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Non-alcoholic steatohepatitis (NASH) and type 2 diabetes (T2D) are both linked to substantial healthcare costs and are often co-occurring. We aim to quantify the incremental cost of NASH and T2D using real-world data. Adults (≥18 years old) with ≥2 diagnosis codes for NASH and/or ≥2 diagnosis codes for T2D between 1/1/2016 and 12/31/2021 and ≥24 months of continuous claims enrollment (study period) were identified in electronic health records or claims in the Veradigm Integrated Dataset. Patients were stratified into 3 cohorts: NASH-only, T2D-only, and NASH + T2D. We calculated annualized costs for the 24-month study period and fit a generalized linear model (excluding the most expensive 1%) that controlled for disease cohort, age, sex, and modified Charlson comorbidity index to estimate the per year all-cause healthcare costs and incremental cost of adding T2D to a NASH diagnosis (or vice versa). We identified 23,111 patients diagnosed with NASH-only, 3,548,786 patients with T2D-only, and 30,339 patients with NASH + T2D. The model-predicted mean costs per year were $7,668 for patients with NASH-only, $11,226 for patients with T2D-only, and $16,812 for patients with NASH + T2D. The incremental increase in costs per year of adding T2D to NASH was 63% (+$4,846), and the incremental increase in costs per year of adding NASH to T2D was 42% (+$4,692). Both NASH and T2D contribute to the high healthcare costs among patients with a dual diagnosis. Results from our analysis indicate that NASH comprises a high portion of total healthcare costs among patients with NASH and T2D. [ABSTRACT FROM AUTHOR]

Objective: To measure the costs of preventive and therapeutic protocols of Photobiomodulation (PBM) for oral mucositis (OM) and their budgetary impact on Brazil’s Ministry of Health (BMH). Material and Methods: A partial economic analysis was performed to estimate the costs using a bottom-up approach from a social perspective. Monetary values were assigned in Brazilian reais (BRL). The costs of the preventive protocol were calculated for five, 30, and 33 consecutive PBM sessions, depending on the antineoplastic treatment instituted. The costs of the therapeutic protocol were calculated for 5 or 10 sessions. The annual financial and budgetary impact was calculated considering the groups of oncologic patients with a higher risk of development of OM, such as those with head and neck and hematological cancer and pediatric patients. Results: The cost of a PBM session was estimated at BRL 23.75. The financial impact of providing one preventive protocol per year for all oncologic patients would be BRL 14,282,680.00, 0.030% of the estimated budget for hospital and outpatient care of the BMH in 2022. The financial and budgetary impacts of providing one treatment for OM for all patients in one year would be BRL 2,225,630.31 (0.005%, most optimistic scenario) and BRL 4,451,355.63 (0.009%, most pessimistic scenario). Conclusion: The budgetary impact of implementing PBM protocols in the Brazilian Healthcare System is small, even in a pessimistic scenario.

Objective: This study leveraged data from 11 independent international diabetes models to evaluate the impact of unrelated future medical costs on the outcomes of health economic evaluations in diabetes mellitus., Methods: Eleven models simulated the progression of diabetes and occurrence of its complications in hypothetical cohorts of individuals with type 1 (T1D) or type 2 (T2D) diabetes over the remaining lifetime of the patients to evaluate the cost effectiveness of three hypothetical glucose improvement interventions versus a hypothetical control intervention. All models used the same set of costs associated with diabetes complications and interventions, using a United Kingdom healthcare system perspective. Standard utility/disutility values associated with diabetes-related complications were used. Unrelated future medical costs were assumed equal for all interventions and control arms. The statistical significance of changes on the total lifetime costs, incremental costs and incremental cost-effectiveness ratios (ICERs) before and after adding the unrelated future medical costs were analysed using t-test and summarized in incremental cost-effectiveness diagrams by type of diabetes., Results: The inclusion of unrelated costs increased mean total lifetime costs substantially. However, there were no significant differences between the mean incremental costs and ICERs before and after adding unrelated future medical costs. Unrelated future medical cost inclusion did not alter the original conclusions of the diabetes modelling evaluations., Conclusions: For diabetes, with many costly noncommunicable diseases already explicitly modelled as complications, and with many interventions having predominantly an effect on the improvement of quality of life, unrelated future medical costs have a small impact on the outcomes of health economic evaluations., (© 2024. The Author(s).)

Introduction: Therapeutic inertia in type 2 diabetes, defined as a failure to intensify treatment despite poor glycemic control, can arise due to a variety of factors, despite evidence linking improved glycemic control with reductions in diabetes-related complications. The present study aimed to evaluate the health and economic burden of therapeutic inertia in people with type 2 diabetes in Saudi Arabia., Methods: The IQVIA Core Diabetes Model (v.9.0) was used to evaluate outcomes. Baseline cohort characteristics were sourced from Saudi-specific data, with baseline glycated hemoglobin (HbA1c) tested at 8.0%, 9.0%, and 10.0%. Modeled subjects were brought to an HbA1c target of 7.0% immediately or after delays of 1-5 years across time horizons of 3-50 years. Outcomes were discounted annually at 3.0%. Costs were accounted from a societal perspective and expressed in 2023 Saudi Arabian Riyals (SAR)., Results: Immediate glycemic control was associated with improved or equal life expectancy and quality-adjusted life expectancy and cost savings in all scenarios compared with delays in achieving target HbA1c. Combined cost savings ranged from SAR 411 (EUR 102) per person with a baseline HbA1c of 8.0% versus a 1-year delay over a 3-year time horizon, to SAR 21,422 (EUR 5291) per person with a baseline HbA1c of 10.0% versus a 5-year delay over a 50-year time horizon. Discounted life expectancy and quality-adjusted life expectancy were projected to improve by up to 0.4 years and 0.5 quality-adjusted life years (QALYs), respectively, with immediate glycemic control., Conclusion: Therapeutic inertia was associated with a substantial health and economic burden in Saudi Arabia. Interventions and initiatives that can help to reduce therapeutic inertia are likely to improve health outcomes and reduce healthcare expenditure., (© 2024. The Author(s).)

Objectives: The objective of this study is to compare different information retrieval methods that can be used to identify utility inputs for health economic models., Methods: The usual practice of using systematic review methods was compared with two alternatives (iterative searching and rapid review), using a health technology assessment (HTA) case study in ulcerative colitis (UC). We analysed whether there were differences in the utility values identified when using the alternative search methods. Success was evaluated in terms of time, burden and relevance of identified information. The identified utility values were tested in an executable health economic model developed for UC, and the model results were compared., Results: The usual practice of using systematic review search approaches identified the most publications but was also the least precise method and took longest to complete. The inclusion of data from the different search methods in the model did not lead to different conclusions across search methods., Conclusions: In this case study, usual practice was less efficient and resulted in the same health economic model conclusions as the alternative search methods. Further case studies are required to examine whether this conclusion might be generalisable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Treatment effect waning (TEW) refers to the attenuation of treatment effects over time. Assumptions of a sustained immuno-oncologic treatment effect have been a source of contention in health technology assessment (HTA). We review how TEW has been addressed in HTA and in the wider scientific literature. We analysed company submissions to English language HTA agencies and summarised methods and assumptions used. We subsequently reviewed TEW-related work in the ISPOR Scientific Presentations Database and conducted a targeted literature review (TLR) for evidence of the maintenance of immuno-oncology (IO) treatment effects post-treatment discontinuation. We found no standardised approach adopted by companies in submissions to HTA agencies, with immediate TEW most used in scenario analyses. Independently fitted survival models do however suggest TEW may often be implicitly modelled. Materials in the ISPOR scientific database suggest gradual TEW is more plausible than immediate TEW. The TLR uncovered evidence of durable survival in patients treated with IOs but no evidence that directly addresses the presence or absence of TEW. Our HTA review shows the need for a consistent and appropriate implementation of TEW in oncology appraisals. However, the TLR highlights the absence of direct evidence on TEW in literature, as TEW is defined in terms of relative treatment effects-not absolute survival. We propose a sequence of steps for analysts to use when assessing whether a TEW scenario is necessary and appropriate to present in appraisals of IOs., (© 2024. The Author(s).)

