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An evaluation was conducted to predict the economic and clinical burden of vaccinating all immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines versus BNT162b2 variant-adapted vaccines in Fall 2023 and Spring 2024 in France. The number of symptomatic SARS-CoV-2 infections, hospitalizations or deaths due to COVID-19, and long COVID cases, costs and quality-adjusted life years (QALYs) were estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from the original and BA.4/5 variant-adapted vaccines, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were evaluated in sensitivity analyses. In an ideal situation where 100% coverage is achieved, the mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs gained. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.

Objectives: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes., Methods: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences., Results: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB., Conclusions: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model., Methods: The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2-4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted., Results: Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses., Conclusion: In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population., (© 2024. The Author(s).)

Background: Venous thromboembolism (VTE) is a serious complication following orthopedic shoulder surgery; however, research is limited involving the break-even cost-effectiveness of VTE prophylaxis. The purpose of this study was to determine whether the cost of aspirin and enoxaparin would break even for VTE prevention in patients following shoulder surgery., Methods: A drug retail database was used to obtain the lowest price for a course of aspirin (81 mg) and enoxaparin (40 mg) to perform a break-even cost analysis. Our institutional purchasing records were then searched to estimate the cost of treating a symptomatic VTE. The TriNetX national database was queried to establish a rate of VTE after shoulder surgery. A break-even cost analysis was performed by determining the absolute risk reduction (ARR). This value was used to calculate the number of patients who are treated to prevent a single VTE while breaking even on cost. Sensitivity analyses were performed for drugs that did not break even at the database-derived VTE rates., Results: Full medication courses of aspirin and enoxaparin were found to cost $1.18 and $125.37, respectively. The cost of treating a symptomatic VTE was determined to be $9407.00. Data from the TriNetX database showed rates of symptomatic VTE following shoulder arthroplasty, hemiarthroplasty, and arthroscopic rotator cuff repair of 1.60%, 1.50%, and 0.68%, respectively. Aspirin broke even on cost for all procedures if the initial rate decreased by an ARR of 0.01% (number needed to treat, 7972). Similarly, enoxaparin broke even for shoulder arthroplasty and hemiarthroplasty if the initial rate of VTE decreased by an ARR of 1.33% (number needed to treat, 75). Enoxaparin did not break even at the initial VTE rate for arthroscopic rotator cuff repair; however, sensitivity analysis found enoxaparin would break even if the drug could be obtained at a cost of ≤$60.00. Enoxaparin broke even if the cost of treating a symptomatic VTE was ≥$20,000.00., Conclusions: The cost of a 3-week course of twice-daily aspirin or once-daily enoxaparin breaks even for VTE prophylaxis following shoulder arthroplasty and hemiarthroplasty if these drugs reduce the VTE rate by a calculated ARR. Given the lower rate of VTE observed for patients undergoing arthroscopic rotator cuff repair, only the 3-week course of aspirin broke even under these conditions. Once-daily enoxaparin did not break even at current market rate. Further research is needed to help determine optimal VTE prophylaxis after shoulder surgery., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: The first direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection were reimbursed via Australia's Pharmaceutical Benefits Scheme (PBS) in March 2016. This was based on the recommendation from the Pharmaceutical Benefits Advisory Committee (PBAC) that the regimens would be acceptably cost-effective at an incremental cost-effectiveness ratio (ICER) no greater than $15,000/quality-adjusted life-year (QALY). Since the initial PBS listings for DAA therapies and subsequent listings of newer DAA treatments such as glecaprevir/pibrentasvir (Maviret ® ), the demographics and some of the disease characteristics of currently treated patients have markedly changed. This analysis aims to reassess the cost-effectiveness of glecaprevir/pibrentasvir, accounting for the changes to the HCV population currently seeking treatment and incorporating retreatment in first-line failures and the treatment of new infections in previously treated individuals., Methods: To assess the cost-effectiveness 7 years after initial listing of DAAs, an update was made to the Markov model used to achieve PBS reimbursement for Viekira-Pak ® in May 2016. Amendments to the Viekira-Pak ® model include: changes to baseline age and fibrosis distribution of treated patients, and inclusion of retreatment of first-line failures [those not achieving a sustained virologic response (SVR12)] and reinfected individuals. Treatment-related inputs including SVR12 response rates, adverse events, treatment-related disutility, and discontinuations were sourced from pivotal glecaprevir/pibrentasvir clinical trials., Results: Using the published price of glecaprevir/pibrentasvir, the ICER is below $15,000/QALY., Conclusions: Despite changes in demographics and disease characteristics of treated patients, and changes to the model structure to reflect retreatment in clinical practice in Australia, DAAs remain cost-effective in 2023., (© 2024. The Author(s).)

This paper thoroughly explores the feasibility, challenges, and proposed solutions for establishing a sustainable human colony on Mars. We quantitatively and qualitatively analyze the Martian environment, highlighting key challenges such as radiation exposure, which astronauts could experience at minimum levels of 0.66 sieverts during a round trip, and the complications arising from Mars' thin atmosphere and extreme temperature variations. Technological advancements are examined, including developing Martian concrete, which utilizes sulfur as a binding agent, and innovative life support strategies like aeroponics and algae bioreactors. The human aspect of colonization is addressed, focusing on long-term space habitation's psychological and physiological impacts. We also present a cost-benefit analysis of in-situ resource utilization versus Earth-based supply missions, emphasizing economic viability with the potential reduction in launch costs through reusable rocket technology. A timeline for the colonization process is suggested, spanning preliminary unmanned missions for resource assessment, followed by short-term manned missions leading to sustainable settlements over several decades. The paper concludes with recommendations for future research, particularly in refining resource utilization techniques and advancing health and life support systems, to solidify the foundation for Mars colonization. This comprehensive assessment aims to guide researchers, policymakers, and stakeholders in planning and executing a strategic and informed approach to making Mars colonization a reality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Sulfuryl fluoride (SF) is a fumigant used to eliminate drywood termites (DWT: Kalotermitidae; Froggatt) and other structural pests. Because of its global warming potential, it has been suggested that SF be restricted as a greenhouse gas (GHG). We present an economic model to assess the net social cost of restricting SF. We consider 3 approaches to address DWT control- no treatment, allowing SF fumigation and localized treatments, and only local treatment. Each approach generates private and public benefits and costs. We estimate that the annual damage and home equity loss by DWT in California is US$4.5-16.8 billion without treatment. If fumigation is used on 20% of the houses and local treatments on the others, the combined social cost of treatment, damage, and GHG emissions are between US$1-US$2 billion annually. The annual cost of local treatments only would be between US$3.2 and US$4.9 billion. If the application of SF is severely restricted or banned, the social costs will increase between US$1.43 and US$4.31 billion annually. The implied cost per ton of CO2 eliminated is between US$624 and US$1,465, much above the price range of CO2 in other applications. The restriction/ban has significant equity and environmental effects, impacting low-income individuals living in rented properties and replacing damaged wood in housing will increase GHG emissions. We further recommend the continued use of SF until a comparable whole-structure alternative is developed that fits the parameters of our model., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health and economic implications of calprotectin as a predictive tool to initiate antimicrobial therapy in a cohort of critically ill patients. Thus, data obtained from a previously published study on calprotectin as a hypothetical early biomarker of bacterial infections in critically ill patients were evaluated regarding the potential cost-effective impact of early analysis of calprotectin on an earlier start of antibiotic treatment. Under the assumption that calprotectin is used predictively and comparators (white blood cells, procalcitonin, and C-reactive protein) are used diagnostically, a cost-effective impact of EUR 11,000-12,000 per patient would be obtained. If calprotectin would be used predictively and comparators would be used predictively for 50% of patients, it is hypothesized that cost-effectiveness would be between EUR 6000 and 7000 per patient, based on reduced stay in the ICU and general ward, respectively. Furthermore, predictive use of calprotectin seems to reduce both mortality and the length of hospital stay. This health economic analysis on the predictive use of plasma calprotectin, which facilitates clinical decision making in cases of suspected sepsis, indicates that such determination has a cost-saving and life-saving impact on the healthcare system.

