Modius Sleep is a low-risk non-invasive transdermal neurostimulation device to treat chronic insomnia. The proposed mechanism of the device is through a technology known as electrical vestibular nerve stimulation (VeNS).

It consists of a battery-powered device designed to transcutaneously deliver low-level electrical energy (up to 1mA) to the skin behind the ears, over the mastoid processes. The delivery of this neurostimulation is through two self-adhesive electrode pads. These pads are placed on the skin behind each ear (mastoid area). The intensity of the electric pulse can be adjusted up or down by the user. When turned on, the device delivers a small electrical impulse which stimulates the vestibular nerve. Adjustments to the stimulation level may be made using the up and down buttons on the device, which are located just above the power button. The device can also be paused by pressing the power button twice. When finished the user removes the device and disposes of the electrode pads after each use. When the device is not being used it can be charged through a micro-USB cable. For safety reasons, it is not possible to recharge the battery while the device is in use in stimulation mode.

The key components of the Modius Sleep include the Modius Sleep device (plastic enclosure and printed circuit board assembly (PCBA), stimulation pads (K210448 and K132588), skin cleansing wipes (K121655) and charging accessories. The PCBA consists of a microcontroller, USB connector (charging only), transformer driver, IO expander and EEPROM memory. The embedded software within the device manages overall functionality of the device from Stimulation Control, Power Management, and user interaction (Indication LED and Audio tones).

AI/ML Overview

The provided text is a 510(k) Summary for the Modius Sleep device. It details a clinical study to demonstrate the device's safety and effectiveness for treating chronic insomnia. Here's a breakdown of the requested information based on the document:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" for performance in a table format. However, it defines the primary effectiveness endpoint as a "change in the Insomnia Severity Index (ISI) score at Week 0 and Week 4 between the Modius Sleep group and sham control group." The study then reports the mean change and statistical significance. The implicit acceptance criterion is a statistically significant greater reduction in ISI score for the Modius Sleep group compared to the sham control.

Metric (Implicit Acceptance Criteria)	Modius Sleep Group (Mean ISI Change from Baseline to Week 4)	Sham Control Group (Mean ISI Change from Baseline to Week 4)	Between-Group Difference (95% CI); P-value (Model 1)	Performance Met?
ISI Score Reduction (Statistically Significant Improvement vs. Sham)	-5.80 (Complete Case Analysis)	-3.52 (Complete Case Analysis)	-2.28 (-3.85, -0.71); 0.005	Yes

Note: The table uses data from the "Complete case" analysis as it represents those who adhered to the intervention and showed a statistically significant difference in Model 1. Other models and ITT analyses are also provided in the document.

2. Sample size used for the test set and the data provenance

Test Set (Participants with available data for analysis): 126 participants (61 in Modius Sleep group, 65 in Sham control group for complete case analysis). A total of 149 participants were enrolled and randomized (75 Modius Sleep, 74 Sham control).
Data Provenance:
- Country of Origin: United Kingdom (UK) and Hong Kong (HK). The UK site also included remote recruitment from the Republic of Ireland (ROI).
- Retrospective or Prospective: Prospective. The study was a "4-week pivotal randomized controlled trial."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense (e.g., radiologists interpreting images). Instead, the "ground truth" for insomnia diagnosis and severity (ISI scores) was established via self-reported patient outcomes and an online survey based on clinical diagnostic criteria (AASM ICSD and DSM-V) prior to enrollment. There is no information provided about the number or specific qualifications of experts involved in the initial diagnosis or ISI score evaluation for the study participants, beyond the general statement that "further information was collected by an online survey to establish that the participants had chronic insomnia at the time of enrolment as defined by ICSD and DSM-V."

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This was a clinical trial evaluating a treatment device based on self-reported patient outcomes (ISI scores), not an AI device requiring reader adjudication of findings.

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. This study evaluated a medical device for treatment of insomnia in a direct patient-use scenario, not an AI-assisted diagnostic tool for human readers.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

This was a clinical trial of a medical device used by patients, not an algorithm. Therefore, "standalone (algorithm only)" performance is not applicable. The device's performance is inherently tied to human interaction (patient use).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for effectiveness was outcomes data based on the Insomnia Severity Index (ISI) scores, which are a validated patient-reported outcome measure for insomnia. The initial diagnosis of chronic insomnia for inclusion criteria was based on patient self-reporting via an online survey aligned with AASM (American Academy of Sleep Medicine) International Classification of Sleep Disorders (ICSD) and The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.

8. The sample size for the training set

Not applicable. This clinical study evaluated the device's performance in a randomized controlled trial. There is no mention of a "training set" in the context of an algorithm or AI development.

9. How the ground truth for the training set was established

Not applicable, as there was no training set in the context of an algorithm.

Summary

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October 27, 2023

Neurovalens Limited Jason McKeown, MD CEO 8 Carmagrim Road Portglenone. BT44 8BP United Kingdom

Re: K230826

Trade/Device Name: Modius Sleep Regulation Number: 21 CFR 882.5800 Regulation Name: Cranial electrotherapy stimulator Regulatory Class: Class II Product Code: QJQ Dated: March 21, 2023 Received: March 24, 2023

Dear Dr. McKeown:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding 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, MS Assistant Director DHT5B: Division of Neuromodulation and Rehabilitation Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K230826

Device Name

Modius Sleep

Indications for Use (Describe)

Modius Sleep is a non-invasive, home-use neurostimulation device to treat chronic insomnia in adults aged 22 and older.

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)

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EUROVALENS

Modius Sleep

Traditional 510(k)

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510(k) Summary

This 510(k) Summary is submitted in accordance with 21 CFR Part 807, Section 807.92.

Submitter l.

Neurovalens Limited 8 Carmagrim Road Portglenone County Antrim BT44 8BP

United Kingdom

Contact person/ official correspondence:

Dr Jason McKeown CEO Neurovalens Ltd. Tel: +44 (0) 7412508707 Email: Jason.mckeown@neurovalens.com

Date Prepared

27th October 2023

II. Device

Name of Device: Modius Sleep Common or usual name: Electrical Vestibular Nerve Stimulator (VeNS) Classification name: Cranial Electrotherapy Stimulator (CES) Regulatory Class: II Product Code: Requested Regulation number: 882.5800 Classification panel: Neurology Special Controls: Modius Sleep complies with the special controls as set in FDA 21 CFR 882.5800 for a Class II, Cranial Electrical Stimulation (CES) device.

