Medication-taking Behavior Research Articles

Leveraging Mobile Sensing to Understand and Develop Intervention Strategies to Improve Medication Adherence.

Interventions to improve medication adherence have had limited success and can require significant human resources to implement. Research focused on improving medication adherence has undergone a paradigm shift, of late, with a shift towards developing personalized, theory-driven interventions. The current research integrates foundational and translational science to implement a mechanisms-focused, context-aware approach. Increasing adoption of mobile and wearable sensing systems presents new opportunities for understanding how medication-taking behaviors unfold in natural settings, especially in populations who have difficulty adhering to medications. When combined with survey and ecological momentary assessment data, these mobile and wearable sensing systems can directly capture the context of medication adherence in situ, including personal, behavioral, and environmental factors. The purpose of this paper is to present a new transdisciplinary research framework in medication adherence, highlight critical advances in this rapidly-evolving research field, and outline potential future directions for both research and clinical applications.

Socioeconomic and Demographic Characteristics of US Adults Who Purchase Prescription Drugs From Other Countries

Little is known about the current use of imported drugs and the factors associated with individual purchase of medications outside the US. To evaluate the proportion of the US adult population that purchases medications in other countries and the patient factors associated with the behavior. This retrospective cross-sectional study used data from the 2015-2017 National Health Interview Survey. The study sample included 61 238 individuals 18 years or older who reported use of prescribed medication by a physician or other practitioner. Data analysis was performed in November 2019. Self-reported experience of purchasing prescription drugs from countries outside the US in the past 12 months. Internet use behaviors for health care included searches for health information and filling of a prescription online. Medication-taking behaviors included skipping or delaying filling a prescription and using alternative therapies to save money. Survey design-adjusted analysis was used to estimate and compare characteristics between those who purchased medications outside the US and those did not. Multivariable logistic regression was fitted to examine the association of medication purchases with internet use and medication-taking behavior factors. Among 61 238 US adults taking prescription medications (mean [SD] age, 50.5 [18.5] years; 56.5% female; 70.8% white), the estimated prevalence of purchasing of medication outside the US was 1.5% (95% CI, 1.4%-1.7%; 2.3 million US individuals). Those who purchased medications outside the US were more likely to be older (age >64 years; adjusted odds ratio [aOR], 1.68; 95% CI, 1.24-2.29), to be from Hispanic (aOR, 1.70; 95% CI, 1.23-2.35) or immigrant populations (aOR, 3.20; 95% CI, 2.44-4.20), and to have higher educational attainment (bachelor's degree; aOR, 1.79; 95% CI, 1.27-2.54), lower family income (low income; aOR, 1.41; 95% CI, 1.06-1.87), and lack of insurance (aOR, 3.14; 95% CI, 2.33-4.21). Data analyses indicated that online health information-seeking behavior (aOR, 1.62; 95% CI, 1.33-1.98) or use of an online pharmacy (aOR, 2.30; 95% CI, 1.83-2.90) was associated with a greater likelihood of medication purchases outside the US. Individuals who skipped medications (aOR, 3.86; 95% CI, 3.05-4.88) or delayed filling a prescription (aOR, 4.04, 95% CI, 3.23-5.06) also had higher odds of purchasing medication outside the US. The findings suggest that patients are not using prescription purchases outside the US to meet their medication needs. However, monitoring to promote safe administration of medications imported into the US should be continued.

Barriers and Strategies for Improving Medication Adherence Among People Living With COPD: A Systematic Review.

While medication is an integral component of the effective management of COPD, contemporary studies report that more than half of all people who are prescribed medication for the management of their COPD do not adhere to therapy. Enhancing medication adherence and improving health outcomes for those living with COPD are among the key challenges for the global health community. This systematic review aims to identify the rate of nonadherence among people who are prescribed controller medication for the management of their COPD, and identifies the barriers and facilitators that influence their medication use behavior. A systematic search of medical databases (ie, MEDLINE, CINHAL, and EMBASE) was conducted using key words to identify literature in the English language, published between January 2003 and December 2019. Included studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. A total of 1,474 studies were identified from the initial database search, of which 38 met the inclusion criteria. Of these 38 studies, 37 reported on rates of nonadherence (ranging from 22% to 93%), 30 reported on barriers to adherence, 24 reported on enablers to adherence, and 16 reported on both. The majority (33) of the studies were conducted in high-income nations. The quality of articles ranged from 47% to 90%. Medication-taking behavior was reported to be influenced by several factors such as subjects' beliefs about medication, their experiences of and satisfaction with medication effectiveness, their concerns regarding medication side effects, their personal circumstances, habits and health status, and their relationships with health care providers. Adherence to COPD medication was generally low, with the majority of studies identifying the presence of depression and subjects' concern about the harmful effects of the medicine as barriers to adherence. Variability exists on the reported rates of nonadherence, possibly due to different measures utilized to assess adherence. Future research in low-income nations is needed.

