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The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore Sapphire device is indicated for:

• · The preventive treatment of migraine headache in adolescent (aged 12 and older) and adult patients
• The acute treatment of pain associated with migraine headache in adolescents (aged 12 and older) and adult patients
• · Adjunctive use for the preventive treatment of cluster headache in adult patients
• · The acute treatment of pain associated with episodic cluster headache in adult patients
• · Treatment of hemicrania continua in adults
• · Treatment of paroxysmal hemicrania in adults

The gammaCore Sapphire (gammaCore) is a multi-use, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and -amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).

The gammaCore Sapphire:

• . Includes a charging station incorporated into the "clamshell" storage case connected to a power adapter for charging of the device as necessary by the end user.
• Provides visible (light and display) and audible (beep) feedback regarding device and stimulation . status.
• Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, after . which the device automatically turns off unless turned off earlier by the user/operator. Note: One dose is defined as one stimulation cycle lasting 120 seconds (2 minutes).
• Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily number . of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
• Indicates on the display the number of remaining doses available in a 24-hour period.

The device will be provided to the patient/user with an initial 10-, 31-, or 93-day RFID card on the basis of the health care provider's prescription. Additional (refill/reload) cards will be provided in response to a user/patient request based on a prescription from his or her health care provider. The refill/reload RFID cards will be programmed by electroCore or its authorized agent. This is a specialized application for dispensing the device therapy.

When a 10-, 31-, or 93-day refill/reload card is requested by a patient/user (in accordance with a prescription from a health care provider) for a unique device serial number, an RFID card is encoded with the appropriate dosage according to the prescription. The gammaCore RFID card-loading application uses a proprietary encoding algorithm to encrypt the therapy days and doses per day on the refill/reload RFID card using near field communication protocols.

The encoded refill/reload RFID card is then provided to the user/patient who requested the refil/reload of the device, along with 1 to 6 additional tubes of conductive gel (the number of conductive gel tubes provided is based on the 10-, 31-, or 93-day refill/reload being provided). On receipt of the RFID card, the user/patient refills/reloads his or her gammaCore device by placing the RFID card across the face of the device (with the device turned on). The device will display "rd" and the "refill" icon as the device reads the RFID card. The device will signal (beeping twice) when it has been loaded with the programmed doses. The device will now be ready for use as treatment. The RFID card can be used for only one refill/reload; upon completion of the device refill/reload, the card can be thrown away.

In addition, a Bluetooth® feature will be enabled to facilitate diagnostics of any devices returned by patients/users to the manufacturer, to allow determination of the number of days the device was used and/or the number of doses as well as any days/doses remaining on the device. The Bluetooth feature will not be accessible to the patient/user; it is accessible only to the device manufacturer.

The subject device delivers the same energy and maintains the same operational characteristics as the gammaCore Sapphire device cleared in K203546. No changes in design or manufacturing process have been made that could affect device functionality. All functional aspects of the device remain the same as K203546, including the strength and nature of the device outputs.

The provided document is a 510(k) summary for the gammaCore Sapphire device, which is an external vagal nerve stimulator. It focuses on demonstrating substantial equivalence to a predicate device (gammaCore Sapphire, K203546) rather than detailing a study that proves the device meets specific acceptance criteria based on performance.

The submission is for an expanded labeling (additional indications for use), and the key argument for substantial equivalence is that the technology of the device itself is identical to the previously cleared predicate device. Therefore, no new performance testing or clinical studies were conducted to prove the device meets new acceptance criteria for its core technical performance. Instead, the "study" proving its acceptance is the demonstration that the expanded indications are supported by existing clinical data and that the device remains safe and effective for these new uses, given its proven performance characteristics.

Here's how to break down the information based on your request, focusing on the expanded indications rather than new hardware performance metrics:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a submission based on substantial equivalence for expanded indications and not a new device with novel performance criteria, the "acceptance criteria" are implicitly tied to demonstrating that the device is as safe and effective as a legally marketed predicate for the new indications.

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

The "test set" in this context refers to the clinical data used to support the expanded indications, as no new hardware performance tests were conducted.

• Sample Size:
  • Hemicrania Continua: 19 patients across various clinical audits and case series/case reports.
  • Paroxysmal Hemicrania: 14 patients across various clinical audits and case series/case reports.
• Data Provenance: The document does not explicitly state the country of origin for the clinical audits and case series/reports. The references include publications in international journals (e.g., Cephalalgia, Headache, J Neurol Neurosurg Psychiatry, J Headache Pain, JAMA Neurol), suggesting a multi-national or at least broader clinical context. The data is presented as a combination of extrapolated data from randomized controlled trials (RCTs) (for cluster headache, DEN150048 and K182369) and retrospective clinical audits and case series/case reports.

