(161 days)
The Embrace is a prescription only device that is indicated for use as an adjunct to seizure monitoring of adults and children age 6 and up in home or healthcare facilities during periods of rest. The device is worn on the wrist and senses Electrodermal Activity (EDA) and motion data to detect patterns that may be associated with generalized tonic clonic seizures in patients with epilepsy or at risk of having epilepsy. When a seizure event is detected, Embrace sends a command to a paired wireless device that is programmed to initiate an alert to a designated caregiver. The System records and stores data from Accelerometer, EDA, and Temperature sensors for subsequent review by a trained healthcare professional.
The Embrace is a wearable biosensor device that can capture, store, and wirelessly transmit sensor data via Bluetooth to a paired remote device. Embrace runs an on-board algorithm to continuously process sensor data and make a decision about whether the data might indicate a generalized tonic clonic seizure (GTCS). The algorithm has been validated on data, labeled using the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 6 epilepsy centers, from epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units. When a likely GTCS is detected, the Embrace sends a message to the Alert smartphone application, which initiates calls and texts to summon the attention of designated caregivers. The device also enables patients to manually record seizure events, and provides contextual information related to activity and sleep.
The provided document describes the FDA 510(k) clearance for the Empatica Embrace device, a non-EEG physiological signal-based seizure monitoring system. The information below is extracted and organized to answer your request.
1. Table of Acceptance Criteria and Reported Device Performance
While the document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical thresholds for clearance, the performance results presented indicate the observed efficacy. The implicit acceptance criteria would be for the device to perform well enough to demonstrate substantial equivalence to the predicate device and ensure safety and effectiveness.
| Performance Metric | Implicit Acceptance Criteria (based on predicate equivalence and clinical utility) | Reported Device Performance (Embrace) |
|---|---|---|
| Positive Percent Agreement (PPA) - All Patients | High PPA to ensure most GTCS events are detected, comparable to predicate. | 0.9815 (53 out of 54 GTCS detected) with 95% CI of [0.9028; 0.9702] |
| False Alarm Rate (FAR) - Overall | Low FAR to minimize non-actionable alerts for caregivers. | 0.94 false alarms per 24 hours with 95% CI of [0.71, 1.21] |
| Mean FAR - Overall | Low mean FAR for individual patients. | 1.25 (average of FARs across patients) |
| PPA (6-12 years) | High PPA for pediatric subgroup. | 0.917 (corrected PPA: 0.799) with 95% CI of [0.601, 0.895] |
| PPA (13-21 years) | High PPA for adolescent subgroup. | 1.0 (corrected PPA: 0.915) with 95% CI of [0.889, 0.934] |
| PPA (Adults, >21 years) | High PPA for adult subgroup. | 1.0 (corrected PPA: 0.924) with 95% CI of [0.910, 0.931] |
| FAR (6-12 years) | Low FAR for pediatric subgroup. | 1.33 false alarms per 24 hours (mean FAR: 1.79) |
| FAR (13-21 years) | Low FAR for adolescent subgroup. | 1.37 false alarms per 24 hours (mean FAR: 1.47) |
| FAR (6-21 years) | Low FAR for combined pediatric subgroup. | 1.35 false alarms per 24 hours (mean FAR: 1.63) |
| FAR (Adults, >21 years) | Low FAR for adult subgroup. | 0.67 false alarms per 24 hours (mean FAR: 0.76) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 141 patients diagnosed with epilepsy.
- 80 pediatric patients (ages 6-21 years, median: 13 years)
- 61 adult patients (ages 22-63 years, median: 39 years)
- Data Provenance: The study was conducted in a hospital Epilepsy Monitoring Unit (EMU) setting. While the document doesn't explicitly state the country of origin, the listed submitter address is in Milan, Italy. The data is prospective as patients were enrolled and monitored during their EMU stay for the purpose of this study.
- Observed GTCS: 31 EMU patients experienced a total of 54 generalized tonic-clonic seizures (GTCSs). 110 EMU patients did not experience any seizure.
- Recorded Data: 141 patients provided overall 409 days (9,806 hours) of ACM (accelerometer) and EDA (electrodermal activity) measurements, with a median of 49.2 hours of data per patient.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Number of Experts: A "panel of three readers" was used.
- Qualifications of Experts: The ground truth was established using "the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 6 epilepsy centers." This implies the "readers" were highly qualified medical professionals experienced in epilepsy diagnosis and seizure classification, likely epileptologists, given the standard of care in EMUs. Specific years of experience are not mentioned.