0511 Patterns of Concomitant Over-the-Counter, Natural Product and Prescription Sleep Aid Use: A Population-Based Study

Abstract Introduction Despite limited evidence, over-the-counter medications (OTC) and natural products (NP) are increasingly combined with prescribed medications (Rx) to manage insomnia symptoms. Self-medication patterns are expected to be heterogenous and may predispose individuals to inappropriate medication-taking behaviors, but little is known about the usage trajectories of sleep aids. This study investigates patterns of concomitant NP, OTC and Rx use in a Canadian population-based sample. Methods Data were derived from a longitudinal study on the natural history of insomnia. Participants were 3416 adults (62% female, Mage = 49.7, MInsomnia Severity Index= 8.4). Self-reported data for OTC, NP and Rx use in the last year (yes/no) was extracted at 0-, 6- and 12-month follow-up. A Latent Class Growth Curve Analysis was conducted to identify patterns of concomitant sleep aid use. Participants also completed a battery of clinical measures including the Ford Insomnia Response to Stress Test, Dysfunctional Beliefs and Attitudes about Sleep scale (16-item), Beck Depression Inventory, Insomnia Severity Index and the Pittsburgh Sleep Quality Index. Preliminary associations between class membership and baseline covariates were evaluated using the χ 2 test or a one-way ANOVA. Sampling weights were applied to all analyses, adjusting for partial non-response. Results Analyses revealed a 6-class solution; each class reflected a preferential agent(s) choice, which remained stable over 12-months: Minimal Use (74.5%), Rx-Dominant (11.3%), NP-Dominant (6.3%), OTC-Dominant (4.3%), Rx-NP-Dominant (2.4%), and Rx-OTC-Dominant (1.1%). Classes with prominent prescribed agent use were older [F(5, 207.6) =27.2, p<0.001], more likely to seek help [χ 2(5, n=2977) =653.1, p< 0.001] and consume alcohol [χ 2(5, n=2968) =49.2, p< 0.001]. Clinically, these individuals reported greater stress reactivity [F(5, 2966) =48.4, p< 0.001], depressive symptoms [F(5,197.4) =32.0, p<0.001], dysfunctional sleep beliefs [F(5, 2987) =54.3, p< 0.001], insomnia severity [F(5, 2983) =88.4, p< 0.001] and poorer sleep quality [F(5, 203.8) =124.2, p< 0.001]. Conclusion A majority of adults used agents minimally. Stability of medication-taking patterns suggests that individuals adopt less sporadic approaches when combining sleep aids than previously assumed. Clinical profiles and sleep aid choice could pre-empt vulnerabilities to inappropriate self-medication. Support Research supported by a grant from the Canadian Institutes of Health Research (MOP#115103)

An Ecologically Valid, Longitudinal, and Unbiased Assessment of Treatment Efficacy in Alzheimer Disease (the EVALUATE-AD Trial): Proof-of-Concept Study.

BackgroundThe current clinical trial assessment methodology relies on a combination of self-report measures, cognitive and physical function tests, and biomarkers. This methodology is limited by recall bias and recency effects in self-reporting and by assessments that are brief, episodic, and clinic based. Continuous monitoring of ecologically valid measures of cognition and daily functioning in the community may provide a more sensitive method to detect subtle, progressive changes in patients with cognitive impairment and dementia.ObjectiveThis study aimed to present an alternative trial approach using a home-based sensing and computing system to detect changes related to common treatments employed in Alzheimer disease (AD). This paper introduces an ongoing study that aims to determine the feasibility of capturing sensor-based data at home and to compare the sensor-based outcomes with conventional outcomes. We describe the methodology used in the assessment protocol and present preliminary results of feasibility measures and examples of data related to medication-taking behavior, activity levels, and sleep.MethodsThe EVALUATE-AD (Ecologically Valid, Ambient, Longitudinal and Unbiased Assessment of Treatment Efficacy in Alzheimer’s Disease) trial is a longitudinal naturalistic observational cohort study recruiting 30 patients and 30 spouse coresident care partners. Participants are monitored continuously using a home-based sensing and computing system for up to 24 months. Outcome measures of the automated system are compared with conventional clinical outcome measures in AD. Acceptance of the home system and protocol are assessed by rates of dropout and protocol adherence. After completion of the study monitoring period, a composite model using multiple functional outcome measures will be created that represents a behavioral-activity signature of initiating or discontinuing AD-related medications, such as cholinesterase inhibitors, memantine, or antidepressants.ResultsThe home-based sensing and computing system has been well accepted by individuals with cognitive impairment and their care partners. Participants showed good adherence to the completion of a weekly web-based health survey. Daily activity, medication adherence, and total time in bed could be derived from algorithms using data from the sensing and computing system. The mean monitoring time for current participants was 14.6 months. Medication adherence, as measured with an electronic pillbox, was 77% for participants taking AD-related medications.ConclusionsContinuous, home-based assessment provides a novel approach to test the impact of new or existing dementia treatments generating objective, clinically meaningful measures related to cognition and everyday functioning. Combining this approach with the current clinical trial methodology may ultimately reduce trial durations, sample size needs, and reliance on a clinic-based assessment.International Registered Report Identifier (IRRID)DERR1-10.2196/17603

Persistence and adherence to nucleos(t)ide analogues in chronic hepatitis B: a multicenter cohort study.