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ROVALENS

Modius Sleep

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Predicate devices lll.

Primary predicate device CES Ultra, K062284 Secondary predicate device Alpha-Stim® CS, K903014

No reference devices were used in this submission.

Device description IV.

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OVALENS

Modius Sleep Traditional 510(k)

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510(k) Summary

Biocompatibility testing in accordance with the endpoints of ISO 10993-1 to be addressed for a surface medical device, with prolonged: > 24 hours less than 30 days contact duration, demonstrated good biocompatibility for all components of the Modius Sleep device.

Device Usage

Daily sessions of Modius Sleep has been shown to improve insomnia when assessed at 4 weeks.

After using Modius Sleep there are usually no physical limitations imposed so most users can resume normal activities immediately. Some users may have a response that affect their ability to perform potentially hazardous tasks, such as operating a motor vehicle or heavy machinery for up to several hours after treatment. However, no significant lasting side effects have been reported.

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EUROVALENS

Modius Sleep

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510(k) Summary

Indications for use V.

Modius Sleep is a non-invasive, home-use neurostimulation device that is indicated to treat chronic insomnia in adults aged 22 and older.

VI. Comparison of the technological characteristics with the predicate device

Modius Sleep is substantially equivalent with respect to indications for use, stimulation parameters (i.e., current levels, frequencies, pulse width and amplitude) and electrode placement to the predicate devices CES Ultra (cleared by K062284), and Alpha-Stim® CS (cleared by K903014).

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Modius Sleep

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Table 1. Summary of substantial equivalence

Property	Proposed Device	Primary Predicate	Secondary Predicate	Comment
Device	Modius Sleep	CES Ultra	Alpha-Stim® CS
Indications for Use	Modius Sleep is a non-invasive, home-use neurostimulation device that is indicated to treat chronic insomnia in adults aged 22 and older.	The CES Ultra is indicated for the treatment of insomnia, depression or anxiety	The Alpha-Stim® 100 is a precision medical instrument used for the management of pain, anxiety, depression, and/or insomnia.	All devices are indicated for the treatment of insomnia.
Target Population	Adults 22 and older	Adults	Adults, and children under adult supervision	N/A
Environment	Home	Home	Home	N/A
Waveform	Symmetrical Biphasic Rectangular Wave	Symmetrical Biphasic Rectangular Wave	Symmetrical Biphasic Rectangular Wave	Identical
Current Intensity Range	$0\u03bc$ A - 1000 $\u03bc$ A	$0\u03bc$ A - 1500 $\u03bc$ A continually adjustable	$0\u03bc$ A - 500 $\u03bc$ A	Modius Sleep and the CES Ultra have near identical current intensity ranges
Pulse Width Range	1s	2ms	250ms - 1s	Pulse width varies depending on frequency range
Number of electrodes	Two	Two	Two	Identical

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Modius Sleep

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Property	Proposed Device	Primary Predicate	Secondary Predicate	Comment
Electrode placement	Mastoid	Mastoid or earlobes	Head - earlobes	The Modius Sleep electrodes are placed onmastoids. CES Ultra also supports mastoid onlyelectrode placement.
Power Source	3.75 Lithium PolymerBattery	9V Alkaline Battery	2 x AAA NiMH
Frequency	0.25Hz	100Hz	0.5Hz, 1.5Hz, 100Hz
Treatment Range	30 min	30min, 60min orcontinuous	10min, 20min, 60 min orcontinuous	Modius Sleep maximum treatment time is withinthe range of the predicates
Unit Controls	Built into the device	Built into the device	Built into the device	Identical
Dimensions	16.5cm x 15.1cm x6.6cm	13.5cm x 6.4cm x3.3cm	9.8cm x 6.3cm x 2cm	Modius Sleep is larger than the predicatedevices
Enclosure	Plastic	Plastic	Plastic	Identical

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Table 2. Safety Information Comparison

Property	Proposed Device	Primary Predicate	Secondary Predicate	Comment
	Modius Sleep	CES Ultra	Alpha-Stim® CS
Electrical Safety	Complies with IEC60601-1	Complies with IEC60601	Complies withIEC 60601	The proposed device and predicate devices areidentical
EMC	Complies with IEC60601-1-2	Complies with IEC60601-1-2	Complies with IEC60601-1-2	The proposed device and predicate devices areidentical
Software	Level ofConcern	Moderate	Moderate	Moderate	The proposed device and predicate devices areidentical
	Verification &Validation	Complies withFDA GuidanceRequirement	Complies with FDAGuidance Requirement	Complies with FDAGuidance Requirement
Biocompatibility	Complies with ISO10993	Complies with ISO10993	Complies withISO 10993	The proposed device and predicate devices areidentical

Modius Sleep

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NEUROVALENS	Modius Sleep
	Traditional 510(k)
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510(k) Summary