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

• The document does not specify the number of experts or their qualifications involved in establishing the "ground truth" for the case series/audits. It refers to published literature (references 5-10) which would inherently involve clinical diagnoses made by medical professionals (neurologists, headache specialists). The diagnoses of hemicrania continua and paroxysmal hemicrania themselves serve as the "ground truth" for these conditions, and their treatment response to nVNS is observed.

4. Adjudication Method for the Test Set

• The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for the clinical data from the case series/audits. These are real-world observational data and published case series, where patient outcomes are typically evaluated by the treating clinician(s) and potentially reviewed by the authors of the respective papers. The RCT data (for cluster headache) would have had their own internal adjudication processes, but these details are not provided here as the data is "extrapolated."

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

• No, an MRMC comparative effectiveness study was not done. This device is a direct treatment device, not an AI-assisted diagnostic tool for human readers. Therefore, this type of study is not applicable.

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

• This is a medical device for direct patient treatment, not a diagnostic algorithm. Therefore, "standalone performance" in the context of an algorithm or AI is not applicable. The device itself performs the function (nerve stimulation).

7. The Type of Ground Truth Used

• The ground truth for the expanded indications (hemicrania continua and paroxysmal hemicrania) is based on clinical diagnoses of these conditions and patient-reported (or clinician-observed) outcomes reflecting "clinically meaningful benefits" from nVNS therapy (e.g., decreases in pain severity, reductions in frequency/severity/duration of attacks). This is essentially outcomes data from real-world clinical experience and existing published literature.

8. The Sample Size for the Training Set

• This submission describes a medical device, not an AI/ML algorithm that requires a "training set" in the computational sense. Therefore, the concept of a training set sample size is not applicable to this 510(k) submission. The device's design and functionality were established through prior development and clearance (K203546).

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

• As explained above, there is no "training set" in the context of an AI/ML device. The "ground truth" for the device's original design and safety/effectiveness (as detailed in the predicate K203546) would have been established through a combination of engineering validation, non-clinical testing, and clinical studies for the original indications. The current submission simply leverages that established ground truth and applies it to new, similar indications based on existing clinical evidence.

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gammaCore Sapphire (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore is indicated for:

• · The preventive treatment of migraine headache in adolescent (age 12 and older) and adult patients.
• · The acute treatment of pain associated with migraine headache in adolescent (age 12 and older) and adult patients.
• · Adjunctive use for the preventive treatment of cluster headache in adult patients.
• · The acute treatment of pain associated with episodic cluster headache in adult patients.

The gammaCore Sapphire (gammaCore) is a multiuse, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).
The gammaCore Sapphire:

• . Includes a charging station incorporated into the "clam shell" storage case connected to a power adapter for charging of the device as necessary by the end user.
• Provides visible (light and display) and audible (beep) feedback regarding device and stimulation . status.
• . Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, after which the device automatically turns off unless turned off earlier by the user/operator. Note: One dose is defined as one stimulation cycle lasting 120 seconds (2 minutes).
• . Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily number of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
• Indicates on the display the number of remaining doses available in a 24-hour period. .

The provided text describes a 510(k) summary for the gammaCore Sapphire device, which is an external vagal nerve stimulator for headache. This submission seeks to expand the indications for use to include the adolescent population for the preventive and acute treatment of migraine headache.

Based on the information provided, here's a breakdown regarding acceptance criteria and supporting studies:

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

   The document does not explicitly state acceptance criteria in terms of numerical performance metrics (e.g., sensitivity, specificity, accuracy) because this is a 510(k) submission for an expanded indication of an already cleared physical medical device, not a new AI/ML-driven diagnostic or prognostic device. The "acceptance criteria" in this context are related to demonstrating substantial equivalence to a predicate device and safety and effectiveness in the new population. The substantial equivalence comparison table (Table 1) acts as the primary "performance" comparison.

   Acceptance Criteria (Implied)	Reported Device Performance (Subject Device vs. Predicate)
   Intended Use	Same
   Indication for Use	Expanded to adolescents (age 12+) for preventive and acute migraine treatment. Supported by extrapolation from adult data and a small adolescent study.
   Rx vs OTC	No change (Prescription use)
   Treatment Protocol for Migraine (Acute & Preventive)	No change compared to adults (same 120-second stimulation cycle, number of stimulations, and daily schedule)
   Patient-Contacting Materials	No change (SS, ABS-PC, SignaGel electrode gel)
   Electrical Classification	No change (UL 60601-1 Class III Type BF Applied Part)
   Waveform/Frequency	No change (Sinusoidal wave, symmetrical biphasic 5000-Hz pulses at 25 Hz)
   Maximum Output	No change (30V, 60 mA peak)
   Load Impedance	No change (450-550 ohms)
   Power Supply	No change (3V LiFePo4 battery)
   Service Life	No change (3 Years from date of manufacture)
   Controls	No change (Control slide)
   Output Regulation	No change (Device software and control slide)
   Device Status Display	Differences in user interface that do not impact safety or effectiveness.
   Battery Charger	No change (Qi-compatible wireless charger in clam shell storage case)
   RFID Refill/Reload Capability	No change (Allows refilling/reloading)
   Device Diagnostics (Bluetooth)	No change (Provides diagnostics for manufacturer)
   Alarm Signals	No change (Start-up, Session complete, Errors/depleted battery, No doses left, Expired/no days left, Low battery, Reloading error, Card error)
   Display/Message	No change to core output display, minor user interface differences considered not to impact safety/effectiveness.

