you woke up 
for the day? 
1, Not at all rested | 2, Slightly rested | 3, Somewhat rested | 4, Well-rested | 
5, Very well-rested 
12a. How many times did you nap or doze? 
12b. In total, how long did you nap or doze? 
13a. How many drinks containing alcohol did you have? 
13b. What time was your last drink? {time_drink}{am_pm_2} 
14a. How many caffeinated drinks (coffee, tea, soda, energy drinks) did you have? 
14b. What time was your last drink? {time_coffee}{am_pm_3} 
15. Did you take any over-the-counter or prescription medication(s) to help you sleep? 
Type of 
medication: 
 
Dose: 
 
Time taken: 
 
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Did you take any additional medications? 
Type of 
medication: 
 
Dose: 
 
Time taken: 
 
16. 
Comments, if 
applicable: 
 
 
 
 
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APPENDIX D - STUDY KIT CLEANING INSTRUCTION 
 
Study sensors are reusable after completion of study procedures and data collection. Used study 
kit containers will be wiped on the outside using Sani-Cloth before handling and placed in a fume 
hood labeled “Contaminated Study Kits” in accordance with the study protocol. 
 
The following procedures will be conducted by a research assistant from the study sites: 
 
1. The researcher assistant is to wear appropriate PPE including lab coat, and nitrile gloves 
before handling any study supplies. 
2. The fume hood labeled “Contaminated Study Kits” will have all surfaces cleaned and 
wiped down with Sani-Cloth and/or 70% EtOH solution.  
3. The outside of study kit containers will be cleaned and wiped down with Sani-Cloth and/or 
70% ETOH solution. 
4. Once all used study kits are cleaned on the outside they may be opened, one at a time, 
to have contents cleaned. All study sensors, devices, chargers, cords and accessories will 
be wiped with Sani-Cloth and allowed 2 minutes to air dry on a cleaned surface.  
5. Sensors will be closely examined for physical breaks, holes or tears in the silicone 
packaging. Any sensors that have physical damage will be sealed in separate plastic 
containers or plastic bags and labeled for return to the manufacturer.  
6. Do not reuse towelette. Dispose of used Sani-Cloth in trash.  
7. Individually wrapped, sealed adhesives may be cleaned in the same process.  
8. Unsealed adhesives will be discarded along with any printed materials from the study kit.  
9. Once all contents of the study kit have been removed from the container, inside of study 
kit containers will be cleaned and wiped down with Sani-Cloth and/or 70% EtOH solution. 
Allow to air dry for 2 minutes. 
10. Return study kit contents to the study container.  
11. The fume hood with Contaminated Study Kits will have all surfaces cleaned and wiped 
down with Sani-Cloth and/or 70% EtOH solution.  
12. Cleaned study kits may be placed in the “Clean Kits” designated area for reuse. 
 
 
Materials and PPE 
Study supply kit list 
● 70% ETOH 
● Super Sani-Cloth Germicidal 
Wipe* 
● Cardboard mailer box.  
● Wearable study sensors 
● Study devices (Tablet(s) or smart 
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● Disposable paper towel 
● Nitrile Gloves 
● Lab coat 
● Face mask* 
 
phone(s) with sensor application).  
● Wireless charger(s), charger cords, 
bricks 
● Device accessories; adhesives for 
both sensors 
● Printed instructions or study other 
study materials 
 
*Super Sani-Cloth is an EPA registered hospital-grade disinfectant to accommodate the many 
situations and hard non-porous environmental surfaces found in healthcare settings. 
This wipe kills bacteria, viruses, and yeast. 
 
* Hospital COVID precautions will be used at all times during the study. . 
 
 
The study sponsor should perform an inspection of each device and ensure cleaning procedures 
should be conducted before shipping and after receiving the return shipment per guidance from 
the Center for Disease Control8.  
 