Table 3. Technical Information for Modius Sleep Output Parameters

	Modius Sleep	CES Ultra	Alpha-Stim CS
510(k) Number	K230826	K062284	K903014
Device Name	Modius Sleep	CES ultra	Alpha-Stim CS
Manufacturer	Neurovalens Ltd	Neuro-Fitness LLC	Electromedical Products Inc.
Power Source†	3.75 Lithium PolymerBattery	9V Alkaline Battery	2 x AAA NiMH
-Method of Line Current Isolation	DC:DC transformer	N/A Non Rechargeable	N/A Non-Rechargeable
- Patient Leakage Current (as per ANSI/AAMI 60601-1)	0μΑ	Unknown	Unknown
-Normal Condition (μΑ)	0-1000μΑ	0-1500μΑ	0-500μΑ
-Single Fault Condition (μΑ)	2.3μA	Unknown	1.3mA
Average DC current through the electrodes when the device is on but no pulses are being delivered (µA)	0μΑ	Unknown	Unknown
Number of output channels	1	1	1
-If more than one channel, is the stimulus delivered to each channel synchronous or alternating between each channel?	N/A	N/A	N/A
-If more than one channel, describe method of channel isolation	N/A	N/A	N/A
Software/Firmware/Microprocessor Control	Yes	Yes	Yes
Automatic Overload Trip?	No	No	No
Automatic Shut Off?	Yes	Yes	Yes
		Modius Sleep	CES Ultra	Alpha-Stim CS
User Override Control?		Yes	Yes	Yes
Mode or Program Name		Stimulation mode	Stimulation mode	Stimulation/Treatment Mode
	Waveform (e.g., pulsed monophasic, biphasic)	Biphasic	Biphasic	Biphasic
	Shape (e.g., rectangular, spike, rectified sinusoidal)	Rectangular	Rectangular	Rectangular
	Maximum Output Voltage (volts) (+/-1%)	500mV @500 Ω	Unknown	@500 Ω
		2 V @ 2 kΩ	Unknown	@ 2 kΩ
		10V @10 kΩ	Unknown	@10 kΩ
	Maximum Output Current (specify units) (+/-2%)	1000μA @500 Ω	Unknown	500μA @ 500 Ω
		1000μA @ 2 kΩ	1.5mA @ 2kΩ	500μA @ 2 kΩ
		1000μA @10 kΩ	Unknown	500μA @10 kΩ
	Duration of primary (depolarizing) phase† (msec)	4000(4 seconds)	10ms	2000ms, 1000ms, 10ms
	Pulse Duration†† (msec)	2000(2 second)	5ms	1000ms, 500ms, 5ms
	Frequency†† (Hz) [or Rate†† (pps)]	0.25Hz	100Hz	0.5Hz, 1Hz, 100Hz
	For interferential modes only: Beat Frequency† (Hz)
	For multiphasic waveforms Symmetrical phases? only:
	Phase Duration† (include units),(state range, if applicable), (both phases, if asymmetrical)		Not Applicable for these devices
		Modius Sleep	CES Ultra	Alpha-Stim CS
Net Charge (microcoulombs (mC) per pulse) (If zero, state method of achieving zero net charge.)		1000 μC @2kΩ	0.75μC @500 Ω	300μC, 150 μC, 1.5 µC
Maximum Phase Charge, (μC)		1000μC @2kΩ	0.75μC@ 2 kΩ	500µC @ 500Ω
Maximum Current Density,††† (mA/cm², r.m.s.)		0.5mA /cm²@500 Ω	1.91mA/cm²@500 Ω	~1.2mA/cm² @ 500Ω
Maximum Average Current (average absolute value), mA		1mA @2kΩ	3.07mA/cm² @2 kΩ	Unknown
Maximum Average Power Density,††† (W/cm²), (using smallest electrode conductive surface area)		0.99mW/cm² @2 kΩ	9.19mW/cm² @2 kΩ	Unknown
Burst Mode†††† (i.e., pulse trains):	(a) Pulses per burst	2	2	2, 2, 2
	(b) Bursts per second	0.25	100	0.5, 1, 100
	(c) Burst duration (seconds)	4	0.01 (10ms)	2, 1, 0.01s
	(d) Duty Cycle: Line (b) x Line (c)	0.5 (50%)	0.2(20%)	0.5 (50%)
ON Time (seconds)		2 sec	10ms	1sec, 0.5sec, 10ms
OFF Time (seconds)		2 sec	40ms	1sec, 0.5sec, 10ms

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NEUROVALENS

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Table 4. Comparison of Device Outputs

Output value	Modius Sleep	CES Ultra	Alpha Stim CS
Output value at	Provide for all load conditions.	Provide for all load conditions.	Provide for all load conditions.
500Ω, 2kΩ and 10kΩ	1mA at all loads	1.5mA at all loads	0.5mA at all loads
Load conditions	0.25Hz	100Hz	0.5Hz
Electrodesurface	Conductive Area (16mm diameter)	Ear clips	1.5cm Diameter
area in cm2	2.0cm²	Diameter 7.9mm0.5cm² Area	1.77cm²
Current density	500Ω0.5mA/cm²,	500Ω1.91mA/cm²	500Ω1.2mA/cm²
	2kΩ0.5mA/cm²	2kΩ3.07mA/cm²	2kΩUnknown
	10kΩ0.5mA/cm²	10kΩUnknown	10kΩUnknown
Charge density	500Ω497.63µC/cm² – Per Pulse	500ΩUnknown	500ΩMax 500uC
	2kΩ497.63µC/cm² – Per Pulse	2kΩUnknown	2kΩMax 500uC
	10kΩ497.63µC/cm² – Per Pulse	10kΩUnknown	10kΩMax 500uC
Power density	500Ω,0.25mW/cm²2KΩ0.99mW/cm²10KΩ4.97mW/cm²	500Ω,Unknown2KΩ9.19ma/cm²10KΩUnknown	500Ω,Unknown2KΩUnknown10KΩUnknown
Max phase charge(pulse width x peakcurrent)	500Ω,1000 μC – Per Pulse2KΩ1000 μC – Per Pulse10KΩ1000 μC – Per Pulse	500Ω,Unknown2KΩ0.75 μC10KΩUnknown	500Ω,500 μC2KΩUnknown10KΩUnknown
Max phase chargedensity (pulse widthx peak current) /electrode surfacearea	500Ω497.63μC/cm² – Per Pulse2KΩ497.63μC/cm² – Per Pulse10KΩ497.63μC/cm² – Per Pulse	500ΩUnknown2KΩUnknown10KΩUnknown	500ΩUnknown2KΩUnknown10KΩUnknown
Max average powerdensity (Duty cycle xpeak current)^2 x	500Ω,0.12mW/cm²	500Ω,Unknown	500Ω,Unknown
(load Ω) ÷ electrodesurface area)	2kΩ0.5mW/cm²10kΩ2.49mW/cm²	2kΩ9.19mW/cm²10kΩUnknown	2kΩUnknown10kΩUnknown
Electrode number	2 Electrodes	2 Electrodes	2 Electrodes

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NEUROVALENS

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NEUROVALENS	Modius Sleep Traditional 510(k)
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NEUROVALENS

Modius Sleep

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Performance Data VII.