Objective: The aim of the current study was to evaluate the cost-effectiveness of serplulimab plus chemotherapy compared chemotherapy alone as first-line strategy for patients with ES-SCLC in China., Methods: A decision-analytic model that based on the Chinese health-care system perspective was conducted to evaluate the economic benefits for the two competing first-line treatment. The clinical survival and safety data were obtained from the ASTRUM-005 trial, cost and utility values were gathered from the local charges and previously published study. Both cost and utility values were discounted at an annual rate of 5%. Sensitivity analyses and subgroup analyses were performed to examine the robustness of the model results., Results: Serplulimab plus chemotherapy could bring additional 0.25 QALYs with the marginal cost of $37,569.32, resulting in an ICER of $147,908.74 per additional QALY gained. Sensitivity analyses confirmed that model results were robust. Subgroup analyses revealed that adding serplulimab to first-line chemotherapy were unlikely to be the cost-effective option for all subgroup patients., Conclusions: Serplulimab plus chemotherapy was unlikely to be the cost-effective first-line strategy compared with chemotherapy alone for patients with ES-SCLC in China. Reduced the price of serplulimab could increase its cost-effective.

Background & Aims: Celiac disease (CD) is a common yet underdiagnosed autoimmune disease with substantial long-term consequences. High-accuracy point-of-care tests for CD antibodies conducted at youth primary health care centers may enable earlier identification of CD, but evidence about the cost-effectiveness of such strategies is lacking. We estimated the long-term cost-effectiveness of active case finding and mass screening compared with clinical detection in the Netherlands., Methods: A decision tree and Markov model were used to simulate a cohort of 3-year-old children with CD according to each strategy, taking into account their impact on long-term costs (from a societal perspective) and quality-adjusted life-years (QALYs). Model parameters incorporated data from the GLUTENSCREEN project, the Dutch Celiac Society, the Dutch Pediatric Surveillance Unit, and published sources. The primary outcome was the incremental cost-effectiveness ratio (ICER) between strategies., Results: Mass screening produced 7.46 more QALYs and was €28,635 more costly compared with current care (ICER: €3841 per QALY), and case finding produced 4.33 more QALYs and was €15,585 more costly compared with current care (ICER: €3603 per QALY). At a willingness to pay of €20,000 per QALY, both strategies were highly cost-effective compared with current care. Scenario analyses indicated that mass screening is likely the optimal strategy, unless no benefit in detecting asymptomatic cases is assumed., Conclusions: An earlier identification of CD through screening or case finding in children using a point-of-care tests leads to improved health outcomes and is cost-effective in the long-term compared with current care. If the feasibility and acceptability of the proposed strategies are successful, implementation in Dutch regular care is needed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The biosimilar market is growing rapidly, as evidenced by 41 approvals and 37 launches to date. As adalimumab biosimilars launch in the United States, competition among biosimilar and reference adalimumab will likely increase across multiple reference indications, including rheumatology, dermatology, and gastrointestinal diseases, which may lead to decreased payer costs., Objective: To evaluate the costs of adding biosimilar adalimumab to a US commercial plan by exploring various utilization and price differential scenarios., Methods: A 3-year budget impact model for a US commercial plan of 1 million people was developed to assess switching from reference adalimumab or any self-injectable reference tumor necrosis factor (TNF) inhibitor to biosimilar adalimumab. Pharmacy and medical costs were analyzed through high- and low-conversion scenarios from reference adalimumab and the TNF inhibitor class. Price reductions of 5% to 60% relative to reference adalimumab based on previous biosimilar launches were also explored. Short-term medical costs were evaluated as additional simple and complex office visits, with scenarios of half of switch patients having 1 visit up to all switch patients having 10 visits., Results: In a target population of 1,863 patients, switching from reference adalimumab to biosimilar adalimumab had cumulative cost savings of $5,756,073 with slow conversion (10%-20% over 3 years) and $28,780,365 with fast conversion (50%-100% over 3 years). Similar results were seen when switching from any other self-injectable reference TNF inhibitor. Cost savings more than $1 million were seen with a 10% conversion from reference adalimumab and a 15% price reduction from reference adalimumab. Additional office visit scenarios had a negligible impact on budget, with no changes in per-member-per-month costs until all switch patients had 10 additional complex visits, in which per-member-per-month costs increased by $0.02., Conclusions: In a hypothetical plan of 1 million lives, use of biosimilar adalimumab in commercial plans can lead to significant cost savings for payers because of increased competition. Greater and faster biosimilar conversion rates from reference adalimumab and other reference TNF inhibitors resulted in decreased costs. Additionally, even with short-term medical expenditures, cost savings were still realized when switching to biosimilar adalimumab.

Jet fuel plays a crucial role as an essential energy source in aerospace and aviation operations. The recent increase in fuel prices has presented airlines with the new challenge of managing jet fuel costs to ensure consistent cash flow and minimize operational uncertainties. The conventional risk prediction models used by airlines often assume that risks are normally distributed according to the classical Central Limit Theorem, which can lead to under-hedging. This paper proposes an innovative approach using the stable Paretian model to analyze the price return of jet fuel in large samples. It comprehensively compares the fitting effect of the stable Paretian distribution with that of the normal distribution based on specific criteria and non-parametric significance tests. Furthermore, it investigates the accuracy of risk measures such as Value at Risk (VaR) and Conditional Value at Risk (CVaR) predicted by both models. In addition to comparing differences in VaR between predicted values and actual values, this paper provides a more comprehensive comparison of risk measures under rolling window forecast situation. Results suggest that despite indistinguishable results in VaR backtest, the stable Paretian distribution has a overall better fitting effect as well as a less biased predicted CVaR based on the AIC of -14099.46, BIC of -14110.98, p = 0.58 in Kolmogorov-Smirnov test and p = 0.46(0.92) in the 0.01(0.05) significance level of Expected Shortfall Regression Test. This might be explained by its ability to capture asset return dynamics while maintaining shape stability with few parameters. This research can provide valuable insights for guiding airlines' risk management decisions. its ability to capture asset return dynamics while maintaining shape stability with few parameters. This research can provide valuable insights for guiding airlines' risk management decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The scale and connectivity of marine resources make them more complex than land resource management. Although digitization has been recognized as an organizational change process that can effectively improve resource efficiency and enhance network resilience, however, gaps remain in establishing the theoretical links between digitization and marine economic performance. Based on a panel fixed-effects model, this study evaluates the interrelationships and potential mechanisms of different firms with data from annual reports of listed firms in the marine economy in the eastern coastal region of China. The results indicate that there is a 'U-shaped' relationship between digitalization and enterprise efficiency in the maritime sector, and significant heterogeneity exists in the characteristics of these enterprises. Notably, firms' technological innovation capability can modulate the 'U-shaped' relationship through the interaction of economies of scale and economies of scope. This paper highlights how digitization mitigates the fragmentation and sectionalization of marine information and addresses the digital overload and productivity paradox that firms may face in the early stages of digitization. The study suggests that institutional diversity shapes resilience. Governments need to promote top-down regulation and industry collaboration, while marine enterprises need to coevolve collaboratively with them through bottom-up internal communication and external interaction to enhance the value chain of marine enterprises., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The agricultural issue is a focal point of concern for each country, and e-commerce assistance to farmers, as an emerging model, is gaining increasing attention. Considering this trend, this paper bases on e-commerce assistance to farmers and considers four types of government subsidies: no subsidy, price subsidy model with the farmer as the subsidy target, price subsidy model with the e-commerce platform as the subsidy target, and area subsidy model. Based on this, a game model of the contract farming supply chain involving a farmer and an e-commerce platform was established to explore the optimal decision-making in the contract farming supply chain considering various government subsidies under the background of e-commerce assistance to farmers. The results indicate that: (1) Consumer preference for supporting farmers and consumer premiums can stimulate the farmer to expand farm size, increase agricultural production, increase the purchase price of agricultural products and promote the growth of profits for the farmer and the e-commerce platform, contributing to the growth of social welfare. Output volatility can lead to a decrease in farm size and a reduction in the purchase price of agricultural products. (2) Government subsidies can support the farmer in expanding farm size and contribute to increased profits for the farmer and the e-commerce platform. However, government subsidies do not universally have a positive impact on every variable. The influence of government subsidies on the purchase price of agricultural products is contingent upon the method of subsidy distribution. Similarly, the effects of government subsidies on social welfare are influenced by factors such as price elasticity and agricultural productions per unit area. (3) From the perspectives of farm size, the purchase price of agricultural products, and profits of the farmer and the e-commerce platform, the government will have different and more targeted subsidy models, and the corresponding subsidy models are influenced by the agricultural productions per unit area. The research conclusion can provide references for optimal decision-making in contract farming under the model of e-commerce assistance to farmers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu, Zhu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Prefilled syringes (PFS) may offer clinical and economic advantages over conventional parenteral medication delivery methods (vials and ampoules). The benefits of converting from vials and ampoules to PFS have been explained in previous drug-specific economic models; however, these models have limited generalisability to different drugs, healthcare settings and other countries. Our study aims to (1) present a comprehensive economic model to assess the impact of switching from vials to PFS delivery; and (2) illustrate through two case studies the model's utility by highlighting important features of shifting from vials to PFS., Methods: The economic model estimates the potential benefit of switching to PFS associated with four key outcomes: preventable adverse drug events (pADE), preparation time, unused drugs, and cost of supplies. Model reference values were derived from existing peer-reviewed literature sources. The user inputs specific information related to the department, drug, and dose of interest and can change reference values. Two hypothetical case studies are presented to showcase model utility. The first concerns a cardiac intensive care unit in the United Kingdom administering 30 doses of 1 mg/10 mL atropine/day. The second concerns a coronavirus (COVID-19) intensive care unit in France that administers 30 doses of 10 mg/25 mL ephedrine/day., Results: Total cost savings per hospital per year, associated with reductions in pADEs, unused drugs, drug cost and cost of supplies were £34 829 for the atropine example and €104 570 for the ephedrine example. Annual preparation time decreased by 371 and 234 hours in the atropine and ephedrine examples, respectively., Conclusions: The model provides a generalisable framework with customisable inputs, giving hospitals a comprehensive view of the clinical and economic value of adopting PFS. Despite increased costs per dose with PFS, the hypothetical case studies showed notable reductions in medication preparation time and a net budget savings owing to fewer pADEs and reduced drug wastage., Competing Interests: Competing interests: MW, HG, AT, and TE were employees of BD at the time this study was developed and conducted. MP received consultancy fees from BD for providing analytical support. Alkemi LLC (BJL and KAC) received consultancy fees from BD for providing analytical medical writing support. Alkemi LLC did not receive budget for publication writing. JFHE does not have any conflicts of interest to declare., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

