(118 days)
EpiMonitor is a prescription only medical device system composed of a wearable device "EmbracePlus" and paired mobile software application "EpiMonitor" intended as an adjunct to seizure monitoring in adults and children aged 6 and up in a home environment or healthcare facilities. The device is worn on the wrist and senses Electrodermal Activity (EDA) and motion data to detect patterns that may be associated with either primary or secondary generalized tonic clonic seizures in patients with epilepsy or at risk of having epilepsy. When a seizure event is detected, the wearable device component of EpiMonitor sends a command to a paired mobile device where the EpiMonitor App is programmed to initiate an alert to a designated caregiver. The EpiMonitor app incorporates additional detection sensitivity modes, "high" for use during periods of rest or sleeping or "low" for use during periods of low-intensity activity, in order to reduce false alarm incidents.
EpiMonitor records, stores and transmits accelerometer, EDA, peripheral skin temperature and activity data for subsequent retrospective review by a trained healthcare professional via a cloud-based software.
The EpiMonitor system consists of a wearable device and mobile application:
- A wearable medical device called EmbracePlus,
- A mobile application running on smartphones called "EpiMonitor"
The EmbracePlus is worn on the user's wrist and continuously collects raw data via specific sensors, these data are continuously analyzed by an on-board algorithm (EpiAlgo 2.1), which assesses the physiological data and determines if the user may be undergoing a generalized tonic-clonic seizure (GTCS). The EpiAlgo has been validated through testing, using the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 4 epilepsy center, from epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units.
When a likely GTCS is detected, EmbracePlus sends, via Bluetooth Low Energy, a message to the EpiMonitor app. The EpiMonitor app communicates to the Empatica Cloud which initiates, through the external provider a voice call and SMS text message is sent to summon the attention of user-designated caregiver(s).
In addition to initiating alerts, the EpiMonitor app also continuously receives all the raw sensor data collected by the EmbracePlus. These data are analyzed by one of the EpiMonitor app software modules, EmpaDSP (paragraph 2.3.2), which computes the additional physiological parameters, such as activity during sleep and peripheral skin temperature.
The EpiMonitor App is also responsible for transmitting, over a cellular data plan or Wi-Fi connection the sensors' raw data, device information, and computed physiological parameters to the Empatica Cloud. On the Empatica Cloud, these data are stored, and made available to healthcare providers via a specific cloud-based software called Care Monitoring Portal.
Here's a summary of the acceptance criteria and study details for EpiMonitor, based on the provided FDA clearance letter:
Acceptance Criteria and Device Performance for EpiMonitor
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for PPA and FAR in a table format. Instead, it presents the device's performance for these metrics, implying that these results were deemed acceptable by the FDA for clearance. For the purpose of this response, I'm interpreting the "reported device performance" as the achieved PPA and FAR values and will frame the "acceptance criteria" as the expectation for these metrics to be within reasonable clinical utility.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Low-Sensitivity Mode) |
|---|---|---|
| Positive Percent Agreement (PPA) - During Non-Rest Activities (Epilepsy Monitoring Unit Data) | Clinically acceptable detection of GTCS | 6-21 years: 0.895 (corrected PPA: 0.791, CI: 0.619-0.925) |
| >21 years: 1.000 (corrected PPA: 0.905, CI: 0.891-0.917) | ||
| False Alarm Rate (FAR) per 24 hours - During Non-Rest Activities (Epilepsy Monitoring Unit Data) | Clinically acceptable false alarm rate | 6-21 years: Overall FAR: 0.70 (CI: 0.41-1.06), Mean FAR: 0.91 (CI: 0.44-1.57) |
| >21 years: Overall FAR: 0.28 (CI: 0.15-0.46), Mean FAR: 0.33 (CI: 0.17-0.53) | ||
| Positive Percent Agreement (PPA) - During Non-Rest Activities (Real-World Data) | Clinically acceptable detection of GTCS | 6-21 years: 0.87 (corrected PPA: 0.86, CI: 0.78-0.92) |
| >21 years: 0.8 (corrected PPA: 0.77, CI: 0.64-0.87) | ||
| False Alarm Rate (FAR) per 24 hours - During Non-Rest Activities (Real-World Data) | Clinically acceptable false alarm rate | 6-21 years: Overall FAR: 0.34 (CI: 0.23-0.50), Mean FAR: 0.35 (CI: 0.28-0.45) |
| >21 years: Overall FAR: 0.25 (CI: 0.22-0.30), Mean FAR: 0.29 (CI: 0.26-0.33) |
2. Sample Size for the Test Set and Data Provenance:
-
Epilepsy Monitoring Unit (EMU) Data (Retrospective Analysis):
- Patients for PPA: 12 patients (6-21 years old) and 12 patients (>21 years old).
- GTCS events for PPA: 19 GTCS events (6-21 years old) and 17 GTCS events (>21 years old).