4. Adjudication Method for the Test Set
The document states "relative to a panel of three readers." While it doesn't explicitly detail the adjudication method (e.g., majority vote, independent assessment with reconciliation), the phrase "panel of three readers" suggests a consensus or majority agreement approach was used to establish the ground truth from the video-EEG data. It is not explicitly stated as 2+1 or 3+1, but rather that the ground truth was derived from the consensus of these three readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
- No MRMC comparative effectiveness study was described where human readers' performance with and without AI assistance was evaluated. This study focused on the standalone performance of the device's algorithm in detecting GTCS.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, a standalone performance study was done. The reported PPA and FAR metrics represent the performance of the Embrace device's algorithm in detecting GTCS events based on its internal processing of EDA and motion data, without direct human intervention in the detection process. The device sends an alert when a likely GTCS is detected, which then initiates actions by caregivers. The study evaluates the accuracy of these automated detections.
7. The Type of Ground Truth Used
- The ground truth used was expert consensus based on gold-standard video-Electroencephalogram (EEG) methodology. This is considered a high-fidelity ground truth for seizure detection in an Epilepsy Monitoring Unit (EMU) setting. Every recorded seizure was classified as epileptic.
8. The Sample Size for the Training Set
The document states: "Embrace runs an on-board algorithm to continuously process sensor data and make a decision about whether the data might indicate a generalized tonic clonic seizure (GTCS). The algorithm has been validated on data, labeled using the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 6 epilepsy centers, from epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units."
- The document describes the validation of the algorithm on data from specific sources but does not explicitly state the sample size used for the training set. The 141 patient dataset is specifically described as the "clinical testing" dataset, suggesting it was used for evaluation, not necessarily for training. It's common for validation data to be distinct from training data.
9. How the Ground Truth for the Training Set Was Established
- Similar to the validation set, the description implies that the data used for training (or at least development and refinement) of the algorithm was "labeled using the gold-standard video-Electroencephalogram (EEG) methodology designed by a group of epileptologists at a top level 6 epilepsy centers, from epilepsy patients experiencing GTCSs in hospital Epilepsy Monitoring Units." This indicates a high-quality, expert-driven ground truth establishment process for the data used to develop and refine the algorithm.
{0}------------------------------------------------
December 20, 2018
Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
Empatica Srl % Rakesh Lal Consultant Rakesh Lal 318 Rindge Ave 407 Cambridge, Massachusetts 02140
Re: K181861
Trade/Device Name: Embrace Regulation Number: 21 CFR 882.1580 Regulation Name: Non-Electroencephalogram (EEG) Physiological Signal Based Seizure Monitoring System Regulatory Class: Class II Product Code: POS Dated: November 20, 2018 Received: November 20, 2018
Dear Rakesh Lal:
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 (Act) that do not require approval of a premarket approval application (PMA). You mav, 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 avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located 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.
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
{1}------------------------------------------------
requirements, including, but not limited to: registration and listing (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Jay R. Gupta -S
For Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K181861
Device Name Embrace
Indications for Use (Describe)
The Embrace is a prescription only device that is indicated for use as an adjunct to seizure monitoring of adults and children age 6 and up in home or healthcare facilities during periods of rest. The device is worn on the wrist and senses Electrodermal Activity (EDA) and motion data to detect patterns that may be associated with generalized tonic clonic seizures in patients with epilepsy or at risk of having epilepsy. When a seizure event is detected, Embrace sends a command to a paired wireless device that is programmed to initiate an alert to a designated caregiver. The System records and stores data from Accelerometer, EDA, and Temperature sensors for subsequent review by a trained healthcare professional.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the word "empatica" in a pink sans-serif font. To the right of the word is a pink symbol that resembles a stylized letter E with an arrow pointing to the right. The symbol is also in a sans-serif font and is the same color as the word.
