Correlation of Changes in PaO2 and ORi in Adult Patients
Conditions: Hyperoxia
Sponsor: Masimo Corporation

 
 
 
 
Official Title: Correlation of Changes in PaO2 and 
ORi in Adult Patients 
 
Date of Protocol: 22 January 2018 
 
NCT Number:   
NCT03488238 

CLINICAL INVESTIGATION PLAN 
FLEM0007 
Correlation of Changes in PaO2 and ORi in Adult Patients 
Version: 1 
 
CONFIDENTIAL AND PROPRIETARY   
© 2021 Masimo Corporation (Unpublished) 
All Rights Reserved 
Page 1 of 16 
 
 
 
 
Correlation of Changes in PaO2 and ORi in Adult Patients 
 
Sponsor: 
Masimo 
52 Discovery 
Irvine, California 92618 
 
 
Principal Investigator: 
Neal W. Fleming, MD, PhD 
 
 
 
Study Devices: 
Masimo Radical 7 rainbow pulse oximeter device  
  Masimo Root Patient Monitoring and Connectivity Platform 
Masimo rainbow disposable sensors  
 
 
 
Sponsor Protocol Number: 
FLEM0007 
 
 
IRB: 
Office of Research 
University of California, Davis 
1850 Research Park Drive Suite 300 
Davis, California 95618 
 
 
 
 
Principal Investigator 
 
Neal Fleming, MD, PhD 
Title 
 
Professor of Anesthesiology & Pain 
Medicine 
Signature 
Date 
Sponsor 
 
Cristina Johnson 
Title 
 
Clinical Research Compliance 
Manager 
Signature 
Date 
 

Correlation of Changes in PaO2 and ORi in Adult Patients  
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1 
 INTRODUCTION 
This document is a clinical investigational plan for a human research study. The study will be conducted in accordance with 
the ethical principles that have their origin in the Declaration of Helsinki. By participating in the study, the Investigator 
agrees to adhere to all stipulations of this protocol, the conditions of IRB approval, federal and local regulatory requirements, 
21CFR 812, ISO-14155 and International Conference on Harmonization Good Clinical Practice guidance ICH GCP.  
1.1 
Background and Rationale 
Masimo Corporation is the developer of noninvasive technologies for the measurement and monitoring of physiological 
variables, such as arterial oxygen saturation (SpO2), total hemoglobin concentration (SpHb), carboxyhemoglobin 
concentration (SpCO), methemoglobin concentration (SpMet), acoustic respiration rate monitoring (RAM), and cerebral and 
regional oximetry (rSO2, O3TM). These technologies are noninvasive and have a good patient safety record.  
A continuous supply of oxygen is essential for normal cell function. Failure of a patient’s oxygen supply to meet metabolic 
needs is common to all forms of circulatory failure, tissue acidosis, and ultimately mortality. Like all essential commodities 
for body functions, optimal quantities of oxygen are required. A patient’s oxygen status can be largely classified into 3 
ranges: Hypoxia (less than normal), Normoxia (normal) and Hyperoxia (more than normal). The three states are typically 
classified using dissolved oxygen levels in the plasma (PaO2), instead of arterial hemoglobin oxygen saturation (SaO2), due 
to sensitivity of PaO2 in all three states including hyperoxia (unlike SaO2). Figure 1 shows the three oxygen states based on 
PaO2 values along with the relationship between PaO2 and SaO2. 
 
Figure 1: The oxygen dissociation curve with the three oxygen states 
In order to prevent episodes of hypoxia, patients in critical care are administered a certain amount of supplemental oxygen to 
prevent hypoxia and improve safety in situations where the oxygen supply may be lost intermittently. However this excess 
supply should be in moderation as large amounts of oxygen may result in lung damage or other complications. Hence it 
becomes imperative to monitor the amount of surplus oxygen in blood. 
Currently, clinicians monitor a patient’s oxygen status, both continuously and non-invasively, using a pulse oximeter to 
obtain SpO2 (a proxy for SaO2) levels. However, SpO2 is sensitive in the normoxic and hypoxic regions and largely remains 
flat in the hyperoxic region (Figure 1). Clinicians consequently must resort to invasive blood sampling to obtain PaO2 values 
for oxygen status within the hyperoxic zone. This method has multiple drawbacks such as limited information from 

