Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

Cost-effectiveness analysis of emicizumab prophylaxis in patients with haemophilia A in India.

INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN-1 and HAVEN-3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. RESULTS: In the base-case analysis, emicizumab was cost-effective compared to HDP, with an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost-effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One-way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost-effective at willingness-to-pay (WTP) thresholds of three and two-times per capita GDP. CONCLUSION: Emicizumab prophylaxis is cost-effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non-inhibitor PwHA in India. Its long-term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource-constrained settings.

Is the Comparator in Your Diagnostic Cost-Effectiveness Model "Standard of Care"? Recommendations from Literature Reviews and Expert Interviews on How to Identify and Operationalize It.

OBJECTIVES: This research aimed to develop best-practice recommendations for identifying the "standard of care" (SoC) and integrate it when it is the comparator in diagnostic economic models (SoC comparator). METHODS: A multi-methods approach comprising 2 pragmatic literature reviews and 9 expert interviews was used. Experts rated their agreement with draft recommendations based on the authors' analysis of the reviews. These were refined iteratively to produce final recommendations. RESULTS: Fourteen best-practice recommendations are provided. Care pathway mapping (using quantitative, qualitative, or mixed-methods approaches) should be used for identifying the SoC comparator. Guidelines analysis can be integrated with expert opinion to identify pathway variability and discrepancies from clinical practice. For integrating the SoC comparator into the model, recommendations around structure, input sourcing, data aggregation and reporting, input uncertainty, and model variability are presented. For example, modelers should consider that the reference standard is not synonymous with the SoC, and the SoC may not be the only comparator. The comparator limitations should be discussed with clinical experts, but elicitation of its diagnostic accuracy is not recommended. Probabilistic sensitivity analysis is recommended when evaluating the overall input uncertainty, and deterministic sensitivity analysis is useful when there is high model uncertainty or SoC variability. Consensus could not be reached for some topics (eg, the role of real-world data, model averaging, and alternative model structures), but the reported discussions provide points for consideration. CONCLUSIONS: To our knowledge, this is the first guidance to support modelers when identifying and operationalizing the SoC comparator in diagnostic cost-effectiveness models.

Validating Health Economic Models With the Probabilistic Analysis Check dashBOARD.

OBJECTIVES: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making. This study aimed to develop and test a generic dashboard to systematically explore the workings of HE models and validate their model parameters and outcomes. METHODS: The Probabilistic Analysis Check dashBOARD (PACBOARD) was developed using insights from literature, health economists, and a data scientist. Functionalities of PACBOARD are (1) exploring and validating model parameters and outcomes using standardized validation tests and interactive plots, (2) visualizing and investigating the relationship between model parameters and outcomes using metamodeling, and (3) predicting HE outcomes using the fitted metamodel. To test PACBOARD, 2 mock HE models were developed, and errors were introduced in these models, eg, negative costs inputs, utility values exceeding 1. PACBOARD metamodeling predictions of incremental net monetary benefit were validated against the original model's outcomes. RESULTS: PACBOARD automatically identified all errors introduced in the erroneous HE models. Metamodel predictions were accurate compared with the original model outcomes. CONCLUSIONS: PACBOARD is a unique dashboard aiming at improving the feasibility and transparency of validation efforts of HE models. PACBOARD allows users to explore the working of HE models using metamodeling based on HE models' parameters and outcomes.

Flexibility trade-offs in conservation offsets.

Conservation offsets promise cost-effective conservation of biodiversity, especially under economic and environmental change, because they represent a more flexible approach to biodiversity conservation, allowing for the economic development of ecologically valuable land provided that this development is offset by restoration of previously developed areas. The level of flexibility is determined by the trading rules. Lax rules allow for more flexibility, which promises cost savings, but will likely lead to unintended loss of biodiversity. I analyzed the trade-off between economic costs and ecological benefits (biodiversity conservation) in biodiversity offsetting with an ecological-economic model that considered the three main types of offset flexibility: spatial, temporal, and ecosystem type. I sought to examine the influence of ecological and economic conditions on offset flexibility trade-offs. Large variation in the conservation costs and small costs of habitat restoration strongly increased trading activity and reduced the ecological benefit. The ecological benefit was most sensitive to spatial flexibility when a short range of ecological interaction was considered. At a large interaction range, spatial flexibility delivered large cost savings without overly reducing the ecological benefit. Risks and time lags associated with habitat restoration favored an offsetting scheme in which credits are awarded with the initiation of restoration projects rather than their successful completion-given appropriate offsetting multipliers were chosen. Altogether, under scarce resources, the level of flexibility in an offsetting scheme should be chosen by carefully balancing ecological benefits and economic costs.

