Validation of the Performance of the COBOX Solution for Measuring Heart Rate and Respiratory Rate
Phase: NA
Conditions: Anyone Who Meets the Eligibility Criteria Can Use the Software
Sponsor: Quantiq.io

Validation of the performance of the COBOX
solution for measuring heart rate and respiratory
rate
Clinical investigation protocol under article 62.1 of regulation 745/2017 relating to a class IIa
medical device: COBOX
Version 1.0.0
IDRCB No.: 2022-A00818-35
Favorable opinion of the CPP Sud-Est VI dated 08/26/2022
ANSM information on 06/26/2022
Sponsor :
Ø Sponsor name: QUANTIQ.IO
Ø Developer's address: 4 allée Jacques Prévert - 92500 RUEIL-MALMAISON
Ø Contact details of the Sponsor: 06.50.89.39.29
Head of research acting on behalf of the sponsor / and authorized to sign the protocol and its
possible modifications on behalf of the sponsor: Fabien Niel
Coordinating investigator (multicentric research): Laure Abensur Vuillaume, MD, PHD
COBOX
Protocol Valid Page 1on42

HISTORY OF PROTOCOL UPDATES
VERSION
DATE
REASON FOR UPDATE
1
05/23/2022
Document creation
2
05/27/2022
Modification of the section: Ethical and regulatory
considerations - type of study MR001
3
05/31/2022
Modification of the title of Arnaud Depil Duval: elimination
of the PhD title
4
06/15/2022
Accuracy of the approximate start and end date of the
investigation.
Addition of signatures: Sponsor and coordinating investigator.
5
07/19/2022
Accuracy of CPP South-East VI.
Modification of the parts: research summary as well as in the
rest of the document of the following points:
1: Changing study dates
2: Duration and timing of the research
3: Elimination of the medico-economic study
Modified recruitment methods.
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MAIN CORRESPONDENTS
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Coordinating/Principal Investigator
Laure Abensur Vuillaume, MD, PhD
CHR METZ-THIONVILLE
Mercy Hospital
1 Castle Driveway - CS 45001
57085 METZ Cedex 03
Associate investigators
Cédric Gil-Jardine, MD, PhD
University Hospital of Bordeaux
Pellegrin Hospital,
Pl. Amélie Raba Léon
33300 Bordeaux
Aurelie Roger, MD
CHR METZ-THIONVILLE
Bel Air Hospital
3 Rue de Friscaty
57100 METZ
Arnaud Depil Duval, MD
Paris Saint-Joseph Hospital
85 Rue Raymond Losserand
75014 Paris
Head of research acting on behalf of the sponsor / and authorized to sign the protocol and its possible
modifications on behalf of the sponsor: Fabien Niel
Center for Methodology and Data Management: CHR METZ-THIONVILLE
Methodologist: Digital Medical Hub (DMH)
Project manager: Fabien Niel
Medico-economic study:
Digital Medical Hub (DMH)
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SUMMARY
Contents
LIST OF ABBREVIATIONS
8
1.
RESEARCH SUMMARY
9
2.
DEFINITION OF THE MEDICAL NEED ADDRESSED: OVERLOADING THE HEALTHCARE SYSTEM
13
3.
IDENTIFICATION AND DESCRIPTION OF THE INVESTIGATIONAL MEDICAL DEVICE
14
General description
14
Other objectives are also targeted:
16
Details about the manufacturer of the investigational medical device
17
Model/type name or number, including software version and accessories, if applicable, for
complete identification.
17
Description of how traceability should be ensured during and after the clinical investigation, for
example by assigning batch, batch or serial numbers.
17
Populations and indications for which the experimental device is intended
17
Description of the experimental device, including any material that will be in contact with tissues
or body fluids
18
Summary of training and experience required to use the experimental device.
18
Description of the specific medical or surgical procedures involved in the use of the
investigational device.
18
4.
RISKS AND BENEFITS OF THE EXPERIMENTAL DEVICE AND THE CLINICAL INVESTIGATION
19
Clinical Benefits
19
The clinical advantages of COBOX
19
Potential side effects
19
Residual risks associated with the experimental device
20
Risks associated with participation in clinical investigation
20
Possible interactions with concomitant medical treatments
20
Measures that will be taken to control or mitigate the risks
20
Justification of the risk/benefit ratio
20
5.
OBJECTIVES AND HYPOTHESES OF THE CLINICAL INVESTIGATION
21
Research hypotheses and expected results
21
Main objective
21
Secondary objectives
21
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Justification of methodological choices
22
Assumptions
22
Claims and expected performance of the investigational device that need to be verified.
23
Expected benefits
23
6.
RESEARCH DESIGN
24
Diagram of research
24
Primary endpoint
24
Secondary endpoints
24
Inclusion criteria
24
Non-inclusion criteria
25
Recruitment methods
25
7.
EXPERIMENTAL DEVICE(S) AND COMPARATOR(S)
26
Description of exposure to comparators
26
List of any other medical device or drug that will be used during the clinical investigation.
26
Number of experimental devices to be used, as well as a justification
26
Treatment(s)/ management of experimental devices
26
8.
RESEARCH PROCESS
27
Research calendar
27
Summary of patient follow-up
27
Collection of consent
28
Rules for stopping research
29
Research-related constraints and possible compensation of subjects/patients
29
9.
MANAGEMENT OF ADVERSE EVENTS AND NEW DEVELOPMENTS
30
10.
STATISTICAL ASPECTS
32
Study size calculation
32
Statistical methods used
32
11.
ACCESS RIGHTS TO SOURCE DATA AND DOCUMENTS
36
Access to data
36
Source data
36
Data Privacy
36
12.
QUALITY CONTROL AND ASSURANCE
37
Guidelines for data collection
37
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Research follow-up
37
Quality Control
37
Data management
37
Audits and inspections
38
13.
ETHICAL AND REGULATORY CONSIDERATIONS
39
Assurance QUANTIQ – Sponsor of the study
39
Amendment to Protocol
40
Deviation from Protocol
40
Declaration of conformity
41
14.
RETENTION OF DOCUMENTS AND RESEARCH DATA
42
15.
PUBLICATION RULES
43
Scientific papers
43
Communicating Results to Patients
43
Transfer of data
43
16.