Computable general equilibrium (CGE) models provide valuable insights into economy-wide impacts of anticipated future structural changes in the transportation sector, yet few CGE models offer detailed transportation representations. We use an enhanced Applied Dynamic Analysis of the Global Economy (ADAGE) CGE model to incorporate disaggregated transportation modes and technologies in on-road passenger and freight transportation. We assess the impacts of these inclusions on U.S. transportation patterns, energy consumption and greenhouse gas emissions. Simulating illustrative global oil price cases with and without transportation detail, we find subsector mode disaggregation and technology additions in a CGE model significantly alter the impacts of oil prices on global trade and freight patterns, energy consumption, and greenhouse gas (GHG) emissions. We find that: (1) alternative technologies are essential for capturing transportation sector impacts, (2) electrification may reduce emissions with electricity decarbonization, and (3) higher oil prices may hasten electrification.

In this work, process models were developed to capture the impact of biomanufacturing costs on a commercial scale and emphasize the way in which facility design and operation must balance meeting product demand while minimizing production costs. Using a scenario-based modeling approach, several facility design strategies were evaluated, including a traditional large stainless-steel facility and a small footprint, portable-on-demand (POD)-based facility. Bioprocessing platforms were compared by estimating their total production costs across different facility types and specifically illustrating how continuous bioprocessing has gained in popularity as a novel and cost-effective approach to manufacture high-quality biopharmaceuticals. The analysis showed how fluctuations in market demand have a dramatic effect on manufacturing costs and plant utilization, with far-reaching implications on the total cost to patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘During the writing of this article, the authors were employees of Just-Evotec Biologics, Inc.’., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Introduction: Recurrent Clostridioides difficile infection (rCDI) is common and associated with considerable clinical and economic consequences. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We sought to evaluate cost-effectiveness of FMBL compared to standard of care (SOC) from a US third-party payer perspective among patients with one or more (≥ 1) recurrences., Methods: A Markov model with a lifetime time horizon was developed. The model population included adult patients who had ≥ 1 recurrence after a primary CDI episode and had completed ≥ 1 round of antibiotics, or had ≥ 2 severe CDI episodes resulting in hospitalization within the last year. The model consisted of six health states with an 8-week model cycle: rCDI, absence of CDI after recurrence, colectomy, ileostomy, ileostomy reversal, and death. Drug costs and rCDI-related medical costs were estimated in 2022 US dollars and discounted at 3% annually. Deterministic sensitivity analyses were performed., Results: Compared to SOC, FMBL at $9000/course resulted in an incremental cost-effectiveness ratio (ICER) of $18,727 per quality-adjusted life year (QALY) gained. The incremental cost was $5336 (FMBL $79,236, SOC $73,900) and the incremental effectiveness was 0.285 QALYs (FMBL 10.346, SOC 10.061). The cumulative drug acquisition and administration costs for the FMBL and SOC arms were $24,245 and $16,876, while rCDI-related medical costs for FMBL and SOC were $54,991 and $57,024, respectively. The ICER in the subgroup of patients at first recurrence was $13,727 per QALY gained. FMBL remained cost-effective across all sensitivity analyses., Conclusions: FMBL was found to be cost-effective compared to SOC for the prevention of rCDI with more benefits among patients at first recurrence, with an ICER far below the payer ICER threshold of $100,000. Patients treated with FMBL experienced higher total QALYs and reduced healthcare resource utilization, including reduced hospitalizations., (© 2023. The Author(s).)

Introduction: Patients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3 years following introduction from a third-party US payer perspective., Methods: A decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3 years were estimated in 2022 US dollars. One-way sensitivity analyses were performed., Results: For an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an» average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3 years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022., Conclusions: FMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence., (© 2023. The Author(s).)

Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost., Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States., Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences., Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH., Funding: The Center for Disease Control and Prevention., Competing Interests: MMR reports contract for work on cervical cancer elimination modeling in South Africa, not related to the manuscript, from World Health Organization, travel and lodging support for attending a research project meeting at the World Health Organization headquarters in Geneva, Switzerland, not related to the manuscript, from World Health Organization. YL reports postdoctoral fellowship stipend (2020–2022) from Harvard T. H. Chan School of Public Health, not related to the manuscript. SY reports doctoral stipend from New York University Grossman School of Medicine, not related to the manuscript. All other authors report no potential conflicts., (© 2023 The Author(s).)

Although social distancing can effectively contain the spread of infectious diseases by reducing social interactions, it may have economic effects. Crises such as the COVID-19 pandemic create dilemmas for policymakers because the long-term implementation of restrictive social distancing policies may cause massive economic damage and ultimately harm healthcare systems. This paper proposes an epidemic control framework that policymakers can use as a data-driven decision support tool for setting efficient social distancing targets. The framework addresses three aspects of the COVID-19 pandemic that are related to social distancing or community mobility data: modeling, financial implications, and policy-making. Thus, we explore the COVID-19 pandemic and concurrent economic situation as functions of historical pandemic data and mobility control. This approach allows us to formulate an efficient social distancing policy as a stochastic feedback control problem that minimizes the aggregated risks of disease transmission and economic volatility. We further demonstrate the use of a deep learning algorithm to solve this control problem. Finally, by applying our framework to U.S. data, we empirically examine the efficiency of the U.S. social distancing policy., (© 2021 Elsevier B.V. All rights reserved.)

Background: Limited data are available describing the global impact of COVID-19 vaccines. This study estimated the global public health and economic impact of COVID-19 vaccines before the emergence of the Omicron variant., Methods: A static model covering 215 countries/territories compared the direct effects of COVID-19 vaccination to no vaccination during 13 December 2020-30 September 2021. After adjusting for underreporting of cases and deaths, base case analyses estimated total cases and deaths averted, and direct outpatient and productivity costs saved through averted health outcomes. Sensitivity analyses applied alternative model assumptions., Results: COVID-19 vaccines prevented an estimated median (IQR) of 151.7 (133.7-226.1) million cases and 620.5 (411.1-698.1) thousand deaths globally through September 2021. In sensitivity analysis applying an alternative underreporting assumption, median deaths averted were 2.1 million. Estimated direct outpatient cost savings were $21.2 ($18.9-30.9) billion and indirect savings of avoided productivity loss were $135.1 ($121.1-206.4) billion, yielding a total cost savings of $155 billion globally through averted infections., Conclusions: Using a conservative modeling approach that considered direct effects only, we estimated that COVID-19 vaccines have averted millions of infections and deaths, generating billions of cost savings worldwide, which underscore the continued importance of vaccination in public health response to COVID-19.