Compromisos de flexibilidad en las compensaciones por conservación Resumen Las compensaciones por conservación prometen conservar la biodiversidad de forma rentable, especialmente de frente al cambio ambiental y económico. Ya que representan una estrategia más flexible para la conservación de la biodiversidad, esto permite el desarrollo económico de suelo con valor ecológico siempre y cuando este desarrollo esté compensado por la restauración de áreas con desarrollo previo. El nivel de flexibilidad está determinado por las reglas de intercambio. Las reglas laxas permiten una mayor flexibilidad, que promete ahorros, pero probablemente derive en la pérdida no intencionada de la biodiversidad. Analicé los compromisos entre los costos económicos y los beneficios ecológicos (conservación de la biodiversidad) en las compensaciones por biodiversidad con un modelo ecológico-económico que consideraba los tres tipos principales de flexibilidad: espacial, temporal y por tipo de ecosistema. Traté de examinar la influencia de las condiciones ecológicas y económicas sobre los compromisos de flexibilidad en las compensaciones. Una gran variación en los costos de conservación y los pequeños costos de la restauración del hábitat incrementaron fuertemente la actividad de intercambio y redujeron el beneficio ecológico. El beneficio ecológico fue más sensible a la flexibilidad espacial cuando consideré un corto alcance de la interacción ecológica. Con un alcance extenso, la flexibilidad espacial ofreció grandes ahorros son reducir por mucho el beneficio ecológico. Los riesgos y retrasos temporales asociados con la restauración del hábitat favorecieron un esquema de compensaciones en el que los créditos se otorgan al inicio del proyecto de restauración en lugar de con la conclusión exitosa del mismo-siempre y cuando se hayan elegido multiplicadores de compensación adecuados. En conjunto, si se tienen pocos recursos, el nivel de flexibilidad en un esquema de compensaciones debería elegirse con un balance cuidadoso entre los beneficios ecológicos y los costos económicos.

Exploring the potential cost-effectiveness of a new computerised decision support tool for identifying fetal compromise during monitored term labours: an early health economic model.

BACKGROUND: Around 60% of term labours in the UK are continuously monitored using cardiotocography (CTG) to guide clinical labour management. Interpreting the CTG trace is challenging, leading to some babies suffering adverse outcomes and others unnecessary expedited deliveries. A new data driven computerised tool combining multiple clinical risk factors with CTG data (attentive CTG) was developed to help identify term babies at risk of severe compromise during labour. This paper presents an early health economic model exploring its potential cost-effectiveness. METHODS: The model compared attentive CTG and usual care with usual care alone and simulated clinical events, healthcare costs, and infant quality-adjusted life years over 18 years. It was populated using data from a cohort of term pregnancies, the literature, and administrative datasets. Attentive CTG effectiveness was projected through improved monitoring sensitivity/specificity and potential reductions in numbers of severely compromised infants. Scenario analyses explored the impact of including litigation costs. RESULTS: Nationally, attentive CTG could potentially avoid 10,000 unnecessary alerts in labour and 2400 emergency C-section deliveries through improved specificity. A reduction of 21 intrapartum stillbirths amongst severely compromised infants was also predicted with improved sensitivity. Attentive CTG could potentially lead to cost savings and health gains with a probability of being cost-effective at £25,000 per QALY ranging from 70 to 95%. Potential exists for further cost savings if litigation costs are included. CONCLUSIONS: Attentive CTG could offer a cost-effective use of healthcare resources. Prospective patient-level studies are needed to formally evaluate its effectiveness and economic impact in routine clinical practice.