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

   For the expansion of indications to adolescents, the primary "test set" for safety and effectiveness relied heavily on:

   • Extrapolation from adult clinical data: This is clearly stated, meaning the adult data from prior studies (PRESTO, PREMIUM, EVENT) served as a large part of the basis.
   • Small adolescent study: "a small study was performed evaluating the use of gamma Core Sapphire in the acute treatment of migraine in adolescent population. As described in Grazzi et al¹, in nine (9) adolescents, 46.8% of treated migraine attacks were considered successfully treated and did not require any rescue medication."
   • Sample size for adolescent study: 9 adolescents.
   • Data provenance: The Grazzi et al. study is a published peer-reviewed paper (Neurol Sci. 2017 May). The document does not specify the country of origin for the Grazzi study, but typically these are international clinical trials. It is a prospective study as it evaluates the use in a group of adolescents.

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

   This information is not provided in the 510(k) summary. For a device like nVNS, the efficacy is typically self-reported by patients (e.g., pain reduction, headache freedom) and assessed by clinicians based on established diagnostic criteria for migraine. The Grazzi et al. paper would contain specifics on patient selection and outcome assessment, but that detail is not within this 510(k) summary. Given it's a treatment device, "ground truth" would be clinical outcomes (e.g., headache resolution) rather than an expert-adjudicated label on an image.

4. Adjudication method for the test set

   Not applicable in the context of this device. Adjudication methods like 2+1 or 3+1 are common in image-based AI studies where expert consensus is needed to establish a definitive diagnosis for a test image. Here, clinical outcomes are measured after device use.

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

   No MRMC comparative effectiveness study was done, as this is not an AI-assisted diagnostic device. It is a physical neuromodulation device. Therefore, no information on human reader improvement with AI assistance is applicable or provided.

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

   Not applicable. The gammaCore Sapphire is a physical device that delivers therapy and is used by a human patient. It does not operate as a standalone algorithm or AI.

7. The type of ground truth used

   The ground truth for the effectiveness of the device in the expanded indication (adolescents) is based on:

   • Clinical Outcomes Data: Self-reported pain relief and resolution of migraine symptoms, as well as the absence of requiring rescue medication. The Grazzi et al. study reported "46.8% of treated migraine attacks were considered successfully treated and did not require any rescue medication."
   • Adult Clinical Trial Results: The prior 510(k)s (K173442, K191830) relied on outcomes from multi-center, randomized, double-blind, sham-controlled clinical studies (PRESTO, PREMIUM, EVENT) for adults.

8. The sample size for the training set

   Not explicitly applicable in the context of this device because it's not an AI/ML algorithm that is "trained" on data in the traditional sense. The device's technological characteristics are fixed. The clinical studies (PRESTO, PREMIUM, EVENT, and the Grazzi et al. study) provide the evidence base that informed the safety and effectiveness, rather than a "training set" for an algorithm. The total sample sizes for these studies are not fully detailed in this 510(k) summary but would be found in the referenced prior 510(k) documents and publications. The adult studies would have had considerably larger sample sizes than the 9 adolescents mentioned.

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

   Again, "training set" and "ground truth" establishment in the AI/ML sense are not directly applicable. The "ground truth" for the effectiveness shown in the supporting clinical studies (for both adults and adolescents) was established through clinical trial methodology:

   • Randomized, double-blind, sham-controlled study designs comparing the device to a sham control.
   • Measurement of defined clinical endpoints, such as pain reduction, headache freedom, and reduction in headache frequency.
   • Reporting of adverse events to assess safety.

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The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore Sapphire device is indicated for:

• · Adjunctive use for the preventive treatment of cluster headache in adult patients.
• · The acute treatment of pain associated with episodic cluster headache in adult patients.
• · The acute treatment of pain associated with migraine headache in adult patients.
• · The preventive treatment of migraine headache in adult patients.

The gammaCore Sapphire (gammaCore) is a multiuse, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).