BIBLIOGRAPHIC REFERENCES
44
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ABREVIATIONS LIST
ANSM
National Agency for the Safety of Medicines and Health Products
ARC
Clinical Research Associate
CPP
Committee for the Protection of Persons
CNIL
National Commission for Computing and Liberties
CRF
Case Report Form
SAE
Serious Adverse Event
EIGI
Serious Unexpected Adverse Effect
IOA
Reception organization nurse
MR
Reference Methodology
TEC
Clinical Study Technician
API
Application Programming Interface
SAUV
Reception room for vital emergencies
SaaS
Software as a Service
PPG
Photoplethysmography
rPPG
Remote Photoplethysmography
HR
Heart rate
EN
Respiratory rate
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1. Research Summary
Sponsor
Quantiq.io
REFERENCE
2022-A00818-35
Coordinating/Principal
Investigator
Laure Abensur Vuillaume, MD, PhD
CHR METZ-THIONVILLE
Mercy Hospital
1 Castle Driveway - CS 45001
57085 METZ Cedex 03
Title
Validation of the performance of the COBOX solution for
measuring heart rate and respiratory rate
Acronym
COBOX
Goals
The main objective is to validate the performance of the
measurement of the heart rate (HR) measured by the
COBOX medical device compared to a measurement carried
out
by
applying
the
reference
processes
for
taking
measurements via a CE marked device. The concordance
between the two measurement methods is sought here.
The secondary (ranked) objectives of the study are:
-
Evaluate the performance of the measurement of the
respiratory rate (RR) measured by the COBOX
medical device compared to a measurement carried
out by a reference method of manual counting .
-
Establish and verify the clinical safety of COBOX
and detect any adverse side effects under normal
conditions of use of the device and assess whether
these constitute an acceptable risk in relation to the
expected benefits of the device concerned.
Research scheme
Clinical, prospective and observational investigation
Inclusion criteria
- Adult patient (18 years and over)
And
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-Patient consultant in the emergency department of a
participating center
And
- Patient having constant FC and FR taken by the reception
organizing nurse (IOA) in the area dedicated to the reception
of patients
And.
- Patient having given their consent to participate in the
study.
Non-inclusion criteria
-
Patient in a state of vital emergency with direct entry
into SAUV or intensive care.
-
Patient who did not consent to participate in the
study.
-
Patient unable to express consent.
-
Patient unable, for health reasons, to face the
COBOX solution.
-
Patient unable to stand for 30 seconds facing the
COBOX solution .
-
Patient with skin stigma over more than 50% of the
face (burn, graft).
-
Patient having the face covered or not allowing
access to the entire face (clothing ).
Treatments/Strategies/
research procedures
The patients included in the study will have their HR and
HR constants taken simultaneously at the reception of the
emergencies by a reference medical device and by COBOX.
Judgment criteria
The main judgment criterion for the HR will be the
evaluation of the concordance between the measurements
obtained following the application of the reference technical
processes of non-operator dependent measurement taking via
a CE marked device and via COBOX.
The
secondary judgment criterion associated with the
measurement of the RR will also be the subject of an
evaluation of the concordance between the measurements
obtained
via
a reference method of manual counting
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according
to
the
good
practices
of
the
medical
or
paramedical nursing staff (or arc or tec) and via COBOX.
For each of the parameters measured, we will establish the
repeatability
of
the
measurement
and
its
accuracy
(comparison of the relative error expressed as a percentage
between the two types of measurement).
Study size
323 patients
Planned number of centers
4
Search duration
Duration of participation for each patient: less than 30
minutes
Total research duration: 3 months
Approximate study start date: mid-July 2022
Approximate study end date: mid-October 2022
Statistical analysis of data
The performance of the tool will be estimated by the
concordance between the measurements obtained from the
application of the reference technical process via a CE
marked device and with the measurements obtained by
COBOX.
An intraclass correlation coefficient (ICC) with its 95%
confidence
interval
(95%
CI)
will
be
calculated.
Measurement errors will be calculated and expressed as a
percentage (root mean square error, etc.).
The two study samples will be compared by Student's t test
and Fischer's F, with a desired significance for P value =
0.05, for all the analyses.
A DIXON test will be performed to assess the presence of
statistically outliers within the samples.
Expected benefits
These data will enable the COBOX tool, a class IIA medical
device, to be validated in terms of measurement performance
compared to a CE-marked device used in a reference
technical process for taking measurements and a reference
method
for
manual
counting.
Applications
for taking
constants without contact have a wide field of application in
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the field of routine care, saving medical time, increasing
quality by limiting manual copying errors, better quality
with
a
tool
without
contact,
limiting
the
risk
of
contamination
and
better
accessibility
to
vital
sign
measurements thanks to its purely software side which only
requires a camera.
Provisional
schedule
of
the
study
-Start of inclusions: Mid-July 2022
-Duration of the inclusion period: 2 months
-Duration of participation of each patient: The time of their
passage in the IOA box (less than 30 minutes)
-Total research duration: 3 months
Obtaining
authorization
from
the CNIL
Certificate of compliance with MR001
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2. Definition of the medical need addressed: the overload of the
healthcare system
The overload of an Emergency Department (SU) is considered a threat to the quality and safety of
care, and leads to an increase in morbidity and mortality during hospitalization [1-4]. This
overload also generates negative effects for caregivers and their quality of life at work [5]. It would
seem that inappropriate recourse to emergencies is from 13.5% to 27.4% [6]. Many patients turn to
emergencies and this is partly linked to a need felt to be urgent and to the limited nature of the
devices available to guide home routes.
In this global context, the care access service (SAS) was created and is currently being
tested. The SAS aims to improve the conditions of access to the healthcare system by developing
an information and orientation center in addition to the medical regulation of the SAMU-15 based
in part on city medicine. It is a medical orientation device, in response to a request for care and / or
information, answering health questions. This system will be accessible at any time and by various
means such as telephone calls and teleconsultations. It will be conducted by the staff of the
professional territorial health communities (CPTS) and the SAMU-15 of each of these territories
[7]. The call, through a single number for the management of unscheduled care (SNP) and
emergencies, will initially be taken into account by a medical dispatch assistant (ARM) in charge
of identifying the place of distress, the caller and the nature of the call. This call is then redirected
either to an ARM in the urgent medical aid sector in the face of a medical emergency, or redirected
to a liberal regulatory doctor in the SNP sector. Currently being deployed in 22 pilot sites
(including SAMU 10), the system covers more than 40% of the French population and ensures the
widest possible territorial coverage, in mainland France and overseas, concerning both urban poles
than less dense territories which are experiencing problems of medical desertification.
Other care systems already use models that include initial patient orientation contacts.
Sweden has also equipped itself with an innovative tool based on artificial intelligence
technologies to help with the role of Gatekeeper, allowing pre-orientation of patients. However,
this type of tool available to the patient at home must prove its safety in terms of sorting
performance. To date, the most reproducible and controlled sorting is carried out in emergency
services by reception and orientation staff. Also, a tool comparing the performance of a tool versus
this reference process would make it possible to show all its interest, particularly in France.
