Medication Event Monitoring System Research Articles

Monitoring System of Medical Device Adverse Events in the US and Application of MAUDE Database in Medical Device Registration

In order to achieve precise risk control of medical devices, it is necessary to establish a scientific evaluation system throughout the entire life cycle of medical devices that focuses on risk identification and risk control. This study summarizes the medical device adverse event monitoring system of the US on regulatory agencies and regulatory law, adverse events reporting forms and time limits, adverse event database, adverse event report analysis and evaluation, as well as adverse event feedback and control. Furthermore, some examples are provided to illustrate the application of the MAUDE database in risk analysis, physical and mechanical performance research, and clinical evaluation of medical device registration and application materials.

Evaluating the impact of individuals' morningness-eveningness on the effectiveness of a habit-formation intervention for a simple and a complex behavior.

Planning-based interventions are often used to help individuals form habits. Existing literature suggests a one-size-fits all approach to habit formation, but planning interventions may be optimized if tailored to individual differences and/or behavioral complexity. We test the hypothesis that planning to do a relatively complex behaviour (exercise) at a time that matches an individuals' diurnal preference will facilitate behavioral engagement; whereas for a simpler behaviour (calcium supplementation), the optimal time-of-day for a new behavior will occur in the morning. Young, women volunteers (N = 317) were randomly assigned to take calcium supplements or to exercise for 4 weeks and to control (no planning) or to one of three planning interventions (morning plan; evening plan; unassigned-time plan). Participants reported diurnal preference at baseline and habit strength and behavioral frequency weekly. Fitbit Zips and Medication Event Monitoring System Caps (MEMS) were used to objectively assess behavioral engagement. Multilevel modelling found that calcium-supplementation was greatest for morning-types in the morning-cue condition, whereas exercise was greatest for morning-types with morning cues and evening-types with evening cues. Habit-formation strategies may depend on diurnal preference and behavioral complexity. Future research can evaluate the role of other individual differences.

Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens. We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions. Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change). Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or "stockpiling" medication. By comparison, physicians rated all participants as either "totally compliant" or "mostly compliant". UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P<0.001). These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making. This study was preregistered on ClinicalTrials.gov (NCT03752411).

Is CONNECTDROP®, a Medication Event Monitoring System Add-On Paired with a Smartphone Application, Acceptable to Patients with Glaucoma for Taking Their Daily Medication? The CONDORE Pilot Study

ObjectiveThis pilot study tested the feasibility of a future efficacy trial examining the effect of CONNECTDROP®, a novel Medication Event Monitoring System (MEMS) paired with a mHealth application, on medication adherence in patients with glaucoma. DesignA single-center, single-arm, prospective interventional pilot study (NCT04552964) ParticipantsAdults with glaucoma managed with at least a fixed combination timolol/dorzolamide who are adherent to treatment. MethodsParticipants (n=31) were provided with the MEMS device and a smartphone with the Application installed. They were required to use the MEMS with their usual timolol/dorzolamide prescription for nine weeks. The study endpoint was at the end of week nine, when all study materials were returned, and participants completed a 17-item patient satisfaction questionnaire. Data collected continuously by each MEMS for the nine weeks was analyzed for its suitability to quantify adherence of the individual participant and characterize adherence trends within the study cohort. Clinical data were collected at baseline, week eight and week nine for the safety evaluation. Main outcome measuresThe primary outcome was global patient satisfaction after nine weeks. Secondary outcome measures included participant feedback on handling the MEMS and its usability, along with that of the connected Application. Objective data was used to determine participant medication adherence. The proportion of participants who successfully changed the MEMS to a new bottle at week eight was reported. ResultsThe MEMS-connected device achieved a global satisfaction score of 74.1% from study participants after nine weeks. Furthermore, 70.4 % of participants found the MEMS easy to use. However, only 59.2% reported feedback from the mHealth Application useful in reminding them to take their treatment. MEMS-derived data showed that 70.4% of participants achieved an "adherence score" of 80% or above after eight weeks and that 40.7% who completed the study had not changed the bottle correctly. No adverse events were reported. ConclusionIn this pilot study, the MEMS device had high satisfaction amongst this cohort of patients and was easy to use. The user satisfaction score for the Application was lower. The objective adherence data obtained appears reliable but must be validated for use in an efficacy trial.