Correlation of Changes in PaO2 and ORi in Adult Patients  
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intermittent sampling to potential delay due to the time difference between blood draw and when the PaO2 value is obtained 
through blood gas machines, and potentially significant loss of blood due to multiple blood draws. 
The Oxygen Reserve Index (ORi) is a reference that could help clinicians with their assessments of normoxic and hyperoxic 
states by scaling the measured absorption information between 0.00 and 1.00. The scale was obtained by observing the 
changes in absorption measurements in a large group of healthy volunteers as they transitioned between normoxic and 
hyperoxic regions. An ORi of 0.00 corresponds to PaO2 values of 100mmHg and below and an ORi of 1.00 corresponds to 
PaO2 values of 200mmHg and above. Refer to Figure 2. 
While not a direct measurement of PaO2, ORi provides a continuous and non-invasive index which correlates with changes 
in PaO2 values in the range of 100 to 200mmHg. 
ORi together with pulse oximetry may provide useful reference information about a patient’s partial pressure of oxygen in 
arterial blood (PaO2) and the transition between oxygen regions such as moving from normoxic to hypoxic regions. This can 
be useful during clinical applications such as during endotracheal intubation, in which unintended desaturations may occur. 
Additionally, ORi may be used as reference information for clinicians when they monitor the patient’s reserve oxygen 
supply. 
 
Figure 2: PaO2 vs SaO2 and SvO2 
This protocol is designed to evaluate the correlations between ORi and PaO2 and the potential use of ORi as an early 
warning of impending arterial oxygen desaturation.                                                                                                                                                 
 
2 
STUDY OBJECTIVES 
2.1 Specific aims: 
- evaluate the clinical utility of the change in the Oxygen Reserve Index as an early warning of impending arterial 
oxygen desaturation in  adult patients  
- characterize the correlations between the Oxygen Reserve Index and the arterial oxygen content during pre-
oxygenation and induction of general anesthesia in adult patients 

Correlation of Changes in PaO2 and ORi in Adult Patients  
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2.2 Hypothesis (constructed as the null):  
Intraoperative changes in ORi will not correlate with increases in arterial oxygen content during pre-oxygenation or induction 
of general anesthesia and ORi will not provide clinically significant additional warning of impending arterial desaturation. 
3 
STUDY DESIGN 
This is a prospective, non-blinded, non-randomized study of the Oxygen Reserve Index (ORi) in a clinical setting. It is 
designed to evaluate the correlations with ORi and PaO2 and the potential use of ORI as an early warning of 
impending arterial oxygen desaturation. 
3.1 
Study Endpoints 
This is a prospective clinical study designed with the following endpoints: 
 
Primary endpoint – measure the PaO2and it’s correlation with changes in ORi (ORi) during the 
induction of general anesthesia in patients in whom continuous arterial pressure monitoring is a planned 
component of the anesthetic monitoring. 
 
Secondary endpoint – evaluate the potential clinical utility of the ORi as an early warning for impending 
desaturation. 
4 
CLINICAL TEST SITE 
University of California Davis Medical Center 
2315 Stockton Blvd, Sacramento, CA 95817 
5 
SUBJECT SELECTION AND WITHDRAWAL 
5.1 
Number of Subjects 
A minimum of 22 completed subjects will be needed for the study with enrollment of a maximum of 100 subjects. 
5.2 
Inclusion Criteria 
 
Age greater than 18 years 
 
ASA physical status III or IV 
 
Scheduled for an elective surgical procedure requiring endotracheal intubation and the use of an arterial 
pressure monitoring catheter placed prior to induction of general anesthesia 
5.3 
Exclusion Criteria 
 
Age less than 18 years 
 
Adults unable to give primary consent 
 
Pregnancy 
 
Prisoners 
5.4 
Study Timelines 
- Each individual patient will participate only for the duration of their anesthetic induction which may vary from 5 to 15 
minutes. 
- This study is anticipated to require up to 3 months for completion of patient enrollment. 
- Primary analysis of the data is expected to require an additional 6 months. 

