No abstract

A recent, phase 3b, mirror-image clinical trial of outpatients with schizophrenia found that use of aripiprazole tablets with sensor (AS; Abilify MyCite ® , comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptomseverity measures assessed by clinical raters. Participants and Methods: This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18-65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated. Results: A total of 277 outpatients were enrolled (discontinued, n = 164; moderate engagement, n = 63; high engagement, n = 50). All groups experienced symptom improvement from baseline to end-of-study, with significant changes in the more-engaged groups. Highly engaged participants showed significant improvement for all clinical scores and subscores (all P < 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement. Conclusion: Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.

Background Suboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate. Objective The primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence. Methods This open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS. Results We enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers. Conclusions There was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS. Trial Registration ClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449

Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods: Participants used AS for 3-6 months. HCPs were instructed to check the dashboard regularly, identify features used, and report impact on treatment decisions. After stratifying HCPs by frequency of dashboard checks and resulting treatment decisions, changes from baseline were calculated for Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI)-Severity of Illness and CGI-Improvement (CGI-I), and Personal and Social Performance (PSP), and compared using Mann-Whitney U-tests and rank-biserial correlation coefficient (r) effect sizes. Results: To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: −9.2 versus −3.1 [p=0.0002]), PANSS positive subscale (−3.2 versus −1.5 [p=0.003]), PANSS general subscale (−4.3 versus −1.2 [p=0.02]), and Marder factor for negative symptoms (−1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion: This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.

BACKGROUND Wearable sensors in digital health help facilitate real-time, point-of-care monitoring. However, wearable sensors may pose a risk for skin irritation through the use of adhesive patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite®) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder. AS includes aripiprazole tablets with an embedded ingestible event marker, a wearable sensor attached to the skin through an adhesive patch, a smartphone app, and a web-based portal. To continuously improve the final product, successive iterations of sensor patches were developed, including RP4, which was replaced by DW5, followed by RW2. OBJECTIVE This analysis pooled safety data of clinical studies in adult participants using the RP4, DW5, and RW2 patches of AS and evaluated adverse events related to patch wear. METHODS We analyzed safety data from 6 long-term and 6 short-term studies in adults aged 18–65 years from May 2010 to August 2020. All studies evaluated safety, with short-term studies also specifically examining human factors associated with use of the components of AS. Healthy volunteers or patients with schizophrenia, bipolar I disorder, or major depressive disorder were enrolled; those who received ≥ 1 exposure to the patch component of AS were included in the safety analysis. Adverse events related to patch wear were evaluated: abrasions, blisters, dermatitis, discoloration, erythema, irritation, pain, pruritus, rash, and skin reactions were grouped as skin irritation events (SIEs). RESULTS The analysis included 763 participants (mean age 42.6 years, 47.1% White, 55% male). Participants were healthy volunteers (35.3%) or patients with schizophrenia (52.7%), bipolar I disorder (7.5%), or major depressive disorder (4.6%). Overall, 13.6% (n/N = 104/763) of the participants reported at least 1 SIE; any SIEs experienced were localized to the patch site. Incidence of SIEs decreased as the patch versions developed; ≥ 1 SIE was experienced by 18.1% (28/155), 14.2% (55/387), and 9.2% (28/306) of participants who used RP4, DW5, and RW2 patches, respectively. Incidence of SIE-related treatment discontinuation was low, reported in 1.9% (3/155), 3.1% (12/387), and 1.3% (4/306) of participants who used RP4, DW5, and RW2 patches, respectively. Incidence of SIEs was higher in long-term studies than in short-term studies (15.8% vs 8.8%), with 22.4%, 17.6%, and 5.6% of participants in long-term studies reporting ≥ 1 SIE for RP4, DW5, and RW2 patches, respectively. CONCLUSIONS The pooled safety analysis indicated that incidence of SIEs decreased as the patch versions evolved from RP4 through RW2. These results further suggest that information derived from reported adverse events may have informed product design and development, which improved both tolerability and wearability of successive products. CLINICALTRIAL 316-13-204, 316-13-205, 316-13-206A (NCT02091882), 316-13-206B (NCT02091882), 316-13-215 (NCT02722967), 316-14-220 (NCT02219009), 031-201-00186 (NCT03568500), 031-201-00266, 031-201-00301 (NCT03892889), 031-201-00383, 031-201-00420, 031-201-00469.