The BAR Monitor is intended to monitor the state of the brain by real-time data acquisition and processing of EEG signals. The system displays a patient's EEG and Composite Cortical State (CCS), a proprietary computed EEG index related to the effect of certain anesthetic or hypnotic agents include inhalation agents and propofol in combination with opioids.

The BAR Monitor is intended to assist medical professionals monitor adult patients (22 to 65 years of age) in the operating room (OR) and clinical research laboratory.

Device Description

The Brain Anaesthesia Response Monitor (BARM) is a device designed to non-invasively monitor brain function in response to anesthetic agents including inhalation agents in the operating room (OR) and clinical research laboratory. The system consists of the following three components:

. Brain Anaesthesia Response (BAR) Terminal - Provides a user interface to control the DAM, set configuration parameters and display the DAM output for users.
. Data Acquisition Module (DAM) - Collects and processes the signal sent by the electrodes and calculates the Composite Cortical State (CCS) index and outputs the information to the BAR Terminal.
Disposable cutaneous electrode sensor- The electrodes collect Brain electrical activity (EEG) signals and transfers them to the DAM. The electrodes are made from pre-gelled Ag-AgCl. The electrodes are connected with patient leads which is plugged into the DAM. The electrodes are applied to the patients' forehead and behind the ear and is held in place via biocompatible adhesives.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the studies proving the device meets those criteria, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a formal table with pass/fail metrics. Instead, it demonstrates substantial equivalence to a predicate device (BIS EEG VISTA MONITOR SYSTEM) through a comparison of technological characteristics and then presents clinical performance data to support the device's intended use and show its comparable performance to existing technologies.

Here's a table synthesizing the implied acceptance criteria (based on the predicate device's features and the subject device's performance claims) and the reported device performance.

Acceptance Criteria (Implied from Predicate/Claims)	Reported Device Performance (BAR Monitor)
Safety and Electrical Standards Compliance	- IEC 62133 (Battery Safety) met
	- IEC 60601-1 (Electrical and Environmental Safety) met
	- IEC 60601-2-26 (Electrical Safety and Essential Performance) met
	- IEC 60601-1-2 (EMC Testing) met
	- ISO 14971 (Risk Assessment) met
	- FDA Software Guidance (Software V&V) met
	- IEC 60601-1-6 & IEC 62366-1 (Usability Evaluation) met
	- ISO 10993-1 (Biocompatibility) met
EEG Index Related to Anesthetic/Hypnotic Agents	CCS (Composite Cortical State) index, 0-100 range, related to effect of certain anesthetic or hypnotic agents.
Accuracy in Predicting Loss of Response (Anesthetic Induction)	U111-1124-2523 Study: CCS equivalently predictive of loss of response (OAA/S 0) as BIS™ index. Prediction Probability (Pr) 0.9 for both devices.
Accuracy in Monitoring Emergence from Anesthesia	ACTRN12618000916246 Study: CCS observed to increase across signs of emergence with comparable values to BIS™. Prediction probabilities calculated across emergence endpoints for CCS were equivalent to or better than that for the BIS.
Correlation with OAA/S Levels (Anesthetic Depth)	6001-004 Study: CCS observed to decrease with decreasing OAA/S level. Findings support a recommended range of CCS > 80 for awake and CCS between 40-60 for unresponsive. Prediction probabilities across all OAA/S levels were 0.85, 0.84, 0.78, and 0.83 (for 0, 2, 4 ng/ml remifentanil and all combined, respectively), equivalent to GE M-Entropy™. Prediction probabilities between OAA/S 5 and OAA/S 0 were ≥0.99.
Predictive of Response to Vocal Stimulus	6001-004 Study: P ≥ 0.86.
Comparable EEG Processing & Display (e.g., Amplitude, Chart Speed, Analog Noise)	- EEG Waveforms Amplitude: 25 µV/division (default), with additional options. Equivalent to predicate.
	- EEG Chart Speed: 32mm/sec (default), with additional options. Equivalent to predicate.
	- Analog Noise: < 0.4µV (RMS), < 1.25 µV (peak to peak). Equivalent to predicate.
	- A/D: 16 bit. Equivalent to predicate.
	- CMR: > 108 dB. Equivalent to predicate.
	- Bandwidth: 0.5 - 200 Hz. Equivalent to predicate.
	- Unprocessed EEG available: Yes. Equivalent to predicate.
	- Display of EEG time series: Yes. Equivalent to predicate.
Appropriate Device Hardware & Environmental Specifications	(Various specifications listed in the comparison table, generally found "Equivalent" to predicate, e.g., power, battery runtime, operating temperature, humidity, storage, etc.)
Electrode Specifications	(Various specifications listed in the comparison table, generally found "Equivalent" to predicate, e.g., product code, where used, material, single-use, non-sterile, single cable). However, number of electrodes is different (3 vs 4).