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5.5 
Subject Recruitment and Screening 
Patient recruitment and informed consent will be obtained in the UCDMC perioperative suite. Recruitment will be by direct 
discussion between the prospective candidates and the study investigators prior to their scheduled surgical procedure. The 
investigators will provide the consent form in person and give the prospective subject sufficient time to review the consent 
form and discuss the study with friends and family. 
All items of the Informed Consent will be explained in a way that is easily understandable. The patient will be given adequate 
time to read through the Informed Consent, and they will be given adequate time and privacy to consider the decision of 
whether or not to sign the Informed Consent Form. Once all of the patient’s questions have been answered and the Informed 
Consent Form signed, the patient is now adequately consented. Now the patient will be enrolled as a study subject, at which 
time the subject will be assigned a study identification number or enrollment number.  
All subjects will have their medical history reviewed at the time of screening by either the PI or the study staff who is 
delegated for this task. Subjects will be evaluated based on the inclusion and exclusion criteria to determine eligibility to be 
enrolled into the study. If a subject is deemed ineligible after screening, the subject will be withdrawn from the study.  
Information regarding the subject’s demographic (including, but not limited to age, weight, race, ethnicity, etc.), preexisting 
allergies, skin abnormalities, and other preexisting diseases/conditions that may be relevant to the study will be recorded 
within a paper-based Case Report Form (CRF).  
HIPAA 
The screening of patients will require the investigators to access personal health information to identify prospective subjects 
without HIPAA authorization.  The research could not be practicably carried out without this waiver of consent.  The risk of 
harm from contacting the participants is greater than the risk of the study procedures. The research is of minimal risk and 
does not involve any procedures for which written consent is normally required outside the research setting. The participants’ 
rights and welfare will not be adversely affected by waiving consent. This protected health information will not be 
inappropriately reused or disclosed to any other person or entity. To further safeguard all protected health information, the 
data will not be labeled with any personal identifying information, or with a code that this research team can link to personal 
identifying information. The data will not be stored with any protected health information identifiers. 
5.6 
Early Withdrawal of Subjects 
5.6.1 
Withdrawal of Individual Subjects 
Subjects can leave the study at any time for any reason if they wish to do so without any consequences or loss of benefits to 
which they are otherwise entitled.  Subjects may be withdrawn from the study prior to expected completion for reasons such 
as safety concerns, failure to adhere to protocol requirements, subject consent withdrawal, etc.   
Any data collected until the time of subject withdrawal may be included in the final data analysis. Information on the 
subject’s withdrawal should be documented in the case report form and should include clear documentation of the reason for 
withdrawal to the Sponsor. 
5.6.2 
Follow-up for subjects withdrawn from study 
None. There are no long term effects anticipated from participating in this study. 
5.6.3 
Data from individual subjects after withdrawal 
In case a subject leaves the study prematurely, the data collected may be included in data analysis. 
6 
STUDY DEVICE  
6.1 
Study Device 
The Masimo Radical-7 is a noninvasive monitor that measures arterial oxygen saturation (SpO2), pulse rate (PR), and 
perfusion index (PI), along with optional measurements of hemoglobin (SpHb), carboxyhemoglobin (SpCO®), total oxygen 

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content (SpOC), methemoglobin (SpMet), Pleth Variability Index (PVI®), Oxygen Reserve Index (ORI™), Acoustic 
Respiration Rate (RRa®), and Pleth Respiration Rate (RRp). Masimo SET® technology is clinically proven to satisfy all 
sensitivity and specificity requirements for pulse oximetry. Masimo rainbow® technology uses 7+ wavelengths of light to 
continuously and noninvasively measure carboxyhemoglobin (SpCO), methemoglobin (SpMet), and total hemoglobin 
(SpHb®), as well as providing a more reliable probe-off detection. Total oxygen content (SpOC) provides a calculated 
measurement of the amount of oxygen in arterial blood, which may provide useful information about oxygen both dissolved 
in plasma and combined with hemoglobin. Perfusion Index (PI) with trending capability indicates arterial pulse signal 
strength and may be used as a diagnostic tool during low perfusion. Pleth Variability Index (PVI) may show changes that 
reflect physiologic factors such as vascular tone, circulating blood volume, and intrathoracic pressure excursions. [The utility 
of PVI is unknown at this time and requires further clinical studies. Technical factors that may affect PVI include probe 
malposition and patient motion.] Oxygen Reserve Index (ORI) is an index measured noninvasively and continuously to 
provide an earlier indication of impending hypoxia by extending oxygen monitoring of pulse-oximetry to the moderate 
hyperoxic regions. Respiration rate can be determined by the acoustic (RRa) or plethysmographic waveform (RRp). Signal 
IQ is a feature for signal identification and quality indication during excessive motion and low signal to noise situations. 
FastSat® tracks rapid changes in arterial O2. A detailed description of the Masimo Radical-7 can be found in the attached 
manual. For this study, the software in Radical-7 has been modified to enable the measurement of the oxygen reserve index 
(ORI). This modified software has not been cleared by the FDA. 
The Masimo Root System is also being used in this study. The Root System is indicated for use by healthcare professionals 
for the monitoring of multiple physiological parameters in healthcare environments. The Root works together with the 
Radical-7 to display data. The Root serves as a convenient alternative user interface to integrate modules to provide health 
care professionals the ability to access, control and monitor measurement technologies (within the respective modules) that 
have been previously cleared by the FDA. 
Rainbow Adhesive Sensors are FDA cleared for the measurement of functional oxygen saturation of arterial hemoglobin 
(SpO2), pulse rate (PR), perfusion index (PI), pleth variability index (PVI), carboxyhemoglobin saturation (SpCO), 
methemoglobin saturation (SpMet), total hemoglobin (SpHb) and total oxygen content (SpOC). Although no modifications 
are required for the Rainbow Adhesive sensors for the study, the sensors have not been cleared for the indications for use of 
measuring ORi. 
 
