Smartphone and Wearable Device-Based Digital Phenotyping to Understand Substance use and its Syndemics.

Digital phenotyping is a process that allows researchers to leverage smartphone and wearable data to explore how technology use relates to behavioral health outcomes. In this Research Concepts article, we provide background on prior research that has employed digital phenotyping; the fundamentals of how digital phenotyping works, using examples from participant data; the application of digital phenotyping in the context of substance use and its syndemics; and the ethical, legal and social implications of digital phenotyping. We discuss applications for digital phenotyping in medical toxicology, as well as potential uses for digital phenotyping in future research. We also highlight the importance of obtaining ground truth annotation in order to identify and establish digital phenotypes of key behaviors of interest. Finally, there are many potential roles for medical toxicologists to leverage digital phenotyping both in research and in the future as a clinical tool to better understand the contextual features associated with drug poisoning and overdose. This article demonstrates how medical toxicologists and researchers can progress through phases of a research trajectory using digital phenotyping to better understand behavior and its association with smartphone usage.

Acceptance of digital phenotyping linked to a digital pill system to measure PrEP adherence among men who have sex with men with substance use.

Once-daily oral HIV pre-exposure prophylaxis (PrEP) is an effective strategy to prevent HIV, but is highly dependent on adherence. Men who have sex with men (MSM) who use substances face unique challenges maintaining PrEP adherence. Digital pill systems (DPS) allow for real-time adherence measurement through ingestible sensors. Integration of DPS technology with other digital health tools, such as digital phenotyping, may improve understanding of nonadherence triggers and development of personalized adherence interventions based on ingestion behavior. This study explored the willingness of MSM with substance use to share digital phenotypic data and interact with ancillary systems in the context of DPS-measured PrEP adherence. Adult MSM on PrEP with substance use were recruited through a social networking app. Participants were introduced to DPS technology and completed an assessment to measure willingness to participate in DPS-based PrEP adherence research, contribute digital phenotyping data, and interact with ancillary systems in the context of DPS-based research. Medical mistrust, daily worry about PrEP adherence, and substance use were also assessed. Participants who identified as cisgender male and were willing to participate in DPS-based research (N = 131) were included in this subsample analysis. Most were White (76.3%) and non-Hispanic (77.9%). Participants who reported daily PrEP adherence worry had 3.7 times greater odds (95% CI: 1.03, 13.4) of willingness to share biometric data via a wearable device paired to the DPS. Participants with daily PrEP adherence worry were more likely to be willing to share smartphone data (p = 0.006) and receive text messages surrounding their daily activities (p = 0.003), compared to those with less worry. MSM with substance use disorder, who worried about PrEP adherence, were willing to use DPS technology and share data required for digital phenotyping in the context of PrEP adherence measurement. Efforts to address medical mistrust can increase advantages of this technology for HIV prevention.

Real-World Implementation Challenges Associated with a Digital Pill System to Measure Adherence to HIV Pre-Exposure Prophylaxis from Two Studies of Men Who Have Sex With Men.

Once-daily oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but its efficacy is dependent on adherence, which can be challenging for men who have sex with men (MSM) with substance use. Digital pill systems (DPS) represent a novel tool for directly measuring adherence through ingestible radiofrequency sensors that confirm ingestions in real-time. We examined operational challenges across two studies involving DPS to measure PrEP adherence. While most participants successfully operated the system, a number of technological and sociobehavioral challenges requiring intervention were identified across both studies. Technological issues were both system- and participant-related, and were primarily addressed with technical updates and participant re-education, while sociobehavioral issues, including health and housing changes and issues with technology access, warranted innovative solutions. Future research leveraging DPS technology should develop robust supportive infrastructure and mitigation procedures to promptly identify and resolve operational issues to optimize the potential benefits of DPS use.

Preliminary feasibility of a wrist-worn receiver to measure medication adherence via an ingestible radiofrequency sensor.

Adherence to medications is a complex task that requires complex biobehavioral support. To better provide tools to assist with medication adherence, digital pills provide an option to directly measure medication taking behaviors. These systems comprise a gelatin capsule with radiofrequency emitter, a wearable Reader that collects the radio signal and a smartphone app that collects ingestion data displays it for patients and clinicians. These systems are feasible in measuring adherence in the real-world, even in stigmatized diseases like HIV treatment adherence. While the current iteration of the digital pill system utilizes a wearable Reader worn like a necklace, preliminary feedback demonstrated that a miniaturized system that was worn on the wrist could be more functional in the real-world. This paper therefore describes the development and preliminary field testing of a wrist-borne wearable Reader to facilitate acquisition of oral HIV pre-exposure prophylaxis (PrEP) adherence data among individual prescribed PrEP.

Diversity in Digital Pill Systems: Differences in Perceptions and Attitudes Towards Use of a Digital Pill System for HIV Pre-Exposure Prophylaxis Among Men Who Have Sex with Men with Diverse Racial and Ethnic Identities.

Nonadherence, particularly among men who have sex with men (MSM) with substance use disorders, increases the risk of HIV acquisition. Measuring adherence to HIV pre-exposure chemoprophylaxis (PrEP), and responding to suboptimal adherence or changes in adherence behavior remains a challenging public health problem. Despite the importance of accurate adherence measurement, there is no gold standard for detecting medication ingestion events in HIV research. Current adherence measures indirectly infer ingestion events or measure medication concentrations over time, yet such approaches fail to provide direct confirmation of ingestions and contextual information surrounding adherence and nonadherence. A digital pill system (DPS) - a novel tool that leverages ingestible radiofrequency sensors to measure actual ingestion events - may advance adherence measurement in HIV research. We examined and compared the willingness of MSM across racial and ethnic identities to operate a DPS in the context of PrEP adherence measurement and suggest potential future applications of this technology.