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3. Identification and description of the experimental medical
device
General description
“COBOX” by Quantiq.io is Class IIa stand-alone software pursuant to Rule 11 of Regulation
745./2017. It is an API (Application Programming Interface) put into service through a SaaS
solution (Software as a Service) whose technology is based on remote photoplethysmography,
allowing the physiological parameters of a patient to be measured without contact by a healthcare
professional or lay user. The SaaS API is accessible from a smartphone, a computer or a health
post equipped with an optical camera.
The technology at the heart of “COBOX” is remote photoplethysmography (or remote
photoplethysmography in English, abbreviated as rPPG). rPPG is a technique derived from
photoplethysmography (PPG). Photoplethysmography is an optical technique used to detect blood
volumetric changes in the peripheral circulation. It is an inexpensive and non-invasive method that
performs measurements on the surface of the skin. The technique provides valuable information
related to our cardiovascular system. Recent technological advancements have revived interest in
this technique, which is widely used in clinical physiological monitoring and measurement.
The PPG uses a low intensity red and infrared (IR) LED. When light passes through
biological tissues, it is absorbed by bones, skin pigments, and venous and arterial blood. Since
light is more strongly absorbed by blood than surrounding tissue, changes in blood flow can be
detected by PPG sensors as changes in light intensity. The electrical voltage signal from the PPG is
proportional to the amount of blood flowing through the blood vessels. Even small changes in
blood volume can be detected using this method.
A PPG signal has several components, including an AC component of volumetric changes
in arterial blood that are associated with cardiac activity, changes in venous blood volume that
modulate the PPG signal, and a DC component showing the optical property of tissues and bones
in the body. Changes in blood flow occur mainly in the arteries and not in the veins).
The PPG can operate in 2 main configurations: either by transmission, where the light is
transmitted through the finger and captured on the opposite photodetector, or by reflection where
the photodetector and the LED are on the same side and the light is transmitted then reflected on
the finger towards the photodetector (see figure 1).
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Source: AT Ayance, HS Ramírez, JMR Pérez and CGT Palacios, "Low-cost microcontrolled based wireless heart rate and oxygen
saturation monitor," 2018 International Conference on Electronics, Communications and Computers (CONIELECOMP), 2018, pp. 176-180, doi:
10.1109/CONIELECOMP.2018.8327195.
The rPPG on the other hand works on the same basic principle as the PPG in reflection
except that the ambient light plays the role of the LED and the camera the role of the photodetector
(see figure 2).
Source: Verkruysse, Wim PhD*; Bartula, Marek MSc†; Bresch, Erik PhD‡; Rocque, Mukul MSc†; Meftah, Mohammed BSc†; Kirenko,
Ihor PhD† Calibration of Contactless Pulse Oximetry, Anesthesia & Analgesia: January 2017 - Volume 124 - Issue 1 - p 136-145 doi:
10.1213/ANE.0000000000001381
In its current version, the technologies embedded in this SaaS platform (COBOX) allow
remote tracking, calculation and processing of several biological markers (cardio-respiratory rate).
The idea is therefore to transform any camera into a medical device. From this camera. It is a SaaS
platform type product that can be integrated and integrated into any other existing or future device.
The data can be sent to the patient and the practitioner or managed in real time by trained and
qualified nursing staff.
Finally, for its operation, the SaaS API requires a high-speed internet connection and an
image capture device by optical camera.
The objectives of this solution are multiple:
●
Standardization & reproducibility of the measurement :
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Taking the constant “manually” by observation is today the reference method for measuring the
respiratory rate. According to good training practices for medical or paramedical nursing staff, this
method consists of counting the respiratory movements (inspiration and expiration) of the rib cage
for 30 seconds extrapolated to 1 minute (by multiplying the value by two). This technology makes
it possible to standardize the measurement of the respiratory rate by a reproducible and repeatable
method with considerably reduced operator bias.
●
Save time by automating vital signs measurements
The measurement of vital parameters is essential for: assessing the patient's health status; follow
the evolution of his state of health; check the effectiveness of the treatments; assist in medical
diagnosis. In the state of this taking of vital signs includes the measurement of heart rate and
respiratory rate.
Taking constants manually is now the reference in the hospital context, it consists of auscultating
the patient by performing all the measurements manually with the help of tools such as a blood
pressure cuff, a saturometer or another thermometer. It is a time-consuming operation for the
healthcare professional and may involve risks depending on the patient's profile, in particular the
risk of infection and the risk of error.
Excluding respiratory constants, the taking of electronic constants is the most used by the medical
profession, it is carried out thanks to multiparametric monitors in the vast majority of cases. A
multi-parameter monitor is a medical device for monitoring a patient's vital parameters. Typically,
basic models monitor heart activity, blood pressure, respiration, oxygen saturation, and
temperature. They display the value of the parameters while presenting their evolution curves over
time.
●
Risk limitation
This solution differs from its competitors thanks to a feature that makes it its strength: the user has
no physical contact with the camera, which is the only measurement tool. Nosocomial infections,
or "care-associated infections", are infections contracted in a healthcare establishment such as a
hospital or clinic. Santé Publique France estimates that approximately one hospitalized patient in
20 was confronted with it in France in 2017. The World Health Organization estimates on its
website at 1.4 million the number of people who have contracted an infection with 'hospital. The
Ministry of Health estimates that nosocomial infections are responsible for 4,000 deaths each year
in France.
Other objectives are also targeted:
• Relieve medical and paramedical staff thanks to automated metrics
taking.
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• Secure and reassure patients through constant monitoring of their state of health
• Facilitate taking metrics without human intervention.
Details of the manufacturer of the investigational medical device
Name: Quantiq.io
Head office address (Kbis): 4 allée Jacques Prévert - 92500 RUEIL MALMAISON
Model/type name or number, including software version and accessories, if
applicable, for complete identification.
The name of the SaaS API is COBOX, a software-only solution.
As part of this study, we will use “COBOX” version 1.0.0.
During the clinical investigation, this API will be integrated into the “DemoCOBOX” version 0001
application in order to allow its use by medical personnel (or arc or tec) . This application will be installed
on a Samsung S6 tablet. The tablet will be placed on a tablet support equipped with an anti-theft device.
Description of how traceability should be ensured during and after the clinical
investigation, for example by assigning batch, batch or serial numbers.
During the clinical investigation, Quantiq.io will keep an identical model of the tablet with the
same version of COBOX installed in order to be able to reproduce any possible deviation in a
measurement and to investigate whether it comes from the tablet or the clinical trial conditions.
The reference of each tablet distributed for the trial as well as the DemoCOBOX application
version installed on it will be stored on our servers. The use of the application may be monitored
on our servers. Quantiq reserves the right to make extremely minor patches to the API as well as
the demo application during the trial, in order to meet a potential request from medical staff (or arc
or tec) and/or patients. In the event of a bug fix, or non-substantial modification, the server may be
put on hold. A system for updating the version on the “device” side can be used (telephone, pc).
