Determination of SpO2 and PR Accuracy Specifications During Motion Accuracy of Pulse Oximeters With Profound Hypoxia Pulse Oximeter Accuracy Evaluation Protocol
Conditions: Hypoxia
Sponsor: Nihon Kohden

NK IRB No.: 70Ag_Vital-00008 
Date: March 16, 2021  
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Identifiers: NCT04814342 Protocol ID: 70Ag_Vital-00008 
Title: Accuracy of Pulse Oximeters With Profound Hypoxia During Motion (NIHO12) 
Original Date: 16 Mar 2021 
Redaction: 1 Sep 2025 
 
 

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Date: March 16, 2021  
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Determination of SpO2 and PR accuracy specifications during motion 
ACCURACY OF PULSE OXIMETERS WITH PROFOUND HYPOXIA NIHO12 
Pulse Oximeter Accuracy Evaluation Protocol 
During Controlled Motion 
 
Study Site: The UCSF Hypoxia Research Laboratory, 513 Parnassus Ave San Francisco, CA 94133 
Principal Investigator (PI): Philip E. Bickler, M.D 
Study Period: March 25, 2021 
 
Breathe-down Test During Motion 
 
1. Objective 
 
This study is intended to evaluate performance of the following pulse oximeter: 
Device name 
Model name 
Quantity 
Intended populations 
Materials that will be in 
contact with subject’s 
skin 
Pulse oximeter 
OVL-4000 series, OLV-
4202 (SW version: 01-11) 
4 
Adult/Child/Neonate 
- 
Disposable 
probe 
TL-273TA 
5 
Adult/Neonate 
Polyurethane, 
polyester, acrylic 
adhesive 
Disposable 
probe 
TL-535U 
1 
Neonate/Preterm infant 
- 
Attachment 
tape 
XL  
(option for TL-535U) 
5 
Neonate 
Polyurethane, Styrene-
based elastomer 
Multi-site 
probe 
TL-220T 
1 
Adult/Child/Neonate 
- 
Attachment 
tape 
- 
(option for TL-220T) 
5 
Adult/Child/Neonate 
Polyvinyl chloride 
 
 
 
 
 
Multi-site Y 
probe 
TL-260T 
1 
Adult/Child/Neonate/ 
Preterm infant 
- 
TL-260T clip 
adapter 
- 
(option for TL-260T) 
1 
Adult 
Silicone 
 
 
 
 
 
 
 
 
 
 
 
SpO2 probe, TL-281-IB will be used for monitoring SpO2 for reference.  Bedside monitor, PVM-4763 (SW 
version 01-10) will be used for monitoring heart rate for reference.  All test devices can be identified by serial 
number or lot number.  Nihon Kohden will be responsible of keeping records documenting the delivery, use, 
return, and disposal of the test devices. 
The following requirements are to be met during motion: 
 
• 
SpO2 value range 70% to 100% 
• 
5 subjects, with 2 of dark pigment 
 
Safety of the test devices will be evaluated by assessing adverse events occurred to subjects. 
 
This test is designed in response to the 2013 FDA Guidance on Pulse Oximeters – Premarket Notification 
Submissions and by ISO 80601-2-61:2017 on Pulse Oximeters, specifically the sections listed below. 
 
• 2013 FDA Guidance on Pulse Oximeters – Premarket Notification Submissions:  
o   4.1 
Accuracy of Pulse Oximeters 
o   4.1.1 In vivo testing for SpO2 accuracy under laboratory conditions 
o   4.1.3 Testing for SpO2 accuracy for oximeters making motion performance claims 
o   4.1.5 Testing for Pulse Rate Accuracy claims 
o   4.1.6 Testing for Pulse Rate Accuracy for oximeters labeled with motion performance 
claims 
• ISO 80601-2-61:2017 Annex EE.2 and clause 201.12.1.101.2 
o   201.12.1.101 SpO2 accuracy of pulse oximeter equipment  

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o   201.12.1.101.2 
Determination of SpO2 accuracy  
o   201.12.1.102 Accuracy under conditions of motion  
o   201.12.1.104 Pulse rate ACCURACY  
 
NOTE: This study has been designed per ISO 80601-2-61:2017, and it has been also designed to respond to 
the recommendations on subject safety added on ISO 80601-2-61:2011.  Since ISO 80601-2-61:2011 has 
been updated as ISO 80601-2-61:2017 with no changes in the requirements for conducting the study and 
demonstrating SpO2 and PR accuracy, this study results can be referred for demonstrating SpO2 and PR 
accuracy per ISO 80601-2-61:2011 as well as per ISO 80601-2-61:2017. 
 