6.2 
Risk/Benefits 
Benefits: There is no specific benefit to the individual subjects for participation in this research protocol.  
Sensor risks: As with all optical sensors, the investigational device has the risk of thermal burn. Pulse CO-oximeter 
noninvasive measurement uses wavelengths in the red and near infrared range like a conventional pulse oximeter used in 
routine clinical practice for over 15 years. The additional LEDs from Rainbow sensors have been tested and meet the Exempt 
classification for photo-biological safety of light sources.  
All patient-contact materials, including the adhesive used in the design of the Masimo Rainbow sensors, have been subjected 
to biocompatibility tests per ISO 10993-1 and results demonstrate that the materials are non-toxic, non-irritating, and non-
sensitizing. The sensors have been subjected to performance, mechanical, and electrical testing and results demonstrate that 
the sensors meet the requirements for safety and effectiveness for the intended use of the product. 
No other physical, financial, social or psychological risks are anticipated to be associated with participation in this study as it 
only observation with the recording of intraoperative ORI and ABG measurements. Precautions taken to safeguard protected 
personal health information are described in the section on recruitment.  The risks associated with the anesthetic and surgical 
procedure are not discussed in this proposal. 

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6.3 
Device Accountability 
6.3.1 
Receipt of Study Device 
Upon receipt of the of the study device supplies, an inventory must be performed and the device accountability log filled out 
and signed by the person accepting the shipment.  It is important that the designated study staff counts and verifies that the 
shipment contains all the items noted in the shipment inventory.  Any damaged or unusable study devices in a given shipment 
will be documented in the study files.  The investigator must notify the study sponsor of any damaged or unusable study 
devices that were supplied to the investigator’s site. 
6.3.2 
Use of Study Device 
Use of devices and sensors will be documented on case report forms for each subject. Any unused devices must be returned 
to the Sponsor at the end of the study or before product expiration date. 
6.3.3 
Return or Destruction of Study Device 
At the completion of the study, there will be a final reconciliation of study devices and sensors shipped, devices/sensors used, 
and devices/sensors remaining.  This reconciliation will be logged on the device accountability log.  Any discrepancies noted 
will be investigated, resolved, and documented prior to return or destruction of unused study devices.  Devices destroyed on 
site will only be upon written instruction from the sponsor and will be documented in the study files. 
 
6.3.4 
Device Deficiencies 
Device deficiencies are defined as the inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance. Record all device deficiencies on the case report form and report to the Sponsor. 
7 
STUDY PROCEDURES 
7.1 Following arrival of the patient in the operating room all standard and planned physiological monitors will be placed.  A 
baseline ORi will be measured and an arterial blood gas (ABG) sample will be collected for measurement of the PaO2.  
7.2 As per routine, the patient will then be pre-oxygenated with 100% oxygen.  When the ORI plateaus, a second ORI will 
be recorded and ABG sample collected. 
7.3 General anesthesia will be induced with a combination of amnestics, narcotics, intravenous induction agents and muscle 
relaxants as clinically indicated.  With stable mask ventilation, a third ORI will be recorded and ABG sample collected 
immediately prior to initiating laryngoscopy and endotracheal intubation. 
7.4 Intubation will be under direct visualization using a GlideScope. When the arterial hemoglobin saturation reaches 94% a 
fourth ORi will be recorded, an ABG sample will be collected and ventilation will be initiated with 100% oxygen either 
via the endotracheal tube or resumed mask ventilation. 
7.5 A final post-induction ORi measurement and ABG sampling will occur 5 minutes following initiation of controlled 
ventilation with 100% oxygen. 
 
This planned protocol sequence can be summarized graphically as: 

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Arterial blood gas measurement: ABG samples will be analyzed using Radiometer’s ABL blood gas analysis system.  Each 
sample will use 0.5 mL of blood for a total blood volume of 2.5 mL for this study. 
8 
STATISTICAL PLAN 
8.1 Sample Size 
The same sample size calculation used for the healthy subjects is used to determine the sample size for this study with 
sick subjects, which is calculated to be a minimum of 22 subjects. Based on this, the sample size for the study with 
sick subjects is established as the following for 95% confidence interval: 
 
 
Number of Subjects 
Number of Invasive 
Measurements per Subject 
Number of Noninvasive 
Sensors Per Subject 
22 minimum4 
4 minimum 
1 minimum 
8.2 Acceptance criteria 
In accordance with ISO-80601-2-61, SpO2 accuracy is determined as accuracy root mean square (ARMS), where 
SpO2 measurements are compared with reference SaO2 measurements. However unlike SpO2, ORi is an index 
value without a unit and ORi does not directly measure PaO2. Therefore, sensitivity and specificity analysis is used 
to evaluate ORI’s performance relative to the changes in PaO2. 
Although concordance calculation is based on sensitivity and specificity analysis, concordance analysis is not 
applicable for the sick subjects because of the lack of sample size. Thus the specifications for ORI are the 
following: 
 
