Digital Pills Research Articles

Digital pills: a scoping review of the empirical literature and analysis of the ethical aspects

BackgroundDigital Pills (DP) are an innovative drug-device technology that permits to combine traditional medications with a monitoring system that automatically records data about medication adherence as well as patients’ physiological data. Although DP are a promising innovation in the field of digital medicine, their use has also raised a number of ethical concerns. These ethical concerns, however, have been expressed principally from a theoretical perspective, whereas an ethical analysis with a more empirically oriented approach is lacking. There is also a lack of clarity about the empirical evidence available concerning the application of this innovative digital medicine.MethodsTo map the studies where DP have been tested on patients and discuss the ethically relevant issues evident therein, we performed a scoping review of the empirical literature concerning DP.ResultsOur search allowed us to identify 18 papers reporting on studies where DP were tested on patients. These included studies with different designs and involving patients with a variety of conditions. In the empirical literature, a number of issues with ethical relevance were evident. At the patient level, the ethical issues include users’ interaction with DP, personal sphere, health-related risks and patients’ benefits. At the provider level, ethically relevant issues touch upon the doctor-patient relationship and the question of data access. At the societal level, they concern the benefits to society, the quality of evidence and the dichotomy device-medicine.ConclusionsWe conclude that evidence concerning DP is not robust and that more research should be performed and study results made available to evaluate this digital medicine. Moreover, our analysis of the ethically relevant aspects within empirical literature underscores that there are concrete and specific open questions that should be tackled in the ethical discussion about this new technological solution.

Attitudes and Response to a Smartphone-Based Digital Pill Intervention to Enhance PrEP Adherence Among Men Who Have Sex With Men With Stimulant Use

Background Digital pills contain a radiofrequency emitter and gelatin capsule that over-encapsulate a study medication. The radiofrequency emitter, activated by the chloride ion gradient in the stomach, transmits a signal to a wearable Reader device following ingestion. The Reader relays ingestion data to a smartphone app and cloud-based server, allowing for real-time verification of ingestion events and adherence measurement. Digitized pre-exposure prophylaxis (PrEP) may improve outcomes in populations with suboptimal adherence related to substance use. Stimulant use is particularly prevalent among men who have sex with men (MSM) and is associated with increased HIV risk behavior and transmission. We conducted seven focus groups with MSM who use stimulants (N=16) to inform the development of PrEPsteps, a novel smartphone-based adherence intervention respondent to data from digitized PrEP and designed to augment adherence. Objective To inform the specification of the design, content, and delivery of the smartphone-based PrEPsteps adherence system via focus groups with HIV-negative MSM who use stimulants. Methods Seven focus groups were conducted with HIV-negative MSM reporting stimulant use (eg, cocaine, methamphetamine) in the past six months. Participants self-reported medical history, substance use and sexual activity. Focus groups explored responses to digital pill technology, willingness and barriers to use, content and timing of adherence messaging, and three intervention components: (1) abbreviated cognitive behavioral therapy (CBT) adherence counseling (LifeSteps); (2) contingent reinforcement/corrective feedback; and (3) substance use-related Screening, Brief Intervention and Referral to Treatment (SBIRT). Focus groups were transcribed and analyzed using applied thematic analysis. Results Sixteen individuals participated in focus groups. All were male; age ranged from 24 to 63 (mean 39.9, SD 14.1) and most self-identified as gay (N=13). Participants were primarily non-Hispanic or Latino (N=12); 10 identified as white, two as black, and four as multiracial. Most had at least a college degree (N=14). Twelve participants were taking PrEP, 5 of whom reported missed doses in the past two weeks. Number of sexual partners in the past three months ranged from 1 to 200 (M=28.1; SD=50.9). Fifteen participants reported using stimulants during the last 30 days. Participants viewed digital pills as a tool to enhance PrEP adherence and accountability. They expressed a willingness to use the digital pill and identified physicians, family members, and partners as people with whom they would share adherence data. The Reader was viewed as the most difficult technological component to use, although participants also described the device as itself an adherence reminder. Participants identified customizability as a valuable aspect of the technology; message and reminder content, structure, and scheduling were all considered customizable. With regard to the intervention, participants were accepting of and willing to interact with corrective feedback messages linked to a brief CBT LifeSteps booster session. Conclusions PrEPsteps, a smartphone-based adherence intervention, was viewed as acceptable by HIV-negative MSM who use stimulants. Individuals perceived corrective feedback notifications to be the most helpful component of the system, and expressed a strong preference for customizability across the intervention.

Short Communication: Bioequivalence of Tenofovir Component of Tenofovir/Rilpivirine/Emtricitabine in Digital Pills.

Digital pills, gelatin capsules with radiofrequency transmitters activated by stomach chloride ions, directly measure antiretroviral therapy adherence. In individuals with substance use disorders and HIV, real-time nonadherence detected by digital pills creates a platform to deliver substance use and adherence interventions. In this study, we determined the bioequivalence of tenofovir (TFV), administered as tenofovir disoproxil fumarate (TDF) in healthy human volunteers administered a commercial drug product and a digital pill formulation. We adhered generally to the US FDA Analytical Procedures and Methods for Validation for Drugs and Biologics guidelines. Ten HIV-uninfected adults without reported allergy to TFV, emtricitabine, or rilpivirine were enrolled. Participants ingested a digital pill containing TDF/emtricitabine/rilpivirine. Peripheral venous blood samples were collected at 0.5, 1, 2, 4, 8, and 24 h postingestion. After a 14-day washout period, the same participants ingested Complera™. Serial venous blood samples were collected using the same protocol as the digital pill. Liquid chromatography/mass spectrometry was used to determine a maximum concentration (Cmax), area under curve from time zero to last measured concentration (AUCo-t), and area under curve from time zero to infinity (AUCoo) of TFV. Ten participants with an average age of 27 and body mass index of 25.4 successfully completed the study. Predose TFV was undetectable before the second administration of Complera confirming adequate washout period after ingestion of the digital pill. The geometric means of AUCo-t, AUCoo, and Cmax for test and reference products were within the 95% confidence intervals and, therefore, bioequivalent. TFV overencapsulated in digital pills are bioequivalent to TFV in commercial formulations.

Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals. The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.

Rethinking agency and medical adherence technology: applying Actor Network Theory to the case study of Digital Pills.

Much literature surrounding medical technology and adherence posits that technology is a mechanism for social control. This assumes that the medical establishment can take away patients' agency. Although power relationships and social control can play a key role, medical technology can also serve as an agentive tool to be utilized. We (1) offer the alternative framework of Actor Network Theory to view medical technology, (2) discuss the literature on medication adherence and technology, (3) delve into the ramifications of looking at adherence as a network and (4) use Digital Pills as a case study of dispersed agency.

Feasibility and Acceptability of Digital Pills to Monitor PrEP Adherence in MSM With Substance Use

Feasibility and Acceptability of Digital Pills to Monitor PrEP Adherence in MSM With Substance Use