The traceability of the software version used during the clinical investigation will be recorded
on secure databases for the duration of the study and for a period of 10 years from the end of the
study.
1.
The populations and indications for which the experimental device is intended
COBOX is a medical software intended for the measurement of clinical parameters of heart rate
and respiratory rate, in a medicalized or non-medicalized environment. COBOX is a solution
intended to be used by healthcare personnel and lay users. As part of this test and in order to
validate its performance, the COBOX device will be used by health professionals in real conditions
of use.
As part of the study, the COBOX device is intended to be used:
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-
For measuring HR and HR in a clinical setting or at home for regular pathology monitoring
or teleconsultation.
-
In the context of reception and emergency care by trained personnel .
-
On patients defined by the inclusion or exclusion criteria of this protocol.
Description of the experimental device, including any material that will be in
contact with tissues or body fluids
The COBOX device and the equipment that supports it do not come into contact with the patient.
The COBOX solution is purely software-based and poses no danger to the patient.
COBOX is an autonomous software type medical device. It consists of a SAAS API that works on
devices equipped with a camera such as smartphones, computers or tablets with an operating
system described as compatible in the user manual.
Summary of training and experience required to use the experimental device.
The use of this solution does not require specific training, beyond becoming familiar with the user
manual prior to its use and following the indications present on the user interface respecting the
specifications of Quantiq.io. The user manual is the same for the patient and the nursing staff (or
arc or tec).
Description of the specific medical or surgical procedures involved in the use of
the investigational device.
The measurement of Heart Rate and Respiratory Rate are usual and routine elements necessary for
the diagnosis and management of patients. The measurement of these two physiological constants
will be made using the COBOX solution in addition to the reference measurement processes and
methods. As a result, there is no heavy interventional procedure added to the care of the patient at
the emergency department.
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4. Risks and benefits of the experimental device and the clinical
investigation
Clinical benefits
The clinical advantages of COBOX are:
-
Measurements are simplified via a single tool thanks to the solution.
-
They do not require any particular medical procedure.
-
They are non-invasive.
-
They are contactless and do not require disinfection after use.
-
They make it possible to measure the Respiratory Rate in an automated and reliable way.
-
It offers an opportunity to standardize the measurement of respiratory rate.
-
It allows more regular monitoring and possible continuous monitoring:
o
Faster identification of decompensation and/or acutisation of a pathology –
Tachypnea/Polypnea.
o
Monitoring of risky drug intake (morphinics and derivatives – Bradypnea)
In current practice, measurements of respiratory rhythms and frequencies are taken visually
by identifying the movements of the rib cage: The operator (nursing staff or arc or medical or
paramedical tec) in current practice counts the complete respiratory movements (inspiration +
exhale) for 30 seconds and multiply by 2 to extrapolate the result to 1 minute (Cycles per minute).
This medical decision-making can therefore vary according to these results, 2 to 3 cycles
per minute varying around a "risk zone" (Above 20 cycles/minute or below 12/minute) can decide
to whether or not to put on oxygen (these results are always interpreted with the oxygen
saturation). Beyond the lack of robustness and reproducibility of this measurement in routine care,
the purely human intervention makes its regular or continuous monitoring complex and
time-consuming.
Finally, this data without a real monitoring standard is data that is almost unusable in
epidemiological and/or clinical research.
Potential side effects
There are no direct or indirect adverse effects for the patient identified to date.
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Residual risks associated with the experimental device, as identified in the risk
analysis report
After implementation of risk reduction actions (in accordance with document REC-M2-016
Product risk analysis of the Technical File), all the residual risks assessed are deemed acceptable.
Risks associated with participating in the clinical investigation
No associated risk has been identified, the non-inclusion measures having been identified in this
regard. The data collected for the evaluation will be observational and the information provided by
COBOX will not be used in clinical decision-making.
Possible interactions with concomitant medical treatments
No interactions have been identified.
Measures that will be taken to control or mitigate the risks
The COBOX application poses no risk to the patient.
Justification of the risk/benefit ratio
As stated previously, the implementation of the risk management process led to the absence of
unacceptable residual risks for the conduct of this study. Furthermore, the assessment of the
benefit/risk is the subject of provisions documented within the PRO-M2-004 Risk Management
procedure.
It follows that the absence of unacceptable residual risk and the identification of expected
clinical benefits, established on the basis of preclinical performance verification trials, are such as
to establish a favorable benefit/risk ratio for the conduct of the study. .
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5. Objectives and hypotheses of the clinical investigation
Research hypotheses and expected results
In order to meet safety and quality standards, new health technologies require rigorous clinical
validation with measurement performance at least equivalent to that obtained through the
application of reference measurement processes using marked devices. CE, as well as those
obtained via the manual counting reference method.
In this context, we hypothesize that the COBOX device will take measurements of heart
and respiratory rates consistent with those obtained through the application of reference processes
for taking measurements via CE marked devices, as well as those obtained via the manual counting
reference method.
We also make the assumption of an economic superiority by a release of time allowed by
the automation of these catches, and the suppression of the protocols of decontamination allowed
by the taking of measurement remotely.
The tool (COBOX) will reduce the cognitive load of caregivers in favor of a higher quality of
care. It will also allow greater access to vital sign measurements thanks to its purely software
nature and requiring only a smartphone or tablet (or a computer or any other device with a
camera).
Primary objective
The main objective is to validate the performance of the measurement of the heart rate (HR)
measured by the COBOX medical device compared to a measurement carried out by applying the
reference processes for taking measurements via a CE marked device. The concordance between
the two measurement methods is sought here.
Secondary objectives
The secondary (ranked) study objectives are:
-
Evaluate the performance of the measurement of the respiratory rate (RR) measured by the
COBOX device compared to a measurement carried out using the manual counting
reference method. The concordance between the two measurement methods is sought here.
-
Evaluate the additional parameters allowing to establish the clinical performance of
COBOX for the measurement of HR and RR:
o
Measurement repeatability.
o
The accuracy of the measurement: concordance within a tolerated margin between
the measurement taken by the COBOX device and current practices.
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-
Establish and verify the clinical safety of COBOX and detect any adverse side effects under
normal conditions of use of the device and assess whether these constitute an acceptable risk
in relation to the expected benefits of the device concerned.
-
Evaluate ergonomics and user feedback.
-
Evaluate the ease of use of the device (assessed by an ad-hoc questionnaire completed by
the caregivers (or arc or tec), one questionnaire per caregiver and per type of device).
