The Canary Breathing" System is intended for use as a relaxation treatment for the reduction of stress by leading the user through guided and monitored breathing exercises. The device is indicated as an adjunctive treatment of symptoms associated with panic disorder, to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.

Device Description

The CBS is a biofeedback device that provides the user with a series of tone-guided breathing exercises and an awareness of his or her physiological data. The CBS uses standard biofeedback concepts to teach the patient to regulate their end-tidal CO2 (EtCO2) and respiratory rate (RR). The user's physiological data display allows the patient to see l ) the actual rate of their breathing and 2) how changes in breathing mechanics (depth and volume) affect EtCO2 levels. The CBS consists of a biofeedback training software program (mobile app) and an EtCO2 sensor (capnometer) used with a nasal cannula. The mobile app guides the user through an exercise and displays physiological data, while the sensor collects physiological data and feeds it to the mobile application for biofeedback. The patient's EtCO2 levels and RR are relaved from the capnometer to the mobile application via Bluetooth and are displayed on a tablet device, through the mobile application.

AI/ML Overview

Here's an analysis of the acceptance criteria and supporting studies for the Canary Breathing™ System, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Testing Type	Acceptance Criteria (Implied)	Reported Device Performance
Non-Clinical Testing
CBS Design Verification (Functional)	All functional requirements met, product specifications satisfied.	The CBS passed all functional testing and met all product specification requirements.
CBS Integration Testing	Accurate and successful transmission of RR, EtCO₂, and error information to the CBS software.	RR, ETCO₂ and error information were successfully and accurately transmitted to the Nexus tablet running the CBS software.
Software Verification and Validation	All requirements of the Software Requirements Specification (SRS) met.	The Canary CO₂ Sensor Software met all requirements of the SRS.
Capnometer Equivalency Verification (Accuracy)	Performance equivalent to the predicate LoFlo C5 CO₂ capnometer for EtCO₂ and respiratory rate.	The performance of the Canary CO₂ Sensor is equivalent to the LoFlo predicate device, for EtCO₂ and respiratory rate measurements.
Electrical Safety and Electromagnetic Compatibility	Compliance with IEC 60601-1, IEC 60601-1-2, IEC 60601-1-4, IEC 60601-1-11 standards.	The CBS met all acceptance criteria in accordance with: IEC 60601-1:1988, IEC 60601-1-2:2007, IEC 60601-1-4:2000, IEC 60601-1-11:2010.
Clinical Testing
Efficacy for Panic Disorder (Adjunctive Treatment)	Long-lasting reductions in panic attack frequency/severity, anxiety, avoidance behaviors; improvements in mood/quality of life; normalization of CO₂.	"Findings of these empirical studies have shown that completing the CART training led to long-lasting reductions in panic attack frequency and severity, anxiety symptoms, avoidance behaviors, along with improvements in mood and quality of life in the majority of patients. Causal analysis linked the normalization in CO2 to the observed improvements."
Safety	No adverse events reported.	"Respiratory training using the CART protocol is safe, and no adverse events associated with the use of the device have been reported."

2. Sample Size Used for the Test Set and Data Provenance

The 510(k) summary does not describe a separate, de novo clinical test set specifically for the Canary Breathing System (CBS). Instead, it relies on previously published clinical trials of the Capnometry-Assisted Respiratory Training (CART) protocol, which the CBS aims to implement.

Therefore:

Sample Size for Test Set: Not explicitly stated for a CBS-specific test set. The clinical efficacy claims are based on studies of the CART protocol. The general provenance is "Dr. Meuret and colleagues at Stanford University, Boston University and Southern Methodist University" in the US.
Data Provenance: The referenced studies are "randomized clinical trials." They appear to be prospective studies conducted in the US (Southern Methodist University, Stanford University, Boston University).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Since no de novo clinical test set for the CBS is described, this information is not directly provided for this specific device's ground truth establishment. However, the CART protocol, which forms the basis for the CBS's clinical claims, was developed by:

Experts: Alicia Meuret, Ph.D., a clinical psychologist and Associate Professor in the Department of Psychology at Southern Methodist University, in collaboration with colleagues at Stanford University and Boston University.
Qualifications: Dr. Meuret is a clinical psychologist and Associate Professor. The qualifications of her colleagues are not detailed but are implied to be medical/clinical researchers in relevant fields given the academic institutions.