Study Details

The document describes three studies that support the performance of the BAR Monitor.

1. Study U111-1124-2523

Sample Size: 20 subjects
Data Provenance: Melbourne, Australia; Prospective, double-blinded, randomized controlled design.
Number of Experts & Qualifications (Ground Truth):
- Number of Experts: Not explicitly stated how many experts established the OAA/S ground truth for each subject. Assuming standard clinical practice, it would likely involve the anesthesiologist(s) and/or trained research staff present.
- Qualifications: "Observer's Assessment of Alertness/Sedation (OAA/S) level 4" and "OAA/S 0" indicate clinical assessments by qualified personnel familiar with these scales. Specific qualifications (e.g., anesthesiologist experience) are not provided.
Adjudication Method: Not explicitly stated.
MRMC Comparative Effectiveness Study: The study compared the predictive ability of CCS with the BIS™ index for loss of response.
- Effect Size: CCS and BIS™ were found to be equivalently predictive, with a prediction probability (Pr) of 0.9 for both devices. This indicates no significant improvement by AI (CCS) over the established technology (BIS™) in this specific outcome, but rather a comparable performance.
Standalone (Algorithm only) Performance: Yes, the prediction probability (Pr) of 0.9 for CCS indicates its standalone performance in predicting loss of response.
Type of Ground Truth: Clinical assessment (Observer's Assessment of Alertness/Sedation - OAA/S levels).
Training Set Sample Size: Not specified in this document. This study appears to be a clinical validation, not part of the algorithm's training.
Ground Truth for Training Set: Not specified in this document.

2. Study ACTRN12618000916246

Sample Size: 21 patients (10 sevoflurane, 11 xenon)
Data Provenance: Melbourne, Australia; Prospective, double-blinded, randomized controlled design.
Number of Experts & Qualifications (Ground Truth):
- Number of Experts: Not explicitly stated how many experts established the emergence criteria (first response to name, first eyes open, spontaneously ventilating). Likely clinical staff.
- Qualifications: Not explicitly stated, but implies clinical observation by trained medical professionals (e.g., anesthesiologists, nurses).
Adjudication Method: Not explicitly stated.
MRMC Comparative Effectiveness Study: The study compared CCS with the BIS™ index during emergence from anesthesia.
- Effect Size: Prediction probabilities for CCS were equivalent to or better than that for the BIS for the sevoflurane group, the xenon group, and both groups combined. This suggests comparable to slightly improved performance of CCS over BIS for emergence monitoring.
Standalone (Algorithm only) Performance: Yes, prediction probabilities for CCS were calculated independently.
Type of Ground Truth: Clinical assessments of emergence endpoints (first response to name, first eyes open, spontaneously ventilating).
Training Set Sample Size: Not specified in this document.
Ground Truth for Training Set: Not specified in this document.

3. Study 6001-004

Sample Size: 42 subjects (14 subjects per remifentanil group: 0, 2, or 4 ng/ml)
Data Provenance: Belgium; Retrospective re-analysis of previously recorded EEG data from a randomized, multi-arm study.
Number of Experts & Qualifications (Ground Truth):
- Number of Experts: Not explicitly stated from the original study that collected the OAA/S data.
- Qualifications: OAA/S assessments imply clinical observation by qualified personnel. Specific qualifications are not provided.
Adjudication Method: Not explicitly stated.
MRMC Comparative Effectiveness Study: CCS was compared to GE M-Entropy™ state and response entropy measures.
- Effect Size: Prediction probabilities for CCS across all OAA/S levels were equivalent to values obtained using GE M-Entropy™ state and response entropy measures. This indicates comparable performance of CCS.
Standalone (Algorithm only) Performance: Yes, prediction probabilities for CCS were calculated. E.g., Prediction probabilities between OAA/S 5 and OAA/S 0 were ≥0.99.
Type of Ground Truth: Clinical assessment (Observer's Assessment of Alertness/Sedation - OAA/S levels).
Training Set Sample Size: Not specified in this document. This study describes a re-analysis of previously recorded EEG data, suggesting it was used for validation purposes rather than initial model training.
Ground Truth for Training Set: Not specified in this document.