Introduction: Many diseases have a sequential treatment pathway. Compared with patients without previous treatment, patients who fail initial treatment may have lower success rates with a second treatment. This phenomenon can be explained by a correlation between treatment effects., Methods: We developed a statistical model of covariance for the underlying unobserved correlation between treatments and established a mathematical expression for the magnitude of the latent correlation term. We conducted a simulation study of clinical trials to investigate the correlation between two treatments and explored clinical examples based on published literature to illustrate the identification and evaluation of these correlations., Results: Our simulation study confirmed that a treatment correlation reduces the probability of success for the second treatment, compared with no correlation. We found that treatment correlations may be observable in clinical trials, such as for depression and lung cancer, and the magnitude of correlation may be estimated. We illustrated that treatment correlations can be incorporated into an economic model, with possible impacts on cost-effectiveness results. Additional applications of correlation concepts are also discussed., Conclusions: We evaluated the correlation between treatment effects and our approach can be applied to clinical trial design and economic modeling of sequential clinical treatment pathways.

Background: Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model., Methods: The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective., Results: The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates., Conclusion: Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.

Background: Early diagnosis of sepsis has been shown to reduce treatment delays, increase appropriate care, and reduce mortality. The sepsis machine learning algorithm NAVOY® Sepsis, based on variables routinely collected at intensive care units (ICUs), has shown excellent predictive properties. However, the economic consequences of forecasting the onset of sepsis are unknown. Objectives: The potential cost and cost-effectiveness impact of a machine learning algorithm forecasting the onset of sepsis was estimated in an ICU setting. Methods: A health economic model has been developed to capture short-term and long-term consequences of sepsis. The model is based on findings from a randomized, prospective clinical evaluation of NAVOY® Sepsis and from literature sources. Modeling the relationship between time from sepsis onset to treatment and prevalence of septic shock and in-hospital mortality were of particular interest. The model base case assumes that the time to treatment coincides with the time to detection and that the algorithm predicts sepsis 3 hours prior to onset. Total costs include the costs of the prediction algorithm, days spent at the ICU and hospital ward, and long-term consequences. Costs are estimated for an average patient admitted to the ICU and for the healthcare system. The reference method is sepsis diagnosis in accordance with clinical practice. Results: In Sweden, the total cost per patient amounts to €16 436 and €16 512 for the algorithm and current practice arms, respectively, implying a potential cost saving per patient of €76. The largest cost saving is for the ICU stay, which is reduced by 0.16 days per patient (5860 ICU days for the healthcare sector) resulting in a cost saving of €1009 per ICU patient. Stochastic scenario analysis showed that NAVOY® Sepsis was a dominant treatment option in most scenarios and well below an established threshold of €20 000 per quality-adjusted life-year. A 3-hour faster detection implies a reduction in in-hospital mortality, resulting in 356 lives saved per year. Conclusions: A sepsis prediction algorithm such as NAVOY® Sepsis reduces the cost per ICU patient and will potentially have a substantial cost-saving and life-saving impact for ICU departments and the healthcare system., Competing Interests: The Swedish Institute for Health Economics (IHE), where OE and JH are employed, has received compensation from AlgoDx AB to conduct the research upon which this manuscript is based. AlgoDx AB is also sponsoring an ongoing study for prospective evaluation of the algorithm used in this manuscript, and FS’s institution is reimbursed for costs related to performing that study. IP and JS are shareholders of AlgoDx AB.

Background : In the United Kingdom (UK), a cell-based quadrivalent influenza vaccine (QIVc) and a recombinant vaccine (QIVr) are recommended for eligible adults under 65 years. The objective of this analysis was to determine the potential cost-effectiveness of QIVc compared to QIVr for this age group using a range of assumptions about relative vaccine effectiveness (rVE). Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The list price was £12.50 for QIVc and £22.00 for QIVr. The base case effectiveness of QIVc was 63.9%. As there are no data comparing the vaccines in the 18 to 64-year-old age group, rVE was varied. Results: For the base case, the rVE of QIVr compared with QIVc must be at least 25% in order for the cost per quality-adjusted life-year gained to be £20,000 or lower. Sensitivity analysis demonstrated that the rVE required for QIVr to be cost-effective was most dependent on the absolute effectiveness of QIVc. Conclusion: At list prices, our analysis predicts that the rVE for QIVr must be at least 25% compared to QIVc in order to be considered cost-effective.

The cost-effectiveness of genetic screen-and-treat strategies for women at increased risk for breast and ovarian cancer often depends on the women's willingness to make use of risk-reducing mastectomy (RRM) or salpingo-oophorectomy (RRSO). To explore the uptake rates of RRM and RRSO applied in health economic modeling studies and the impact of uptake rates on the incremental cost-effectiveness ratios (ICER), we conducted a scoping literature review. In addition, using our own model, we conducted a value of information (VOI) analysis. Among the 19 models included in the review, the uptake rates of RRM ranged from 6% to 47% (RRSO: 10% to 88%). Fifty-seven percent of the models applied retrospective data obtained from registries, hospital records, or questionnaires. According to the models' deterministic sensitivity analyses, there is a clear trend that a lower uptake rate increased the ICER and vice versa. Our VOI analysis showed high decision uncertainty associated with the uptake rates. In the future, uptake rates should be given more attention in the conceptualization of health economic modeling studies. Prospective studies are recommended to reflect regional and national variations in women's preferences for preventive surgery.

Background: As the body of evidence on COVID-19 and post-vaccination outcomes continues to expand, this analysis sought to evaluate the public health impact of the Pfizer-BioNTech COVID-19 Vaccine, BNT162b2, during the first year of its rollout in the US., Methods: A combined Markov decision tree model compared clinical and economic outcomes of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) versus no vaccination in individuals aged ≥12 years. Age-stratified epidemiological, clinical, economic, and humanistic parameters were derived from existing data and published literature. Scenario analysis explored the impact of using lower and upper bounds of parameters on the results. The health benefits were estimated as the number of COVID-19 symptomatic cases, hospitalizations and deaths averted, and Quality Adjusted Life Years (QALYs) saved. The economic benefits were estimated as the amount of healthcare and societal cost savings associated with the vaccine-preventable health outcomes., Results: It was estimated that, in 2021, the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to averting almost 9 million symptomatic cases, close to 700,000 hospitalizations, and over 110,000 deaths, resulting in an estimated $30.4 billion direct healthcare cost savings, $43.7 billion indirect cost savings related to productivity loss, as well as discounted gains of 1.1 million QALYs. Scenario analyses showed that these results were robust; the use of alternative plausible ranges of parameters did not change the interpretation of the findings., Conclusions: The Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to generate substantial public health impact and vaccine-preventable cost savings in the first year of its rollout in the US. The vaccine was estimated to prevent millions of COVID-19 symptomatic cases and thousands of hospitalizations and deaths, and these averted outcomes translated into cost-savings in the billions of US dollars and thousands of QALYs saved. As only direct impacts of vaccination were considered, these estimates may be conservative.

