Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States.

BACKGROUND: In the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), empagliflozin plus standard of care reduced the composite of cardiovascular death or hospitalization for heart failure versus standard of care in adults with heart failure with reduced ejection fraction. This analysis investigated the cost-effectiveness of the 2 regimens from the perspective of US payors. METHODS AND RESULTS: A Markov cohort model was developed based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score quartiles and death. Transition probabilities between health states, risk of cardiovascular/all-cause death, hospitalization for heart failure and adverse events, treatment discontinuation, and health utilities were estimated from trial data. Medicare and commercial payment rates were combined for treatment acquisition, acute event management, and disease management. An annual discount rate of 3% was used. Empagliflozin plus standard of care yielded 18% fewer hospitalizations for heart failure and 6% fewer deaths versus standard of care over a lifetime, providing cost-offsets while adding 0.19 life years and 0.19 quality-adjusted life years at an incremental cost of $16 815/patient. The incremental cost-effectiveness ratio was $87 725/quality-adjusted life years gained. Results were consistent across payors, subpopulations, and in deterministic sensitivity analyses. In probabilistic sensitivity analyses, empagliflozin plus standard of care was cost-effective in 3%, 62%, and 80% of iterations at thresholds of $50 000, $100 000, and $150 000/quality-adjusted life years. CONCLUSIONS: Empagliflozin plus standard of care may prevent hospitalizations for heart failure, extend life, and increase quality-adjusted life years for patients with heart failure with reduced ejection fraction at an acceptable cost for US payors.

A European multinational cost-effectiveness analysis of empagliflozin in heart failure with reduced ejection fraction.

PURPOSE: This research examined the cost-effectiveness of adding empagliflozin to standard of care (SoC) compared with SoC alone for treatment of heart failure with reduced ejection fraction (HFrEF) from the perspective of healthcare payers in the United Kingdom (UK), Spain and France. METHODS: A lifetime Markov cohort model was developed to simulate patients' progression through health states based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The model predicted risk of death, hospitalisation for worsening heart failure (HHF), treatment-related adverse events, and treatment discontinuation each monthly cycle. Clinical inputs and utilities were derived from EMPEROR-Reduced trial data, supplemented by published literature and national costing databases. Costs (2021 pound sterling/euro) and quality-adjusted life-years (QALYs) were discounted annually for the UK (3.5%), Spain (3.0%) and France (2.5%). RESULTS: In the UK, Spain and France, empagliflozin plus SoC yielded additional QALYs (0.19, 0.23 and 0.21) at higher cost (£1185, €1770 and €1183 per patient) than SoC alone, yielding incremental cost-effectiveness ratios of £6152/QALY, €7736/QALY and €5511/QALY, respectively. Reduced HHF incidence provided most cost offsets for empagliflozin plus SoC. Similar results were obtained for a range of subgroups and sensitivity analyses. Probabilistic sensitivity results indicated empagliflozin plus SoC remained cost-effective vs. SoC at willingness-to-pay thresholds of £20,000/QALY, €20,000/QALY and €30,000/QALY in 79.6%, 75.5% and 97.3% of model runs for the UK, Spain and France, respectively. CONCLUSIONS: Empagliflozin added to SoC leads to health benefits for patients with HFrEF and is a cost-effective treatment option for payers in multiple European countries (UK, Spain, France).

Cost-effectiveness models for Alzheimer's disease and related dementias: IPECAD modeling workshop cross-comparison challenge.

INTRODUCTION: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge. METHODS: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross-comparisons were discussed during a structured workshop. RESULTS: A broad concordance was established among participants. Mean 10-year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia). DISCUSSION: The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost-effectiveness outcomes, an important step toward transparent and credible AD models.

The Potential Value-Based Price of a Multi-Cancer Early Detection Genomic Blood Test to Complement Current Single Cancer Screening in the USA.