4. Adjudication Method for the Test Set

Not applicable, as no de novo clinical test set for the CBS is described. The referenced CART studies would have had their own methodologies for data collection and outcome assessment, but this detail is not present in the 510(k) summary.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. The Canary Breathing System is a biofeedback device that directly interacts with the user to guide breathing. It is not an AI-assisted diagnostic device where human "readers" (e.g., radiologists interpreting images) would use it to improve their performance with or without AI.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The device itself is a "standalone" system in the sense that the biofeedback algorithm operates without a human operator directly interpreting its output for diagnostic purposes. The "human-in-the-loop" is the patient, who follows the guided exercises.

The "clinical data" section refers to studies of the underlying CART protocol, which demonstrably showed reductions in panic disorder symptoms. The 510(k) argues that since "The CBS and CART protocol lead the user through identical exercises, however, the user interface for the CBS device is different from that used in the CART protocol studies," the clinical results of the CART protocol can be directly applied to the CBS. This is an argument for standalone clinical effectiveness based on prior research, rather than a new standalone study of the CBS as a diagnostic algorithm.

7. The Type of Ground Truth Used

For the clinical claims, the ground truth was based on:

Clinical Outcomes: "reductions in panic attack frequency and severity, anxiety symptoms, avoidance behaviors, along with improvements in mood and quality of life."
Physiological Correlation: "Causal analysis linked the normalization in CO2 to the observed improvements."
This type of ground truth is best described as clinical outcomes data and physiological measurements.

8. The Sample Size for the Training Set

Not applicable. The CBS is a predetermined biofeedback system based on the CART protocol. It doesn't describe a machine-learning model that requires a "training set" in the conventional sense of AI/ML algorithm development. The "training" in this context refers to the clinical studies that established the efficacy of the CART protocol itself.

The referenced studies are:

Meuret AE, et al. Journal of Psychiatric Research 2008;42;560-8.
Meuret AE, et al. Journal of Psychiatric Research 2009;43;634-41.
Meuret AE. et al. Journal of Consulting and Clinical Psychology 2010:78:691-704.

To find the exact sample sizes, one would need to consult these publications. The 510(k) summary does not provide them.

9. How the Ground Truth for the Training Set Was Established

Since there is no "training set" in the AI/ML sense, this question refers to how the evidence for the efficacy of the underlying CART protocol was established.

The ground truth for the efficacy of the CART protocol was established through two randomized clinical trials (as stated in the "Clinical Data" section).
These trials involved detailed assessment of patient symptoms (panic attack frequency/severity, anxiety, avoidance behaviors), mood, quality of life, and physiological parameters (CO2 levels and respiratory rate) to demonstrate the therapeutic impact of the protocol.
The methodology of randomized clinical trials, which often includes objective and subjective outcome measures, standardized psychological assessments, and physiological data collection, is inherently the method of establishing ground truth for therapeutic interventions.

Summary

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510(k) Summary

510(k) Notification K131586

GENERAL INFORMATION

Applicant:

Palo Alto Health Sciences, Inc. 555 Bryant Street #312 · Palo Alto, CA 94301-1704 U.S.A. Phone: 650-269-4633

Contact Person:

Lori Adels, PhD Regulatory Consultant for Palo Alto Health Sciences Experien Group, LLC 755 N. Mathilda Avenue, Suite 100 Sunnyvale, CA 94085 U.S.A. Phone: 408-400-0856 ext. 112 FAX: 408-400-0865

Date Prepared: December 1, 2013

DEVICE INFORMATION

Trade Name:

Canary Breathing™ System

Generic/Common Name:

Biofeedback device Carbon dioxide gas analyzer

Classification :

21 CFR8882.5050, Class II 21 CFR§868.1400, Class II

Product Code:

HCC ССК

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PREDICATE DEVICES

. InterCure, Inc. RESPeRATE (K020399)
. Respironics Novametrix, LLC, LoFlo C5 CO2 Sensor (K053174)

INDICATIONS FOR USE

INTENDED USE

The Canary Breathing™ System ("CBS") is a device used to provide biofeedback based respiratory training to patients with panic disorder. It is intended to train the patient to control their respiratory rate and end-tidal CO2 levels, which may allow the patient to alleviate abnormal breathing and therefore stress associated with panic attacks.

