An ingestible sensor for measuring medication adherence.

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.

Feasibility of an ingestible sensor-based system for monitoring adherence to tuberculosis therapy.

Poor adherence to tuberculosis (TB) treatment hinders the individual's recovery and threatens public health. Currently, directly observed therapy (DOT) is the standard of care; however, high sustaining costs limit its availability, creating a need for more practical adherence confirmation methods. Techniques such as video monitoring and devices to time-register the opening of pill bottles are unable to confirm actual medication ingestions. A novel approach developed by Proteus Digital Health, Inc. consists of an ingestible sensor and an on-body wearable sensor; together, they electronically confirm unique ingestions and record the date/time of the ingestion. A feasibility study using an early prototype was conducted in active TB patients to determine the system's accuracy and safety in confirming co-ingestion of TB medications with sensors. Thirty patients completed 10 DOT visits and 1,080 co-ingestion events; the system showed 95.0% (95% CI 93.5-96.2%) positive detection accuracy, defined as the number of detected sensors divided by the number of transmission capable sensors administered. The specificity was 99.7% [95% CI 99.2-99.9%] based on three false signals recorded by receivers. The system's identification accuracy, defined as the number of correctly identified ingestible sensors divided by the number of sensors detected, was 100%. Of 11 adverse events, four were deemed related or possibly related to the device; three mild skin rashes and one complaint of nausea. The system's positive detection accuracy was not affected by the subjects' Body Mass Index (p = 0.7309). Study results suggest the system is capable of correctly identifying ingestible sensors with high accuracy, poses a low risk to users, and may have high patient acceptance. The system has the potential to confirm medication specific treatment compliance on a dose-by-dose basis. When coupled with mobile technology, the system could allow wirelessly observed therapy (WOT) for monitoring TB treatment as a replacement for DOT.

A digital health solution for using and managing medications: wirelessly observed therapy.

Taking oral medication on a prescribed schedule can be a nuisance, especially for elderly individuals and busy people with lots of things on their minds. Nonetheless, taking medication as prescribed is important for maintaining health and well-being. In cases where medication use is part of a clinical trial, taking prescribed medication is important to the entire investigation and outcome of the study, including the determination of whether a drug is effective and safe.

Early clinical experience with networked system for promoting patient self-management.

OBJECTIVE: To gain early experience with a networked system designed to assess a patient's adherence to oral medication and physiologic metrics in an ambulatory, at-home setting. STUDY DESIGN: Prospective, observational studies. MATERIALS AND METHODS: This networked system for patient self-management consists of ingestible markers and a wearable, personal monitor. When a marker is ingested, it communicates to a monitor that time-stamps the ingestion and identifies the marker as unique. The monitor also records heart rate and activity. Data from third-party monitoring equipment (eg, sphygmomanometer, weight scale) can be integrated into the system. Collected data are summarized for patient and physician review. Directly observed ingestion (DOI) of placebo tablet markers was used to assess the system's technical performance. Markers were also coencapsulated with drugs to capture at-home adherence. A performance criterion of <95% was set as the objective for system performance. RESULTS: A total of 111 subjects ingested 7144 ingestible markers; 3298 were DOIs. The system's positive detection accuracy and negative detection accuracy in detecting ingested markers were 97.1% and 97.7%, respectively. It differentiated 100% of multiple drugs and doses taken simultaneously by type and by dose. Medication adherence was >85%. The most common adverse effect was mild skin rash from the monitor's electrodes. No definitive marker-related adverse effects were reported. CONCLUSION: The system appears to be safe and effective in capturing and integrating adherence and physiologic data. Efforts are under way to enhance system functionalities and refine user interfaces. By providing context-rich information, this system may enhance patient-provider collaboration.