Patient-Led Urate Self-Monitoring to Improve Clinical Outcomes in People With Gout: A Feasibility Study.

Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life. People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0plus) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons. Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of "missed doses" (two or fewer allopurinol doses missed consecutively) and "drug holidays" (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04). Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.

The association between glaucoma treatment adherence with disease progression and loss to follow-up

Prospective cohort study from Brazil to evaluate glaucoma treatment adherence using a medication event monitoring system (MEMS) device and correlate with glaucoma progression and loss to follow-up (LTF) after one year of follow up. We included primary open glaucoma (POAG) patients treated with at least one ocular hypotensive eye drop. MEMS devices was used to monitor adherence for 60 days and evaluate the percentage of doses prescribed taken within the 60-day period. We classified patients according to rates of adherence: low adherence (less than 75% from MEMS measurements) and high adherence (more than 75% from MEMS measurements). We applied a questionnaire to investigated self-reported behavior towards treatment behaviors (glaucoma treatment compliance assessment tool, GTCAT). We also correlated rates of treatment adherence with clinical, demographical variables and the occurrence of glaucoma progression or LTF after one year of observation. We included 110 POAG patients and found that 28.18% of them were considered low adherent. We identify several variables associated with poor adherence such as glaucoma progression, LTF, younger age, low educational and income levels, absence of health insurance, years of disease and peak intraocular pressure. Several constructs from the self-reported GTCAT were also correlated with the rates of treatment adherence. To date, this is the first study in Latin America to evaluate glaucoma treatment adherence with MEMS devices and correlate adherence rates with glaucoma progression and LTF. We found a low-adherence rate of 28.18% and several additional risk factors were statistically associated with poor adherence.

Medication adherence: measurement methods and approaches.

Medication adherence is crucial for optimal treatment outcomes, yet many patients struggle to follow their prescribed regimens, impacting patients, families, and healthcare systems. Measurement of adherence is vital for effective care planning and intervention. This review explores medication adherence challenges and measurement methods, including therapeutic drug monitoring (TDM), medication event monitoring system (MEMS), analysis of adherence in insurance/pharmacy database, pill counts, and self-reports, each with its advantages and limitations.This review advocates apartnership-based approach to adherence, stressing standardized reporting and team-based care. Adherence is influenced by many factors such as complex regimens, packaging, patient perspectives, side effects. Effectively addressing these factors is crucial for improving patient outcomes. In summary, medication adherence is vital but complex. The article covers various adherence measurement methods to promote medication adherence as an important matter (Tab. 5, Fig. 2, Ref. 91). Text in PDF www.elis.sk Keywords: medication adherence, adherence barriers, primary non-adherence, medication event monitoring system, pill count, self-report.