Adherence and persistence to long-term therapy with nucleos(t)ides analogues are crucial to the outcome of treatment in chronic hepatitis B. Our aim was to determine the persistence and adherence rates to nucleos(t)ides analogues in chronic hepatitis B patients under maintenance therapy and to identify relative to prediction of adherence factors. We retrospectively analyzed electronic prescription data of patients (2011-2016; n = 400) with chronic hepatitis B treated with nucleos(t)ides analogues at 4 tertiary liver centers in Greece. Two hundred ninety-six of 400 patients were under or initiated treatment in 2011-2012 (existing patients), while the remainder initiated or switched medication from January 2013 and onward (new patients). The median adherence rate was 99%, with 89.7% achieving adherence >80% during a mean follow-up of 28 ± 14 months. The overall 12-month persistence rate was 57%, with no difference between patients receiving tenofovir, entecavir or double therapy (57.8%, 52.8% and 68.4%, respectively, P = 0.399). The decline in persistence was more pronounced during the first 3 months of follow-up and in existing patients (P = 0.057). Overall, 80% and 55.1% of nonpersistent patients succeeded adherence to nucleos(t)ides analogues >80% and >90%, respectively. Multivariate analyses showed that existing (vs. new) patients were less likely to have >80% adherence (odds ratio: 0.324, P = 0.44) and persistence (odds ratio: 0.562, P = 0.057) to nucleos(t)ides analogues therapy. In this real-world cohort of chronic hepatitis B patients, high adherence to nucleos(t)ides analogues was coupled with suboptimal persistence with prescribing the medication. Our data indicate that persistence and adherence are distinct measures that should be approached separately in educational programs targeting to improve medication-taking behavior in chronic hepatitis B.

Copayment Reduction Voucher Utilization and Associations With Medication Persistence and Clinical Outcomes: Findings From the ARTEMIS Trial.

Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown. The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y12 inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y12 inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y12 inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction P=0.03, odds ratio, 1.86 [95% CI, 1.48-2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56-1.16]) among patients with high likelihood of voucher use (adjusted interaction P=0.04). Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02406677.

Prescriber adherence to guidelines for chronic noncancer pain management with opioids: Systematic review and meta-analysis.

This review quantified prescriber adherence to opioid prescribing guidelines for chronic noncancer pain (CNCP). We searched CINAHL, Embase, MEDLINE, PsycINFO, the Cochrane Library, and the Joanna Briggs Institute EBP Database from inception until June 3, 2019. Studies that focused on provider adherence to opioids guidelines for CNCP in North America were eligible. Four reviewers screened studies, extracted data, and assessed study quality. Thirty-eight studies were eligible, comprising 17 cross-sectional studies (n = 11,835 providers) and 22 chart reviews (n = 22,512 patients). Survey data indicated that adherence was 49% (95% CI [40, 59]) for treatment agreements, 33% (95% CI [19%, 47%]) for urine drug testing, 48% (95% CI [26%, 71%]) for consultation with drug monitoring program, 57% (95% CI [35%, 79%]) for assessing risk of aberrant medication-taking behavior, and 61% (95% CI [35%, 87%]) for mental health screening. Chart review data indicated that the proportion of patients with documentation was 40% (95% CI [29, 51]) for treatment agreements, 41% (95% CI [32%, 50%]) for urine drug testing, 40% (95% CI [2%, 78%]) for consultation with drug monitoring program, 41% (95% CI [20%, 64%]) for assessing risk of aberrant medication-taking behavior, and 22% (95% CI [9%, 33%]) for mental health screening. Year of publication, practice guideline referenced, and risk of bias explained significant heterogeneity. No study evaluated whether nonadherence to recommendations reflected well-justified deviations to care. Adherence to guideline recommendations for opioids for CNCP is low. It is unclear whether nonadherence reflects thoughtful deviations in care. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Patient factors associated with diabetes medication adherence at different health literacy levels: a cross-sectional study at a family medicine clinic

