(118 days)
The Nerivio is indicated for acute and/or preventive treatment of migraine with or without aura in patients 12 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura for acute treatment, or every other day for preventive treatment.
The Nerivio is a wearable, battery-powered device that is controlled by a mobile application. The system delivers low energy electrical pulses to the upper arm for 45 minutes per treatment, after which the device turns off automatically. The device is composed of a pair of UltraStim® electrodes (K130987) covered with hydrogel and removable protective film, an electronic circuitry that includes firmware, LED indicator and a power button for activating the device and for wireless connection with Android and iOS mobile platforms and a battery contained in a plastic case situated within thermoplastic elastomers ("TPE") shell. In addition, an armband that is wrapped over the device to secure the Nerivio position on the user's arm is included. The device is operated and controlled via software that is installed and run on a user's personal mobile device such as a mobile phone or tablet. The device hardware communicates with the mobile application through a Bluetooth protocol. This mobile application software allows the user to control the stimulation intensity from 0 to 100% (representing intensity levels of 0-40mA), to start or stop the stimulation program, and to view device status such as the device's connection state, stimulation duration, remaining number of treatments, and user notifications. The user is instructed to adjust the intensity to the strongest stimulation level just below the perceived pain level. Treatments with Nerivio are intended to be self-administered by the user immediately after the onset of migraine headache or aura.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
Device Name: Nerivio
Indications for Use (New/Expanded): Acute and/or preventive treatment of migraine with or without aura in patients 12 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura for acute treatment, or every other day for preventive treatment.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes a clinical study for the preventive indication for Nerivio, comparing it against a sham device. The "acceptance criteria" are implied by the primary and secondary efficacy endpoints of the clinical trial designed to demonstrate superiority over sham for migraine prevention.
| Acceptance Criterion (Clinical Endpoint) | Reported Device Performance (Active Group vs. Sham Group) |
|---|---|
| Primary Efficacy Endpoint: Mean change in number of migraine days per month | Reduction of 3.97 ± 0.41 migraine days in the active group vs. 1.28 ± 0.43 in the sham group (mean ± SEM, p= 50% reduction, compared to 11.9% (10 out of 84) in the Sham group. Resulted in 2.21 folds in favor of the Active group (p=0.015). |
| Secondary Efficacy Endpoint: Mean change in number of acute headache/migraine medication days per month | Reduction of 3.5 ± 0.42 in Active group vs. 1.4 ± 0.47 in the Sham group (mean ± SEM, p=0.001). Therapeutic gain: -2.08 ± 0.63 (95% C.I [-3.33, -0.83]) acute headache/migraine medications days. |
| Safety Endpoint: Absence of device-related Serious Adverse Events (SAEs) | Two SAEs occurred (suicidal attempt, appendicitis), but were deemed non-related to the device or study. |
| Safety Endpoint: Low incidence of device-related Adverse Events (AEs) | Only one device-related adverse event in the sham group (0.83%, 1/120). No statistically significant differences in type or rate of AEs between active and sham groups during the treatment phase. |
2. Sample Size and Data Provenance
- Test Set Sample Size: 248 participants randomized (Active: 128, Sham: 120) for the Intent-to-Treat (ITT) dataset. Analysis for the primary endpoint was also performed on a modified ITT (mITT) dataset of 95 active and 84 sham participants (total 179) who completed at least 12 treatments.
- Data Provenance: The randomized, controlled trial was prospective and multicenter. While the specific countries are not mentioned, the context of FDA submission suggests it was likely conducted, at least primarily, within the United States. It was a prospective study.
- For the adolescent real-world data: 61 patients. Data collected prospectively through the Nerivio App between January 2, 2021, and November 26, 2022, from US patients.
3. Number of Experts and Qualifications for Ground Truth (Clinical Trial)
- The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical trial. However, the ground truth was based on participants' self-reported data using an electronic daily migraine diary application installed on their smartphones, following the International Classification of Headache Disorders (ICHD-3) criteria for migraine. This suggests that the diagnostic criteria were applied by healthcare professionals at the 15 study sites, who would be qualified to diagnose migraine. The assessment of efficacy endpoints (migraine days, headache days, medication usage) relied on the self-reported diary data.
4. Adjudication Method for the Test Set
- The document does not mention an adjudication method for the test set data (e.g., 2+1, 3+1 for imaging reads). The data collection for efficacy endpoints was through self-reported daily diaries.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not performed. This study was a Randomized Controlled Trial (RCT) comparing the device directly against a sham control for migraine prevention, not a study evaluating human reader performance with or without AI assistance.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop)
- This device is a physical neuromodulation device, not an AI algorithm for diagnosis or image interpretation. Therefore, the concept of "standalone performance" for an algorithm without human-in-the-loop does not directly apply in the typical sense of AI/imaging devices. The "performance data" presented is clinical efficacy and safety data from a human-device interaction (patients using the device).
7. Type of Ground Truth Used
- For the main clinical trial: The ground truth for headache/migraine days and medication usage was established through patient self-reported daily migraine diaries collected prospectively via an electronic application on smartphones. Migraine diagnosis itself was based on ICHD-3 criteria.
- For the adolescent real-world data: Similar to the clinical trial, the ground truth for migraine headache days was collected through the Nerivio App from self-reported data.
8. Sample Size for the Training Set
- This device is not an AI/ML algorithm that requires a "training set" in the conventional sense of supervised learning. The device's mechanism of action is electrical neuromodulation, not a learned algorithm.
- The clinical trial mentioned (K223169) is a validation study for the new preventive indication, building upon prior studies (like K203181) for acute treatment. The "training data" for the device's design would effectively be the pre-clinical research and prior clinical studies that informed its development and established its mechanism of action (conditioned pain modulation).
9. How the Ground Truth for the Training Set Was Established
- As a hardware medical device with a well-defined physical mechanism, there's no "training set" ground truth in the AI sense. The "ground truth" for the device's development and prior understanding of its mechanism (e.g., conditioned pain modulation) would be based on previous basic science, preclinical studies, and prior clinical trials (such as K203181 which established its acute treatment efficacy). The current submission leverages this existing knowledge and demonstrates expanded efficacy for prevention using a randomized controlled trial. For the extrapolation to adolescents, the "ground truth" relies on the established mechanism of action (CPM) being the same across age groups, supported by real-world evidence collected via the device's app.
§ 882.5899 Trunk and limb electrical stimulator to treat headache.
(a)
Identification. A trunk and limb electrical stimulator to treat headache is a device intended to treat headache through the application of electrical stimulation anywhere on the body of the patient apart from the patient's head or neck through electrodes placed on the skin. The stimulation may be provided transcutaneously or percutaneously.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. This testing must include:
(i) Characterization of the electrical stimulation, including the following: Waveforms; output modes; maximum output voltage and maximum output current (at 500Ω, 2kΩ, and 10kΩ loads); pulse duration; frequency; net charge per pulse; and maximum phase charge, maximum current density, maximum average current, and maximum average power density (at 500Ω);
(ii) Characterization of the impedance monitoring system; and
(iii) Characterization of the electrode performance including the electrical performance, adhesive integrity, shelf-life, reusability, and current distribution of the electrode surface area.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Performance testing must demonstrate electromagnetic compatibility and electrical, mechanical, and thermal safety in the intended use environment.
(4) Software verification, validation, and hazard analysis must be performed.
(5) Labeling must include the following:
(i) Instructions for use, including the typical sensations experienced during treatment;
(ii) A detailed summary of the electrical stimulation output, and the device technical parameters, including any wireless specifications;
(iii) A shelf life for the electrodes and reuse information; and
(iv) Instructions on care and cleaning of the device.