Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial.
ABSTRACT: Importance:Forgetfulness is a major contributor to nonadherence to chronic disease medications and could be addressed with medication reminder devices. Objective:To compare the effect of 3 low-cost reminder devices on medication adherence. Design, Setting, and Participants:This 4-arm, block-randomized clinical trial involved 53 480 enrollees of CVS Caremark, a pharmacy benefit manager, across the United States. Eligible participants were aged 18 to 64 years and taking 1 to 3 oral medications for long-term use. Participants had to be suboptimally adherent to all of their prescribed therapies (with a medication possession ratio of 30% to 80%) in the 12 months before randomization. Participants were stratified on the basis of the medications they were using at randomization: medications for cardiovascular or other nondepression chronic conditions (the chronic disease stratum) and antidepressants (the antidepressant stratum). In each stratum, randomization occurred within blocks defined by whether all of the patient's targeted medications were dosed once daily. Patients were randomized to receive in the mail a pill bottle strip with toggles, digital timer cap, or standard pillbox. The control group received neither notification nor a device. Data were collected from February 12, 2013, through March 21, 2015, and data analyses were on the intention-to-treat population. Main Outcomes and Measures:The primary outcome was optimal adherence (medication possession ratio ≥80%) to all eligible medications among patients in the chronic disease stratum during 12 months of follow-up, ascertained using pharmacy claims data. Secondary outcomes included optimal adherence to cardiovascular medications among patients in the chronic disease stratum as well as optimal adherence to antidepressants. Results:Of the 53 480 participants, mean (SD) age was 45 (12) years and 56% were female. In the primary analysis, 15.5% of patients in the chronic disease stratum assigned to the standard pillbox, 15.1% assigned to the digital timer cap, 16.3% assigned to the pill bottle strip with toggles, and 15.1% assigned to the control arm were optimally adherent to their prescribed treatments during follow-up. There was no statistically significant difference in the odds of optimal adherence between the control and any of the devices (standard pillbox: odds ratio [OR], 1.03 [95% CI, 0.95-1.13]; digital timer cap: OR, 1.00 [95% CI, 0.92-1.09]; and pill bottle strip with toggles: OR, 0.94 [95% CI, 0.85-1.04]). In direct comparisons, the odds of optimal adherence were higher with a standard pillbox than with the pill bottle strip (OR, 1.10 [95% CI, 1.00-1.21]). Secondary analyses yielded similar results. Conclusions and Relevance:Low-cost reminder devices did not improve adherence among nonadherent patients who were taking up to 3 medications to treat common chronic conditions. The devices may have been more effective if coupled with interventions to ensure consistent use or if targeted to individuals with an even higher risk of nonadherence. Trial Registration:clinicaltrials.gov Identifier: NCT02015806.
Project description:BACKGROUND:Poor medication adherence contributes to inadequate control of hypertension. However, the value of adherence monitoring is unknown. OBJECTIVE:To evaluate the impact of monitoring adherence with electronic pill bottles or bidirectional text messaging on improving hypertension control. DESIGN:Three-arm pragmatic randomized controlled trial. PATIENTS:One hundred forty-nine primary care patients aged 18-75 with hypertension and text messaging capabilities who were seen at least twice in the prior 12 months with at least two out-of-range blood pressure (BP) measurements, including the most recent visit. INTERVENTIONS:Patients were randomized in a 1:2:2 ratio to receive (1) usual care, (2) electronic pill bottles for medication adherence monitoring (pill bottle), and (3) bidirectional text messaging for medication adherence monitoring (bidirectional text). MAIN MEASURES:Change in systolic BP during the final 4-month visit compared with baseline. KEY RESULTS:At the 4-month follow-up visit, mean (SD) change values in systolic blood pressure were -?4.7 (23.4) mmHg in usual care, -?4.3 (21.5) mmHg in the pill bottle arm, and -?4.6 (19.8) mmHg in the text arm. There was no significant change in systolic blood pressure between control and the pill bottle arm (p?=?0.94) or the text messaging arm (p?=?1.00), and the two intervention arms did not differ from each other (p?=?0.93). CONCLUSIONS:Despite good measured adherence, neither feedback with electronic pill bottles nor bidirectional text messaging about medication adherence improved blood pressure control. Adherence to prescribed medications was not improved enough to affect BP control or it was not the primary driver of poor control. TRIAL REGISTRATION:clinicaltrials.gov (NCT02778542).