The realized recurrent conditional heteroscedasticity (RealRECH) model improves volatility prediction by integrating long short-term memory (LSTM), a recurrent neural network unit, into the realized generalized autoregressive conditional heteroskedasticity (RealGARCH) model. However, at present, there is no literature on the ability of the RealRECH model to fit and predict volatility in the Chinese market. In this paper, a study is conducted to test the in-sample explainability and out-of-sample prediction ability of the RealRECH model for the SSE50, CSI300, CSI500 and CSI1000 indices in the Chinese market and to determine whether it performs better than the RealGARCH model. The results of the in-sample analysis show that the RealRECH model not only provides better in-sample interpretability for all four indices but also captures the complex dynamics of time series volatility that the RealGARCH model cannot capture, such as long-term dependence and nonlinearity. The results of out-of-sample volatility prediction show that the RealRECH model better predicts the volatility of the CSI500 and CSI1000 indices but yields worse predictions for the SSE50 and CSI300 indices. Thus, the RealRECH model can be used for CSI500 and CSI1000 prediction., Competing Interests: This commercial funder had no competing interests along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The past performance and the capital structure of the companies that are involved in mergers and acquisition (M&As) are considered into the analysis of the circular causality relationship between financial performance and market value. Considering two models, one for value relevance and one for accounting conservatism, this paper aims to analyze if the capital market influences the accounting practices of a target company or that the accounting figures influence the capital market. The analyzed sample used in the study is represented by the target companies involved in M&As which took place in the European Union Enlarged in 2017-2018. Financial and market data were considered for eight years (2011-2018). Using the conservatism model, the results show that targets' earnings are significantly influenced by their financial leverage as an indicator for financial structure. Using the value relevance model, the capital market reaction is influenced by prices and return on equity that indicates the capital market influence on accounting figures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Herghiligiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A System Dynamics Model (SDM) is a computer simulation to alleviate the problem by comparing strategies and policies. Addressing the costs by using SDM helps in allocating the resources efficiently in managing the strategies., Objective: To describe the costs of primary, secondary, and tertiary prevention of dental caries for 0-5-year-old children by SDM., Methods: The SDM was developed to explore the cost of primary and secondary prevention (supervised toothbrushing, STB and fluoride varnish, FV), the treatment cost for caries (tertiary prevention), and the total cost under three scenarios; STB, FV and base case (no intervention)., Results: When the children aged 5 years, the treatment cost under the base case was the highest at 57.6 million baht while 53.5 million baht in FV and 51.9 million baht in STB. As a total cost, 64.1 million baht under FV, 60.9 million baht under STB, and 57.6 million baht under base case. Sensitivity analysis reveals that the effective rate of STB must be at least 30%, and FV should be a minimum of 50% to ascertain the total cost reduction relative to the base case scenario., Conclusion: Caries treatment costs were lower when STB and FV were implemented than in the base case scenario. The overall cost under FV was the highest, followed by STB, with no total cost savings observed as compared to the base case situation. Despite that, carrying out the STB rather than the FV would save a total of 3.2 million baht. Treatment costs under interventions would be lower than expected, and overall cost reductions might be obtained by comparing the base case if the intervention's effective rates are higher, according to sensitivity analysis., (© 2024. The Author(s).)