Justification of methodological choices
We are carrying out an observational, multicenter, prospective clinical investigation, evaluating the
performance of the COBOX device in the context of and within the framework of usual care. Heart
rate and respiratory rate are two physiological parameters measured when a patient arrives at the
emergency room, so, given the high attendance of these services, it seemed to us to be an excellent
place for this study. This measurement is carried out as part of the patient's care pathway using
reference technical processes for taking measurements via a CE marked device and a reference
method of manual counting. The inclusions of patients consulting in the emergency department
make it possible to quickly obtain both a large number of inclusions, and on the other hand, a great
variability of the constants noted due to the various pathological states. This approach allows great
reproducibility in all clinical situations and thus makes it possible to validate performance in
different contexts. In addition, a medico-economic study of the tool will be carried out.
Hypotheses
•
Routine care measurements in French care services, taken by the COBOX solution are
𝐻0 :
different from measurements obtained through the application of reference technical processes
and a manual counting reference method.
•
The current care measurements in French care services taken by the COBOX solution are
𝐻1 :
consistent with the measurements obtained via the application of the reference technical
processes and a reference method of manual counting.
Claims and expected performance of the investigational device that need to be
verified.
COBOX is a tool for measuring cardiac and respiratory rhythm in routine clinical practice for
patients outside intensive care and outside continuous monitoring. We expect a correlation
coefficient of more than 0.7 between the COBOX measurements and those obtained using the
reference method. Regarding the secondary endpoints, we expect average standard deviations
COBOX Protocol Valid
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between COBOX and the reference methods of 5 bpm for the heart rate and 3 bpm for the
respiratory rate.
Expected benefits
These data will validate the COBOX tool in terms of measurement performance compared to the
results obtained through the application of reference processes for taking measurements using CE
marked devices, as well as those obtained using the reference method of counting. manual.
Applications for taking physiological constants without contact have a wide field of application in
the field of routine care and save medical time, increase quality by limiting manual copying errors
and the risk of contamination.
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6. Research design
Research scheme
This is an observational study, responding to Article 62.1 of the European medical device
regulations, prospective, comparative.
Primary endpoint
The main judgment criterion will be the intra-class correlation coefficient between the
measurement by COBOX and the measurement obtained thanks to the application of the reference
processes for taking measurements via a measurement by a CE marked tool (for HR).
In order to ensure the repeatability of the device, three successive comparative measurements
(each spaced 5 seconds apart) on the same patient will be carried out.
Secondary endpoints
The additional secondary judgment criteria will be:
-
For RF (ranked criterion): comparison with a manual measurement following a reference
method of manual counting according to good training practices for healthcare personnel
trained in taking measurements (ide, as, internal external).
-
The reliability of the reproducibility of the measurement
-
The time in seconds dedicated to taking the parameters with and without the COBOX tool
(time for installing and removing the tool if applicable, time for completing the medical file
if applicable, effective time for taking the HR constants and FR).
-
Assessment of treatment costs:
o
Pick-up times / delays
o
Total treatment costs (direct medical and non-medical costs)
Inclusion criteria
-
Adult patient (18 years and over)
AND
-
Patient consulting in the emergency department of a participating center
AND
-
Patient having constant FC and FR taken by the nursing staff (or arc or tec) of emergency
reception
AND
-
Patient who did not express his opposition to participate in the study
AND
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-
Patient affiliated to a social security scheme
Non-inclusion criteria
-
Patient in a state of vital emergency with direct entry into SAUV or intensive care.
-
Patient unable to express consent.
-
Patient unable, for health reasons, to face the COBOX tool.
-
Patient unable to stand for 30 seconds facing the COBOX solution.
-
Patient with skin stigma over more than 50% of the face (burn, graft)
-
Patient with the face covered or not allowing access to the entire face (clothing)
Recruitment methods
In order not to delay the care of patients in the emergency room, recruitment is carried out by the
IOA (or arc or tec) at the time of their usual care. She communicates oral information to the patient
on the use of the tool during the measurements and presents the consent letter in electronic format
in the tablet. If the patient gives consent, the test is performed. In case of opposition, the COBOX
device will not be used.
It is therefore a serial recruitment, without selection of the participants.
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7. Experimental device(s) and comparator(s)
Description of exposure to comparators
In order to standardize the measurements of the four hospital centers, QUANTIQ will provide each
center with a CMS60D digital pulse oximeter from the Contec brand. This device is CE marked
and commonly used in hospitals. This device will be used at the same time as the CE marked
device used during the reference technical process of the hospital center, without modifying the
practices of each center . The comparison of results will be between the Contec CMS60D and the
COBOX tool.
Device
Acquisition
cost
Trolley
(300 to
700 Euros)
Whip Set
and
Monobase
Cables
Lifespan
(Year)
Annual
Maintenance
Cost
Annual cost
for 1
technical
platform
Contec CMS60D Digital
Pulse Oximeter
(SpO2 - Heart Rate)
242.50 €
N / A
N / A
2
YEARS
(AVERAGE
)
Replaced/No
Maintenance -
PURCHASE
Management
(12.1 €)
133.4 €
List of any other medical device or drug that will be used during the clinical
investigation.
The Contec CMS60D reference DM will be provided by Quantiq while COBOX will be installed
on a Samsung S6 tablet also provided by Quantiq.
Number of experimental devices to be used, along with a rationale
3 reference Contec CMS60D oximeters will be provided per center.
Treatment(s)/ management of experimental devices
QUANTIQ provides users with one tablet per site per physician. Delivery of a functional tablet in
the event of a malfunction within 5 working days. Bug fix within 3 days in case of software
malfunction with continuous information for professionals.
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8. Research process
Research timeline
-Start of inclusions: Mid-July 2022
-Duration of the inclusion period: 2 months
-Duration of participation of each patient: The time of their passage in the IOA box (less
than 30 minutes)
-Total research duration: 3 months
Summary of patient follow-up
-Oral information by the IOA. If necessary, an investigating physician can complete the
information at the patient's request.
-Informed consent with electronic signature.
-Collection of the patient's age, gender and Fitzpatrick phototype.
-Collection of patient identification number.
-The nursing staff (or arc or tec) installs the oximeter on the patient's finger.
-The nursing staff (or arc or tec) starts COBOX and begins to count the breaths in parallel.
-After 15s, a first measurement is made by COBOX. The pulse oximeter reference result is
acquired in parallel, associated with the patient ID number and stored with the COBOX
result at the same time on an electronic database.
-After 20s (5s after the previous measurement), a second measurement is made by
COBOX. The pulse oximeter reference result is acquired in parallel, associated with the
patient ID number and stored with the COBOX result at the same time on an electronic
database.
-After 25s (5s after the previous measurement), a third measurement is made by COBOX.
The pulse oximeter reference result is acquired in parallel, associated with the patient ID
number and stored with the COBOX result at the same time on an electronic database.