ABSTRACT Background Type 2 diabetes (T2D) incurs tremendous health costs associated with various complications due to poor diabetes control. Medication adherence, which is correlated with patients’ health literacy, should be consistently practiced achieving optimal diabetes control. A deeper understanding of the specific communication and psychosocial factors related to medication-taking behaviors across different levels of health literacy among people with T2D will guide the development of effective interventions and strategies to enhance medication adherence. Objectives This cross-sectional study aimed to identify salient patient factors associated with diabetes medication adherence across different levels of health literacy. Methods A questionnaire was administered via a face-to-face approach with 205 participants at a family medicine clinic. Study participants were all above 20 years of age with T2D, were prescribed at least one oral diabetes medication, and understood English. The questionnaire assessed participants’ health literacy, self-efficacy for medication use, beliefs in medicines, patient-provider communication, perceived barriers to medication adherence, and self-reported medication adherence. Separate analysis of covariance was used to compare the mean scores of patient factors related to medication adherence across people with different health literacy levels. Results The mean age of participants was 61 years old, and the majority of the participants were female (57%), White (75%), and college educated (62%). Thirty-three percent of the participants had adequate health literacy, but only 43% of them reported high adherence to their diabetes medications. Analysis of covariance showed that having stronger self-efficacy (P < 0.001), lower concern beliefs about medication (P = 0.047), and fewer perceived barriers to medication-taking (P < 0.001), are necessary for better medication adherence. Conclusion Findings suggest that practitioners should address concern beliefs among low-adherent patients with low health literacy, help improve self-efficacy, and address perceived barriers to medication adherence among all low-adherent patients to optimally support patients’ diabetes care.

Understanding HIV-positive drug users' experiences of taking highly active antiretroviral treatment: Identity-Values-Conscious engagement model.

To explore HIV-positive drug users' experiences of taking antiretroviral medications in Taiwan and further develop a conceptual model that can be used to understand their adherence to the long-term treatment. The global vision of ending AIDS by 2030 cannot be achieved without addressing HIV-positive drug users' experience of taking antiretroviral treatment. There remains a paucity of qualitative evidence on HIV-positive drug users' experiences of taking antiretroviral medications globally and in East Asia. Nurses play a key role in supporting HIV-positive drug users throughout their treatment process. Therefore, it is pivotal to understand HIV-positive drug users' experiences of managing long-term anti-HIV treatment. This qualitative study drew on a constructivist grounded theory approach to achieve the aims. Semi-structured in-depth interviews with 22 HIV-positive drug users were conducted in Taiwan between September 2015 and July 2016. Data were analysed using Charmaz's coding principles. The integration and formation of the model began with focused coding and proceeded through the subsequent analytic process. The reporting of this study was based on the Consolidated Criteria for Reporting Qualitative Research checklist. This study shows that integrating HIV-positive identity into sense of self laid a solid foundation for the acceptance of self and antiretroviral treatment. Valuing of antiretroviral treatment played a central role in driving their medication-taking behaviour. While valuing the treatment appeared to drive participants' behavioural change, data revealed that conscious engagement was an important element for their behaviour maintenance. The evidence from this study can extend our knowledge of the mechanisms that influence the change and maintenance of HIV-positive drug users' adherence to antiretroviral treatment. The Identity-Values-Conscious engagement model developed and proposed in this study can serve as a guide for the development of tailored adherence assessment and associated nursing interventions for this population.

Agreement and Accuracy of Medication Persistence Identified by Patient Self-report vs Pharmacy Fill

Pharmacy fill data are increasingly accessible to clinicians and researchers to evaluate longitudinal medication persistence beyond patient self-report. To assess the agreement and accuracy of patient-reported and pharmacy fill-based medication persistence. This post hoc analysis of the cluster randomized clinical trial ARTEMIS (Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) enrolled patients at 287 US hospitals (131 randomized to intervention and 156 to usual care) from June 5, 2015, to September 30, 2016, with 1-year follow-up and blinded adjudication of major adverse cardiovascular events. In total, 8373 patients with myocardial infarction and measurement of P2Y12 inhibitor persistence by both patient self-report and pharmacy data were included. Serum P2Y12 inhibitor drug levels were measured for 944 randomly selected patients. Data were analyzed from May 2018 to November 2019. Patients treated at intervention-arm hospitals received study vouchers to offset copayments at each P2Y12 inhibitor fill for 1 year after myocardial infarction. Nonpersistence was defined as a gap of 30 days or more in P2Y12 inhibitor use (patient report) or supply (pharmacy fill) and as serum P2Y12 inhibitor levels below the lower limit of quantification (drug level). Among patients in the intervention arm, a "criterion standard" definition of nonpersistence was a gap of 30 days or more in P2Y12 inhibitor use by both voucher use and pharmacy fill. Major adverse cardiovascular events were defined as adjudicated death, recurrent myocardial infarction, or stroke. Of 8373 patients included in this analysis, the median age was 62 years (interquartile range, 54-70 years), 5664 were men (67.7%), and 990 (11.8%) self-reported as nonwhite race/ethnicity. One-year estimates of medication nonpersistence rates were higher using pharmacy fills (4042 patients [48.3%]) compared with patient self-report (1277 patients [15.3%]). Overall, 4185 patients (50.0%) were persistent by both pharmacy fill data and patient report, 1131 patients (13.5%) were nonpersistent by both, and 3057 patients (36.5%) were discordant. By application of the criterion standard definition, the 1-year nonpersistence rate was 1184 of 3703 patients (32.0%); 892 of 3318 patients (26.9%) in the intervention arm who self-reported persistence were found to be nonpersistent, and 303 of 1487 patients (20.4%) classified as nonpersistent by pharmacy fill data were actually persistent. Agreement between serum P2Y12 inhibitor drug levels and either patient-reported (κ = 0.11-0.23) or fill-based (κ = 0.00-0.19) persistence was poor. Patients who were nonpersistent by both pharmacy fill data and self-report had the highest 1-year major adverse cardiac event rate (18.3%; 95% CI, 16.0%-20.6%) compared with that for discordant patients (9.7%; 8.7%-10.8%) or concordantly persistent patients (8.2%; 95% CI, 7.4%-9.0%). Patient report overestimated medication persistence rates, and pharmacy fill data underestimated medication persistence rates. Patients who are nonpersistent by both methods have the worst clinical outcomes and should be prioritized for interventions that improve medication-taking behavior. ClinicalTrials.gov Identifier: NCT02406677.

