Pulse Oximeter Accuracy During Stable Hypoxia Plateaus
Conditions: Hypoxia
Sponsor: Nihon Kohden

Pulse Oximeter Accuracy during stable hypoxia plateaus Test Protocol 
11/28/25 Page 1 
 
 
 
 
 
 
 
 
Sponsor  
Nihon Kohden Corporation  
1-31-4 Nishiochiai Shinjuku-ku, Tokyo, 161-8560 Japan  
 
Sponsor contacts  
Nami Wakabayashi  
Manager Clinical Development Department  
Email: Nami_Wakabayashi@mb1.nkc.co.jp 
 
Study Principal Investigator  
Greg Stratmann MD, PhD 
 
Investigation site  
Vital Sign Research Group 
650 5th Street  
San Francisco, Ca 94107 
 
 
Title:  
Pulse oximeter accuracy during stable hypoxia plateaus 
Device Names: 
Nihon Kohden Pulse oximeter and sensors 
Regulatory Sponsor: 
Nihon Kohden Corporation 
Protocol Date: 
Version 1.0 November 7, 2025 
Study ID: 
75Ag-00030 
Amendment 1 Date:  
 
Amendment 2 Date:  
 

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Contents 
Aims ................................................................................................................................................. 4 
Reference: ........................................................................................................................................ 4 
Subjects ............................................................................................................................................ 4 
Investigational Device ...................................................................................................................... 5 
Procedures ........................................................................................................................................ 7 
Statistics ........................................................................................................................................... 8 
Data Analysis ................................................................................................................................... 8 
Subject Safety ................................................................................................................................ 10 
Risks and Benefits .......................................................................................................................... 10 
Risk Mitigations ............................................................................................................................. 10 
Informed Consent ........................................................................................................................... 10 
Adverse event reporting ................................................................................................................. 11 
Device Deficiencies ....................................................................................................................... 11 
Monitoring ..................................................................................................................................... 11 
Termination of the Study ............................................................................................................... 12 
Data Storage ................................................................................................................................... 13 
Amendments to the Protocol .......................................................................................................... 13 
Statement of Compliance ............................................................................................................... 13 
 
 
 
 

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Abbreviations and Definitions of Terms 
SpO₂ Peripheral capillary oxygen saturation 
SaO₂ Arterial oxygen saturation 
FDA Food and Drug Administration 
ISO 
International Organization for Standardization 
MST Monk Skin Tone 
ITA 
Individual Topology Angle 
BMI 
Body Mass Index 
CPAP Continuous Positive Airway Pressure 
COHb Carboxyhemoglobin 
MetHb Methemoglobin 
ctHb 
Total hemoglobin concentration 
ECG Electrocardiogram 
CRF 
Case Report Form 
VSRG Vital Sign Research Group 
PI 
Principal Investigator 
IRB 
Institutional Review Board 
SaDE Serious Adverse Device Effect 
UADE Unanticipated Adverse Device Effect 
Rms 
Root mean square  
ABL Radiometer ABL  
DUT Device Under Test 
NK 
Nihon Kohden  
 
 
 

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Aims 
This study aims to test the accuracy of Nihon Kohden pulse oximeters in range of arterial HbO2 
saturations from 100 down to 70%. This is done by comparing the pulse oximeter reading during a 
brief, steady-state hypoxia plateaus with a gold-standard measurement of blood oxyhemoglobin 
saturation, i.e., an arterial blood sample processed in a multi-wavelength hem oximeter. This study 
is designed in accordance with ISO and FDA regulatory standards. Nihon Kohden may submit the 
data obtained to the FDA for device clearance. 
 
Reference 
• 
ISO 80601-2-6:2024(E). DIS 
• 
ISO 14155:2020 
• 
Pulse Oximeters for Medical Purposes - Non-Clinical and Clinical Performance Testing, 
Labeling, and Premarket Submission Recommendations (FDA Guidance draft) 
 
Subjects 
Enrollment 
At least 48 subjects (up to 56 subjects) will be enrolled.  
According to ISO/DIS 80601-2-61:2024, it is required that 25% of all subjects be allocated to each 
MST category (1–4, 5–7, and 8–10). To ensure at least 24 subjects in each category, the study is 
designed to enroll a total of at least 96 subjects. We aim for a total of 98 subjects by combining 50 
cases from previous research with 48 new cases. To account for an anticipated dropout rate of 
approximately 15%, we plan to recruit 56 subjects for the current study. 
 
