Clinical Evaluation of the RHEA Vital Sign Vigilance System in Hospital Patients
Phase: NA
Conditions: Vital Sign Monitoring
Sponsor: Darma Inc.

Protocol Number:  RHEA EL30-2017-001 
Clinical Evaluation of the RHEA Vital Sign Vigilance System in 
Hospital Patients 
Device:  
 
 
 
 
 
 
RHEA Vital Sign Vigilance System 
Model:  
 
 
 
 
 
 
EL30 
Sponsor: 
 
 
 
 
 
 
Darma, Inc. 
  
Contract Research Organization: 
Technical Resources International, Inc.  
Protocol Version：  
 
 
 
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TABLE OF CONTENTS 
1.
Key Roles 
5 
..................................................................................................................................
1.1.
Sponsor 
5 
1.2.
Sponsor Contact Person 
5 
......................................................................................................
1.3.
Contract Research Organization 
5 
.........................................................................................
2.
Introduction 
6 
.............................................................................................................................
2.1.
Background and Rationale 
6 
.................................................................................................
2.2.
Study Objectives 
7 
.................................................................................................................
3.
Study Design 
7 
............................................................................................................................
4.
Subject Selection 
8 
......................................................................................................................
4.1.
Inclusion Criteria 
8 
................................................................................................................
4.2.
Exclusion Criteria 
8 
...............................................................................................................
5.
Investigational Device and Reference Device 
8 
........................................................................
5.1.
Investigational Device Information 
9 
....................................................................................
5.2.
Design Principle and Characteristics 
9 
..................................................................................
5.3.
Device Components 
9 
...........................................................................................................
5.4.
Operation Training 
9 
.............................................................................................................
6.
Study Procedures 
10 
...................................................................................................................
6.1.
Screening 
10 
..........................................................................................................................
6.2.
Baseline 
10 
6.3.
Testing Procedures 
10 
...........................................................................................................
7.
Device Safety and Stability Evaluation 
12 
...............................................................................
7.1.
Safety Assessments 
12 
...........................................................................................................
7.2.
Stability 
13 
8.
Test Termination and Adverse Event Reporting 
13 
................................................................
8.1.
Adverse Device Effects 
13 
....................................................................................................
8.2.
Contact Information 
13 
.........................................................................................................
9.
Data Management 
13 
.................................................................................................................
9.1.
Data Handling 
14 
...................................................................................................................
9.2.
Data Entry and Validation 
14 
................................................................................................
10. Statistical Analysis 
14 
.................................................................................................................
10.1. General Statistics Design 
14 
..................................................................................................
10.2. Primary Variables 
14 
.............................................................................................................
10.3. Primary Analyses 
15 
..............................................................................................................
10.4. Secondary Analyses 
15 
..........................................................................................................
10.5. Subgroup Analyses 
16 
...........................................................................................................
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10.6. Sample Size 
16 
......................................................................................................................
11. Regulatory and Reporting Requirements 
17 
...........................................................................
11.1. IRB Approval  
17 
..................................................................................................................
11.2. Informed Consent 
17 
.............................................................................................................
11.3. Clinical Monitoring 
17 
..........................................................................................................
11.4. Confidentiality 
18 
..................................................................................................................
12. Risk-Benefit Analysis 
18 
............................................................................................................
13. References 
19
..............................................................................................................................
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE  
 
 
Adverse Event 
CRF 
 
 
Case Report Form 
ECG 
 
 
Electrocardiogram 
EDC 
 
 
Electronic Data Capture 
etCO2 
 
 
End-tidal CO2 
FDA 
 
 
U.S. Food & Drug Administration 
GCP 
 
 
Good Clinical Practice 
HR  
 
 
Heart Rate 
ICU 
 
 
Intensive Care Unit 
ID  
 
 
Identification 
IEC  
 
 
International Electrotechnical Commission 
IRB 
 
 
Institutional Review Board 
LoS 
 
 
Length of Stay 
mm  
 
 
Millimeter 
RMSD  
 
Root Mean Square Difference 
RR  
 
 
Respiratory Rate 
sqrt  
 
 
Square Root 
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1.
Key Roles 
1.1.
Sponsor 
Darma Inc. 
1172 Castro St, Mountain View 
California 94040 
1.2.
Sponsor Contact Person 
Wu Zicui 
Master of Biomedical Engineering 
Regulatory Affairs and Quality Assurance Manager 
(415) 439-3645 
zicui@darma.co 
1.3.
Contract Research Organization 
Technical Resources International, Inc. 
6500 Rock Spring Drive, Suite 650 
Bethesda, Maryland 20817 
(301) 564-6400 
  