The gammaCore Sapphire:

• . Includes a charging station incorporated into the "clam shell" storage case connected to a power adapter for charging of the device as necessary by the end user.
• Provides visible (light and display) and audible (beep) feedback regarding device and . stimulation status.
• Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, . after which the device automatically turns off unless turned off earlier by the user/operator.
• Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily . number of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
• Indicates on the display the number of remaining doses available in a 24-hour period. .

This document is a 510(k) summary for the gammaCore Sapphire device and doesn't explicitly state "acceptance criteria" in a quantitative table. Instead, it demonstrates substantial equivalence to a predicate device by proving that the expansion of indications for use (specifically, for the preventive treatment of migraine headache) does not raise new questions of safety or effectiveness.

The "acceptance criteria" effectively are that the new indication performs similarly in terms of safety and efficacy to the existing cleared indications and comparable to the predicate device, as demonstrated through clinical studies.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

As noted, the document doesn't provide a formal table of "acceptance criteria" and "reported device performance" in the typical sense of a pass/fail metric for a specific algorithm. Instead, it presents clinical study results to demonstrate that the expanded indication for the gammaCore Sapphire device (preventive treatment of migraine headache) is safe and effective and does not raise new questions of safety or effectiveness compared to the predicate device and previously cleared indications.

The key "performance" is the therapeutic gain and P-value for migraine reduction and the safety profile demonstrated in the clinical trials.

• Therapeutic gain in mean reduction of migraine days per month: -0.74 (P=0.043)
• Therapeutic gain in mean reduction of headache days per month: -0.86 (P=0.045)
• Therapeutic gain in mean reduction of acute medication days per month: -0.80 (P=0.039)

EVENT Study (for preventive chronic migraine):

• Change in mean headache days from baseline to month 2: -1.4 (nVNS) vs. -0.2 (sham)
• Continued nVNS use led to significant reductions over time. |
  | Technological characteristics, intended use, and other device specifications remain unchanged or demonstrably equivalent. | "There have been no changes in the technological characteristics or intended use of the gammaCore Sapphire in the proposed Indications for Use statement."
  (Detailed comparison in Table 5 showing no changes in patient-contacting materials, electrical classification, waveform/frequency, maximum output, load impedance, power supply, service life, controls, output regulation, display, charger, RFID, Bluetooth, and alarm signals). |

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

The "test set" in this context refers to the clinical study populations used to support the expanded indication.

• PREMIUM Study:

  • ITT (Intent-to-treat) Population: 332 subjects (ITT nVNS: 165, ITT Sham: 167)
  • mITT (modified Intent-to-treat) Population: 278 subjects (mITT nVNS: 138, mITT Sham: 140)
  • Data Provenance: Prospective, randomized, double-blind, sham-controlled, multicenter study conducted at 22 European sites from June 1, 2015, to November 21, 2017.

• EVENT Study:

  • ITT (Intent-to-treat) Population: 59 subjects (ITT nVNS: 30, ITT Sham: 29)
  • PP (Per-protocol) Population: 49 subjects (PP nVNS: 26, PP Sham: 23)
  • Data Provenance: Prospective, randomized, sham-controlled, multicenter pilot study for the prevention of chronic migraine, conducted at 6 sites in the United States from October 2012 to April 2014.

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

Clinical trials for medical devices like this typically rely on patient-reported outcomes validated by medical professionals and objective measures (like headache day diaries). The "ground truth" here is less about image interpretation by experts and more about the clinical definition of migraine, headache days, and adverse events, as assessed by the investigators and patients themselves.

The document does not specify a separate panel of experts establishing ground truth in the way it might for an AI-powered diagnostic device. Instead, the "ground truth" for efficacy (e.g., reduction in migraine days) is derived from the comprehensive data collected during the trials, including patient diaries and clinical assessments by the investigators at the study sites. The inclusion criteria for patients required a diagnosis of migraine with or without aura in accordance with international classification criteria (ICHD-3 Beta for PREMIUM, ICHD-2 for EVENT), implying that the diagnosing clinicians (experts) established the baseline condition.

4. Adjudication Method for the Test Set

This type of information (e.g., 2+1, 3+1 adjudication) is typically relevant for studies where subjective assessments (like imaging reads) require a consensus for ground truth. For a clinical trial involving patient symptoms and objective measurements, this type of adjudication method is generally not applicable. The studies were randomized, sham-controlled, and double-blind, which are methods designed to reduce bias in treatment efficacy evaluation.

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

No, an MRMC comparative effectiveness study was not done. This device is a therapeutic stimulation device, not an AI-powered diagnostic tool requiring human reader assistance.

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

This question is not applicable. The gammaCore Sapphire is a non-invasive vagus nerve stimulator, a physical device used by patients under a prescription, not an algorithm. The "performance" is the physiological effect of the stimulation.