This study does not include socially vulnerable individuals as study subjects. 
 
Clinical Validation Study 
SpO2 data 
Subjects will have an average of 20 +/-4 SaO2-SpO2 data pair with a maximum range of 16-30 data 
points and 90% of participants will have at least one usable data point below 85% and at least 69% 
of subjects will have one usable data pair between 70-80%. 
 
SaO2 data 
When two ABLs are determined to be valid, the SaO2 reference value is the average of the SaO2 
measurements of the two ABLs.  The validity of ABL measurements is determined by the following 
procedure: 
• 
Check if the difference between two ABL readings is within 2% 
• 
If the difference between two ABL readings is within 2%, the readings of two ABLs are 
valid. 
• 
Readings of two ABL differed by more than 2% saturation will be excluded from the 
analysis. 
• 
If only one ABL returns the value, the value will be assumed to be correct. 
 
 
The skin tone distribution of subjects will be divided into 3 cohorts based on the Monk Skin Tone 
scale and ITA (Individual Topology Angle) determined at the dorsal distal phalanx. 
1) 
At least 30% of subjects will be Monk Skin Tone (MST) 1-4 with an ITA less than 30 
2) 
At least 30% of subjects will be MST 5-7 and have an ITA between -30 and 30 

Pulse Oximeter Accuracy during stable hypoxia plateaus Test Protocol 
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3) 
At least 30% of subjects will be MST 8-10 with an ITA less than -30 (with one half of MST 
8-10 subjects having an ITA of less than -50) 
4) 
In each MST group, at least 40% of participants are male, and at least 40% of participants 
are female. 
 
At least 33% of each sex will be included in the study. 
 
Inclusion Criteria 
1. The subject is male or female, aged 18 to 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 has a BMI above 40 
2. The subject has blood pressure above 160 systolic or 95 diastolic 
3. The subject has a known history of heart disease, lung disease, kidney or liver disease. 
4. Diagnosis of asthma, sleep apnea, or use of CPAP. 
5. Subject has diabetes. 
6. Subject has a clotting disorder. 
7. The subject has 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. 
(COHb<3%, MetHb＜2%, ctHb＞10 g/dL). 
8. The subject has any other serious systemic illness. 
9. The subject has smoked in the last 12 hours. 
10. Any injury, deformity, or abnormality at the sensor sites that in the opinion of the investigators 
would interfere with the sensors working correctly. 
11. The subject has a history of fainting or vasovagal response. 
12. The subject has a history of sensitivity to local anesthesia. 
13. The subject has a diagnosis of Raynaud’s disease. 
14. The subject has unacceptable collateral circulation based on exam by the investigator (Allen’s 
test). 
15. The subject is pregnant, lactating or trying to get pregnant. 
16. Subjects who have uneven skin tones at the forehead or the sensor site.  
17. The subject is unable or unwilling to provide informed consent or is unable or unwilling to 
comply with study procedures. 
18. The subject has any other condition, which in the opinion of the investigators would make them 
unsuitable for the study. 
 
Investigational Device 
This study is to evaluate the performance of the following pulse oximeter sensors shown in Table 1. 
Table 1. Study devices 
Device name 
Model name 
Pulse oximeter 
OLV-4202  
SpO2 probe 
TL-271T3 
SpO2 probe 
TL-273T3 
SpO2 probe 
TL-220T 

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SpO2 probe 
TL-631T 
SpO2 probe 
TL-201T_BASE1 
SpO2 probe 
TL-201T_BASE3 
SpO2 Connection Cord 
JL-400T 
 
Sensor Placement 
Table 2 and 3 shows how the sensors will be placed on the study subjects. 
 