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2.
Introduction 
2.1.
Background and Rationale 
The IntelliVue Patient Monitors MP/MX series (with the etCO2 module) is an FDA-approved 
device made by PHILIPS MEDIZINSYSTEME BOEBLINGEN GMBH (FDA 510(k) clearance 
K161531). It is commonly used in U.S. hospital and serves as the gold standard for the 
measurement of heart rate (HR) derived from an ECG signal and for the respiratory rate (RR) 
derived from etCO2 density. However, it requires attachment to the patient’s body, and cable 
connection to a display unit. 
The RHEA Vital Sign Vigilance System was developed by Shenzhen Fiber Medical Technology 
Co. Ltd.  It is designed for automatic, continuous and contact-less measurement of heart rate and 
respiratory rate of patients in a hospital or clinic setting. The system uses a sensor placed under 
the patient’s mattress, and does not require a sensor to be fixed to the body. This provides a more 
comfortable solution for long-term continuous patient monitoring. Continuous monitoring of 
people's vital signs, in particular heart rate (HR) and respiratory rate (RR), may provide a 
mechanism to alert doctors or nurses of disease deterioration or an imminent severe clinical 
event. Monitoring people's vital signs outside an ICU often relies on nursing staff conducting 
checks at set intervals. The device can reduce the workload for nursing staff in non-ICU wards. 
The FDA-cleared EarlySense System 2.0 (K131379) developed by EarlySense Ltd. is also a 
contact-less system designed for continuous monitoring heart rate and respiratory rate of 
patients. It has been sold in over 20 U.S. hospitals since 2013. No recalls and adverse events 
have been reported. According to publicly available clinical results, the EarlySense System has 
shown an 86% reduction in Code Blue events, and a 45% reduction in Length of Stay (LoS) in 
the ICU for patients coming from the medical/surgical unit (1, 2). The EarlySense device applies 
the piezoelectric sensor while in comparison, the RHEA investigational device applies the optical 
fiber sensor. This difference leads to the RHEA device having a higher accuracy, capacity for 
greater patient weight range, longer sensor life and a lower cost. A Pilot Study on 25 healthy 
volunteers (20 adults and 5 children) showed that the RHEA device can obtain accuracy of 
overall mean root mean square difference (RMSD) of both HR and RR of 1.9 with the same 
testing procedure described in this current protocol (3). When comparing with the reference 
device- the EarlySense device on 9 adults, the RHEA device obtained results with no significant 
difference (pair t test is used to evaluate the results according to this protocol.) 
Heart beat or respiratory movement produces a slight vibration which cannot be observed 
visually. However, the fiber sensor contained in the RHEA sensor unit will be deformed by the 
vibration, resulting in a change in the optical signal being transmitted. This changed optical 
signal is received by the bedside unit and converted into an electrical signal. The HR and RR 
then can be calculated by the bedside and displayed in real-time. The change in the optical signal 
can also be used to determine if the patient has exited the bed with a notification displayed on the 
bedside unit. 
The system is intended for use as a ‘contact-free’ under-mattress device monitoring heart rate 
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and respiratory rate during sleep or resting condition, and to notify users when the patient exits 
the bed. The data can be displayed, exported and reviewed. 
This protocol aims at verifying the safety and effectiveness of the investigational device in a 
general-care clinical environment. 
2.2.
Study Objectives 
This clinical trial aims to verify that the RHEA Vital Sign Vigilance System can fulfill its 
intended use and meet its declared performance and functional specifications. Statistical analysis 
comparing the performance of the RHEA Vital Sign Vigilance System and the reference device 
EarlySense System 2.0 to the MP/MX series separately aims to demonstrate that the 
investigational device is substantially equivalent to the cleared reference device-EarlySense 
System 2.0 in safety and effectiveness. 
3.
Study Design 
This will be a cross-over, ‘self-controlled’ study comparing the investigational device RHEA 
Vital Sign Vigilance System to an approved under-mattress device, EarlySense System (Model 
2.0) (K131379). Both will be compared to the ‘gold standard’ Philips MP/MX series model 
Patient Monitor. The same Monitor Device must be used across all hospital wards in this study. 