-After 30s, the nursing staff (or arc or tec) enters the number of breaths counted since the
start. This result is converted into a respiratory rate (RR) then associated with the patient
number and stored in the database.
The data is blocked on the database until the end of the study. At the end of the study, they will be
sent to the coordinating centre.
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In order not to disrupt the general operation of the emergency department and patient care, the
usual patient circuit is not modified. The COBOX tool is used by the reception staff in a
contemporary way to their usual collection of input parameters.
Collection of consent
The information is compiled by the IOA and if necessary completed by a doctor. This
information must make it possible to answer all the patient's questions concerning the objective,
the nature of the constraints, the foreseeable risks and the expected benefits of the research. It also
specifies the patient's rights in the context of a clinical investigation and verifies the eligibility
criteria. A copy of the information note and the electronic consent form are then given to the
patient by the investigating physician.
The consent form is electronic and must be signed before data can be collected for research.
After electronic acceptance of the consent, a copy of the consent form is sent to the patient with his
identification number allowing him at any time to ask the Sponsor to delete his data. For his part,
the Sponsor only has access to the patient's identification number but his email address is not
stored.
The data will include:
-Taking FC and FR by the reference method
-HR and FR taken by the COBOX tool at the same time as those of the reference tool.
-The patient's age, sex and Fitzpatrick phototype.
The different copies of the information notice and the consent form are then distributed as
follows:
-A copy of the information note and the signed consent is given/sent by email to the
patient.
-The original copy is kept by the investigating physician (even if the patient moves during
the duration of the research) in a safe place inaccessible to third parties.
-When accepting the patient's participation on the electronic form. This is automatically
sent to the Sponsor.
Search stopping rules
The temporary stoppage of the research can be pronounced by technical problems concerning the
evaluated tool. The research stops definitively when the necessary number of subjects is reached
and all the data allow the analysis.
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Constraints related to research and possible compensation of subjects/patients
Patients can simultaneously participate in another research. No compensation is provided for in
this study. The patient will not be registered in the national file of people who lend themselves to
biomedical research.
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9. Management of adverse events and new facts
In accordance with article 2 of regulation 745/2017, the following terms mean:
Adverse Event: Any harmful manifestation, unintended illness or injury, or untoward clinical sign,
including an abnormal laboratory finding, in Participants, Users, or others, in a clinical
investigation, related or no to the medical device that is the subject of a clinical investigation.
Serious adverse event: any adverse event resulting in: a) death; b) a serious deterioration in the
Participant's state of health, which results in: i) an illness or injury endangering the life of the
Participant; ii) a permanent impairment of an anatomical structure or function; (iii) hospitalization
or prolongation of the participant's hospitalization; (iv) medical or surgical intervention to prevent
any life-threatening illness or injury or permanent impairment of anatomical structure or function;
(v) chronic illness; (c) fetal distress, fetal death, congenital physical or mental impairment or birth
defect.
Defectiveness of a medical device: any defect in the identity, quality, durability, reliability, safety
or performance of a medical device under investigation, including any malfunction, error of use or
any defect in the information provided by the manufacturer
In accordance with article 80 of regulation 745/2017 as well as "MDCG-2020-10/1 Safety
reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745" and
"MDCG 2021-6 Regulation (EU ) 2017/745 – Questions & Answers regarding clinical
investigation”,
Sponsor :
A/ records the following events:
The sponsor records the following data sent to it by the investigator within the time limits specified
in point C/ of this document: a) any adverse event defined in the protocol as decisive for the
evaluation of the results of the clinical investigation. B) any serious adverse event; c) any defect in
an MD which could have led to a serious adverse event in the absence of appropriate measures or
intervention, or if the circumstances had been less favourable; d) any new element concerning an
event referred to in points a) to c).
B/ declare to the authorities
The sponsor notifies the authorities according to the procedures described in the following
sections: a) any serious adverse event with a proven or reasonably foreseeable causal link with: -
the MD subject to the investigation, - or the comparator MD - or the investigation procedure which
precedes it; b) any defect in an MD which could have led to a serious adverse event in the absence
of appropriate measures or intervention, or if the circumstances had been less favourable; c) any
new element concerning an event referred to in points a) and b).
C Reporting deadlines
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C.1 Deadlines for reporting by the investigator to the sponsor
The events and defects are declared to the sponsor by the investigator without delay (immediately)
and no later than within 3 calendar days from the moment when the investigator became aware of
them.
C.2 Deadlines for reporting by the Sponsor to the competent authority
All events and defects resulting in death or risk of imminent death, serious injury or illness and
which require prompt corrective action for participants/patients, users or other persons, or any new
information relating to these events: Without delay (immediately), and no later than 2 calendar
days from the day on which the Sponsor becomes aware of the event to be declared or of new
information concerning an event already declared.
Other events and defects or any new information/update concerning them: Without delay
(immediately), and no later than 7 calendar days from the day on which the Sponsor becomes
aware of the event to be declared or of new information concerning an event already declared.
All safety reports in clinical investigations of medical devices under Regulation (EU) 2017/745
will be carried out in accordance with MDCG 2020-10/1 and MDCG 2020-10/2.
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10.
STATISTICAL ASPECTS
Study size calculation
Considering the results of the performance verification tests of the medical device under study,
we have established the study hypotheses in connection with the calculation of the size of the
study set out below:
Minimum
acceptable
value
of
the
ICC
correlation coefficient (ρ0)
0.6
Expected
value
of
the
ICC
correlation
coefficient (ρ1)
0.7
The number of observations per subject k
3
Two-sided significance level (α)
0.05
Power (1 - β):
90%
Minimum size (n)
226
Size at 30% safety margin
323
A final study size of 323 patients is retained; taking into account a rate of unusable data of 30% in
order to maintain the statistical power of the study in the event of exclusion of outliers.
Statistical methods used
The analysis will carry an initial descriptive part. The qualitative variables will be expressed in
frequencies (with their 95% CI), and the quantitative variables expressed in means (with their
standard deviation) if the distribution is normal. Otherwise, the quantitative variables will be
expressed as the median (with their interquartile range).
Then, we will perform a comparative analysis, using chi 2 tests (or Fisher's exact) for the
qualitative variables and student test (or Mann-Whitney test if applicable) for the quantitative
variables. For performance estimation, we will determine the intra-class correlation coefficient
with its confidence interval and we will perform a graphical analysis of Bland and Altman. In
addition, we will calculate the mean square errors between the measurement with COBOX and the
reference measurements, and they will be expressed as a percentage.
All our analyzes will be carried out at the 5% significance level.
An analysis of the repeated and compared measurements between COBOX and the CE marked
device (used during the technical reference process for taking measurements) for the heart rate will
make it possible to evaluate the reproducibility of the COBOX on repeated measurements in the
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same individual. A secondary statistical analysis will be done for the measurement times T+5s and
T+10s.