Non-clinical tests

The Modius Sleep was evaluated for its safety and effectiveness based on the following testing:

Table 5: Non-clinical tests

Test Name	Test Description	Results
Device Ship/TransportTesting	Ensure device, enclosed in the selected shipping container,meets ASTM D4169 specifications.	Passed
Biocompatibility Testing	Testing and analysis of the Modius Sleep device hasdemonstrated compliance to ISO 10993-1: Biologicalevaluation of medical devices - Guidance	Passed
Electrical Safety	The Modius Sleep device was tested to confirm that it metthe applicable standards for electrical safety (IEC 60601-1)	Passed
EMC	The Modius Sleep device was tested to confirm that it metthe applicable standards for electromagnetic compatibility(EMC) (IEC 60601-1-2)	Passed
Usability Testing	Modius Sleep was assessed with regards to usability forcompliance with IEC 62366 - Medical devices - Applicationof usability engineering to medical devices	Passed
Maximum Current &Phase Charge Testing	The Maximum Current & Phase Charge Testing was to detailthe Max Current / Power output of the system under differentload conditions and determine the Max Phase Charge, MaxCurrent Density and Max Power Density of the Modius Sleepdevice.	Passed
System Verification andValidation Testing	The system verification and validation testing was performedto verify the hardware and firmware of the Modius SleepDevice	Passed

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510(k) Summary

Labeling

The labeling for the device included the intended use population and the intended use environment; warning that patients should be monitored by their physician for signs of worsening; A warning that instructs patients on how to mitigate the risk of headaches, and what to do should a headache occur; a warning that instructs patients on how to mitigate the risk of dizziness, and what to do should dizziness occur; a detailed summary of the clinical testing, which includes the clinical outcomes associated with the use of the device, and a summary of adverse events and complications that occurred with the device; Instructions for use that address where to place the electrodes, what stimulation parameters to use, and duration and frequency of treatment sessions based on the results of clinical studies for the device; A detailed summary of the device technical parameters, including waveform, output mode, pulse duration, frequency, train delivery, and maximum charge and energy; and Information on validated methods for reprocessing any reusable components between uses.

Software Verification and Validation Testing

Software verification and validation testing were conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."

The software for this device was considered as a "moderate" level of concern, since a failure or latent design flaw could directly result in minor injury to the patient or a failure or latent flaw could indirectly result in minor injury to the patient or operator through incorrect or delayed information or through the action of a care provider.

Animal Studies

No animal studies were conducted as part of submission to prove substantial equivalence.

Clinical Studies

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510(k) Summary

CES devices collectively demonstrate a class effect of CES for treating anxiety and/or insomnia. However, it cannot be concluded, based on available information alone, that specific CES devices or stimulation parameters are effective for treating anxiety and/or insomnia. As such, individuals using this device should work with the prescribing medical provider to determine the best treatment settings to use. As such, please see below for a general summary of pertinent clinical literature that has been published using various combinations of CES devices, stimulation settings, and electrode positions.

General CES Summary (January 1, 1970 to November 8, 2022)

As of November 2022, there were a total of 23 studies that evaluated the effectiveness of CES on insomnia. Of the 11 randomized control trials (RCT), some reported greater reduction in insomnia symptoms in the CES group compared to placebo12345, while others reported no significant differences in measures of insomnia symptoms between the 2 groups®73,9;10;11 .Among the 8 observational studies, CES treatment was associated with less frequent12 and less intense13 sleep disturbances, improved soundness of sleep14, less difficulty falling asleep14;15;16 and feeling more rested15 or improved mood14 in the morning. Several observational studies reported no impact of CES on insomnia1718 or reported an effect that did not persist after the first week19. A meta-analysis of 14 RCTs indicated that CES versus sham treatment had no impact on insomnia20. Lastly, 3 reviews evaluated the effectiveness of CES on insomnia. One review found 23 studies, 6 of which were RCTs of which only 2 studied participants with insomnia21. Of these two RCTs, only 1 showed improved patient-reported sleep latency and objective changes in sleep, while the other did not show any change21. The other 2 reviews concluded that studies evaluating the effectiveness of CES on insomnia were inconclusive22 or inconsistent²3. In studies that reported improvement in insomnia with use of CES, the reported stimulation parameters, electrode placement, and treatment schedule varied widely and were only evaluated in a small number of combinations.

Please note that not all combinations of parameters provided below have been studied for safety and effectiveness; therefore, individuals using this device should work with the prescribing medical provider to determine the best treatment settings to use and should not apply electrodes to locations that are not indicated in the specific product's labeling. Please

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also note that not all CES devices are capable of providing the same stimulation parameters or combination of stimulation parameters.

Please see information below on the 23 studies (January 1, 1970 to November 8, 2022) noted above that evaluated the effectiveness of CES on insomnia:

Electrode placement:

. Over orbits and mastoids
Over eyelid and mastoids .
Over orbits and occiput .
. Earlobes

Waveform:

. Square
Rectangular, monophasic .

Frequency:

. 100 Hz
350 Hz
0.5 Hz ●
14 Hz ●

Pulse Width:

0.7 ms .
1 ms
2 ms .

Maximum current:

0.01-1.9mA
Treatment schedule:
30 minutes, 5 times a week for 1-2 weeks ●

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30-minute sessions twice a day ●
single 20-30 minute session
. 15 minutes daily for 24 days
30 minutes for 1-7 days .

Clinical Testing of Modius Sleep

Clinical testing of Modius Sleep included a pivotal randomized, double blind sham controlled clinical trial to evaluate the safety and efficacy of the Modius Sleep Electrical Vestibular Stimulation (VeNS) device, for the treatment of chronic insomnia.

Study design

A 4-week pivotal randomized controlled trial with two groups 1) Modius Sleep device group and 2) Sham (placebo) control group was used to evaluate the safety and efficacy of the Modius Sleep device as a treatment for chronic insomnia.

The study was a multi-site, randomised, double blinded, sham-controlled trial conducted from May 2022 to January 2023. The study has been registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04452981). Research sites included University of Ulster, United Kingdom (UK), and Hong Kong Polytechnic University, Hong Kong (HK). The study protocol was approved at the UK site by Wales Research Ethics Committee 7 (Ref: 22/WA/0022) and at the HK site by the Human Subjects Ethics Sub-Committee, Hong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Kong Polytechnic University (Ref: HSEARS20220320001). Informed consent was obtained from all participants.

