A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020).

BACKGROUND: Heart failure presents a growing clinical and economic burden in the USA. Robust cost data on the burden of illness are critical to inform economic evaluations of new therapeutic interventions. OBJECTIVES: This systematic literature review of heart failure-related costs in the USA aimed to assess the quality of the published evidence and provide a narrative synthesis of current data. METHODS: Four electronic databases (MEDLINE, EMBASE, EconLit, and the Centre for Reviews and Dissemination York Database, including the NHS Economic Evaluation Database and Health Technology Assessment Database) were searched for journal articles published between January 2014 and March 2020. The review, registered with PROSPERO (CRD42019134201), was restricted to cost-of-illness studies in adults with heart failure events in the USA. RESULTS: Eighty-seven studies were included, 41 of which allowed a comparison of cost estimates across studies. The annual median total medical costs for heart failure care were estimated at $24,383 per patient, with heart failure-specific hospitalizations driving costs (median $15,879 per patient). Analyses of subgroups revealed that heart failure-related costs are highly sensitive to individual patient characteristics (such as the presence of comorbidities and age) with large variations even within a subgroup. Additionally, differences in study design and a lack of standardized reporting limited the ability to compare cost estimates. The finding that costs are higher for patients with heart failure with reduced ejection fraction compared with patients with preserved ejection fraction highlights the need for differentiating among different heart failure types. CONCLUSIONS: The review underpins the conclusion drawn in earlier reviews, namely that hospitalization costs are the key driver of heart failure-related costs. Analyses of subgroups provide a clearer understanding of sources of heterogeneity in cost data. While current cost estimates provide useful indications of economic burden, understanding the nuances of the data is critical to support its application.

Anti-vascular endothelial growth factor in neovascular age-related macular degeneration - a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems.

BACKGROUND: Systematically review the evidence describing the impact of anti-vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. METHODS: A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. RESULTS: The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients' VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment). CONCLUSIONS: The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.

Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making.

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

A new method for valuing health: directly eliciting personal utility functions.

BACKGROUND: Standard methods for eliciting the preference data upon which 'value sets' are based generally have in common an aim to 'uncover' people's preferences by asking them to evaluate a subset of health states, then using their responses to infer their preferences over all dimensions and levels. An alternative approach is to ask people directly about the relative importance to them of the dimensions, levels and interactions between them. This paper describes a new stated preference approach for directly eliciting personal utility functions (PUFs), and reports a pilot study to test its feasibility for valuing the EQ-5D. METHODS: A questionnaire was developed, designed to directly elicit PUFs from general public respondents via computer-assisted personal interviews, with a focus on helping respondents to reflect and deliberate on their preferences. The questionnaire was piloted in England. RESULTS: Seventy-six interviews were conducted in December 2015. Overall, pain/discomfort and mobility were found to be the most important of the EQ-5D dimensions. The ratings for intermediate improvements in each dimension show heterogeneity, both within and between respondents. Almost a quarter of respondents indicated that no EQ-5D health states are worse than dead. DISCUSSION: The PUF approach appears to be feasible, and has the potential to yield meaningful, well-informed preference data from respondents that can be aggregated to yield a value set for the EQ-5D. A deliberative approach to health state valuation also has the potential to complement and develop existing valuation methods. Further refinement of some elements of the approach is required.

Capsaicin 8% Patch Versus Oral Neuropathic Pain Medications for the Treatment of Painful Diabetic Peripheral Neuropathy: A Systematic Literature Review and Network Meta-analysis.

PURPOSE: A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch (capsaicin 8% patch) compared with oral, centrally acting agents (ie, pregabalin, gabapentin, duloxetine, amitriptyline) in patients with painful diabetic peripheral neuropathy (PDPN). METHODS: A systematic search of EMBASE/MEDLINE, Cochrane Library, and the National Health Service Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects was conducted to identify all randomized controlled trials. Data from eligible studies according to predefined inclusion and exclusion criteria were extracted, and analyses were based on aggregate-level data. Efficacy outcomes were the proportions of patients with ≥30% and ≥50% reductions in pain, and tolerability outcomes were somnolence, dizziness, nausea, diarrhea, constipation, headache, fatigue, insomnia, and rate of discontinuation due to adverse events (AEs). Data were analyzed by using a Bayesian NMA. Fixed and random effects models were estimated. Relative treatment effect was presented as odds ratios (ORs) with 95% CIs. Sources of heterogeneity were assessed. FINDINGS: The NMA included 25 randomized controlled trials. For ≥30% pain reduction, the capsaicin 8% patch was significantly more effective than placebo (OR, 2.28 [95% CI, 1.19-4.03]), exhibited a numerical advantage compared with pregabalin (OR, 1.83 [95% CI, 0.91-3.34]) and gabapentin (OR, 1.66 [95% CI, 0.74-3.23]), and had similar efficacy compared with duloxetine (OR, 0.99 [95% CI, 0.5-1.79]). The evidence available was not sufficient to assess the relative efficacy of amitriptyline. In the NMA for tolerability, the capsaicin 8% patch was only included for headache because the incidence was 0% for the other outcomes. Oral, centrally acting agents had a significantly elevated risk compared with placebo for somnolence (pregabalin, gabapentin, duloxetine, and amitriptyline), dizziness (pregabalin, gabapentin, duloxetine, and amitriptyline), nausea (duloxetine), diarrhea (duloxetine), fatigue (duloxetine), and discontinuation because of AEs (pregabalin, gabapentin, and duloxetine). Compared with pregabalin and gabapentin, duloxetine had a significantly lower risk of dizziness but a significantly higher risk of nausea. IMPLICATIONS: This NMA suggests that the efficacy observed with the capsaicin 8% patch is similar to that observed with oral agents (ie, pregabalin, duloxetine, gabapentin) in patients with PDPN. The oral agents were associated with a significantly elevated risk of somnolence, dizziness, fatigue, and discontinuation because of AEs compared with placebo. The capsaicin 8% patch was as effective as oral centrally acting agents in these patients with PDPN but offers systemic tolerability benefits.