The impact of heart failure on patients and caregivers: A qualitative study.

BACKGROUND: Heart failure is rising in prevalence but relatively little is known about the experiences and journey of patients and their caregivers. The goal of this paper is to present the symptom and symptom impact experiences of patients with heart failure and their caregivers. METHODS: This was a United States-based study wherein in-person focus groups were conducted. Groups were audio recorded, transcribed and a content-analysis approach was used to analyze the data. RESULTS: Ninety participants (64 patients and 26 caregivers) were included in the study. Most patients were female (52.0%) with mean age 59.3 ± 8 years; 55.6% were New York Heart Association Class II. The most commonly reported symptoms were shortness of breath (81.3%), fatigue/tiredness (76.6%), swelling of legs and ankles (57.8%), and trouble sleeping (50.0%). Patients reported reductions in social/family interactions (67.2%), dietary changes (64.1%), and difficulty walking and climbing stairs (56.3%) as the most common adverse disease impacts. Mental-health sequelae were noted as depression and sadness (43.8%), fear of dying (32.8%), and anxiety (32.8%). Caregivers (mean age 55.5 ± 11.2 years and 52.0% female) discussed 33 daily heart failure impacts, with the top three being reductions in social/family interactions (50.0%); being stressed, worried, and fearful (46.2%); and having to monitor their "patience" level (42.3%). CONCLUSIONS: There are serious unmet needs in HF for both patients and caregivers. More research is needed to better characterize these needs and the impacts of HF along with the development and evaluation of disease management toolkits that can support patients and their caregivers.

Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients.

OBJECTIVES: To estimate the real-world (RW) impact of adherence to once-daily (QD: rivaroxaban and edoxaban) and twice-daily (BID: apixaban and dabigatran) non-vitamin K antagonist (NOACs) on the risk of stroke and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients. METHODS: First, claims from the Optum Clinformatics Data Mart database (July 2012-December 2016) were analyzed. Adult NVAF patients with ≥2 NOAC dispensings (index date) were included. The relationship between NOAC adherence (proportion of days covered ≥80%) and stroke/MB 1-year post-index was evaluated using adjusted Cox proportional hazards models. Second, the natural logarithm of hazard ratios (HRs) was multiplied to a literature-derived mean adherence difference between QD and BID NOACs yielding stroke and MB rates. Third, these rates were multiplied by 1-year Kaplan-Meier rates of stroke and MB which yielded the number of strokes prevented and MBs caused. Annual cost savings were evaluated using literature-based stroke ($81,414/patient) and MB ($63,905/patient) cost estimates. RESULTS: In total, 54,280 patients were included. HRs for adherent vs non-adherent patients were 0.67 (p < .001) for stroke and 1.09 (p = .179) for MB. The claims-derived 1-year Kaplan-Meier rates were 3.0% and 3.4% for strokes and MBs, respectively. For 100,000 AF patients, 64 strokes were prevented (p < .001), and a non-significant number of MBs (n = 15, p < .191) were caused by QD vs BID NOACs annually, which leads to cost savings estimated at $58 million for QD NOACs. CONCLUSION: QD NOACs prevented a significant number of strokes and caused no significant increase in MBs compared to BID NOACs, which leads to significant net cost savings for NVAF patients in the US.

Exploring the implementation of patient-reported outcome measures in cancer care: need for more real-world evidence results in the peer reviewed literature.

BACKGROUND: To explore the existing evidence of the real-world implementation of patient-reported outcomes (PROs) in oncology clinical practice and address two aims: (1) summarize available evidence of PRO use in clinical practice using a framework based on the International Society for Quality of Life Research (ISOQOL) PRO Implementation Guide; and (2) describe reports of real-world, standardized PRO administration in oncology conducted outside of scope of a research study. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was developed to guide the systematic literature review (SLR) that was conducted in MEDLINE and Embase databases. A two step search strategy was implemented including two searches based on previously completed reviews. Studies published from 2006 to 2017 were synthesized using a framework based on the ISOQOL PRO Implementation Guide. RESULTS: After screening 4427 abstracts, 36 studies met the eligibility criteria. Most elements of the ISOQOL PRO Implementation Guide were followed. Two notable exceptions were found: 1) providing PRO score interpretation guidelines (39% of studies); and 2) providing patient-management guidance for addressing issues identified by PROs (25% of studies). Of the 22 studies with an intervention component, 19 (86%) reported intervention effects on study outcomes. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) was the most commonly used PRO (n = 10, 28%); use of 38 other PRO measures was also reported. Only three studies (8%) reported real-world PRO implementation. CONCLUSION: Reports of real-world PRO implementation are limited. Reports from studies conducted in clinical settings suggest gaps in information on PRO score interpretation and the use of PRO results to inform patient management. Before the promise of practice-based PRO assessment in oncology can be truly realized, investigators need to advance the state-of-the-art of real-time PRO score interpretation as well as developing guidance on how to use PRO insights to drive clinically-meaningful patient-management strategies.

