An Ingestible Sensor for Measuring Medication Adherence

Abstract

In this paper, we describe the design and performance of the first integrated-circuit microsensor developed for daily ingestion by patients. The ingestible sensor is a device that allows patients, families, and physicians to measure medication ingestion and adherence patterns in real time, relate pharmaceutical compliance to important physiologic metrics, and take appropriate action in response to a patient's adherence pattern and specific health metrics. The design and theory of operation of the device are presented, along with key in-vitro and in-vivo performance results. The chemical, toxicological, mechanical, and electrical safety tests performed to establish the device's safety profile are described in detail. Finally, aggregate results from multiple clinical trials involving 412 patients and 5656 days of system usage are presented to demonstrate the device's reliability and performance as part of an overall digital health feedback system.

Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co‐encapsulation

“…The DHFS appears reliable, and highly accurate, with a positive detection accuracy of sensor‐detected ingestions of ∼99% (99.1%; 321/324 ingested under direct observation, 95% confidence interval (CI) 97.3–99.7) 21. From a total of almost 30,000 sensor ingestions, no serious adverse events were observed in clinical studies 21.…”

“…This system consists of an ingestion sensor, ∼1 mm 3 (1 × 1 × 0.45 mm microchip), coated with very thin layers of commonly ingested excipients (i.e., minerals and metals) ( Figure 1 a ), a small adhesive‐backed detector patch worn on the torso, and a paired mobile device. When ingested with a medication, the sensor readily separates from the carrier, is energized, and communicates with the detector patch 21. The detector patch interprets the information as unique to the ingested sensor.…”

“…Data from the patch are transmitted wirelessly, via bluetooth technology, to a paired device, such as a mobile phone, tablet, or a personal computer. Subsequently, all of the data on the paired device are uploaded to a secured, centralized data storage location21 ( Figure 1 b ). These data are available in near‐real‐time to the patient user on their mobile device and, with patient permission, to healthcare personnel and other significant persons, who can access these data from a secure web portal 22, 23, 24, 25…”

“…From a total of almost 30,000 sensor ingestions, no serious adverse events were observed in clinical studies 21. Early versions of the patch were associated with self‐limited, localized skin rashes in ∼10% of users 21, 22.…”

“…From a total of almost 30,000 sensor ingestions, no serious adverse events were observed in clinical studies 21. Early versions of the patch were associated with self‐limited, localized skin rashes in ∼10% of users 21, 22. The Proteus Digital Health Feedback Device (DHFD) was issued CE Mark approval in 2010 to market its ingestible sensor and personal physiologic monitor system in the European Union and was approved for marketing as a medical device by the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) in 2012.…”