Medication adherence in patients with mental illness and recent homelessness: contributing factors and perceptions on mobile technology use.

The primary objective was to determine medication-taking behaviours and factors influencing adherence in patients with mental illness and recent homelessness. Secondary objectives were to explore patients' perceptions on mobile technology use to support adherence. A constructivist approach and qualitative description method was used. The sample population consisted of patients with recent homelessness and mental illness affiliated with a community-based outreach programme in Canada. Participants were purposefully selected; semi-structured interviews were conducted to elicit information on medication-taking strategies and mobile technology to support adherence. A standardized questionnaire collected demographic and medical information; the Medication Adherence Rating Scale (MARS) was used to evaluate self-reported adherence. Questionnaire data were analysed using summary descriptive statistics. Interview data were subject to qualitative content analysis. Fifteen participants with a mean age of 44years were included. The mean MARS score±standard deviation was 7.3±1.5. Themes arising from the data included patient factors (i.e. insight, attitudes towards medications, coping strategies) and external factors (i.e. therapeutic alliance, family support that impacted adherence) and technology use and health. Eight participants (53%) had access to a mobile phone. There was a moderate interest in the use of mobile technology to support adherence, with cost and technology literacy identified as barriers. External supports and individual medication management strategies were important in supporting medication adherence in this patient group. Perceived need for mobile technology, in addition to existing supports for adherence, was not high. Challenges accessing and maintaining consistent mobile technology and individual preferences should be considered when developing mobile technology-based interventions.

The use of discrete choice experiments in adherence research: A new solution to an old problem.

Theory can play an important role in providing the framework, and underpinning the design and implementation of interventions to improve medication adherence. Interventions that are grounded in a theory are relatively more effective in improving medication adherence than interventions which do not have a theoretical support. However, a large body of adherence research does not appear to be linked to any theory or model, which therefore may have resulted in interventions that are either ineffective or not sustainable. Interventions that are based on theory have mainly employed socio-behavioural models to explain, and design interventions to address, the complex phenomenon of adherence. Yet, the effectiveness of these interventions is inconclusive, supporting the argument that socio-behavioural models alone have limited applicability in explaining behaviour associated with medication-taking. An important reason for this limitation may be the complex and dynamic nature of adherence. There is a need to include a wide variety of factors in a model and examine adherence in the context of its three phases (initiation, implementation, and discontinuation). One possible way forward is to also examine medication-taking behaviour from an economic perspective, for example, by using a discrete choice experiment (DCE), which provides a different approach to understanding human behaviour about medication-taking and the complexities of decision-making in adhering to medication. DCEs can help in understanding how patients decide to initiate, continue or discontinue taking medication, factors that influence their decision, and the relative importance of those factors, which can assist researchers to prioritise interventions to improve medication adherence. Integration of multiple theories is needed to examine adherence from multiple perspectives and design interventions that are effective and sustainable. This commentary focusses on the pros and cons of some of the commonly used socio-behavioural models in adherence research and suggests a way forward by incorporating DCEs in adherence research.

Abstract P2-11-12: The influences of adherence to tamoxifen and CYP2D6 pharmacogenetics on plasma concentrations of the active metabolite (Z)-endoxifen in breast cancer