Specificity of PaO2 vs. ORI > 80% 
 
Sensitivity of PaO2 vs. ORI > 85% 
 
Concordance of PaO2 vs. ORI > 80% 
Where PaO2 is the change in PaO2 and ORi is the change in ORi. These specifications are based on the study by 
Applegate et al. The Applegate study evaluated the ORI to PaO2 relationship during surgery of 106 patients. The data 
showed that decreasing ORI had 77.7% sensitivity and 76.7% specificity for detecting decreasing PaO2. 
In determining specificity and sensitivity, ΔPaO2 and ΔORi are defined as: 
ΔPaO2 = PaO2(t) – PaO2(tref) 
ΔORI = ORI(t) – ORI(tref) 
Where tref is the time of the sample closest to PaO2threshold in a ± 10 mmHg window. Thus, a ± 10 mmHg window is 
used as it is not possible to draw a blood sample at the exact value of PaO2 threshold. 
Samples with ΔPaO2 of ± 10 mmHg are ignored.  
 

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8.3 Statistical analysis 
Similar statistical analysis as described in the study with healthy subjects (TP-Clinical-0001) will be performed on 
the data for this study with sick subjects. However unlike healthy subjects, the FiO2 levels for sick subjects cannot 
be easily varied. Therefore, substantially fewer PaO2 samples are available for sick subjects. As a result, all PaO2 
samples for sick subjects are accounted for in data analysis even if the PaO2 sample is outside the 100 to 200 
mmHg range. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3: Specificity and Sensitivity Illustration for ΔPaO2 vs ΔORi 
In accordance with Figure 3, the following relationships are defined as: 
            Specificity =                       N1 / (N1 + N4), where tref is the baseline sample time 
Sensitivity = 
N3 / (N2 + N3), where tref is the sample time at the end of 100% pre-oxygenation. 
9 
SAFETY AND ADVERSE EVENTS 
9.1 
Definitions 
The definitions for adverse event, adverse device effect, serious adverse event, serious adverse device effect, and 
unanticipated adverse device effect are provided below (ISO 14155:2011, 21 CFR 812.3(s)). 
 
Adverse Event (AE): an adverse event is any untoward medical occurrence in a subject which need not be related to 
the device under investigation. 
 
Adverse Device Effect (ADE): an adverse device effect is any untoward or unintended response to a medical device 
which may result from insufficiencies in the instructions for use or deployment of the device, or from use error.  
 
Serious Adverse Event (SAE): a serious adverse event is an adverse event that results in death, inpatient 
hospitalization, severe or permanent disability, a life threatening illness or injury, fetal distress, fetal death, a 
congenital abnormality, a birth defect, or medical or surgical intervention to prevent permanent impairment to body 
or structure. 

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 
Serious Adverse Device Effect (SADE): a serious adverse device effect is an adverse device effect that results in 
death, inpatient hospitalization, severe or permanent disability or is life threatening. 
 
Unanticipated Adverse Device Effect (UADE): any serious adverse effect on health or safety or any life threatening 
problem or death cause by or associated with, a device, if the effect, problem, or death was not previously identified 
in nature, severity or degree of incidence in the investigational plan, or application (including a supplementary plan 
or application) or any other unanticipated serious problem associated with a device that related to the rights, safety 
or welfare of subjects.  Refer to the Device Risk Analysis and Risk Assessment section for details on anticipated 
adverse device effects. 
9.2 
Anticipated Adverse Events: 
Mild allergic reaction to sensor material and adhesives. 
Discomfort, redness or skin irritation.  
9.3 
Adverse Event Reporting: 
 
All Adverse Events, both Anticipated and Unanticipated, must be recorded in the within the CRF and in the Adverse 
Event Report Form. 
 
All Adverse Events must be promptly reported to the Sponsor.  
 
All Unanticipated Adverse Device Effects will be also reported to both the Sponsor and the IRB.   
 
Both Serious Adverse Events and Unanticipated Adverse Device Effects must be reported to the Sponsor within 48 
hours. All other Adverse Events should be reported to the Sponsor within 5 business days.  
 