Project description:BACKGROUND:Many recently approved medications to manage multiple myeloma (MM) are oral, require supportive medications to prevent adverse effects, and are taken under complex schedules. Medication adherence is a concern; however, little attention has been directed toward understanding adherence in MM or associated barriers and facilitators. Advanced sensored medication devices (SMDs) offer opportunities to intervene; however, acceptability among patients with MM, particularly African American patients, is untested. OBJECTIVE:This study aimed to explore patients' (1) perceptions of their health before MM including experiences with chronic medications, (2) perceptions of adherence barriers and facilitators, and (3) attitudes toward using SMDs. METHODS:An in-person, semistructured, qualitative interview was conducted with a convenience sample of patients being treated for MM. Patients were recruited from within an urban, minority-serving, academic medical center that had an established cancer center. A standardized interview guide included questions targeting medication use, attitudes, adherence, barriers, and facilitators. Demographics included the use of cell phone technology. Patients were shown 2 different pill bottles with sensor technology-Medication Event Monitoring System and the SMRxT bottle. After receiving information on the transmission ability of the bottles, patients were asked to discuss their reactions and concerns with the idea of using such a device. Medical records were reviewed to capture information on medication and diagnoses. The interviews were audio-recorded and transcribed. Interviews were independently coded by 2 members of the team with a third member providing guidance. RESULTS:A total of 20 patients with a mean age of 56 years (median=59 years; range=29-71 years) participated in this study and 80% (16/20) were African American. In addition, 18 (90%, 18/20) owned a smartphone and 85% (17/20) were comfortable using the internet, text messaging, and cell phone apps. The average number of medications reported per patient was 13 medications (median=10; range=3-24). Moreover, 14 (70%, 14/20) patients reported missed doses for a range of reasons such as fatigue, feeling ill, a busy schedule, forgetting, or side effects. Interest in using an SMD ranged from great interest to complete lack of interest. Examples of concerns related to the SMDs included privacy issues, potential added cost, and the size of the bottle (ie, too large). Despite the concerns, 60% (12/20) of the patients expressed interest in trying a bottle in the future. CONCLUSIONS:Results identified numerous patient-reported barriers and facilitators to missed doses of oral anticancer therapy. Many appear to be potentially mutable if uncovered and addressed. SMDs may allow for capture of these data. Although patients expressed concerns with SMDs, most remained willing to use one. A feasibility trial with SMDs is planned.
Project description:Medication nonadherence is an important obstacle to cardiovascular disease management.To improve adherence through real-time feedback based on theories of how social forces influence behavior.Two randomized controlled pilot trials called PROMOTE and SUPPORT. Participants stored statin medication in wireless-enabled pill bottles that transmitted adherence data to researchers.Adults with diabetes and a history of low statin adherence based on pharmacy refills (i.e., Medication Possession Ratio [MPR] <80% in the pre-randomization screening period).In PROMOTE, each participant was randomized to 1) weekly messages in which that participant's statin adherence was compared to that of other participants (comparison), 2) weekly summaries of that participant's statin adherence (summary), or 3) control. In SUPPORT, each participant identified another person (the Medication Adherence Partner [MAP]) to receive reports about that participant's adherence, and was randomized to 1) daily reports to MAP, 2) weekly reports to MAP, 3) reports to MAP only if dose was missed, or 4) control.Adherence measured by pill bottle.Among 45,000 health plan members contacted by mail, <1% joined the trial. Participants had low baseline MPRs (median?=?60%, IQR 41-72%) but high pill-bottle adherence (90% in PROMOTE, 92% in SUPPORT) during the trial. In PROMOTE (n?=?201) and SUPPORT (n?=?200), no intervention demonstrated significantly better adherence vs.In a subgroup of PROMOTE participants with the lowest pre-study MPR, pill-bottle-measured adherence in the comparison arm (89%) was higher than the control (86%) and summary (76%) arms, but differences were non-significant (p?=?0.10).Interventions based on social forces did not improve medication adherence vs. control over a 3-month period. Given the low percentage of invited individuals who enrolled, the studies may have attracted participants who required little encouragement to improve adherence other than study participation.
