Prism is a neurofeedback software device intended for relaxation and stress reduction through the use of EEG biofeedback. The device is indicated as an adjunctive treatment of symptoms associated with posttraumatic stress disorder (PTSD), to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.

Device Description

Prism is a software as medical device, to be prescribed for treatment of patients with PTSD by clinicians as adjunct to standard of care. Prism is a software device running on a laptop that uses EEG signal input from an EEG device (g.Nautilos PRO (K171669)). Prism therapy consists of 15, 30-minute sessions and optional periodic refresher sessions. During a session, the patient is connected to 8 or more EEG channels and views an interactive audio/visual interface.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Prism Device

The Prism device is a neurofeedback software device intended for relaxation and stress reduction through the use of EEG biofeedback, specifically indicated as an adjunctive treatment for symptoms associated with Posttraumatic Stress Disorder (PTSD). The acceptance criteria for its effectiveness were defined by the primary performance measure of a prospective, single-arm, open-label, unblinded study.

The primary effectiveness hypothesis was that from baseline to the 3-month follow-up, at least 50% of study participants would experience a response to the treatment, defined as a 6-point reduction in the Clinician Administered PTSD Scale (CAPS-5) score from baseline.

1. Acceptance Criteria and Reported Device Performance

Table: Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Primary Endpoint)	Reported Device Performance (Efficacy Analysis Set)
At least 50% of study participants will experience a 6-point (or more) reduction in CAPS-5 score from baseline to the 3-month follow-up visit.	66.67% of participants showed a ≥6-point reduction in CAPS-5 at 3 months follow-up.
	Secondary Performance Measures (additional context, not primary acceptance criteria): - 54.55% of participants showed a ≥10-point reduction in CAPS-5 at 3 months follow-up. - 50.00% of participants showed a ≥13-point reduction in CAPS-5 at 3 months follow-up.

Safety Acceptance Criteria (Implicit):
The pre-specified safety goals of the study were met, indicating an acceptable safety profile. This would implicitly mean that the incidence and severity of adverse events were within acceptable clinical limits for the target population and device type.

2. Sample Size and Data Provenance

Test Set (Clinical Study Participants):
- Screened: 101 subjects
- Full Analysis Dataset: 79 subjects
- Efficacy Analysis Set: 66 subjects (This is the primary sample size for evaluating the effectiveness against the acceptance criteria).
- Per-Protocol Analysis Set: 63 subjects
Data Provenance: The study was a prospective, single-arm, open-label, unblinded study. It was conducted at 4 sites outside the United States (OUS) in Israel and one US site. This indicates a combination of Israeli and US data.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts used to establish ground truth for the test set. However, it mentions:

Diagnosis of PTSD: Established according to the DSM-5 criteria and CAPS-5.
Clinician assessments: Performed and documented by the investigator or qualified and trained designee.

This implies that the ground truth for PTSD diagnosis and symptom severity (CAPS-5 scores) was established by licensed healthcare professionals (investigators or their designees) who were qualified to administer and interpret DSM-5 and CAPS-5. While specific qualifications (e.g., "radiologist with 10 years of experience") are not provided, "qualified and trained designee" suggests adherence to clinical standards for diagnostic assessment.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the initial PTSD diagnosis or CAPS-5 scoring. The assessments were performed by the "investigator or qualified and trained designee." This implies that the initial assessment by a single qualified professional served as the ground truth.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

There is no indication of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance. The study described is a single-arm clinical study evaluating the device's adjunctive efficacy.

6. Standalone (Algorithm Only) Performance

The study evaluates the Prism software in conjunction with an EEG device (g.Nautilos PRO) as an adjunctive treatment for PTSD. Therefore, this is not a study of standalone algorithm performance without human-in-the-loop, as the device provides visual feedback to the patient to aid in learning to control EEG activity, and it is used under the direction of a healthcare professional.

7. Type of Ground Truth Used

The ground truth for effectiveness was based on:

Clinical Assessments: Clinician Administered PTSD Scale (CAPS-5) scores. CAPS-5 is a structured interview administered by a trained clinician and is considered the gold standard for PTSD diagnosis and severity assessment.
Self-Report Questionnaires: (Secondary measures, not primary ground truth for the acceptance criteria) PTSD Checklist for DSM-5 (PCL-5), Emotion Regulation Questionnaire (ERQ), Patient Health Questionnaire (PHQ-9), Clinical Global Impression (CGI).