Adherence to rivaroxaban versus apixaban among patients with non-valvular atrial fibrillation: Analysis of overall population and subgroups of prior oral anticoagulant users.

BACKGROUND: Medication non-adherence can result in poor health outcomes. Understanding differences in adherence rates to non-vitamin K oral anticoagulants (NOACs) could guide treatment decisions and improve clinical outcomes among patients with non-valvular atrial fibrillation (NVAF). OBJECTIVE: To compare adherence to rivaroxaban and apixaban among the overall NVAF population and subgroups of prior oral anticoagulant (OAC) users (e.g., multiple comorbidities, non-adherence risk factors). METHODS: Using healthcare claims from the Truven Health Analytics MarketScan (7/2012-7/2015), adult patients with ≥2 dispensings of rivaroxaban or apixaban ≥ 180 days apart with > 60 days of supply, ≥ 6 months of pre- and post-index eligibility, ≥ 1 atrial fibrillation diagnosis pre- or on the index date, and without valvular involvement were identified. Propensity-score methods adjusting for potential baseline confounders were used to create matched cohorts of rivaroxaban and apixaban patients. Adherence was assessed during the implementation phase using the percentage of patients with proportion of days covered (PDC) ≥0.8 at 6 months. Subgroups of patients with prior OAC use were evaluated; additional subgroups were identified and evaluated by Quan-Charlson Comorbidity index ≥2 and presence of non-adherence risk factors (i.e., mental disorders, stress, isolation, and rheumatoid arthritis). RESULTS: A total of 13,890 NVAF subjects were included in each of the 2 matched cohorts. All baseline characteristics were balanced between cohorts. At 6 months, significantly more rivaroxaban users were adherent to treatment compared to apixaban users (81.8% vs. 78.0%; absolute difference of 3.8%; p<.001). Rivaroxaban users had significantly higher adherence rates in all subgroups examined. CONCLUSION: Rivaroxaban users had consistently higher adherence rates than apixaban users overall and among all NVAF subgroups examined.

Beyond study participants: a framework for engaging patients in the selection or development of clinical outcome assessments for evaluating the benefits of treatment in medical product development.

BACKGROUND: Patients are participating more actively in health care decision-making with regard to their health, as well as in the broader realm of assessing the value of medical products and influencing decisions about their registration and reimbursement. There is an increasing trend to include patients' perspectives throughout the stages of medical product development by broadening the traditional study-participant role to that of an active partner throughout the process. Including patients in the selection and development of clinical outcome assessments (COAs) to evaluate the benefit of treatment is particularly important. Still, despite widespread enthusiasm, there is substantial uncertainty regarding how and when to engage patients in this process. PURPOSE: This manuscript proposes a methodological framework for engaging patients at varying levels in the selection and development of COAs for medical product development. FRAMEWORK: The framework builds on the Food and Drug Administration's roadmap for patient-focused COA. Methods for engaging patients across each stage in this roadmap are summarized by levels of engagement. Opportunities and examples of patient engagement (PE) in the selection and/or development of COAs are summarized, together with best practices and practical considerations. CONCLUSION: This paper offers a framework for understanding, planning, and implementing methods to advance PE in the selection and/or development of COAs for evaluating the benefit of medical products. The intent is to further this important discussion and enhance the process and outcome of PE in this context.