We will use imputation methods or sensitivity analysis for the management of missing data.
11.
Access rights to source data and documents
Access to data
The sponsor is responsible for obtaining the agreement of all the parties involved in the clinical
investigation in order to guarantee direct access to all the places where the research is carried out,
to the source data, to the source documents and to the reports in a purpose of quality control and
audit by the Sponsor.
The investigators will make available the documents and individual data strictly necessary for the
monitoring, quality control, audit of the clinical investigation and available to persons having
access to these documents in accordance with the legislative and regulatory provisions in force (
articles L.1121-3 and R.5121-13 of the public health code).
Source data
Any original document or object that proves the existence or accuracy of data or a fact recorded
during the research is defined as a source document.
List the type of source document as part of the research (medical record, original biological
examination result, imaging examination report, etc.).
Data Privacy
In accordance with the legislative provisions in force (articles L.1121-3 and R.5121-13 of the
Public Health Code), persons having direct access to the source data will take all the necessary
precautions to ensure the confidentiality of the information. relating to the research, to the persons
who take part in it and in particular with regard to their identity as well as to the results obtained.
These people, like the investigators themselves, are subject to professional secrecy.
During the clinical investigation or at its end, the data collected on the people who agree to it and
transmitted to the sponsor by the investigators (or any other specialized contributors) will be made
anonymous. Under no circumstances should they clearly show the names of the persons concerned
or their addresses.
The Sponsor will ensure that each person who lends himself to the research has given his written
consent for access to the individual data concerning him and strictly necessary for the quality
control of the research.
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12.
Quality control and assurance
Guidelines for data collection
All the information required by the protocol must be recorded in the tablet in the boxes dedicated
to this purpose. Data should be collected as it is obtained.
Research follow-up
The clinical investigation will be monitored by a clinical research technician. He will be
responsible, alongside the coordinating investigator, for:
-
Research logistics and monitoring,
-
Reporting on its progress,
-
Verification of data collection with the tablet,
-
The transmission of SAEs to the Sponsor.
He will work in accordance with standard operating procedures, in collaboration with the clinical
research associate delegated by the Sponsor.
Quality control
A clinical research associate mandated by the sponsor visits each investigating center on a regular
basis, during the setting up of the research, one or more times during the research depending on the
rate of inclusions and at the end of the research. During these visits, the following elements will be
reviewed:
informed consent,
Compliance with the research protocol and the procedures defined therein,
Quality of data collected in the tablet: accuracy, consistency of data with source documents
(medical records, appointment books, original laboratory results, etc.),
Any visit will be the subject of a monitoring report in written form.
Data managment
Data processing will be carried out under the responsibility of Fabien Niel.
The data will be entered automatically and stored in the tablet reserved for the study and provided
by the sponsor.
The data validation and freezing processes will be carried out according to the procedures in force.
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Auditing and inspection
An audit may be carried out at any time by persons appointed by the Sponsor and independent of
the research managers. Its objective is to ensure the quality of research, the validity of its results
and compliance with the law and regulations in force.
Investigators agree to comply with the requirements of the sponsor and the competent authority
with respect to an audit or inspection of the research.
The audit may apply to all stages of the research: from the development of the protocol to the
publication of the results and the classification of the data used or produced within the framework
of the research.
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13.
Ethical and Regulatory Considerations
The sponsor and the investigator(s) agree that this research will be carried out in accordance with
the Public Health Code, as well as in accordance with Good Clinical Practice (ICH version 4 of
May 1 1996 and decision of November 24, 2006) and the Declaration of Helsinki (which can be
found in its integral version on the site http://www.wma.net ) and according to the MDR 745/2017.
The research is conducted in accordance with this protocol. Except in emergency situations
requiring the implementation of specific therapeutic acts, the investigator(s) undertake(s) to respect
the protocol in all respects, in particular with regard to the collection of consent. .
This
research
received
an
ID-RCB
number
on
the
ANSM
website:
https://ictaxercb.ansm.sante.fr/Public/index.php .
Assurance QUANTIQ – Sponsor of the study
As part of this research, subject to Law No. 2018-493 of June 20, 2018 on the protection of
personal data, the data recorded during this research is subject to computerized processing by
Quantiq. io in order to analyze the results of the research with regard to the objectives of the latter.
In accordance with the General Data Protection Regulation (RGPD 2016/679 of the European
Parliament and of the Council of April 27, 2016), health data will be processed for scientific
research purposes in compliance with the fundamental rights and interests of the person. suitable
for research (Article 9 §2, paragraph i and j).
The data controller for this study is Fabien Niel.
People participating in the research have a right of access to their data, a right of rectification,
erasure of their data, a right to limit processing as well as a right of opposition. to the processing of
their personal data. These rights are exercised with the Investigator, who will inform the sponsor of
the research as soon as possible.
People taking part in the research also have the right to lodge a complaint with the supervisory
authority in France, namely the Commission Nationale de l'Informatique et des Libertés (CNIL).
The personal data will only be accessible to the persons concerned (those participating in this
research) and to the persons charged by the sponsor with controlling the quality of the study. These
data will be pseudonymised: they will be marked by a code number comprising an inclusion
number (corresponding to the chronological order of their inclusion and the center number) as well
as the 1st letter of the name and the 1st letter of the first name of each concerned person. The
correspondence table will be kept separately from the entire data set by the only persons authorized
by the Sponsor, who will not be data operators. If necessary, they may also be transmitted to the
authorized health authorities, under the legal conditions provided. In all cases, they will be used
under conditions guaranteeing their confidentiality.
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This data processing may be part of the reference methodology MR001 according to article 62.1 of
the MDR.
For comfort, the company Quantiq.io filed a request for CNIL authorization on December 24,
2021, supported by a PIA.
Protocol amendment
Changes to the protocol will be managed in accordance with the requirements of Regulation
2017/745.
Any substantial modification, i.e. any modification likely to have a significant impact on the
protection of persons, on the conditions of validity and on the results of the research, on the quality
and safety of the products tested, on the interpretation of the scientific documents that support the
progress of the research or the methods of conducting it, is the subject of a written amendment
which is submitted to the sponsor; the latter must obtain, prior to its implementation, a favorable
opinion from the CPP and inform the ANSM.
Non-substantial modifications, ie those having no significant impact on any aspect of the research
whatsoever, are communicated to the CPP for information.
All amendments are validated by the sponsor, and by all the research stakeholders concerned by
the modification, before submission to the CPP.
All amendments to the protocol must be brought to the attention of all investigators participating in
the research. Investigators undertake to respect its content.
Any amendment that modifies the care of patients or the benefits, risks and constraints of research
is the subject of a new information note and a new consent form, the collection of which follows
the same procedure as the one mentioned above. .