General Note on Training Data: The document focuses entirely on clinical validation studies and non-clinical performance testing. It does not provide details regarding the training set sample size or how the ground truth for the training set was established for the BAR Monitor's algorithm (Composite Cortical State - CCS). This information would typically be found in a more detailed technical report on the algorithm development, which is not included in this FDA 510(k) summary. The studies provided demonstrate the performance of the already developed algorithm against clinical ground truth and predicate devices.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

September 1, 2023

Cortical Dynamics Ltd % Tim Marjenin Vice-President Mcra, LLC. 803 7th Street NW, 3rd floor Washington, District of Columbia 20001

Re: K213273

Trade/Device Name: Brain Anesthesia Response Monitor (Bar Monitor) Regulation Number: 21 CFR 882.1400 Regulation Name: Electroencephalograph Regulatory Class: Class II Product Code: OLW, OMC, GXY Dated: August 4, 2023 Received: August 4, 2023

Dear Tim Marjenin:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

{1}------------------------------------------------

statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Ting Song -S

for

Bradley Quinn Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K213273

Device Name

Brain Anesthesia Response Monitor (BAR Monitor)

Indications for Use (Describe)

The BAR Monitor is intended to assist medical professionals monitor adult patients (22 to 65 years of age) in the operating room (OR) and clinical research laboratory.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

K213273

Image /page/3/Picture/2 description: The image shows the logo for Cortical Dynamics. The logo features a stylized letter C in gray and blue, followed by the words "CORTICAL DYNAMICS" in gray and blue. Below the logo is the text "ADVANCED BRAIN MONITORING" in black.

510(k) Summary

Date	August 4, 2023
Owner/Sponsor	CORTICAL DYNAMICS LTD.14 View StreetNorth Perth 6006Western AustraliaTel: +61 3 8741 1130
Contact	Tim MarjeninMCRA, LLC803 7th Street NW, 3rd FloorWashington, DC 20001
Device	Trade Name: Brain Anaesthesia Response Monitor (BARM / BARMonitor)Common Name: Index-Generating Electroencephalograph SoftwareClassification Name: ElectroencephalographRegulation No: 21 CFR 882.1400Product Code(s): OLW, OMC, GXY
Classification	Class II
ClassificationPanel	Neurology
Predicate Device	K072286 - BIS EEG VISTA MONITOR SYSTEM

Device Description

. Brain Anaesthesia Response (BAR) Terminal - Provides a user interface to control the DAM, set configuration parameters and display the DAM output for users.
. Data Acquisition Module (DAM) - Collects and processes the signal sent by the electrodes and calculates the Composite Cortical State (CCS) index and outputs the information to the BAR Terminal.
Disposable cutaneous electrode sensor- The electrodes collect Brain electrical activity (EEG) .

{4}------------------------------------------------

signals and transfers them to the DAM. The electrodes are made from pre-gelled Ag-AgCl. The electrodes are connected with patient leads which is plugged into the DAM. The electrodes are applied to the patients' forehead and behind the ear and is held in place via biocompatible adhesives.

Image /page/4/Figure/2 description: The image shows a medical device setup with three labeled components. The first component, labeled "1 BAR Terminal", is a device with a screen displaying a graph and the number 57. The second component, labeled "2 Data Acquisition Module (DAM)", is a white box connected by wires to both the BAR Terminal and the third component, labeled "3 Electrode", which is attached to a person's head.

Intended Use

The BAR Monitor is intended to monitor the state of the brain by real- time data acquisition and processing of EEG signals. The system displays a patient's EEG as well as Composite Cortical State (CCS), a proprietary computed EEG index related to the effect of certain anesthetic or hypnotic agents. Anesthetic agents include inhalation agents and propofol in combination with opioids.

The BAR Monitor is intended to assist medical professionals monitor adult patients (22 to 65) in the operating room (OR) and clinical research laboratory.