Incorporating frailty to address the key challenges to geriatric economic evaluation.

BACKGROUND: The multidimensional and dynamically complex process of ageing presents key challenges to economic evaluation of geriatric interventions, including: (1) accounting for indirect, long-term effects of a geriatric shock such as a fall; (2) incorporating a wide range of societal, non-health outcomes such as informal caregiver burden; and (3) accounting for heterogeneity within the demographic group. Measures of frailty aim to capture the multidimensional and syndromic nature of geriatric health. Using a case study of community-based falls prevention, this article explores how incorporating a multivariate frailty index in a decision model can help address the above key challenges. METHODS: A conceptual structure of the relationship between geriatric shocks and frailty was developed. This included three key associations involving frailty: (A) the shock-frailty feedback loop; (B) the secondary effects of shock via frailty; and (C) association between frailty and intervention access. A case study of economic modelling of community-based falls prevention for older persons aged 60 + was used to show how parameterising these associations contributed to addressing the above three challenges. The English Longitudinal Study of Ageing (ELSA) was the main data source for parameterisation. A new 52-item multivariate frailty index was generated from ELSA. The main statistical methods were multivariate logistic and linear regressions. Estimated regression coefficients were inputted into a discrete individual simulation with annual cycles to calculate the continuous variable value or probability of binary event given individuals' characteristics. RESULTS: All three conceptual associations, in their parameterised forms, contributed to addressing challenge (1). Specifically, by worsening the frailty progression, falls incidence in the model increased the risk of falling in subsequent cycles and indirectly impacted the trajectories and levels of EQ-5D-3 L, mortality risk, and comorbidity care costs. Intervention access was positively associated with frailty such that the greater access to falls prevention by frailer individuals dampened the falls-frailty feedback loop. Association (B) concerning the secondary effects of falls via frailty was central to addressing challenge (2). Using this association, the model was able to estimate how falls prevention generated via its impact on frailty paid and unpaid productivity gains, out-of-pocket care expenditure reduction, and informal caregiving cost reduction. For challenge (3), frailty captured the variations within demographic groups of key model outcomes including EQ-5D-3 L, QALY, and all-cause care costs. Frailty itself was shown to have a social gradient such that it mediated socially inequitable distributions of frailty-associated outcomes. CONCLUSION: The frailty-based conceptual structure and parameterisation methods significantly improved upon the methods previously employed by falls prevention models to address the key challenges for geriatric economic evaluation. The conceptual structure is applicable to other geriatric and non-geriatric intervention areas and should inform the data selection and statistical methods to parameterise structurally valid economic models of geriatric interventions.

Economic values of some important traits for smallholder dairy production in Central Ethiopia.

Economic value (EV), sensitivity of EV and relative economic importance of milk yield (MY), age at first calving (AFC), calving interval (CI) and herd life (HL) traits were estimated for smallholder dairy cattle production in the central part of Ethiopia. The data on biological and economic parameters were collected using household interview and group discussions methods participating 238 farmers who had crossbred dairy cattle. Bio-economic model was used to calculate EV, sensitivity of EV and relative importance of EV. Cost of animal feed takes the highest share which accounted 81.35% of the total expenditure. The overall average profit per farmer expressed in Ethiopia currency (ETB, 1 US-$ = 39.55696 ETB) was 72,458.10 ± 5068 per year. Profitability of crossbred dairy cattle significantly varied (P < 0.05) between zones. Economic value estimated for MY, AFC, CI and HL in ETB were 13.38/kg, -16.19/day, -33.58/day and 79.55/day. The associated EV per additive standard deviation were 6083.62, -1311.59, -1271.05 and 117.73 ETB for MY, AFC, CI and HL, respectively. Analysis of sensitivity to scenario change (± 20%) showed that milk price had positive association with profit and EV, whereas feed price has inversely influenced both profit and EV. The profit obtained by farmers was altered by ± 29.08% and ± 12.31% as milk price and feed price fluctuated by ± 20%, respectively. Similarly, the EV of MY was changed by ± 20% with change in milk price and ± 7% with feed price. Scenario change in feed price (± 20%) has also caused ± 13.63% change on EV for AFC and ± 17.58% for CI. It can be noted that profit and EV of the traits were less sensitive to the change in price of milk, feed and labor. In general, the results of EV and profitability were encouraging for dairy farmers and the estimates can be used as an input for development of breeding program in the study area.