Abstract One-third of early breast cancer patients with estrogen receptor (ER) positive tumors treated with the selective estrogen receptor modulator tamoxifen either relapse or die from the disease in the following decade. Improvement of tamoxifen efficacy requires a better knowledge of factors determining outcome of which the medication-taking behavior, i.e. adherence, is a strong suspect. Discontinuation and non-adherence to tamoxifen are frequent and result in increased mortality. Commonly used methods to assess drug adherence such as prescription-refill patterns infer that the medication is taken exactly as prescribed yet, partial adherence or actual use of the medication cannot be controlled. An objective surrogate of tamoxifen adherence is the monitoring of drug concentrations in the patients’ plasma including the parent drug and its active metabolite (Z)-endoxifen (endoxifen), however individual concentrations depend on pharmacogene polymorphisms particularly those of the liver enzyme cytochrome P450 2D6 (CYP2D6). Patients without CYP2D6 variants have normal enzyme function (extensive metabolizer, EM) and achieve high endoxifen concentrations compared to patients with variants conferring absent activity (poor metabolizer, PM) or reduced activity (intermediate metabolizer, IM) who have significantly lower plasma concentrations of the active metabolite. A putative threshold of 5.9 ng/mL endoxifen has been proposed suggesting that patients with endoxifen concentration above or below threshold have lower or higher risk for recurrence, assuming that low endoxifen exposure in the tumor likely results in incomplete inhibition of ER-dependent growth signaling. During tamoxifen treatment it is therefore important that patients achieve clinically relevant endoxifen levels while at the same time avoid confounders of which adherence is a prime candidate. To this end, we investigated patients’ ability to achieve relevant plasma concentrations during tamoxifen treatment in relation to their CYP2D6 metabolizer status and their tamoxifen adherence behavior. Our prospective study included 192 Brazilian breast cancer patients treated with 20 mg tamoxifen daily. Two-thirds of the patients were premenopausal. Plasma levels of tamoxifen and its metabolites were measured by LC-MS/MS at 3, 6 and 12 months of treatment. Adherence to tamoxifen was evaluated by the questionnaire-based Morisky medication adherence scale. CYP2D6 polymorphisms were determined by MALDI-TOF mass spectrometry and real-time PCR. Adherence to tamoxifen decreased from 74% at month 3 to 64% at month 12, and explained 47% of the variability of tamoxifen plasma concentrations (P&amp;lt;.001). Accordingly, plasma monitoring of tamoxifen is useful to inform on tamoxifen adherence. Endoxifen concentrations were associated with CYP2D6 status and adherence. While CYP2D6 explained 26.4% of endoxifen variability at 12 months, the combination with adherence explained 40% (P&amp;lt;.001). The influence of low adherence to not achieving therapeutic endoxifen levels was highest in patients with non-compromised CYP2D6 function (EM phenotype, RR 3.65; 95% CI: 1.48-8.99). we conclude that for patients with intact CYP2D6 function adherence to tamoxifen is critical to achieve therapeutic endoxifen plasma levels. CYP2D6 phenotyping and endoxifen plasma monitoring may help to guide EM (and IM) patients to adhere to tamoxifen which is particularly relevant for premenopausal women who are at higher risk to not adhere to tamoxifen. Citation Format: Jose Claudio Casali da Rocha, Jeanine M Nardin, Werner Schroth, Thais A Almeida, Thomas Mürdter, Solange Picolotto, Evelyn CL Vendramini, Reiner Hoppe, Jenifer P Kogin, Diandra Miqueleto, Silvia DR Moraes, Matthias Schwab, Roberto F Pecoits-Filho, Hiltrud Brauch. The influences of adherence to tamoxifen and CYP2D6 pharmacogenetics on plasma concentrations of the active metabolite (Z)-endoxifen in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-12.

Factors Associated with Endocrine Therapy Non-Adherence in Breast Cancer Survivors.

For women with hormone receptor positive breast cancer, long-term endocrine therapy (ET) can greatly reduce the risk of recurrence, yet adherence is low- particularly among traditionally underserved populations. The Carolina Breast Cancer Study oversampled Black and young women (<50 years of age). Participants answered an ET-specific medication adherence questionnaire assessing reasons for non-adherence. We used principal factor analysis to identify latent factors describing ET non-adherence. We then performed multivariable regression to determine clinical and demographic characteristics associated with each ET non-adherence factor. 1,231 women were included in analysis, 59% reported at least one barrier to ET adherence. We identified three latent factors which we defined as: habit - challenges developing medication-taking behavior; tradeoffs - high perceived side effect burden and medication safety concerns; and resource barriers - challenges related to cost or accessibility. Older age (50+) was associated with less reporting of habit (Adjusted Risk Ratio (aRR) 0.54[95% CI: 0.43-0.69] and resource barriers (aRR 0.66[0.43-0.997]), but was not associated with tradeoff barriers. Medicaid-insured women were more likely than privately-insured to report tradeoff (aRR:1.53 [1.10-2.13]) or resource barriers (aRR:4.43[2.49-6.57]). Black race was associated with increased reporting of all factors (habit: aRR 1.29[1.09-1.53]; tradeoffs: 1.32[1.09-1.60], resources: 1.65[1.18-2.30]). Barriers to ET adherence were described by three distinct factors, and strongly associated with sociodemographic characteristics. Barriers to ET adherence appear inadequately addressed for younger, Black, and publicly-insured breast cancer survivors. These findings underscore the importance of developing multi-faceted, patient-centered interventions that address a diverse range of barriers to ET adherence.