The testing will be conducted in three periods. In the Accuracy Tests (periods 1 and 2), one of the 
contact-free devices will be used to monitor the HR and RR, while being compared with the MP/
MX series Patient Monitor. The RHEA investigational device and reference device will be used 
to monitor the same subject at different times (cross-over design), as the sensors of the two 
devices are placed at a similar location of the bed. HR and RR will be recorded for all three 
devices. Comparison of the performance of the two contact-free devices will be performed on the 
recorded results via statistical analysis. The third test will assess the ability of the RHEA device 
to accurately detect motion on or exit from the bed, as compared to the manual observation. 
Three clinical trial sites will be selected in the U.S. A total of 77 adult subjects will be enrolled 
to complete 73 subjects (5% drop-out rate anticipated). Please see Section 10 for Sample Size 
justification. A site may enroll no more than half the total number of subjects for the study; i.e., 
up to 39 total subjects per site.  It is anticipated that 33 days are needed for 77 recruited patients 
in total. 
The testing duration for each subject will be one to two hours, including device placement, 
measurements, and device removal. 
This is a multi-center study to be conducted in three hospitals. Wards in each site should be 
representative of non-ICU wards in U.S. hospitals (e.g., medical/surgical, oncology, orthopedics, 
long term acute care). 
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4.
Subject Selection 
Subjects will be hospitalized patients in general care non-ICU settings, who fulfill the following 
inclusion and exclusion criteria. 
4.1.
Inclusion Criteria 
Subjects will be included if they meet the following inclusion criteria: 
1. Male or female, 18 years old and above. 
2. Provide written informed consent. 
3. Weight ranging from 20 to 150 kg inclusive. 
4. Are located in a non-ICU hospital setting. 
5. Agree to not eat during the testing period. 
6. Agree to keep still. 
4.2.
Exclusion Criteria 
Subjects will be excluded if they have any of the following inclusion criteria: 
1. Are connected to a device which may interfere with the device monitoring in this study. 
2. Are receiving any bedside care which may be incompatible with the study procedures. 
3. Sleep apnea. 
4. Pregnant or breast feeding. 
5. A likely need to receive or undergo a procedure during the testing period. 
6. Cannot accept a nasal cannula, or have a monitor lead placed on the chest. 
7. A significant medical condition in the judgement of the investigator, which may compromise 
the study testing procedures. 
8. Are wearing pacemaker or defibrillator. 
5.
Investigational Device and Reference Device 
The RHEA Vital Sign Vigilance System EL30 developed by Shenzhen Fiber Medical 
Technology Co. Ltd are designed for continuous and contact-less measurement of heart rate and 
respiratory rate. The system will also notify users when the patient exits the bed. The following 
devices will be used in this study. 
Table 1:  Study Devices  
Product name 
Model 
Manufacture
Clearance 
number
Investigational 
device
RHEA Vital Sign Vigilance 
System
EL30
Shenzhen Fiber Medical 
Technology Co. Ltd.
N/A
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5.1.
Investigational Device Information 
The RHEA Vital Sign Vigilance System is designed for continuous and contact-less 
measurement of heart rate and respiratory rate. The system will also notify users when the patient 
exits the bed. The system is intended for continuous measurement of respiration rate and heart 
rate for adults (≤150kg), in an automatic contact-less manner, in a hospital or clinic setting 
during sleep or resting condition. 
The setup includes placing a sensor under the mattress, and a bedside unit on a nearby flat 
surface that can be viewed by the investigator. 
5.2.
Design Principle and Characteristics 
Heart beat or respiratory movement produces a slight vibration which cannot be observed by the 
eyes. However, the fiber sensor contained in the sensor unit will be deformed by the vibration, 
resulting in a change in the optical signal being transmitted. This changed optical signal is 
received by the bedside unit and converted into an electrical signal. The heart rate and respiratory 
rate then can be calculated by the bedside and displayed in real-time. The change in the optical 
signal can also be used to determine if the patient has exited bed and a notification will be 
displayed on the bedside unit. The system does not require a sensor to be fixed to the patient 