BACKGROUND: Multi-cancer early detection (MCED) testing could increase detection of cancer at early stages, when survival outcomes are better and treatment costs are lower, but is expected to increase screening costs. This study modeled an MCED test for 19 solid cancers in a US population and estimated the potential value-based price (the maximum price to meet a given willingness to pay) of the MCED test plus current single cancer screening (usual care) compared to usual care alone from a third-party payer perspective over a lifetime horizon. METHODS: A hybrid cohort-level state-transition and decision-tree model was developed to estimate the clinical and economic outcomes of annual MCED testing between age 50 and 79 years. The impact on time and stage of diagnosis was computed using an interception modeling approach, with the consequences of cancer modeled based on stage at diagnosis. The model parameters were mainly sourced from the literature, including a published case-control study to inform MCED test performance. All costs were inflated to 2021 US dollars. RESULTS: Multi-cancer early detection testing shifted cancer diagnoses to earlier stages, with a 53% reduction in stage IV cancer diagnoses, resulting in longer overall survival compared with usual care. Addition of MCED decreased per cancer treatment costs by $5421 and resulted in a gain of 0.13 and 0.38 quality-adjusted life-years across all individuals in the screening program and those diagnosed with cancer, respectively. At a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained, the potential value-based price of an MCED test was estimated at $1196. The projected survival of individuals diagnosed with cancer and the number of cancers detected at an earlier stage by MCED had the greatest impact on outcomes. CONCLUSIONS: An MCED test with high specificity would potentially improve long-term health outcomes and reduce cancer treatment costs, resulting in a value-based price of $1196 at a $100,000/quality-adjusted life-year willingness-to-pay threshold.

The Potential Economic Value of Lecanemab in Patients with Early Alzheimer's Disease Using Simulation Modeling.

INTRODUCTION: Alzheimer's disease (AD) is a progressive, neurodegenerative disease that affects memory, thinking, and behavior and places a substantial economic burden on caregivers and healthcare systems. This early-phase study aimed to model lecanemab, a humanized monoclonal antibody targeting amyloid protofibrils, for patients with early AD, and estimate the potential value-based price (VBP) of lecanemab + standard of care (SoC) compared to SoC alone given an expected product profile of lecanemab informed by data from a phase II trial from payer and societal perspectives using a broad range of willingness-to-pay (WTP) thresholds in the USA. METHODS: A disease simulation model was used to capture how key AD pathology components relate to the clinical and economic presentation of AD. The effects of disease modification and early intervention on disease progression were simulated on the basis of BAN2401-G000-201 trial data as well as published literature. Model outcomes included patient and caregiver quality-adjusted life years (QALYs), total life years, and total care costs including direct medical and non-medical costs for healthcare resource use and indirect costs for caregiving over a lifetime horizon. RESULTS: Lecanemab + SoC was predicted to result in a gain of 0.61 QALYs (societal, 0.64) and a $8707 decrease in total non-treatment costs (societal, $11,214) vs. SoC alone for patients with early AD. For a WTP threshold range of $50,000 to $200,000 per QALY gained, the potential annual VBP of lecanemab was estimated at $9249 (societal, $10,400) to $35,605 (societal, $38,053), respectively. Other patient subsets, treatment stopping rules, and dosing regimens were used to assess the sensitivity of the VBP estimates. CONCLUSION: The early model predicted that lecanemab would potentially improve long-term health outcomes and reduce formal and informal care costs, resulting in a range of VBPs that reflect the value of lecanemab to society.

Evaluation of the Cost-effectiveness of Drug Treatment for Alzheimer Disease in a Simulation Model That Includes Caregiver and Societal Factors.

Importance: The possibility of widespread use of a novel effective therapy for Alzheimer disease (AD) will present important clinical, policy, and financial challenges. Objective: To describe how including different patient, caregiver, and societal treatment-related factors affects estimates of the cost-effectiveness of a hypothetical disease-modifying AD treatment. Design, Setting, and Participants: In this economic evaluation, the Alzheimer Disease Archimedes Condition Event Simulator was used to simulate the prognosis of a hypothetical cohort of patients selected from the Alzheimer Disease Neuroimaging Initiative database who received the diagnosis of mild cognitive impairment (MCI). Scenario analyses that varied costs and quality of life inputs relevant to patients and caregivers were conducted. The analysis was designed and conducted from June 15, 2019, to September 30, 2020. Exposures: A hypothetical drug that would delay progression to dementia in individuals with MCI compared with usual care. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. Results: The model included a simulated cohort of patients who scored between 24 and 30 on the Mini-Mental State Examination and had a global Clinical Dementia Rating scale of 0.5, with a required memory box score of 0.5 or higher, at baseline. Using a health care sector perspective, which included only individual patient health care costs, the ICER for the hypothetical treatment was $192 000 per QALY gained. The result decreased to $183 000 per QALY gained in a traditional societal perspective analysis with the inclusion of patient non-health care costs. The inclusion of estimated caregiver health care costs produced almost no change in the ICER, but the inclusion of QALYs gained by caregivers led to a substantial reduction in the ICER for the hypothetical treatment, to $107 000 per QALY gained in the health sector perspective. In the societal perspective scenario, with the broadest inclusion of patient and caregiver factors, the ICER decreased to $74 000 per added QALY. Conclusions and Relevance: The findings of this economic evaluation suggest that policy makers should be aware that efforts to estimate and include the effects of AD treatments outside those on patients themselves can affect the results of the cost-effectiveness analyses that often underpin assessments of the value of new treatments. Further research and debate on including these factors in assessments that will inform discussions on fair pricing for new treatments are needed.