Background: Hepatitis C virus (HCV) genotype 1 is the most prevalent HCV infection in China. Sofosbuvir-based direct antiviral agent (DAA) regimens are the current mainstays of treatment. Sofosbuvir/velpatasvir (SOF/VEL) and sofosbuvir/ledipasvir (SOF/LDV) regimens became reimbursable in China in 2020. Thus, this study aimed to identify the optimal SOF-based regimen and to inform efficient use of healthcare resources by optimizing DAA use in treating HCV genotype 1. Methods and Models: A modeling-based cost-utility analysis was conducted from the payer's perspective targeting adult Chinese patients with chronic HCV genotype 1 infection. Direct medical costs and health utilities were inputted into a Markov model to simulate lifetime experiences of chronically infected HCV patients after receiving SOF/LDV, SOF/VEL or the traditional strategy of pegylated interferon (pegIFN) + ribavirin (RBV). Discounted lifetime cost and quality adjusted life years (QALYs) were computed and compared to generate the incremental cost utility ratio (ICUR). An ICUR below the threshold of 31,500 $/QALY suggests cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model findings. Results: Both SOF/LDV and SOF/VEL regimens were dominant to the pegIFN + RBV regimen by creating more QALYs and incurring less cost. SOF/LDV produced 0.542 more QALYs but cost $10,390 less than pegIFN + RBV. Relative to SOF/LDV, SOF/VEL had an ICUR of 168,239 $/QALY which did not meet the cost-effectiveness standard. Therefore SOF/LDV was the optimal strategy. These findings were robust to linear and random variations of model parameters. However, reducing the SOF/VEL price by 40% would make this regimen the most cost-effective option. Conclusions: SOF/LDV was found to be the most cost-effective treatment, and SOF/VEL was also economically dominant to pegIFN + RBV. These findings indicated that replacing pegIFN + RBV with DAA regimens could be a promising strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Cao, Shi, Naidoo, Semba, Wang, Fan and Zhu.)

Introduction: Published estimates of Alzheimer's disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-β (Aβ+) pathology across the disease continuum., Methods: Patient-level longitudinal data from the National Alzheimer's Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages-asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia-and death were measured as transition probabilities. Rates were assessed in "incident" patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that predicted an individual's health state as a function of health state at the previous visit and adjusted for time between initial and follow-up visits, age, sex, years of education, and concomitant symptomatic AD medications., Results: Annual transition probabilities to more severe dementia stages for surviving incident Aβ+ patients were as follows: asymptomatic to MCI-AD, 40.8%; MCI-AD to mild AD dementia or worse, 21.8%; mild AD dementia to moderate AD dementia or worse, 35.9%; moderate AD dementia to severe AD dementia, 28.6%. Transition probabilities to less severe dementia stages were: 5.3% annual reversion from MCI-AD to asymptomatic, 3.0% mild AD dementia to MCI-AD, 1.8% moderate AD dementia to mild AD dementia, and 1.3% for severe AD dementia to moderate AD dementia., Conclusions: These transition probabilities reflect the full continuum of AD progression in Aβ+ individuals and can be used to assess the impact of treatment on expected transitions., (© 2021. The Author(s).)

In the United Kingdom (UK), both the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose QIV (QIV-HD) are preferred for persons aged 65 years and older but only aQIV is reimbursed by the National Health Service (NHS). The objective was to determine the potential cost-effectiveness of vaccinating adults aged 65 years and above with aQIV compared with QIV-HD in the UK. A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the impact of vaccination in 10 influenza seasons. Vaccine effectiveness was based on a meta-analysis that concluded the vaccines were not significantly different. Vaccine coverage, physician visits, hospitalizations, deaths, utility losses and NHS costs were estimated using published UK sources. The list price of aQIV was £11.88 while a range of prices were tested for QIV-HD. The price of the trivalent high-dose vaccine (TIV-HD) is £20.00 but a list price for QIV-HD is not yet available. The projected differences between the vaccines in terms of clinical cases and influenza treatment costs are minimal. Our analysis demonstrates that in order to be cost-effective, the price of QIV-HD must be similar to that of aQIV and may range from £7.57 to £12.94 depending on the relative effectiveness of the vaccines. The results of the analysis were most sensitive to variation in vaccine effectiveness and the rate of hospitalization due to influenza. Given the evidence, aQIV is cost-saving unless QIV-HD is priced lower than the existing list price of TIV-HD.

Background: In response to COVID-19, the UK National Health Service (NHS) extended influenza vaccination in 50- to 64-year-olds from at-risk only to all in this age group for the 2020/21 season. The objective of this research is to determine the cost-effectiveness of continuing to vaccinate all with a quadrivalent cell-based vaccine (QIVc) compared to returning to an at-risk only policy after the pandemic resolves., Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The base case effectiveness of QIVc was 63.9% and the list price was GBP 9.94., Results: Vaccinating 50% of all 50- to 64-year-olds with QIVc reduced the average annual number of clinical infections (-682,000), hospitalizations (-5800) and deaths (-740) in the UK. The base case incremental cost per quality-adjusted life-year gained (ICER) of all compared to at-risk only was GBP6000 (NHS perspective). When the cost of lost productivity was considered, vaccinating all 50- to 64-year-olds with QIVc became cost-saving., Conclusion: Vaccinating all 50- to 64-year-olds with QIVc is likely to be cost-effective. The NHS should consider continuing this policy in future seasons.

There is consumer pressure on the US beef cattle industry to minimize antibiotic use (ABU) in order to aid in the global antimicrobial resistance mitigation efforts. Our objective was to estimate the economic costs of ABU constraints in a conceptual US integrated beef supply chain (IBSC) to aid the beef industry in mitigating the ever-increasing risk of antimicrobial resistance, by reducing their ABU. An IBSC network model was developed and differentiated into 37 different nodes of production. Each node could only raise a specific type of animals, differentiated based on the production technique and animal health status. The cost, as well as the weight gain coefficient, was estimated for each node, using an IBSC cost of production model. Linear programming solutions to this network model provided the least cost path of beef supply through the system, under various ABU constraints. The cost as well as weight gain coefficient of the 37 nodes, initial supply of 28.5 million calves weighing 0.65 million metric tons, and final demand of 16.14 million metric tons of slaughter-ready fed cattle were used as inputs/constraints to the three different linear programming scenarios, with different ABU constraints. Our first scenario, which placed no constraint on ABU, estimated that the minimum total economic cost to meet the final beef demand was $38.6 billion. The optimal solution was to use only the high health status calves for beef production. Because low health calves occur in the beef system, our second scenario required all the calves irrespective of their health status to be used, which increased the system cost to $41.5 billion. Thus, the value of only producing high health status calves is $2.9 billion. Our third scenario, which restricted feedlots from using antibiotics even for low health calves, incurred a total cost of $41.9 billion for antibiotic-free beef production. We concluded that the additional cost of $367 million for implementing antibiotic-free beef production is relatively low, ~0.90% of the minimum cost incurred for the conventional beef supply chain (model 2 cost of $41.5 billion). However, a much higher cost savings is obtained by producing only high health status calves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kaniyamattam, Tauer and Gröhn.)

While substantial public health investment in anti-smoking initiatives has had demonstrated benefits on health and fiscal outcomes, similar investment in reducing obesity has not been undertaken, despite the substantial burden obesity places on society. Anti-obesity medications (AOMs) are poorly prescribed despite evidence that weight loss is not sustained using other strategies alone.We used a simulation model to estimate the potential impact of 100% uptake of AOMs on Medicare and Medicaid spending, disability payments, and taxes collected relative to status quo with negligible AOM use. Relative to status quo, AOM use simulation would result in Medicare and Medicaid savings of $231.5 billion and $188.8 billion respectively over 75 years. Government tax revenues would increase by $452.8 billion. Overall, the net benefit would be $746.6 billion. Anti-smoking efforts have had substantial benefits for society. A similar investment in obesity reduction, including broad use of AOMs, should be considered.