Adherence to the antirheumatic drugs: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to analyze the adherence rate for conventional and biological disease-modifying antirheumatic drugs (DMARDs) utilizing different assessment measures. A systematic literature search was performed in four electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), covering the time frame from April 1970 to April 2023. Studies that present data on medication adherence among adult patients with rheumatoid arthritis (RA), specifically focusing on DMARDs (conventional or biological), were included in the analysis. The adherence rate for different assessment measures was documented and compared, as well as for conventional and biological DMARDs. A random-effects meta-analysis was performed to assess adherence rates across different adherence assessment measures and drug groups. The search identified 8,480 studies, out of which 66 were finally included in the analysis. The studies included in this meta-analysis had adherence rates ranging from 12 to 98.6%. Adherence rates varied across several adherent measures and calculation methods. Using the subjective assessment measures yielded the outcomes in terms of adherence rate: 64.0% [0.524, 95% CI 0.374-0.675] for interviews and 60.0% [0.611, 95% CI 0.465-0.758] for self-reported measures (e.g., compliance questionnaires on rheumatology CQR-5), p > 0.05. In contrast, the objective measurements indicated a lower adherence rate of 54.4% when using the medication event monitoring system (p > 0.05). The recorded rate of adherence to biological DMARDs was 45.3% [0.573, 95% CI 0.516-0.631], whereas the adherence rate for conventional DMARDs was 51.5% [0.632, 95% CI 0.537-0.727], p > 0.05. In the meta-regression analysis, the covariate "Country of origin" shows a statistically significant (p = 0.003) negative effect with a point estimate of -0.36, SE (0.12), 95% CI, -0.61 to -0.12. Despite its seemingly insignificant factors that affect the adherence rate, this meta-analysis reveals variation in adherence rate within the types of studies conducted, the methodology used to measure adherence, and for different antirheumatic drugs. Further research is needed to validate the findings of this meta-analysis before applying them to clinical practice and scientific research. In order to secure high reliability of adherence studies, compliance with available reporting guidelines for medication adherence research is more than advisable.

The correlation between 4 adherence measurements methods in patients with rheumatoid arthritis using methotrexate.

Methotrexate (MTX) is the cornerstone in the treatment of rheumatoid arthritis (RA) patients. However, adherence to MTX therapy is not optimal, and instruments to assess medication nonadherence are warranted. To date there is no consensus on the best method to determine adherence to MTX. The aim of this study was to assess the correlation between adherence assessed with a Medication Event Monitoring System (MEMS) vs. pill count, MTX-polyglutamate (PG) concentration and Compliance Questionnaire-Rheumatology (CQR) in patients with established RA. Second, the correlations between these methods and the Disease Activity Scores of 28 joints (DAS28) were examined. Adult RA patients currently treated with MTX were included. Multivariable linear and logistic regression were used, with adherence assessed with MEMS as dependent variable vs. pill count, MTX-PG concentrations, CQR as independent variables and DAS28 vs. each of the 4 adherence measurements. Covariates were included, such as comedication, age and use of corticosteroids. In total, 190 consecutive RA patients were included. Pill count was correlated with adherence assessed with MEMS (linear regression, β =0.588, 95% confidence interval =0.255-0.921, P< .001), whereas CQR and MTX-PGs were not. Logistic regression confirmed the correlation between dichotomized adherence and pill count only (β =4.47, 95% confidence interval =1.31-7.64, P= .006). No other correlations were found, either for all adherence outcomes or DAS28. Measuring adherence with MEMS is correlated with pill count, whereas other methods were not correlated with MEMS or with DAS28. Pill count can be used to estimate adherence to MTX therapy, in case MEMS is not achievable.

Treatment Adherence and Adherence Patterns of Tofacitinib and Self-Injectable TNFi Use in People with Rheumatoid Arthritis.

To assess tofacitinib and self-injectable tumor necrosis factor inhibitor (TNFi) adherence using the Medication Event Monitoring System (MEMS) and characterize association with adherence in patients with rheumatoid arthritis (RA). Eligible patients were enrolled from the Forward Databank within 6 months of initiating tofacitinib or injectable TNFi or from participating clinics where these were first prescribed. MEMS caps and patient diaries were used to compile dosing over 9 months. Demographics and disease characteristics were collected every 6 months, and the Beliefs about Medicines Questionnaire only at baseline. Adherence along with its components, initiation, implementation, and persistence, were calculated. Of the 112 consented to participate, 82 (73%) remained in the final analysis with recruitment from clinics 47 (57%) and Forward 35 (43%). Sixty-two (76%) initiated tofacitinib with 87% taking it quaque die and twenty (24%) TNFi. At 9 months, 77% of tofacitinib were persistent versus 70% for TNFi (P = 0.65), and implementation was similar (0.84 vs. 0.82; P = 0.57). In multivariable models, increased baseline patient global assessment was consistently associated with discontinuation (hazard ratio 1.31 [1.07-1.61]). There was increased adherence to methotrexate (MTX) when taking tofacitinib that led to higher combined adherence for tofacitinib than TNFi (0.81 vs. 0.69; P = 0.03), but no significant differences remained in multivariable models. In sensitivity analysis, consistent morning intake for tofacitinib and evening intake for MTX was associated with improved adherence. We found no statistical differences in adherence between patients with RA initiating tofacitinib and self-injectable TNFi, although 15% to 30% were nonadherent. Concomitant MTX, patient global assessment, and a consistent time of day intake were associated with adherence.