Adherence to Rivaroxaban Compared with Other Oral Anticoagulant Agents Among Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Adherence to oral anticoagulant (OAC) agents is important for patients with nonvalvular atrial fibrillation (NVAF) to prevent potentially severe adverse events. OBJECTIVE: To compare real-world adherence rates and time to discontinuation for rivaroxaban versus other OACs (apixaban, dabigatran, and warfarin) among patients with NVAF using claims-based data. METHODS: Health care claims from the IMS Health Real-World Data Adjudicated Claims database (July 2012-June 2015) were analyzed. Adherence rate was defined as the percentage of patients with proportion of days covered (PDC) ≥ 0.80 and ≥ 0.90. Discontinuation was defined as a gap of more than 30 days between the end of a dispensing days of supply and the start date of the next fill, if any. Patients were included if they had ≥ 2 dispensings of rivaroxaban, apixaban, dabigatran, or warfarin at least 180 days apart (the first was considered the index date), had > 60 days of supply, had ≥ 6 months of pre-index eligibility, had ≥ 1 atrial fibrillation (AF) diagnosis pre-index or at index date, and had no valvular involvement. A logistic regression model was used to evaluate adherence to OAC therapy, while a Cox model was used to compare time to discontinuation; both models adjusted for baseline confounders. RESULTS: A total of 13,645 rivaroxaban, 6,304 apixaban, 3,360 dabigatran, and 13,366 warfarin patients were identified. A significantly higher proportion of rivaroxaban users (80.1%) was adherent to therapy (PDC ≥ 0.80 at 6 months) versus apixaban (75.8%), dabigatran (69.2%), and warfarin users (64.5%). After adjustment, the proportion of patients adherent to therapy remained significantly higher for rivaroxaban users versus apixaban (absolute difference [AD] = 5.8%), dabigatran (AD = 9.5%), and warfarin users (AD = 13.6%; all P < 0.001). More pronounced differences were found with a PDC ≥0.90. In addition, rivaroxaban users were significantly less likely to discontinue therapy compared with other OACs after adjustments (all P < 0.05). CONCLUSIONS: Among NVAF patients, rivaroxaban was associated with significantly higher adherence rates relative to other OACs whether using either a PDC of > 0.80 or > 0.90. Such differences in adherence could translate into improved patient outcomes and lower health care costs. DISCLOSURES: This research was funded by Janssen Scientific Affairs. Ashton, Crivera, and Schein are employees and stockholders of Janssen Scientific Affairs. Laliberté, Germain, Wynant, and Lefebvre are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs in connection with this study. McHorney is an employee of Evidera, a consulting company that received research grants from Janssen Scientific Affairs in connection with this study. Peterson received research grants from Janssen Scientific Affairs in connection with this study. All authors contributed to concept and design. The data were collected by Germain, Wynant, Laliberté, and Lefebvre and interpreted primarily by McHorney and Peterson, with the assistance of Lefebvre, Laliberté, Ashton, Crivera, and Schein. The manuscript was written primarily by Laliberté, Germain, and Lefebvre, with the assistance of Wynant. Revisions were made primarily by Ashton, Crivera, McHorney, Schein, and Peterson.

Reliability and validity of the Psoriasis Itch Visual Analog Scale in psoriasis vulgaris.

INTRODUCTION: The single-item Psoriasis Itch VAS was developed to measure itch intensity within the last 24 hours in psoriasis vulgaris to assess treatment benefit. Its psychometric properties were explored in two trials. METHODS: Data from two randomized, parallel-group phase 3 trials with subjects suffering from psoriasis vulgaris on the body (n = 426, 463) were analyzed. Cross-sectional distributional properties and construct validity of the Psoriasis Itch VAS as well as longitudinal test-retest reliability and sensitivity to change of the Psoriasis Itch VAS were investigated. All statistical tests were two-tailed. RESULTS: Across both trials, acceptable distributional properties were observed. Convergent-validity correlations between the Psoriasis Itch VAS and other patient-reported and clinician-reported outcomes provided strong endorsement for construct validity as did tests of known-groups validity. Longitudinal measurement properties, involving test-retest reliability and sensitivity to change, also offered evidence for the measurement integrity of the Psoriasis Itch VAS. DISCUSSION: Results from the assessment of validity, reliability, and sensitivity to change support the use of the Psoriasis Itch VAS to measure itch intensity in psoriasis vulgaris. Data from two trials provided evidence that the Psoriasis Itch VAS is well-defined and reliable for measuring itch in psoriasis vulgaris to assess treatment benefit (i.e. therapeutic response).

Using Individual Experiences With Experimental Medications to Predict Medication-Taking Behavior Postauthorization: A DIA Study Endpoints Workstream.