Background: It is challenging to predict long-term outcomes of interventions without understanding how they work. Health economic models of public health interventions often do not incorporate the many determinants of individual and population behaviours that influence long term effectiveness. The aim of this paper is to draw on psychology, sociology, behavioural economics, complexity science and health economics to: (a) develop a toolbox of methods for incorporating the influences on behaviour into public health economic models (PHEM-B); and (b) set out a research agenda for health economic modellers and behavioural/ social scientists to further advance methods to better inform public health policy decisions., Methods: A core multidisciplinary group developed a preliminary toolbox from a published review of the literature and tested this conceptually using a case study of a diabetes prevention simulation. The core group was augmented by a much wider group that covered a broader range of multidisciplinary expertise. We used a consensus method to gain agreement of the PHEM-B toolbox. This included a one-day workshop and subsequent reviews of the toolbox., Results: The PHEM-B toolbox sets out 12 methods which can be used in different combinations to incorporate influences on behaviours into public health economic models: collaborations between modellers and behavioural scientists, literature reviewing, application of the Behaviour Change Intervention Ontology, systems mapping, agent-based modelling, differential equation modelling, social network analysis, geographical information systems, discrete event simulation, theory-informed statistical and econometric analyses, expert elicitation, and qualitative research/process tracing. For each method, we provide a description with key references, an expert consensus on the circumstances when they could be used, and the resources required., Conclusions: This is the first attempt to rigorously and coherently propose methods to incorporate the influences on behaviour into health economic models of public health interventions. It may not always be feasible or necessary to model the influences on behaviour explicitly, but it is essential to develop an understanding of the key influences. Changing behaviour and maintaining that behaviour change could have different influences; thus, there could be benefits in modelling these separately. Future research is needed to develop, collaboratively with behavioural scientists, a suite of more robust health economic models of health-related behaviours, reported transparently, including coding, which would allow model reuse and adaptation., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) risk increases with age. Statins reduce cardiovascular risk but their effects are less certain at older ages. We assessed the long-term effects and cost-effectiveness of statin therapy for older people in the contemporary UK population using a recent meta-analysis of randomised evidence of statin effects in older people and a new validated CVD model., Methods: The performance of the CVD microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration (CTTC) and UK Biobank cohort, was assessed among participants ≥70 years old at (re)surveys in UK Biobank and the Whitehall II studies. The model projected participants' cardiovascular risks, survival, quality-adjusted life years (QALYs) and healthcare costs (2021 UK£) with and without lifetime standard (35%-45% low-density lipoprotein cholesterol reduction) or higher intensity (≥45% reduction) statin therapy. CTTC individual participant data and other meta-analyses informed statins' effects on cardiovascular risks, incident diabetes, myopathy and rhabdomyolysis. Sensitivity of findings to smaller CVD risk reductions and to hypothetical further adverse effects with statins were assessed., Results: In categories of men and women ≥70 years old without (15,019) and with (5,103) prior CVD, lifetime use of a standard statin increased QALYs by 0.24-0.70 and a higher intensity statin by a further 0.04-0.13 QALYs per person. Statin therapies were cost-effective with an incremental cost per QALY gained below £3502/QALY for standard and below £11778/QALY for higher intensity therapy and with high probability of being cost-effective. In sensitivity analyses, statins remained cost-effective although with larger uncertainty in cost-effectiveness among older people without prior CVD., Conclusions: Based on current evidence for the effects of statin therapy and modelling analysis, statin therapy improved health outcomes cost-effectively for men and women ≥70 years old., Competing Interests: Competing interests: AK reports research support from Abbott, Amgen, ASPEN, Bayer, Mylan, Novartis, Sanofi, Viatris; speaker fees from Novartis; and is a Data Safety Monitoring Board member for Kowa. JR reports funding from North East London Integrated Care Service. JA reports receiving a grant to their research institution from Novartis for the ORION 4 trial of inclisiran. JS reports receiving grants for his institution from Amgen, Bayer, BMS, MSD, Pfizer and Roche; consulting fees from FivepHusion, and is a chair (unpaid) of STAREE DSMB. CB reports research grants from Boehringer Ingelheim and Health Data Research UK and is a chair (unpaid) of a Data Safety Monitoring Board for Merck. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This paper quantifies the economic impact of regime changes and macroeconomic indicators on debt stress in Zambia using the Autoregressive Distributed Lag (ARDL) Bounds test. A 1% short run increase in gross domestic products (GDP) increases debt stress by 3.16% and in the subsequent year lowers it by 7.21%; in the long-run the 1% GDP increases lowers debt stress by 22%. In the long-run, a 1% rise in inflation and the lending rate negatively and positively impacted debt stress levels by -1.52% and 3.90%, respectively. Short-run shocks culminated regime change had short-run adverse impact on debt stress by 3.45% in one year and in the subsequent year by -10.35%, with the variables adjusting to long-run equilibrium at a speed of 71.5%. This is the first paper to quantify the empirical effect of macroeconomic indicators and change in Presidents on debt stress, especially in Africa were the problem of the debt trap is perpetuated. The results from the study implies that to deescalate the impact of debt stress on the economy, the electorate should vote in governments that will not fall short on growth driven macroeconomic policies, making it possible for economic sustainability to prevail; and paper seeks to promote good governance and good economic policies as a premise for sustained macroeconomic stability and development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Phiri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The impact of the degree and effectiveness corporate social responsibility (CSR) fulfillment on corporate value assessment by investors is significant. However, prior research on effects of CSR on stock price crash risk has showed contrasting results. Certain studies suggest that an abundance of CSR can become a self-serving tool for management. This may lead to concealing and accumulating negative information, resulting in stock price collapse. Based on principal-agent theory, we suggest that CSR equilibrium could be an effective approach to prevent the concealment of negative events by managers. Employing data from Chinese A-share listed companies spanning 2010 to 2020, we examine how CSR equilibrium and corporate governance levels influence the risk of stock price collapse across entities with different property rights. Empirical findings indicate that a balanced distribution of CSR can mitigate the risk of stock price collapse. Furthermore, we find that higher levels of corporate governance can mitigate the negative impact of CSR equilibrium on stock price collapse risk. Interestingly, this governance effect is more pronounced in state-owned enterprises compared to private enterprises, where the likelihood of hiding adverse information is higher. Additionally, it provides a theoretical explanation for the impact of CSR equilibrium on the risk of stock price collapse, based on the principal-agent problem, thereby expanding the applicability of the theory. Practically, the research findings carry significant implications for listed companies, CSR rating agencies, and investors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu, Tian. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Chronic migraine is a disabling condition, affecting 2-4% of adults globally. With the introduction of expensive calcitonin gene-related peptide monoclonal antibodies, it is timely to compare the clinical effectiveness and cost-effectiveness of preventive drugs for chronic migraine., Objective: To assess the clinical effectiveness and cost-effectiveness of medications used for chronic migraine through systematic reviews and economic modelling., Eligibility Criteria: Randomised controlled trials of drug treatments for efficacy with > 100 participants with chronic migraine per arm; for adverse events > 100 participants with episodic or chronic migraine per arm. Previous economic analyses of preventive drugs for chronic migraine., Data Sources: Eight databases., Reviews Methods: Systematic reviews, network meta-analysis and economic modelling., Outcomes: Monthly headache days, monthly migraine days, headache-related quality of life, cost-effectiveness., Results: We found 51 individual articles, reporting 11 randomised controlled trials, testing 6 drugs (topiramate, Botox, eptinezumab, erenumab, fremanezumab, galcanezumab), versus placebo, on 7352 adults with chronic migraine. Calcitonin gene-related peptide monoclonal antibodies, Botox and topiramate reduced headache/migraine days by 2.0-2.5, just under two, or by less than 1.5 days per month, respectively. In the network meta-analysis, eptinezumab 300 mg and fremanezumab monthly ranked in first place in both monthly headache day and monthly migraine day analyses. The calcitonin gene-related peptide monoclonal antibodies were consistently the best choices for headache/migraine days and headache-related quality of life. Topiramate was very unlikely to be the best choice for headache/migraine days and headache-related quality of life when compared to calcitonin gene-related peptide monoclonal antibodies or Botox. We found no trials of the commonly used drugs, such as propranolol or amitriptyline, to include in the analysis. The adverse events review included 40 randomised controlled trials with 25,891 participants; 3 additional drugs, amitriptyline, atogepant and rimegepant, were included. There were very few serious adverse events - none of which were linked to the use of these medications. Adverse events were common. Most people using some calcitonin gene-related peptide monoclonal antibodies reported injection site issues; and people using topiramate or amitriptyline had nervous system or gastrointestinal issues. The cost-effectiveness review identified 16 studies evaluating chronic migraine medications in adults. The newer, injected drugs are more costly than the oral preventatives, but they were cost-effective. Our economic model showed that topiramate was the least costly option and had the fewest quality-adjusted life-year gains, whereas eptinezumab 300 mg was more costly but generated the most quality-adjusted life-year gains. The cost-effectiveness acceptability frontier showed that topiramate was the most cost-effective medication if the decision maker is willing to pay up to £50,000 per quality-adjusted life-year. Our consensus workshop brought together people with chronic migraine and headache experts. Consensus was reached on the top three recommendations for future research on medications to prevent chronic migraine: (1) calcitonin gene-related peptide monoclonal antibodies and Botox versus calcitonin gene-related peptide monoclonal antibodies, (2) candesartan versus placebo and (3) flunarizine versus placebo., Limitations: Topiramate was the only oral drug for which we were able to include data. We did not find sufficient quality evidence to support the use of other oral drugs., Conclusions: We did not find evidence that the calcitonin gene-related peptide monoclonal antibodies are more clinically and cost-effective when compared to topiramate or Botox. We identified directions for future research these drugs might take., Study Registration: This study is registered as PROSPERO CRD42021265990, CRD42021265993 and CRD42021265995., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132803) and is published in full in Health Technology Assessment ; Vol. 28, No. 63. See the NIHR Funding and Awards website for further award information.

