Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.

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.

Impact of financial medication assistance on medication adherence: a systematic review.

BACKGROUND: The prevalence of financial medication assistance (FMA), including patient assistance programs, coupons/copayment cards, vouchers, discount cards, and programs/pharmacy services that help patients apply for such programs, has increased. The impact of FMA on medication adherence and persistence has not been synthesized. OBJECTIVE: The primary objective of this study was to review published studies evaluating the impact of FMA on the three phases of medication adherence (initiation [or primary adherence], implementation [or secondary adherence], and discontinuation) and persistence. Among these studies, the secondary objective was to report the impact of FMA on patient out-of-pocket costs and clinical outcomes. METHODS: A systematic review was performed using MEDLINE and Web of Science. RESULTS: Of 656 articles identified, eight studies met all inclusion criteria. Seven studies examined FMA for medications treating cardiovascular diseases, while one study assessed FMA for cancer medications. Among included studies, FMA had a positive impact on medication adherence or persistence, and most measured this impact over one year or less. Of the three phases of medication adherence, implementation (5 of 8) was most commonly reported, followed by discontinuation (3 of 8), and then initiation (1 of 8). Regarding implementation, users of FMA had a higher mean medication possession ratio (MPR) than nonusers, ranging from 7 to 18 percentage points higher. The percentage of patients who discontinued medication was 7 percentage points lower in users of FMA versus nonusers for cardiovascular disease states. In one cancer study, FMA had a larger impact on initiation than discontinuation, ie, compared to nonusers, users of FMA were less likely to abandon an initial prescription (risk ratio= 0.12, 95% confidence interval [CI]: 0.08-0.18), and this effect was larger than the decreased likelihood of discontinuing the medication (hazard ratio = 0.76, 95% CI: 0.66-0.88). In 3 of 8 studies reporting on medication persistence, FMA increased the odds of medication persistence for one year ranged from 11% to 47%, depending on the study. In addition to adherence, half of the studies reported on FMA impacts on patient out-of-pocket costs and 3 of 8 studies reported on clinical outcomes. Impacts on patient out-of-pocket costs were mixed; two studies reported that out-of-pocket costs were higher for users of a coupon or a voucher versus nonusers, one study reported the opposite, and one study reported null effects. Impacts on clinical outcomes were either positive or null. CONCLUSIONS: We found that FMA has positive impacts on all phases of medication adherence as well as medication persistence over one year. Future studies should assess whether FMA has differential impacts based on phase of medication adherence and report on its longer-term (ie, beyond one year) impacts on medication adherence. DISCLOSURES: This work was sponsored by a grant from Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Hung reports past employment by Blue Cross Blue Shield Association and CVS Health and a grant from PhRMA outside of the submitted work. Zullig reports research funding from Proteus Digital Health and the PhRMA Foundation. consulting fees from Novartis. Reed reports receiving research support from Abbott Vascular, AstraZeneca, Janssen Research & Development, Monteris, PhRMA Foundation, and TESARO and consulting fees from Sanofi/Regeneron, NovoNordisk, SVC Systems, and Minomic International, Inc. Bosworth reports research grants from the PhRMA Foundation, Proteus Digital Health, Otsuka, Novo Nordisk, Sanofi, Improved Patient Outcomes, Boehinger Ingelheim, NIH, and VA, as well as consulting fees from Sanofi, Novartis, Otsuka, Abbott, Xcenda, Preventric Diagnostics, and the Medicines Company. The other authors have nothing to report. This work was presented as a poster presentation at the ESPACOMP Annual Meeting in November 2020.

Lessons learned from two randomized controlled trials: CITIES and STOP-DKD.

BACKGROUND: Even well-designed, theoretically driven clinical trials can fall short of achieving the desired clinical outcomes. Our research team had an opportunity to conduct two randomized controlled trials that were enrolling patients in parallel. While both studies were targeting chronic disease management among patients with multiple comorbid conditions, the patient population and settings varied. The studies were the Cardiovascular Intervention Improvement Telemedicine Study (CITIES) and Simultaneous Risk Factor Control Using Telehealth to slow Progression of Diabetic Kidney Disease (STOP-DKD) studies. Both studies had null findings. OBJECTIVES: Our goal is to discuss common design considerations across CITIES and STOP-DKD and potential implications for the design of future randomized controlled trials. METHODS: These were two 1:1 randomized controlled trials with attention control groups that recruited patients from various clinical practices in the Research Triangle area of North Carolina. CONCLUSIONS: We make three recommendations for future studies. First, we assert that it is important to allow for piloting the enrollment process to ensure that it is possible to identify and recruit a patient population that is well aligned with the clinical outcomes of the intervention. Second, analysis plans should be more targeted in their approach and should consider heterogeneity of treatment effects. Third, in order to support the transition of evidence generated from randomized controlled trials into clinical practice, it is important to consider even early stage randomized controlled trials through an implementation science lens. TRIAL REGISTRATION: Simultaneous Risk Factor Control Using Telehealth to slow Progression of Diabetic Kidney Disease (STOP-DKD) NCT01829256; Cardiovascular Intervention Improvement Telemedicine Study NCT01142908.