Adults with an Insomnia Severity Index (ISI) score of 15 or higher were recruited using online platforms and randomly allocation ratio) to receive the Modius Sleep device (intervention group) or the sham device (active control group). Both groups were advised to use their allocated devices for 30 minutes per day prior to going to sleep for a four-week duration. The devices are identical in appearance and therefore neither the participant nor the clinical study team knew whether the Modius Sleep device or sham device was allocated. Primary and secondary outcomes were captured at baseline and at 4 weeks.

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126 participants (aged 19-67 years) with moderate to severe insomnia assessed by the insomnia severity index (ISI) were enrolled. While the ISI is a useful screening tool for insomnia, it does not cover all components of The AASM (American Academy of Sleep Medicine) International Classification of Sleep Disorders (ICSD), and The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) that are used for diagnosis of chronic insomnia. For this reason, further information was collected by an online survey to establish that the participants had chronic insomnia at the time of enrolment as defined by ICSD and DSM-V. Specifically, information was collected regarding the duration and frequency of their sleep disturbance and associated daytime symptoms, confirmation of adequate opportunity and conditions to sleep, and confirmation of no other co-existing conditions. This further information provided confirmation that the participants had Chronic Insomnia at the time of enrolment in the Modius Sleep trial.

For the duration of the study, participants agreed not to take prescribed or over the counter sleeping medication; not to undergo any extreme lifestyle changes that could have impacted their sleep quality; not to use sleep trackers; not to travel to different time zones and to maintain a familiar sleeping routine.

Primary Effectiveness Endpoint

The efficacy of the Modius Sleep device was quantified by change in the Insomnia Severity Index (ISI) score24 at Week 0 and Week 4 between the Modius Sleep group and sham control group.

Primary Safety Endpoint

An evaluation of the safety of the Modius Sleep device was quantified by the occurrence in adverse events between the Modius Sleep group and sham control group.

Results

A total of 149 eligible participants were recruited and randomised to the Modius Sleep group (n=75) or the sham control group (n=74). Twenty-three participants withdrew from the study

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before the 4-week visit. A complete case analysis was undertaken on all participants (n=126) with available data at baseline and at the 4-week visit. The mean age of the sample (67% female) was 41 years (age range: 19 to 67 years).

Table 6: Participant accountability

Stage	Modius Sleep Device	Sham control device	Total
Enrollment	75	74	149
Treatment	75	74	149
Primary safety endpointanalysis	75	74	149
Primary effectivenessendpoint analysis	61	65	126
Secondary endpointanalysis	61	65	126

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Table 7: The effect of Modius Sleep on Insomnia Severity Index (Primary outcome all participants)

	Modius Sleep	Sham control	Between-group difference mean (95% CI);P valueb
	Mean (SD)	Mean (SD)	Model 1	Model 2	Model 3
ITT (MI)
Baseline	19.77 (0.48)c	18.36 (0.52)c
4 weeks	13.99 (0.65)c	14.67 (0.78)c	-2.08(-3.93, -0.24)0.028	-2.13(-4.34, 0.07)0.058	-1.93(-4.02, 0.16)0.070
Within-groupmean change(95% CI); P valuea	-5.78(-6.93, -4.63)<0.001	-3.70(-4.99, -2.41)<0.001
ITT (LOCF)
Baseline	19.77 (4.14)	18.36 (4.51)
4 weeks	14.82 (5.12)	15.22 (6.11)	-1.80(-3.24, -0.35)0.015	-1.88(-3.68, -0.07)0.042	-1.76(-3.62, 0.10)0.064
Within-groupmean change(95% CI); P valuea	-4.95(-5.90, -3.99)<0.001	-3.15(-4.25, -2.05)<0.001
Complete case
Baseline	19.72 (4.03)	18.34 (4.69)
4 weeks	13.92 (4.67)	14.82 (6.30)	-2.28(-3.85, -0.71)0.005	-2.49(-4.45, -0.53)0.013	-2.40(-4.36, -0.44)0.017
Within-groupmean change(95% CI); P valuea	-5.80(-6.79, -4.81)<0.001	-3.52(-4.74, -2.30)<0.001

ª Within-group mean change in ISI scores from baseline to week 4 analysed using paired sample t-test. "Between-group difference in ISI scores (dependent variable) from baseline to week 4 analysed using ANCOVA. Model 1 includes treatment group as the independent variable; model 2 includes treatment group-by-site interaction; and model 3 includes the covariates in model 2 as well as sex (Male vs Female), age continuous, and race (White vs Asian vs Mixed). Standard error in brackets. Intention-to-treat analysis, ITT (Multiple Imputation, MI and Last observation carried forward, LOCF) includes all participants randomised and who had baseline ISI scores (Modius Sleep, n=73 and sham control n=74). Complete case analysis includes participants who had baseline and 4-week ISI scores (Modius Sleep n=61 and sham control n=65).

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Outcomes

The effect of the Modius Sleep device on change in ISI score from baseline to the 4-week visit is shown in Table 7 above. The results show that the Modius Sleep group had a greater and statistically significant reduction in ISI score compared with the sham control group.

AE reports were minor and all self- resolving including, headaches, nystagmus (eye movements), low mood, and mild tinnitus. Rate of AE reporting was 12% (9 participants out of 75) in the Modius Sleep group vs 8% (6 participants out of 74) in the Sham group. There were no device related SAE's reported during the study. One non-device related SAE was reported during the study. Further information below.

Effectiveness

The effect of the Modius Sleep device on change in ISI score from baseline to the 4-week visit is shown in Table 7. The ITT (MI and LOCF) and complete case analyses both demonstrated that both randomization groups reduced their ISI scores; however, the Modius Sleep group had a significantly greater reduction in ISI score (model 1). When site and treatment groupby-site interaction were added as covariates (model 2), the greater reduction in ISI score observed in the Modius Sleep group remained significant for the LOCF ITT and complete case analyses and approached statistical significance for the MI ITT analysis. Model 3 included the covariates from model 2 and demographic variables including age, sex, and race. The greater reduction in ISI score observed in the Modius Sleep group remained statistically significant for the complete case analysis and approached statistical significance for both ITT (MI and LOCF) analyses.