Table 2. Sensor placement on the right-hand side 
Probe 
Subject  1, 4, 7, 10, 
13, 16, 19, 22, 25, 28, 
31, 34, 37, 40, 43, 46, 
49, 52, 55 
Subject 2, 5, 8, 11, 14, 
17, 20, 23, 26, 29, 32, 
35, 38, 41, 44, 47, 50, 
53, 56 
Subject 3, 6, 9, 12, 
15, 18, 21, 24, 27, 30, 
33, 36, 39, 42, 45, 48, 
51,54  
TL-201T_BASE1 
Index 
Middle 
Ring 
TL-201T_BASE3 
Middle 
Ring 
Index 
TL-220T 
Ring 
Index 
Middle 
 
 
Table 3. Sensor placement on the left-hand side 
Probe 
Subject  1, 4, 7, 10, 
13, 16, 19, 22, 25, 28, 
31, 34, 37, 40, 43, 46, 
49, 52, 55 
Subject 2, 5, 8, 11, 14, 
17, 20, 23, 26, 29, 32, 
35, 38, 41, 44, 47, 50, 
53, 56 
Subject 3, 6, 9, 12, 15, 
18, 21, 24, 27, 30, 33, 
36, 39, 42, 45, 48, 51, 
54 
TL-271T3 
Index 
Middle 
Ring 
TL-273T3 
Middle 
Ring 
Index 
TL-631T3 
Ring 
Index 
Middle 
 
Co-oximeter: 
3 ABL-90 multi-wavelength oximeter 
 
ECG monitor 
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. 
 
Safety of the investigational device 
Safety tests have been conducted for the probe (TL-201T-BASE1, TL-201T_BASE3, TL-631T3, 
TL-220T), and the validity of the device's performance has been confirmed. The sensor probes (TL-
271T3) have been approved in Japan and by the FDA in the US for measuring pulse oximetry. In 
addition, The OLV-4200 series has been approved in Japan as a pulse oximeter. Based on the 
above, we consider that there are no issues with the use of the investigational device and related 
equipment in this study. 
 
Device Accountability 
The investigational device used in the study is a single monitor identifiable by its serial number. 
The disposable pulse oximeter probes are designed for single-patient use, and the lot number will be 
recorded on each data collection form. 
 

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Procedures 
Subject skin tone will be measured and recorded by a calibrated colorimeter at the forehead, inner 
bicep and the are closest to the measurement site of the pulse oximeter.  MST and ITA scores shall 
be determined for each subject.   
 
Any nail bed coverings such as acrylic nails, gel-based manicures, nail jewelry, nail polish or long 
nails will be removed prior to testing. 
  
A local anesthetic is injected around the radial artery, and a 22-gauge catheter is inserted in the 
radial artery. Pulse oximeters/device under test will be attached to the fingers, Reference oximeter 
probes may be placed on non-testing fingers, these probes include a Nonin 7500 and Masimo-Rad 
97. ECG electrodes will be placed on the subject to monitor the subject’s heart rate. A quality 
control check of ECG monitor is performed before use. Sensors under test placement and serial 
numbers will be documented for each subject.  Subjects will be placed in a seated semi-reclined 
position. Subjects will breathe a nitrogen-air-carbon dioxide mixture to produce the desired level of 
hypoxemia. Stable, safe and controlled hypoxia is obtained by breath-by-breath analysis of 
respiratory gas using an CWE gas analyzer that permits the inspired gas mixture to be adjusted to 
achieve the desired degree of blood oxygen saturation.  
 