Introduction: Protocol-driven trial activities contribute to the utility gain demonstrated in the phase III clinical trial of a new drug. If this utility gain cannot be distinguished from the effects of the new drug itself, protocol-driven trial costs cannot be easily dismissed for consistency reasons. This study aims to estimate the impact of including per-patient costs of phase III clinical trials on the incremental cost-effectiveness ratio (ICER)., Methods: The analysis utilized a modeling approach with secondary data from an ad-hoc literature review, considering both societal and payer perspectives. While the costs of phase III clinical trials may cancel out during the period of "normal" life-years due to the incremental cost calculation, they do not cancel out when differential early treatment termination occurs (e.g., due to differential mortality). Assuming the presence of differential mortality, per-patient phase III trial costs were calculated for the period of added life-years. These costs were then included in the ICER of a new drug, under the assumption that direct patient-related costs constitute 30-70% of the total trial costs. Capital costs were also incorporated from a societal perspective., Results: Based on assumptions of $40,000 out-of-pocket expenses per patient enrolled in a phase III trial and a life expectancy gain of three months, incremental costs increased by $27,000 from a societal perspective. From a payer perspective, the estimate was $12,000., Conclusions: The costs of phase III trials are a relevant component of the ICER, and excluding it is generally not appropriate for consistency reasons. Properly considering these trial costs is essential for a comprehensive evaluation of a new drug's cost-effectiveness., (© 2024. The Author(s).)

This paper employs Topological Data Analysis (TDA) to detect extreme events (EEs) in the stock market at a continental level. Previous approaches, which analyzed stock indices separately, could not detect EEs for multiple time series in one go. TDA provides a robust framework for such analysis and identifies the EEs during the crashes for different indices. The TDA analysis shows that L1, L2 norms and Wasserstein distance (WD) of the world leading indices rise abruptly during the crashes, surpassing a threshold of μ+4∗σ, where μ and σ are the mean and the standard deviation of norm or WD, respectively. Our study identified the stock index crashes of the 2008 financial crisis and the COVID-19 pandemic across continents as EEs. Given that different sectors in an index behave differently, a sector-wise analysis was conducted during the COVID-19 pandemic for the Indian stock market. The sector-wise results show that after the occurrence of EE, we have observed strong crashes surpassing μ+2∗σ for an extended period for the banking, automobile, IT, realty, energy, and metal sectors. While for the pharmaceutical and FMCG sectors, no significant spikes were noted. Hence, TDA also proves successful in identifying the duration of shocks after the occurrence of EEs. This also indicates that the banking sector continued to face stress and remained volatile even after the crash. This study gives us the applicability of TDA as a powerful analytical tool to study EEs in various fields., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Stakeholder involvement has been proposed as a key strategy for appropriately managing value-laden decisions or 'value judgments' in health economics modelling. Philosophers of science, however, conceive of stakeholder involvement in research in conflicting ways, and also propose alternative strategies for 'managing values' in science. Furthermore, all proposed strategies for managing values in science raise philosophical questions and practical challenges that are difficult to resolve. As a result, health economists who seek to appropriately inform value judgments in modelling must currently go without straightforward guidance. There is a need to further explore how health economists should manage value judgments in modelling, taking into account philosophical debates and contextual constraints. This paper discusses core proposals for managing values in science and identifies philosophical questions and practical challenges these proposals leave unresolved. It further considers how this could potentially inform processes to manage value judgments in health economics modelling, using examples from an ongoing modelling project called LEAP (Lifetime Exposures and Asthma Outcomes Projection). We conclude that all strategies to 'manage values' in health economics modelling have strengths and weaknesses, but are generally compatible with one another, suggesting that health economists may use a combination of strategies. Further research is needed to explore the effects of strategies to 'manage values' in health economics modelling., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Noninvasive prenatal testing (NIPT) was developed to improve the accuracy of prenatal screening to detect chromosomal abnormalities. Published economic analyses have yielded different incremental cost-effective ratios (ICERs), leading to conclusions of NIPT being dominant, cost-effective, and cost-ineffective. These analyses have used different model structures, and the extent to which these structural variations have contributed to differences in ICERs is unclear., Aim: To assess the impact of different model structures on the cost-effectiveness of NIPT for the detection of trisomy 21 (T21; Down syndrome)., Methods: A systematic review identified economic models comparing NIPT to conventional screening. The key variations in identified model structures were the number of health states and modeling approach. New models with different structures were developed in TreeAge and populated with consistent parameters to enable a comparison of the impact of selected structural variations on results., Results: The review identified 34 economic models. Based on these findings, demonstration models were developed: 1) a decision tree with 3 health states, 2) a decision tree with 5 health states, 3) a microsimulation with 3 health states, and 4) a microsimulation with 5 health states. The base-case ICER from each model was 1) USD$34,474 (2023)/quality-adjusted life-year (QALY), 2) USD$14,990 (2023)/QALY, (3) USD$54,983 (2023)/QALY, and (4) NIPT was dominated., Conclusion: Model-structuring choices can have a large impact on the ICER and conclusions regarding cost-effectiveness, which may inadvertently affect policy decisions to support or not support funding for NIPT. The use of reference models could improve international consistency in health policy decision making for prenatal screening., Highlights: NIPT is a clinical area in which a variety of modeling approaches have been published, with wide variation in reported cost-effectiveness.This study shows that when broader contextual factors are held constant, varying the model structure yields results that range from NIPT being less effective and more expensive than conventional screening (i.e., NIPT was dominated) through to NIPT being more effective and more expensive than conventional screening with an ICER of USD$54,983 (2023)/QALY.Model-structuring choices may inadvertently affect policy decisions to support or not support funding of NIPT. Reference models could improve international consistency in health policy decision making for prenatal screening., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Semi-natural grasslands (SNGLs) in Estonia are threatened by abandonment. This threat is leading to concerns about the degradation of biodiversity within grassland communities. Despite the high relevance of economic incentives in this context, how such incentives influence land managers' decision-making regarding the agricultural use of SNGLs has not been investigated. To obtain its socio-ecological implications for policy-making, we developed regionally specific agricultural scenarios (compensation payments, livestock capacity, hey export, and bioenergy production) and an interdisciplinary modelling approach that made it possible to simulate agricultural land use changes through land managers' responses to varied economic conditions. Through this approach, we found that some economic factors hampered the use of SNGLs: the moderate profitability of beef production, labour shortages, and the relatively high profitability of mulching. We observed a positive relationship between SNGLs and habitat suitability for breeding and feeding birds. However, due to the high maintenance costs of SNGLs, the modelling results indicated that increasing the use of SNGLs through public budgets caused crowding-out effects, i.e., the deteriorating market integration of regional agriculture. This study emphasises the need for policy measures aimed at cost-effective, labour-efficient management practices for SNGLs., (© 2024. The Author(s).)

Twenty genetic therapies have been approved by the US Food and Drug Administration to date, a number that now includes the first CRISPR genome-editing therapy for sickle cell disease-CASGEVY (exagamglogene autotemcel, Vertex Pharmaceuticals). This extraordinary milestone is widely celebrated owing to the promise for future genome-editing treatments of previously intractable genetic disorders and cancers. At the same time, such genetic therapies are the most expensive drugs on the market, with list prices exceeding US$4 million per patient. Although all approved cell and gene therapies trace their origins to academic or government research institutions, reliance on for-profit pharmaceutical companies for subsequent development and commercialization results in prices that prioritize recouping investments, paying for candidate product failures and meeting investor and shareholder expectations. To increase affordability and access, sustainable discovery-to-market alternatives are needed that address system-wide deficiencies. Here we present recommendations of a multidisciplinary task force assembled to chart such a path. We describe a pricing structure that, once implemented, could reduce per-patient cost tenfold and propose a business model that distributes responsibilities while leveraging diverse funding sources. We also outline how academic licensing provisions, manufacturing innovation and supportive regulations can reduce cost and enable broader patient treatment., (© 2024. Springer Nature Limited.)