Medication rebates and health disparities: Mind the gap.

Compared to white patients in the United States, people of racial and ethnic minority groups face higher rates of chronic disease including diabetes, obesity, stroke, cardiovascular disease and cancer. Minority groups are also less likely to receive medication therapy to manage complications of chronic disease as well as be adherent to these therapies. A recently announced proposed rule by the Department of Health and Human Services Office of the Inspector General (HHS OIG), which would discourage rebates between manufacturers and payers in favor of discounts directly provided to patients, has received significant attention for its anticipated impact on prescription drug pricing and reimbursement in Medicare. This commentary describes the proposed rule and how it may impact adherence among patients of racial minority groups through an illustrative case study and discussion.

Primary Care Providers' Acceptance of Pharmacists' Recommendations to Support Optimal Medication Management for Patients with Diabetic Kidney Disease.

BACKGROUND: Patients with diabetic kidney disease (DKD) often struggle with blood pressure control. In team-based models of care, pharmacists and primary care providers (PCPs) play important roles in supporting patients' blood pressure management. OBJECTIVE: To describe whether PCPs' acceptance of pharmacists' recommendations impacts systolic blood pressure (SBP) at 36 months. DESIGN: An observational analysis of a subset of participants randomized to the intervention arm of the Simultaneous risk factor control using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. PARTICIPANTS: STOP-DKD participants for whom (1) the pharmacist made at least one recommendation to the PCP; (2) there were available data regarding the PCP's corresponding action; and (3) there were SBP measurements at baseline and 36 months. INTERVENTION: Participants received monthly telephone calls with a pharmacist addressing health behaviors and medication management. Pharmacists made medication-related recommendations to PCPs. MAIN MEASURES: We fit an unadjusted generalized linear mixed model to assess the association between the number of pharmacists' recommendations for DKD and blood pressure management and PCPs' acceptance of such recommendations. We used a linear regression model to evaluate the association between PCP acceptance and SBP at 36 months, adjusted for baseline SBP. KEY RESULTS: Pharmacists made 176 treatment recommendations (among 59 participants), of which 107 (61%) were accepted by PCPs. SBP significantly declined by an average of 10.5 mmHg (p < 0.01) among 47 of 59 participants who had valid measurements at baseline and 36 months. There was a significant association between the number of pharmacist recommendations and the odds of PCP acceptance (OR 1.19; 95%CI 1.00, 1.42; p < 0.05), but no association between the number of accepted recommendations and SBP. CONCLUSIONS: Pharmacists provided actionable medication-related recommendations. We identified a significant decline in SBP at 36 months, but this reduction was not associated with recommendation acceptance. TRIAL REGISTRATION: NCT01829256.

Potential impact of pharmaceutical industry rebates on medication adherence.

Many patients struggle to take their prescription medications as prescribed. Multiple interacting factors influence medication nonadherence. The cost of medications, particularly a patient's out-of-pocket cost, spans several of these domains. One proposed option for reducing a patient's out-of-pocket cost involves directly sharing manufacturer rebates with patients to lower their out-of-pocket costs at the pharmacy counter. Rebates are widely used across industries (eg, pharmaceutical manufacturers, tourism taxes, automobile manufacturers) in negotiations between sellers and buyers for a particular product. Medication rebates play an important role in the current US pharmaceutical marketplace. However, rebate contract terms are not publicly reported, so it is difficult for patients to determine if, and how, a rebate is reflected in their out-of-pocket costs. This commentary addresses the role of rebates in the current US healthcare landscape and their relationship with medication adherence.

Using a geriatric oncology assessment to link with services (GOAL).