We will reduce subjects SpO2 to about the 90s, 80s and 70s, collecting four samples in each plateau 
where a blood sampling is taken, and the DUT measurement will be recorded simultaneously.  This 
equals 12 blood samples; we will do this twice to achieve 24 data pair samples, for a total of at least 
960 data pairs. Before desaturation, a blood sample is taken to ensure the subject meets the 
inclusion and exclusion criteria equaling 25 blood samples. At each plateau (90s, 80s, and 70s), in 
order to ensure that the arterial blood sample measured is from a stable state, a discarded blood 
sample (which will not be analyzed) is collected before the first blood sampling. Each level of 
saturation is held for up to 3 minutes.  Arterial blood samples are obtained from the radial artery 
catheter at least 20 seconds apart when SpO2 levels are stable.  Before sampling, the gas operator 
will keep the subject at a stable blood oxygen level for 45 seconds to ensure that the test pulse 
oximeter readings are stable.  During the test, a stable plateau is defined as a change in SpO2 levels 
being no greater than 2%.  SaO2 readings will also be reviewed during the test to determine the 
stability of the plateau.  SaO2 will be measured using three sets of co-oximeters (ABL-90 multi-
wavelength oximeter) that have undergone quality control and calibration by VSRG prior to use. 
The operator then changes the inspired air concentration to attain the next desired level of hypoxia.    
This takes about 10-15 minutes.  Each desaturation run is terminated by a breath of 100% O2 
followed by room air.  Two desaturation runs together enable obtaining a total of 20-25 blood 
samples.  Up to 30 samples may be obtained from each subject. A self-calibrated Radiometer ABL-
90 multi-wavelength oximeter determines the saturation of each arterial blood sample. The target 
saturation levels shall satisfy ISO and FDA standards for testing, which is 70% to 100%, with an 
approximate even distribution of samples in each of the decadal ranges of 70%-80%, 80%-90%, and 
above 90%.  Each Monk Skin Tone and ITA cohorts shall contribute approximately equal number 
of data points in each SaO2 decade range. 
 
The study takes about an 1 hour and 15 minutes of each subject’s time.  Total expected duration of 
the study is 10 days. 

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If the subject attests to being a smoker, the subject will be asked to abstain from smoking for 12 
hours prior to the study.  If the subject has a carboxyhemoglobin above 3% after taking the first 
blood sample the subject may be given 100% oxygen for about 20 minutes to lower their 
carboxyhemoglobin levels.   
 
Statistics 
The number of subjects and comparisons (paired-pulse oximeter readings and arterial saturation 
values) is determined by current FDA and ISO guidance requirements [2].  In this type of study, some 
subjects may drop out; some readings can be lost due to motion or other interference, and 
occasionally, some may not consent.   During analysis, plateau stability will be defined as a no-
greater-than change of 2.% SaO2 between blood samples.   
 
The following demographic data will be collected on the subjects: 
l Gender (male, female, other) 
l Age  
l Skin tone by Monk score determined by 3 observers.  In the case of disagreement, when 2 of 
3 values are the same, use that value. If there is disagreement between all observers, the 
middle value will be used.   
l Height (cm) 
l Weight (kg) 
l BMI 
l Dominant hand (left or right) 
l ITA / Monk skin tone values at the device under test site, forehead and inner bicep  
l Race 
l Ethnicity 
l Thickness of the measurement site (finger) 
 
The following CRFs will be used to record data and information: 
• 
Subject demographics CRF: Subject information will be recorded. 
• 
Adverse event CRF: An adverse event related or not related to the test devices will be 
recorded. 
• 
Subject withdrawal CRF: Any subject withdrawal after the subject signs informed consent 
will be recorded. 
• 
Device deficiency CRF: A deficiency occurred to the test devices will be recorded. 
• 
Protocol deviation CRF: Any deviation from the defined procedures as outlined in the 
protocol including mistake in recording of blood draw time will be recorded. 
 
Data Analysis  
Endpoints are ARMs and Bias. 
 
The blood analysis data are provided in all cases, including the SaO2, MetHb, COHb and Hgb 
concentration. After all subjects’ data have been collected, data management and statical analysis 
will be conducted by VSRG . ABL devices will be set to display the upper limit at 100%. The SaO2 
readings will not be provided to the sponsor until the device under test readings are provided to 
Vital Signs Research Group. The data analysis report will follow ISO 80601-2-61:2024.  A 
summary of the data analysis is as follows: 

