The Proteus® Digital Health Feedback Device consists of a miniaturized, wearable sensor for ambulatory recording of physiological and behavioral metrics such as heart rate, activity, body angle relative to gravity (body position), and time-stamped patient-logged events, including events signaled by the co-incidence with, or co-ingestion with, the ingestible sensor accessory. When the ingestible sensor is ingested, the Proteus Digital Health Feedback Device is intended to log, track and trend intake times. When co-ingested with medication, the tracking and trending of intake times may be used as an aid to measure medication adherence. The Proteus Digital Health Feedback Device may be used in any instance where quantifiable analysis of event-associated physiological and behavioral metrics is desirable, and enables unattended data collection for clinical and research applications.

Device Description

The Proteus Digital Health Feedback Device consists of a wearable sensor, an ingestible sensor, and a software application.

The Proteus wearable sensor is a body-worn sensor that collects physiological and behavioral metrics such as heart rate, activity, body angle relative to gravity (body position), skin temperature, and time-stamped user-logged events signaled by the co-incidence with, or coingestion with, the Proteus ingestible sensor. The display application of the Proteus Digital Health Feedback Device may be used to analyze circadian rhythms and patterns.

The ingestible sensor is embedded inside an inactive tablet. (the Proteus Pill or sensorenabled pill) for ease of handling and swallowing. After the ingestible sensor reaches the stomach, it activates and communicates its presence with a unique identifier to the wearable sensor. When the ingestible sensor is co-ingested with medication, the Proteus device is intended to log, track, and trend medicine intake times as an aid to measure medication adherence.

The software application receives the data from the wearable sensor for further processing and analysis of the physiological and behavioral metrics. The processed data is then sent to the user interface (UI) for display as well as to Proteus databases for storage and sharing.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study information for the Proteus Digital Health Feedback Device:

Based on the provided text, a comprehensive study proving the device meets acceptance criteria, including specific quantifiable acceptance criteria and detailed study results, is not present. The document is a 510(k) summary for FDA clearance, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed clinical study report with acceptance criteria.

However, we can extract information regarding non-clinical performance data and the general approach to validating different aspects of the device.

1. Table of Acceptance Criteria and Reported Device Performance

As noted above, explicit acceptance criteria with specific thresholds are not provided in this document. The text describes how different parameters were validated or quantified, rather than defining performance targets.

Parameter	"Acceptance Criteria" (Implied/Description of Validation)	Reported Device Performance
Wearable Sensor
Motion and Angle (Body Position)	Validated against a known acceleration applied against each of its three axes (for the three-axis accelerometer).	Not explicitly stated with specific numerical results, but implies successful detection and measurement of motion/angle.
Heart Rate	Quantified by measuring R-wave frequency based on a proprietary algorithm, tested using selected guidelines set forth in the ANSI/AAMI EC 13 standard.	Not explicitly stated with specific numerical results, but implies successful heart rate measurement according to standard guidelines.
Skin Temperature	Quantified by applying a small current across the thermistor and comparing the difference in voltage to a reference resistor.	Not explicitly stated with specific numerical results, but implies successful temperature measurement.
Ingestible Sensor
Activation Time	Tested for activation time.	Not explicitly stated with specific numerical results.
Lifetime After Activation	Tested for lifetime after activation.	Not explicitly stated with specific numerical results.
Ingestible Event Marker Function	Bio-galvanically powered ingestible circuit communicates via volume conduction. (Implied that this detection and communication works).	Not explicitly stated with specific numerical results for detection accuracy or communication reliability over time.

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

Test Set Sample Size: Not specified. The document mentions "tested using selected guidelines" or "validated against," but does not provide details on the number of subjects or samples used in these non-clinical evaluations.
Data Provenance: The document does not specify the country of origin. It indicates that the data are from "Non-Clinical Performance Data" and implies laboratory or controlled test environments. The data is retrospective in the sense that it was collected prior to this submission for FDA clearance.

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

Not Applicable / Not Specified. The evaluations described are primarily technical performance tests of sensors and algorithms, not evaluations against human expert ground truth for diagnostic purposes. For example, the accelerometer was "validated against a known acceleration," which implies a controlled physical standard rather than expert consensus. Similarly, heart rate was tested against "selected guidelines set forth in the ANSI/AAMI EC 13 standard," which refers to industry standards, not human interpreters.

4. Adjudication Method for the Test Set

Not Applicable / Not Specified. Since there is no mention of human experts establishing ground truth or making judgments, there is no adjudication method described.

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 or described. This device focuses on objective physiological and behavioral data collection, not on aiding human interpretation of complex medical images or data that typically require MRMC studies.

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

Yes, standalone non-clinical performance data was done for individual device components. The section "Summary of Non-Clinical Performance Data" describes evaluating the accelerometer, biopotential low-frequency amplifier (for heart rate), thermistor, and ingestible sensor activation/lifetime independently. For example, "The three-axis accelerometer provided motion and angle relative to gravity (body position) data and was validated against a known acceleration applied against each of its three axes." This indicates direct evaluation of the device's technical output.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth used was primarily controlled physical inputs, laboratory standards, and industry guidelines.
- For the accelerometer: "known acceleration."
- For heart rate: "selected guidelines set forth in the ANSI/AAMI EC 13 standard."
- For skin temperature: "compared to a reference resistor" (implying a controlled reference temperature/voltage).
- For ingestible sensor: Testing "activation time and lifetime" implies comparison against internal specifications or direct observation.

8. The Sample Size for the Training Set

Not specified. The document does not provide details on a separate training set for any algorithms. It describes a "proprietary algorithm" for heart rate, but does not detail its development or training data. Given the context of a 510(k) for a sensor device, emphasis would be on device performance rather than complex machine learning algorithm training.

