(114 days)
The Nerivio is intended for acute treatment of migraine with or without aura in patients 18 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.
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 hardware consists of an armband intended to be worn on a user's upper arm. The armband contains the electronic circuitry and the battery in a plastic storage case as well as two electrodes that are attached to the interior of the armband and placed against the user's skin. 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, a progress bar for stimulation duration, battery level, and user notifications. The patient is instructed to adjust the intensity to the strongest stimulation level 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.
The provided document describes the Nerivio device and its substantial equivalence to a predicate device (Nerivio Migra), primarily based on clinical studies rather than an AI/ML algorithm's performance. Therefore, many standard AI/ML acceptance criteria and study elements (like training set size, ground truth for training, expert adjudication, MRMC studies, standalone performance with metrics like sensitivity/specificity, or specific effect sizes of AI with human readers) are not present in this document.
However, I can extract the acceptance criteria and performance data related to the clinical studies conducted for device efficacy and safety as described in the provided text. The "acceptance criteria" here refer to the primary efficacy endpoints defined for the clinical trials, which demonstrate the device's effectiveness.
1. Table of Acceptance Criteria and Reported Device Performance
Note: The document outlines clinical study endpoints as measures of device performance, which serve as "acceptance criteria" for demonstrating efficacy and safety. The primary endpoint for efficacy was "pain relief at 2 hours post-treatment."
| Acceptance Criteria (Primary Efficacy Endpoint) | Reported Device Performance (Study 1) | Reported Device Performance (Study 2) |
|---|---|---|
| Pain relief at 2 hours post-treatment | 50.0% (19/38 participants; CI95% 33.4-66.6%) achieved pain relief. | 59.3% (54/91 participants; CI95% 48.5-69.5%) achieved pain relief. |
| Additional Metrics (Secondary Endpoints) | ||
| Pain-free at 2 hours | 26.3% (10/38 participants; CI95% 13.4-43.1%) achieved pain-free. | 20.9% (19/91 participants; CI95% 13.0-30.6%) achieved pain-free. |
| Sustained pain relief for 24 hours | 83.3% (10/12 participants; CI95% 51.6-97.9%) of those with 2-hr pain relief. | 71.1% (32/45 participants; CI95% 51.6-97.9%) of those with 2-hr pain relief. |
| Disappearance of Nausea at 2 hours | 58.8% (10/17 participants; CI95% 32.9-81.6%). | 48.8% (20/41 participants; CI95% 32.8-64.8%). |
| Disappearance of Photophobia at 2 hours | 37.5% (9/24 participants; CI95% 18.8-59.4%). | 40.5% (30/74 participants; CI95% 29.2-52.5%). |
| Disappearance of Phonophobia at 2 hours | 50.0% (8/16 participants; CI95% 24.7-75.3%). | 44.6% (29/65 participants; CI95% 32.2-57.4%). |
| Improvement in functional ability at 2 hours | 46.7% (14/30 participants; CI95% 28.3-65.7%). | 59.4% (19/32 participants; CI95% 40.6-76.3%). |
| Improvement in functional ability at 24 hours | 72.7% (16/22 participants; CI95% 49.8-89.3%). | 50.0% (7/14 participants; CI95% 23.0-76.9%). |
| Device-related Adverse Events | 1 reported (1.8% of patients [1/42] or 0.003% of treatments [1/296]). Mild, resolved within 48 hours with drug. | 1 reported (1.0% [1/99]). Mild, resolved within 24 hours without medication. |
2. Sample size used for the test set and the data provenance
The clinical studies acted as the primary "test set" for validating the device's performance.
- Study 1 Sample Size:
- 42 patients recruited initially.
- 38 participants completed at least one treatment in response to a migraine.
- 296 qualifying migraine headaches treated.
- Study 2 Sample Size:
- 97 participants completed at least one treatment.
- 91 participants formed the final analysis set for test treatment.
- 493 evaluable treatments of qualifying migraine headaches conducted.
- Data Provenance: The document states that Study 2 was conducted at 9 sites in the USA. Study 1 was conducted at 2 sites, but the country of origin is not explicitly stated, although it's within the context of FDA submission, suggesting US or international sites adhering to US standards. Both studies were prospective, open-label, single-arm, multicenter studies.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The concept of "experts" establishing ground truth in the traditional sense of medical image analysis (e.g., radiologists) is not applicable here. The ground truth for efficacy was self-reported by the patients using an electronic diary application:
- Pain scores: Self-reported by participants (e.g., severe or moderate pain to mild or none, or mild pain to none).
- Absence/presence of associated migraine symptoms: Self-reported.
- Functional disability: Self-reported.
The diagnostic criteria for chronic migraine (ICHD-3) were applied to select eligible participants, implying medical professionals (neurologists/headache specialists) were involved in patient selection. However, their role wasn't in establishing ground truth for individual treatments but in determining study eligibility.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
No specific adjudication method (like 2+1 or 3+1 for expert review) is mentioned for the patient-reported outcomes. Given that the data collected was patient self-reported via an electronic diary, it implies direct measurement of patient experience, not subject to expert adjudication of the outcome itself, although clinical staff would have monitored data collection.
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
This is not an AI/ML device, and no MRMC comparative effectiveness study involving human readers or AI assistance was conducted or reported. This device is a direct treatment device, not a diagnostic imaging or AI-assisted diagnostic tool.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is not an AI/ML algorithm. The device, Nerivio, operates as a standalone therapeutic device that patients self-administer. Its "performance" refers to its direct therapeutic effect on migraine symptoms.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the efficacy studies was primarily patient-reported outcomes data. This includes:
- Self-reported pain levels (e.g., severe, moderate, mild, none).
- Self-reported presence or absence of associated migraine symptoms (nausea, photophobia, phonophobia).
- Self-reported functional ability.
8. The sample size for the training set
The concept of a "training set" in the context of an AI/ML algorithm is not applicable here. The device does not employ an AI/ML model that requires training data. The "training treatment" mentioned in Study 2 (97 participants completed at least one training treatment) refers to an initial treatment session to familiarize participants with the device, not an AI model training phase.
9. How the ground truth for the training set was established
Not applicable, as there is no AI/ML training set. The "training treatment" phrase refers to the initial use of the device by patients.
§ 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.