 
 
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APPENDIX E - STOP-BANG QUESTIONNAIRE 
 
Snoring: Do you snore? Loud enough to be heard through closed doors or loud enough 
to disturb your partner? 
Yes 
No 
 Tired: Do you often feel tired, fatigued or sleepy during the daytime? 
Yes 
No 
Observed: Has anyone observed you stop breathing, choking or gasping while you were 
sleeping? 
Yes 
No 
Pressure: Are you being treated for high blood pressure? 
Yes 
No 
Body Mass: What is your Body Mass Index (BMI)? 
Height (in inches): 
Weight (in pounds): 
Less than 25 
  
Greater than 25 
Greater than 30 
  
Greater than 35 
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Age: Are you older than 50? 
Yes 
No 
 
Is your shirt collar 16 inches / 40 cm or larger? 
Yes 
No 
Unknown 
 
Gender: Are you male? 
Yes 
No 
 
OSA - Low Risk: Yes to 0 - 2 questions 
OSA - Intermediate Risk: Yes to 3 - 4 questions 
OSA - High Risk: Yes to 5 - 8 questions 
or Yes to 2 or more of 4 STOP questions + male gender 
or Yes to 2 or more of 4 STOP questions + BMI > 35kg/m2 
or Yes to 2 or more of 4 STOP questions + neck circumference 17 inches / 43cm in male or 16 
inches / 41cm in female 
 
 
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APPENDIX F: Eligibility Screening Questions: 
Do you have significant cardiorespiratory disease including any of the following: 
         Chronic obstructive pulmonary disease (COPD) 
         Congestive Heart Failure 
         Atrial Fibrillation 
         Other (please describe) 
Have you previously been hospitalized for cardiorespiratory issues? 
-If yes, please describe. 
Do you have an implanted pacemaker or defibrillator? 
Do you use oxygen while sleeping? 
Do you have respiratory muscle weakness due to neuromuscular condition? 
Have you experienced awake hypoventilation or suspicion of sleep related hypoventilation 
(breathing at an abnormally slow rate)? 
Have you used opioid medication for more than 3 months? 
Have you ever had a stroke? 
Do you have a history of severe insomnia? 
Do you have a history of dementia? 
Follow up enrollment questions: 
What is the best phone number to reach you at? 
What is your preferred email address? 
What is the best time to contact you? (Day(s), time(s)) 
 
 
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APPENDIX G: ANNE Sleep Scoring Manual 
 
 
 
 
 
 
ANNE® Sleep Scoring Manual 
Version 1.1 
 
 
 
 
 
Sibel Inc. 
6650 W. Touhy Ave 
Niles, IL 60714 
 
Table of Contents 
 
1.0 Introduction 
4 
2.0 Background 
5 
2.1 Indication for use of ANNE™ Sleep 
5 
2.2 ANNE Sensors Description 
6 
2.3 Signals Acquired by ANNE Sleep 
7 
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3.0 Scoring Procedure 
8 
3.1 Data Flow Overview 
8 
3.2 EnsoSleep 9 
3.1.1 Choosing a patient to Score 
9 
3.1.2 Creating a Score Set 
10 
3.1.3 Configuring the Scoring Screen 11 
3.1.4 Adding Sleep Disordered Breathing Events 13 
3.1.5 Deleting Sleep Disordered Breathing Events 14 
3.2 Detecting Sleep Disordered Breathing Events with ANNE Sleep System
 
15 
3.3 Examples 
18 
3.3.1 Example 1 
18 
3.3.2 Example 2 
19 
3.3.3 Example 3 
20 
3.3.4 Example 4 
21 
3.3.5 Example 5 
22 
3.3.6 Motional Artifact Example 23 
 
 
 
 
 
 
 
 
 
 
 
 
Change Log 
 
Revision Effective 
Date 
Description of Revision 
A 
12/1/2021 
Initial Release 
1.0 
1.0 Introduction 
ANNE Sleep is a wireless physiological recorder for use as an aid in the diagnosis of 
sleep-related breathing disorders by healthcare professionals. The system features two 
wearable sensors that pair with the ANNE Sleep application for the transmission and 
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storage of data. The sensors, which are placed on the chest and finger, collect 
peripheral arterial tonometry (PAT), chest movement, oximetry, snoring, body position, 
and heart rate. The device is intended for use in the clinical and home setting under the 
direction of a Healthcare Professional (HCP). 
 
The purpose of the ANNE Sleep Scoring Manual is to provide guidelines and step-by-
step instructions for sleep technicians and physicians to score the ANNE Sleep 
recordings. 
2.0 
2.0 Background   
2.1 Indication for use of ANNE™ Sleep 
 
ANNE Sleep is a wearable sensor system intended for use in the collection, analysis, 
display, and storage of physiological parameters to aid in the evaluation of sleep-related 
breathing disorders of adult patients suspected of sleep apnea. The device is intended 
for use in the clinical and home setting under the direction of a Healthcare Professional 
(HCP). 
 