The epistemic value of models has traditionally been approached from a representational perspective. This paper argues that the artifactual approach evades the problem of accounting for representation and better accommodates the modal dimension of modeling. From an artifactual perspective, models are viewed as erotetic vehicles constrained by their construction and available representational tools. The modal dimension of modeling is approached through two case studies. The first portrays mathematical modeling in economics, while the other discusses the modeling practice of synthetic biology, which exploits and combines models in various modes and media. Neither model intends to represent any actual target system. Rather, they are constructed to study possible mechanisms through the construction of a model system with built-in dependencies., Competing Interests: Conflict of interestThe author declares that she has no conflict of interest., (© The Author(s) 2021.)

Aims: Ravulizumab, engineered from eculizumab, provides sustained C5 inhibition in atypical hemolytic uremic syndrome (aHUS) while reducing dosing frequency (every 8 vs 2 weeks, respectively). Treatment choice often carries significant financial implications. This study compared the economic consequences of ravulizumab and eculizumab for treating aHUS., Materials and Methods: A cost-minimization model compared direct medical costs for ravulizumab and eculizumab in treating aHUS, assuming equivalent efficacy and safety, and took a US payer perspective, a lifetime horizon, and a 3.0% cost discount rate. The base case modeled adult and pediatric treatment-naïve populations, with characteristics based on clinical trials, and treatment patterns (duration, discontinuation, re-initiation) derived from eculizumab studies with long-term follow-up. Treatment costs (2019 US$) were based on wholesale drug acquisition costs, Centers for Medicare & Medicaid fee schedules, and published disease management studies. Sensitivity analyses were conducted by adjusting relevant variables., Results: Ravulizumab provided lifetime per-patient cost reductions (discounted) of 32.4% and 35.5% vs eculizumab in adult and pediatric base cases, respectively. Total costs for ravulizumab vs eculizumab were $12,148,748 and $17,979,007, respectively, for adults, and $11,587,832 and $17,959,814, respectively, for children. Pre-discontinuation treatment contributed the largest proportion of total costs for ravulizumab (94.8% and 88.0%) and eculizumab (94.8% and 87.8%) in adults and children, respectively. Across sensitivity analyses, ravulizumab provided cost reductions vs eculizumab., Limitations: The model included several typical assumptions. Base case patients with more severe stages of chronic kidney disease were assumed not to discontinue treatment, nor to experience an excess mortality risk in either treatment arm, which may not reflect real-world clinical observations. Additionally, rebates and discounts on medication acquisition or administration were not considered., Conclusions: In US patients with aHUS, ravulizumab provided cost reductions of 32.4-35.5% vs eculizumab, with a reduced dosing frequency for ravulizumab. The magnitude of reductions was consistent across sensitivity analyses.

Objectives: We conduct a cost-utility analysis of inotuzumab ozogamicin (INO) versus chemotherapy as the standard of care (SOC) for adults with relapsed or refractory B cell acute lymphoblastic leukemia., Methods: A Markov model incorporating transition probabilities between health states was applied to simulate disease progression. The model inputs, including overall survival, progression-free survival, and utility parameters, were obtained from the INO-VATE ALL trial and literatures. The Taiwan Cancer Registry Database and the Health and Welfare Database were utilized to identify the patient cohort and medical costs from the perspective of National Health Insurance Administration. The lifetime medical costs (in 2017 US dollars), quality-adjusted life years (QALYs) gained, and associated incremental cost-effectiveness ratio (ICER) were the main study outcomes., Results: The lifetime medical costs for INO and SOC were $176,795 and $69,496, and the QALYs gained were 2.25 and 0.84, respectively. The ICER for INO versus SOC was $76,044 per QALY gained, which is slightly more than three times Taiwan's gross domestic product per capita (i.e., $73,224). Favorable economic results for INO versus SOC were found with an increased time horizon for model simulation, less discounting for the future benefit, and higher stem cell transplantation (SCT) rate after INO treatment; and among patients aged less than 55 years, with no SCT history, or in the first salvage treatment., Conclusions: INO versus SOC has higher costs but is more effective. The use of INO is favorable for patients in the early treatment course and when more future benefit associated with INO is considered.

Porcine reproductive and respiratory syndrome (PRRS) causes substantial financial losses in pig farms and economic losses to societies worldwide. Vaccination against PRRS virus (PRRSV) is a common intervention in affected farms. The aim of this study was to assess the economic impact and profitability of potential new PRRS vaccines with improved efficacy at animal, herd, and national level. Two vaccination strategies were modeled; (i) mass vaccination of sows only (MS) and (ii) mass vaccination of sows and vaccination of piglets (MSP), comprising different scenarios of vaccine effectiveness, vaccine price, and vaccination coverage. A farrow-to-finish farm with 1,000 working sows from a pig-dense region in Germany served as an example farm. Financial benefits were obtained from gross margin analyses and were defined as difference in gross margin between a PRRSV-infected farm without vaccination (baseline) and with vaccination (intervention). Financial benefits were highest if both sows and piglets (MSP) were vaccinated. In these scenarios, median annual net benefits per working sow ranged from €170 to 340. If sows only were vaccinated (MS), estimated benefits attributable to vaccination were between €148 and 270. Decisive variables for the estimation of national level benefits were the number of farmers switching from existing to a better protecting vaccine, the number of previously non-vaccinating herds adopting the new vaccine, and the effectiveness of the new vaccine relative to those already available. Benefits were greatest when the new vaccine was adopted by previously non-vaccinating herds. The analyses showed that vaccination against PRRS was beneficial for all modeled scenarios. The magnitude of benefits derived from vaccination was more susceptible to changes in vaccination effectiveness than to vaccine price changes. This study provides evidence to support future vaccine development. The estimates indicate that the introduction of more efficient vaccines might lead to substantial financial benefits, is of socio-economic importance and that new vaccines might significantly contribute to the reduction of disease burden., (Copyright © 2020 Thomann, Rushton, Schuepbach-Regula and Nathues.)

With their article, Grutters et al raise an important question: What do successful health technology assessments (HTAs) look like, and what is their real-world utility in decision-making? While many HTAs are published in peer-reviewed journals, many are considered proprietary and their attributes remain confidential, limiting researchers' ability to answer these questions. Models for economic evaluations like cost-effectiveness analyses (CEAs) synthesize a wide range of evidence, are often statistically and mathematically sophisticated, and require untestable assumptions. As such, there is nearly universal agreement among researchers that enhancing transparency is an important issue in health economic modeling. However, the definition of transparency and guidelines for its implementation vary. Model registration combined with a linked database of model-based economic evaluations has been proposed as a solution, whereby registered models and their accompanying technical and nontechnical documentation are sourced into a single publicly-available repository, ideally in a standardized format to ensure consistent and complete representation of features, code, data sources, results, validation exercises, and policy recommendations. When such a repository is ultimately created, modelers will not have to reinvent the wheel for every new drug launched or new treatment pathway. These more open and transparent approaches will have substantial implications for model accuracy, reliability, and validity, improving trust and acceptance by healthcare decision-makers., (© 2020 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Respiratory syncytial virus (RSV) is the most common cause of pediatric acute lower respiratory tract infection worldwide. Detailed data on the health and economic burden of RSV disease are lacking from tropical settings with year-round RSV transmission. We developed a statistical and economic model to estimate the annual incidence and healthcare cost of medically attended RSV disease among young children in Singapore, using Monte Carlo simulation to account for uncertainty in model parameters. RSV accounted for 708 hospitalizations in children <6 months of age (33.5/1,000 child-years) and 1,096 in children 6-29 months of age (13.2/1,000 child-years). The cost of hospitalization was SGD 5.7 million (US $4.3 million) at 2014 prices; patients bore 60% of the cost. RSV-associated disease burden in tropical settings in Asia is high and comparable to other settings. Further work incorporating efficacy data from ongoing vaccine trials will help to determine the potential cost-effectiveness of different vaccination strategies.