Discussion (Effectiveness)

To determine if the treatment effect found in model 1 was homogeneous across the research sites (HK and UK), model 2 additionally included the variables site and treatment-by-site interaction. The statistically significant treatment effect remained for the LOCF ITT and complete case approaches as described above. Furthermore, the treatment-by-site interaction was not significant in the ITT (MI & LOCF) or complete case models, which indicates that the treatment effects can be combined across the sites to create an overall estimate of treatment effect. The treatment effect, however, did not remain significant for the MI ITT approach. This

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approach accounts for uncertainty and is less bias than the single imputation method (LOCF); however, it provides the most conservate estimate of treatment effect.

To investigate consistency of the treatment effect across subgroups, model 3 included the covariates sex (Male vs Female), continuous age, and race (White vs Asian vs Mixed). Results showed that the covariates added in the model were not significant in the ITT (MI or LOCF) or complete case models which indicates the treatment effect is consistent across these subgroups. As mentioned above, the statistically significant treatment effect remained for the complete case analysis and only approached statistical significance for both ITT (MI and LOCF) analyses. An ITT analysis includes all the participants who were randomized and analysed according to the treatment group they were assigned. The benefit of this type of analysis is that it produces unbiased estimates of treatment effects, provides the greatest generalisability, and preserves the sample size. The treatment effects, however, are usually conservative because it includes people who have withdrawn from the study and those who did not comply with treatment. The complete case analysis includes participants who completed the study and had data collected at baseline and at the 4 week follow up visit. This type of analysis provides information on how the treatment (Modius Sleep) performs in an ideal situation, i.e., includes only people who adhered to the intervention. The addition of the covariates in model 3 may have also reduced the power to detect a significant treatment effect in the ITT analyses.

Safety

A total of 22 Adverse Events were reported during the 4-week study (16 reported by the Modius Sleep group vs. 6 reported by the sham control group), these included headaches and nausea, which are known side effects of cranial electrical stimulation. One finding of a Serious Adverse Event (minor cerebrovascular accident) was reported during follow up with a participant who had been previously withdrawn. Assessment of the participant by the hospitalbased medical team reported previously undiagnosed hypertension (high blood pressure) which is believed to have been the cause of this event, and therefore this was not classified as a device related SAE. The patient's hypertension was subsequently treated with no further events reported.

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The adverse events were all minor, caused a minimal discomfort to participants, and all selfresolved during the period of the study. Clinical and research studies report the possibility of mild adverse effects including skin irritation, discomfort from the stimulation, sensation of feeling off-balance, dizziness, nystagmus (eye movements), blurred or flashing vision, headache, nausea, and tinnitus.

Table 8: Number (%) of Adverse Events (Safety Data Analysis) according to Randomisation Group (all participants, n=149)

		Totaln (%)	ModiusSleepn (%)	ShamControln (%)
Nervous System Disorders	Headache/migraine	7 (4.7)	6 (4.0)	1 (0.7)
Eye Disorders	Flashes in peripheral vision	2 (1.3)	2 (1.3)	0 (0)
	Shadow in peripheral vision	1 (0.7)	1 (0.7)	0 (0)
	Tingling in eye	1 (0.7)	1 (0.7)	0 (0)
Ear disorders	Ear pain	2 (1.3)	0 (0)	2 (1.3)
	Tinnitus	2 (1.3)	1 (0.7)	1 (0.7)
	Itching in ear	1 (0.7)	0 (0)	1 (0.7)
Mood disorders	Low Mood	2 (1.3)	2 (1.3)	0 (0)
Mouth/dental disorders	Metal fillings pulsing	1 (0.7)	0 (0)	1 (0.7)
	Grinding teeth	1 (0.7)	1 (0.7)	0 (0)
Gastrointestinal Disorders	Nausea	1 (0.7)	1 (0.7)	0 (0)
Other	Tingling in arm	1 (0.7)	1 (0.7)	0 (0)

Adverse Events are grouped by Body System and Reported Term and sorted by descending frequency of reported event. Includes withdrawals. Participants could have reported more than one event.

The AE's reported in this study are listed in the table above. There was no significant difference between the AE's reported in both groups. All AE's were self-limiting and resolved when the device usage was stopped.

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The risk of these adverse effects occurring is usually mitigated by reducing or stopping the stimulation. If a user does experience these adverse effects, they should stop stimulation by turning off or removing the device.

The following warnings have been included in the labelling:

. To mitigate the risk of dizziness, the device must be worn when seated, and start stimulation at a low level and increase gradually to the highest comfortable level. If you do experience dizziness, stop stimulation by turning off or removing the device. If dizziness persists, please consult your physician.
. To mitigate the risk of headaches, the device must be worn when seated, and start stimulation at a low level and increase gradually to the highest comfortable level. If you do experience a headache, stop stimulation by turning off or removing the device. If the headache persists, please consult your physician.
. The Modius Sleep device should only be used as prescribed by a trained physician.

Generalizability of study data

The Modius Sleep trial consisted of two clinical sites, with one based in the United Kingdom (UK) and the other in Hong Kong (HK). It should be noted that the UK site received ethical approval to recruit remotely, and additionally this extended to include remote recruitment across The Republic of Ireland (ROI). Therefore, three populations were included in the Modius Sleep study, with two of these populations being recruited nationwide (as opposed to the close proximity of the clinical site).

UK and HK participants met the same definition of insomnia and had the same ISI inclusion criteria of 15 or greater. The baseline ISI scores reported for the Modius Sleep study are in

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line with literature, and comparable across the two sites (HK 19.11 and UK 18.82). An Insomnia study involving Hong Kong participants, that utilized the ISI to measure sleep improvement, has reported comparable baseline ISI scores to the US. Yin et al.25 conducted a randomised controlled trial (RCT) to evaluate the efficacy and safety of acupuncture treatment for primary insomnia. The study enrolled patients from Shanghai Municipal Hospital of Traditional Chinese Medicine, and the primary outcome was change in ISI score, and the intention to treat population demonstrated a baseline ISI score of 17. Ong et al.20, evaluated the efficacy of mindfulness meditation for the treatment of chronic insomnia recruiting patient from Rush University, US. The average baseline ISI score for the three treatment groups was 16.8. Another trial evaluating mindfulness in Los Angeles reported an average baseline ISI score of 17.8.27

