Long-Term Stability of the Electronic Sensor Component of a Digital Pill System in Real-World Storage Settings.

Background: Digital pill systems comprise an ingestible sensor integrated into a gelatin capsule that overencapsulates medication allowing real-time measures of medication ingestion. These systems may improve the manner in which medication adherence can be assessed and supported. Objective: In this investigation, we tested the durability of the ingestible sensor as part of a clinical trial to measure the feasibility and acceptability of the system to measure adherence to once daily tenofovir disoproxil fumarate/emtricitabine (NCT03842436). Methods: Digital pills not dispensed during the study were stored in a pharmacy. Seventeen sensors were selected from digital pills stored for at least 12 months and activated in a simulated gastric environment. A radiofrequency spectrum analyzer and the reader device used in the clinical trial to capture ingestion events were used to measure activation of emitters. A passing evaluation was defined as an energized emitter within 30 minutes of immersion, ability to broadcast a signal for 10 minutes, and successful acquisition by the reader. Results: All ingestible sensors passed the stability test. Mean activation time in simulated gastric fluid was 3.33 minutes (SD = 1.47); emitters remained active for a mean of 47.72 minutes (SD = 1.78). These parameters matched guidelines defined in the ID-Cap system requirements for use in patients. Conclusions: Ingestible sensor components of the ID-Cap system were therefore stable after long-term storage.

DigiPrEP: A Pilot Trial to Evaluate the Feasibility, Acceptability, and Accuracy of a Digital Pill System to Measure PrEP Adherence in Men Who Have Sex With Men Who Use Substances.

BACKGROUND: Adherence to once daily oral preexposure prophylaxis (PrEP) for HIV prevention can be challenging for men who have sex with men (MSM) with substance use. Digital pill systems (DPS) comprise a radiofrequency emitter integrated into a gelatin capsule containing PrEP, which transmits data to a wearable Reader following ingestion, thereby enabling direct, real-time adherence measurement. This study evaluated the feasibility, acceptability, and accuracy of a DPS to measure PrEP adherence. METHODS: A 90-day, single-arm, open-label, pilot demonstration trial was conducted with adult, cisgender, HIV-negative MSM on PrEP with nonalcohol substance use. Feasibility was measured via DPS engagement and timeline followback. Acceptability was assessed via qualitative user experience interviews. Accuracy was evaluated via DPS performance metrics, pill counts, and DBS to quantify tenofovir diphosphate. RESULTS: Sixteen MSM enrolled (median age, 32 years), and 15 completed the study. Engagement remained stable over time. Emergent nonadherence patterns included intercurrent substance use. The DPS was largely acceptable based on interviews; the predominant barrier to use was the Reader. DPS-recorded ingestions totaled 1099, including 83.9% were detected by Reader and 16.1% were reported manually. The DPS recorded 92.2% of 1192 total expected ingestions per pill counts. Point-biserial correlation (R = 0.58; 95% CI: 0.21 to 0.80; P = 0.047) and Pearson correlation (month 1: R = 0.85; 95% CI: 0.57 to 0.95; P = 0.0002; month 3: R = 0.75; 95% CI: 0.17 to 0.94; P = 0.0197) showed strong correlations between DPS-recorded adherence and tenofovir diphosphate in dried blood spots. CONCLUSION: DPS are a feasible, acceptable, and accurate method of measuring PrEP adherence in MSM with substance use. Future investigations should incorporate DPS into behavioral interventions targeting nonadherence.

A Novel Digital Pill System for Medication Adherence Measurement and Reporting: Usability Validation Study.

BACKGROUND: Medication nonadherence is a costly problem that is common in clinical use and clinical trials alike, with significant adverse consequences. Digital pill systems have proved to be effective and safe solutions to the challenges of nonadherence, with documented success in improving adherence and health outcomes. OBJECTIVE: The aim of this human factors validation study is to evaluate a novel digital pill system, the ID-Cap System from etectRx, for usability among patient users in a simulated real-world use environment. METHODS: A total of 17 patients with diverse backgrounds who regularly take oral prescription medications were recruited. After training and a period of training decay, the participants were asked to complete 12 patient-use scenarios during which errors or difficulties were logged. The participants were also interviewed about their experiences with the ID-Cap System. RESULTS: The participants ranged in age from 27 to 74 years (mean 51 years, SD 13.8 years), and they were heterogeneous in other demographic factors as well, such as education level, handedness, and sex. In this human factors validation study, the patient users completed 97.5% (196/201) of the total use scenarios successfully; 75.1% (151/201) were completed without any failures or errors. The participants found the ID-Cap System easy to use, and they were able to accurately and proficiently record ingestion events using the device. CONCLUSIONS: The participants demonstrated the ability to safely and effectively use the ID-Cap System for its intended use. The ID-Cap System has great potential as a useful tool for encouraging medication adherence and can be easily implemented by patient users.