- Patients for FAR: 80 patients (6-21 years old) and 61 patients (>21 years old).
- Data Provenance: Retrospective analysis of previously collected clinical data from patients observed in Epilepsy Monitoring Units. The document mentions data from "epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units" for the validation of the algorithm (EpiAlgo 2.1).
-
Real-World Data (Longitudinal Analysis) for Low-Sensitivity Mode:
- Patients for PPA/FAR: 601 patients (6-21 years old) and 843 patients (>21 years old).
- GTCS events for PPA: 1157 GTCS events (6-21 years old) and 3625 GTCS events (>21 years old).
- Observation days for FAR: 37594.2 days (6-21 years old) and 56389.1 days (>21 years old).
- Data Provenance: Longitudinal analysis of real-world data, based on sensor data captured using the Embrace2 wearable device. This suggests the data was collected prospectively in a real-world setting, but its analysis for this specific submission was retrospective.
3. Number of Experts Used to Establish the Ground Truth and Qualifications:
- For the initial validation of EpiAlgo 2.1 (which supports the predicate device and is used in the subject device), the ground truth was "designed by a group of epileptologists at a top level 4 epilepsy center." The exact number of epileptologists and their specific years of experience are not provided. The method mentioned is "gold-standard video-Electroencephalogram (EEG) methodology."
- For the retrospective analyses presented, "adjudicated tonic-clonic seizure data" was used, implying expert review to establish the ground truth of GTCS events. The number and qualifications of the experts performing this adjudication for the analyses presented in Tables 1-4 are not explicitly stated.
4. Adjudication Method for the Test Set:
- The document implies clinical adjudication was performed to establish "adjudicated tonic-clonic seizure data" and the "gold-standard video-Electroencephalogram (EEG) methodology." However, it does not specify a particular adjudication method such as 2+1 or 3+1 for the test set data used in these retrospective analyses. It only mentions that the data was "adjudicated."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No MRMC comparative effectiveness study was done.
- The document describes a standalone algorithm performance without human assistance for seizure detection.
6. Standalone (Algorithm Only) Performance:
- Yes, a standalone performance evaluation of the algorithm (EpiAlgo ver 2.1) was conducted. The PPA and FAR metrics presented (Tables 1-4) reflect the performance of the algorithm without human-in-the-loop assistance for seizure detection and alerting.
7. Type of Ground Truth Used:
- Expert Consensus / Clinical Diagnosis (Video-EEG): For the initial validation of EpiAlgo 2.1, the ground truth was established using "gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists." This indicates a high standard of clinical diagnosis and expert consensus.
- Adjudicated Data: For the retrospective analyses of EMU and real-world data, "adjudicated tonic-clonic seizure data" were used, implying expert review and decision-making on seizure events.
8. Sample Size for the Training Set:
- The document does not explicitly state the sample size for the training set of EpiAlgo ver 2.1. It mentions that EpiAlgo 2.1 was validated using data from epilepsy patients in EMUs, but this typically refers to validation/test sets, not specifically the training data.
9. How the Ground Truth for the Training Set Was Established:
- The method for establishing the ground truth for the training set is not detailed in this document. It only states that the EpiAlgo "has been validated through testing, using the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 4 epilepsy center, from epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units." This description primarily refers to the validation data, not the data used for initial training.
§ 882.1580 Non-electroencephalogram (EEG) physiological signal based seizure monitoring system.
(a)
Identification. A non-electroencephalogram (non-EEG) physiological signal based seizure monitoring system is a noninvasive prescription device that collects physiological signals other than EEG to identify physiological signals that may be associated with a seizure.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The technical parameters of the device, hardware and software, must be fully characterized and include the following information:
(i) Hardware specifications must be provided. Appropriate verification, validation, and hazard analysis must be performed.
(ii) Software, including any proprietary algorithm(s) used by the device to achieve its intended use, must be described in detail in the Software Requirements Specification (SRS) and Software Design Specification (SDS). Appropriate software verification, validation, and hazard analysis must be performed.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) The device must be designed and tested for electrical, thermal, and mechanical safety and electromagnetic compatibility (EMC).
(4) Clinical performance testing must demonstrate the ability of the device to function as an assessment aid for monitoring for seizure-related activity in the intended population and for the intended use setting. Performance measurements must include positive percent agreement and false alarm rate.
(5) Training must be provided for intended users that includes information regarding the proper use of the device and factors that may affect the collection of the physiologic data.
(6) The labeling must include health care professional labeling and patient-caregiver labeling. The health care professional and the patient-caregiver labeling must include the following information:
(i) A detailed summary of the clinical performance testing, including any adverse events and complications.
(ii) Any instructions technicians and clinicians should convey to patients and caregivers regarding the proper use of the device and factors that may affect the collection of the physiologic data.
(iii) Instructions to technicians and clinicians regarding how to set the device threshold to achieve the intended performance of the device.