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.

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.

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.

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.

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.

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.

Reliability and validity of an instrument for assessing patients' perceptions about medications for diabetes: the PAM-D.

PURPOSE: To evaluate the reliability and validity of the Perceptions About Medications for Diabetes (PAM-D) instrument. METHODS: The item pool was generated from a literature review and 18 focus groups of Type 2 diabetes patients. Surveys were mailed to 1,000 low-income diabetes patients; 362 were returned; 65 of 100 re-test surveys were returned. RESULTS: This paper uses data from 343 Type 2 respondents. Mean age and age diagnosed were 59 and 48, respectively; 72% female; 52% African American; 51% were taking oral antihyperglycemic agents [OHA] monotherapy, 18% insulin monotherapy, and 28% insulin plus OHA. The initial 66 items were reduced to 37 across nine scales: scheduling flexibility, portability convenience, regimen inconvenience, medication effectiveness, difficulty remembering medications, gastrointestinal, hypoglycemia-related, and weight/edema physical side effects, and emotional side effects. Scale reliabilities ranged from 0.71 to 0.92 (coefficient alpha) and from 0.54 to 0.83 (test-retest coefficient, 37-81-day interval); factor loadings ranged from 0.35 to 0.86 (median, 0.67); significant scale differences across medication groups (insulin, OHA, insulin plus OHA) were consistent with a priori hypotheses. CONCLUSIONS: The PAM-D has substantial reliability and validity in a low-income, inner-city population of Type 2 diabetes patients and may be valuable for understanding multidimensional perceptions driving patients' treatment preferences.

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.

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.

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.

Evidence-based practice for equating health status items: sample size and IRT model.

BACKGROUND: In the development of health outcome measures, the pool of candidate items may be divided into multiple forms, thus "spreading" response burden over two or more study samples. Item responses collected using this approach result in two or more forms whose scores are not equivalent. Therefore, the item responses must be equated (adjusted) to a common mathematical metric. OBJECTIVES: The purpose of this study was to examine the effect of sample size, test size, and selection of item response theory model in equating three forms of a health status measure. Each of the forms was comprised of a set of items unique to it and a set of anchor items common across forms. RESEARCH DESIGN: The study was a secondary data analysis of patients' responses to the developmental item pool for the Health of Seniors Survey. A completely crossed design was used with 25 replications per study cell. RESULTS: We found that the quality of equatings was affected greatly by sample size. Its effect was far more substantial than choice of IRT model. Little or no advantage was observed for equatings based on 60 or 72 items versus those based on 48 items. CONCLUSIONS: We concluded that samples of less than 300 are clearly unacceptable for equating multiple forms. Additional sample size guidelines are offered based on our results.

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.

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.

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).

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.

An evaluation of patient preferences for osteoporosis medication attributes: results from the PREFER-US study.

OBJECTIVE: To evaluate preferences for eight medication attributes that women may consider when evaluating prescription osteoporosis medications. RESEARCH DESIGN AND METHODS: The eligible sample consisted of women aged 50 years or older who responded to the 2003 or 2004 Internet-based National Health and Wellness Survey as being diagnosed with osteoporosis, considering themselves at risk, or having a family history of osteoporosis. In this Internet survey (the PREFER survey), respondents were asked to: (1) force-rank order the eight attributes from one to eight according to their preferences and (2) separately rate the importance of each attribute on a Likert-type scale from 1 (extremely unimportant) to 7 (extremely important). RESULTS: We collected 999 responses across 3 days from a sample of 3368 women and stopped compiling responses after achieving sample size targets. Drug effectiveness (e.g., ability to reduce the risk of fractures) was force ranked as the No. 1 preferred osteoporosis medication attribute by 37% of the sample. Side effects were force ranked as the No. 1 preferred medication attribute by 36% of the sample. Dosing frequency, dosing procedure, and formulation (i.e., how the drug is taken) were each force ranked as No. 1 by 2% or less of the sample. Drug effectiveness had the highest percentage of 'extremely important' responses (59%) followed by drug interactions (53%). Drug effectiveness was the highest-rated attribute (mean [S.D.] = 6.1 [1.6], median = 7), while dosing frequency was the lowest-rated attribute (mean [S.D.] = 4.7 [1.8], median = 5). CONCLUSIONS: In our sample of women with a diagnosis of osteoporosis or at risk for osteoporosis, drug effectiveness was the most highly ranked and rated of eight osteoporosis medication attributes. Side effects and drug interactions were also highly ranked and rated. Healthcare providers should consider incorporating patient preferences for key medication attributes into their therapeutic decision-making processes.