The Economic Potential of Smoking Cessation Interventions at the Point of Diagnosis of Non-Small Cell Lung Cancer.

OBJECTIVES: Stopping smoking has proven benefits in nearly all illnesses but the impact and health economic benefits of stopping smoking after a diagnosis of lung cancer are less well defined. We assessed the cost-effectiveness of smoking cessation (SC) services for patients with newly diagnosed lung cancer against current usual care, where patients are unlikely to receive SC service referral. METHODS: A health economic model was constructed in Excel. The modelled population comprised of patients with a new diagnosis of non-small cell lung cancer (NSCLC). Data from the LungCast data set (Clinical Trials Identifier NCT01192256) were used to estimate model inputs. A structured search of published literature identified inputs not represented in LungCast, including healthcare resource use and costs. Costs were estimated from a 2020/2021 UK National Health Service and Personal Social Services perspective. The model estimated the incremental quality-adjusted life-year (QALY) gained in patients with newly diagnosed NSCLC receiving targeted SC intervention than those receiving no intervention. Extensive one-way sensitivity analyses explored input and data set uncertainty. RESULTS: In the 5-year base case, the model estimated an incremental cost of £14 904 per QALY gained through SC intervention. Sensitivity analysis estimated an outcome range of between £9935 and £32 246 per QALY gained. The model was most sensitive to the estimates of relative quit rates and expected healthcare resource use. CONCLUSION: This exploratory analysis indicates that SC intervention for smokers with patients with newly diagnosed NSCLC should be a cost-effective use of UK National Health Service resources. Additional research with focused costing is needed to confirm this positioning.

Plugging membranes after fetoscopy in congenital diaphragmatic hernia: early cost-effectiveness analysis.

OBJECTIVES: Fetal endoscopic tracheal occlusion (FETO) improves neonatal survival of fetuses with congenital diaphragmatic hernia (CDH). However, FETO also increases the risk of preterm prelabor rupture of membranes (PPROM) and preterm delivery (PTD), as fetal membrane defects after fetoscopy do not heal. To solve this issue, an advanced sealing plug for closing the membrane defect is being developed. Using early-stage health economic modeling, we aimed to estimate the potential value of this innovative plug in terms of costs and effects, and to determine the properties required for it to become cost-effective. METHODS: Early-stage health economic modeling was applied to the case of performing FETO in women with a singleton pregnancy whose fetus is diagnosed prenatally with CDH. We simulated a cohort of patients using a state-transition model over a 45-year time horizon. In our best-case-scenario analysis, we compared the current-care strategy with the perfect-plug strategy, which reduces the risk of PPROM and PTD by 100%, to determine the maximum quality-adjusted life years (QALYs) gained and costs saved. Using threshold analysis, we determined the minimum percentage reduction in the risk of PPROM and PTD required for the plug to be considered cost-effective. The impact of model parameters on outcome was investigated using a sensitivity analysis. RESULTS: Our model indicated that a perfect-plug strategy would yield on average an additional 1.94 QALYs at a cost decrease of €2554 per patient. These values were influenced strongly by the percentage of cases with early PTD (27-34 weeks). Threshold analysis showed that, for €500 per plug, the plug strategy needs a minimum percentage reduction of 1.83% in the risk of PPROM and PTD (i.e. reduction in the risk from 47.50% to 46.63% for PPROM and from 71.50% to 70.19% for PTD) to be cost-effective. CONCLUSIONS: Our model-based approach showed clear potential of the plug strategy when applied in the context of FETO for CDH fetuses, as only a minor reduction in the risk of PPROM and PTD is needed for the plug to be cost-effective. Its value is expected to be even higher when used in conditions associated with a higher rate of early PTD. Continued investment in research and development of the plug strategy appears to provide value for money. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The health, economic and social burden of smoking in Argentina, and the impact of increasing tobacco taxes in a context of illicit trade.