body. This provides a more comfortable solution for long-term patient monitoring and solve the 
cable problems. 
5.3.
Device Components 
The system incorporates the following three components: 
•
The bedside unit with battery [35 mm(Height) ×241mm (Width) × 600mm (Length]  
•
The sensor unit [30mm (Height) ×165mm (Width) × 261mm (Length)] 
•
Proprietary exporting data software 
5.4.
Operation Training 
Investigators will be trained on the device prior to beginning the study. The training will include: 
basic information regarding the investigational device, device preparation, operational 
instructions, device considerations, possible faults and their solutions, test contents, basic 
requirements and procedures, and records related to the control of the test. 
Reference device
EarlySense System
Model 
2.0
EarlySense Ltd
K131379
Gold Standard 
device
IntelliVue Patient Monitors
MP/MX 
Series
PHILIPS MEDIZINSYSTEME 
BOEBLINGEN GMBH
K161531
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6.
Study Procedures 
6.1.
Screening 
Patients will be screened to assess eligibility per the inclusion and exclusion criteria. Patients 
must provide written informed consent before being enrolled in the study. 
Review of the eligibility criteria checklist will be recorded on the Case Report Form (CRF). 
6.2.
Baseline 
The following information will be recorded prior to beginning the testing procedures: 
•
Gender, age. 
•
Height and weight. 
•
Location (ward/unit) where the subject is located. 
•
Clinical diagnosis (primary, and secondary if applicable) 
6.3.
Testing Procedures 
The test will be conducted in three parts: 
•
Reference Device accuracy test 
•
Investigational Device accuracy test 
•
Motion and bed exit test 
The following terms are used in the testing procedures below: 
•
Investigational Device (RHEA device) 
•
Reference Device (EarlySense device)  
•
Monitor Device (Gold Standard MP/MX series device) 
Reference Device Accuracy Test 
1.
Two testers (Reference Device tester and Monitor Device tester) will record the following 
subject information in the CRF: subject ID, gender, height, weight, primary clinical 
diagnosis, time, site location (hospital and ward). 
2.
Place the Reference Device sensor unit under the mattress and beneath the chest of the 
subject according to the instructions for use. Place the bedside unit on a flat surface. 
3.
Synchronize the date and time of the Reference Device and the Monitor Device (to be 
equivalent). 
4.
Place the main units of the Reference Device and the Monitor Device in different locations in 
the subject’s room such that they can only be viewed by their respective testers. 
5.
After the subject lies down on the bed, place the Monitor Device lead on the subject’s chest 
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in accordance with the operational instruction of the Monitor Device. 
6.
Connect the etCO2 module to the Monitor Device and apply the nasal cannula to the subject. 
7.
Turn on the Monitor Device and the Reference Device. Set the Monitor Device to “real-time 
monitoring mode”. 
8.
Instruct the subject to remain motionless.  At one-minute intervals, the two testers will 
simultaneously record the heart rate (HR), respiratory rate (RR) and the current time using 
their respective device. 
9.
If the HR or RR value does not appear, or turns blurred on the screen (in this state only the 
last value is displayed rather than the current value), the Reference Device tester will mark it 
on the CRF. 
10. Stop the test once 20 valid pairs of data are recorded for each subject. If certain values are 
marked (per Step 9 above), the data at that recorded point will not considered in the analysis. 
More than 20 pairs will be collected in order to ensure that there are at least 20 valid pairs. 
Investigational Device Accuracy Test: 
1. Two testers (Investigational Device tester and the Monitor Device tester) will record the 
following subject information in the CRF: subject ID No., gender, height, weight, primary 
clinical diagnosis, time, site location (hospital and ward). 
2. Place the Investigational Device sensor unit under the mattress and beneath the chest of the 
subject. Place the bedside unit on a flat surface or hang on the wall using the bracket. 
3. Calibrate the device in accordance with the operator’s manual. 
4. Synchronize the date and time of the Investigational Device and Monitor Device (to be 
equivalent). 
5. Place the main units of the Investigational Device and the Monitor in different locations in 
the subject’s room such that they can only be viewed by their respective testers. 
