Accuracy of Owlet Smart Sock Sensor 3rd Generation With Profound Hypoxia
Conditions: Hypoxia
Sponsor: Owlet Baby Care, Inc.

 
Accuracy of pulse oximeters with profound hypoxia 
Test protocol 
 
 
 
 
NCT04446247 
 
January 22, 2019 

IRB # 10-00437 
UCSF Hypoxia Lab 
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Accuracy of pulse oximeters with profound hypoxia 
Test protocol 
 
Principal Investigators 
Philip Bickler MD, PhD and John Feiner, MD 
 
Clinical Research Coordinator 
Koa Gudelunas, 
 
Additional Investigators 
Eilers, Helge, MD 
Lipnick, Michael, MD 
Sall, Jeffrey, MD, PhD 
Schober, Andrew E, MD 
 
Aims 
The aim of this project is to test the accuracy of pulse oximeters during mild, moderate and 
severe hypoxia; i.e. a range of arterial HbO2 saturations from 100 to down to 70%. This is done 
by comparing the reading of the pulse oximeter during brief, steady state hypoxia with a gold- 
standard measurement of blood oxyhemoglobin saturation (arterial blood sample processed in a 
laboratory hemoximeter). The data obtained is submitted by pulse oximeter manufacturers to the 
FDA for device approval, or may be used for engineering or calibration purposes. 
 
Subjects 
A typical study will include at least 10 subjects (up to 14 if needed to reach the 200 necessary 
data points to meet the ISO 80601-2-61:2017). 
 
Per FDA guidance, at least 2, or 15% of the subjects will have dark skin. Equal numbers of men 
and women will be enrolled. 
 
Inclusion Criteria 
1. The subject is male or female, aged ≥18 and <50. 
2. The subject is in good general health with no evidence of any medical problems. 
3. The subject is fluent in both written and spoken English. 
4. The subject has provided informed consent and is willing to comply with the study 
procedures. 
 
Exclusion criteria: 
1. The subject is obese (BMI>30). 
2. The subject has a known history of heart disease, lung disease, kidney or liver disease. 
3. Diagnosis of asthma, sleep apnea, or use of CPAP. 
4. Subject has diabetes. 
5. Subject has a clotting disorder. 

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6. The subject a hemoglobinopathy or history of anemia, per subject report or the first blood 
sample, that in the opinion of the investigator, would make them unsuitable for study 
participation. 
7. The subject has any other serious systemic illness. 
8. The subject is a current smoker. 
9. Any injury, deformity, or abnormality at the sensor sites that in the opinion of the 
investigators’ would interfere with the sensors working correctly. 
10. The subject has a history of fainting or vasovagal response. 
11. The subject has a history of sensitivity to local anesthesia. 
12. The subject has a diagnosis of Raynaud’s disease. 
13. The subject has unacceptable collateral circulation based on exam by the investigator 
(Allen’s test). 
14. The subject is pregnant, lactating or trying to get pregnant. 
15. The subject is unable or unwilling to provide informed consent, or is unable or unwilling to 
comply with study procedures. 
16. The subject has any other condition, which in the opinion of the investigators’ would make 
them unsuitable for the study. 
 
 
Procedures 
After injection of a local anesthetic, a 22-gauge catheter is inserted in one radial artery. 
Pulse oximeters are attached to fingers, ears or flat body surfaces. Subjects are in a comfortable 
semi-recumbent position. Subjects then breathe air mixtures containing reduced amounts of 
oxygen to produce the desired level of hypoxemia. Stable, safe and controlled hypoxia is breath- 
by breath by breath respiratory gas analysis and a computer program that permits the inspired gas 
mixture to be adjusted to achieve a level of lung alveolar gas that will achieve the desired degree 
of saturation. 
Typically, saturation levels involve one period with air breathing and then at one of 6 
levels with reduced oxygen, e.g. 94%, 90%, 85%, 80%, 75% and 70% saturation. Each level of 
saturation is held for 30-60 seconds. At appropriate intervals and when oxygen levels are stable, 
arterial blood samples are obtained from the radial arterial catheter. The operator then changes 
the inspired oxygen concentration to attain the next desired stead-state level of hypoxia. A "run" 
consists of several stable steady-state hypoxia levels and together takes 10-15 minutes. Each run 
is terminated by a breath of 100% O2 followed by room air. Two runs together enable obtaining 
a total of 20-25 blood samples, 2 samples at each plateau. Saturation of each arterial blood 
sample is determined by direct oximetry in a Radiometer ABL-90 multi-wavelength oximeter. 
The precise target levels of saturation can be adjusted to suit the sponsor, but typical testing is 
done to satisfy ISO and FDA standards for testing, which is 70% to 100%. 
The study takes about 1 hour of each subject's time. Analysis of the data requires several 
days. We encourage manufacturer’s representatives to be present for these tests, and to mount the 
probes. An extra charge is made if no representative is present, requiring us to mount the probes 
and record data. 
 