From humanistic, clinical, and economic perspectives, it is important to understand patients' health care attitudes and behavior. Of particular interest in defining the value of a pharmacologic therapy is medication adherence. A DIA workstream was convened to define medication adherence in a drug-development context, explore the relevance of medication nonadherence from various stakeholder perspectives, examine methods of collecting medication adherence data in, or alongside, drug-development programs, and propose a robust approach to predicting medication adherence in routine clinical practice from data derived in, or alongside, drug-development programs. This article summarizes the workstream findings and guidance as it pertains to these objectives. The proposed approach to predicting medication adherence involves a patient-reported outcome (PRO) questionnaire that contains a series of standardized questions for patient self-completion that asks about likelihood of medication adherence in clinical practice, and that queries about perceived benefits and barriers to adherence on exit from an efficacy trial. This methodology can be used to both gain a better understanding of the experimental medication and compare the experimental treatment to comparator therapy as warranted. This approach may assist regulators and payers in making meaningful treatment comparisons and facilitate manufacturers in developing empirically based patient-support programs. This workstream will now turn to the challenge of developing the PRO questionnaire in line with this proposal.

Development and psychometric validation of the Nausea/Vomiting Symptom Assessment patient-reported outcome (PRO) instrument for adults with secondary hyperparathyroidism.

BACKGROUND: We developed the Nausea/Vomiting Symptom Assessment (NVSA©) patient-reported outcome (PRO) instrument to capture patients' experience with nausea and vomiting while on calcimimetic therapy to treat secondary hyperparathyroidism (SHPT) related to end-stage kidney disease. This report summarizes the content validity and psychometric validation of the NVSA©. METHODS: The two NVSA© items were drafted by two health outcomes researchers, one medical development lead, and one regulatory lead: it yields three scores: the number of days of vomiting or nausea per week, the number of vomiting episodes per week, and the mean severity of nausea. An eight-week prospective observational study was conducted at ten dialysis centers in the U.S. with 91 subjects. Criterion measures included in the study were the Functional Living Index-Emesis, Kidney Disease Quality of Life Instrument, EQ-5D-5 L, Static Patient Global Assessment, and Patient Global Rating of Change. Analyses included assessment of score distributions, convergent and known-groups validity, test-retest reliability, ability to detect change, and thresholds for meaningful change. RESULTS: Qualitative interviews verified that the NVSA© captures relevant aspects of nausea and vomiting. Patients understood the NVSA© instructions, items, and response scales. Correlations between the NVSA© and related and unrelated measures indicated strong convergent and discriminant validity, respectively. Mean differences between externally-defined vomiting/nausea groups supported known-groups validity. The scores were stable in subjects who reported no change on the Patient Global Rating of Change indicating sufficient test-retest reliability. The no-change group had mean differences and effect sizes close to zero; mean differences were mostly positive for a worsening group and mostly negative for the improvement group with predominantly medium or large effect sizes. Preliminary thresholds for meaningful worsening were 0.90 days for number of days of vomiting or nausea per week, 1.20 for number of episodes of vomiting per week, and 0.40 for mean severity of nausea. CONCLUSIONS: The NVSA© instrument demonstrated content validity, convergent and known-groups validity, test-retest reliability, and the ability to detect change. Preliminary thresholds for minimally important change should be further refined with additional interventional research. The NVSA© may be used to support study endpoints in clinical trials comparing the nausea/vomiting profile of novel SHPT therapies.

Comparison of Adherence to Rivaroxaban Versus Apixaban Among Patients With Atrial Fibrillation.

PURPOSE: Non-vitamin K antagonist oral anticoagulant medications are increasingly used for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to compare adherence with rivaroxaban and apixaban among patients with NVAF in routine clinical practice. METHODS: Using pharmacy and medical claims from Truven Health Analytics MarketScan databases, we identified NVAF patients aged ≥18 years treated with rivaroxaban or apixaban. Baseline demographic and clinical features were balanced using 1:1 propensity score matching. Adherence to therapy was measured at 90 and 180 days post-index date and was defined by the proportion of days covered (PDC) ≥0.80 and PDC ≥0.90. "Gaps in care," defined as those with 10 or more day gaps in supply, were also evaluated. FINDINGS: Between June 2012 and April 2014, 11,477 rivaroxaban and 2992 apixaban users were identified. Baseline characteristics for rivaroxaban and apixaban users were well matched. Relative to apixaban users, rivaroxaban users were more likely to have a PDC ≥0.80 at both 90 days (85.3% vs 79.9%; P < 0.001) and 180 days (75.8% vs 72.2%; P = 0.001). Similar results were observed with PDC ≥0.90. The proportion of patients with at least one 5+ and 10+ day gap in prescriptions was significantly lower in the rivaroxaban versus apixaban cohorts: 54.2% versus 62.4% (P < 0.001) and 40.0% versus 49.2% (P < 0.001), respectively. IMPLICATIONS: Adherence to non-vitamin K antagonist oral anticoagulants among NVAF patients is less than ideal, and gaps in treatment are common. Those on once-a-day rivaroxaban had significantly higher adherence and fewer gaps in treatment compared with twice-a-day apixaban. Future studies are needed to explore whether these treatment differences affect comparative patient outcomes.