8. Sample Size for the Training Set

The document does not provide information regarding the training set size or how the device's algorithms were trained. The provided text describes the clinical study for device validation, not the development or training phase of the software.

9. How Ground Truth for Training Set was Established

As information on the training set is not provided, the method for establishing its ground truth is also not described in this document.

Summary

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March 17, 2023

GrayMatters Health Ltd. % Allison Komiyama, PhD Principal Consultant ROM+ 2251 San Diego Ave, Suite B-257 San Diego, California 92110

Re: K222101

Trade/Device Name: Prism Regulation Number: 21 CFR 882.5050 Regulation Name: Biofeedback device Regulatory Class: Class II Product Code: HCC Dated: February 13, 2023 Received: February 14, 2023

Dear Dr. Komiyama:

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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's

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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 (OS) 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 mediation-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,

Pamela D. Scott -S

Pamela Scott Assistant Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K222101

Device Name Prism

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary K222101

DATE PREPARED

March 16, 2023

MANUFACTURER AND 510(k) OWNER

GrayMatters 82 Ha' Atzmaut Street, Haifa, Israel Telephone: Official Contact: Adar Shani, VP Clinical and Regulatory affairs

REPRESENTATIVE/CONSULTANT

Allison C. Komiyama, Ph.D., RAC Pierre Bounaud, Ph.D. Matthieu Kirkland, M.S. RQM+ Telephone: +1 (412) 816-8253 Email: akomiyama@rqmplus.com

DEVICE INFORMATION

Proprietary Name/Trade Name:	Prism
Common Name:	Device, Biofeedback
Regulation Number:	21 CFR 882.5050
Class:	Class 2
Product Code:	HCC
Premarket Review:	Neurological and Physical Medicine Devices (OHT5)
	Neuromodulation and Physical Medicine Devices (DHT5B)
Review Panel:	Neurology

PREDICATE DEVICE IDENTIFICATION

Prism is substantially equivalent to the following predicates:

510(k) Number	Predicate Device Name / Manufacturer	Predicate
K122879	EEGer4 / EEG Software LLC.	Primary Predicate
K180173	Freespira / Palo Alto Health Sciences, Inc.	Secondary Predicate

The predicate devices have not been subject to a design related recall.

DEVICE DESCRIPTION

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Prism therapy consists of 15, 30-minute sessions and optional periodic refresher sessions. During a session, the patient is connected to 8 or more EEG channels and views an interactive audio/visual interface.

INDICATIONS FOR USE

Prism is a neurofeedback software device intended for relaxation and stress reduction through the use of EEG biofeedback.

The device is indicated as an adjunctive treatment of symptoms associated with posttraumatic stress disorder (PTSD), to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.

COMPARISON OF SUBSTANTIAL EQUIVALENCE

GrayMatters believes that Prism is substantially equivalent to the predicate devices based on the information summarized here:

The subject device has the same intended use and similar indications for use as the predicate devices. Both the subject and predicate devices utilize biofeedback technology based on visual and/or auditory signals to help patients regulate and voluntarily control their physiological parameters.

The subject device has the same technological characteristics as compared to the primary predicate device and the same intended use. Both the subject device and the primary predicate cleared in K122879 have the same principle of operation and train patients to find strategies to regulate their physiological parameters. The subject device and the primary predicate utilize the same energy input and output. Namely, both the subject device and primary predicate provide biofeedback training to patients supported by EEG data collected from an EEG device. Both devices use, measure, and process EEG signals to produce frequency band energy indications for biofeedback purposes.

Both the subject device and predicate devices do not provide any diagnostic conclusions nor provide any classification, diagnosis, or clinical interpretation of data. Finally, the subject device does not incorporate any changes in method of operation, material or design that could affect safety or effectiveness.

These technological characteristics have undergone testing to ensure the device is as safe and effective as the primary predicate. Based on the testing performed (i.e., software verification and validation, and clinical testing), it can be concluded that the subject device does not raise different questions of safety or effectiveness.

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The similar indications for use, mode of operation (i.e., biofeedback device), and performance characteristics for the proposed Prism are assessed to be substantially equivalent to the predicate devices under product code HCC.

SUMMARY OF NON-CLINICAL TESTING

Software Verification: The software development and testing were executed according to FDA's Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices and according to IEC 62304 Medical device software — Software life cycle processes.