FEATURE	BIS EEG VISTA MONITORSYSTEM AND BISX	Subject Device	Comparison
510(k) Number	K072286	-	N/A
Company	Aspect Medical System Inc.	Cortical Dynamics Ltd.	N/A
Regulation	21 CFR 882.1400	21 CFR 882.1400	Identical
Class	II	II	Identical
Product Code	OLW,OLT, OMC, ORT	OLW, OMC, GXY	Equivalent
Indications for Use	The BIS VISTA MonitoringSystem is intended for useunder the direct supervision ofa licensed healthcarepractitioner or by personnel	The BAR Monitor isintended to monitor thestate of the brain by real-time data acquisition andprocessing of EEG signals.	-
FEATURE	BIS EEG VISTA MONITORSYSTEM AND BISX	Subject Device	Comparison
	trained in its proper use. TheBIS VISTA Monitor is intendedfor use on adult and pediatricpatients within a hospital ormedical facility providingpatient care to monitor thestate of the brain by dataacquisition of EEG signals.The BIS™ may be used as anaid in monitoring the effects ofcertain anesthetic agents. Useof BIS monitoring to help guideanesthetic administration maybe associated with thereduction of the incidence ofawareness with recall in adultsduring general anesthesia andsedation.	The system displays apatient's EEG andComposite Cortical State(CCS), a proprietarycomputed EEG indexrelated to the effect ofcertain anesthetic orhypnotic agents.Anesthetic agents includeinhalation agents andpropofol in combinationwith opioids.The BAR Monitor isintended to assist medicalprofessionals monitor adultpatients (22 to 65) in theoperating room (OR) andclinical research laboratory
EEG WaveformsAmplitude (default)	25 µV/ division	25 µV/ division(Default)Additional sensitivity optionsof 10 µV, 20 µV, 50 µV, 100µV, 200 µV which displayssignals at 5, 10, 25, 50,100 µV /division.	Equivalent
EEG Chart Speed(default)	30 mm/sec	32mm/sec(Default)Additional options 8 & 16mm/sec	Equivalent
Index calculatedrelated to effect ofanesthetic agents	BIS (0 to 100)	CCS (0 to 100)	Equivalent
Electromyograph(EMG) Indicator	30 – 55dB	Not Available	Different
Suppression Ratio(SR)	0 to 100%	SR is incorporated into theSignal Quality measureand not displayed	Different
Burst Count	0 - 20/min	Parameter not calculatednor displayed	Different
Signal QualityIndicator (SQI)	0-100 (20 points per bar)	0 - 100%. Displayed ontrend chart when less than100%	Different
ElectrodeImpedance	Parameter displayed as Pass,High, Noise, or Lead Off.Unknown range.	Parameter not displayed	Different
Index calculatedrelated to effect ofanesthetic agents	1 (BIS)	1 (CCS)	Equivalent
Storage / recording	The duration of	BARM has data and trendstorage space for > 1000	Equivalent
FEATURE	BIS EEG VISTA MONITOR SYSTEM AND BISX	Subject Device	Comparison
	trend data stored is approximately 72 hours. The duration of BISx data (processed EEG parameters, including the BIS value, with time and date of acquisition) stored is approximately 1200 hours.	hours
AC Power	100-240 VAC, 50-60 Hz 24 W	100~240VAC, 50-60Hz, 30W	Equivalent
Rechargeable battery	A rechargeable lithium-ion battery inside the monitor provides approximately 45 minutes of back-up power when power cannot be supplied via the power cord.	BARM contains backup battery with > 1 hour runtime	Equivalent
Module Connection	BISX interfaces with BIS VISTA Monitoring system	DAM interfaces with BARM Terminal	Equivalent
Module: Dimensions	2.6 in x 1.00 in x 4.25 in (6.6 cm x 2.5 cm x 10.8 cm)	DAM: 155x123x28mm (6.10x4.84x1.10 in)	Equivalent
Operating Temperature	0°C to +40°C32°F to 104°F	0°C to +40°C32°F to 104°F	Equivalent
Operating Humidity	15% to 95% (non-condensing)	10% to 95% @ +40°C non-condensing	Equivalent
Transport and Storage Environment
Temperature	-10°C to +60°C14°F to 140°F	-20°C to +60°C-4°F to +140°F	Equivalent
Humidity	15% to 95% (non-condensing)	10% to 95% @ +40°C non-condensing	Equivalent
Pressure	48 kPa to 106.7 kPa	70kPa to 106 kPa	Equivalent
Cutaneous Electrode
Product code	GXY	GXY	Equivalent
Where used	Head	Head	Equivalent
Material	Pre-gelled silver/silver chloride electrode array	Pre-gelled Ag-AgCl electrodes	Equivalent
Quantity	FourImage: Four electrodes on a head	Three (green)Image: Three electrodes on a head	Different
FEATURE	BIS EEG VISTA MONITORSYSTEM AND BISX	Subject Device	Comparison
Number of cables	Single Cable	Single Cable	Equivalent
Single Use or Re-useable	Single-Use	Single-Use	Equivalent
Sterile or non-sterile	Non-sterile	Non-sterile	Equivalent
Analog Noise	< 0.3 µV RMS(2.0 µV peak-to-peak);0.25 Hz to 50 Hz	< 0.4µV (RMS).< 1.25 µV (peak to peak)	Equivalent
A/D	16 bit	16 bit	Equivalent
CMR	110 dB	> 108 dB	Equivalent
Bandwidth	0.16 - 450 Hz	0.5 - 200 Hz	Equivalent
SamplingFrequency	256 Hz	480 Hz	Different
Sampling Rate	16,384 samples/second	100,000 samples/second	Different
Unprocessed EEGavailable	Yes	Yes	Equivalent
Display	4" x %.25" Colour Touchscreen	4" x 5.5" ColourTouchscreen	Equivalent
Algorithm Output	The Bispectral Index(BIS) is the output from amultivariate discriminateanalysis that quantifies theoverall bispectral properties(frequency, power, andphase)throughout the entirefrequency range.	Composite Cortical State(CCS) is derived from thepatients EEG using thelinearised Liley model ofEEG genesis. CCS isderived every second fromthe patients EEG afterautomatic removal of datamaterially contaminated bydiathermy or artifacts	Equivalent
Display of EEGtime series	Yes	Yes	Equivalent
Displays Depth ofAnesthesia indexvalue and trendgraph	BIS	CCS	Equivalent
Burst Suppression	Suppression is quantified as aSuppression Ratio (SR). SR isdisplayed and is notincorporated into signal qualitymeasure	Burst suppression isincorporated in signalquality measure	Different
Medical devicesafety andEMC/EMIcertificates	UL 60601-1, IEC 60601-1, IEC60601-2-26, CAN/CSA-C22.2#601.1IEC 60601-1-2:2001	IEC60601-1:2005IEC60601-1:2005/AMD1:2012IEC60601-1-6:2010IEC60601-1-6:2010/AMD1:2013IEC60601-2-26:2016	Equivalent