Tobacco tax increases, the most cost-effective measure in reducing consumption, remain underutilized in low and middle-income countries. This study estimates the health and economic burden of smoking in Argentina and forecasts the benefits of tobacco tax hikes, accounting for the potential effects of illicit trade. Using a probabilistic Markov microsimulation model, this study quantifies smoking-related deaths, health events, and societal costs. The model also estimates the health and economic benefits of different increases in the price of cigarettes through taxes. Annually, smoking causes 45,000 deaths and 221,000 health events in Argentina, costing USD 2782 million in direct medical expenses, USD 1470 million in labor productivity loss costs, and USD 1069 million in informal care costs-totaling 1.2% of the national gross domestic product. Even in a scenario that considers illicit trade of tobacco products, a 50% cigarette price increase through taxes could yield USD 8292 million in total economic benefits accumulated over a decade. Consequently, raising tobacco taxes could significantly reduce the health and economic burdens of smoking in Argentina while increasing fiscal revenue.

Economic model of community-based falls prevention: seeking methodological solutions in evaluating the efficiency and equity of UK guideline recommendations.

BACKGROUND: Falls significantly harm geriatric health and impose substantial costs on care systems and wider society. Decision modelling can inform the commissioning of falls prevention but face methodological challenges, including: (1) capturing non-health outcomes and societal intervention costs; (2) considering heterogeneity and dynamic complexity; (3) considering theories of human behaviour and implementation; and (4) considering issues of equity. This study seeks methodological solutions in developing a credible economic model of community-based falls prevention for older persons (aged 60 +) to inform local falls prevention commissioning as recommended by UK guidelines. METHODS: A framework for conceptualising public health economic models was followed. Conceptualisation was conducted in Sheffield as a representative local health economy. Model parameterisation used publicly available data including English Longitudinal Study of Ageing and UK-based falls prevention trials. Key methodological developments in operationalising a discrete individual simulation model included: (1) incorporating societal outcomes including productivity, informal caregiving cost, and private care expenditure; (2) parameterising dynamic falls-frailty feedback loop whereby falls influence long-term outcomes via frailty progression; (3) incorporating three parallel prevention pathways with unique eligibility and implementation conditions; and (4) assessing equity impacts through distributional cost-effectiveness analysis (DCEA) and individual-level lifetime outcomes (e.g., number reaching 'fair innings'). Guideline-recommended strategy (RC) was compared against usual care (UC). Probabilistic sensitivity, subgroup, and scenario analyses were conducted. RESULTS: RC had 93.4% probability of being cost-effective versus UC at cost-effectiveness threshold of £20,000 per QALY gained under 40-year societal cost-utility analysis. It increased productivity and reduced private expenditure and informal caregiving cost, but productivity gain and private expenditure reduction were outstripped by increases in intervention time opportunity costs and co-payments, respectively. RC reduced inequality delineated by socioeconomic status quartile. Gains in individual-level lifetime outcomes were small. Younger geriatric age groups can cross-subsidise their older peers for whom RC is cost-ineffective. Removing the falls-frailty feedback made RC no longer efficient or equitable versus UC. CONCLUSION: Methodological advances addressed several key challenges associated with falls prevention modelling. RC appears cost-effective and equitable versus UC. However, further analyses should confirm whether RC is optimal versus other potential strategies and investigate feasibility issues including capacity implications.

Health economic assessment of negative pressure wound therapy use in the management of subcutaneous abdominal wound healing impairment (SAWHI) in the out-of-hospital setting.