The results of these tests indicate that Prism is substantially equivalent to the predicate device.

SUMMARY OF CLINICAL TESTING

GrayMatters Health performed a prospective, single arm study, open label, unblinded study to assess of the Safety and Effectiveness of Prism, as an Adjunct to Standard of Care, in Subjects with Posttraumatic Stress Disorder (PTSD). The purpose of the study was to assess the safety and effectiveness of fifteen (15) EEG-Neurofeedback training sessions using the Prism software in reducing PTSD-related symptoms. Fifteen neurofeedback sessions were delivered twice per week, on non-consecutive days, over 8 consecutive weeks. Subjects (ages 22 to 65) had been diagnosed with PTSD from 1 year to 20 years after index trauma, (i.e., patients with Chronic PTSD). Diagnosis of PTSD was established according to the DSM-5 criteria and CAPS-5. The study was conducted at 4 outside the United States (OUS) sites in Israel and one US site.

The following activities were performed as part of the Baseline Assessment:

. Clinician assessments performed and documented by the investigator or qualified and trained designee: CAPS-5, CGI-S
Subjects instructed to complete all questionnaires on the ePRO system: PCL-5, ERQ, . PHQ-9

During the study, the subjects were provided with a short pre-training session during the baseline assessment visit or combined with the 1st Prism EEG-NF training to become familiar with the system operation prior to the actual Prism EEG-NF training sessions.

Device

Prism software processes EEG signals to provide visual feedback to the patient to aid the patient in learning to control the EEG activity. The EEG signal was provided by the g.Nautilus PRO EEG device.

Primary Performance Measures

The primary measure of this study was to assess the proportion of subjects who demonstrate a 6-point reduction in the Clinician Administered PTSD Scale (CAPS-5) score from Baseline to the 3 months follow-up visit.

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Safety Performance Measures

The safety objectives of this study were to assess the safety of Prism Neurofeedback training by evaluating the incidence, severity, and frequency of adverse events.

Secondary Performance Measures

1. Assess the proportion of subjects who demonstrate a 10-point reduction or more in the PTSD Checklist for DSM-5 (PCL-5).
1. Assess the change from Baseline to the 3 months follow-up in the following scores:
- a. Clinician Administered PTSD Scale (CAPS-5)
- b. PTSD Checklist for DSM-5 (PCL-5)
- Emotion Regulation Questionnaire (ERQ) C.
- Patient Health Questionnaire (PHQ-9) d.
- e. Clinical Global Impression (CGI)

Analysis Set

There were 101 subjects screened for the study with 79 included in the full analysis dataset, 66 included in the efficacy analysis set, and 63 in the per protocol analysis set. The mean time from traumatic event in these subjects was 10 years and ranged between 1 and 20 years with the mean time from first PTSD symptoms being 8.8 years. The majority of the US and OUS patients reported military related PTSD symptoms.

Primary Endpoint

The response rate, i.e., the percent of subjects (50%) with at least 6 points improvement in CAPS-5 from baseline to the 3 months follow up visit (primary effectiveness endpoint) as well as at 8 weeks (exploratory endpoint) was deemed to have been successfully met.

Efficacy Analysis Set (EF)	Response (reduction ≥)
	6 points	10 points	13 points	16 points	21 points
8 weeks	69.70%	50.00%	45.45%	33.33%	22.73%
3 months follow-up	66.67%	54.55%	50.00%	40.91%	27.27%

Safety Conclusions

The serious adverse event (SAE) rate was 2.53% (2/79). None of the SAEs were considered related to the software or to the EEG device. While 50.6% (40/79) of the subjects experienced adverse events (AE's), the majority were mild AEs (headache, fatigue) and recovered right after the training sessions with no further intervention. The pre-specified safety goals of this study were met, and the safety profile was found to be acceptable.

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Study Conclusion

The primary endpoint of this study was responder rate based on a quantitative improvement as measured using the Clinician Administered PTSD Scale (CAPS-5). Using this scale, "Response" was defined as a reduction of 6 or more points. The primary effectiveness hypothesis was that from baseline to the 3 months follow-up, at least 50% of study participants will experience a response to the treatment (defined as a 6-point reduction in CAPS-5 score from baseline). From baseline to the 3-month follow-up, 54.55% of study participants experienced a reduction in the CAPS-5 of 10 points or more and 50% of study participants experienced a reduction of 13 points or more

The totality of the clinical data collected in the study demonstrates that Prism is substantially equivalent to the predicate device in terms of safety and effectiveness.