Background: In order to facilitate sound economic evaluations of novel treatments, health-economic models of polycythemia vera (PV) must combine effects on surrogate endpoints in trials with disease progression (DP) and mortality in long-term cohort data., Objective: We validate an economic model for PV that uses Janus Kinase 2 (JAK2) burden as a surrogate endpoint to predict DP (thrombosis, myelofibrosis, and acute leukemia) and overall survival (OS) based on progression-specific mortality., Methods: Long-term observational studies that include information about baseline JAK2 burden were identified via PubMed searches and used to validate the model. Kaplan-Meier (KM) OS curves were extracted using a digitizing software. External validity of the model was analyzed by visually comparing OS curves of the model with the KM curves of the included studies, as well as calculating differences in mean OS estimated as area under the curve (AUC)., Results: The model's predictions of cumulative DP were somewhat lower than the published studies. Over 20 years' time, our base case model predicted a mean OS for a PV patient (15.0-16.5 years), which was in line with the published studies (15.8-17.5 years). Modeled mean OS was almost two years longer (1.6-1.9 years) for patients with JAK2 <50% than patients with JAK2 ≥50%. Only three long-term observational studies that satisfied the predefined criteria were found and could be used in the validation, but these studies did not capture JAK2 evolution over time. Improved model predictions of DP and mortality based on the longitudinal evolution of JAK2 could be derived from real-world data sources. Such data are currently scarce and future observational studies should be designed to capture the long-term impact of JAK2 on DP and mortality in PV., Conclusions: Our model, based on JAK2 burden as a marker for DP, generated OS estimations that are in line with results of published data.

Aims: Cost-utility (CU) modeling is a common technique used to determine whether new treatments represent good value for money. As with any modeling exercise, findings are a direct result of methodology choices, which may vary widely. Several targeted immuno-modulators have been launched in recent years to treat moderate-to-severe rheumatoid arthritis (RA) which have been evaluated using CU methods. Our objectives were to identify common and innovative modeling choices in moderate-to-severe RA and to highlight their implications for future models in RA. Materials and methods: A systematic literature search was conducted to identify CU models in moderate-to-severe RA published from January 2013 to June 2019. Studies must have included an active comparator and used quality-adjusted life-years (QALYs) as the common measure of effectiveness. Modeling methods were characterized by stakeholder perspective, simulation type, mapping between parameters, and data sources. Results: Thirty-one published modeling studies were reviewed spanning 13 countries and 9 drugs, with common methodological choices and innovations observed among them. Over the evaluated time period, we observed common methods and assumptions that are becoming more prominent in the RA CU modeling landscape, including patient-level simulations, two-stage models combining trial results and real-world evidence, real-world treatment durations, long-term health consequences, and Health Assessment Questionnaire (HAQ)-related hospitalization costs. Models that consider the societal perspective are increasingly being developed as well. Limitations: This review did not consider studies that did not report QALYs as a utility measure, models published only as conference abstracts, or cost-consequence models that did not report an incremental CU ratio. Conclusions: CU modeling for RA increasingly reflects real-world conditions and patient experiences which are anticipated to provide better information in the assessment of health technologies. Future CU models in RA should consider applying the observed advances in modeling choices to optimize their CU predictions and simulation of real-world outcomes.

Epidemiological data establish that lameness is second only to mastitis as the dairy industry's most prevalent and costly animal welfare issue. Using an automatic lameness detection (ALD) system in which continuous, accurate detection is coupled with proper treatment, is key for reducing economic losses due to lameness. It is reasonable to assume that the cost of lameness would vary with its severity. Therefore, our first objective was to estimate the cost of different lameness severity levels as a function of milk production, lameness risk, conception probability, and treatment cost using a dynamic programming (DP) model. Our second objective was to conduct a cost benefit analysis for ALD systems which can reduce production losses through early detection and treatment of lameness, when compared to visual-detection (VD; i.e., performed by humans) systems. The default production loss parameters for the VD system used as inputs to the DP model were either sourced from the literature or were estimated based on data from a field trial. The production loss parameters for the ALD system used as inputs to the DP model were based on extrapolations of parameter values used for the VD system. The profit per present cow per year under assumed expenses and revenues decreased from $426.05 (when lameness incidence was assumed to be 0%) to $389.69 when lameness incidence was 19.5 %. Out of the 19.5 % lameness incidence in our default scenario, 9.8 % were moderate cases and 9.7 % were severe cases. Average cost of lameness was $36.36 at 19.5 % incidence. Average cost of lameness increased with increased incidence and was respectively $82.05, $195.05, and $286.87 at the low, medium, and high incidence scenarios. We used an operational framework which compared the lameness costs between the VD and ALD systems with 25 %, 50 % and 75 % net avoided costs (NAC) for the 10 year lifespan of the ALD system, at default, low, medium and high lameness incidence scenarios. The net return per cow per year from using an ALD system over a VD system was $13, at low incidence and 25 % NAC. The net return per cow per year for the ALD system was as high as $99 at high incidence and 75 % NAC. Out of 351 (3 system prices, 3 system efficiencies, 3 levels of lameness incidence and 13 different herd sizes) scenarios tested, 295 resulted in a net profit within the system lifespan of 10 years, thus justifying the investment in ALD systems., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of this study was to estimate, from an obesity prevention perspective, the cost-effectiveness of two potential policies that increase the price of alcohol in Australia: a volumetric tax applied to all alcohol (Intervention 1) and a minimum unit floor price (Intervention 2). Estimated changes in alcoholic drink consumption and corresponding changes in energy intake were calculated using the 2011-12 Australian Health Survey data, published price elasticities, and nutrition information. The incremental changes in body mass index (BMI), BMI-related disease outcomes, healthcare costs, and Health Adjusted Life Years (HALYs) were estimated using a validated model. Costs associated with each intervention were estimated for government and industry. Both interventions were estimated to lead to reductions in mean alcohol consumption (Intervention 1: 20.7% (95% Uncertainty Interval (UI): 20.2% to 21.1%); Intervention 2: 9.2% (95% UI: 8.9% to 9.6%); reductions in mean population body weight (Intervention 1: 0.9 kg (95% UI: 0.84 to 0.96); Intervention 2: 0.45 kg (95% UI: 0.42 to 0.48)); HALYs gained (Intervention 1: 566,648 (95% UI: 497,431 to 647,262); Intervention 2: 317,653 (95% UI: 276,334 to 361,573)); and healthcare cost savings (Intervention 1: $5.8 billion (B) (95% UI: $5.1B to $6.6B); Intervention 2: $3.3B (95% UI: $2.9B to $3.7B)). Intervention costs were estimated as $24M for Intervention 1 and $30M for Intervention 2. Both interventions were dominant, resulting in health gains and cost savings. Increasing the price of alcohol is likely to be cost-effective from an obesity prevention perspective in the Australian context, provided consumers substitute alcoholic beverages with low or no kilojoule alternatives.