Impact of once- or twice-daily dosing frequency on adherence to chronic cardiovascular disease medications: A meta-regression analysis.

BACKGROUND: Most cardiovascular diseases require patients to take one or more chronic medications, often administered multiple times daily. We sought to determine the impact of once- vs. twice-daily dosing of chronic cardiovascular disease medication on adherence. METHODS: We searched Medline and Embase from 1/1/86 to 10/15/15 for prospective studies electronically measuring adherence for at least four weeks to oral, chronic cardiovascular disease medications taken one to two times daily. Regimen adherence (the proportion of days with the appropriate number of doses taken) and timing adherence (the number of doses taken within an assigned interval divided by the total number of intervals) were outcomes of interest. Meta-regression was performed to assess how dosing frequency, adjusted for study-level covariates, impacted regimen and timing adherence. RESULTS: We identified 26 studies that met inclusion criteria. Forty study arms consisting of 1834 patients (range: 12-501) evaluated once-daily dosing and 18 arms consisting of 451 patients (range: 9-82) evaluated twice-daily dosing. Based upon evaluation of the regimen and timing definitions, unadjusted adherence rates were lower for twice-daily (73.8% and 50.4%) than once-daily dosing (83.1% and 74.2%) of chronic cardiovascular disease medications (p≤0.02 for both). Upon meta-regression, adjusted mean percent regimen and timing adherence for twice-daily dosing was 14.2% (95% confidence interval [CI] 6.8-21.7%) and 22.9% (95%CI 13.0-32.8%) worse than once-daily dosing (p≤0.002 for both). CONCLUSION: Patients appear to be more adherent to cardiovascular disease medications dosed once-daily compared to twice-daily. Dosing frequency may be a factor for providers to consider when selecting an agent to prescribe.

Adherence to non-vitamin-K-antagonist oral anticoagulant medications based on the Pharmacy Quality Alliance measure.

BACKGROUND: CMS Star Ratings help inform beneficiaries about the performance of health and drug plans. Medication adherence is currently weighted at nearly half of a Part D plan's Star Ratings. Including the adherence to non-vitamin-K-antagonist oral anticoagulants (NOACs) as a measure in the Star Ratings program may increase a plan's incentives to improve patient adherence. OBJECTIVE: To assess the adherence to medication of patients who used the NOACs rivaroxaban, dabigatran, or apixaban in 2014 based on the Pharmacy Quality Alliance (PQA) adherence measure. METHODS: Healthcare claims from the Humana database between July 2013 and December 2014 were analyzed. Adult patients with ≥2 dispensings of NOAC agents in 2014, at least 180 days apart, with >60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. The PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥0.8. Multivariate logistic regression analyses were also conducted adjusting for baseline confounders. RESULTS: A total of 11,095 rivaroxaban, 6548 dabigatran, and 3532 apixaban users were identified. Based on the PQA adherence measure (PDC ≥0.8), a significantly higher proportion of rivaroxaban users (72.7%) was found to be adherent compared to dabigatran (67.2%: p < 0.001) and apixaban (69.5%: p < 0.001) users. Compared to apixaban users, the adjusted likelihood of being adherent was significantly higher for rivaroxaban users (unadjusted OR [95% CI]: 1.17 [1.08-1.27], p < 0.001; adjusted OR [95% CI]: 1.20 (1.10-1.31), p < 0.001) and significantly lower for dabigatran users (unadjusted OR [95% CI]: 0.90 [0.82-0.98], p = 0.019; adjusted OR [95% CI]: 0.85 [0.77-0.93], p < 0.001). LIMITATIONS: Limitations of the study are potential inaccuracies in claims data, possible change in patterns over time, and the impossibility of knowing whether all supplied tablets were taken. CONCLUSION: Using the PQA's adherence measure, rivaroxaban users were found to have significantly higher adherence compared to apixaban and dabigatran users.