7. The Type of Ground Truth Used

The "ground truth" for the efficacy endpoints was based on:

• Patient-reported outcomes: Primarily the number of migraine days per month, headache days per month, and acute medication days per month, typically recorded in diaries.
• Clinical assessment: Diagnosis of migraine based on established International Classification of Headache Disorders (ICHD) criteria by trained clinicians at the study sites.
• Safety monitoring: Assessment of adverse events by investigators.

8. The Sample Size for the Training Set

There isn't a "training set" in the context of an algorithm or AI. The device itself is a physical medical device. The "training" that occurs is the patient's and clinician's understanding of how to use the device, not an algorithmic learning process. The clinical studies described (PREMIUM and EVENT) serve as the validation datasets for safety and efficacy for the expanded indication.

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

Not applicable, as there is no algorithmic "training set" for this device.

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gammaCore Sapphire (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore is indicated for:

• · Adjunctive use for the preventive treatment of cluster headache in adult patients.
• · The acute treatment of pain associated with episodic cluster headache in adult patients.
• · The acute treatment of pain associated with migraine headache in adult patients.

The gammaCore Sapphire (gammaCore) is a multiuse, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).

The gammaCore Sapphire:

• . Includes a charging station incorporated into the "clam shell" storage case connected to a power adapter for charging of the device as necessary by the end user.
• . Provides visible (light and display) and audible (beep) feedback regarding device and stimulation status.
• . Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, after which the device automatically turns off unless turned off earlier by the user/operator. Note: One dose is defined as one stimulation cycle lasting 120 seconds (2 minutes).
• . Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily number of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
• Indicates on the display the number of remaining doses available in a 24-hour period. ●

The provided documentation describes the gammaCore Sapphire (non-invasive vagus nerve stimulator), which is indicated for:

• Adjunctive use for the preventive treatment of cluster headache in adult patients.
• The acute treatment of pain associated with episodic cluster headache in adult patients.
• The acute treatment of pain associated with migraine headache in adult patients.

The information primarily focuses on demonstrating substantial equivalence to predicate devices rather than defining specific acceptance criteria for performance benchmarks against a gold standard for a diagnostic AI device. However, based on the clinical study presented, we can infer a primary efficacy outcome as an "acceptance criteria" and the reported device performance from that study.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

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The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide noninvasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.

gammaCore Sapphire (gammaCore), like the predicate gammaCore-2 device, is a multi-use, hand-held, rechargeable, portable device consisting of a rechargeable battery, signal generating and amplifying electronics, with a slide control switch for user / operator control of the signal amplitude (relative range 0-40 continuous). Like gammaCore-2, gammaCore Sapphire:

• includes a charging station incorporated into the "clam shell" storage case connected to a power adapter to charge the device as necessary by the end user
• provides visible (light and display) and audible feedback (beep) regarding device and . stimulation status
• allows for multiple stimulations or doses. Each stimulation or dose lasts 120 . seconds, after which the device automatically turns off, unless turned off earlier by the user / operator
• . delivers a fixed number of doses within a 24-hour period. Once the maximum daily number of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
• the number of remaining doses available in a 24-hour period is indicated on the . Display.

In comparison to the gammaCore-2 predicate K172270 (programmed by the manufacturer to deliver 24 doses per day up to a maximum of 99 days), gammaCore Sapphire can be programmed to deliver 24 doses per day for 10, 31, or 93 days and can be refilled / reloaded for additional 10, 31, or 93 day periods via an RFID card encoded and provided by electroCore or its authorized agent.

This document is a 510(k) Summary for the gammaCore Sapphire device, which is an external vagus nerve stimulator for headache. It focuses on demonstrating substantial equivalence to a predicate device (gammaCore-2) rather than presenting a novel device's performance data against acceptance criteria from a clinical study. Therefore, most of the requested information regarding acceptance criteria and a study proving the device meets them (especially in the context of clinical efficacy) is not present in this document.

The document highlights non-clinical testing to demonstrate that the modifications to the device are safe and effective, focusing on the RFID refill functionality.

Here's a breakdown of what can and cannot be extracted from the provided text:

Preamble: The document states, "The verification and validation activities, as identified by the risk analysis to ensure that the modified device is as safe and effective as the predicate device, have been completed and demonstrate that the predetermined acceptance criteria have been met." However, it does not provide the specific acceptance criteria or the detailed results of these verification and validation activities.

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

• Not explicitly provided. The document states that "predetermined acceptance criteria have been met" for non-clinical testing related to the modifications (RFID refill functionality), but it does not list these criteria or the performance results. The focus is on demonstrating that the modification doesn't negatively impact safety or effectiveness compared to the predicate, not on a new clinical performance study.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Not applicable for a clinical test set. The document refers to "verification and validation activities" for non-clinical aspects (e.g., RFID functionality). No clinical test set data is provided.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• Not applicable. This relates to clinical studies establishing ground truth, which were not conducted for this 510(k) submission regarding the device modifications.