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• 
A Table of the oximeter readings versus corresponding blood SaO2 values for each data pair 
and each cohort along with heart rate, heart rate from the device under test, assessment for 
stability for each arterial sample, all removed data points and justification, and perfusion 
readings from the device under test.  
• 
A modified Bland-Altman plot for each instrument or instrument/probe combination of the 
bias between the oximeter reading and the SaO2 measured by the hemoximeter. 
• 
A bland Altman plot of the hemoximeter vs the device under tests readings 
• 
Linear regression equations and plots for the bias of each instrument across the range of 
70% to 100% SaO2 
• 
Tables of the root mean square error or bias, its standard deviation, standard error, 95% 
confidence interval, maximum and minimum and root mean square error, all computed both 
overall and in each decadal range tested. 
• 
A table of the demographics of the subject population. 
• 
For each subject a mean bias will be calculated in the ranges of 70%-85% and 85% to 
100%. 
• 
A differential bias in the ranges of 70% to 85% and 85% to 100% will be reported by 
regressing each subject’s individual mean bias in each of the two SaO2 ranges vs ITA. 
• 
A graphical representation of the regression to determine differential bias will be provided 
along with a table.  
• 
Using the linear regressions, estimate the differential bias between the values at an ITA of -
50 and +50. 
• 
Tables of the root mean square error or bias, its standard deviation, standard error, 95% 
confidence interval, maximum and minimum and root mean square error, all computed both 
overall and in each decadal range tested for each MST group.   
• 
Tables of the root mean square error or bias, its standard deviation, standard error, 95% 
confidence interval, maximum and minimum and root mean square error, all computed both 
overall and in each decadal range tested for each sex.   
 
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. 
 
 
 
 
The analysis is limited to participants who complied entirely with the study protocol, including 
fulfilling all inclusion and exclusion criteria, undergoing the specified procedures, and completing 
all required assessments. 
 
Success criteria is as follows: 
Primary outcome measure 
SpO2 accuracy 
Rms of within ±3 [%SpO2] (70 to 100 [%]) 
Secondary outcome measure 
SpO2 accuracy 
Rms of within ±2 [%SpO2] (80 to 100 [%]) 
Rms of within ±3 [%SpO2] (70 to 80 [%]) 
 
Missing data will not be supplemented. If missing data occurs, the reason must be documented.  
The number of incomplete pairs and ratio of incomplete pairs will be calculated.  

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Data that meets the following conditions will be also thrown out: 
• 
The CO-oximeter experienced error conditions 
• 
Two CO-oximeter readings differed by more than 2% saturation 
• 
Data points from CO-oximeter at a plateau which differ by more than 2% from the average 
of the others 
• 
Data points from CO-oximeter which are the only ones at a plateau 
 
Demographic characteristics will be summarized using standard descriptive summaries (e.g. means 
and standard deviations for continuous variables such as age and percentages for categorical 
variables such as gender). 
 
Subject Safety 
Pulse oximeters are 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 absorbance ratio of different 
light wavelengths, the device calculates the oxygen saturation. 
 
Risks and Benefits 
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. This study will not seek to reach saturations below 70%. Hypoxia may cause tachycardia 
and increased blood pressure during the test.  A much more severe and prolonged lack of oxygen 
could cause brain injury or death, but the duration and depth of hypoxia are limited by the test protocol 
to short intervals. The needle catheter used to take blood may hurt when inserted despite local 
anesthesia, and there may be a black and blue spot afterward.  A vasovagal response due to the 
catheter placement is possible.  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 in healthy 
human subjects with an arterial line for such a short duration.  There are also risks of burns and skin 
problems from poor blood circulation. 
Subjects will not receive any direct personal benefit from participation in this study. 
 
Risk Mitigations 
Subjects are all monitored with accurate FDA approved reference oximeters and continuous end-tidal 
gas analysis to prevent the risk of more profound hypoxia than desired. The subject’s heart rate and 
blood pressure will be monitored throughout the study. Investigators are experienced 
anesthesiologists adept at assessing breathing and in maintaining appropriate airway conditions. The 
lab has all resuscitation equipment immediately available.  
A risk of burns and skin problems due to poor blood circulation can be avoided by not placing SpO₂ 
probes too tightly. 
 
Informed Consent 
Written informed consent is obtained before any study procedures. 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.  
 

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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.  
 
Adverse event reporting 
Adverse events and serious adverse events will be assessed throughout the study by the PI, or research 
nurse designated by the PI. If any adverse event occurs during the study, 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. 
 
Adverse Effects will be collected throughout the study on the source document worksheet and 
reported on the CRF.  Information reported on the CRF will include:  
• 
Adverse Effect diagnosis term to be determined by investigator. 
• 
A detailed description of the event.  
• 
The date of event onset.  
• 
The relatedness of the event to the device as determined by investigator. 
• 
Seriousness.  
• 
Actions taken as a result of the event.  
• 
The outcome of the event.  
• 
The date the investigator was first informed of the event.  
 