Comparison Of Technological Characteristics With The Predicate Device

{5}------------------------------------------------

{6}------------------------------------------------

{7}------------------------------------------------

Non-clinical Performance Testing

The following non-clinical testing was conducted:

{8}------------------------------------------------

Battery Safety Testing per IEC 62133 .
Electrical and Environmental Safety Testing per IEC 60601-1
Electrical Safety and Essential Performance Testing per IEC 60601-2-26
. EMC Testing per IEC 60601-1-2
. Risk Assessment per ISO 14971
Software Verification and Validation per FDA Software Guidance
. Usability Evaluation per IEC 60601-1-6 and IEC 62366-1
. Biocompatibility testing per ISO 10993-1

Per the completed testing the requirements and performance specifications for the subject device were met, including compliance with the requirements for electro-encephalographic medical devices and is as safe and effective for brain function monitoring in clinical settings.

Clinical Performance Data

Study U111-1124-2523

The U111-1124-2523 study was a double-blinded, randomized controlled design conducted in Melbourne, Australia with 20 subjects undergoing cardiac surgery. BARM was used to monitor anesthetic induction using propofol, fentanyl and benzodiazepines. Subjects were pre-sedated with lorazepam and midazolam to an Observer's Assessment of Alertness/Sedation (OAA/S) level 4 (lethargic response to name spoken). Subjects then received a 1mg/kg bolus of propofol followed by an infusion at 6mg/kg/hr until loss of response to verbal command and painful stimulus (OAA/S 0). Subjects then received either a low (FLD, 8μg/kg) or moderate dose (FMD, 16μg/kg) of fentanyl. CCS was observed to decrease from OAA/S 4 (FLD: 73, FMD: 79) to OAAS/0 (FLD: 57, FMD: 58). CCS was found to be equivalently predictive of loss of response as the BIS™ index, based on prediction probability (Pr 0.9 for both devices). Py has a value of 1 when the indicator variable (e.g., CCS, BIS) predicts observed anesthetic depth perfectly and a value of 0.5 when the indicator predicts no better than a 50:50 chance.