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

• Not applicable. This relates to clinical studies and ground truth establishment, which were not performed in this context.

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

• No, a MRMC comparative effectiveness study was not done. This is a modification to an existing device (gammaCore-2 to gammaCore Sapphire), and the submission states: "Clinical Data: Clinical studies were not required to validate the modifications in the gammaCore Sapphire." Therefore, there's no data on human reader improvement with AI assistance. The device is a stimulator, not an AI diagnostic tool.

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

• Not applicable. This device is a medical stimulator, not an algorithm, so "standalone performance" in the context of an algorithm is not relevant here. The device itself operates "standalone" in delivering stimulation.

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

• Not applicable. This relates to clinical studies. For the non-clinical "verification and validation activities," the "ground truth" would be engineering specifications and functional performance (e.g., does the RFID card successfully load the correct number of doses, is the Bluetooth feature accessible only by the manufacturer, etc.). No clinical ground truth on patient outcomes is presented for a new study.

8. The sample size for the training set

• Not applicable. This is for machine learning models. This document describes a medical device, not an AI algorithm.

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

• Not applicable. This is for machine learning models.

Summary of what the document DOES state regarding studies:

• Nonclinical Testing: "The verification and validation activities, as identified by the risk analysis to ensure that the modified device is as safe and effective as the predicate device, have been completed and demonstrate that the predetermined acceptance criteria have been met." This implies internal engineering and functional testing, not clinical studies.
• Clinical Data: "Clinical studies were not required to validate the modifications in the gammaCore Sapphire." This is a key point, meaning no new clinical trials were conducted to support this 510(k) submission for the device modifications. The substantial equivalence relies on the predicate device's existing clinical evidence and the non-clinical testing of the modifications.

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The gammaCore-S Non-invasive Vagus Nerve Stimulator is intended to provide noninvasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore -S device is indicated for the acute treatment of pain associated with episodic cluster headache and migraine headache in adult patients.

The gammaCore-S device (Catalog # 10009-40601 gammaCore-S, 31 day, 300 treatment device) is a hand-held portable device consisting of an outer plastic case, a battery, signal generating and amplifying electronics, LED and horn (indicate device status), and a pair of stainless steel skin contact surfaces (referred to as the "stimulation surfaces"). The device operating status is visible on a LCD display screen. Caps are provided to cover the stimulation surfaces when the device is not in use. Conductive electrode gel is provided for use with the device.

The gammaCore-S device produces a low voltage electric signal consisting of five 5000 Hz pulses that are repeated at a rate of 25 Hz. The waveform of the electric pulses is approximately a sine wave with a peak voltage limited to 24 Volts when placed on the skin and a maximum output current of 60mA. The signal is transmitted through the skin of the neck to the vagus nerve. The device allows up to 30 seconds for the operator to position and adjust the stimulation intensity, treatment is intended to be applied for 90 seconds (the treatment automatically stops 120 seconds after the device is powered on). Each device allows for multiple treatments (up to 300 2-minute treatments).

The document provided is a 510(k) Pre-market Notification from the FDA regarding the gammaCore-S device. This type of submission focuses on demonstrating "substantial equivalence" to a legally marketed predicate device, rather than proving safety and efficacy through a de novo clinical trial with defined acceptance criteria for individual performance metrics.

Therefore, the typical structure for outlining acceptance criteria and a study proving a device meets them (as would be seen for a new device requiring a full PMA or specific performance claims in a de novo classification) is not directly applicable here.

However, I can extract the relevant information from the provided text that describes the evidence used to support the expanded indication for migraine headaches, which implicitly serves the purpose of demonstrating that the device is "substantially equivalent" for this new indication.

Here's how the information aligns with your requested points, with an emphasis on how "substantial equivalence" is demonstrated rather than strict performance acceptance criteria for a novel device:

Device: gammaCore-S
Indication Expansion: Acute treatment of pain associated with migraine headache in adult patients.
Predicate Device: gammaCore-S (K171306), indicated for acute treatment of pain associated with episodic cluster headache.

1. Table of "Acceptance Criteria" (Implicit for Substantial Equivalence) and Reported Device Performance

As this is a 510(k) for an expanded indication of an identical device, the "acceptance criteria" are not reported as specific performance metrics (e.g., sensitivity, specificity, accuracy) like they would be for a diagnostic AI. Instead, the "acceptance criteria" are implicitly met by demonstrating safety and effectiveness for the new indication, showing superiority over sham, and confirming no new safety or effectiveness questions.