A Brief Training Program to Support the Use of a Digital Pill System for Medication Adherence: Pilot Descriptive Study.

BACKGROUND: Digital pill systems (DPSs), which comprise ingestible radiofrequency sensors integrated into a gelatin capsule that overencapsulates a medication, can directly measure ingestion events. OBJECTIVE: Teaching users to operate a DPS is vital to ensure the collection of actionable ingestion and adherence data. In this study, we aim to develop and pilot a training program, grounded in the Technology Acceptance Model, to instruct individuals on DPS operation. METHODS: A two-part training program, comprising in-person and text message-based components, was used with HIV-negative men who have sex with men with nonalcohol substance use, who had enrolled in a 90-day pilot demonstration study using the DPS to measure adherence to pre-exposure prophylaxis. We assessed the number of responses to text check-ins, the number and types of episodes where technical support was requested, the resolutions of such issues, and engagement with the program over the study period. Participant feedback on the program was evaluated through qualitative user experience interviews. RESULTS: A total of 15 participants were enrolled in and completed the program. Seven technical challenges related to DPS operations were reported across 5 participants. Most commonly, participants requested support connecting the wearable Reader device with their smartphone, charging the Reader, and operating the mobile app. A total of 6 issues were resolved asynchronously or in real time via phone; 1 required in-person evaluation and resolution. Preliminary qualitative findings indicate that both the in-person and remote follow-up components of the training program were perceived as acceptable. Suggested improvements included repeated DPS refresher sessions at in-person follow-up visits and enhanced written materials for the independent resolution of technological issues. CONCLUSIONS: A brief two-part DPS training program, drawing from individuals' experiences and from the Technology Acceptance Model, can provide valuable insights for users. The program also identifies and addresses several areas of actual or potential challenges related to operating a DPS and allows for the resolution of such issues within the first week of DPS use.

Performance, Reliability, Usability, and Safety of the ID-Cap System for Ingestion Event Monitoring in Healthy Volunteers: A Pilot Study.

Background: Nonadherence to prescribed medications is an important consideration in the clinical management of patients and in clinical research and drug development. The ID-Cap System is a novel technology that provides an objective measure of medication ingestion and enables real-time reporting of verified medication adherence data at the dose level. The ID-Cap System consists of an ingestible microsensor that is embedded in an oral dosage form and, once activated by stomach fluid, communicates digital messages to an external wearable reader to confirm ingestion. Objective: The objective of this exploratory study was to evaluate the performance, reliability, usability, and safety of the ID-Cap System for remote monitoring of 20 ingestion events over four weeks in 20 healthy volunteers. Design: This study was an open-label, single-arm, exploratory study of the ID-Cap System. The study design included the following three phases: 1) screening phase, 2) treatment phase consisting of 20 daily capsule ingestion events over a four-week period, and 3) follow-up phase consisting of a follow-up study visit that included an abdominal X-ray and a follow-up phone call. The initial use of the ID-Cap Reader and ingestion of the first study capsule were directly observed by the investigator during the first study visit. Subsequent study capsule ingestions were completed outside the research facility at the study participant's home or other location of his or her choice with ingestion assessed using the ID-Cap System. Setting: The study was conducted at a single clinical research site in Gainesville, Florida. Participants: Twenty healthy volunteers were enrolled in this four-week pilot study that was conducted between September and November 2014. Measurements: Study measurements included ID-Tag detection indicating capsule ingestion, utilization of the ID-Cap System consistent with instructions for use, adverse event reports, discontinuations of the System during the study, and safety assessments related to excretion of the ID-Tags through abdominal X-ray evaluations. Results: Positive detection accuracy was 100 percent for the 20 directly observed ingestions of study capsules that occurred during the initial study visits. Of the 384 ingestion events that were self-administered by the study participants without direct observation, 371 were accurately detected using the ID-Cap System. Overall adherence to the prescribed study capsules as measured by the ID-Cap System was 97.75 percent (391 detections/400 expected ingestion events). Significant intra-individual and inter-individual variability in the timing of self-administered doses was observed in this study. No adverse events were reported, and no study participants discontinued use of the ID-Cap System for any reason during the study. There was no evidence indicating retention of ID-Tags based on abdominal X-ray evaluations. Conclusion: The ID-Cap System enables accurate measurement of medication adherence for oral drug therapy at the dose level. This study supports the clinical validation of the technology and feasibility in using the system for the collection and real-time reporting of medication adherence in the clinical management of patients and in clinical research and drug development.