Objectives: Effective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia., Methods: Real-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model's applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV., Results: Clinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments., Conclusions: PRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Value-based trials aim to maximize the expected net benefit by balancing technology adoption decisions and clinical trial costs. Adaptive trials offer additional efficiency. This article provides guidance on determining whether a value-based sequential design is the best option for an adaptive 2-arm trial, illustrated through a case study., Methods: We outlined 4 steps for the value-based sequential approach. The case study re-evaluates the Big CACTUS trial design using pilot trial data and a model-based health economic analysis. Expected net benefit is computed for (1) original fixed design, (2) value-based design with fixed sample size, and (3) optimal value-based sequential design with adaptive stopping. We compare pretrial modeling with the actual Big CACTUS trial results., Results: Over 10 years, the adoption decision would affect approximately 215 378 patients. Pretrial modeling shows that the expected net benefit minus costs are (1) £102 million for the original fixed design, (2) £107 million (+5.3% higher) for the value-based design with optimal fixed sample size, and (3) £109 million (+6.7% higher) for the optimal value-based sequential design with maximum sample size of 435 per arm. Post hoc analysis using actual Big CACTUS trial data indicates that the value-adaptive trial with a maximum sample size of 95 participant pairs would not have stopped early. Bootstrap simulations reveal a 9.76% probability of early completion with n = 95 pairs compared with 31.50% with n = 435 pairs., Conclusions: The 4-step approach to value-based sequential 2-arm design with adaptive stopping was successfully implemented. Further application of value-based adaptive approaches could be useful to assess the efficiency of alternative study designs., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment., Methods: We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted., Results: The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions., Conclusions: Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Health economic evaluation (HEE) provides guidance for decision-making in the face of scarcity but ignores ecological scarcities as long as they involve external costs only. Following the imperative to account for planetary health, this study explores how this blind spot can be addressed., Areas Covered: The study is based on a critical review of relevant work, particularly in the fields of HEE and life cycle assessment (LCA). LCA can provide information on a technology's environmental impacts which can be accounted for on both the effect and cost sides of HEE. Cost-benefit analyses can incorporate environmental impacts in case vignettes used for eliciting consumers' willingness to pay. Existing LCA impact models can be used to estimate human health risks associated with environmental impacts and add them to the health benefits in cost-utility analyses. Many jurisdictions offer lists of shadow prices that can be used to incorporate environmental impacts on the cost side of HEE. Also, environmental impacts can be reported in a disaggregated manner., Expert Opinion: Accounting for planetary boundaries is likely to become a key field of methodological innovation in HEE. Decision relevance is likely to be highest for technologies with similar cost-effectiveness but different ecological impacts.

Background: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied., Objective: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015., Data and Methods: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs., Results: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs., Conclusion: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.)

There is increasing interest in the use of cure modelling to inform health technology assessment (HTA) due to the development of new treatments that appear to offer the potential for cure in some patients. However, cure models are often not included in evidence dossiers submitted to HTA agencies, and they are relatively rarely relied upon to inform decision-making. This is likely due to a lack of understanding of how cure models work, what they assume, and how reliable they are. In this tutorial we explain why and when cure models may be useful for HTA, describe the key characteristics of mixture and non-mixture cure models, and demonstrate their use in a range of scenarios, providing Stata code. We highlight key issues that must be taken into account by analysts when fitting these models and by reviewers and decision-makers when interpreting their predictions. In particular, we note that flexible parametric non-mixture cure models have not been used in HTA, but they offer advantages that make them well suited to an HTA context when a cure assumption is valid but follow-up is limited., (© 2024. The Author(s).)

Background: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK., Research Design and Methods: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection)., Results: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic., Conclusion: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Background: Recent advances in the development of biomarker-directed therapy and immunotherapy, for advanced and metastatic gastric cancers, have the potential to improve survival and quality of life. Much attention has been directed towards second- and later-line treatments, and the landscape here is evolving rapidly. However, uncertainty in relative effectiveness, high costs and uncertainty in cost effectiveness represent challenges for decision makers., Objective: To identify economic evaluations for the second-line or later-line treatment of advanced and metastatic gastric cancer. Also, to assess key criteria (including model assumptions, inputs and outcomes), reporting completeness and methodological quality to inform future cost-effectiveness evaluations., Methods: A systematic literature search (from database inception to 5 March 2023) of EconLit via EBSCOhost, Cochrane Library (restricted to National Health Service [NHS] Economic Evaluation Database and Health Technology Assessment [HTA] Database), Embase, MEDLINE and of grey literature was conducted. This aimed to identify systemic treatments that align with National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) Clinical Practice Guidelines. Data were collected on key criteria and on reporting completeness and methodological quality. A narrative synthesis focussed on cost-effectiveness and cost-of-illness studies. Outcomes of interest included total and incremental costs and outcomes (life-years and quality-adjusted life-years), ratios of incremental costs per unit outcome and other summary cost and outcome measures. Also, for cost-effectiveness studies, reporting completeness and the methodological quality were assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and the Philips Checklist, respectively., Results: A total of 19 eligible economic evaluations were identified (cost-effectiveness studies [n = 15] and cost-of-illness studies [n = 4]). There was a general lack of consistency in the methodological approaches taken across studies. In the main, the cost-effectiveness studies indicated that the intervention under consideration was more effective and more costly than the comparator(s). However, most interventions were not cost effective. No studies were fully compliant with reporting-completeness and methodological-quality requirements. Given the lack of consistency in the approaches taken across cost-of-illness studies, outcomes could not be directly compared., Conclusions: To our knowledge, this is the first published systematic literature review that has qualitatively synthesised economic evaluations for advanced and metastatic gastric cancer. There were differences in the approaches taken across the cost-effectiveness studies and the cost-of-illness studies. The conclusions of most of the cost-effectiveness studies were consistent despite identified differences in approaches. In the main, the interventions under consideration were not cost effective, presenting challenges to sustainability and affordability. We highlight a requirement for cost-effectiveness evaluations and for second-line or later-line treatments of advanced and metastatic gastric cancer that consider all relevant comparators and that are compliant with reporting-completeness and methodological-quality requirements. By addressing the methodological gaps identified here, future healthcare decision-making, within the context of this rapidly changing treatment landscape, would be better informed., Prospero Registration Number: CRD42023405951., (© 2024. The Author(s).)