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

• Sample Size: The document does not explicitly state the total number of patients enrolled but describes it as a "multicenter" study.
• Data Provenance: The study was conducted across 10 expert headache centers in Italy from January 11, 2016, through March 31, 2017. It was a prospective, randomized, double-blind, parallel-group, sham-controlled clinical study.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This is not applicable in the context of this 510(k) submission. The "ground truth" here is the patient's subjective experience of pain and its resolution, as measured by standard clinical pain scales and reported outcomes in a sham-controlled trial. There are no "experts" establishing a "ground truth" in the sense of image annotation or disease diagnosis for an AI algorithm. The study was conducted by medical professionals at "expert headache centers."

4. Adjudication Method for the Test Set

Not explicitly stated regarding an adjudication method in the context of expert review. The study was a randomized, double-blind, parallel-group, sham-controlled study, which is the primary method of minimizing bias and establishing the effectiveness of the treatment itself. Blinding (patient and potentially assessor) serves a similar purpose to adjudication in ensuring unbiased outcome assessment.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC study was not conducted. This is not an AI-assisted diagnostic device where human readers interact with AI. It is a direct treatment device where patients use the device themselves.

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

Yes, in a sense. The "standalone" performance here refers to the device's ability to treat migraine pain when used by patients, as compared to a sham device. The clinical study directly assessed the device's therapeutic effect (i.e., its "performance") in real-world use by patients. There isn't an "algorithm" in the typical AI sense that would have separate standalone performance metrics (like AUC or accuracy) outside of its direct therapeutic application.

7. The Type of Ground Truth Used

The ground truth was based on patient-reported outcomes and clinical assessments of pain, pain intensity, and responder rates, as documented in a randomized controlled trial. This is directly tied to the primary and secondary endpoints:

• Primary Endpoint: Aborting the first treated attack at 30, 60, and 120 minutes.
• Secondary Endpoints: Mild or no pain at 120 minutes, changes in pain intensity from baseline, and ≥50% responder rates (pain-free and mild/pain-free) at 120 minutes.
• Safety Data: Adverse events reported.

8. The Sample Size for the Training Set

This is not applicable. The gammaCore-S is a direct treatment device, not an AI/ML algorithm that requires a "training set" in the computational sense. The clinical study served as a validation of the device's effectiveness for the expanded indication.

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

Not applicable, as there is no "training set" in the AI/ML context for this device. Ground truth (patient outcomes) was established through direct measurement and reporting in a clinical trial setting using standard pain assessment methodologies.

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The gammaCore-2 Non-invasive Vagus Nerve Stimulator is intended to provide noninvasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore-2 device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.

gammaCore-2 is a device that provides non-invasive Vagus Nerve Stimulation (nVNS) when applied to the side of the neck. This is a mild electrical stimulation of the vagus nerve, which runs through the neck and carries information to the central nervous system. Each stimulation with gammaCore-2 lasts two minutes. The patient controls the stimulation strength.

This document describes the gammaCore-2 device and its substantial equivalence to a predicate device (gammaCore-S). It's a 510(k) submission, which focuses on demonstrating equivalence rather than proving de novo safety and effectiveness. Therefore, the information provided is tailored to that purpose.

Based on the provided text, here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

For a 510(k) submission like this, "acceptance criteria" and "device performance" are typically framed in terms of meeting recognized standards and demonstrating that the modified device is as safe and effective as the predicate device, rather than explicit numerical performance metrics for a clinical indication. The document states that clinical studies were not required to validate the modifications.

The acceptance criteria are implied by the conformity to various IEC standards and the verification/validation activities. The "reported device performance" is that these activities demonstrated that the predetermined acceptance criteria have been met.

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

This document does not describe a clinical "test set" in the traditional sense of a study involving human subjects for performance evaluation of the device's indications for use. The testing described is primarily nonclinical verification and validation testing against engineering standards and risk analysis. Therefore, there is no information on:

• Sample size for a test set (clinical data was not required for the modifications).
• Data provenance (country of origin, retrospective/prospective).

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

Since no clinical test set for performance evaluation was involved, this information is not applicable and not provided in the document. The evaluation was focused on engineering and design changes.

4. Adjudication Method for the Test Set

As there was no clinical test set in the context of performance studies, no adjudication method is mentioned or relevant to this 510(k) submission.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is typically for image-based diagnostic devices to assess human reader performance with and without AI assistance. The gammaCore-2 is an external vagal nerve stimulator, and its modifications (user interface, charging) did not necessitate such a study.

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

Not applicable/Not done. The gammaCore-2 is a nerve stimulator, not an algorithm or AI system for standalone performance evaluation in the way this question typically implies (e.g., in diagnostic imaging AI). The "device performance" here refers to its physical and functional attributes, not an algorithm's output.

7. The Type of Ground Truth Used

The "ground truth" in this context is the established engineering standards and safety/performance requirements outlined in the IEC and ISTA standards, as well as the functional specifications for the device's wireless charging and battery performance. The device's performance was validated against these predetermined technical criteria. There is no mention of expert consensus, pathology, or outcomes data being used as ground truth for the modifications described in this 510(k).