This study will be conducted in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki, ISO 14155:2011 and :2020. 
 
2. Subjects 
 
This study is performed on volunteers who have previously been determined to be healthy enough for this 
study, have signed an informed consent form and met the following IRB requirements.  These volunteers are 
compensated by the laboratory for their participation.  Point of enrolment is defined as time at which subjects 
sign and date the informed consent form and screening based on subject demography and 
inclusion/exclusion criteria is complete. Expected duration of each subject’s participation will be about 45 
minutes. 
 
The inclusion criteria for the test subjects are: 
 
1. 
Both male and female subjects who can give written informed consent 
2. 
Healthy subjects capable of undergoing controlled hypoxemia to the levels outlined in the desaturation 
profile below 
3. 
Meeting the demographic requirements listed above. 
 
The exclusion criteria for the test subjects are: 
 
1. 
Age below 18 or over 50 
2. 
Pregnant women 
3. 
Significant arrhythmia 
4. 
Blood pressure above 150 systolic or 90 diastolic 
5. 
Subjects whom the investigator consider ineligible for the study. 
 
5 subjects will be recruited to complete the test.  Of these 2 will be dark pigment. 
 
 
3. Desaturation 
 
Each subject shall have their right arm positioned on a motion generating machine.  The right hand is 
called the motion hand, the left is called the control hand. 
 
For each subject, a series of desaturation runs are performed.  Run 1 starts with a stabilized period at 
room air and is followed by stabilized plateaus at various lower saturation levels.  Run 2 starts with a 
stabilized period at 100% and is followed by stabilized plateaus at various lower saturation levels.  The 
following are value targets: 
 
Run 1 
room air, 90%, 80%, 70% 
Run 2 
100%, 95%, 85%, 75% 
 
The objective of these targets is to spread the data points evenly over the desired range.  Achieving them 
exactly is not important, though every effort will be made to be within 2%. 
 
The SpO2 value is reduced by delivering a mixture of medical air and nitrogen, controlled by 2 manually 
controlled needle valve flowmeters.  The operator controls the SpO2 by observing the breath by breath 
arterial saturation, which is in turn computed from end tidal PO2 and PCO2.  FiO2 is reduced suddenly at first 
then adjusted to achieve a stable plateau value at the desired target.  A plateau is defined as stable when 
the readings of the sponsor Control instruments have not changed more than 1 % for 20 seconds (they do not 
have to agree with each other).  Each desaturation plateaus should not exceed 10 minutes. When the 

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sponsor confirms that stability is achieved, the plateau is held for 90 seconds.  The gas mixture is then 
changed for the next value.  This is then repeated for each plateau value.  
 
During this procedure, the subject is coached on breathing.  If he/she appears to fall asleep, he/she is 
woken up.  At any signs of distress, he/she is given 100% oxygen. 
 
Each run should take Between 15 and 25 minutes.  It is normal to schedule as many as 10 subjects per 
day. 
 
Trained Nihon Kohden personnel will be present at the procedure.  The role of the Nihon Kohden person is 
to give technical support relative to the use of the test pulse oximeters and to perform study monitoring. All 
these actions will be done under the careful direction of the investigator. 
 
Data of the test devices will be obtained in an SD card inserted into the pulse oximeter OLV-4202.  
Subject’s demographic data will be collected using specific data collection forms. 
 
4. Reference Data 
 
The reference SpO2 will be measured using a Nihon Kohden OLV-4202 as a secondary standard pulse 
oximeter equipment.  The equipment should be quality control checked at the study site to be functioning 
properly before use. 
 
The heart rate will be measured using a Nihon Kohden PVM-4763 as an ECG monitor.  The monitor 
should be quality control checked at the study site to be functioning properly before use. 
 
5. Motions 
 
This study evaluates the effect of several motions.  The main attributes are rubbing and tapping.  For 
each subject one run will use tapping and the other rubbing.  Motion types will be arranged as follows: 
 
On the motion-hand side 
 
Subject 1 + 3 + 5 
Subject 2 + 4 
Run 1 
rubbing 
tapping 
Run 2 
tapping 
rubbing 
 
 
Each of these motions can be driven in the following ways. 
 