Oral Chemotherapy Adherence in Pediatric Acute Lymphoblastic Leukemia (ALL): A Report from the Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 16-001

Background: Successful treatment of pediatric acute lymphoblastic leukemia (ALL) requires 2 years of risk-directed therapy, much of which is built on a backbone of oral chemotherapy including 6-mercaptopurine (6MP) and dexamethasone (DEX). Studies conducted in the Children's Oncology Group (COG) demonstrate that poor adherence to 6MP during the maintenance phase confers increased relapse risk; however, little is known about the rates of 6MP adherence in non-COG ALL regimens. DFCI ALL Consortium protocols utilize 3-week cycles including 14-day pulses of 6MP with weekly intravenous or intramuscular methotrexate. This treatment approach requires more frequent contact between families and healthcare providers and reduces the number of oral chemotherapy agents prescribed. Whether this higher-touch regimen might reduce the frequency of non-adherence as compared to published COG data is not known. Additionally, there remains a paucity of data investigating incidence of non-adherence to DEX, 6MP, and to any medications during the first year of therapy. Methods: Oral chemotherapy adherence was prospectively evaluated as an embedded ancillary study on the DFCI ALL Consortium Protocol 16-001. Eligible participants included English-, Spanish-, or French-speaking caregivers of patients (&amp;lt;22 years) receiving 6MP and DEX (both liquid and tablet formations) and did not utilize a pillbox. Adherence to 6MP and DEX were measured using Medication Event Monitoring Systems (MEMS) caps, which record the date and time of medicine bottle opening. MEMS caps were used to measure adherence for three consecutive cycles during the first year of therapy, and again for three consecutive cycles during the second year of therapy. Caregivers completed surveys reporting sociodemographic determinants of health (SDOH), medication-taking behaviors, and chemotherapy comprehension. MEMS-based medication adherence rates were calculated as a percentage based upon the ratio of the number of days with MEMS cap openings to the number of days 6MP and/or DEX were prescribed. Adherent patients were defined as those with ≥95% adherence based on prior COG trials that observed an excess risk of relapse below this threshold (Bhatia JAMA Onc 2015). Results: Between 2018 - 2022, 252/429 (59%) eligible patients consented to study participation, and adherence data was successfully collected for 207 (82%). Sixty-six (26%) participants were enrolled from Canadian hospital centers, and 186 (74%) participants were enrolled from US hospital centers. Participant age included 159 (77%) &amp;lt;10 years of age, 31 (15%) 10 - 14 years, and 17 (8%) 15 - 21 years (see Table 1). Thirty-four (16%) patients identified as Hispanic, 13 (6%) non-Hispanic Black, 18 (9%) non-Hispanic Other, and 142 (69%) non-Hispanic White. 57 (31%) patients relied on public insurance at time of diagnosis, 61 (34%) patients reported a primary household language other than English, and 36 (20%) patients lived in lone-parent households. A third, 61 (34%) and 62 (34%), of caregivers reported being unsure of what would happen if their child stopped taking 6MP or DEX, respectively. Over the course of six cycles, MEMS-measured adherence rates to 6MP (N = 180) and DEX (N = 195) were 73% (range 21 - 100) and 86% (range 10 - 100), respectively. Preliminary data suggest that adherence rates to 6MP improved during year 2 of treatment (cycles 4-6 of monitoring) (Table 2). In unadjusted analyses, there was a non-significant association between patient age and likelihood of adherence to oral medication: adherence to 6MP was 71% in those &amp;lt;10 years, 80% in those 10 - 14 years, and 71% in those 15 years or older (Jonckheere-Terpstra test p = 0.66). Conclusion: Among a diverse cohort of patients treated with a DFCI ALL Consortium regimen, adherence to oral chemotherapy is suboptimal with rates of 73% to 6MP and 86% to DEX. This finding recapitulates published data from COG ALL trials, suggesting more frequent contact with healthcare providers in the DFCI Consortium protocol does not mitigate non-adherence. Numerical differences between age groups suggest patients ages 10 - 14 years (N=31) have higher adherence compared to patients both younger and older. These preliminary findings suggest that there may be a behavioral component when it comes to medication adherence - with barriers among young children differing from those in both younger and older adolescents.