PRODUCT DESCRIPTION

SUBSTANTIAL EQUIVALENCE

The technological characteristics and intended use of the CBS are substantially similar to an existing biofeedback device, the InterCure. Inc. RESPERATE. The RESPeRATE trains the patient to synchronize his or her breathing to the guiding tones and biofeedback displays on the device. The RESPeRATE gradually prolongs the exhalation tone to slow down breathing as an adjunctive treatment for high blood pressure, with other pharmacological and/or non-pharmacological interventions. The difference in the specific intended use (reduction in blood pressure vs. reduction in symptoms of panic disorder) does not raise new issues of safety and effectiveness as in both cases the devices use normalized breathing to help alleviate an abnormal condition caused in part by stress and in both cases the biofeedback device is used as an adjunct to other pharmacological and/or non-pharmacological interventions.

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Both the CBS and the RESPeRATE provide a respiratory training protocol that uses biofeedback for relaxation (reduction of stress), and both devices are intended as adjunctive devices to other forms of pharmacological and/or non-pharmacological therapy. Both devices include a computerized control unit and a sensor. The RESPeRATE sensor is a band that goes around the patient's upper abdomen to measure breathing rate and depth. The CBS uses a capnometer to measure breathing rate and EtCO2.

The capnometer is substantially equivalent to an existing portable capnometer (LoFlo C5 CO2 capnometer manufactured by Respironics Novametrix, LLC) as determined by bench testing. The LoFlo C5 CO2 capnometer, per the predicate IFU, is used to monitor carbon dioxide in recovery and emergency medicine or respiratory care. Its use in measuring carbon dioxide and respiratory rate in the CBS system for the adjunctive treatment of panic attacks does not raise new issues of safety and effectiveness. Thus, the CBS is substantially equivalent to the predicate devices.

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TESTING IN SUPPORT OF SUBSTANTIAL EQUIVALENCE DETERMINATION

All necessary non-clinical and clinical testing was conducted to support a determination of substantial equivalence to the predicate devices.

NON-CLINICAL DATA

The following table lists the non-clinical testing performed and the results for each test.

Testing Type	Test Description	Result
CBS Design Verification	Canary CO₂ Sensor FunctionalTesting	The CBS passed all functionaltesting and met all productspecification requirements.
	Canary CO₂ Cannula FunctionalTesting
	Nexus 7 tablet Functional Testing
	Canary Mobile ApplicationFunctional Testing
CBS Integration Testing	The integration testing assessed theintegrity of RS232 serial output datagenerated by an OEM purchasedRespironics LoFlo capnometermodule integrated into a CanaryBreathing System (CBS)capnometer.	RR, ETCO₂ and error informationwere successfully and accuratelytransmitted to the Nexus tabletrunning the CBS software.
Software Verificationand Validation	Canary CO₂ Sensor Software Testing(The Level of Concern for the CBSsoftware was determined to be"Minor".)	The Canary CO₂ Sensor Softwaremet all requirements of the SRS.
CapnometerEquivalencyVerification	Canary CO₂ Sensor AccuracyTesting	The performance of the Canary CO₂Sensor is equivalent to theLoFlopredicate device, for EtCO₂ andrespiratory rate measurements.
Electrical Safety andElectromagneticCompatibility	Testing in accordance with thefollowing standards:● IEC 60601-1:1988● IEC 60601-1-2:2007● IEC 60601-1-4:2000● IEC 60601-1-11:2010	The CBS met all acceptance criteriain accordance with:● IEC 60601-1:1988● IEC 60601-1-2:2007● IEC 60601-1-4:2000● IEC 60601-1-11:2010