Public sector employment in China has exhibited pronounced non-cyclical characteristics, with a recruiting scale and wage level showing limited responsiveness to economic fluctuations. The allure of civil service jobs in China has seen a significant resurgence post-COVID-19, with an observable increase in demand among educated job seekers for stable government positions amid growing economic uncertainties. This study investigates the implications of public sector employment rigidity on macroeconomic stability using a dynamic stochastic general equilibrium (DSGE) model integrated with search and matching (S&M) theory. Simulations incorporating alternative government job policies reveal that non-cyclical public employment exacerbates macroeconomic cyclical fluctuations. The low elasticity of public sector wages with respect to corporate wages fosters stable expectations among workers regarding the future value of government jobs, increasing the perceived value of the current state of unemployment. This leads job seekers to voluntarily remain unemployed, reducing labor supply to firms. Meantime, it preserves workers' bargaining power with firms, reinforcing wage stickiness and undermining the stabilizing role of price adjustments in employment. Hypothetical scenario analyses indicate that adopting a pro-cyclical wage policy for the public sector can mitigate the obstacles of wage cuts for firms, stimulate the creation of new jobs during economic downturns, and consequently reduce the magnitude and duration of rising unemployment rates. In contrast, maintaining a non-cyclical public sector wage may not prevent a continuous rise in unemployment or a worsening economic situation, even with expanded sector recruitment. This finding holds significant relevance in the context of the post-COVID era characterized by an economic slump and employment tension, providing theoretical support for establishing a transparent and flexible wage adjustment mechanism in the public sector that is linked to market conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xiaodi Zhang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the tobacco-attributable burden on disease, medical costs, productivity losses and informal caregiving; and to estimate the health and economic gains that can be achieved if the main tobacco control measures (raising taxes on tobacco, plain packaging, advertising bans and smoke-free environments) are fully implemented in eight countries that encompass 80% of the Latin American population., Design: Markov probabilistic microsimulation economic model of the natural history, costs and quality of life associated with the main tobacco-related diseases. Model inputs and data on labour productivity, informal caregivers' burden and interventions' effectiveness were obtained through literature review, surveys, civil registrations, vital statistics and hospital databases. Epidemiological and economic data from January to October 2020 were used to populate the model., Findings: In these eight countries, smoking is responsible each year for 351 000 deaths, 2.25 million disease events, 12.2 million healthy years of life lost, US$22.8 billion in direct medical costs, US$16.2 billion in lost productivity and US$10.8 billion in caregiver costs. These economic losses represent 1.4% of countries' aggregated gross domestic products. The full implementation and enforcement of the four strategies: taxes, plain packaging, advertising bans and smoke-free environments would avert 271 000, 78 000, 71 000 and 39 000 deaths, respectively, in the next 10 years, and result in US$63.8, US$12.3, US$11.4 and US$5.7 billions in economic gains, respectively, on top of the benefits being achieved today by the current level of implementation of these measures., Conclusions: Smoking represents a substantial burden in Latin America. The full implementation of tobacco control measures could successfully avert deaths and disability, reduce healthcare spending and caregiver and productivity losses, likely resulting in large net economic benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study presents a novel Buyback Rail Freight Option (BRFO), leveraging Stackelberg game theory to enhance the strategic management of rail freight transactions. By integrating traditional buyback theory with a multi-phase trigeminal tree pricing model and parameter identification through a nonparametric Ito stochastic method, the research addresses key challenges of information asymmetry and market uncertainty. The proposed methodology emphasizes dynamic pricing strategies and market adaptation, constructing a Nash equilibrium framework within railway freight pricing. The findings suggest significant strategic benefits for railway enterprises, positioning BRFO as a crucial tool for improving competitiveness in the face of alternative transport options., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Throughout, the effects of related-party transactions (RPTs) have been a hot topic in financial markets and corporate governance research. This paper analyzes the theoretical foundation of the effects of RPTs and constructs a new indicator, the quasi-profit margin, to assess the effects of RPTs by studying their impact on the quasi-profit margin. Based on the information asymmetry between transaction parties and the information screening theory, the paper proposes the buying inferior to selling theory, systematically explaining the impact of transaction direction on the effects of RPTs. Subsequently, using panel data from Chinese A-share listed companies from 2016 to 2021, the paper constructs fixed-effects models and conducts empirical studies from both exogenous and endogenous perspectives, employing estimation methods such as high dimensional fixed effects method, two-stage least squares method, and three-stage least squares method. The research indicates that RPTs of Chinese A-share listed companies generally exhibit a tunneling effect, and the transaction direction significantly affects the effects of RPTs. The higher the proportion of RPTs conducted as sellers to the total RPTs, the smaller the overall tunneling effect of the RPTs. This study has implications for reducing the tunneling risk of RPTs and improving corporate governance for listed companies, as well as providing some references for financial regulatory authorities to identify and rectify illegal RPTs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li, He. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the aim of exploring the impact mechanism of scientific and technological financial efficiency on regional real economy growth in the context of ecological civilization construction, this study introduces environmental regulation as a mediating factor. By analyzing changes in science and financial efficiency of science and technology, we provide an effective basis for regional real economy development. To achieve this goal, we define concepts such as science and financial efficiency of science and technology and regional real economy, measure data from 2012 to 2021, analyze the impact of science and financial efficiency of science and technology on economic growth using intermediary models, test mediation effects with bootstrap methods, and identify significant differences between regions. It indicates that enhancing science and financial efficiency of sci-tech benefits China's regional real economy growth, but there's unbalanced development across regions. Additionally, environmental regulation serves as a crucial intermediary in the relationship between sci-tech finance and economic growth. There exist regional disparities in the mediation effects of environmental regulation, with eastern regions demonstrating stronger effects compared to central and western regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang, Tian. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The Social Accounting Matrix (SAM) is an extension of Input-Output tables that records macro and meso-economic accounts of a socio-economic system. Its main objective is to provide a comprehensive understanding of the interrelationships among different economic sectors and agents. The SAM can be used for various purposes, including economic analysis, policy evaluation, and economic modelling. It allows policymakers to make more informed decisions, understand potential consequences of different policy options and serve as the foundation for constructing Computable General Equilibrium (CGE) models., Data Description: The SAM for Germany is a comprehensive source of data that reveals the incomes and expenditures of 163 different production sectors, along with data on factors of production, households, corporations, government, and external accounts with the rest of the world. Additionally, it provides information on gross fixed capital formation, changes in inventories, and natural capital accounts. This SAM was compiled by extending the EXIOBASE Input-Output (IO) accounts with data from the Federal Statistical Office of Germany. Balancing items were also used to ensure that the Total Income and Total Expenditure of the main transactors are in balance., (© 2024. The Author(s).)