Medication Adherence, Health Care Utilization, and Costs Among Patients Initiating Oral Oncolytics for Multiple Myeloma or Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Oral oncolytic therapies have improved survival in hematologic cancers, such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and multiple myeloma (MM), which are now being managed like chronic conditions. However, compared with other cancers, there is a lack of studies assessing adherence, health care resource utilization, and costs in patients with these cancers. To assess factors associated with adherence to oral oncolytic therapies, health care utilization, and costs in patients with CLL/SLL or MM. A retrospective database study was conducted using the IBM MarketScan Commercial Claims and Medicare Supplement databases. Adults (aged ≥ 18 years) diagnosed with and prescribed an oral oncolytic for CLL/SLL (ibrutinib or idelalisib) or MM (thalidomide, lenalidomide, or pomalidomide) between 2013 and 2016 and with continuous eligibility 6 months before and 12 months after oral oncolytic initiation were identified. Adherence to oral oncolytics was measured using the proportion of days covered (PDC) metric. Multiple linear regression and multivariable logistic regression were used to identify adherence predictors. Count models assessed the relationship between adherence and resource utilization, and generalized linear models assessed the relationship between adherence and health care costs. A total of 701 and 2,385 patients were identified with CLL/SLL or MM, respectively. Mean PDC (SD) for CLL/SLL and MM patients was 75.3 (22.5) and 57.6 (26.5), respectively. For CLL/SLL patients, those aged ≥ 65 years (beta [B] = -4.00) had lower medication use. Among MM patients, multiple predictors of higher medication use emerged: aged ≥ 65 years (B = 3.44), higher than average outpatient resource utilization (B = 3.53), insurance plan other than preferred provider organization (PPO; B = -2.58), previous cancer therapy (B = -2.81), higher number of concurrent unique therapeutic classes (B = -0.35), and higher comorbidity burden (B = -2.55). Patients with CLL/SLL and enrolled in plans other than a PPO were more likely to be adherent (OR = 1.41, 95% CI = 1.01-1.98), whereas patients who were aged ≥ 65 years, were residents of the southern United States, and had visited the emergency department in the baseline period were less likely to be adherent. For MM patients, those aged ≥ 65 years (OR = 1.68, 95% CI = 1.38-2.04) and with higher than average outpatient services utilization (OR = 1.24, 95% CI = 1.01-1.52) were more likely to be adherent, whereas those enrolled in plans other than a PPO, previously treated with cancer therapy, and with higher comorbidity burden were less likely to be adherent. In both cohorts, adherent patients had significantly lower odds of health care utilization and incurred lower medical costs, but higher prescription costs, following oncolytic initiation; however, total costs were not significantly lower in those adherent. Factors were identified that influenced adherence at the patient, treatment, and health system levels. These factors can be used to identify patients requiring interventions for improving medication-taking behavior and associated health care burden. This study received no outside funding. Dashputre was recently employed by Novartis; K. Gatwood has received speaker fees from Jazz Pharmaceuticals; and J. Gatwood has received research funding from Merck & Co. and GlaxoSmithKline, unrelated to this study..

Using Real-Time Adherence Feedback to Enhance Communication About Adherence to Antiretroviral Therapy: Patient and Clinician Perspectives.

New technologies for real-time adherence monitoring hold the potential to enhance antiretroviral therapy adherence interventions by providing objective information about daily medication-taking behavior. To realize this potential, we need to understand how to integrate real-time adherence feedback into existing best practices to promote antiretroviral therapy adherence at the point of care. Using in-depth interviews with 30 HIV-infected patients and 29 HIV care clinicians, our primary aims were to understand patients' and clinicians' perceptions of anticipated benefits and preferred uses of objective feedback to enhance conversations about adherence and to identify concerns about the impact of objective monitoring on patient-clinician relationships and communication. Both patients and clinicians suggested that identifying patterns of nonadherence with real-time feedback could (a) facilitate collaborative adherence problem-solving, (b) motivate patient adherence, and (c) reinforce the importance of optimal adherence. Some clinicians worried that delivery of real-time feedback could imply mistrust of patient-reported adherence and suggested careful framing of monitoring results. A few patients and clinicians were concerned that negative reactions to monitoring could discourage retention in care and reduce adherence motivation. These results indicate the potential of real-time feedback to enhance existing evidence-based adherence interventions targeting the key adherence precursors of adherence information, motivation, and behavioral skills. Guidance for the delivery of real-time adherence feedback should focus on both optimizing adherence and mitigating negative perceptions of adherence monitoring.