Attitudes towards participating in research involving digital pill systems to measure oral HIV pre-exposure chemoprophylaxis: a cross-sectional study among men who have sex with men with substance use in the USA.

OBJECTIVES: This quantitative survey sought to understand, among men who have sex with men (MSM) with potentially problematic substance use, the attitudes towards participation in research involving digital pill systems (DPS) for HIV pre-exposure prophylaxis (PrEP) adherence measurement, and the barriers and facilitators to research participation. DESIGN: One-time, cross-sectional, online sampling-based survey. SETTING: US social networking app predominantly focused on MSM. PARTICIPANTS: MSM without HIV who reported current use of oral PrEP, potentially problematic substance use and sexual activity in the past 3 months. A total of 157 participants were eligible, passed validity checks and enrolled. OUTCOME MEASURES: Perceptions of DPS usefulness, accuracy and usability (System Usability Scale (SUS)); willingness and motivations to participate in DPS research; preferences for access to and feedback on DPS adherence data; data sharing considerations; and medical mistrust (Group-Based Medical Mistrust Scale (GBMMS)). RESULTS: Most of the sample (N=157) was white (n=119, 75.8%), gay (n=124, 79.0%) and cisgender (n=150, 95.5%). The median age was 33 years (IQR: 14). The mean GBMMS score was 13.5 (SD=5.2), and the median SUS score was 70 (IQR: 27.5). In the past 3 months, 36.3% (n=57) reported frequent use of substances before or during sex, and 62.4% (n=98) engaged in condomless sex. While most were adherent to PrEP, approximately 34.4% (n=54) expressed significant worry about daily adherence. Participants wished to monitor their PrEP adherence daily (n=66, 42.0%) and 52% (n=82) were very willing to participate in DPS-based research. The majority were minimally concerned about sharing DPS-detected adherence data with research teams (n=126, 80.3%), and were extremely willing to share these data with healthcare providers (n=109, 69.4%). CONCLUSIONS: In this sample, MSM without HIV who use substances reported willingness to use DPS to measure PrEP adherence in a research context, and identified benefits to accessing real-time, DPS-detected adherence data.

Ingestible Electronic Sensors for Monitoring Real-time Adherence to HIV Pre-exposure Prophylaxis and Antiretroviral Therapy.

PURPOSE OF REVIEW: This review summarizes the recent advancements and future directions of digital pill systems (DPS) - which utilize ingestible sensors to directly measure medication ingestion events in real-time - in the context of HIV prevention and treatment. RECENT FINDINGS: Two DPS are cleared by the US Food and Drug Administration. The bioequivalence and stability of digitized pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) have been established, and pilot studies have demonstrated the feasibility and acceptability of using DPS for PrEP and ART adherence measurement. Important bioethical and implementation considerations have been identified for future clinical trials. Continued technological advancement may reduce barriers to use, and integration of DPS into behavioral interventions may facilitate adherence improvement efforts. DPS represent an innovative tool for PrEP and ART adherence measurement. Future work will optimize the technology to reduce operational barriers. DPS have significant potential for expansion across a diverse array of diseases, though key bioethical considerations must be examined prior to large-scale implementation.

Ingestible electronic sensors to measure instantaneous medication adherence: A narrative review.

OBJECTIVE: Medication nonadherence contributes to significant morbidity and mortality worldwide. While many techniques to measure adherence exist, digital pill systems represent a novel, direct method of measuring adherence and a means of providing instantaneous adherence supports. In this narrative review, we discuss digital pill system research based on clinical trials and qualitative investigations conducted to date and potential future applications of digital pill system in medication adherence measurement. METHODS: We conducted a literature search in PubMed of English language peer-reviewed articles describing the use of digital pill system for medication adherence measurement between 2000 and 2021. We included all articles that described the deployment of ingestible sensors and those involving qualitative investigations of digital pill system with human subjects. RESULTS: A total of 95 articles were found on initial search; 75 were removed based on exclusion criteria. Included articles were categorized as investigations that deployed an ingestible sensor in human populations (n = 18), or those that conducted qualitative work (n = 3). For pilot studies, the mean accuracy of the sensor to successfully detect a medication ingestion event ranged from 68% to 100%. When digital pill systems were deployed in real-world clinical settings, accuracy ranged from 68% to 90% with lower accuracy due to nonadherence to digital pill system technology. Qualitative studies demonstrated that providers and patients perceive the digital pill system as a facilitator for improving adherence and as a potential platform for delivering adherence interventions. Additionally, ingestion data from digital pill system was viewed as useful in facilitating adherence discussions between clinicians and patients. CONCLUSIONS: This narrative review demonstrates that the use of digital pill system is broadly feasible across multiple disease states including human immunodeficiency virus, hepatitis C infection, solid organ transplants, tuberculosis, schizophrenia, cardiovascular disease, and acute fractures, where adherence is closely linked to significant morbidity and mortality. It also highlights key areas of research that are still needed prior to broad-scale clinical deployment of such systems.