2.2 ANNE Sensors Description 
ANNE Sleep uses the ANNE Chest and ANNE Limb sensors to detect sleep distorted 
breathing. The sensors are worn by the patient during a night of sleep. Both sensors 
wirelessly measure biosignals and transfer them to the ANNE Sleep mobile application 
through Bluetooth. 
 
The ANNE Chest sensor is placed under the suprasternal notch as shown below 
(Figure 1) with a silicone gel adhesive. The ANNE Chest measures snoring through the 
accelerometer z-axis sampled at a high-frequency and chest movement through the x 
and y-axis.  
 
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Figure 1: Placement of the ANNE Chest Sensor 
 
The ANNE Limb sensor is worn on the finger and collects photoplethysmograph (PPG) 
signals for the calculation of SpO2, PAT, and pulse rate. The ANNE Limb Sensor is 
secured to the finger with a medical foam tape adhesive as shown below in Figure 2. 
 
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Figure 2: Limb Sensor worn 
 
2.3 Signals Acquired by ANNE Sleep 
 
The signals listed in Table 1 are used by ANNE Sleep to detect respiratory events. The signals 
will be available in the EDF file that is generated as part of the data flow. The signals are 
downsampled to be easily transmitted and viewed. 
 
Table 1: Sleep Signal Generated from the ANNE Sensors 
Signal 
Device Description 
Sampling Rate 
(Hz) 
PAT (A.U) 
Limb 
Peripheral Arterial tone 
32 
Pulse Amplitude 
(A.U) 
Limb 
Pulse amplitude from the PAT signal 
2 
Accel Vertical (g) 
Chest 
Chest movement picked up by ANNE Chest’s vertical 
roll. Refer to Figure 3 
32 
Accel Horizontal 
(g) 
Chest 
Chest movement picked up by ANNE Chest’s 
horizontal roll. Refer to Figure 3 
32 
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Snore (g) 
Chest 
Snore signal from ANNE Chest 
256 
Pulse Rate (bpm) 
Limb 
Pulse rate derived from ANNE Limb Sensor  
2 
SpO2 (%) 
Limb 
Oxygen saturation derived from ANNE Limb Sensor  
2 
Body Position 
Chest 
Position of the Body 
1 
 
The ANNE Chest Sensor derives horizontal roll and vertical roll from the 3-axis accelerometer to 
measure the tilt of the sensor in both directions. Displaying the roll of the sensor instead of the 
acceleration allows the chest movements to be more clearly shown graphically. 
 
Figure 3: Accelerometer axis orientation of ANNE Chest 
 
The body position of the patient is also derived by the 3-axis accelerometer. The system 
provides 5 body positions - upright, supine, prone, left, and right. 
 
3.0 
3.0 Scoring Procedure 
3.1 Data Flow Overview 
The high-level data flow is shown below (Figure 4). After the patient has received the ANNE 
Sleep system and successfully finished their sleep night data collection, the data is downloaded 
from the sensors and automatically uploaded to the ANNE Sleep Hub. In the ANNE Sleep Hub, 
the data collected from the ANNE sensors are processed and converted into an EDF format file 
so that it can be consumed by EDF viewers and scoring platforms such as EnsoSleep. After the 
dataset has been scored, the scored data is transferred back to the ANNE Sleep Hub for sleep 
report generation. The report generated can then be reviewed by a Healthcare Professional 
(HCP) to aid in the evaluation of sleep-related breathing disorders. 
 
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Figure 4: ANNE Sleep Data Flowchart 
 
pAHI (peripheral arterial tonometry AHI) is calculated by counting the number of sleep-
disordered breathing events for the patient divided by the TST (total sleep time). TST is 
automatically calculated in ANNE Sleep Hub using pulse rate. 
 
pAHI=Total Number of Disordered Breathing EventsTotal Sleep Time (hrs) 
3.2 EnsoSleep 
The ANNE Sleep system uses EDF viewers or scoring platforms such as EnsoSleep for scoring 
the sleep recordings. This section contains the steps for scoring ANNE Sleep data with 
EnsoSleep. 
3.1.1 Choosing a patient to Score 
Select the dataset to score by identifying them through the Patient column. After selecting the 
patient, click the vital icon as shown below in Figure 5 to proceed to create a score set. 
 