Medication intake reminders via a smartphone app improve real-world adherence to oral anticoagulation in atrial fibrillation patients

Abstract Introduction Treatment with oral anticoagulation (OAC) is one of the main pillars in managing atrial fibrillation (AF). Education and intake monitoring are recommended to improve therapy adherence to OAC. Over the past few years, the importance of smart devices has increased, opening up new potential for patient education and better patient follow-up. Purpose We wanted to evaluate the usage of a medication module of an in-house developed application, AF-EduApp, and its effect on patients’ therapy adherence to OAC. Methods The AF-EduApp multicenter study included 152 AF patients. The educational AF-EduApp contains, besides other modules, a medication module with the possibility to add a medication list. Patients also had the possibility to configure pill intake reminders which they could easily tick off. Adherence was calculated as the proportion of days that the medication was correctly taken, as indicated by the patient. This was compared with adherence measured by the Electronic Medication Event Monitoring System (MEMS, Aardex Group, Liège), which formed the primary outcome of this study. The MEMS cap registered the date and time of bottle opening and was used at baseline and after 12 months, each time for a monitoring period of 3 months (M1 respectively M2). Regimen adherence was defined as the proportion of days with the correct number of openings as recorded by MEMS. Results The 152 patients (Age: 68.8 ±6.7 years; Time since AF diagnosis: 5.1 ±6.6 years) used the application on 130.1 ±144.7 days during a mean follow-up of 386.8 ±108.1 days. A total of 137 patients were on OAC, of whom 87 patients set a reminder for the OAC in their medication list. If based on checking off the reminder, patients had a median therapy adherence of only 5.6% (IQR: 0.2-64.3%). This contrasts with a high regimen adherence based on MEMS: in 84 patients who completed both monitoring periods, adherence was 94.5 ±7.0% at M1 and 94.1 ±6.6% at M2 (p=0.266 between M1 and M2). At M1, there was already a trend towards a significant difference in MEMS regimen adherence between patients who did or did not set a reminder (96.3 ±4.8% vs 93.1 ±8.0%, n=84; p=0.067). At M2, patients who set a reminder took their medication significantly better than those who did not (96.2 ±5.3% vs 92.6 ±7.1%; p=0.048) (Fig 1). Conclusion The medication module was used by most of the patients, and 63.5% installed an intake reminder for at least their OAC therapy. However, checking off reminders is rarely done and cannot be used to judge adherence. On the other hand, patients who installed a reminder had a significantly higher real-world regimen adherence for OAC compared to patients who did not set a reminder. Medication intake reminders can contribute to improving adherence to OAC therapy.MEMS based real-world regimen adherence

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol.

Accurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess thepairwise concordance between three commonly used non-biological medication adherence assessment methods in adolescents who use alcohol to inform the selection of medication adherence measures for use in future youth SUD trials. Participants (N = 32, 17-19-years-old) took N-acetylcysteine and placebo, in a randomized cross-over design, for 10 days each. Medication adherence was assessed (20 days total) via pill count, medication videos submitted twice daily, and the Medication Event Monitoring System (MEMS®). Lin's Concordance Correlation Coefficient (CCC) assessed concordance and Bland-Altman plots are reported. Linear mixed-effects models with main effects of medication, treatment block (first medication, second medication), and sequence were also run. Medication videos yielded the lowest (64%) and pill count yielded the highest (89%) adherence estimates. CCC values indicated poor correspondence, except between pill count and MEMS. The Bland-Altman plots showed good pairwise agreement between all methods. Linear mixed-effects models indicated a difference between the first and second cross-over medication, with adherence estimates being lower for the second medication, regardless of whether it was N-acetylcysteine or placebo. The study yielded important and practical information. First, incorporating more than one method of adherence assessment may capture estimated floor and ceiling adherence in the absence of a biological marker. This is particularly relevant for remote or hybrid studies where bio-marker collection is challenging. Selection of the assessment methods will depend on study goals. Second, the continuation of medication adherence research can benefit each phase of clinical trials and inform rigorous pharmacotherapy evaluation.

Medication adherence to obeticholic acid: a real-world experience using medication event monitoring systems

ObjectiveWe designed a clinical study to analyze patterns of adherence to obeticholic acid, factors influencing the adherence and potential correlation with treatment efficacy by using MEMS® cap in practice daily. MethodA multicenter prospective observational study of patients with primary biliary cholangitis. Adherence will be measured by MEMS® cap, pill count, and patient-reported outcomes during 3 months. The quality of life will be self-reported using the Chronic Liver Disease Questionnaire test, European Quality of Life 5-Dimension Questionnaire test and Itch Severity Scale. ConclusionsWe expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor compliance and introduce measures to reduce its prevalence.

Randomized phase III trial evaluating motivational interviewing and text interventions to optimize adherence to breast cancer endocrine therapy (Alliance A191901): the GETSET protocol

BackgroundHormone receptor-positive (HR +) breast cancer is the most common type of breast cancer in the USA but has excellent long-term outcomes in recent decades, in part due to effective oral endocrine therapy (ET). ET medications are typically prescribed for 5 to 10 years, depending on the risk of recurrence, and must be taken daily. One limiting factor to ET efficacy is nonadherence, with high-risk groups for nonadherence including younger women and Black women.MethodsThe Alliance for Clinical Trials in Oncology (Alliance) trial A191901 is an ongoing, four-arm (text message reminder (TMR), motivational interviewing (MI), TMR plus MI, or enhanced usual care) randomized clinical trial that tests the efficacy and effect of two interventions (TMR and/or MI) on improved ET adherence, patient-reported outcomes (PROs), and resource use requirements among HR + breast cancer survivors. Participants are randomized in a 1:1:1:1 ratio to the four arms. With an assumed loss to follow-up of approximately 11%, we plan to recruit 1180 participants. Randomization is stratified based on age and race to ensure balance between the arms, and we oversample younger and Black women, with each group representing 30% of the study population. Participants randomized to an intervention will actively participate in the intervention for 9 months, and all participants will be followed for adherence data and PRO endpoints, through the use of the Pillsy cap medication event monitoring system and Alliance ePRO survey app (i.e., Patient Cloud). The primary analysis will compare Pillsy-measured ET adherence among study arms at 12 months.DiscussionThis multisite study will not only define strategies to improve adherence to breast cancer oral therapies, but it will also potentially support strategies in large cooperative research groups that can increase delivery and tolerability of ET, involve diverse patient populations in clinical research, and engage patients effectively in interventional studies, using remote and cost-effective delivery methods.Trial registrationClinicaltrials.gov NCT04379570. Registered on 7 May 2020.