Deviation from protocol
Any deviation from this protocol, the signed agreement, applicable regulations and any condition
of approval imposed by an EC or by applicable regulatory authorities, which affects the rights,
safety and well-being of the subjects or the scientific integrity of the clinical investigation, must be
documented (including the date and reason for the deviation). Site staff must identify and report
deviations to the sponsor within 5 working days.
In emergency circumstances, deviations from this protocol to protect the rights, safety, or
well-being of participants are permitted without the prior approval of the sponsor and
investigators. The site must document and report these emerging deviations to Fabien Niel and
Nicolas Desrumaux and to the EC within 5 working days of the occurrence of the emergency.
Where appropriate, measures to ensure compliance may be taken by the data controller. These
actions may include discontinuation of device shipments, removal/disposal of devices from the
investigator, or termination of the investigator's participation in the study.
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Declaration of conformity
A) This clinical investigation will be conducted in accordance with the ethical principles
which have their origin in the Declaration of Helsinki, the ISO 14155:2020 standard (Clinical
investigation of medical devices for human subjects - Good clinical practice).
B) This clinical investigation will be conducted in accordance with this International
Standard and any regional or national regulations, where applicable, including Regulation
2017/745.
C) This clinical investigation will not commence until the required approval/favourable
opinion has been obtained from the EC or the regulatory authority, as the case may be.
D) Any additional requirements imposed by the EC or regulatory authority will be followed,
as applicable.
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14.
Preservation of documents and data relating to research
The following documents relating to this research are archived in accordance with Good Clinical
Practice:
-By the medical investigators:
- for a period of 15 years (research relating to drugs, medical devices or in vitro
diagnostic medical devices or research not relating to a product mentioned in Article
L.5311-1 of the Public Health Code) ,
• The protocol and any amendments to the protocol
• Observation notebooks (copies)
• The electronically signed informed consents of the participants
• The source files of the participants who signed a consent
• All other documents and letters relating to the research
All these documents are the responsibility of the investigator for the regulatory
archiving period.
-By the Sponsor:
- for a period of 15 years (research relating to drugs, medical devices or in vitro
diagnostic medical devices or research not relating to a product mentioned in Article
L.5311-1 of the Public Health Code) ,
• The protocol and any amendments to the protocol
• The original observation notebooks
• A copy of the electronically signed informed consents of the participants
• Documents relating to serious adverse events
• All other documents and letters relating to the research
All these documents are under the responsibility of the Sponsor for the regulatory archiving period.
No displacement or destruction can be carried out without the agreement of the Sponsor. At the
end of the regulatory archiving period, the Sponsor will be consulted for destruction. All data,
documents and reports are subject to audit or inspection.
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15.
Posting Rules
Scientific papers
The data provided by the investigating centers are centralized by the coordinating center and sent
to Quantiq.io for statistical analysis (statistical analysis is done by Quantiq.io). This analysis gives
rise to a written report which must then be sent to the Committee for the Protection of Persons and
to the competent authority.
Any written or oral communication of the results of the research must receive the prior agreement
of the coordinating investigator and, where applicable, of any committee set up for the research.
The publication of the main results mentions the name of the sponsor, of all the investigators who
included or followed patients in the research, of the methodologists, biostatisticians and data
managers who participated in the research, of the members of the committee(s) set up( s) for
research and funding source(s). International rules for writing and publication will be taken into
account (The Uniform Requirements for Manuscripts of the ICMJE, April 2010).
Communication of results to patients
In accordance with law n°2002-303 of March 4, 2002, patients are informed, at their request, of the
overall results of the research.
Transfer of data
Data collection and management are handled by the coordinating centre. The conditions for the
transfer of all or part of the research database are decided by the research sponsor and are the
subject of a written contract.
Sponsor
COORDINATING INVESTIGATOR
Last name
Date and signature
Last name
Date and signature
Fabien Niel
07/19/2022
Laure Abensur
Vuillaume
07/19/2022
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Bibliographic references
1.
CHIU IM. LY, SYUE YJ., ET AL. THE INFLUENCE OF CROWDING ON CLINICAL PRACTICE IN THE
EMERGENCY DEPARTMENT. AM J EMERG MED. 2018;36:56-60.
2.
VAN DER LINDEN N. VDLM, RICHARDS JR., ET AL. EFFECTS OF EMERGENCY DEPARTMENT CROWDING
ON THE DELIVERY OF TIMELY CARE IN AN INNER-CITY HOSPITAL IN THE NETHERLANDS. EUR J EMERG MED.
2016;23:337-43.
3.
PATON A. MB, CONSIDINE J. LONGER TIME TO TRANSFER FROM THE EMERGENCY DEPARTMENT
AFTER BED REQUEST IS ASSOCIATED WITH WORSE OUTCOMES. EMERGMED AUSTRALIA. 2018;31:211-5.
4.
BERG LM, EHRENBERG A, FLORIN J, OSTERGREN J, DISCACCIATI A, GORANSSON KE.
ASSOCIATIONS BETWEEN CROWDING AND TEN-DAY MORTALITY AMONG PATIENTS ALLOCATED LOWER
TRIAGE ACUITY LEVELS WITHOUT NEED OF ACUTE HOSPITAL CARE ON DEPARTURE FROM THE EMERGENCY
DEPARTMENT. ANN EMERG MED. 2019. EPUB 2019/06/24. DOI: 10.1016/J.ANNEMERGMED.2019.04.012.
PUBMED PM ID: 31229391.
5.
QUINTANA JM, UNZURRUNZAGA A, GARCIA-GUTIERREZ S, GONZALEZ N, LAFUENTE I, BARE M,
ET AL. PREDICTORS OF HOSPITAL LENGTH OF STAY IN PATIENTS WITH EXACERBATIONS OF COPD: A
COHORT
STUDY.
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2015;30(6):824-31.
EPUB
2014/12/05.
DOI:
10.1007/S11606-014-3129-X.
PUBMED
PM
ID:
25472508;
PUBMED
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PMCID:
PMCPMC4441653.
6.
NAOURI D, RANCHON G, VUAGNAT A, SCHMIDT J, EL KHOURY C, YORDANOF Y, ET AL. FACTORS
ASSOCIATED WITH INAPPROPRIATE USE OF EMERGENCY DEPARTMENTS: FINDINGS FROM A CROSS-SECTIONAL
NATIONAL STUDY IN FRANCE. BMJ QUAL SAF. 2019. EPUB EPUB AHEAD OF PRINT: [NOV 2019]. DOI:
10.1136/BMJQS-2019-009396.
7.
PRIBILE P, NABET N. RETHINKING THE TERRITORIAL ORGANIZATION OF CARE. 2018;22.
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