 
 
Figure 5: EnsoSleep Dashboard 
 
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3.1.2 Creating a Score Set 
Create a new score set based on the “sibel” score set. It will contain pre-labeled sleep events 
from EnsoSleep. Left-click “proceed” to get to the scoring screen as shown in Figure 7. 
 
 
Figure 6: EnsoSleep Scoreset selection Screen 
 
 
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Figure 7: EnsoSleep Scoring Screen 
 
3.1.3 Configuring the Scoring Screen 
On the top right corner of the scoring screen, click the settings icon to modify the time span. A 
5-minute timespan is recommended for optimal view of PAT signal changes. 
 
 
Figure 8: Enso Sleep Settings Screen 
 
Utilize the “R” key on the keyboard to rescale all the signals throughout the scoring process.  
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Figure 9: Before and After pressing the R key 
 
Auto scaling obfuscates any evidence of the changes in signal due to heterogeneity in 
amplitude attributed to regular chest movements and motion artifacts. In order to rescale the two 
signals only, EnsoSleep provides features to manually adjust the desired scale for each 
channel. Below is an example where it might look like a chest movement reduction but is 
actually a zoomed-out view due to motion artifacts. 
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Figure 10: Signal Zoomed Out Due to Motion Artifact 
 
When you see motion artifacts, manually rescale these two signals. You can rescale for each 
channel by right-clicking on the signal name on the far left side to get a pop-up screen as shown 
below. Click + or - to adjust the scale. 
 
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Figure 11: Rescale Feature 
 
3.1.4 Adding Sleep Disordered Breathing Events 
Drag the cursor on the PAT signal to label a sleep-disordered breathing event as Obstructive 
Hypopnea. Do not use other event types as the ANNE Sleep system will not distinguish 
differences among Obstructive Apnea, Hypopnea, and Central Apnea. 
 
 
Figure 12: Enso Sleep Marked Events Scoring Screen  
 
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3.1.5 Deleting Sleep Disordered Breathing Events 
 
To delete an event, right-click the event and click delete.  
 
Figure 13: Deleting Events 
 
 
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For further instructions on how to use the platform described in this section, please refer to 
EnsoSleep’s instruction manual. 
3.2 Detecting Sleep Disordered Breathing Events with ANNE Sleep System 
Respiratory events (Apnea episodes) are caused either by an upper airway obstruction following 
the collapse of the upper airway wall or central dysfunction in which the brain doesn’t send 
proper signals to the muscles that control breathing. During the apnea episodes, sympathetic 
activation causes vasoconstriction and acceleration of the heart rate. This results in attenuation 
of the PAT signals. PAT amplitude may vary due to reasons other than apnea events such as 
periodic limb movements or spontaneous arousals. This section described the steps necessary 
to differentiate the true respiratory event resulting in attenuation of the PAT signal and the ones 
caused by events not related to it. 
 
  
 
Figure 14: Typical pattern of PAT Amp attenuation and HR increase  
 
 
 
 
 
 
 
 
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When scoring for sleep-disordered breathing (SDB) events, the first step is to see if the area 
that is being analyzed has (1) motion artifact or (2) body position change. If there are any of the 
two signals, do not continue on to see if it is an SDB event.  
Next, look at the Accel Vertical and Accel Horizontal signal for chest movement reduction. If 
the amplitude of both signals drops by 90% or more for more than 10 seconds, it is categorized 
as an SDB event. If one or both signals does not look as below, move to analyze the attenuation 
of the PAT signal. Label the event as an SDB regardless of the limb sensor output. 
 
 
Figure 15: Chest Movement Reduction Example 
 
If there are motion artifacts in between the chest movement reduction, do not grade the signal 
as SDB. An example of it is shown below. This is usually created as part of changing the body 
position and should be disregarded. 
 
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Figure 16: Motion Artifact example 
After analyzing the two accelerometer signals and concluding that there is no chest movement 
reduction,  proceed to analyze attenuation of the PAT signal, heart rate increase, and SpO2 
drop. PAT attenuation can be easily identified by seeing the PAT amplitude signal drop. Also, 
heart rate should increase by at least 3 bpm within 15 seconds, and the SpO2 should drop by at 
least 3% within 60 seconds. If the conditions above are met, label the event as SDB.  
 