510K Embrace Documentation
510(k) Summary
{4}------------------------------------------------
| Submitter Name: | Empatica S.r.l. |
|---|---|
| Submitter Address: | Via Stendhal 3620144 Milano, Italy |
| 510(k) Submission Contact: | Rakesh Lal817-734-8303 |
| Sponsor Contact Person: | Matteo Lai,+393497888125 |
| Date Prepared: | December 19, 2018 |
| Device Trade Name:Device Common Name:Device Classification: | EmbraceNon-EEG physiological signal based seizure monitoring system21 CFR 882.1580, Product Code POS |
| Predicate Device:Predicate Device Classification: | Embrace, K17293521 CFR 882.1580, Product Code POS |
| Device Description: | The Embrace is a wearable biosensor device that can capture, store, andwirelessly transmit sensor data via Bluetooth to a paired remote device.Embrace runs an on-board algorithm to continuously process sensor data andmake a decision about whether the data might indicate a generalized tonicclonic seizure (GTCS). The algorithm has been validated on data, labeled usingthe gold-standard video-Electroencephalogram (EEG) methodology designed bya group of epileptologists at a top level 6 epilepsy centers, from epilepsypatients experiencing GTCSs in hospital Epilepsy Monitoring Units. When alikely GTCS is detected, the Embrace sends a message to the Alert smartphoneapplication, which initiates calls and texts to summon the attention ofdesignated caregivers. The device also enables patients to manually recordseizure events, and provides contextual information related to activity andsleep. |
| Indications for Use: | The Embrace is a prescription only device that is indicated for use as an adjunctto seizure monitoring of adults and children age 6 and up in home or healthcarefacilities during periods of rest. The device is worn on the wrist and sensesElectrodermal Activity (EDA) and motion data to detect patterns that may beassociated with generalized tonic clonic seizures in patients with epilepsy or atrisk of having epilepsy. When a seizure event is detected, Embrace sends acommand to a paired wireless device that is programmed to initiate an alert toa designated caregiver. The System records and stores data fromAccelerometer, EDA, and Temperature sensors for subsequent review by atrained healthcare professional. |
{5}------------------------------------------------
Substantial Equivalence:
A comparison of Embrace to the predicate device is provided in the table below.
| Attribute | Embrace | Embrace (K172935) | Comparison |
|---|---|---|---|
| Intended Use | Non-EEG physiologicalsignal based seizuremonitoring system. | Non-EEG physiologicalsignal based seizuremonitoring system. | EQUIVALENTBoth devices have thesame intended use. |
| Indications for use | The Embrace is aprescription only devicethat is indicated for useas an adjunct to seizuremonitoring of adults andchildren age 6 and up inhome or healthcarefacilities during periods ofrest. The device is wornon the wrist and sensesElectrodermal Activity(EDA) and motion data todetect patterns that maybe associated withgeneralized tonic clonicseizures in patients withepilepsy or at risk ofhaving epilepsy. When aseizure event is detected,Embrace sends acommand to a pairedwireless device that isprogrammed to initiatean alert to a designatedcaregiver. The Systemrecords and stores datafrom Accelerometer,EDA, and Temperaturesensors for subsequentreview by a trainedhealthcare professional. | The Embrace is aprescription only devicethat is indicated for useas an adjunct to seizuremonitoring of adults inthe home or healthcarefacilities during periods ofrest. The device is wornon the wrist, and sensesElectrodermal Activity(EDA) and motion data todetect patterns that maybe associated withgeneralized tonic clonicseizures in patients withepilepsy or at risk ofhaving epilepsy. When aseizure event is detected,Embrace sends acommand to a pairedwireless device that isprogrammed to initiatean alert to a designatedcaregiver. The Systemrecords and stores datafrom Accelerometers,EDA, and Temperaturefor subsequent review bya trained healthcareprofessional. | Patient Population:EQUIVALENTBoth devices areindicated for use onpatients with epilepsy orat risk of having epilepsy.Embrace 2.0 isadditionally indicated foruse in children age 6 andup. This difference doesnot raise new questionsof safety andeffectiveness.Healthcare Environment:EQUIVALENTBoth the subject andpredicate devices areindicated for use in thehome and healthcaresettings.Seizure Type:EQUIVALENTBoth devices areindicated to provide analert to caregivers whenthey each detect GTCwhile the patient is atrest.Effect on ClinicalOutcome: EQUIVALENTBoth devices areindicated as an adjunct toother monitoring devicesin the EMU. Neither ofthe devices is intended toguide therapy decisions. |
| Sensor Technology | Utilizes an electrodermalsensor to acquire | Utilizes an electrodermalsensor to acquire | EQUIVALENT |