6. After the subject lies down on the bed, place the Monitor Device lead on the subject’s chest 
in accordance with the operational instruction of the MP/MX series Patient Monitor. 
7. Connect the etCO2 module to the Monitor device and apply the nasal cannula to the subject. 
8. Turn on the Monitor Device and the Investigational Device. Set the Monitor Device to “real-
time monitoring mode”. 
9. Instruct the subject to remain motionless. At one-minute intervals, the two testers will 
simultaneously record the HR, RR and the current time using their respective device. 
10. If HR or RR value does not appear or turns darker and with a mark “?” after the value on the 
screen (in this state only the last value is displayed rather than the current value), the 
Investigational Device tester will mark it on the CRF. 
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11. Stop the test once 20 valid pairs of data are recorded for each subject. If certain values are 
marked (per Step 10 above), the data at that recorded point will not considered in the 
analysis. More than 20 pairs will be collected in order to ensure that there are at least 20 valid 
pairs. 
Motion and Bed Exit Test:
This test will be conducted only on subjects who can move and exit the bed easily. 
The Monitor Device tester will ask the subject to turn or move ten times and exit the bed for 
three times randomly in five minutes. The Monitor Device tester will record the time of these 
events on the CRF. At the same time, the Investigational Device tester will observe if there is an 
“unexpected motion” or “bed exit” notification on the screen of the Investigational Device and 
will record the time of this event on the CRF. 
Device Testing Considerations: 
1. At the baseline for each subject, make sure the following information is recorded: subject 
ID, date of birth, gender, height, weight, location, time and clinical diagnosis. Adverse 
events should be recorded and kept during the tests. The record should be signed by the 
testers. 
2. It is important that nothing be allowed to shake the bed during the test. Anything that will 
produce vibration (such as a phone or another person) is not allowed to be on the bed during 
the test. 
3. Make sure there is sufficient stable time before the HR and RR results are recorded for the 
Investigational Device and Reference Device. Thirty seconds is considered to be reasonable 
for Investigational Device and 1 min for Reference Device. That is to say, if the subject has 
to turn, stand up or move during the test, record data 30 seconds after the subject lies down 
and keeps still again. One minute should be left between two record groups for the 
independence of the data. If the subject moves or is out of the bed, record data 30 seconds 
after the subject lies down and keeps still again. 
7.
Device Safety and Stability Evaluation 
Safety and stability data should be recorded in the CRF for Investigational device only. 
7.1.
Safety Assessments 
Included but shall not be limited to the following: 
1)
Electrical shock 
2)
Loose components leading to device failure 
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3)
Failure of the device to resume normal operation after power is interrupted 
7.2.
Stability 
Included but shall not be limited to the following: 
1)
Failure in starting the device 
2)
System shuts off unexpectedly during use 
3)
System pauses unexpectedly during use 
8.
Test Termination and Adverse Event Reporting 
The Investigators will complete training before using the devices on any subjects. There is 
minimal risk of electric shock, overheating, or other mechanical harm from the devices. 
8.1.
Adverse Device Effects 
If an Adverse Event (AE) occurs, the Investigator should terminate the test and take appropriate 
measures to treat the subject. 
The Investigator will report unanticipated adverse device effects and adverse events to the IRB 
and the Sponsor no later than 10 working days after the Investigator first learns of the effects, 
and record it in the CRF. The date, time, treatment given, outcome, and relationship to the device 
in use should be recorded. 
If a Serious Adverse Event happens, investigator should terminate the test and take appropriate 
treatment measures to the subject. The Investigator should also report to the IRB and the 
Sponsor, and the Sponsor should report to the authority 5 working days after he knows, and will 
notify the other investigators taking part in this trial. 
8.2.
Contact Information 
Sponsor：Darma Inc. 
Contact Person: Wu Zicui 
Master of Biomedical Engineering 
Regulatory Affairs and Quality Assurance Manager 
Email: zicui@darma.co 
Phone number：415-439-3645 