All Serious Adverse Events will be also reported to the IRB per IRB reporting requirements.  These reports may 
include, but will not be limited to: date of onset; brief description of the events; their treatment; whether they 
resulted in death, inpatient hospitalization, severe or permanent disability or were life threatening; their relationship 
to the study device; and resolution. 
9.4        Deviations from the study protocol 
Deviations from the protocol must receive both Sponsor and the investigator’s IRB approval before they are initiated with the 
exception that under emergency circumstances, deviations from the CIP to protect the rights, safety and well-being of human 
subjects may proceed without prior approval of the sponsor or the EC. Any protocol deviations initiated without Sponsor and 
the investigator’s IRB approval that may affect the scientific soundness of the study, or affect the rights, safety, or welfare of 
study subjects, must be documented and reported to the Sponsor and to the investigator’s IRB as soon as a possible, but no 
later than 5 working days of the protocol deviation. If protocol deviations continue to occur frequently at a study site, a 
corrective and preventive action (CAPA) may be opened by the Sponsor.   
9.5         Withdrawal of IRB approval 
An investigator shall report to the sponsor a withdrawal of approval by the investigator’s reviewing IRB as soon as a 
possible, but no later than 5 working days of the IRB notification of withdrawal of approval. 
 
10 
VULNERABLE POPULATIONS 
10.1 
Definition 
10.1.1 
Vulnerable populations are defined as disadvantaged sub-segment of the community requiring utmost care, special 
considerations and protections in research. This study will recruit subjects from the following: economically 
disadvantaged or unemployed, educationally disadvantaged, and limited English skills and/or Non-US citizens.  
10.2 
Protection of vulnerable subjects  
 
There is no compensation provided for economically disadvantaged subjects to eliminate possibility of undue 
influence due to financial incentive. 
 
Educationally disadvantaged subjects will be provided ample time to ask questions and comprehend information.  

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 
Medical care will be provided to these subjects if they are injured as a direct result of participating in this research 
study. The cost of treatment for any research related injury will be covered by Masimo.  
10.3 
Responsible Parties  
 
The IRB will review research with vulnerable populations and evaluate consent, level of risk, coercion, and the 
reason for choosing this particular subject population. The IRB will be responsible for determining what practices 
will include continuing review for compliance while monitoring these studies.  
 
The Investigator holds the ultimate responsibility for protecting the rights, safety, and welfare of research subjects 
by ensuring that all regulations and proper documentation of consent is handled in a compliant and timely manner. 
11 
DATA MANAGEMENT 
11.1 
Confidentiality of Records 
Information about the patients will be kept confidential. The data will be stored on a password protected database on a secure 
server, accessible only to the Investigators.  Study data that will be released to Masimo and other regulatory authorities will 
be de-identified and will only pertain to study data collection, demographics, finger location of the sensor, and the recordings 
from the pulse oximeter.  
11.2 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial.  Source data are contained in source documents.  Examples of 
these original documents and data records include: hospital records, clinical and office charts, laboratory notes, memoranda, 
recorded data from automated instruments, and copies or transcriptions certified after verification as being accurate and 
complete. For this study, the case report forms may also be used as source worksheets.  
11.3 
Case Report Forms 
The Site shall capture study data in the CRFs for each subject enrolled. The CRFs will be completed and initial and dated by 
the PI or delegated personnel. This also applies to those subjects who fail to complete the study. If a subject withdraws from 
the study, the reason must be noted on the CRF. Case report forms are to be completed on an ongoing basis. CRF entries and 
corrections will only be performed by study site staff, authorized by the investigator. Entries and corrections to the CRF will 
be made following Good Documentation Practices.  
The CRF will include the following information, including but not limited to: inclusion/exclusion criteria, whether patient 
consent obtained before start of study, demographic information, device readings, and if occurrence of any adverse event, 
protocol deviation, and device deficiencies, etc. The CRFs will be signed by the PI to attest that the data is complete and 
accurate and forward a copy to Masimo.  
CRF entries will be verified by study monitor and any errors or inconsistencies will be queried to the site on an ongoing 
basis. Any changes will be made directly on the paper CRFs and re-verified. Query resolution will be assessed and confirmed 
by study monitor during site visit. The monitor or study manager will collect original completed and signed CRFs at the end 
of the study. A copy of the completed and signed CRFs will remain on site 
11.4 
Data Transfer and Storage 
The information will be stored in a password protected electronic database at the study site.  Device data along with an 
electronic copy of the CRF will periodically be securely uploaded to sponsor via secure FTP portal. Only authorized sponsor 
personnel will have access to the transferred data, and will move it to a secure and backed-up drive at Masimo.  
CRFs will be checked for accuracy and completeness of data. If there are inconsistent or missing data points, a data query list 
will be generated and submitted to the PI or designee, who shall both follow GDP practices for data correction by striking 
through the old entry, adding in new entry with initial and date, and resend to Masimo the corrected CRF. Once all queries 