Furthermore, a recent population-based survey of adults in Hong Kong estimated the prevalence of insomnia to be 20.7%.20 This was twofold higher than the insomnia estimate (11.9%) from a 2002 survey, using a comparable measure29. Approximately 10% of the adult population suffers from an insomnia disorder and another 20% experiences occasional insomnia symptoms30. Data from The National Health Interview Survey reported 14.5% of adults had trouble falling asleep and 17.8% of adults had trouble staying asleep. As such, the prevalence of insomnia in Hong Kong is comparable to both global and US estimates. Additionally, a study comparing the both the prevalence of insomnia according to different diagnostic measures, and between Hong Kong and the United States by adopting a similar methodology used by the America Insomnia Survey (AIS), showed that the prevalence of insomnia disorder was similar for Hong Kong and the United States.31

An important consideration regarding generalizability for this body of evidence is that because we were seeking to treat individuals prior to their use of other interventions (e.g., drugs), the remaining potential confounding factor would be if there were differences in the presentation and diagnosis of the disease based on race/ethnicity. We were unable to find any evidence to suggest that such a difference exists. We also note that when verifying the presence of insomnia at each site as described above, the same criteria were used in both cases. Even if

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both sites were within either the UK or Hong Kong, it would have been entirely possible for the baseline mean to vary between those two sites and yet not affect overall generalizability.

Study Limitations

As with all clinical trials, confounding factors can make it difficult to interpret how well the intervention has worked. Therefore, to ensure a robust dataset with a low number of variables, several conditions and medications were excluded in this clinical trial.

. Persons currently taking over the counter or prescribed medications for sleep, beta blockers, or who regularly use antihistamines.
. Persons with a history of stroke, or severe injury to the brain.
Persons with an active significant mental health disorder or cognitive impairment. ●
. Persons with any disease which may cause vestibular neuropathy.
. Persons with myelodysplastic syndromes, or history of malignancy in the past 12months.

Conclusion

A complete case analysis of this pivotal study reported that participants using the Modius Sleep device daily demonstrated a statistically significant improvement in their insomnia at 4 weeks.

Safety and Effectiveness Conclusion VIII.

Based on the clinical performance as documented in the pivotal clinical study, Modius Sleep is a low-risk, non-invasive, drug-free therapy, that provides a statistically significant benefit at 4 weeks when used to treat chronic insomnia.

Based on this clinical testing and technical comparison, it can be determined that Modius Sleep device is substantially equivalent to the listed predicate devices.

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References

Electrosleep: A double-blind clinical study. Rosenthal, S H. 2, 1972, Biological 1 Psychiatry, Vol. 4, pp. 179-185.
2 Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients: A double-blind study. Philip, P, et al. 5, Mar 1, 1991, Biol Psychiatry, Vol. 29, pp. 451-456.
3 Electrosleep therapy: A controlled double blind study. Feighner, J P, Brown, S L and Olivier, J E. 2, 1973, Journal of Nervous and Mental Disease, Vol. 157, pp. 121- 128.
4 The treatment of insomnia through the use of electrosleep: An EEG study. Weiss, M F. 2, 1973, Journal of Nervous and Mental Disease, Vol. 157, pp. 108-120.
5 The effect of a single cranial electrotherapy stimulation on multiple stress measures. Heffernan, M. 1995, The Townsend Letter for Doctors and Patients, Vol. 147, pp. 60-64.
6 A clinical trial of electrosleep therapy with a psychiatric inpatient sample. Levitt, E A, James, McI N and Flavell, P. 4. 1975, Australian and New Zealand Journal of Psychiatry, Vol. 9, pp. 287-290
7 The management of chronic hysteria: A review and double-blind trial of electrosleep and other relaxation methods. Scallet, A, Cloninger, R and Othmer, E. 6, 1976, Diseases of the Nervous System, Vol. 37, pp. 347-353.
Electrosleep therapy: A double-blind trial. Hearst. E D. et al. 4, 1974, Archives of 8 General Psychiatry, Vol. 30, pp. 463-466.
റ A comparison of relaxation techniques with electrosleep therapy for chronic, sleeponset insomnia: A sleep-EEG study. Coursey, R D, et al. 1, 1980, Biofeedback & Self Regulation, Vol. 5, pp. 57-73.
10 Cranial Electrotherapy Stimulation to Improve the Physiology and Psychology Response, Response-Ability, and Sleep Efficiency in Athletes with Poor Sleep Quality. Chang, W D, et al. 4, Feb 9, 2022, Int J Environ Res Public Health, Vol. 19.
11 Cranial electrostimulation improves slow wave sleep in collegiate population: a polysomnographic study. Aseem, A, Chaudhry, N and Hussain, M E. 1, Jan-Mar 2022, Sleep Sci, Vol. 15, pp. 88-94.
12 Electrosleep: A preliminary communication. Rosenthal, S H and Wulfsohn, N L. 2. 1970, Journal of Nervous and Mental Disease, Vol. 151, pp. 146-151.
13 An exploratory investigation of CES as an employee stress management technique. Matteson, M T and Ivancevich, John M. 1986, Journal of Health and Human Resource Administration, Vol. 9, pp. 93-109.
14 Studies of electrosleep on normal adults, insomniacs, and hypertensive patients. Nagata, K, et al. 3-4, 1981, Tokushima Journal of Experimental Medicine, Vol. 28, pp. 69-83.