| and an accelerometersensor to acquiremovement data. | and an accelerometersensor to acquiremovement data. | ||
| Software Level ofConcern | Moderate | Moderate | EQUIVALENT |
| Data Communication | Communicates wirelesslyto a smartphoneapplication, which alertsthe healthcare provideror caregiver in one ormore ways (phone call,text message, etc.). | Communicates wirelesslyto a smartphoneapplication, which alertsthe healthcare provideror caregiver in one ormore ways (phone call,text message, etc.). | EQUIVALENT |
| Algorithm | Uses algorithms toanalyze EDA andaccelerometer data todetect patterns in thedata that may beassociated with GTCseizures. | Uses algorithms toanalyze EDA andaccelerometer data todetect patterns in thedata that may beassociated with GTCseizures. | EQUIVALENT |
| Biocompatibility | All patient contactingparts are identical to thepredicate device. | All patient contactingparts are tested toapplicable tests in ISO10993 (Cytotoxicity - ISO10993-5, Sensitization -ISO 10993-10, and SkinIrritation - ISO 10993-10). | EQUIVALENT |
| Electrical Safety | All electrical andelectronic parts areidentical to the predicatedevice. | Electrical Safety testingperformed to IEC 60601-1Electromagneticcompatibility testingperformed to IEC 60601-1-2 4th Edition | EQUIVALENT |
| Thermal Safety | Not applicable. Thedevice does not generateany localized heat | Not applicable. Thedevice does not generateany localized heat | EQUIVALENT |
| Chemical Safety | Not applicable. Patient isnot exposed to anychemicals during use ofthe device | Not applicable. Patient isnot exposed to anychemicals during use ofthe device | EQUIVALENT |
| Radiation Safety | Not applicable. Devicedoes not use any ionizingradiation | Not applicable. Devicedoes not use any ionizingradiation | EQUIVALENT |
{6}------------------------------------------------
{7}------------------------------------------------
Performance Testing: Performance testing demonstrates that Embrace complies with IEC 60601-1:2005+AMD1:2012, IEC 60601-1-2:2014, ISO 10993-5:2009, and ISO 10993-10:2010
Clinical testing was performed to demonstrate the ability of the Embrace to function as an assessment aid for monitoring for seizure related activity in the intended population and for the intended use setting.
Patients:
Clinical Testing:
141 patients diagnosed with epilepsy were admitted to the Epilepsy Monitoring Unit (EMU) for standard care were enrolled in the studies: 80 pediatrics, ages 6-21 years, median: 13 years; 61 adults, ages: 22-63 years, median: 39 years.
Observed GTCS:
31 EMU patients experienced a total of 54 generalized tonic clonic seizures (GTCSs) while 110 EMU patients did not experience any seizure. Every recorded seizure was classified as epileptic.
Recorded data:
141 patients provided overall 409 days (9,806 hours), with a median of 49.2 hours of data per patient of ACM and EDA measurements.
Performance:
On all the 141 patients, the Positive percent agreement (PPA) was found to be 0.9815 (53 out of 54 GTCSs detected), with a 95% confidence interval (CI) of [0.9028; 0.9702], relative to a panel of three readers, and the overall false alarm rate (FAR) was found to be 0.94 false alarms per 24 hours with a 95% confidence interval of [0.71, 1.21], corresponding to a mean FAR (average of FARs across patients) of 1.25. Table 1 and Table 2 report the PPA and the FAR separately on the adult patients (age 22 and up) and on pediatrics subgroups.
| Table 1 | |||||||
|---|---|---|---|---|---|---|---|
| age | #patients | #GTCS | # detectedGTCS | PPA | correctedPPA1 | CI PPA | |
| 6-12 | 6 | 12 | 11 | 0.917 | 0.799 | 0.601 | 0.895 |
| 13-21 | 11 | 20 | 20 | 1 | 0.915 | 0.889 | 0.934 |
| 6-21 | 17 | 32 | 31 | 0.969 | 0.915 | 0.834 | 0.953 |
| >21 | 14 | 22 | 22 | 1 | 0.924 | 0.910 | 0.931 |
| age | #patients | #FA | #days | OverallFAR | CI overall FAR | MeanFAR | CI mean FAR |
|---|---|---|---|---|---|---|---|
| 6-12 | 39 | 89 | 67.02 | 1.33 | 0.82 1.98 | 1.79 | 0.99 2.73 |
| 13-21 | 41 | 129 | 93.98 | 1.37 | 0.75 2.17 | 1.47 | 0.72 2.41 |
| 6-21 | 80 | 218 | 161 | 1.35 | 0.92 1.87 | 1.63 | 1.06 2.28 |
| >21 | 61 | 165 | 247.6 | 0.67 | 0.43 0.95 | 0.76 | 0.43 1.17 |
Tahla 2
1 A conservative correction was applied to PPA to account for extreme probability values (PPA ~= 1) and the presence of multiple seizures for some patients (Chew, The American Statistician, 25(5), 47-50, 1971; Saha et al, Int J Biostat., 12(2), 2016).
{8}------------------------------------------------
Conclusion:
The subject device has the same intended use as the predicate device, and differences in technological characteristics do not raise different questions of safety and effectiveness. On this basis, Embrace is substantially equivalent to the legally marketed predicate device.
§ 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.