The Economic Impact of New Therapeutic Interventions on Neuropsychiatric Inventory (NPI) Symptom Scores in Patients with Alzheimer Disease.

BACKGROUND/AIMS: Few studies have modeled individual Neuropsychiatric Inventory (NPI) symptom scores for Alzheimer disease (AD) patients and assessed the value of therapeutic interventions that can potentially impact them. The main objective of this study was to evaluate the impact of new AD symptomatic treatments on relevant health economic outcomes via their potential effects on cognition and neuropsychiatric symptoms such as depression, irritability, anxiety, and sleep disorder. METHODS: We enhanced the previously published AHEAD model (Assessment of Health Economics in Alzheimer's Disease) by including new variables and functional relations to capture the NPI's individual neuropsychiatric symptoms in addition to the total NPI score. This update allowed us to study the longitudinal effect of improvements in specific NPI subscale scores and the downstream impact on outcomes such as psychiatric medication use, survival, and institutional placement. RESULTS: The model base-case results showed that a hypothetical treatment with symptomatic effects on anxiety, depression, and irritability NPI subscales was not cost-effective; however, the treatment's cost-effectiveness was improved once a direct link between NPI subscales and mortality was explored or under relatively stronger treatment effects. CONCLUSION: Treatments that influence specific symptoms within the overall NPI have the potential to improve patient outcomes in a cost-effective way. This model is a useful tool for evaluating target product profiles of drugs with effect on NPI symptoms in early stages of development.

Alzheimer's disease Archimedes condition-event simulator: Development and validation.

INTRODUCTION: Several advances have been made in Alzheimer's Disease (AD) modeling, however, there remains a need for a simulator that represents the full scope of disease progression and can be used to study new disease-modifying treatments for early-stage and even prodromal AD. METHODS: We developed AD Archimedes condition-event simulator, a patient-level simulator with a focus on simulating the effects of early interventions through changes in biomarkers of AD. The simulator incorporates interconnected predictive equations derived from longitudinal data sets. RESULTS: The results of external validations on AD Archimedes condition-event simulator showed that it provides reasonable estimates once compared to literature results on transition to dementia AD, institutionalization, and mortality. A case study comparing a disease-modifying treatment and a symptomatic treatment also showcases the benefits of early treatment. DISCUSSION: The AD Archimedes condition-event simulator is designed to perform economic evaluation on various interventions through close tracking of disease progression and the related clinical outcomes.

Financial impact of ivabradine on reducing heart failure penalties under the Hospital Readmission Reduction Program.

OBJECTIVE: The introduction of the Hospital Readmission Reduction Program (HRRP) has led to renewed interest in developing strategies to reduce 30 day readmissions among patients with heart failure (HF). In this study, a model was developed to investigate whether the addition of ivabradine to a standard-of-care (SoC) treatment regimen for patients with HF would reduce HRRP penalties incurred by a hypothetical hospital with excess 30 day readmissions. RESEARCH DESIGN: A model using a Monte Carlo simulation framework was developed. Model inputs included national hospital characteristics, hospital-specific characteristics, and the ivabradine treatment effect as quantified by a post hoc analysis of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). RESULTS: The model computed an 83% reduction in HF readmission penalty payments in a hypothetical hospital with a readmission rate of 22.95% (excess readmission ratio = 1.056 over the national average readmission rate of 21.73%), translating into net savings of $44,016. A sensitivity analysis indicated that the readmission penalty is affected by the specific characteristics of the hospital, including the readmission rate, size of the ivabradine-eligible population, and ivabradine utilization. CONCLUSIONS: The results of this study indicate that the addition of ivabradine to an SoC treatment regimen for patients with HF may lead to a reduction in the penalties incurred by hospitals under the HRRP. This highlights the role ivabradine can play as part of a wider effort to optimize the care of patients with HF.

Cost-Effectiveness of Ivabradine for Heart Failure in the United States.

BACKGROUND: Ivabradine is a heart rate-lowering agent approved to reduce the risk of hospitalization for worsening heart failure. This study assessed the cost-effectiveness of adding ivabradine to background therapy in the United States from the perspective of a commercial or Medicare Advantage payer. METHODS AND RESULTS: A cost-effectiveness, cohort-based Markov model using a state transition approach tracked a cohort of heart failure patients with heart rate ≥70 beats per minute in sinus rhythm who were treated with ivabradine+background therapy or background therapy alone. Model inputs, including adjusted hazard ratios, rates of hospitalization and mortality, adverse events, and utility-regression equations, were derived from a large US claims database and SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial). In the commercial population, ivabradine+background therapy was associated with a cost savings of $8594 versus the cost of background therapy alone over a 10-year time horizon, primarily because of reduced hospitalization. Ivabradine was associated with an incremental benefit of 0.24 quality-adjusted life years over a 10-year time horizon. In the Medicare Advantage population, the incremental cost-effectiveness ratio for ivabradine was estimated to be $24 920/quality-adjusted life years. CONCLUSIONS: The cost-effectiveness model suggests that for a commercial population, the addition of ivabradine to background therapy was associated with cost savings and improved clinical outcomes. For a Medicare Advantage population, the analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost.

Cost-effectiveness of DTG + ABC/3TC versus EFV/TDF/FTC for first-line treatment of HIV-1 in the United States.

OBJECTIVE: Data from the SINGLE trial demonstrated that 88% of treatment-naïve HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG + ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate long-term cost-effectiveness of DTG + ABC/3TC vs EFV/TDF/FTC from a US payer perspective. METHODS: This study is an individual discrete-event simulation which tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, clinical events occurrence (opportunistic infections, cancer, and cardiovascular events), treatment switch, and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy, and safety of DTG + ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent treatment lines, clinical event risks, mortality, cost, and utility inputs were based on literature and expert opinion. Outcomes were lifetime discounted medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with EFV/TDF/FTC, DTG + ABC/3TC increased lifetime costs by $19,153 and per person survival by 0.12 QALYs, resulting in an ICER of $158,890/QALY. ICERs comparing DTG + ABC/3TC to EFV/TDF/FTC remained above the traditional, US willingness-to-pay threshold of $50,000/QALY gained in all scenarios, and above $100,000 or $150,000/QALY gained in most scenarios. LIMITATIONS: Due to data limitations, the treatment patterns, CD4 count during viral rebound and treatment switch, viral rebound after trial end, and long-term adverse event-related treatment discontinuation were based on assumptions, presented to and approved by clinical experts. CONCLUSIONS: Compared with EFV/TDF/FTC, DTG + ABC/3TC resulted in higher cost and only slightly increased QALYs over a lifetime, with an ICER that exceeded the standard cost-effectiveness threshold. This indicates that the incremental benefit in effectiveness associated with DTG + ABC/3TC may not be worth the incremental increase in costs.

Cost-effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC for first-line treatment of HIV-1 in the United States.

INTRODUCTION: Data from the SINGLE trial demonstrated that 88% of treatment-naive HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG+ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate the long-term cost-effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC from a US payer perspective. MATERIALS AND METHODS: An individual discrete-event simulation model tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, occurrence of clinical events (opportunistic infections, cancer and cardiovascular events), treatment switch and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy and safety of DTG+ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent lines of treatment, clinical event risks, mortality, cost and utility inputs were based on literature and expert opinion. Outcomes were lifetime medical costs, quality-adjusted life-years (QALYs) (both discounted at 3% per annum) and the incremental cost-effectiveness ratio (ICER). RESULTS: Compared with EFV/TDF/FTC, DTG+ABC/3TC increased lifetime costs by $58,188 and per-person survival by 0.12 QALYs, resulting in an ICER of $482,717/QALY. In sensitivity analyses testing conservative assumptions about EFV/TDF/FTC's efficacy beyond the trial period, ICERs comparing DTG+ABC/3TC to EFV/TDF/FTC remained high (lowest reported ICER of $365,662/QALY). In a scenario in which the price of EFV/TDF/FTC was reduced by 10% to reflect the potential for price reduction as EFV goes off patent, DTG+ABC/3TC's ICER compared to EFV/TDF/FTC was $600,916/QALY. When DTG+ABC/3TC's price was reduced by 10%, the resulting ICER comparing DTG+ABC/3TC to EFV/TDF/FTC was $302,171/QALY. CONCLUSIONS: Compared with EFV/TDF/FTC, DTG+ABC/3TC resulted in substantially higher cost, slightly better QALY over lifetime, and ICERs far exceeding standard cost-effectiveness thresholds, indicating that the incremental benefit in efficacy associated with DTG+ABC/3TC may not be worth the incremental increase in costs.