OBJECTIVE: Geriatric screening tools assess functional limitations and inform clinical decision-making for older adults with cancer. Our objective was to evaluate the feasibility and effectiveness of a screener in community-based oncology clinics. MATERIALS AND METHODS: Eligible patients were from two rural, underserved community-based cancer clinics; within 12 months of a cancer diagnosis (breast, lung, colorectal, pancreas, esophageal); aged ≥60 years; and not exclusively pursuing palliative care. We used a previously validated tool that was embedded in the electronic health record (EHR). Patient-reported responses identified memory impairment, depressive symptoms, deficits in activities of daily living, poor nutrition, and polypharmacy. At the discretion of the oncologist, responses prompted service referrals. From the EHR, we extracted information about referrals and completion of planned therapy. We present descriptive statistics. RESULTS: Enrolled patients (n = 44) had a mean age of 71.5 years (SD = 6.9). Most were non-white (61%), women (66%), with government-sponsored health insurance (80%). The most commonly identified geriatric syndromes: polypharmacy (89%), reduced quality of life (39%), and poor nutrition (39%). The screener triggered a referral in 98% of patients. Generated referrals were for depressive symptoms (52% needed, 39% received), nutrition (43% needed, 37% received), and polypharmacy (89% needed, 26% received). Patients were referred to social work (56%), nutrition (44%), and pharmacy (25%). Many patients completed planned radiation therapy (100%), surgery (70%), and chemotherapy (60%). CONCLUSIONS: Use of an EHR-embedded brief geriatric oncology assessment in rural oncology clinics identified geriatric syndromes that would benefit from provision of services in nearly all enrolled patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02906592.

The new landscape of medication adherence improvement: where population health science meets precision medicine.

Despite the known health and economic benefits of medications, nonadherence remains a significant, yet entirely preventable public health burden. Over decades, there have been numerous research studies evaluating health interventions and policy efforts aimed at improving adherence, yet no universal or consistently high impact solutions have been identified. At present, new challenges and opportunities in policy and the movement toward value-based care should foster an environment that appreciates adherence as a mechanism to improve health outcomes and control costs (eg, fewer hospitalizations, reduced health care utilization). Our objective was to provide a commentary on recent changes in the landscape of research and health policy directed toward improving adherence and an actionable agenda to achieve system level savings and improved health by harnessing the benefits of medications. Specifically, we address the complementary perspectives of precision medicine and population health management; integrating data sources to develop innovative measurement of adherence and target adherence interventions; and behavioral economics to determine appropriate incentives.

Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a randomized controlled trial.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m2, mean eGFR was 80.7 ml/min/1.73 m2, and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided. TRIAL REGISTRATION: NCT01829256.

Racial differences in nocturnal dipping status in diabetic kidney disease: Results from the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) study.

While racial variation in ambulatory blood pressure (BP) is known, patterns of diurnal dipping in the context of diabetic kidney disease have not been well defined. The authors sought to determine the association of race with nocturnal dipping status among participants with diabetic kidney disease enrolled in the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) trial. The primary outcome was nocturnal dipping-percent decrease in average systolic BP from wake to sleep-with categories defined as reverse dippers (decrease <0%), nondippers (0%-<10%), and dippers (≥10%). Twenty-four-hour ambulatory BP monitoring was completed by 108 participants (54% were nondippers, 24% were dippers, and 22% were reverse dippers). In adjusted models, the common odds of reverse dippers vs nondippers/dippers and reverse dippers/nondippers vs dippers was 2.6 (95% confidence interval, 1.2-5.8) times higher in blacks than in whites. Without ambulatory BP monitoring data, interventions that target BP in black patients may be unable to improve outcomes in this high-risk group.

Health Information Technology: Meaningful Use and Next Steps to Improving Electronic Facilitation of Medication Adherence.

BACKGROUND: The use of health information technology (HIT) may improve medication adherence, but challenges for implementation remain. OBJECTIVE: The aim of this paper is to review the current state of HIT as it relates to medication adherence programs, acknowledge the potential barriers in light of current legislation, and provide recommendations to improve ongoing medication adherence strategies through the use of HIT. METHODS: We describe four potential HIT barriers that may impact interoperability and subsequent medication adherence. Legislation in the United States has incentivized the use of HIT to facilitate and enhance medication adherence. The Health Information Technology for Economic and Clinical Health (HITECH) was recently adopted and establishes federal standards for the so-called "meaningful use" of certified electronic health record (EHR) technology that can directly impact medication adherence. RESULTS: The four persistent HIT barriers to medication adherence include (1) underdevelopment of data reciprocity across clinical, community, and home settings, limiting the capture of data necessary for clinical care; (2) inconsistent data definitions and lack of harmonization of patient-focused data standards, making existing data difficult to use for patient-centered outcomes research; (3) inability to effectively use the national drug code information from the various electronic health record and claims datasets for adherence purposes; and (4) lack of data capture for medication management interventions, such as medication management therapy (MTM) in the EHR. Potential recommendations to address these issues are discussed. CONCLUSION: To make meaningful, high quality data accessible, and subsequently improve medication adherence, these challenges will need to be addressed to fully reach the potential of HIT in impacting one of our largest public health issues.