9.
Data Management 
The Sponsor or designee will provide the sites with source document templates although sites 
may use their standard documentation processes if these collect all required data. Data will be 
reported to the sponsor through an Electronic Data Capture (EDC) system, which will include 
automated checks for completeness and accuracy. All users will attend a training webinar before 
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they are given access to the EDC system. Data should be entered in the EDC system not later 
than 48 hours after each subject testing. The Investigator is responsible for maintaining accurate, 
complete and up-to-date records for each subject. 
9.1.
Data Handling 
The investigators should record the data clearly and correctly in the EDC based on observations 
on the subjects as collected in the source documents. 
The sponsor should monitor whether the test is proceeding as per the protocol and make sure the 
CRF is reliable, complete and accurate. If omission and mistakes are found, the Investigator will 
make corrections in the EDC. 
9.2.
Data Entry and Validation 
Data entered in the EDC system will be reviewed by the sponsor. If incomplete or inaccurate 
data are found a data clarification request will be forwarded to the site for a response. Manual 
and automated discrepancies will be presented to the site user for resolution or justification.  A 
sponsor representative will review the justification for all unresolvable discrepancies and will 
close or re-query them. Once all discrepancies and queries have been resolved, the Investigator 
will review the data and confirm their accuracy with his/her electronic signature in the EDC. 
10. Statistical Analysis 
10.1. General Statistics Design 
•
Investigation site selection: three sites will be selected: 
•
Randomization: consecutive selection: selecting every subject in the order they present in 
the site if they meet the inclusion/exclusion criteria till it reach the pre-specified number. 
•
Blinding: Two investigators observe the results from the investigational device and 
reference device separately. Time-stamp method (see time synchronization as described 
in Section 6.3, Testing Procedures) will be used in the comparison. 
10.2. Primary Variables 
The primary variables for the analysis of heart rate (HR) and respiratory rate (RR) are each the 
overall mean root mean square difference (RMSD), defined as the mean of the individual subject 
RMSDs.  For each subject, the RMSD is calculated as: 
RMSD = sqrt{ Σ(YR – YG)2/n} 
where YR and YG are the paired values for the RHEA Vital Sign Vigilance System and the gold 
standard method (Patient Monitor), respectively, and n is the number of data pairs. If motion or a 
bed exit occurs within 20 seconds preceding the recording period for a given data pair, the data 
pair at that time point will not be used in the analysis. A total of 20 pairs of measurements are 
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planned for each subject. If more than 20 measurements are collected for a subject, then only the 
first 20 will be used. If fewer than 20 measurements are collected for a subject for any reason, 
that subject will still be included in the analyses. 
The primary hypotheses for HR, are as follows: 
Adults 
HO: µ = 3.25 
vs. 
HA: µ < 3.25, 
The primary hypotheses for RR, are as follows: 
Adults 
HO: µ = 2.25 
vs. 
HA: µ < 2.25, 
where µ represents the population mean HR or RR. 
10.3. Primary Analyses 
For each subject, the RMSD will be calculated for both HR and RR. These individual values will 
be presented in both a listing and graphically as a cumulative distribution. The mean RMSD and 
its two-sided 95% confidence interval (mean RMSD ± t0.975 * std err RMSD) will be presented. 
If the upper bound of the confidence interval is less than the hypothesized value, the 
corresponding null hypothesis will be rejected. For each rejected hypothesis, the study will have 
met its primary objective. 
10.4. Secondary Analyses 
Accuracy of the RHEA will be compared with that of the Reference Device-EarlySense device. 
The RMSD for the Reference Device will be calculated for each subject in the same manner as 
described for the RHEA. Mean accuracy will then be compared between the RHEA and the 
Reference Device by comparing the individual subject RMSDs by a paired t test at the 5% level 
of significance. 
Bland Altman plots will be presented separately for each subject’s raw data, including the limits 
of agreement, for both the RHEA and the Reference Device methods. In addition, Bland Altman 