Background: By design, existing scenario-based nutrition economics studies on the financial benefits of healthy dietary behaviors generally report uncertainty in inputs and wide ranges of outcome estimates., Objectives: This modeling exercise aimed to establish precision in prediction of the potential healthcare cost savings that would follow a reduction in the incidence of cardiovascular disease (CVD) consistent with an increase in adherence to a Mediterranean-style diet (MedDiet)., Design: Using a Monte Carlo simulation model on a cost-of-illness analysis assessing MedDiet adherence, CVD incidence reduction, and healthcare cost savings in the United States and Canada, short- and long-term cost savings that are likely to accrue to the American and Canadian healthcare systems were estimated using 20 and 80% increases in MedDiet adherence scenarios., Results: Increasing percentage of population adhering to a MedDiet by 20% beyond the current adherence level produced annual savings in CVD-related costs of US$8.2 billion (95% confidence interval [CI], $7.5-$8.8 billion) in the United States and Can$0.32 billion (95% CI, $0.29-$0.34 billion) in Canada. An 80% increase in adherence resulted in savings equal to US$31 billion (95% CI, $28.6-$33.3 billion) and Can$1.2 billion (95% CI, $1.11-$1.30 billion) in each respective country., Conclusion: Computational techniques with stochastic parameter inputs, such as the Monte Carlo simulation, could be an effective way of incorporating variability of modeling parameters in nutrition economics studies for improved precision in estimating the monetary value of healthy eating habits., Competing Interests: The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2019 Jason P.H. Jones et al.)

Background: The 'German Consortium for Hereditary Breast and Ovarian Cancer' (GC-HBOC) offers women with a family history of breast and ovarian cancer genetic counseling. The aim of this modeling study was to evaluate the cost-effectiveness of genetic testing for BRCA 1/2 in women with a high familial risk followed by different preventive interventions (intensified surveillance, risk-reducing bilateral mastectomy, risk-reducing bilateral salpingo-oophorectomy, or both mastectomy and salpingo-oophorectomy) compared to no genetic test., Methods: A Markov model with a lifelong time horizon was developed for a cohort of 35-year-old women with a BRCA 1/2 mutation probability of ≥ 10%. The perspective of the German statutory health insurance (SHI) was adopted. The model included the health states 'well' (women with increased risk), 'breast cancer without metastases', 'breast cancer with metastases', 'ovarian cancer', 'death', and two post (non-metastatic) breast or ovarian cancer states. Outcomes were costs, quality of life years gained (QALYs) and life years gained (LYG). Important data used for the model were obtained from 4380 women enrolled in the GC-HBOC., Results: Compared with the no test strategy, genetic testing with subsequent surgical and non-surgical treatment options provided to women with deleterious BRCA 1 or 2 mutations resulted in additional costs of €7256 and additional QALYs of 0,43 (incremental cost-effectiveness ratio of €17,027 per QALY; cost per LYG: €22,318). The results were robust in deterministic and probabilistic sensitivity analyses., Conclusion: The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.

Poor mental health has profound economic consequences. Given the burden of poor mental health, the economic case for preventing mental illness and promoting better mental health may be very strong, but too often prevention attracts little attention and few resources. This article describes the potential role that can be played by economic evidence alongside experimental trials and observational studies, or through modeling, to substantiate the need for increased investment in prevention. It illustrates areas of action across the life course where there is already a good economic case. It also suggests some further areas of substantive public health concern, with promising effectiveness evidence, that may benefit from economic analysis. Financial and economic barriers to implementation are then presented, and strategies to address the barriers and increase investment in the prevention of mental illness are suggested.

Background: Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact., Objective: We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER)., Study Design: Retrospective analysis of pharmaceutical sales data., Methods: From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed "unmanaged uptake," and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market)., Results: Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The "unmanaged uptake" assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data., Conclusions: This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S. Gonzalez-McQuire and M. Campioni are employees of Amgen (Europe) GmbH and hold stock. K. Weisel has received consultancy fees and honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Onyx, and Takeda. M.A. Dimopoulos has received honoraria from Amgen, Celgene, Janssen, Novartis, and Takeda. S. Knop has received honoraria from Amgen Germany, Bristol-Myers Squibb, Celgene, Janssen, and Onyx Inc. C. Bennison has acted as consultant for Amgen. W. W. Xu has acted as consultant for Amgen. K. Pantiri has acted as consultant for Amgen. M. Hensen has acted as consultant for Amgen. E. Terpos has received honoraria from Amgen, Celgene, Janssen, Novartis, and Takeda, and research grants from Amgen. W. Bouwmeester has received funding from, and has acted as a consultant for, Amgen. R. Hájek has received funding from Celgene and Amgen and has worked as a consultant for Amgen, Celgene, and Takeda. He has also received honoraria from Amgen. The following authors are employed by the sponsor (Amgen): Sebastian Gonzalez-McQuire and Marco Campioni.

Background: Omadacycline is an oral and intravenous (IV) once-daily aminomethylcycline antibiotic that was recently approved by the US Food and Drug Administration for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). In 2 phase 3 clinical trials, IV-to-oral switch and oral-only administration of omadacycline achieved the primary end points of noninferiority compared with linezolid in treating patients with ABSSSI., Objective: To estimate the potential cost-savings with bioequivalent IV-to-oral antibiotics, such as omadacycline, compared with the standard of care with IV vancomycin by avoiding hospitalizations and reducing hospital stays in patients presenting from the emergency department for ABSSSI treatment., Methods: We used hospital avoidance models to examine the potential cost-savings of managing patients with ABSSSI and no or limited comorbidities and without life-threatening conditions by using omadacycline in the outpatient setting compared with the current standard of care. Early hospital discharge models were used to evaluate the hospital stay reduction that would be required to be achieved with omadacycline treatment relative to IV vancomycin to confer cost-savings compared with standard of care among patients with ABSSSI and ≥2 comorbidities but no life-threatening conditions., Results: In the hospital stay avoidance models, cost-savings may be realized by using therapeutically bioequivalent IV-to-oral antibiotics, such as omadacycline, compared with inpatient treatment with IV vancomycin. Based on a sensitivity analysis, further savings could be possible with outpatient administration of omadacycline, even if 20% of omadacycline outpatients were subsequently admitted and incurred the full inpatient cost, with no reimbursement penalties. Of more than 300 patients, only 1 was admitted to the hospital after a full course of omadacycline in the oral-only clinical trial. In the early hospital discharge models, the maximum cost-minimizing daily expense of omadacycline varied from $173 to $936, depending on the presence of active comorbidities or systemic symptoms, hospital stay reduction, and model perspective., Conclusion: These results suggest that the targeted use of antibiotics with bioequivalent IV-to-oral formulations, such as omadacycline, for select patients with ABSSSI may lead to cost-savings compared with inpatient IV vancomycin treatment by shifting care to the outpatient setting or by facilitating earlier hospital discharge among hospitalized patients.

Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients., Materials and Methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management., Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy., Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves., Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens., Materials and Methods: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes., Results: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10)., Limitations: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant., Conclusions: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.

Our objectives were to develop an economic model to estimate the economic impact of twinning in dairy cows and to evaluate management strategies to mitigate the negative economic impact of twinning in dairy herds. A probabilistic tree considering spontaneous embryo reduction, early pregnancy loss, abortion, metritis, retained placenta, and culling rate at 120 d of the second, at the end of the second, and at the end of the third lactation was developed for a single pregnancy; we also developed 3 management options upon diagnosis of a twin pregnancy: (1) do nothing, (2) induce abortion using PGF 2α , or (3) attempt manual embryo reduction. A value was given to each branch of the tree by simulating cow states on a farm for 1,400 d to encompass 4 consecutive lactations. The incomes considered in the simulations included milk income over feed cost, income from calves, and slaughter value upon culling. The expenses taken into account depending on each branch included additional inseminations and synchronization protocols, embryo reduction, induction of abortion, replacement heifers, and costs due to metritis and retained placenta. The gross value for a singleton pregnancy and the 3 management options upon diagnosis of a twin pregnancy were calculated by adding the value of all braches multiplied by their probability. The costs for the 3 management options were calculated by subtracting its gross value minus the gross value of a singleton pregnancy. The negative economic impact of a twin pregnancy ranged from $97 to $225 depending on the type of twin pregnancy (unilateral vs. bilateral), parity, and DIM when the twin pregnancy occurred. The overall negative economic impact of twinning on dairy farm profitability in the United States was estimated to be $96 million per year. Attempting manual embryo reduction early during gestation upon diagnosis of a twin pregnancy was the optimal management strategy for mitigating the negative economic impact of twinning under a wide variety of scenarios., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

This work presents the optimization and critical evaluation of continuous capture chromatography in the downstream process of a recombinant enzyme. For the upstream manufacturing of this molecule, a perfusion process was implemented due to benefits for product quality and productivity. This process is, however, characterized by low titer and significant changes over the course of the harvest duration in terms of active enzyme concentration and impurity content. We evaluated the feasibility and benefits of a continuous capture operation. This case study illustrates the design approach that can be utilized to address challenges presented by a changing feedstream, and the statistical measures that can be employed to characterize and optimize the operating space under material and time constraints. Process economic modeling in conjunction with Monte Carlo simulations indicate that even for a nonaffinity capture step utilizing a relatively cheap ion-exchange resin, the smaller column volume used in a continuous set-up results in cost savings compared to the batch process. We compare this option to the scenario of repeated processing using a small capture column in batch mode. Our analysis establishes that continuous processing becomes economically attractive for processes where only a small portion of the potential column lifetime can be utilized or for column steps with slow mass transport and shallow breakthrough curves. In cases where column breakthrough is sharp and resin lifetime is relatively short, continuous processing may offer an improvement over traditional batch processing, but much of the productivity and cost savings can be realized through repeated column cycling. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1195-1204, 2018., (© 2018 American Institute of Chemical Engineers.)

Objectives: To establish whether the four-dimensional Assessment of Quality of Life (AQoL-4D) produces robust utility values in adults with psychotic illness, and identify health inequalities compared with the general population., Methods: The AQoL-4D was completed by 1613 individuals with an International Classification of Diseases, Tenth Revision, psychotic illness in the 2010 Australian National Survey of Psychosis. Utilities were assessed for this sample and 20 subgroups, and were compared with general population norms. Modified Cohen d was used as an index of effect size. Utilities were collapsed into 10 health-related quality-of-life (HRQOL) bands or decades., Results: HRQOL in people with psychotic illness was half of the maximum achievable utility (half-"full health") with a mean utility of 0.49 (95% confidence interval [CI] 0.48-0.51), and showing substantial variability across subgroups. Participants with essentially normal functioning had the highest mean utility (0.72; 95% CI 0.68-0.77), and those with very poor perceived mental health had the lowest (0.22; 95% CI 0.18-0.26). These subgroups showed the most variability. Negative symptoms also gave rise to substantial variation. Among diagnostic categories, only depressive psychosis had a large effect relative to delusional disorders. The distribution of utilities in people with psychotic illness differed markedly from that in the general population, with 6.8% versus 47.2% having values in the highest decade (>0.90-1.00). Utilities were lower in every age group in people with psychosis., Conclusions: Profound HRQOL impacts are revealed by the AQoL-4D in people with psychotic illness, and marked variations in utilities were observed for key subjective and objective measures. We provide a suite of utility values for economic modeling studies and recommend the AQoL-4D for assessing HRQOL in people with psychotic illness., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Policy Points: The Pay for Success (PFS) financing approach has potential for scaling the implementation of evidence-based prevention interventions in Medicaid populations, including a range of multicomponent interventions for childhood asthma that combine home environment risk mitigation with medical case management. Even though this type of intervention is efficacious and cost-saving among high-risk children with asthma, the main challenges for implementation in a PFS context include legal and regulatory barriers to capturing federal Medicaid savings and using them as a source of private investor repayment. Federal-level policy change and guidance are needed to support PFS financing of evidence-based interventions that would reduce expensive acute care among Medicaid enrollees., Context: Pay for Success has emerged as a potential financing mechanism for innovative and cost-effective prevention programs. In the PFS model, interventions that provide value to the public sector are implemented with financing from private investors who receive a payout from the government only if the metrics identified in a performance-based contract are met. In this nascent field, little has been written about the potential for and challenges of PFS initiatives that produce savings and/or value for Medicaid., Methods: In order to elucidate the basic economics of a PFS intervention in a Medicaid population, we modeled the potential impact of an evidence-based multicomponent childhood asthma intervention among low-income children enrolled in Medicaid in Detroit. We modeled outcomes and a comparative benefit-cost analysis in 3 risk-based target groups: (1) all children with an asthma diagnosis; (2) children with an asthma-related emergency department visit in the past year; and (3) children with an asthma-related hospitalization in the past year. Modeling scenarios for each group produced estimates of potential state and federal Medicaid savings for different types or levels of investment, the time frames for savings, and some overarching challenges., Findings: The PFS economics of a home-based asthma intervention are most viable if it targets children who have already experienced an expensive episode of asthma-related care. In a 7-year demonstration, the overall (undiscounted) modeled potential savings for Group 2 were $1.4 million for the federal Medicaid and $634,000 for the state Medicaid programs, respectively. Targeting children with at least 1 hospitalization in the past year (Group 3) produced estimated potential savings of $2.8 million to federal Medicaid and $1.3 million to state Medicaid. However, current Medicaid rules and regulations pose significant challenges for capturing federal Medicaid savings for PFS payouts., Conclusions: A multicomponent intervention that provides home remediation and medical case management to high-risk children with asthma has significant potential for PFS financing in urban Medicaid populations. However, there are significant administrative and payment challenges, including the limited ability to capture federal Medicaid savings and to use them as a source of investor repayment. Without some policy reform and clear guidance from the federal government, the financing burden of PFS outcome payments will be on the state Medicaid program or some other state-level funding source., (© 2018 Milbank Memorial Fund.)