CLINICAL DATA

The CBS is based on the capnometry-assisted respiratory training (CART) protocol developed by Alicia Meuret, Ph.D., a clinical psychologist and Associate Professor in the Department of Psychology at Southern Methodist University (Dallas, Texas) in collaboration with colleagues at Stanford University, Boston University and Southern Methodist University. Dr. Meuret and colleagues have published three peer reviewed articles describing the results of two randomized clinical trials using the CART protocol to treat patients with panic disorder. The references are listed below. Findings of these empirical studies have shown that completing the CART training led to long-lasting

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reductions in panic attack frequency and severity, anxiety symptoms, avoidance behaviors, along with improvements in mood and quality of life in the majority of patients. Respiratory training using the CART protocol is safe, and no adverse events associated with the use of the device have been reported. Causal analysis linked the normalization in CO2 to the observed improvements.

The CBS and CART protocol lead the user through identical exercises, however, the user interface for the CBS device is different from that used in the CART protocol studies. .The CBS uses a tablet based mobile application, in place of the tape recorder used in the CART protocol. Both devices use a capnometer to measure EtCO2 levels and respiratory rate and to provide the patient with feedback on these parameters. Therefore, the clinical results obtained by following the CART protocol in the above mentioned studies can be directly applied to the CBS device.

Clinical Study References:

Meuret AE, et al. Feedback of end-tidal pCQ2 as a therapeutic approach for panic disorder. Journal of Psychiatric Research 2008;42;560-8.

Meuret AE, et al. Changes in respiration mediate changes in fear of bodily sensations in panic disorder. Journal of Psychiatric Research 2009;43;634-41.

Meuret AE. et al. Respiratory and Cognitive Mediators of Treatment Change in Panic Disorder: Evidence for Intervention Specificity. Journal of Consulting and Clinical Psychology 2010:78:691-704.

The collective performance testing demonstrates that the CBS does not raise new questions of safety or effectiveness when compared to the predicate devices. The results of the performance testing demonstrate that the CBS performs as intended and that its biofeedback protocol is safe and effective for reducing symptoms associated with panic disorder.

CONCLUSION

The CBS has the same intended use and similar technological characteristics as the predicate biofeedback devices as well as the same physiological parameter measurements as the predicate capnometer. The differences in the means for collecting physiological data for biofeedback does not change the intended use or raise any new issues of safety or effectiveness as compared to the predicate biofeedback devices.

SUMMARY

The CBS is substantially equivalent to the predicate devices.

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Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 10, 2013

Palo Alto Health Sciences, Inc. c/o Dr. Lori Adels Regulatory Consultant 755 N Mathilda Ave., Suite 100 Sunnyvale, CA 94085

Re: K131586

Trade/Device Name: Canary Breathing System Regulation Number: 21 CFR 882.5050 Regulation Name: Biofeedback Device Regulatory Class: Class II Product Code: HCC and CCK Dated: November 1, 2013 Received: November 4, 2013

Dear Dr. Adels:

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. 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 is 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 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

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Page 2 - Dr. Adels

CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industrv/default.htm.

Sincerely yours,

Victor Krauthamer -A

Victor Krauthamer, Ph.D. Acting Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K131586

Device Name: Canary Breathing System

Indications For Use:

The Canary Breathing System is intended for use as a relaxation treatment for the reduction of stress by leading the user through quided and monitored breathing exercises. The device is indicated as an adjunctive treatment of symptoms associated with panic disorder, to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of Center for Devices and Radiological Health (CDRH)

Victor Krauthar 2013.12.10 14

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Regulation Number and Section

§ 882.5050 Biofeedback device.

(a)
Identification. A biofeedback device is an instrument that provides a visual or auditory signal corresponding to the status of one or more of a patient's physiological parameters (e.g., brain alpha wave activity, muscle activity, skin temperature, etc.) so that the patient can control voluntarily these physiological parameters.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter when it is a prescription battery powered device that is indicated for relaxation training and muscle reeducation and prescription use, subject to § 882.9.