Objective: Global treatment guidelines recommend treatment with oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and an elevated stroke risk. However, not all patients with NVAF and an elevated stroke risk receive guideline-recommended therapy. A literature review and synthesis of observational studies were undertaken to identify the body of evidence on untreated and undertreated NVAF and the association with clinical and economic outcomes. Methods: An extensive search (1/2010-4/2020) of MEDLINE, the Cochrane Library, conference proceedings, and health technology assessments (HTAs) was conducted. Studies must have evaluated rates of nontreatment or undertreatment in NVAF. Nontreatment was defined as absence of OACs (but with possible antiplatelet treatment), while undertreatment was defined as treatment with only antiplatelet agents. Results: Sixteen studies met our inclusion criteria. Rates of nontreatment for patients with elevated stroke risk ranged from 2.0-51.1%, while rates of undertreatment ranged from 10.0-45.1%. The clinical benefits of anticoagulation were reported in the evaluated studies with reductions in stroke and mortality outcomes observed among patients treated with anticoagulants compared to untreated or undertreated patients. Adverse events associated with all bleeding types (i.e. hemorrhagic stroke, major bleeding or gastrointestinal hemorrhaging) were found to be higher for warfarin patients compared to untreated patients in real-world practice. Healthcare resource utilization was found to be lower among patients highly-adherent to warfarin compared to untreated patients. Conclusions: Rates of nontreatment and undertreatment among NVAF patients remain high and are associated with preventable cardiovascular events and death. Strategies to increase rates of treatment may improve clinical outcomes.

Introduction: Global treatment guidelines (e.g., AHA/ACC/HRS, ESC, JCS) recommend treatment with oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and an elevated stroke risk, defined by CHA 2 DS 2 -VASc score ≥2. However, not all patients with NVAF and an elevated stroke risk receive guideline-recommended therapy. A systematic literature review of observational studies was undertaken based on PRISMA guidelines to identify the body of evidence on untreated and undertreated NVAF among patients with elevated stroke risk, and assess its epidemiological and clinical burden. Methods: An extensive search of MEDLINE, GoogleScholar, the Cochrane Library, relevant conference proceedings, and health technology assessments (HTAs) was conducted for RWE studies. Studies published between 1/2010-4/2020 were included if they evaluated rates of nontreatment or undertreatment in NVAF. Nontreatment was defined as absence of OACs, while undertreatment was defined as treatment with only antiplatelet agents. Studies focusing on valvular AF were excluded. Results: Thirty-nine published studies (13 countries) met inclusion criteria. Rates of nontreatment for patients with elevated stroke risk ranged from 2.0%-51.1% (median: 23.3%), while rates of undertreatment ranged from 10.0%-45.1% (median: 34.6%). Few studies assessed the relationship between nontreatment or undertreatment and clinical outcomes in the evaluated population. Among US outpatients with NVAF and an elevated stroke risk, those undertreated had a higher likelihood of death (HR: 1.22; 95% CI: 1.05-1.41; p=.006) compared to patients treated with OACs. Also, in a separate US study of NVAF patients with varying levels of warfarin exposure, patients with no warfarin exposure had significantly higher rates of ischemic stroke than patients with low adherence (4.41 vs. 1.87 per 100 person-years, p<.001) or high adherence (4.41 vs. 0.72 per 100 person years, p<.001). Conclusion: Rates of nontreatment and undertreatment among NVAF patients with elevated stroke risk remain high and are associated with potentially preventable cardiovascular events and death. Strategies to increase rates of treatment may reduce adverse clinical outcomes.