plots will be presented for the set of RMSD estimates across all subjects, along with two-sided 
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95% confidence intervals for their limits of agreement. Finally, Bland Altman plots of the raw 
data across all subjects will be presented, along with two-sided 95% confidence intervals for 
their limits of agreement. Methods discussed in Bland, JM and Altman, DG (4) and (5) will be 
used to calculate the confidence intervals of the limits of agreement due to the lack of 
independence of the repeated measurements on the same subject. 
Motion and no motion accuracy will each be calculated along with their respective two-sided 
95% confidence intervals. Motion accuracy will be calculated as the proportion of times that the 
device correctly detected motion among all actual occurrences of motion detected manually. 
Non-motion accuracy will be calculated as the proportion of times that the device correctly did 
not detect motion among all actual occurrences of no motion detected manually. 
10.5. Subgroup Analyses 
Between subject subgroup analyses will include the following subgroups: 
•
Primary disease 
•
Type of hospital ward 
•
Body weight in quartiles 
•
Study site 
Each subgroup analysis will be based on a one-way analysis of variance on the individual 
RMSDs which includes the subgroup as the factor. Each analysis will be done at a significance 
level of 0.05. 
Within subject subgroup analyses will be performed to compare results under awake and asleep 
conditions. The RMSD will be calculated for each subject while awake and while asleep. Mean 
RMSDs will be compared by paired t tests at a significance level of 0.05. 
10.6. Sample Size 
In a pilot study of 20 adult healthy volunteers with 20 paired observations each, the standard 
deviation of their RMSDs vs. the reference method were found to be approximately 0.75 for both 
HR and RR (2). Based on this standard deviation, 73 adult subjects will provide 80% power to 
reject each primary hypothesis if the population mean RMSD for HR is 3.0 and the population 
mean for RR is 2.0. To account for a dropout rate as high as 5%, a total of 77 adult subjects will 
be enrolled. 
SAS Version 9.4 PROC POWER was used for all sample size calculations. 
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11. Regulatory and Reporting Requirements 
11.1. IRB Approval  
The investigator will ensure that IRB review and approval are obtained before beginning the 
study, or allowing any subject to participate. The Investigator will notify the Sponsor of any 
withdrawal of IRB approval of the study. 
Any deviation from the investigational plan shall be reported to the Sponsor, and to the IRB per 
its requirements. Any revision to this protocol cannot be implemented without approval from the 
IRB and the Sponsor. The Investigator will submit a final report to the IRB after termination or 
completion of the study. 
11.2. Informed Consent 
The Investigator shall ensure that informed consent is obtained from subjects or their guardians.   
11.3. Clinical Monitoring 
The Sponsor or designee will be responsible for monitoring of compliance with the trial protocol, 
GCPs, and all applicable federal regulations concerning human subject research. The study 
monitors will perform on-site monitoring visits, including source document verification, device 
accountability, and assess compliance with safety reporting in accordance with Sponsor’s 
procedures and all applicable regulatory requirements. The Investigator will agree to give full 
access of all study data, site procedures, and other relevant information to the study monitor (and 
auditor if needed) during each site visit. 
At the site initiation visit the Sponsor or designee will review the study protocol and all 
associated study documentation and procedures with the Investigator and study personnel. All 
site personnel will receive training for device use and use of the data collection tool, as 
appropriate to their role.  In addition, study-specific GCP training will be provided. 
During the course of the study, the Sponsor or designee will maintain regular contact with the 
investigative sites and may conduct on-site monitoring visits and/or source data verification on a 
regular basis to ensure compliance with this study protocol. 
The investigators shall conduct this study in accordance with this protocol. Failure to comply 
with and/or inability to meet these regulations may jeopardize further participation of the 
Investigator or investigative site in this and future clinical studies. 
Investigators must report major protocol deviations that affect the safety and welfare of subjects 