Impact of health literacy on medication adherence: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature and estimate the effect size of the relationship between health literacy and medication adherence through meta-analysis. DATA SOURCES: Databases searched included Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982-2013), International Pharmaceutical Abstracts (IPA; 1970-2013), MEDLINE OVID (1966-2013), PubMed (1966-2013), PsycInfo (1966-2013), and Web of Science (1966-2013). STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were as follows: English language; published through May 1, 2013; medication adherence as the outcome variable; use of validated measures of health literacy and medication adherence; availability of a direct (not mediating) relationship between health literacy and medication adherence; and identifiable effect size and statistical significance of the relationship. Exclusion criteria were as follows: duplicated results, irrelevant results, conference abstracts, proceeding papers, books, dissertations, reviews, editorial letters, continuing education units, or book reviews. Data included author, publication year, disease area, sample size, sampling method, location, study design, effect size of the relationship between health literacy and medication adherence, and measures of health literacy and medication adherence. DATA SYNTHESIS: There is a small statistically significant and positive association between health literacy and medication adherence. In the conservative results, the unweighted and weighted correlation coefficients were 0.081 and 0.056 with P values <0.001. In the less conservative results, the unweighted and weighted correlation coefficients were 0.088 and 0.072. CONCLUSIONS: The relationship between health literacy and medication adherence is statistically significant but weak. It is plausible that health literacy has a mediator relationship with other adherence determinants. Future research should explore such relationships.

Structural equation modeling of the proximal-distal continuum of adherence drivers.

OBJECTIVES: Nonadherence to prescription medications has been shown to be significantly influenced by three key medication-specific beliefs: patients' perceived need for the prescribed medication, their concerns about the prescribed medication, and perceived medication affordability. Structural equation modeling was used to test the predictors of these three proximal determinants of medication adherence using the proximal-distal continuum of adherence drivers as the organizing conceptual framework. METHODS: In Spring 2008, survey participants were selected from the Harris Interactive Chronic Illness Panel, an internet-based panel of hundreds of thousands of adults with chronic disease. Respondents were eligible for the survey if they were aged 40 years and older, resided in the US, and reported having at least one of six chronic diseases: asthma, diabetes, hyperlipidemia, hypertension, osteoporosis, or other cardiovascular disease. A final sample size of 1072 was achieved. The proximal medication beliefs were measured by three multi-item scales: perceived need for medications, perceived medication concerns, and perceived medication affordability. The intermediate sociomedical beliefs and skills included four multi-item scales: perceived disease severity, knowledge about the prescribed medication, perceived immunity to side effects, and perceived value of nutraceuticals. Generic health beliefs and skills consisted of patient engagement in their care, health information-seeking tendencies, internal health locus of control, a single-item measure of self-rated health, and general mental health. Structural equation modeling was used to model proximal-distal continuum of adherence drivers. RESULTS: The average age was 58 years (range = 40-90 years), and 65% were female and 89% were white. Forty-one percent had at least a four-year college education, and just under half (45%) had an annual income of $50,000 or more. Hypertension and hyperlipidemia were each reported by about a quarter of respondents (24% and 23%, respectively). A smaller percentage of respondents had osteoporosis (17%), diabetes (15%), asthma (13%), or other cardiovascular disease (8%). Three independent variables were significantly associated with the three proximal adherence drivers: perceived disease severity, knowledge about the medication, and perceived value of nutraceuticals. Both perceived immunity to side effects and patient engagement was significantly associated with perceived need for medications and perceived medication concerns. CONCLUSION: Testing the proximal-distal continuum of adherence drivers shed light on specific areas where adherence dialogue and enhancement should focus. Our results can help to inform the design of future adherence interventions as well as the content of patient education materials and adherence reminder letters. For long-term medication adherence, patients need to autonomously and intrinsically commit to therapy and that, in turn, is more likely to occur if they are both informed (disease and medication knowledge and rationale, disease severity, consequences of nonadherence, and side effects) and motivated (engaged in their care, perceive a need for medication, and believe the benefits outweigh the risks).

Unintentional non-adherence to chronic prescription medications: how unintentional is it really?