Development of subcutaneous abdominal wound healing impairment (SAWHI) can greatly affect patient care. Complications from SAWHI include delayed healing, increased risk of infection, and fascial dehiscence resulting in increased patient care and associated costs. Treatment options include conventional wound treatment or negative pressure wound therapy, both of which can be used in the out-of-hospital setting. However, limited published evidence on cost-effectiveness exists. A conservative health economic model was created to assess the cost-benefit of negative pressure wound therapy in the out-of-hospital setting for the management of SAWHI. Study data from a published multicentre randomised controlled trial were used and represented 221 patients that received care in the out-of-hospital setting. The mean per-patient total cost within 42 days was slightly higher in the negative pressure wound therapy group (2034.98 € versus 1918.91 €); however, when wound closure rates were considered, a cost savings of 4155.98 € per closed wound was observed with the use of negative pressure wound therapy (4324.34 € versus 8480.32 €). A cost-effectiveness analysis was constructed, and negative pressure wound therapy was observed to have a lower cost of care and a higher incremental closure rate.

Economic values of reproductive and growth traits in Chinese Yiling sheep.

This study aimed to calculate the economic value (EV) of reproductive and growth traits for Yiling sheep. A bio-economic model was developed to assess the economic value of litter size (LS), litter size at weaning (LSW), age at first lambing (AFL), lambing interval (LI), birth weight (BW), weaning weight (WW), and 6-month body weight (6MW). The sensitivity of the economic value of traits to changes in market prices was also analyzed. In this study, the trait with the highest EV was LSW (427.97 ¥), followed by LS (419.96 ¥), BW (52.13 ¥), 6MW (14.46 ¥), WW (11.03 ¥), AFL (-0.51 ¥), and LI (-9.09 ¥). LS was the most important trait in the production system with a relative economic weight of 22.81%, followed by 6MW and LSW with relative economic weights of 18.98% and 19.01%, respectively. All traits assessed, except AFL and LI, had positive economic values, indicating that genetic improvement of these traits would have a positive impact on profitability. The results of the sensitivity analysis showed that the economic value of AFL was not sensitive to price changes. All growth traits were unaffected by price changes in labor and medical costs. In addition, the LS, LSW, LI, WW, and 6MW were sensitive to changes in liveweight and feed prices. Generally, as feed prices increased, the economic value of all traits except LI and BW decreased. Except for LI and BW, the economic value of all traits increased due to the rise in liveweight prices. This suggested that liveweight and feed prices significantly affect the profitability of the production system.

Pharmacokinetic parameter driven outcomes model predicts a reduction in bleeding events associated with BAY 81-8973 versus antihemophilic factor (recombinant) plasma/albumin-free method in a Chinese healthcare setting.

BACKGROUND: Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. METHODS: Head-to-head PK profile data of BAY 81-8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. RESULTS: Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. BAY 81-8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. CONCLUSION: Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81-8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81-8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

An approach to quantify parameter uncertainty in early assessment of novel health technologies.

Health economic modeling of novel technology at the early stages of a product lifecycle has been used to identify technologies that are likely to be cost-effective. Such early assessments are challenging due to the potentially limited amount of data. Modelers typically conduct uncertainty analyses to evaluate their effect on decision-relevant outcomes. Current approaches, however, are limited in their scope of application and imposes an unverifiable assumption, that is, uncertainty can be precisely represented by a probability distribution. In the absence of reliable data, an approach that uses the fewest number of assumptions is desirable. This study introduces a generalized approach for quantifying parameter uncertainty, that is, probability bound analysis (PBA), that does not require a precise specification of a probability distribution in the context of early-stage health economic modeling. We introduce the concept of a probability box (p-box) as a measure of uncertainty without necessitating a precise probability distribution. We provide formulas for a p-box given data on summary statistics of a parameter. We describe an approach to propagate p-boxes into a model and provide step-by-step guidance on how to implement PBA. We conduct a case and examine the differences between the status-quo and PBA approaches and their potential implications on decision-making.

Defining smallholders' breeding objectives for common Tigray highland sheep in Northern Ethiopia.