or affect integrity of study (or if the investigator deviated from the protocol in order to save a life 
or prevent further harm to the subject) to the Sponsor within 5 working days of investigational 
site knowledge of the deviation. 
a.
Monitoring Method and Times 
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On-site visits will be made 3 times for each site when: 
•
the 1st patient completes testing 
•
the 5th patient completes testing 
•
the 15th patient completes testing 
Remote monitoring will be done for the following items: 
•
Data on EDC system; 
•
Feedback from the investigators; 
•
Signature of the informed consent. 
b. On-site monitoring procedures 
1.
Check if the device is used per the User’s Manual. 
2.
Check if the investigator performs the procedures as per the clinical protocol and if there 
is any deviation from the protocol. 
3.
Check if subjects meet the inclusion criteria and excluded per the exclusion criteria. 
4.
Check if the informed consent is obtained before the testing. 
5.
Check the data, the date on the CRF. Check the consistency of CRF. Mark the 
questioned data and require the investigator to validate or correct it. 
6.
Check device preservation condition and device quantity to make sure to provide 
supplement in time. 
7.
Check if there is adverse event and if the adverse event is recorded. 
8.
Keep the monitoring record. 
If there is any discrepancy or inconsistency found in remote monitoring, Sponsor can issue 
queries and require investigator to submit justification or corrections. 
11.4. Confidentiality 
Disclosure or making public the clinical research results to a third party is not allowed without 
written approval from the Sponsor. Documents provided by the Sponsor should be kept 
confidential. 
Investigator shall maintain accurate, complete, and current records relating to the Investigator’s 
participation 5 years after the completion or termination of the study, in a confidential and secure 
manner. 
12. Risk-Benefit Analysis 
This clinical trial aims at demonstrating the RHEA Vital Sign Vigilance System can fulfill its 
intended use and meet its accuracy and specification criteria. The contact-less manner of 
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monitoring can solve current cable management problem. It will decrease the possibility of 
accident arising from cables or leads. It also makes it possible to collect more vital sign 
information for analysis and diagnosis, in a more comfortable manner to the patient in long-term 
care monitoring. 
The sensor of the RHEA Vital Sign Vigilance System will be placed under the mattress during 
the whole test. There is no patient contact part. The RHEA Vital Sign Vigilance System has been 
tested under the International Electrotechnical Commission (IEC) technical standards IEC 
60601-1, IEC 60601-1-2, IEC 62304 and IEC 62366. Bench tests have been performed to help to 
ensure the safety of the system for this clinical trial. 
The possibility of electricity shock, over heat, mechanical harm, over voltage and 
biocompatibility harm are small due to the above analysis. Training on the investigators before 
the clinical trial can also help in preventing the occurrence of the harm. 
In conclusion, clinical trial on the Investigational Device may bring some risks, but the 
occurrence probability and severity of all risks have been minimized. Therefore, it is determined 
that the benefits of the product are more significant than the risks. 
13. References 
1. EarlySense Proactive Patient Care (http://www.earlysense.com/news-and-events/news/mar-20-2014/) 
2. Harvey Brown, MD, Jamie Terrence, RN (2014), Continuous Monitoring in an Inpatient 
Medical-Surgical Unit: A Controlled Clinical Trial, The American Journal of Medicine 127: 
226-232. 
3. Pilot Study (January 17, 2017) and Pilot Study (March 25, 2017) 
4. Bland JM, Altman DG (2007) Journal of Biopharmaceutical Statistics 17:571–82 
5. Bland, JM and Altman, DG (1999) Statistical Methods in Medical Research 8:135-160 
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Investigator Statement 
I agree to： 
1.
Conduct the clinical trial per Declaration of Helsinki, FDA regulations and this protocol. 
2.
Start the clinical trial only after IRB approval is obtained. 
3.
Start the clinical trial testing on each subject only after informed consent is obtained. 
4.
Fulfill the obligations in the signed agreement. 
I have read all the contents of the protocol including the statement above. I agree to all of 
contents above. 
Sponsor   
Name:  
Signature:  
Date:
Investigator 
Name:  
Signature: 
Date:
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