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

Not specified, as no training set details are provided.

Summary

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 27, 2015

Proteus Digital Health, Inc. Jafar Shenasa Head, Regulatory Affairs 2600 Bridge Parkway, Suite 101 Redwood City, California 94065

Re: K150494

Trade/Device Name: Proteus Digital Health Feedback Device Regulation Number: 21 CFR 880.6305 Regulation Name: Ingestible Event Marker Regulatory Class: Class II Product Code: OZW, DXH Dated: May 22, 2015 Received: May 28, 2015

Dear Jafar Shenasa:

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 may, therefore, market the device, subject to the general controls provisions of the Act. 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 requirements, including, but not limited to: registration and listing (21 CFR

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Page 2 - Jafar Shenasa

Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Mitchell Stein

for Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known)

Device Name Proteus® Digital Health Feedback Device

The Proteus® Digital Health Feedback Device consists of a Indications for Use miniaturized, wearable sensor for ambulatory recording of physiological and behavioral metrics such as heart rate, activity, body angle relative to gravity (body position), and time-stamped patientlogged events, including events signaled by the co-incidence with, or co-ingestion with, the ingestible sensor accessory. When the ingestible sensor is ingested, the Proteus Digital Health Feedback Device is intended to log, track and trend intake times. When co-ingested with medication, the tracking and trending of intake times may be used as an aid to measure medication adherence. The Proteus Digital Health Feedback Device may be used in any instance where quantifiable analysis of event-associated physiological and behavioral metrics is desirable, and enables unattended data collection for clinical and research applications.

Prescription Use X(Per 21 CFR 801.109)	OR	Over-the-Counter Use
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PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED

Concurrence of CDRH, Office of Device Evaluation (ODE)

Proteus Digital Health, Inc.

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510(k) Summary

Submitted by: Address:

Telephone: Facsimile:

Contact Name:

Proteus Digital Health Inc. 2600 Bridge Parkway, Suite 101 Redwood City, CA, 94065 (650) 637-6230 (650) 362-1860

Arezou Azar, PhD aazar(a)proteus.com

Date Submitted:

May22, 2015

Name of Device

Trade name: Common name: Classification name: Product Code: Subsequent Codes:

Proteus® Digital Health Feedback Device Ingestible Event Marker Ingestible Event Marker (21 CFR 880.6305) OZW DXH

Predicate Device

. Proteus® Patch Including Ingestible Sensor (K133263)

General Device Description

The Proteus Digital Health Feedback Device consists of a wearable sensor, an ingestible sensor, and a software application.

Proteus Digital Health, Inc.

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Intended Use

Parameter	Values
	The Wearable Sensor
	One Piece	Two Piece
Shape	Ovoid	Rectangular
Size	102mm x 60mm x9.8mm	98mm x 42mm x11mm
Weight	11 grams	16 grams
Battery Type	Lithium Manganese(LiMn) Coin Cell	Lithium Manganese(LiMn) Coin Cell
MoistureSusceptibility	Water-Resistant	Water-Resistant
Memory	4 MB	16 MB
StorageTemperature	Room Temperature	Room Temperature
Relative Humidity	Ambient	Ambient
	The Pill
Shape	Round
Size	6.5mm x 2.0mm
Weight	80mg

Physical Characteristics

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Technological Characteristics

The technological characteristics of the current device are identical to the predicate device.

Parameter	Sensor Technology	Method
Heart rate	Biopotential low-frequencyamplifier	Digitized R wave
Activity	Accelerometer	Digitized accelerometer output
Body Angle	Accelerometer	Double integration ofaccelerometer output
Skin Temperature	Thermistor	Digitized voltage from smallauxiliary current
Manual Event Logging	Patient activated button	Digital pulse
Inter-Electrode	Biopotential high-frequencyamplifier	Digitized impedance from smallauxiliary current
Impedance
Ingestible Event Marker	Bio-galvanically poweredingestible circuit	Volume conductioncommunication

Summary of Non-Clinical Performance Data

The three-axis accelerometer provided motion and angle relative to gravity (body position) data and was validated against a known acceleration applied against each of its three axes.

The biopotential low-frequency amplifier was used to quantify heart rate by measuring Rwave frequency based upon a proprietary algorithm, tested using selected guidelines set forth in the ANSI/AAMI EC 13 standard.

The thermistor provided local skin environment temperature. A small current was applied across the thermistor, and the difference in voltage was quantifed and compared to a reference resistor.

The ingestible sensor was tested for activation time and lifetime after activation.

Summary of Clinical Performance Data

No additional clinical data were required to confirm substantial equivalence to predicate devices.

Conclusion

Based on technological characteristics, risk evaluation, and design verification of the Proteus Digital Health Feedback Device, Proteus Digital Health believes that the product is safe and effective, and is substantially equivalent to its predicate device.

Proteus Digital Health, Inc.

Regulation Number and Section

§ 880.6305 Ingestible event marker.

(a)
Identification. An ingestible event marker is a prescription device used to record time-stamped, patient-logged events. The ingestible component links wirelessly through intrabody communication to an external recorder which records the date and time of ingestion as well as the unique serial number of the ingestible device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must be demonstrated to be biocompatible and non-toxic;
(2) Nonclinical, animal, and clinical testing must provide a reasonable assurance of safety and effectiveness, including device performance, durability, compatibility, usability (human factors testing), event recording, and proper excretion of the device;
(3) Appropriate analysis and nonclinical testing must validate electromagnetic compatibility performance, wireless performance, and electrical safety; and
(4) Labeling must include a detailed summary of the nonclinical and clinical testing pertinent to use of the device and the maximum number of daily device ingestions.