Project description:Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence. Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D(3)/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels. Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses. Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications.
Project description:BACKGROUND:Simple nudges such as reminders and feedback reports to either a patient or a partner may facilitate improved medication adherence. OBJECTIVE:To test the impact of a pill bottle used to monitor adherence, deliver a daily alarm, and generate weekly medication adherence feedback reports on statin adherence. DESIGN:Three-month, three-arm randomized clinical trial (ClinicalTrials.gov identifier: NCT02480530). PARTICIPANTS:One hundred and twenty-six veterans with known coronary artery disease and poor adherence (medication possession ratio <80 %). INTERVENTION:Patients were randomized to one of three groups: (1) a control group (n = 36) that received a pill-monitoring device with no alarms or feedback; (2) an individual feedback group (n = 36) that received a daily alarm and a weekly medication adherence feedback report; and (3) a partner feedback group (n = 54) that received an alarm and a weekly feedback report that was shared with a friend, family member, or a peer. The intervention continued for 3 months, and participants were followed for an additional 3 months after the intervention period. MAIN MEASURES:Adherence as measured by pill bottle. Secondary outcomes included change in LDL (mg/dl), patient activation, and social support. KEY RESULTS:During the 3-month intervention period, medication adherence was higher in both feedback arms than in the control arm (individual feedback group 89 %, partner feedback group 86 %, control group 67 %; p < 0.001 and = 0.001). At 6 months, there was no difference in medication adherence between either of the feedback groups and the control (individual feedback 60 %, partner feedback 52 %, control group 54 %; p = 0.75 and 0.97). CONCLUSIONS:Daily alarms combined with individual or partner feedback reports improved statin medication adherence. While neither an individual feedback nor partner feedback strategy created a sustainable medication adherence habit, the intervention itself is relatively easy to implement and low cost.
Project description:The need for antiretroviral therapy coupled with treatment of chronic co-morbidities places HIV-infected patients at risk for polypharmacy. However, few studies have described overall pill burden among HIV-infected patients. HIV-infected outpatients of the UNC Infectious Diseases Clinic were enrolled in this cross-sectional study. Subjects were contacted prior to a scheduled appointment and asked to bring all their medications to the visit. Daily total pill burden and medication type were recorded. 151 subjects were recruited: 76% male, 58% African American, 97% receiving antiretrovirals (ARVs). Median age was 48 (IRQ: 42-54) years. The median number of medications per subject was 8 (IQR: 6-11), and the median individual daily pill burden was 8 pills (IQR: 5-15): 3 pills (range: 2-5) for ARVs and 6 (range: 3-12.5) pills for non-ARVs. Duration of ART (per 2 years increase) and more than 3 co-morbidities was significantly associated with high pill burden (over 10 pills per day) with adjusted OR of 2.09 (95% CI, 1.14-3.84) and 8.04 (95% CI, 2.30-28.15), respectively. As patients with HIV age, strategies to reduce pill burden and number of medications will become increasingly critical to maintaining adherence, preventing medication errors, and serious drug-drug interactions.