If there is a reduction in PAT amplitude and an increase in heart rate but the SpO2 drop is not 
present, look at the snoring signal. If the area of interest has no snoring but there is snoring 
before that point, label the event as SDB.   
 
A flow diagram is shown below to summarize the steps necessary to label SDB events using 
ANNE Sleep. 
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Figure 17: Flow for detection Sleep Disordered Breathing 
3.3 Examples 
The following are example snapshots of various SDB (Sleep Disordered Breathing) events 
covering the different cases in the flow diagram. 
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3.3.1 Example 1 
 
Figure 18: Example 1: Snapshot of SDB events 
 
Event 1, 4: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
≥ 3% drop in SpO2 ✅ 
• 
Pulse Rate Increase ✅ 
 
Conclusion: SDB Event 
Event 3, 5, 6: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
≥ 3% drop in SpO2  ❌ 
• 
Pulse Rate Increase  ✅ 
 
Conclusion: Not an SDB Event 
Event 2: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
≥ 3% drop in SpO2  ❌ 
• 
Pulse Rate Increase ❌ 
 
Conclusion: Not an SDB Event 
 
 
 
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3.3.2 Example 2 
 
Figure 19: Example 2: Snapshot of SDB events 
 
Event 1: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ❌ 
• 
Pulse Rate Increase  ✅ 
• 
3% drop in SpO2 ✅ 
 
Conclusion: Not an SDB Event 
 
Event 2: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase  ✅ 
• 
3% drop in SpO2 ✅ 
 
Conclusion: SDB Event 
 
Event 3: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ❌ 
• 
Pulse Rate Increase  ❌ 
• 
3% drop in SpO2 ❌ 
 
Conclusion: Not an SDB Event 
 
3.3.3 Example 3 
 
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Figure 20: Example 3: Snapshot of SDB events 
 
Event 1: 
• 
Chest movement reduction ❌ 
• 
3% drop in SpO2  ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase  ✅ 
• 
Snoring reduction for more than 10 seconds ❌ 
 
Conclusion: Not an SDB Event 
 
Event 2: 
• 
Chest movement reduction for more than 10 seconds ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase  ✅ 
• 
3% drop in SpO2 ❌ 
• 
Snoring reduction for more than 10 seconds ✅ 
 
Conclusion: SDB Event 
 
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3.3.4 Example 4 
 
Figure 21: Example 4: Snapshot of SDB events 
 
Event 1: 
• 
Chest movement reduction ❌ 
• 
≥ 3% drop in SpO2  ✅ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase ✅ 
 
Conclusion: SDB Event 
 
Event 2: 
• 
Chest movement reduction ✅ 
• 
≥ 3% drop in SpO2  ✅ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase ✅ 
• 
 
Conclusion: SDB Event 
 
Event 3: 
• 
Chest movement reduction ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase  ✅ 
• 
3% drop in SpO2 ✅ 
 
Conclusion: SDB Event 
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3.3.5 Example 5 
 
Figure 22: Example 5: Snapshot of SDB events 
 
Event 1: 
• 
Chest movement reduction ❌ 
• 
3% drop in SpO2  ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase ✅ 
• 
Snoring reduction for more than 10 seconds ❌ 
 
Conclusion: Not an SDB Event 
 
Event 2: 
• 
Chest movement reduction ❌ 
• 
3% drop in SpO2  ❌ 
• 
PAT Amplitude decrease  ✅ 
• 
Pulse Rate Increase ✅ 
• 
Snoring reduction for more than 10 seconds ❌ 
 
Conclusion: Not an SDB Event 
 
Event 3: 
• 
Body Position Change ❌ 
 
Conclusion: Not an SDB Event 
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3.3.6 Motional Artifact Example 
The following is an example of a snapshot that contains large movements. Any events under or 
between big motion artifacts should not be labeled as SDB. Continuous motion artifacts often 
relate to the patient being awake or switching body position. With large motion affecting signal 
quality, the associating vital signs may be invalid.  
 
0 
Figure 23: Snapshot of motion artifacts 
 
 
 
 
 
 
 
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