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have been resolved, Masimo engineers are notified that data is ready for analysis. To ensure data integrity, Masimo engineers 
will only have read access to study data, therefore are unable to unintentionally tamper with the original data files.  
11.5 
Record Retention 
All study information, including but not limited to study correspondence, study logs, device accountability records, consent 
forms, subject records, and copies of CRFs should be maintained in the Investigator site files.   
Study records shall be retained during the study and for a minimum of two years after date of study closure or date when 
records are not required to support 510(k) clearance. The Institution’s own retention policies and regulations may apply in 
addition to the minimal requirement.  
The Sponsor is responsible for verifying study data, retaining records, analyzing data, and authoring study reports. 
12 
MONITORING PLAN 
12.1 
As the sponsor of this clinical investigation, Masimo Corporation is required by 21 CFR Part 812, of the Food and 
Drug Administration regulations to monitor and oversee the progress of the investigation.  The monitor(s) assigned 
by Masimo Corporation to this task will be a direct employee from the Clinical Research department trained on 
departmental SOPs on conduct and monitoring of sponsored studies. 
12.2 
In accordance with good clinical practices guidelines, there will be at least three scheduled monitoring visits to 
ensure overall regulatory compliance of the study: 
• 
An initiation visit, prior to any subject enrollment to confirm site readiness, and to document training on the 
study protocol and procedures, and use of equipment. 
• 
At least one monitoring visit during enrollment, when about 10-15% done and/or every year  
• 
A final close out visit after the last patient had finished the study.  
12.3 
The monitor will contact and visit the investigator and will be allowed, on request, to have access to all source 
documents needed to verify the entries in the CRFs and other GCP-related documents (IRB approvals, IRB 
correspondences, and ICFs) provided that subject confidentiality is maintained in agreement with HIPAA 
regulations.  
12.4 
It will be the monitor's responsibility to inspect the CRFs at regular intervals throughout the study, to verify the 
adherence to the CIP and the completeness, consistency and accuracy of the data being entered on them.  
12.5 
During each visit, the monitor will also verify presence of informed consent, adherence to the inclusion/exclusion 
criteria, and documentation of SAEs/SADEs and protocol deviations/violations, and check CRF against source 
documentation. 
12.6 
After each visit, the monitor will provide a monitoring report to the investigator within 4 weeks of visit completion. 
The monitoring report will detail findings and open action items observed during the visit. It is the responsibility of 
the Principal Investigator and Study Coordinator(s) to respond to the findings of the monitoring report, and complete 
any open action items as soon as possible but no later than 60 days of receiving the monitoring report. Any open 
action items not completed within the time allowed may be sufficient grounds for study site suspension or 
termination; it will be up to the sponsor to determine whether any incomplete action items are sufficient grounds for 
suspension or termination. See Section 13 for details on suspension and termination.  
12.7 
Depending on the quality of the data and/or changes to factors affecting patient safety, additional monitoring visits 
may be necessary according at the sponsor’s discretion. 
 

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13 
ADMINISTRATIVE ASPECTS 
 
13.1 
Protection of Human Subjects 
Per 21 CRF 50, written consent must be obtained from each subject or from their legal guardian prior to any study procedures 
in accordance with applicable federal, state, and study site regulations. The Investigator must keep a copy of the signed 
consent form in each subject’s record and provide a copy to the subject as well. The Investigator shall not allow a subject to 
participate in a study or sign consent prior to IRB approval.  
Prior to the start of data collection or subject enrollment, the Investigator must provide documentation of IRB approval of the 
study protocol and a copy of the approved informed consent form (21 CFR 50).  
All subjects will be monitored closely throughout the study. The following measures will be taken to ensure the privacy of 
subjects: 
 
A code (unique identification) number for each subject will be kept on file. 
 
Only their correspondence identification number will identify subjects. 
 
Access to the documents and data will only be made to the Investigators and study staff in the study.  
 
The confidentiality of these documents will be protected to the extent provided by the law.  
13.2 
Institutional Review Boards 
The Sponsor and/or Investigator must submit the protocol to the appropriate IRB and obtain a copy of the written and dated 
approval letter.  
The approval letter should state the name of the documents reviewed, date of review, date of approval, and reference the 
study name (protocol title, study number, and version). 
The informed consent used by the Investigator must be reviewed and approved by the Sponsor prior to submission to the 
IRB. The Investigator cannot enroll subjects until a copy of the approved informed consent is obtained from the IRB.  
Any amendments to the protocol or informed consent should be submitted to the IRB for review and approval per 21 CFR 56. 
The IRB should be notified of any changes that may affect conduct of the study or pose safety risks to the subjects. 
13.3 
Confidentiality 
All data collected will be kept confidential and de-identified. It can only be accessed by researchers and will be used for 
research purposes only.  
13.4 
Protocol Amendments 
Any changes made to the clinical investigational plan/study protocol will be documented by way of an amendment. Before 
submitting protocol amendment to the IRB for approval, the protocol amendment must be agreed upon and signed by both 
the Investigator and the Sponsor. The Investigator shall not make any changes to the protocol without Sponsor approval and 
documented approval from the IRB. Both PI and Sponsor will retain the IRB approval letter and approved protocol as 
confirmation that the protocol amendment was approved.  
13.5 
Suspension or Termination of Study Site 
The Sponsor can suspend or prematurely terminate the PI’s and study site’s participation in the study, particularly if Sponsor 
finds serious non-compliance by the PI or site, and if such non-compliance was not resolved in a timely manner. The Sponsor 
will document the decision to suspend or terminate the investigation in writing. A suspended study site cannot enroll new 
subjects.  
If the Sponsor determine that the study site’s compliance to GCP and federal regulations to be inadequate at any point during 
the study, and Sponsor move to suspend or terminate the study site, the Sponsor will provide notification in writing to the 
principal investigator and IRB as necessary. The study site is eligible for reinstatement upon correction of any findings and 