• 
2Hz sine (2Hz) 
• 
4Hz sine (4Hz) 
• 
Sequence of moves of a pseudo random distance from 1mm to 30mm (Rand) 
• 
The amplitude of the sine motion and the maximum slope of the random motion will be determined at 
the beginning of each Desaturation Run. 
• 
For 2Hz sine and 4Hz sine, motion artifact red p-p amplitude will be equal to the PPG p-p amplitude 
of the subject.  For Rand, the largest motion artifact red p-p amplitude will be equal to the PPG p-p 
amplitude of the subject. 
 
In each plateau, the motion drive type will be sequentially changed in the following ways. 
 
• 
30 seconds’ no motion 
• 
30 seconds’ 2Hz 
• 
30 seconds’ 4Hz 
• 
30 seconds’ Rand 
 
6. Sensor Placements 
 
A reference SpO2 will be taken on each subject with the sponsor Control instrument.  The SpO2 probes 
for the sponsor Control instrument will be the TL-281-IB disposable SpO2 probes.  These probes will be 
arranged as follows: 
 
On the control-hand side 
 
Subject 1 + 4 
Subject 2 + 5 
Subject 3 

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TL-281T-IB 
Middle 
Ring 
Index 
 
A 3-lead ECG will be taken on each subject with the sponsor Control instrument.  The electrodes for the 
sponsor Control instrument will be the L-150X disposable ECG electrodes. 
 
The probes for the primary test instruments will be the TL-273TA Neonatal and Adult disposable probe, the 
TL-535U Neonatal disposable probe, the TL-220T Multisite reusable probe.  These probes will be arranged 
as follows: 
 
On the motion-hand side 
 
Subject 1 + 4 
Subject 2 + 5 
Subject 3 
TL-273TA 
Index 
Middle 
Ring 
TL-535U 
Middle 
Ring 
Index 
TL-220T 
Ring 
Index 
Middle 
 
7. Subject Safety 
 
The sensors will be isolated as follows 
 
1. 500V between the sensor and earth ground 
 
2. 4 KV between AC mains power and the low voltage power supply and 1.5 KV between the low 
voltage power supply and the sensor, OR 5 KV between AC mains and the sensor. 
Non-invasive blood pressure will be measured at a screening.  EtCO2, respiratory rate, and FiO2 of the 
subjects will be monitored.  In addition, the laboratory maintains criteria for subject selection that have been 
proven to minimize the risk of any problems during the study. 
 
Adverse event and serious adverse event will be assessed throughout the study by the Principal 
Investigator and Co-Investigator or research nurse designated by Principal Investigator.  If any adverse 
event occurs during the study, an appropriate medical treatment will be provided to the subject by a medical 
staff at the laboratory.  Nihon Kohden may suspend or prematurely terminate the study when there are 
serious violations and deviations from the GCP which could adversely affect subject’s safety and correct data 
recording. 
 
The test will be discontinued when a subject requests to withdraw from the study or the Co-investigator will 
terminate the desaturation procedure and/or a subject’s participation in the study because of the reasons 
including: 1) the subject experiences unexpected oxygen desaturation or 2) the subject loses consciousness. 
 
Risks associated with participation in the study include the following: 
a. 
The risks of the brief exposures to hypoxia are include feeling short of breath, headache, and 
dizziness.  Brief loss of consciousness may occur but is not expected at the levels of oxygen targeted 
for these tests. 
 
Nihon Kohden has determined that there is no residual risk associated with the test devices. Nihon Kohden 
will be responsible for maintaining the test devices. 
 
8. Data Analysis 
 
Data from subjects who did not complete the protocol will be thrown out.  Missing data will not be 
supplemented. 
 
Data points at a plateau where the equipment output for TL-281-IB changes over 2% saturation will be 
thrown out. 
 
Data from unstable pulse wave signal due to the uncontrolled motion will be thrown out.  
 
SpO2 data will be reduced using the ARMS method and accuracy will be reported as the ARMS deviation 
between the co-oximeter and the test instruments for all points gathered from each sensor. 
 
 
 
 

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PR data points where heart rate changes over 4bpm for 10 seconds will be thrown out. 
 
PR data points at a plateau where heart rate changes over 19bpm for 10 seconds will be thrown out. 
 
PR data will be reduced using the ARMS method and accuracy will be reported as the ARMS deviation 
between the ECG monitor and the test instruments for all plateaus gathered from each sensor. Accuracy will 
be determined by comparing the noninvasive pulse rate measurement of the pulse oximeter (PRi) to the heart 
rate obtained from an electrocardiography reference device (HRRi) and calculating the arithmetic root mean 
square (Arms) error value as follows: