Cost Offset of Dapagliflozin in the US Medicare Population with Cardio-Kidney Metabolic Syndrome.

INTRODUCTION: Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter 2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type 2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy. METHODS: All US 2022 Medicare beneficiaries (≥ 65 years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin. RESULTS: In a population of 13.1 million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355 fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3 billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3 billion; hSoC, $211.0 billion). CONCLUSION: By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon. Graphical abstract available for this article.

Clinical and Economic Value of Reducing Antimicrobial Resistance in the Management of Hospital-Acquired Infections with Limited Treatment Options in Greece.

INTRODUCTION: Antimicrobial resistance (AMR) is a major public health threat worldwide. Greece has the highest burden of infections due to antibiotic-resistant bacteria among European Union/European Economic Area (EU/EEA) countries. One of the most serious AMR threats in Greece is hospital-acquired infections (HAIs) with limited treatment options (LTO) caused by resistant gram-negative pathogens. Thus, this study sought to estimate the current AMR burden in Greece and the value of reducing AMR to gram-negative pathogens for the Greek healthcare system. METHODS: The current model was adapted from a previously published and validated model of AMR to investigate the overall and AMR-specific burden of treating the most common HAIs with LTO in Greece and scenarios to demonstrate the benefits associated with reducing AMR levels from a third-party payer perspective. Clinical and economic outcomes were estimated over a 10-year time horizon; life years (LYs) and quality-adjusted life years (QALYs) were calculated over a lifetime (based on the annual number of infections over 10 years) at a willingness-to-pay of €30,000 per QALY gained and a 3.5% discount rate. RESULTS: In Greece, the current AMR levels in HAIs with LTO caused by four gram-negative pathogens account for > 316,000 hospital bed days, €73 million in hospitalisation costs, and > 580,000 LYs and 450,000 QALYs lost over 10 years. The monetary burden is estimated at €13.9 billion. A reduction in current AMR levels by 10-50% results in clinical and economic benefit; 29,264-151,699 bed days may be saved, leading to decreased hospitalisation costs (€6.8 million-€35.3 million) and a gain in LYs (85,328-366,162) and QALYs (67,421-289,331), associated with a monetary benefit of between €2.0 billion and €8.7 billion. CONCLUSION: This study shows the substantial clinical and economic burden AMR represents to the Greek healthcare system and the value that can be achieved by effectively reducing AMR levels.

Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.

INTRODUCTION: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making. METHODS: A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied. RESULTS: Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million. DISCUSSION: Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here. CONCLUSION: These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.

An Economic Evaluation Estimating the Clinical and Economic Burden of Increased Vancomycin-Resistant Enterococcus faecium Infection Incidence in Japan.

INTRODUCTION: While incidence rates of vancomycin-resistant Enterococcus faecium have remained comparatively low in Japan, there have been increasing reports of more vancomycin-resistant Enterococcus (VRE) outbreaks, requiring costly measures to contain. Increased incidence of VRE in Japan may lead to more frequent and harder to contain outbreaks with current control measures, causing a significant burden to the healthcare system in Japan. This study aimed to demonstrate the clinical and economic burden of vancomycin-resistant E. faecium infections to the Japanese healthcare system and the impact of increasing rates of vancomycin resistance. METHODS: A de novo deterministic analytic model was developed to assess the health economic outcomes of treating hospital-acquired VRE infections; patients are treated according to a two-line treatment strategy, dependent on their resistance status. The model considers hospitalisation costs and the additional cost of infection control. Scenarios investigated the current burden of VRE infections and the additional burden of increased incidence of VRE. Outcomes were assessed over a 1-year and 10-year time horizon from a healthcare payer's perspective in a Japanese setting. Quality-adjusted life years (QALYs) were valued with a willingness-to-pay threshold of ¥5,000,000 ($38,023), and costs and benefits were discounted at a rate of 2%. RESULTS: Current VRE incidence levels in enterococcal infections in Japan equates to ¥130,209,933,636 ($996,204,669) in associated costs and a loss of 185,361 life years (LYs) and 165,934 QALYs over 10 years. A three-fold increase (1.83%) is associated with an additional ¥4,745,059,504 ($36,084,651) in total costs on top of the current cost burden as well as an additional loss of 683 LYs over a lifetime, corresponding to 616 QALYs lost. CONCLUSION: Despite low incidence rates, VRE infections already represent a substantial economic burden to the Japanese healthcare system. The substantial increase in costs associated with a higher incidence of VRE infections could result in a significant economic challenge for Japan.

Estimating the Clinical and Economic Impact of Introducing a New Antibacterial into Greek Clinical Practice for the Management of Hospital-Acquired Infections with Limited Treatment Options.

INTRODUCTION: Hospital-acquired infections (HAIs) and growing antimicrobial resistance (AMR) represent a significant healthcare burden globally. Especially in Greece, HAIs with limited treatment options (LTO) pose a serious threat due to increased morbidity and mortality. This study aimed to estimate the clinical and economic value of introducing a new antibacterial for HAIs with LTO in Greece. METHODS: A previously published and validated dynamic model of AMR was adapted to the Greek setting. The model estimated the clinical and economic outcomes of introducing a new antibacterial for the treatment of HAIs with LTO in Greece. The current treatment pathway was compared with introducing a new antibacterial to the treatment sequence. Outcomes were assessed from a third-party payer perspective, over a 10-year transmission period, with quality-adjusted life years (QALYs) and life years (LYs) gained considered over a lifetime horizon. RESULTS: Over the next 10 years, HAIs with LTO in Greece account for approximately 1.4 million hospital bed days, hospitalisation costs of more than €320 million and a loss of approximately 403,000 LYs (319,000 QALYs). Introduction of the new antibacterial as first-line treatment provided the largest clinical and economic benefit, with savings of up to 93,000 bed days, approximately €21 million in hospitalisation costs and an additional 286,000 LYs (226,000 QALYs) in comparison to the current treatment strategy. The introduction of a new antibacterial was linked to a monetary benefit of €6.8 billion at a willingness to pay threshold of €30,000 over 10 years. CONCLUSION: This study highlights the considerable clinical and economic benefit of introducing a new antibacterial for HAIs with LTO in Greece. This analysis shows the additional benefit when a new antibacterial is introduced to treatment sequences. These findings can be used to inform decision makers to implement policies to ensure timely access to new antibacterial treatments in Greece.

Antimicrobial resistance is a major issue for the Greek healthcare system. The overuse of antibacterial agents contributes to the growing resistance levels, making currently available treatment options less effective. As a result, there is an imperative need to address antimicrobial resistance in Greece. This study developed a mathematical model to investigate the clinical and economic benefits of introducing a new antibacterial to current treatment practice. The model uses regression equations to describe the relationships between inputs and outputs from a published and validated model, which describes the transmission and treatment of infections. The model is used to estimate the impact of a new treatment in Greece, considering differing treatment sequence scenarios. The largest health and financial benefits were seen when a new antibacterial was introduced at first line prior to currently used treatments. Over 10 years, savings of up to 93,000 hospital bed days and €21 million in hospitalisation costs could be achieved, as well as a gain of 286,000 patient life years and 226,000 patient quality-adjusted life years (QALYs), a measure of a patient's quality and length of life, over their remaining lifetime. The introduction of a new antibacterial into the current treatment pathway resulted in an overall monetary benefit of €6.8 billion over 10 years, when additional QALYs are valued at €30,000. This study demonstrates considerable health economic benefits of introducing a new antibacterial in Greece and can help inform decision makers when developing a national action plan to combat resistance and improve access to treatments.