CONCLUSION

Based on the testing performed, including software verification and clinical testing, it can be concluded that the subject device does not raise different questions of safety or effectiveness compared to the predicate devices. The similar indications for use, technological characteristics, and performance characteristics for the proposed Prism are assessed to be substantially equivalent to the predicate devices.

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	Subject Device	Primary Predicate DeviceSecondary Predicate Device		Statement of Equivalence
	GrayMatters Health Ltd.	EEG Software LLC	Palo Alto Health Sciences, Inc.
	Prism for PTSD	EEGer4K122879	FreespiraK180173
Intended Use	Utilize biofeedback technology based onvisual and/or auditory signals to helppatients regulate and voluntarily controltheir physiological parameters	Utilize biofeedback technology based onvisual and/or auditory signals to helppatients regulate and voluntarily controltheir physiological parameters	Utilize biofeedback technology based onvisual and/or auditory signals to helppatients regulate and voluntarily controltheir physiological parameters	Identical to the predicate devices.
Indications forUse	Prism is a neurofeedback softwaredevice intended for relaxation andstress reduction through the use of EEGbiofeedback. The device is indicated asan adjunctive treatment of symptomsassociated with posttraumatic stressdisorder (PTSD), to be used under thedirection of a healthcare professional,together with other pharmacologicaland/or non-pharmacologicalinterventions.	This device is to be used for generalrelaxation training when used withsupported amplifier/encoders.	Freespira is intended for use as arelaxation treatment for the reduction ofstress by leading the user through guidedand monitored breathing exercises. Thedevice is indicated as an adjunctivetreatment of symptoms associated withpanic disorder (PD) and/or post-traumatic stress disorder (PTSD), to beused under the direction of a healthcareprofessional, together with otherpharmacological and/or non-pharmacological interventions.	Substantially equivalent to the predicatedevices. No impact on safety andeffectiveness.
Product Codes/ RegulationNumber	HCC / 21 CFR 882.5050	HCC / 21 CFR 882.5050	HCC / 21 CFR 882.5050CCK / 21 CFR 868.1400	Identical to the predicate devices. Noimpact on safety and effectiveness.
Class	Class 2	Class 2	Class 2	Identical to the predicate devices. Noimpact on safety and effectiveness.
RegulationDescription	Device, Biofeedback	Device, Biofeedback	Device, Biofeedback	Identical to the predicate devices. Noimpact on safety and effectiveness.
Principle ofOperation	This system trains patients to findmental strategies to regulate theirphysiological parameters (e.g., brainactivity level) to reduce symptomsassociated with PTSD	This system trains patients to find mentalstrategies to regulate their generalrelaxation	This system trains patients to control andnormalize their physiological parameters(e.g., breathing patterns) to reducesymptoms associated with PTSD	Substantially equivalent to the predicatedevices. No impact on safety andeffectiveness.
Intended User	Healthcare professional	Healthcare professional	Patient	Identical to the primary predicate device.No impact on safety and effectiveness.
AssessmentMode forBiofeedback	This is a software-only component thatreceives EEG signals from the g.NautilusPRO EEG and processes those signals tovisual and audio feedback that are usedfor biofeedback training.	This software-only component of an EEGbiofeedback system accepts EEG datafrom an external FDA-approvedamplifier/encoder and providesbiofeedback information.	Respiratory information usingcapnography	Identical to the primary predicate device.No impact on safety and effectiveness.
SupportedDevices	FDA-cleared medical-grade wearableEEG headset to record brain activity inmedical and clinical environments.	FDA-cleared medical-grade wearable EEGheadsets to record brain activity inmedical and clinical environments.	N/A	Identical to the primary predicate device.No impact on safety and effectiveness.
Number ofEEG Channels	8 - 16	4	N/A	Substantially equivalent to the primarypredicate device. No impact on safety andeffectiveness.
Sampling Rate	250 Hz	256 Hz	N/A	Substantially equivalent to the primarypredicate device. No impact on safety andeffectiveness.
Bandwidth	0 – 60 Hz	0 - 50 Hz	N/A	Substantially equivalent to the primarypredicate device. No impact on safety andeffectiveness.

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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.