Adherence to oral anticoagulation measured by electronic monitoring in a Belgian atrial fibrillation population

IntroductionStroke prevention using oral anticoagulation (OAC) is the first management priority in atrial fibrillation (AF). Despite the importance of good therapy adherence, real-world adherence is still suboptimal. Patient education and adherence monitoring with new technologies are recommended. The main purpose of this sub-analysis of the AF-EduCare trial was to evaluate the effect of personalized follow-up strategies on adherence to OAC.MethodsRegimen adherence was monitored by the electronic Medication Event Monitoring System cap at the start of the trial (M1) and after 12 months (M2), each for three months. Patients were part of one of three education groups (In-person, Online or App-based) or the standard care (SC) group. All are qualified for OAC therapy.ResultsA total of 768 patients were evaluated (11.8% SC vs. 86.8% any education group, mean age: 70.1 ± 7.9 years). Patients were taking non-vitamin K OAC (once daily 53.8%; twice daily 35.9%) or vitamin K antagonists (9.4%), equally distributed over the different study arms (p = 0.457). Mean therapy adherence was high (M1:93.8 ± 10.8%; M2:94.1 ± 10.1%). During both monitoring periods, the education group scored significantly higher than SC (M1:94.2 ± 10.0% vs. 91.3 ± 15.0%; p = 0.027; M2:94.4 ± 9.3% vs. 91.6 ± 14.0%; p = 0.006). More patients in the In-person and Online groups were able to keep or improve their adherence to > 90% compared to the SC.ConclusionOverall adherence to OAC in all study groups, even in SC, was very high, without attrition over time. Nevertheless, targeted education led to a small but significantly improved adherence compared to SC.Graphical

Loneliness Among Black/African American Adults Living with HIV: Sociodemographic and Psychosocial Correlates and Implications for Adherence

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, social determinants of health, health outcomes, and loneliness. Antiretroviral therapy (ART) adherence was assessed electronically with the medication event monitoring system. Bivariate linear regressions analysis showed higher loneliness scores among those with higher levels of internalized HIV stigma, depression, unmet needs, and discrimination related to HIV serostatus, race, and sexual orientation. In addition, participants who were married or living with a partner, had stable housing, and reported receiving more social support had lower levels of loneliness. In multivariable regression models controlling for correlates of loneliness, loneliness was found to be a significant independent predictor of worse general physical health, worse general mental health, and greater depression. Loneliness was marginally associated with lower ART adherence. Findings suggest that Black adults living with HIV, who experience multiple intersectional stigmas, require targeted interventions and resources.

#2846 DEVELOPMENT OF THE JAPANESE VERSION OF THE BASEL ASSESSMENT OF ADHERENCE TO IMMUNOSUPPRESSIVE MEDICATIONS SCALE

Abstract Background and Aims One of the major barriers for long-term transplant outcomes in kidney transplant recipients is medication non-adherence, which is a risk factor for de novo donor-specific antibody development leading to antibody-mediated rejection and graft loss. Identifying non-adherent patients is the first step in minimizing the risk of complications of medication non-adherence. However, to date, there is no validated Japanese self-report instrument to evaluate the MA for transplant patients. This study aimed to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (J-BAASIS). Method We conducted a single-center cross-sectional study for kidney transplant recipients who visited our hospital. The eligible and willing participants were randomly assigned to two groups, the J-BAASIS group and the J-BAASIS+MEMS group, with random numbers generated by computer. All participants filled out a questionnaire including the J-BAASIS (the first survey). They filled out a questionnaire again including the J-BAASIS in similar conditions during their following outpatient visit 4-6 weeks later (the second survey). The participants in the J-BAASIS+MEMS group took the methylprednisolone tablets daily using the MEMS until the second survey. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system (MEMS) and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias tool. Results A total of 106 kidney transplant recipients (the J-BAASIS group, 56; the J-BAASIS+MEMS group, 50) were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the MEMS, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the “medication compliance” subscale was 0.38 (p&amp;lt;0.001). Conclusion The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate medication adherence may help clinicians to identify non-adherent transplant patients and institute appropriate corrective measures to improve transplant outcomes. Moreover, this study, which demonstrated the concurrent validity with the MEMS, the gold standard for measuring medication adherence, further strengthens the evidence for the psychometric properties of the original BAASIS.