BACKGROUND: Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior (forgetfulness or carelessness). Our objectives were to: (1) study the prevalence and predictors of unintentional non-adherence; and (2) explore the interrelationship between intentional and unintentional non-adherence in relation to patients' medication beliefs. METHODS: We conducted a cross-sectional survey of adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, or depression from the Harris Interactive Chronic Illness Panel. The analytic sample for this study included 24,017 adults who self-identified themselves as persistent to prescription medications for their index disease. They answered three questions on unintentional non-adherence (forgot, ran out, being careless), 11 questions on intentional non-adherence, and three multi-item scales assessing perceived need for medication (k = 10), perceived medication concerns (k = 6), and perceived medication affordability (k = 4). Logistic regression was used to model predictors of each unintentional non-adherence behavior. Baron and Kenny's regression approach was used to test the mediational effect of unintentional non-adherence on the relationship between medication beliefs and intentional non-adherence. Bootstrapping was employed to confirm the statistical significance of these results. RESULTS: For the index disease, 62% forgot to take a medication, 37% had run out of the medication, and 23% were careless about taking the medication. Common multivariate predictors (p < .001) of the three behaviors were: (1) lower perceived need for medications; (2) more medication affordability problems; (3) worse self-rated health; (4) diabetes or osteoporosis (relative to hypertension); and (5) younger age. Unique statistically-significant predictors of the three behaviors were: (a) 'forgot to take medications' - greater concerns about the index medication and male gender; (b) 'run out of medications' - non-white race, asthma, and higher number of total prescription medications; (c) 'being careless' - greater medication concerns. Mediational tests confirmed the hypothesis that the effect of medication beliefs (perceived need, concerns, and affordability) on intentional non-adherence is mediated through unintentional non-adherence. CONCLUSIONS: For our study sample, unintentional non-adherence does not appear to be random and is predicted by medication beliefs, chronic disease, and sociodemographics. The data suggests that the importance of unintentional non-adherence may lie in its potential prognostic significance for future intentional non-adherence. Health care providers may consider routinely inquiring about unintentional non-adherence in order to proactively address patients' suboptimal medication beliefs before they choose to discontinue therapy all together.

Beliefs that influence cost-related medication non-adherence among the "haves" and "have nots" with chronic diseases.

BACKGROUND AND OBJECTIVE: Some patients continue taking their medication as prescribed despite serious financial pressures, while others with the ability to pay forego treatment due to cost concerns. The primary goal of this study was to explore how patients' beliefs about the necessity of treatment and treatment side effects, influence cost-related non-adherence (CRN). METHODS: 27,302 participants in the Harris Interactive Chronic Illness Panel completed an internet survey. The current study focused on two subsamples representing: (a) the most economically-vulnerable survey respondents (ie, individuals with household incomes of US$25,000 per year or less and monthly out-of-pocket medication costs of at least US$60, n = 1321); and (b) respondents who were the most likely to have the financial resources to pay for medications (ie, those with incomes of US$125,000 or more and monthly medication costs of less than US$60.00, n = 1195). Multivariate models were constructed for each group to determine the independent impact on CRN of perceived need for medications and side-effect concerns. Increased risk for CRN associated with depression and asthma diagnoses also was examined. RESULTS: Twenty-one percent of economically vulnerable respondents reported continuing to take their medication as prescribed despite serious cost pressures, while 14% of high-income respondents reported CRN despite apparently manageable out-of-pocket costs. Both low perceived need for medications and concerns about side-effects affected CRN risk in low-income and high-income groups. Within groups of both low-income and high-income respondents, depression and asthma significantly increased patients' odds of reporting CRN. CONCLUSION: Beyond objective financial measures, CRN is influenced by patient beliefs, which can influence the perceived value of prescription drugs. Addressing these beliefs, as well as the unique adherence concerns of patients with depression and asthma, could decrease CRN rates even if cost pressures themselves cannot be reduced.

Survey nonresponders to a medication-beliefs survey have worse adherence and persistence to chronic medications compared with survey responders.

OBJECTIVE: The primary objective of this study was to investigate whether nonresponders to a medication-beliefs survey exhibited different adherence and persistence patterns than survey responders. METHODS: A medication-beliefs survey was mailed to 7795 adults aged from 40 to 88 years, who filled a qualifying index prescription (cardiovascular, dyslipidemia, oral-antihyperglycemic, oral-bisphosphonate, and asthma-controller medications) in June 2008 at 1 national and 2 regional retail pharmacies. Adherence and persistence to the index drug class was measured using pharmacy-claims data over 12 months. A multivariate generalized linear model with a negative binomial distribution and log-link function was used to determine whether response status was a significant predictor of adherence. Kaplan-Meier estimates of survival curves were used to assess the time to discontinuation (persistence). Differences between nonresponders and responders were assessed using the log-rank test. RESULTS: The survey response rate was 24.25%. The final analytic sample size after exclusions was 6740 patients (5044 nonresponders and 1696 responders). On the basis of multivariate generalized linear model analysis, survey nonresponders had 11% lower medication adherence compared with responders (P < 0.01; goodness-of-fit=1.09 as defined by deviance/df statistics). The proportion of nonresponders deemed nonpersistent at day 305 was 66.3% compared with 58.1% of responders (P < 0.001). The Kaplan-Meier persistence curves were significantly different for nonresponders and responders as assessed by the log-rank test (χ statistic=49.38; P < 0.001). CONCLUSIONS: Our study found that the responders and nonresponders to a medication-beliefs survey differed significantly in their subsequent adherence and persistence, suggesting that biased survey results are likely to accompany low response rates in surveys of medication use. The use of modest monetary incentives had a small effect on survey response; multiple survey levers are recommended to reduce nonresponse and the potential for biased results.