Understanding diabetes medications from the perspective of patients with type 2 diabetes: prerequisite to medication concordance.

PURPOSE: The purpose of this qualitative study was to explore diabetes medication experiences of patients with type 2 diabetes. METHODS: Study participants were recruited through newspaper advertisements and letters from primary and specialty clinics in Indianapolis, Indiana. The same professional facilitator conducted 18 focus groups (7 male, 11 female) at a Veteran Affairs facility in Indianapolis, Indiana. Participants were 138 socioeconomically diverse individuals with type 2 diabetes (68% female, 74% > or = 50 years old, 61% non-Hispanic Caucasian). Participants were on a variety of diabetes medication regimens (61% injectable insulin monotherapy or in combination with orals). Content analysis of focus group transcripts was used to establish themes. RESULTS: Three major themes emerged across the focus groups: (1) the inconvenience and inflexibility of the timing and frequency of administration of many diabetes treatments on participants' lives, (2) the desire to avoid injections and/or insulin therapy, and (3) the physical and emotional side effects of diabetes medications. Assuming equivalent effectiveness of 2 medications, participants would weigh the convenience and flexibility, route of administration, side effects, and cost of the medications to arrive at a treatment preference. Participants believed they currently had no opportunity to express their treatment preference to their health care provider. CONCLUSIONS: The best therapeutic option for a patient with type 2 diabetes will be one that is clinically effective and consistent with the patient's needs and preferences. The challenge for diabetes educators is to support patients in articulating and incorporating their needs and preferences into the treatment decision-making process.

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.

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.

Preliminary validation of a patient-based self-assessment measure of severity of illness in type 2 diabetes: results from the pilot phase of the Veterans Health Study.

Measures of case mix are needed to control for patients' clinical status in studies assessing the process and outcomes of care. The Veterans Health Study (VHS) is a longitudinal study of determinants of health outcomes in ambulatory veterans. This study assessed the validity of a case-mix measure developed to quantify severity of illness in ambulatory type 2 diabetic patients. As part of the pilot phase of the VHS, 245 veterans using 4 primary care clinics in Boston were screened for diabetes and 5 other chronic illnesses when they presented for care. Subjects screening positive for diabetes returned to complete severity of illness and outcome measures. The variables for the diabetes case-mix module were chosen based upon the principles of parsimony, duration of follow-up, and clinical validity and credibility. Variables were selected to predict function, as measured by the Medical Outcomes Study Short-Form 36 (SF-36). The diabetic patients in this study had a heavy burden of chronic illness, with an average of 3.9 comorbid conditions and a mean general health perceptions score of 48 on the SF-36 (scored from 0 to 100, with 100 indicating best health). A summary variable called DMSEV was created for "diabetes severity". This included atherosclerotic complications(stroke, transient ischemic attack or myocardial infarction; chest pain frequency; and claudication), plus any history of eye, foot, or neuropathic symptoms. DMSEV correlated with all 8 outcome scales of the SF-36, and in particular was highly associated with physical function (r=0.49, P=.0001). Least squares linear regression analysis controlling for age and comorbidity confirmed the association of DMSEV with all 8 SF-36 scales. The correlation with physical function remained highly significant (P<.0001), with an R of 0.31. This patient-based self-assessment questionnaire and the summary variable DMSEV appear to be valid measures of severity of illness in ambulatory diabetic veterans with multiple comorbidities. After further testing, this case-mix measure may be suitable for controlling for severity of illness in ambulatory-based studies of diabetic patients with multiple chronic illnesses.