Prediction and pattern analysis of medication refill adherence through electronic health records and dispensation data

Background and purposeLow adherence to medication in chronic disease patients leads to increased morbidity, mortality, and healthcare costs. The widespread adoption of electronic prescription and dispensation records allows a more comprehensive overview of medication utilization. In combination with electronic health records (EHR), such data provides new opportunities for identifying patients at risk of nonadherence and provide more targeted and effective interventions. The purpose of this article is to study the predictability of medication adherence for a cohort of hypertensive patients, focusing on healthcare utilization factors under various predictive scenarios. Furthermore, we discover common proportion of days covered patterns (PDC-patterns) for patients with index prescriptions and simulate medication-taking behaviours that might explain observed patterns. ProceduresWe predict refill adherence focusing on factors of healthcare utilization, such as visits, prescription information and demographics of patient and prescriber. We train models with machine learning algorithms, using four different data splits: stratified random, patient, temporal forward prediction with and without index patients. We extract frequent, two-year long PDC-patterns using K-means clustering and investigate five simple models of medication-taking that can generate such PDC-patterns. FindingsModel performance varies between data splits (AUC test set: 0.77–0.89). Including historical information increases the performance slightly in most cases (approx. 1–2% absolute AUC uplift). Models show low predictive performance (AUC test set: 0.56–0.66) on index-prescriptions and patients with sudden drops in PDC (Recall: 0.58–0.63). We find 21 distinct two-year PDC-patterns, ranging from good adherence to intermittent gaps and early discontinuation in the first or second year. Simulations show that observed PDC-patterns can only be explained by specific medication consumption behaviours. ConclusionsPrediction models developed using EHR exhibit bias towards patients with high healthcare utilization. Even though actual medication-taking is not observable, consumption patterns may not be as arbitrary, provided that medication refilling and consumption is linked.

Psychosocial aspects and contributions of behavioural science to medication-taking for adults with type 2 diabetes.

The aim of this narrative review was to determine the contribution of behavioural and psychosocial research to the field of medication-taking for adults with type 2 diabetes over the past 25 years. We review the behavioural and psychosocial literature relevant to adults with type 2 diabetes who are treated with oral antidiabetes agents, glucagon-like peptide-1 receptor agonists and insulin. Delayed uptake of, omission of and non-persistence with medications are significant problems among adults with type 2 diabetes. At each stage of the course of diabetes, during which medication to lower blood glucose is initiated or intensified, ~50% of people take less medication than prescribed. Research aimed at increasing optimal medication-taking behaviour has targeted 'forgetfulness', developing interventions which aid medication-taking, such as reminder devices, with limited success. In parallel, investigation of beliefs about medication has provided insights into the perceived necessity of and concerns about medication and how these inform medication-taking decisions. Guidance is available for health professionals to facilitate shared decision-making, particularly with insulin therapy; however, interventions addressing medication beliefs are limited. Optimal medication-taking behaviour is essential to prevent hyperglycaemia in adults with type 2 diabetes. Evidence from the past 25 years has demonstrated the association between medication beliefs and medication-taking behaviour. Health professionals need to address medication concerns, and establish and demonstrate the utility of diabetes medication with the individual within the clinical consultation. There are interventions that may assist diabetes health professionals in the shared decision-making process, but further development and more robust evaluation of these tools and techniques is required.

Awareness, attitude and behavior regarding proton pump inhibitor among medical staff in the Southwest of China

BackgroundProton pump inhibitors (PPIs) are one of the most frequently prescribed classes of drug in the world and there is a growing number of publications on correct versus incorrect use of PPIs worldwide. The knowledge of PPIs among the medical staff is essential for improving the rationality of PPI application. The present study aimed to investigate awareness, attitude and behavior toward PPI use among medical staff in the Southwest of China.MethodsThe present descriptive-analytical study was conducted on 900 medical staff from three professional groups (300 doctors, 300 nurses and 300 pharmacists) in China. The study data were collected through a self-designed questionnaire which included demographics, awareness, attitude and behavior toward PPI use. The study was carried out in 22 hospitals in Luzhou between February and June 2018.ResultsOf 900 surveys issued, 851valid questionnaires (295doctors, 268 nurses and 288 pharmacists) were returned. Of all respondents, 33.25% were men and 66.75% were women. The score related to PPI awareness score of medical staff was low (59.47 ± 15.75). The level of awareness of pharmacist was significantly higher than that of doctors and nurses (P < 0.01), which was related to gender, age, occupation, educational level, professional title, hospital nature and hospital grade. Similarly, on the attitude towards PPI use, the pharmacists scored also significantly higher than doctors and the nurses (P < 0.01). Three hundred eighty-one of 851 medical staff had used PPI in the past 1 year, of which omeprazole was the most widely used. Among doctors, nurses and pharmacists, the usage rate of PPI was 50.85, 42.16, 40.97%, respectively. The use frequency was related to occupation and professional title. The score about the behavior toward PPIs of the nurses was also significantly lower than that of doctors and pharmacists (P < 0.01).ConclusionsThe study indicated that the medical staff lack of awareness concerning rational use of PPI in China, especially nurse. Thus, it is necessary to call for action on the improvement of PPI awareness and medication-taking behaviors to reduce PPI overuse and to promote the rationality of PPI application.