Sponsor Pulse oximeter study data 
Data from test pulse oximeters for comparison to blood values can be obtained in several 
ways. In every case, the goal is to obtain a reading from the oximeter that corresponds to the 

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associated blood sample or a reference oximeter. Because of circulation delays and instrument 
averaging time, we attempt to create steady state conditions at each level of oxygenation. 
Therefore, a means should be provided to record the instrument reading at each blood sample. 
This instrument reading may be obtained with several different approaches. Some instruments 
have no digital or analog output and the instrument reading may be recorded manually or 
recorded by a video of the instrument display. Other instruments may have an analog output. 
The laboratory can record analog data by use of LabView. Digital recording of output can also 
be obtained via LabView but his requires information from the sponsor concerning the structure 
of the digital signal. Consultation with us is recommended. 
If a manufacturer prefers to collect and analyze the data, the continuous digital signal of 
each oximeter should be read, for comparison with the blood sample, 9 seconds before the record 
shows a sudden fall or rise in oxygen saturation, not at the time of blood sampling. This 
procedure accounts for the delays of finger circulation and uses the estimated delay from the 
lung to the sample site. There is no useful correlation between the actual time of blood sampling 
and the oximeter recording because of the variability of tissue blood flow lag. As mentioned, 
steady-state hypoxia avoids the concern that oximeter reading is not aligned with a blood sample 
reading. 
 
Statistics 
The number of subjects and the number of comparisons (paired pulse oximeter readings 
and arterial saturation values) is determined by current FDA guidance requirements [2]. This is a 
minimum of 200 data points and 10 subjects. In the course of this type of study, some subjects 
may drop out, some readings can be lost due to motion or other interference and occasionally some 
do not consent. 
 
The following demographic data will be collected on the subjects: 
- 
gender (male, female, other) 
- 
age 
- 
skin tone (dark, medium, light) 
- 
height (cm) 
- 
weight (kg) 
- 
wrist circumference (cm) 
- 
dominant hand (left or right) 
 
Data Analysis 
In all cases, the blood analysis data are provided, including the SaO2, MetHb, COHb and Hgb 
concentration. 
The data analysis report will consist of the following: 
• A Table of the oximeter readings versus corresponding blood SaO2 values. 
• Graphic plots of the bias between the oximeter reading and the SaO2 measured by the 
hemoximeter (on the blood sample, i.e Modified Bland -Altman plots for each instrument or 
instrument probe combination. 
• Regression equations for the bias of each instrument. 
• Tables of the mean error or bias, its standard deviation, standard error, 95% confidence 
interval, maximum and minimum and root mean square error, all computed both overall and 
by several sub-ranges of desaturation. 

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• A table of the demographics of the subject population is provided. 
 
Subject Safety 
Pulse oximeters are typically considered non-significant risk medical devices. The LED light 
energy utilized in typical test measurements is within the same range as other cleared marketed 
devices and introduces no further risks. An LED light emits light that passes through the tissue. A 
light detector then measures how much light was absorbed by the tissue. Based on the ratio of 
absorbance of different wavelengths of light, the device calculates the oxygen saturation. 
 
Risks 
Breathing a very low oxygen mixture may cause dizziness and might cause loss of 
consciousness for a few seconds. It may make one feel very short of breath during the test and for 
a few seconds afterwards. There is a remote possibility that if the subject loses consciousness 
he/she might have muscular twitching or convulsions. This study will not seek to reach saturations 
below 70%. Hypoxia may cause tachycardia and increased blood pressure during the test, and 
might cause headache. In all the years of conducting the study no subject has mentioned headache. 
Much more severe and prolonged lack of oxygen could cause brain injury or death, but the duration 
and depth of hypoxia is limited by the test protocol to short intervals. The needle catheter used to 
take blood may hurt when it is inserted despite the use of local anesthesia, and there may be a black 
and blue spot afterward. It is remotely possible the artery might be damaged or clot, or a tendon 
sheath near it be injured by the needle, resulting in some soreness. These risks are unlikely because 
none of the enrolled 2000+ subjects has ever had a serious complication. Hyperventilating during 
the part of the study requiring reduced PCO2 may make subjects lightheaded or dizzy. Breathing 
air with added CO2 may make subjects feel short of breath and cause a headache. Some subjects 
feel faint when they arrive for the study, apparently related to the thought of having an arterial line. 
These subjects were excluded from the study and suffered no further discomfort. 
 
Risk Mitigations 
Subjects are all monitored with accurate reference oximeters and continuous end-tidal 
gas analysis to prevent the risk of more profound hypoxia than desired. Investigators are 
experienced anesthesiologists adept at assessing breathing and in maintaining appropriate airway 
conditions. The study room is set up like an OR with all resuscitation equipment immediately 
available. 
 
Informed Consent 
Written informed consent is obtained before any study interventions. In discussions with 
the study coordinator before the day of the study, potential subjects will be offered the consent 
form to review. On the day of the study subjects are given the consent form which they read and 
sign if they wish to participate. A study doctor is present to answer questions. 
 
Only subjects clearly able to understand and read English will be enrolled. Subjects will be asked 
if they have any questions and are told they can withdraw at any time. 
 
Data Storage 

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Identifiable subject information is always stored securely following all applicable rules 
and regulations. Consent forms and other study related documents are retained following UCSF 
data retentions policy. 
 
Other testing 
Special testing, with various conditions or with special subject populations can also be 
arranged, at extra charge. 
We also offer testing for performance during controlled subject hand motion. Three types 
of motion are typically used: tapping, rubbing and random motion. Tapping and random motion 
are done with a computer-controlled motion machine. 
Testing during low perfusion conditions is also available at an extra charge.