Comparing adherence to MDR-TB treatment among patients on self-administered therapy and those on directly observed therapy: non-inferiority randomized controlled trial

BackgroundAdherence is key to the treatment success of multi-drug resistant tuberculosis (MDR-TB) and prevention of community transmission. Directly observed therapy (DOT) is the recommended approach for the management of patients with MDR-TB. Uganda implements a health facility-based DOT approach where all patients diagnosed with MDR-TB report to the nearest private or public health facility for daily observation of ingesting their medicines by a health care provider. Directly observed therapy is very costly for both the patient and health care system. It follows the assumption that MDR TB patients have a history of poor adherence to TB treatment. But only 21% of MDR-TB patients notified globally and 1.4–12% notified in Uganda had been previously treated for TB. The shift to all oral treatment regimen for MDR-TB provides an opportunity for the exploration of self-administered therapy for this group of patients even with use of remotely operated adherence technology. We are conducting a non-inferiority open-label randomized controlled trial to compare adherence to MDR-TB treatment among patients on self-administered therapy (measured by Medication Events Monitoring System (MEMS) technology) with a control group on DOT.MethodsWe plan to enrol 164 newly diagnosed MDR-TB patients aged ≥ 8 years from three regional hospitals based in rural and urban Uganda. Patients with conditions that affect their dexterity and ability to operate the MEMS-operated medicine equipment will not be eligible to participate in the trial. Patients are randomized to either of the two study arms: self-administered therapy with adherence being monitored using MEMS technology (intervention arm) or health facility-based DOT (control arm) and will be followed up monthly. Adherence is measured by the number of days the medicine bottle is open to access medication as recorded by the MEMS software in the intervention arm and treatment complaint days as recorded in the TB treatment card in the control arm. The primary outcome is the comparison of adherence rates between the two study arms.DiscussionThe evaluation of self-administered therapy for patients with MDR-TB is important to inform cost-effective management strategies for these patients. The approval of all oral regimens for the treatment of MDR-TB provides an opportunity for innovations such as MEMS technology to support sustainable options for MDR-TB treatment adherence support in low-resource settings.Trial registrationPan African Clinical Trials Registry, Cochrane #PACTR202205876377808. Retrospectively registered on 13 May 2022

Pharmacokinetic Model of Tenofovir and Emtricitabine and Their Intracellular Metabolites in Patients in the ANRS 134-COPHAR 3 Trial Using Dose Records.

Tenofovir (TFV) and emtricitabine (FTC) are part of the recommended highly active antiretroviral therapy (ART). Both molecules show a large interindividual pharmacokinetic (PK) variability. Here, we modeled the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV diphosphate [TFV-DP] and FTC triphosphate [FTC-TP]) collected after 4 and 24 weeks of treatment in 34 patients from the ANRS 134-COPHAR 3 trial. These patients received daily (QD) atazanavir (300 mg), ritonavir (100 mg), and a fixed-dose combination of coformulated TFV disoproxil fumarate (300 mg) and FTC (200 mg). Dosing history was collected using a medication event monitoring system. A three-compartment model with absorption delay (Tlag) was selected to describe the PK of, respectively, TFV/TFV-DP and FTC/FTC-TP. TFV and FTC apparent clearances, 114 L/h (relative standard error [RSE] = 8%) and 18.1 L/h (RSE = 5%), respectively, were found to decrease with age. However, no significant association was found with the polymorphisms ABCC2 rs717620, ABCC4 rs1751034, and ABCB1 rs1045642. The model allows prediction of TFV-DP and FTC-TP concentrations at steady state with alternative regimens.