Objectives: To assess pill burden, health care resource utilization (HRU), and costs among patients with long-term immediate release (IR) hydrocodone use. MethOds: We performed a retrospective analysis of health care claims from 2011-2012 Truven MarketScan® Commercial, Medicare supplemental, and Medicaid Multistate databases. Patients with IR hydrocodone prescription for ≥ 90 days during 6 month baseline period (July 2011-December 2011) with continuous enrollment during baseline and 12 month follow-up periods were selected. The final population was sub-categorized by prescribed coverage days (PCD) of IR hydrocodone during baseline into 90-119, 120-179, and ≥ 180 days. Chi-square or ANOVA analyses were used to test pill burden, HRU and costs (standardized to 2013 US dollars) during baseline and follow-up periods across subpopulations. Results: A total of 36,174 commercial, 32,699 Medicaid, and 8,873 Medicare IR hydrocodone users were selected. In the baseline period, subgroups with longer PCD had significantly more average hydrocodone pills per month yet fewer HRU and medical costs (all p< 0.05). However, during the follow-up period, groups with longer PCD had greater increase in number of inpatient hospitalizations and other types of HRU (length of stay, outpatient hospital visits, office visits, and emergency room visits). The subgroup of patients with PCD < 120 days had lower annual all-cause medical costs during follow-up compared with baseline (decreasing $2,624, $2,955, $4,209 per patient per year in Medicaid, Medicare and commercial patients, respectively), while patients with longer PCD during baseline had increased costs (p< 0.05). For example, Medicaid patients with 120-179 PCD had an increase of $1,874 and those with ≥ 180 PCD had an increase of $4,348. These trends were similar for all insurance types. cOnclusiOns: Extended length of PCD, particularly after 120 days, corresponds with higher patient burden including elevated pill burden and rising HRU and costs in both commercial and public insurance patients with long-term IR hydrocodone use.

Aims: Cost-utility (CU) modeling is a common technique used to determine whether new treatments represent good value for money. As with any modeling exercise, findings are a direct result of methodology choices, which may vary widely. Several targeted immuno-modulators have been launched in recent years to treat moderate-to-severe rheumatoid arthritis (RA) which have been evaluated using CU methods. Our objectives were to identify common and innovative modeling choices in moderateto-severe RA and to highlight their implications for future models in RA. Materials and methods: A systematic literature search was conducted to identify CU models in moderate-to-severe RA published from January 2013 to June 2019. Studies must have included an active comparator and used quality-adjusted life-years (QALYs) as the common measure of effectiveness. Modeling methods were characterized by stakeholder perspective, simulation type, mapping between parameters, and data sources.Results: Thirty-one published modeling studies were reviewed spanning 13 countries and 9 drugs, with common methodological choices and innovations observed among them. Over the evaluated time period, we observed common methods and assumptions that are becoming more prominent in the RA CU modeling landscape, including patient-level simulations, two-stage models combining trial results and real-world evidence, real-world treatment durations, long-term health consequences, and Health Assessment Questionnaire (HAQ)-related hospitalization costs. Models that consider the societal perspective are increasingly being developed as well. Limitations: This review did not consider studies that did not report QALYs as a utility measure, models published only as conference abstracts, or cost-consequence models that did not report an incremental CU ratio. Conclusions: CU modeling for RA increasingly reflects real-world conditions and patient experiences which are anticipated to provide better information in the assessment of health technologies. Future CU models in RA should consider applying the observed advances in modeling choices to optimize their CU predictions and simulation of real-world outcomes.

BackgroundDespite treatment guidelines recommending the use of oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and moderate to high risk of stroke (CHA 2 DS 2 -VASc score ≥1), many patients remain untreated. A study conducted among Medicare beneficiaries with AF and a CHA 2 DS 2 -VASc score of ≥2 found that 51% of patients were not prescribed an OAC despite being eligible for treatment. When left untreated, NVAF poses an enormous burden to society, as stroke events are estimated to cost the US healthcare system about $34 billion each year in both direct medical costs and indirect productivity losses. This research explored the short-term clinical implications and budget impact (BI) of increasing OAC use among Medicare beneficiaries with NVAF. MethodsA decision-analytic model was developed from the payer and societal perspectives to estimate the impact of increasing treatment rates among Medicare-eligible NVAF patients with a moderate-to-high risk of stroke over 1 year. Results of the model compared (1) a base case scenario using literature-derived rates of OAC use, and (2) a hypothetical scenario assuming an absolute 5% increase in overall OAC use. Clinical outcomes included the incremental annual number of ischemic stroke, hemorrhagic stroke, and gastrointestinal bleeding events, and stroke-related deaths. Economic outcomes included incremental annual and per-member per-month (PMPM) direct medical costs for the payer perspective and the incremental sum of annual direct medical and indirect costs from productivity loss and caregiver burden for the societal perspective. ResultsIn total, 1.95 million Medicare patients with NVAF were estimated to be treated with OACs in the base case (3.8% of beneficiaries). In the hypothetical scenario analysis, nearly 200,000 more patients were treated resulting in 3,705 fewer ischemic strokes, 14 fewer gastrointestinal bleeds, 141 more hemorrhagic strokes, and 175 fewer deaths. The total