Project description:The purpose of this study was to test the association between a self-report measure of 24-hour adherence to antihypertensive medication and blood pressure (BP) among African Americans. The primary analysis included 3558 Jackson Heart Study participants taking antihypertensive medication who had adherence data for at least one study examination. Nonadherence was defined by self-report of not taking one or more prescribed antihypertensive medications, identified during pill bottle review, in the past 24 hours. Nonadherence and clinic BP were assessed at Exam 1 (2000-2004), Exam 2 (2005-2008), and Exam 3 (2009-2013). Associations of nonadherence with clinic BP and uncontrolled BP (systolic BP ? 140 mm Hg or diastolic BP ? 90 mm Hg) were evaluated using unadjusted and adjusted linear and Poisson repeated measures regression models. The prevalence of nonadherence to antihypertensive medications was 25.4% at Exam 1, 28.7% at Exam 2, and 28.5% at Exam 3. Nonadherence was associated with higher systolic BP (3.38 mm Hg) and diastolic BP (1.47 mm Hg) in fully adjusted repeated measures analysis. Nonadherence was also associated with uncontrolled BP (prevalence ratio = 1.26; 95% confidence interval = 1.16-1.37). This new self-report measure may be useful for identifying nonadherence to antihypertensive medication in future epidemiologic studies.
Project description:BACKGROUND:Despite initial high motivation, individuals receiving antiretroviral therapy (ART) for several years may experience incomplete adherence over time, increasing their risk of HIV-related morbidity and mortality. Habits, defined as automatic and regular practices, do not rely on conscious effort, and may therefore support high long-term ART adherence. METHODS:This qualitative study contributes to the evidence on how clients with adherence problems remember and form habits to take ART medications. Free-listing and unstructured interviewing were used among 42 clinic-enrolled adults in Kampala, Uganda who were receiving ART and participating in a randomized clinical trial for treatment adherence (clinicaltrials.gov: NCT03494777). Data were coded and analyzed using inductive content analysis. RESULTS:Findings indicated that clients' most routine habits (eating, bathing, sleeping) did not always occur at the same time or place, making it difficult to reliably link to pill-taking times. Efforts to improve ART habits included having a relative to ask about pill-taking, re-packaging medications, leaving medications in view, using alarms, carrying water, or linking pill-taking to radio/prayer schedules. Reported challenges were adhering to ART schedules during changing employment hours, social activities, and travel. CONCLUSION:While habit-forming interventions have the potential to improve ART adherence, targeting treatment-mature clients' existing routines may be crucial in this population.
Project description:OBJECTIVE:Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission. DESIGN:Prospective cohort study. METHODS:Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. Associations between postpartum antiretroviral adherence and rate of breast milk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. RESULTS:Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were less than 90% adherent. Having at least 90% adherence was associated with a 52% [95% confidence interval (CI) 3-76] relative reduction in the rate of breast milk HIV-1 transmission, compared with having less than 90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n?=?501; relative reduction 59%, 95% CI 6-82). CONCLUSION:Nonadherence to extended postpartum antiretroviral regimens in 'real world' settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of antiretroviral provision throughout breastfeeding.
Project description:BACKGROUND:To address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended that countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness of the intervention from the patient and provider perspectives. METHODS:This is a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial. The study is designed to enroll 144 outpatients with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who are eligible to start the standard 6-month first-line anti-TB regimen. Participants in the intervention arm (n?=?72) will receive 15 days of HRZE-isoniazid, rifampicin, pyrazinamide, and ethambutol-fixed-dose combination therapy in the evriMED500 medication event reminder monitor device for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits. Providers will handle participants in the control arm (n?=?72) according to the standard in-person DOT. Both arms will be followed up throughout the 2-month intensive phase. The primary outcomes will be medication adherence and sputum conversion. Adherence to medication will be calculated as the proportion of patients who missed doses in the intervention (pill count) versus DOT (direct observation) arms, confirmed further by IsoScreen urine isoniazid test and a self-report of adherence on eight-item Morisky Medication Adherence Scale. Sputum conversion is defined as the proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase BACTEC MGIT TB liquid culture. Pre-post treatment MGIT drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion. Secondary outcomes will include other clinical outcomes (treatment not completed, death, or loss to follow-up), cost-effectiveness-individual and societal costs with quality-adjusted life years-and acceptability and usability of the intervention by patients and providers. DISCUSSION:This study will be the first in Ethiopia, and of the first three in sub-Saharan Africa, to determine whether electronic pillbox-enabled SAT improves adherence to TB medication and treatment outcomes, all without affecting the inherent dignity and economic wellbeing of patients with TB. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04216420. Registered on 2 January 2020.