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any open action items prior to the suspension, and provides a written guarantee that the same non-compliance will not 
reoccur in the future. Site can only resume patient enrollment upon receiving written notification of reinstatement from the 
Sponsor and/or IRB.  
13.6 
Termination of Clinical Investigation/Study due to UADE 
The clinical investigation may be terminated if Sponsor determines that an unanticipated adverse device effect presents an 
unreasonable risk to the subjects. Termination shall occur not later than 5 working days after the Sponsor makes this 
determination, and not later than 15 working days after the Sponsor first received notice of the effect.  
The Sponsor may resume the terminated clinical investigation with prior IRB approval if the device is non-significant risk.  
14 
AGREEMENT BETWEEN INVESTIGATOR AND SPONSOR REGARDING RESPONSIBILITIES FOR 
GOOD CLINICAL PRACTICE 
International Conference of Harmonization (ICH) E6 Good Clinical Practice guidance is an international ethical and 
scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human 
subjects. 
It specifies general requirements intended to: 
 
Protect the rights, safety and well-being of human subjects, 
 
Ensure the scientific conduct of the clinical investigation and the credibility of the clinical investigation results, 
 
Assist sponsors, monitors, investigators, ethics committees, regulatory authorities and other bodies involved in the 
conformity assessment of medical devices. 
The Principal Investigator of the clinical investigation shall: 
 
Obtain and maintain IRB approval of the study. 
 
Ensure all subjects are consented prior to enrollment, per FDA Code of Federal Regulations titled 21 CFR 50. 
 
Ensure only appropriately trained personnel will be involved in clinical investigation. 
 
Maintain study records mentioned in the CIP. 
 
Maintain logs for study team delegation, site visit/monitoring, equipment disposition, study team training, subject 
recruitment and enrollment. 
 
Evaluate all adverse events and adverse device effects and determining whether the study is safe to continue. 
 
Allow the sponsor to conduct periodic monitoring of study activities to ensure GCP compliance. 
 
Not promote device prior to clearance by FDA for commercial distribution, except for academic purposes and 
scientific presentations. 
The Sponsor shall insure existence and record of all necessary compliance documents, and will conduct monitoring visits to 
ensure appropriate conduct of the study. 
15 
REVISION HISTORY 
 
Version Number 
Version Date 
Summary of Revisions Made: 
1 
14Nov2017 
Original version  
16 
REFERENCES 
 
Martin, L. (1999). All you really need to know to interpret arterial blood gases, page 73, Lippincott Williams & Wilkins. 
D. S. Martin and M. P. W. Grocott III. , Oxygen therapy in anaesthesia: the yin and yang of O2 Br. J. Anaesth. (2013) 
111 (6): 867-871 doi:10.1093/bja/aet291 

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Habre W1, Peták F2. Perioperative use of oxygen: variabilities across age. Br J Anaesth. 2014 Dec;113 Suppl 2:ii26-ii36. 
doi: 10.1093/bja/aeu380 
ISO-80601-2-61:2011, Medical Electrical Equipment: Particular Requirements for Basic Safety and Essential 
Performance of Pulse Oximeter Equipment for Medical Use 
Applegate et al., The relationship between oxygen reserve index and arterial partial pressure of oxygen during 
surgery, International Anesthesia Research Society, 2016 (See Appendix 7.1) 
Applegate RL, Dorotta IL, Wells B, Juma D, Applegate PM. Relationship Between Oxygen Reserve Index and Arterial 
partial Pressure of Oxygen During Surgery.  Anesthesia & Analgesia, 2016;123:626–33 
Oxygen Reserve Index (ORITM). Available at: http://www.masimo.co.uk/pdf/ori/LAB8543A_Whitepaper_ORI_British.pdf 
Accessed March 11, 2016 
Szmuk p, Steiner JW, Olomu PN, Ploski RP, Sessler DI, Ezri T. Oxygen Reserve Index: A novel Noninvasive Measure of 
Oxygen Reserve – A Pilot Study. Anesthesiology 2016; 124:779-84