Study ACTRN12618000916246

The ACTRN12618000916246 study was a double-blinded, randomized controlled design in conducted in Melbourne, Australia with 21 patients. BARM was used to monitor emergence from sevoflurane (10 subjects) and xenon (11 subjects) anesthesia with remifentanil (0.1µg/kg/min). Anesthesia was maintained at 90% of the minimum alveolar concentration (MAC) equivalent of the respective agents while a lithotripsy procedure was performed. After the procedure was complete all anesthetic agents were ceased and the subject monitored every 30s for signs of emergence, including first response to name, first eyes open and spontaneously ventilating sufficient to remove the laryngeal mask. CCS was observed to increase from the cessation of anesthetic and across the signs of emergence, with comparable values to the BIS™ index. CCS and BIS values were only significantly different at cease gas in the sevoflurane group, but without a ground truth assessment at cease gas, it is unclear whether CCS or BIS more accurately reflects actual patient state. BIS and CCS values were lower at emergence endpoints for xenon than for

{9}------------------------------------------------

sevoflurane. This effect has been previously reported for the BIS. Prediction probabilities calculated across the emergence endpoints for CCS were equivalent to or better than that for the BIS for the sevoflurane group, the xenon group and both groups combined.

Image /page/9/Figure/2 description: The image contains two boxplot graphs comparing CCS and BIS values for two different groups: Sevoflurane and Xenon. Each graph plots the CCS and BIS values at four different time points: Cease Gas, First Response, Eyes Open, and Remove Mask. In the Sevoflurane group, there is a statistically significant difference (*) between the CCS and BIS values at the Cease Gas time point. The CCS and BIS values tend to increase over time in both groups.

CCS and BIS values at clinical endpoints and cessation of gas for sevoflurane and xenon groups. * p < 0.05 (Wilcoxon sign rank test)

Study 6001-004

The BARM algorithms have also been investigated by re-analysing previously recorded EEG data. In one randomized, multi-arm study in Belgium, anesthesia was induced by progressively

{10}------------------------------------------------

increasing the effect-site concentration of propofol (0.75µg/ml starting dose, 0.25µg/ml increments every 4 minutes). Subjects were also co-administered either 0, 2 or 4ng/ml remifentanil (14 subjects per group, 42 total subjects). OAA/S assessments were performed before each increase in propofol dose. CCS was observed to decrease with decreasing OAA/S level - OAA/S 5 (awake) median CCS: 86 (0ng/ml group), 80 (2ng/ml group), 78 (4ng/ml group); OAA/S 0 (unresponsive) median CCS: 38 (0ng/ml), 44 (2ng/ml), 53ng/ml (4ng/ml).

These findings support a recommended range of CCS>80 corresponding to awake and CCS between 40-60 corresponding to unresponsive. CCS varies comparably to other depth of anesthesia indices. Prediction probabilities calculated across all OAA/S levels were 0.85, 0.84, 0.78, and 0.83 (0, 2, 4ng/ml and all combined respectively), equivalent to values obtained using GE M-Entropy™ state and response entropy measures. Prediction probabilities between OAA/S 5 and OAA/S 0 were ≥0.99 indicating near perfect discrimination, CCS is also highly predictive of response to vocal stimulus (P) 3 0.86). Across all OAA/S levels, CCS has comparable prediction probabilities to the State and Response Entropy indexes of the M-Entropy monitor.

Image /page/10/Figure/3 description: The image is a boxplot comparing CCS and OAA/S level at different concentrations of remifentanil. The x-axis is the OAA/S level, ranging from 0 to 5. The y-axis is the CCS, ranging from 0 to 100. There are three different concentrations of remifentanil: 0ng/ml, 2ng/ml, and 4ng/ml.

Box and whisker plots for CCS vs OAA/S level for each remifentanil group

Conclusion

Evaluation of the risks and performance data based on the differences between the subject and predicate devices does not raise any new issues or concerns related to safety or effectiveness. Cortical Dynamics has concluded that the BARM device is as safe and effective as the predicate device for its intended use and is substantially equivalent to the predicate device.

Regulation Number and Section

§ 882.1400 Electroencephalograph.

(a)
Identification. An electroencephalograph is a device used to measure and record the electrical activity of the patient's brain obtained by placing two or more electrodes on the head.(b)
Classification. Class II (performance standards).