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15 The effects of electrosleep on insomnia revisited. Cartwright, R D and Weiss, M F. 2, 1975, Journal of Nervous and Mental Disease, Vol. 161, pp. 134-137.
16 Quantitative EEG analysis of electrosleep using analog frequency analyzer and digital computer methods. Itil, T, et al. 6, 1972, Diseases of the Nervous System, Vol. 33, pp. 376-381
17 Does electrosleep induce natural sleep? Empson, J J A. 6, 1973, Electroencephalography & Clinical Neurophysiology, Vol. 35, pp. 663-664.
18 Ineffectiveness of electrosleep in chronic primary insomnia. Frankel, B L, Buchbinder, R and Snyder, F. 4, 1973, Archives of General Psychiatry, Vol. 29, pp. 563-568.
19 A double blind study of electrosleep for anxiety and insomnia. Moore. J A, et al. 1, 1975, Biological Psychiatry, Vol. 10, pp. 59-63.
20 Meta-analysis of randomized controlled trials of cranial electrostimulation: Efficacy in treating selected psychological and physiological conditions. Klawansky, S, et al. 7, 1995, Journal of Nervous and Mental Disease, Vol. 183, pp. 478-484.\
21 Impact of Cranial Electrostimulation on Sleep: A Systematic Review. Aseem, A and Hussain, M E. 2019, Sleep Vigilance, Vol. 3, pp. 101-112.
22 Benefits and Harms of Cranial Electrical Stimulation for Chronic Painful Conditions, Depression, Anxiety, and Insomnia: A Systematic Review. Shekelle, P G, et al. 6, Mar 20, 2018, Ann Intern Med, Vol. 168, pp. 414-421.
23 A Critical Review of Cranial Electrotherapy Stimulation for Neuromodulation in Clinical and Non-clinical Samples. Brunyé, TT, et al. Feb 1, 2021, Front Hum Neurosci, Vol. 15
24 Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4. PMID: 11438246.
25 Yin X, Gou M, Xu J, Dong B, Yin P, Masquelin F, Wu J, Lao L, Xu S. Efficacy and safety of acupuncture treatment on primary insomnia: a randomized controlled trial. Sleep Med. 2017 Sep;37:193-200. doi: 10.1016/j.sleep.2017.02.012. Epub 2017 Mar 8. PMID: 28899535.
26 Onq JC, Manber R, Seqal Z. Xia Y, Shapiro S, Wyatt JK. A randomized controlled trial of mindfulness meditation for chronic insomnia. Sleep. 2014 Sep 1;37(9):1553-63. doi: 10.5665/sleep.4010. PMID: 25142566; PMCID: PMC4153063.
27 El Rafihi-Ferreira R, Morin CM, Toscanini AC, Lotufo Neto F, Brasil IS, Gallinaro JG, Borges DS, Conway SG, Hasan R. Acceptance and commitment therapy-based behavioral intervention for insomnia: a pilot randomized controlled trial. Braz J Psychiatry. 2021 Sep-Oct;43(5):504-509. doi: 10.1590/1516-4446-2020-0947. PMID: 3331495; PMCID: PMC8555642.

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28 Chan WS, Cheng C. Elevated Prevalence of Probable Insomnia among Young Men during Social Unrest in Hong Kong: A Population-Based Study. Behav Sleep Med. 2022 Mar-Apr;20(2):204-211. doi: 10.1080/15402002.2021.1902813. Epub 2021 Mar 24. PMID: 33757388.
29 Li, R. H., Wing, Y. K., Ho, S. C. and Fong, S. Y. Gender differences in insomnia a study in the Hong Kong Chinese population. J. Psychosom. Res., 2002, 53: 601–609
30 Morin CM, Jarrin DC. Epidemiology of Insomnia: Prevalence, Course, Risk Factors, and Public Health Burden. Sleep Med Clin. 2022 Jun;17(2):173-191. doi: 10.1016/j.jsmc.2022.03.003. Epub 2022 Apr 23. PMID: 35659072.
31 Chung KF, Yeung WF, Ho FY, Yung KP, Yu YM, Kwok CW. Cross-cultural and comparative epidemiology of insomnia: the Diagnostic and statistical manual (DSM), International classification of diseases (ICD) and International classification of sleep (ICSD). Sleep Sleep Sleep Med. 2015 disorders doi: 10.1016/j.sleep.2014.10.018. Epub 2015 Jan 21. PMID: 25761665.

Regulation Number and Section

§ 882.5800 Cranial electrotherapy stimulator.

(a)
Identification. A cranial electrotherapy stimulator is a prescription device that applies electrical current that is not intended to induce a seizure to a patient's head to treat psychiatric conditions.(b)
Classification. (1) Class II (special controls) when intended to treat insomnia and/or anxiety. The special controls for this device are:(i) A detailed summary of the clinical testing pertinent to use of the device to demonstrate the effectiveness of the device to treat insomnia and/or anxiety.
(ii) Components of the device that come into human contact must be demonstrated to be biocompatible.
(iii) The device must be designed and tested for electrical safety and electromagnetic compatibility (EMC) in its intended use environment.
(iv) Appropriate software verification, validation, and hazard analysis must be performed.
(v) The technical parameters of the device, including waveform, output mode, pulse duration, frequency, train delivery, maximum charge, and energy, must be fully characterized and verified.
(vi) The labeling for the device must include the following:
(A) The intended use population and the intended use environment;
(B) A warning that patients should be monitored by their physician for signs of worsening;
(C) A warning that instructs patients on how to mitigate the risk of headaches, and what to do should a headache occur;
(D) A warning that instructs patients on how to mitigate the risk of dizziness, and what to do should dizziness occur;
(E) A detailed summary of the clinical testing, which includes the clinical outcomes associated with the use of the device, and a summary of adverse events and complications that occurred with the device;
(F) Instructions for use that address where to place the electrodes, what stimulation parameters to use, and duration and frequency of treatment sessions. This information must be based on the results of clinical studies for the device;
(G) A detailed summary of the device technical parameters, including waveform, output mode, pulse duration, frequency, train delivery, and maximum charge and energy; and
(H) Information on validated methods for reprocessing any reusable components between uses.
(vii) Cranial electrotherapy stimulator devices marketed prior to the effective date of this reclassification must have an amendment submitted to the previously cleared premarket notification (510(k)) demonstrating compliance with these special controls.
(2) Class III (premarket approval) when intended to treat depression.
(c) Date premarket approval application (PMA) or notice of completion of product development protocol (PDP) is required. A PMA or notice of completion of a PDP is required to be filed with the Food and Drug Administration on or before March 19, 2020, for any cranial electrotherapy stimulator device with an intended use described in paragraph (b)(2) of this section, that was in commercial distribution before May 28, 1976, or that has, on or before March 19, 2020, been found to be substantially equivalent to any cranial electrotherapy stimulator device with an intended use described in paragraph (b)(2) of this section, that was in commercial distribution before May 28, 1976. Any other cranial electrotherapy stimulator device with an intended use described in paragraph (b)(2) of this section shall have an approved PMA or declared completed PDP in effect before being placed in commercial distribution.