Medication cost problems among chronically ill adults in the US: did the financial crisis make a bad situation even worse?

A national internet survey was conducted between March and April 2009 among 27,302 US participants in the Harris Interactive Chronic Illness Panel. Respondents reported behaviors related to cost-related medication non-adherence (CRN) and the impacts of medication costs on other aspects of their daily lives. Among respondents aged 40-64 and looking for work, 66% reported CRN in 2008, and 41% did not fill a prescription due to cost pressures. More than half of respondents aged 40-64 and nearly two-thirds of those in this group who were looking for work or disabled reported other impacts of medication costs, such as cutting back on basic needs or increasing credit card debt. More than one-third of respondents aged 65+ who were working or looking for work reported CRN. Regardless of age or employment status, roughly half of respondents reporting medication cost hardship said that these problems had become more frequent in 2008 than before the economic recession. These data show that many chronically ill patients, particularly those looking for work or disabled, reported greater medication cost problems since the economic crisis began. Given links between CRN and worse health, the financial downturn may have had significant health consequences for adults with chronic illness.

Development and validation of motivational messages to improve prescription medication adherence for patients with chronic health problems.

OBJECTIVE: Poor adherence with prescription medications is a serious problem in health care, especially true for patients with chronic diseases. Previous strategies to promote adherence have generally not resulted in long-term improvements. This research program is designed to improve on past intervention strategies by developing evidence-based and theoretically grounded communication interventions to promote increased adherence. METHODS: Phase 1 of this research program used qualitative methods to examine the uncertainties and concerns that influence medication adherence, identify messages for addressing these concerns, and develop refined motivational messages for promoting medication adherence. Phase 2 of this research program experimentally assessed chronic disease patients' evaluations of the refined motivational messages. RESULTS: Phase 1 qualitative research indicated that patient concerns about their need for the prescribed medication (commitment) was the primary adherence issue, followed by concerns about side effects and the safety of prescription medications, and concerns about the medication costs. These three key issues were translated into draft motivational messages which were evaluated, validated, and refined. Phase 2 experimental research showed that exposure to motivational messages increased consumers' intention to adhere with medication recommendations. CONCLUSION: Follow-up intervention research is warranted to test the use of these motivational messages to promote medication adherence. PRACTICE IMPLICATIONS: Pharmacies and pharmacists have the potential to perform a central role in providing consumers with the relevant information they need to make responsible decisions that lead to increased adherence with prescription medication recommendations.

Frequency of and reasons for medication non-fulfillment and non-persistence among American adults with chronic disease in 2008.

OBJECTIVE To identify self-reported reasons why adults with chronic disease do not fill a new prescription (medication non-fulfillment) and/or stop taking a medication without their physician telling them to do so (lack of medication persistence). METHODS Participants were sampled in 2008 from a national, internet-based panel of American adults with chronic disease. A total of 19 830 respondents answered questions about medication non-fulfillment and medication non-persistence and reasons for non-fulfillment and non-persistence. Among persons self-identified as non-fulfillers and non-persisters, statistical analyses assessed the association between reported reasons for non-fulfillment and non-persistence and chronic disease. A subsample of respondents completed an additional survey which included multi-item scales assessing matched constructs of most of the reasons for non-fulfillment and non-persistence. The convergent validity of the self-reported reasons was assessed against the multi-item scales. RESULTS The same four reasons were most commonly reported for both medication non-fulfillment and medication non-persistence: paying for the medication a financial hardship (56 and 43%, respectively); fear or experience of side effects (46 and 35%, respectively); generic concerns about medications (32 and 23%, respectively); and lack of perceived need for the medication (25 and 23%, respectively). The frequency with which the reasons were reported varied somewhat by chronic disease. The convergent validity of most of the self-reported reasons was confirmed against multi-item scales measuring matched constructs. CONCLUSIONS The same top reasons for medication non-fulfillment and non-adherence were observed in a large internet-based sample of American adults with chronic disease. Future efforts to improve medication adherence should address patients' medication concerns, perceived need for medications, and perceived medication affordability.