Unanticipated adverse device effect (UADE) and serious adverse device effects (SADEs) will be 
reported to the sponsor and IRB, as applicable, as soon as the PI becomes aware, but in no event later 
than 10 working days after the investigator first learns of the effect. 
 
Device Deficiencies 
All device deficiencies related to the investigational device will be documented throughout the 
duration of the clinical investigation. Information reported on the CRF will include: 
• 
Date device deficiency discovered 
• 
Date device deficiency occurred 
• 
Description of the device deficiency 
• 
Date of final observation 
• 
A device deficiency occurred during use on the subject. 
• 
An adverse event related to device deficiency occurred. 
• 
Description of the action taken 
 
Monitoring 
It is the responsibility of the sponsor to ensure proper monitoring of the study per regulations. 
Appropriately trained personnel or delegates appointed by the sponsor will perform study monitoring 
at the study center to ensure that the study is conducted in accordance with the protocol, the Clinical 
Trial Agreement, and applicable regulatory requirements. The sponsor must, therefore, be allowed 
access to the subject’s records as requested per the Informed Consent Form and Clinical Trial 
Agreement. 

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Monitoring visits will be conducted throughout the clinical study. Remote monitoring is acceptable. 
 
The frequency of monitoring visits will occur based on subject enrollment for each test, duration of 
the study, study compliance, findings from previous monitoring visits and any suspected 
inconsistency in data that requires investigation. Regulatory documents (e.g., Informed Consent 
Form, IRB/EC approval letters and Clinical Trial Agreements, etc.) will be reviewed at the study 
center. 
 
Monitoring visits may be conducted periodically to assess site study progress, the investigator’s 
adherence to the protocol, and regulatory compliance, including but not limited to IRB review and 
approval of the study, maintenance of records and reports, and review of source documents against 
subject CRFs. Monitors facilitate site regulatory and study compliance by identifying findings of non-
compliance 
and 
communicating 
those 
findings 
along 
with 
recommendations 
for 
preventative/corrective actions to site personnel. This may be done in collaboration with the study 
management and the local field personnel, if available. Communication with the site personnel occurs 
during and after the visit via a written follow-up letter. Monitors may work with study personnel to 
determine appropriate corrective action recommendations and to identify trends within the study or 
at a particular center. Study closure visits will be conducted via telephone, letter, or on-site at each 
enrolling study center. 
 
Termination of the Study 
The test will be discontinued when a subject requests to withdraw from the study, or the PI 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. 
 
If the principal investigator or sponsor determines that a significant violation of ISO 14155:2020, this 
protocol, or continued non-compliance or breach of the clinical investigation agreement constitutes a 
serious impediment to the proper conduct of the clinical investigation, the trial will be suspended. 
Such cases include: 
1. Concerns regarding the safety of the subjects 
2. Inability to collect appropriate data 
3. Discovery of significant falsification in records or reports 
4. Major deviations or non-compliance with the clinical investigation protocol (excluding cases 
where it is necessary to avoid imminent danger to the subject or for other unavoidable medical 
reasons) 
 
Either the principal investigator or the sponsor will notify the ethics committee of the suspension. 
The investigator will promptly inform the subjects of the suspension and take appropriate medical 
and other necessary measures. 
 

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Data Storage 
Identifiable subject information is always stored securely following all applicable rules and 
regulations.  Consent forms and other study related documents are retained following VSRG data 
retentions policy. 
 
Amendments to the Protocol 
Any amendments or revisions to the protocol shall be made in accordance with the Nihon Kohden 
Standard Operating Procedure “NKC03010-180038: Preparation and Revision of Clinical 
Investigation Plans and Case Report Forms”.  Such changes require prior approval from the Ethics 
Committee. The study shall not proceed under the amended plan until such approval has been 
obtained. 
 
Statement of Compliance 
This study will be conducted in compliance with the following: 
• 
ISO 80601-2-6:2024(E). DIS 
• 
ISO 14155:2020 
• 
Pulse Oximeters for Medical Purposes - Non-Clinical and Clinical Performance Testing, 
Labeling, and Premarket Submission Recommendations (FDA Guidance draft) 
• 
Declaration of Helsinki (2024 revision)