The article explains the economic dynamics of the sports industry with adoption of deep learning algorithms and data mining methodology. Despite outstanding improvements in research of sports industry, a significant gap prevails with regard to proper quantification of economic benefits of this industry. Therefore, the current research is an attempt to filling this gap by proposing a specific economic model for the sports sector. This paper examines the data of sports industry covering the time span of 2012 to 2022 by using data mining technology for quantitative analyses. Deep learning algorithms and data mining techniques transform the gained information from sports industry databases into sophisticated economic models. The developed model then makes the efficient analysis of diverse datasets for underlying patterns and insights, crucial in realizing the economic trajectory of the industry. The findings of the study reveal the importance of sports industry for economic growth of China. Moreover, the application of deep learning algorithm highlights the importance of continuous learning and training on the economic data from the sports industry. It is, therefore, an entirely novel approach to build up an economic simulation framework using deep learning and data mining, tailored to the intricate dynamics of the sports industry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haishan Liu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Today, with a growing emphasis on sustainable economic development, corporate environmental, social and governance (ESG) performance is attracting increasing attention and favor from investors. This triggers a question: can good ESG performance of listed companies mitigate the "up and down" of the stock market by drawing investor attention? This paper utilizes the data from China's A-share listed companies from 2011 to 2020, with investor attention as a mediating variable, to explore how the ESG performance of listed companies influences abnormal stock price volatility. The findings suggest that stronger ESG performance of listed companies significantly reduces abnormal stock price volatility, in which investor attention plays a partial mediating role. This paper confirms the robustness of the findings through multiple robustness and endogeneity tests. Heterogeneity analysis reveals that listed companies with good ESG performance during the growth period are more likely to significantly mitigate abnormal stock price volatility. Similarly, firms that maintain commendable ESG performance in bear markets significantly reduce abnormal stock price volatility. These findings enrich the theoretical research on the impact of ESG performance on abnormal stock price volatility, provide empirical evidence for listed companies to emphasize ESG investment and encourage investors to consider ESG ratings. Additionally, the study provides a new perspective for government agencies to utilize corporate ESG performance to maintain the sound development of the capital market., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess whether Mediterranean diet and physical activity are also cost-effective in patients with established CVD., Methods and Results: A cost-utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in patients with CVD. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100 000 patients with CVD sampled from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study (n = 8947, mean age 62 ± 8.7 years, and 74% male). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of €1236 per person compared with usual care, resulting in an ICER of €-626/QALY [95% confidence interval (CI) -1929 to 2673]. At a willingness-to-pay of €20 000/QALY, INHB was 2.04 (95% CI 0.99-3.58) QALYs and INMB was €40 757 (95% CI 19 819-71 605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs., Conclusion: In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared with usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all patients with CVD., Competing Interests: Conflicts of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The green economy has been advocated globally as a solution to environmental issues. In China, it is considered a national strategy for future economic development. This study utilizes methods such as Industry Network, Maximum Spanning Tree (MST) method, Leiden Community Clustering (LCC) algorithm, and Weaver-Thomas (WT) model to explore the contribution and position of the green economy and industries in China's economic development. The findings are as follows: (1) The density of China's green industry network has experienced a process of initially tightening and then loosening, ultimately tending towards stability. (2) The trunk structure of China's industrial network remains relatively stable, forming an industrial structure with electricity, heat production and supply as the core. (3) China's industrial and green industry communities continue to improve and become more cohesive, but some green industries are still on the periphery of communities. (4) The ability of green industries to pull other industries is weak, and the subsequent promotion momentum needs to be improved. However, the green industry still has enormous room for growth and potential to unleash its long-term positive multiplier effects. More attention and support need to be given by managers and decision-makers, so that it can make better contributions to society and the economy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: In Zambia, 19.1% of the adult population had elevated blood pressure. Hence, the Ministry of Health in Zambia designated the improvement of hypertension (HTN) care services as a priority policy. However, there are limited data on cost-effective interventions to address HTN and their budget impact in sub-Saharan Africa. The objective of this paper is to investigate the cost-effectiveness of primary-level interventions for HTN (pharmaceutical treatments) compared with no treatment, and the budget impact, in the Chongwe District, rural Zambia., Methods: A cost-utility analysis was undertaken from the perspective of healthcare provider, employing a cohort Markov model with a lifetime horizon. The model was developed and populated with evidence from the literature, including novel locally collected cost data. The analysis was run for the overall population aged 40 years and above and for subpopulations stratified by three levels of risk and gender in Chongwe District by using cost data directly collected. A probabilistic analysis was performed to assess the probability of cost-effectiveness., Results: The dominant treatment for the general population was a combination therapy of diuretics and calcium blockers. The incremental cost-effectiveness ratio was US$1114 compared with no treatment. This was the most cost-effective first-line medication for HTN for all subgroup populations, except for the subgroups classified as low-risk defined by WHO. The estimated annual budget impact was US$1 015 605 in total if all HTN patients in Chongwe District received the most cost-effective treatment. Considering only material costs, the annual total budget was US$29 435., Conclusion: The most cost-effective first-line medication for HTN in rural Zambia was the combination therapy of diuretics and calcium blockers for the general population. From the perspective of budget impact, local government could need to secure approximately US$30 000 to facilitate the delivery of the most cost-effective HTN medications to the entire population over 40 years in need., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Missed opportunities to reduce numbers of primary major lower-limb amputation and increase limb-salvage procedures when treating chronic limb-threatening ischaemia have previously been identified in the literature. However, the potential economic savings for healthcare providers when salvaging a chronic limb-threatening ischaemia-affected limb have not been well documented., Methods: A model using National Health Service healthcare usage and cost data for 1.6 million individuals and averaged numbers of primary surgical procedures for chronic limb-threatening ischaemia from England and Wales in 2019-2021 was created to perform a budget impact analysis. Two scenarios were tested: the averaged national rates of major lower-limb amputation (above the ankle joint), angioplasty, open bypass surgery or arterial endarterectomy in the National Vascular Registry (current scenario); and revascularization rates adjusted based on the lowest amputation rate reported by the National Vascular Registry at the time of the study (hypothetical scenario). The primary outcome was the net impact on costs to the National Health Service over 12 months after the index procedure., Results: In the current scenario, the proportions of different index procedures were 10% for lower-limb major amputation, 55% for angioplasty, 25% for open bypass surgery and 10% for arterial endarterectomy. In the hypothetical scenario, the procedure rates were 3% for major lower-limb amputation, 59% for angioplasty, 27% for open bypass surgery and 11% for arterial endarterectomy. For 16 025 index chronic limb-threatening ischaemia procedures, the total care cost in the current scenario was €243 924 927. In the hypothetical scenario, costs would be reduced for index procedures (-€10 013 814), community care (-€633 943) and major cardiovascular events (-€383 407), and increased for primary care (€59 827), outpatient appointments (€120 050) and subsequent chronic limb-threatening ischaemia-related surgery (€1 179 107). The net saving to the National Health Service would be €9 645 259., Conclusion: A shift away from primary major lower-limb amputation towards revascularization could lead to substantial savings for the National Health Service without major cost increases later in the care pathway, indicating that care decisions taken in hospitals have wider benefits., (© Crown copyright 2024.)

Background: Stroke or transient ischaemic attack patients are at increased risk of secondary vascular events. Antiplatelet medications, most commonly clopidogrel, are prescribed to reduce this risk. Factors including CYP2C19 genetic variants can hinder clopidogrel metabolism. Laboratory-based or point-of-care tests can detect these variants, enabling targeted treatment., Objective: To assess the effectiveness of genetic testing to identify clopidogrel resistance in people with ischaemic stroke or transient ischaemic attack. Specific objectives: Do people tested for clopidogrel resistance, and treated accordingly, have a reduced risk of secondary vascular events? Do people with loss-of-function alleles associated with clopidogrel resistance have a reduced risk of secondary vascular events if treated with alternative interventions compared to clopidogrel? Do people with loss-of-function alleles associated with clopidogrel resistance have an increased risk of secondary vascular events when treated with clopidogrel? What is the accuracy of point-of-care tests for detecting variants associated with clopidogrel resistance? What is the technical performance and cost of CYP2C19 genetic tests? Is genetic testing for clopidogrel resistance cost-effective compared with no testing?, Design: Systematic review and economic model., Results: Objective 1: Two studies assessed secondary vascular events in patients tested for loss-of-function alleles and treated accordingly. They found a reduced risk, but confidence intervals were wide (hazard ratio 0.50, 95% confidence interval 0.09 to 2.74 and hazard ratio 0.53, 95% confidence interval 0.24 to 1.18). Objective 2: Seven randomised controlled trials compared clopidogrel with alternative treatment in people with genetic variants. Ticagrelor was associated with a lower risk of secondary vascular events than clopidogrel (summary hazard ratio 0.76, 95% confidence interval 0.65 to 0.90; two studies). Objective 3: Twenty-five studies compared outcomes in people with and without genetic variants treated with clopidogrel. People with genetic variants were at an increased risk of secondary vascular events (hazard ratio 1.72, 95% confidence interval 1.43 to 2.08; 18 studies). There was no difference in bleeding risk (hazard ratio 0.98, 95% confidence interval 0.68 to 1.40; five studies). Objective 4: Eleven studies evaluated Genomadix Cube accuracy; no studies evaluated Genedrive. Summary sensitivity and specificity against laboratory reference standards were both 100% (95% confidence interval 94% to 100% and 99% to 100%). Objective 5: Seventeen studies evaluated technical performance of point-of-care tests. Test failure rate ranged from 0.4% to 19% for Genomadix Cube. A survey of 8/10 genomic laboratory hubs revealed variation in preferred technologies for testing, and cost per test ranging from £15 to £250. Most laboratories expected test failure rate to be < 1%. Additional resources could enhance testing capacity and expedite turnaround times. Objective 6: Laboratory and point-of-care CYP2C19 testing strategies were cost-saving and increase quality-adjusted life-years compared with no testing. Both strategies gave similar costs, quality-adjusted life-years and expected net monetary benefit., Conclusions: Our results suggest that CYP2C19 testing followed by tailored treatment is likely to be effective and cost-effective in both populations., Future Work: Accuracy and technical performance of Genedrive. Test failure rate of Genomadix Cube in a National Health Service setting. Value of testing additional loss-of-function alleles. Appropriateness of treatment dichotomy based on loss-of-function alleles., Limitations: Lack of data on Genedrive. No randomised 'test-and-treat' studies of dipyramidole plus aspirin., Study Registration: This study is registered as PROSPERO CRD42022357661., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135620) and is published in full in Health Technology Assessment ; Vol. 28, No. 57. See the NIHR Funding and Awards website for further award information.