Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol Despite Statin Use: A Threshold Analysis.

BACKGROUND: Inclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US. OBJECTIVE: The aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds. DESIGN, SETTING AND PARTICIPANTS: A lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0-1 years, 1-2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy. INTERVENTIONS: Inclisiran as an adjunct to standard of care, compared with standard of care alone. MAIN OUTCOMES AND MEASURES: The threshold price of inclisiran. RESULTS: Inclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. CONCLUSIONS AND RELEVANCE: This study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.

Modeling in Real Time During the Ebola Response.

To aid decision-making during CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC activated a Modeling Task Force to generate estimates on various topics related to the response in West Africa and the risk for importation of cases into the United States. Analysis of eight Ebola response modeling projects conducted during August 2014-July 2015 provided insight into the types of questions addressed by modeling, the impact of the estimates generated, and the difficulties encountered during the modeling. This time frame was selected to cover the three phases of the West African epidemic curve. Questions posed to the Modeling Task Force changed as the epidemic progressed. Initially, the task force was asked to estimate the number of cases that might occur if no interventions were implemented compared with cases that might occur if interventions were implemented; however, at the peak of the epidemic, the focus shifted to estimating resource needs for Ebola treatment units. Then, as the epidemic decelerated, requests for modeling changed to generating estimates of the potential number of sexually transmitted Ebola cases. Modeling to provide information for decision-making during the CDC Ebola response involved limited data, a short turnaround time, and difficulty communicating the modeling process, including assumptions and interpretation of results. Despite these challenges, modeling yielded estimates and projections that public health officials used to make key decisions regarding response strategy and resources required. The impact of modeling during the Ebola response demonstrates the usefulness of modeling in future responses, particularly in the early stages and when data are scarce. Future modeling can be enhanced by planning ahead for data needs and data sharing, and by open communication among modelers, scientists, and others to ensure that modeling and its limitations are more clearly understood. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Preventive malaria treatment for contacts of patients with Ebola virus disease in the context of the west Africa 2014-15 Ebola virus disease response: an economic analysis.

BACKGROUND: After the detection of an Ebola virus disease outbreak in west Africa in 2014, one of the elements of the response was to contact trace and isolate patients in specialised Ebola treatment units (ETUs) at onset of fever. We aimed to assess the economic feasibility of administering preventive malaria treatment to all contacts of patients with Ebola virus disease, to prevent the onset of febrile malaria and subsequent admission to ETUs. METHODS: We used a decision tree model to analyse the costs of preventive malaria treatment (artemisinin-based combination treatment [ACT]) for all contacts of patients with Ebola virus disease (in terms of administration and averted ETU-stay costs) and benefits (in terms of averted ETU admissions) in west Africa, from a health-care provider perspective. The period of analyses was 1 year, which is roughly similar to the duration of the 2014-15 west Africa Ebola outbreak response. We calculated the intervention's cost per ETU admission averted (average cost-effectiveness ratio) by season (wet and dry), country (Liberia, Sierra Leone, and Guinea), and age of contact (<5 years, 5-14 years, and ≥15 years). We did sensitivity analyses to assess how results varied with malaria parasite prevalence (in children aged 2-10 years), daily cost of ETU stay (for Liberian malaria incidence levels), and compliance and effectiveness of preventive malaria treatment. FINDINGS: Administration of ACTs to contacts of patients with Ebola virus disease was cost saving for contacts of all ages in Liberia, Sierra Leone, and Guinea, in both seasons, from a health-care provider perspective. In the wet season, preventive malaria treatment was estimated to reduce the probability of a contact being admitted to an ETU by a maximum of 36% (in Guinea, for contacts aged <5 years), and a minimum of 10% (in Guinea and Sierra Leone, for those aged ≥15 years). Assuming 85% compliance and taking into account the African population pyramid, the intervention is expected to be cost saving in contacts of all age groups in areas with malaria parasite prevalence in children aged 2-10 years as low as 10%. In Liberia during the wet season, malaria preventive treatment was cost saving even when average daily bed-stay costs were as low as US$5 for children younger than 5 years, $9 for those aged 5-14 years, and $22 for those aged 15 years or older. INTERPRETATION: Administration of preventive malaria treatment to contacts of patients with Ebola virus disease should be considered by public health officials when addressing Ebola virus disease outbreaks in countries and seasons where malaria reaches high levels of transmission. FUNDING: Centers for Disease Control and Prevention.