Going Forward: Potential Impact of Protein-Based COVID-19 Vaccination Coverage on Population Outcomes and Costs in the United States.

Policymakers in the United States (US) recommend coronavirus disease 2019 (COVID-19) vaccination with a monovalent 2023-2024 vaccine formulation based on the Omicron XBB.1.5 variant. We estimated the potential US population-level health and economic impacts of increased COVID-19 vaccine coverage that might be expected with the availability of a protein-based vaccine with simpler storage requirements in addition to messenger ribonucleic acid (mRNA) vaccines. A Markov model was developed to estimate 1-year COVID-19-related costs, cases, hospitalizations, and deaths with and without the availability of a protein-based vaccine option. The model population was stratified by age and risk status. Model inputs were sourced from published literature or derived from publicly available data. Our model estimated that a five-percentage-point increase in coverage due to the availability of a protein-based vaccine option would prevent over 500,000 cases, 66,000 hospitalizations, and 3000 COVID-19-related deaths. These clinical outcomes translated to 42,000 quality-adjusted life years (QALYs) gained and an incremental cost-effectiveness ratio of USD 16,141/QALY from a third-party payer perspective. In sensitivity analyses, outcomes were most sensitive to COVID-19 incidence and severity across age groups. The availability of a protein-based vaccine option in the US could reduce hospitalizations and deaths and is predicted to be cost-effective.

Low-molecular-weight heparins for the prevention of recurrent venous thromboembolism in patients with cancer: A systematic literature review of efficacy and cost-effectiveness.

BACKGROUND: Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. METHODS: A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. RESULTS: Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. CONCLUSIONS: The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.

Assessing the Value of Biosimilars: A Review of the Role of Budget Impact Analysis.

Biosimilar drugs are highly similar to an originator (reference) biologic, with no clinically meaningful differences in terms of safety or efficacy. As biosimilars offer the potential for lower acquisition costs versus the originator biologic, evaluating the economic implications of the introduction of biosimilars is of interest. Budget impact analysis (BIA) is a commonly used methodology. This review of published BIAs of biosimilar fusion proteins and/or monoclonal antibodies identified 12 unique publications (three full papers and nine congress posters). When evaluated alongside professional guidance on conducting BIA, the majority of BIAs identified were generally in line with international recommendations. However, a lack of peer-reviewed journal articles and considerable shortcomings in the publications were identified. Deficiencies included a limited range of cost parameters, a reliance on assumptions for parameters such as uptake and drug pricing, a lack of expert validation, and a limited range of sensitivity analyses that were based on arbitrary ranges. The rationale for the methods employed, limitations of the BIA approach, and instructions for local adaptation often were inadequately discussed. To understand fully the potential economic impact and value of biosimilars, the impact of biosimilar supply, manufacturer-provided supporting services, and price competition should be included in BIAs. Alternative approaches, such as cost minimization, which requires evidence demonstrating similarity to the originator biologic, and those that integrate a range of economic assessment methods, are needed to assess the value of biosimilars.

Dalteparin versus vitamin K antagonists for the prevention of recurrent venous thromboembolism in patients with cancer and renal impairment: a Canadian pharmacoeconomic analysis.

BACKGROUND: Patients with cancer are at increased risk of venous thromboembolism (VTE) and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA) is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al), extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002). A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011). To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. METHODS: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs). RESULTS: For the entire CLOT trial population (n=676), the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001). However, the utility assessment revealed that 21 of 24 respondents (88%) selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200-$Can25,800) per QALY gained. The analysis in patients with renal impairment suggested even better economic value with the cost per QALY gained being <$14,000. CONCLUSION: Extended duration dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer, especially in those with renal impairment.

Dalteparin or vitamin K antagonists to prevent recurrent venous thromboembolism in cancer patients: a patient-level economic analysis for France and Austria.

BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. METHODS: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. RESULTS: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries. CONCLUSIONS: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.