A sound breeding objective is a basis for genetic improvement in the overall economic merit of farm animals. This study aimed to define smallholders' sheep breeding objectives using a conjoint-based choice experiment and bio-economic model. Multinomial logistic regression analysis showed differences (p < 0.001) among the derived weights allocated by farmers to body size, twining rate, mothering ability, libido, tail type, colour and lambing interval which formed the high priority traits. The likelihood values of farmer's top three preferred traits for ram were body size (0.659 ± 0.009), tail type (0.325 ± 0.016) and libido (0.247 ± 0.016) while body size (0.459 ± 0.010), twining rate (0.313 ± 0.010) and mothering ability (0.261 ± 0.010) were more preferred traits for selection of breeding ewes. Conjoint-based choice experiment and bio-economic model indicated that live body weight at 6 months of age, twining rate (litter size) and mothering ability (preweaning lamb survival) were the most economically important traits of the breeding ewes. A genetic improvement by one genetic standard deviation (σa ) in these traits resulted in a profit of Ethiopian Birr 36.03-60.47/ewe/year. A fair correlation (r = 0.63) was observed between farmers' traits preference (conjoint-based choice card experiment) and the estimated economic value of traits indicating a good relationship between farmers' preferences for traits and economic values of the traits. This would indicate that weighting traits in selection indexes with farmers' trait selection using a conjoint-based choice experiment would direct genetic improvement towards desired profitability. Moreover, the fair correspondence between the two methods suggests that bio-economic modelling, if designed properly considering farmers' concerns, could be used to reflect farmers' breeding objectives. Therefore, for reasonable genetic progress and sheep flock profitability, more attention should be given to litter size, preweaning lamb survival and body weight at 6 months of age as they are preferred by farmers and their economic weights. Further, research on the modalities for complementary use of the two methods to define breeding objectives under smallholder conditions is warranted.

Economic Linear Parameter Varying Model Predictive Control of the Aeration System of a Wastewater Treatment Plant.

This work proposes an economic model predictive control (EMPC) strategy in the linear parameter varying (LPV) framework for the control of dissolved oxygen concentrations in the aerated reactors of a wastewater treatment plant (WWTP). A reduced model of the complex nonlinear plant is represented in a quasi-linear parameter varying (qLPV) form to reduce computational burden, enabling the real-time operation. To facilitate the formulation of the time-varying parameters which are functions of system states, as well as for feedback control purposes, a moving horizon estimator (MHE) that uses the qLPV WWTP model is proposed. The control strategy is investigated and evaluated based on the ASM1 simulation benchmark for performance assessment. The obtained results applying the EMPC strategy for the control of the aeration system in the WWTP of Girona (Spain) show its effectiveness.

Adoption of water reuse technologies: An assessment under different regulatory and operational scenarios.

Water reuse technologies may alleviate the water scarcity problems that affect many world regions, but their adoption is still limited. In particular, key actors in the adoption of water reuse technologies are water utilities, that provide both urban water and wastewater treatment services. Water utilities are embedded in the urban water system, which includes several stakeholders (urban water users, citizens at large, the environment) that may drive or pose barriers to water reuse adoption. Therefore, to ensure a smooth introduction of water reuse technologies, it is fundamental to understand how water reuse interacts with the existing urban water system and impacts its stakeholders. This paper contributes to the ongoing debate on water reuse by conceptualizing the interaction between water reuse technologies and the urban water system and its stakeholders, and addressing the adoption decision of water utilities by assessing its economic and environmental consequences. Based on a review of literature, policy and other secondary documents, and on primary data coming from interviews with experts from a water utility operating in Southern Italy, the study models the utility's response to a shift from urban to reuse water. It then simulates how reuse water introduction impacts on the utility and other stakeholders of the water system, under various regulatory and operational scenarios defined through a thorough analysis of policy documents and literature. Results show that the adoption of water reuse reduces the utility's margin by cannibalizing urban water demand, but appropriate policy measures may enhance the economic sustainability of reuse. System-level performances, such as impact on freshwater savings, costs for users, effects on the public budget, are also assessed, showing how different regulatory options moderate the intensity of impacts for the different stakeholders of the water system. Furthermore, the adoption of reuse water by the most distant users is found to enhance the economic sustainability of reuse and positively impact the utility's margin.

Cost-Effectiveness Analysis of Smoking Cessation Interventions in the United Kingdom Accounting for Major Neuropsychiatric Adverse Events.

OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom. METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information. RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose. CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.