8. The Sample Size for the Training Set

Not applicable/Not provided. There is no "training set" mentioned or implied, as this is not an AI/machine learning device that would require a training set for model development. The submission focuses on hardware and software modifications and their compliance with existing standards.

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

Not applicable/Not provided. As mentioned above, there is no training set for an AI/ML model.

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The gammaCore-S Non-invasive Vagus Nerve Stimulator is intended to provide noninvasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore-S device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.

gammaCore-S is a device that provides non-invasive Vagus Nerve Stimulation (nVNS) when applied to the side of the neck. This is a mild electrical stimulation of the vagus nerve, which runs through the neck and carries information to the central nervous system. Each stimulation with gammaCore-S lasts two minutes. The patient controls the stimulation strength.

This document is a 510(k) premarket notification for the gammaCore-S device, which is an external vagal nerve stimulator for headache. The document does not contain the information requested in the prompt regarding acceptance criteria and a study proving the device meets those criteria.

The document states:

• "Clinical Data: Clinical studies were not required to validate the modifications in the gammaCore-S."
• "The verification and validation activities, as identified by the risk analysis to ensure that the modified device is as safe and effective as the predicate device, have been completed and demonstrate that the predetermined acceptance criteria have been met."

Therefore, I cannot provide the requested information from this document because it explicitly states that clinical studies (which would typically contain such data) were not performed for this specific submission, as it relates to a modification of an already approved device.

To answer your request, a document detailing the clinical study or non-clinical performance data for the original gammaCore device (the predicate device) would be needed, or a document outlining the specific "predetermined acceptance criteria" and how they were met through non-clinical verification and validation activities for the gammaCore-S modifications.

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The gammaCore Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.

The gammaCore Non-invasive Vagus Nerve Stimulator (hereafter referenced as "gammaCore device") is a hand-held portable device (Figure 1) consisting of an outer plastic case, a battery, signal generating and amplifying electronics, a thumbwheel to power on the device and control stimulation intensity (range 0-5 continuous, relative), LED and horn (indicate device status), and a pair of stainless steel skin contact surfaces (referred to as the "stimulation surfaces"). Electrode conductive gel is applied to the electrode surfaces prior to placement on the skin of the neck over the pathway of the vagus nerve.

The provided text describes clinical trials for the gammaCore Non-invasive Vagus Nerve Stimulator, but it is not an AI/ML-driven medical device. The focus of the acceptance criteria and the "study that proves the device meets the acceptance criteria" in the prompt implies an AI/ML context, which is not present in the provided document.

Therefore, many of the requested elements regarding sample size for test sets, data provenance, expert-established ground truth, adjudication methods, MRMC studies, standalone algorithm performance, and training set details are not applicable to this non-AI/ML device.

However, I can extract and present the information available regarding the device's performance in clinical trials relative to its intended use and any implied "acceptance criteria" based on the FDA's decision to grant De Novo classification.

Here's an attempt to structure the available information as requested, while acknowledging the limitations due to the non-AI/ML nature of the device:

Acceptance Criteria and Device Performance for gammaCore Non-invasive Vagus Nerve Stimulator (Non-AI/ML Device)

The FDA granted De Novo classification for the gammaCore Non-invasive Vagus Nerve Stimulator based on a clinical comparison of probable risks and benefits to health. The "acceptance criteria" are implied by the clinical endpoints studied and the FDA's determination of probable benefit outweighing probable risks for the indicated population.

1. Table of Acceptance Criteria (Implied) and Reported Device Performance

Since this is a non-AI/ML device and not a diagnostic/AI model, the acceptance criteria are not in terms of traditional metrics like sensitivity, specificity, AUC. Instead, for a therapeutic device, acceptance is based on demonstrating a clinically meaningful benefit and an acceptable safety profile. The primary clinical endpoints in the studies serve as the de facto "performance metrics."

• Response rate (pain 0 or 1 at 15 min, no rescue med at 60 min): 34.2% (nVNS) vs. 10.6% (Sham) (P=0.008, statistically significant in post-hoc subgroup analysis).
• Sustained treatment response rate (pain 0 or 1 at 60 min, no rescue med at 60 min): 34.2% (nVNS) vs. 10.6% (Sham).
• Subjects who were responders at 15 min for ≥50% of treated attacks: 34.2% (nVNS) vs. 14.9% (Sham) (P=0.04).
• Change in duration of attacks from baseline: -14.4 minutes (nVNS) vs. 16.3 minutes (Sham) (P=0.03). |
  | | ACT2 Study (Primary Endpoint):
• Attacks pain-free at 15 min (no rescue med at 30 min): 47.5% (nVNS) vs. 6.2% (Sham) (P

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