Second-order Monte Carlo Simulation Research Articles

Cost-Effectiveness of a Shock Team Approach in Refractory Cardiogenic Shock.

Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care. We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations. The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18-92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%; P=0.04 and 55.0% versus 40.5%; P=0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations. The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.

Microbiological risk assessment of Bacillus cereus in popular hot dishes eaten by plant-based diet consumers in France

There is a current trend towards plant-based diets in Western countries. Since changes in the diet imply possible changes in exposure to foodborne pathogens, there is an increasing need to assess the microbiological risks associated with these diets. This study aims to assess microbiological risks for French adults associated with Bacillus cereus group III and group IV in hot, homemade cereal- and lentil-based dishes. A probabilistic retail-to-fork risk assessment model was developed considering cooking, cooling at ambient temperature, and storage under chilled conditions. Data came from a representative national survey, public database and literature. The model was developed in R, and uncertainty and variability were separated using second-order Monte Carlo simulations. Not all consumers have the same storage and cooling practices, so the results were expressed by probabilistic distributions built by specific storage time. The mean concentration of Bacillus cereus in portions at the time of consumption after 72 h of storage was 1.2 log CFU.g−1 for cereal-based dishes and 3.4 log CFU.g−1 for lentil-based dishes. After 72 h of storage under chilled conditions, the risk per portion, defined as the probability of contamination over 5 log CFU.g−1, was 0 (95 % CI: 0 - 0) for cereal-based dishes and 7.95 × 10−4 (95 % CI: 5.55 × 10−4 - 1.12 × 10−3) for lentils-based dishes. However, if cooling time at room temperature reached 24 h, the risk for cereal- and lentil-based dishes increased to 2.39 × 10−3 (95 % CI: 1.15 × 10−3 - 4.90 × 10−3) and 4.66 × 10−1 (95 % CI: 3.16 × 10−1 - 6.07 × 10−1), respectively. The sensitivity analysis indicated that the initial prevalence and level of contamination were key factors in limiting the risk, ranking before cooling time or refrigeration conditions. Besides, the scenario analysis revealed an influence of consumer behaviour regarding cooling and storage time on the risk per portion. The environmental trend towards plant-forward diets, combined with the emerging no-food waste and batch cooking practices in France, will likely favour new consumption patterns and increase the risk associated with Bacillus cereus. Our model will help quantify this extra burden.

Investigating the Reliability of an Existing Top Angle and Seat Pad Semi-Rigid Connection System Using Advanced Modelling Techniques

The investigation introduces an advanced model procedure for evaluating the structural reliability of semi-rigid frame connections in existing aged buildings. Specifically, the focus is on the top angle and seat pad (TA–SP) semi-rigid connection, which was not initially considered in the current design standards. The approach employs a plastic hinge model to predict the ultimate strength of the connection and its beam-to-column behaviour. In order to increase computational efficiency, the investigation leverages the nonlinear behaviour of the finite element (FE) model to validate critical parameters. The statistical properties of the existing connection were obtained based on past experimental data, highlighting the weakest elements in the system. The first-order and second-order reliability methods and Monte Carlo simulations were employed to estimate the reliability index. Percentile errors were assessed to understand their impact on higher-order interactions. This new technique of identification quantifies the probability of the system failure interactions. Notably, a 45% lesser error aligns with the target reliability index, while a 114.5% larger error indicates a significant deviation from actual failure probability values. Each methodology introduced adheres to the current standard, and the system reliability analysis provides a vigorous conclusions scheme framework for assessing the existing TA–SP semi-rigid connection.

Cumulative risk assessment of dietary exposure of the adult population in Serbia to pesticides that have chronic effects on the thyroid gland through fresh fruits and vegetables

In contrast to the traditional approach to risk assessment, which focuses on a single chemical, cumulative exposure and risk assessment considers the consequences of exposure to multiple chemical combinations. A cumulative risk assessment of dietary exposure of adult females and adult males to pesticides with chronic effects on the thyroid was conducted by estimation of the Total Margin of Exposure (MOET). Exposure to each active substance was estimated using a second-order Monte Carlo simulation. Input values for the simulation were based on over 2300 conventionally produced fruit and vegetable samples analysed from 2021 to 2023 and consumption data collected using the Food Frequency Questionnaire (FFQ) and 24h recall method. MOET values, for both populations assessed, did not exceed thresholds for regulatory consideration established by risk managers. Considering that MOETs values from consumption of fresh fruits and vegetables were relatively close to the threshold value, total exposure to the pesticides could likely reach risk-associated MOET levels, through the consumption of other food products that may be contaminated.

Abstract 17955: Cost-Effectiveness of a Shock Team Approach in Refractory Cardiogenic Shock

Background: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock (CS), but their implementation costs have not been studied. Objectives: To compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared to standard of care (SoC). Methods: We examined patients with refractory CS, treated with or without a Shock Team at a tertiary academic hospital from 2009-2018. Real-world hospital data was used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality adjusted life years (QALYs) gained at 1 year. Incremental cost-effectiveness ratios (ICER) were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using (PSA) 1000 second-order Monte Carlo simulations. Results: The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving SoC. Patients were predominantly male (77.5%), with a mean age of 58 years (18-92). The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% vs 47.9%; p=0.04 & 55.0% vs 40.5%; p=0.03, respectively). The ICER for increases in survival probability at discharge for the multidisciplinary Shock Team compared to SoC was $102,088. The ICER for increases in survival probability at 1-year was estimated at $96,152 and at $127,862 per one QALY gained. PSA estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150,000, while it was also dominant in almost one-third of the simulations. Conclusion: The Shock Team approach for treating refractory CS may be a cost-effective alternative to traditional SoC. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.

Cost-effectiveness of weekly gastro-resistant risedronate 35mg, compared with weekly alendronate 70mg tablets, in the treatment of postmenopausal osteoporosis in Spain.

Aim: To estimate the cost-effectiveness of treating postmenopausal osteoporosis (PMO) with weekly gastro-resistant risedronate 35mg gastro-resistant tablets (RIS-GR), compared with weekly alendronate 70mg tablets (ALN) in Spain. Methods: A probabilistic analysis (second-order Monte Carlo simulation) was performed with a time horizon of 5years, from the perspective of the Spanish National Health System. The bone fracture probabilities were obtained from a cohort study of 3614 women from USA with PMO treated with RIS-GR (1807) or ALN (1807) (Thomasius, 2022). The pharmacological cost and the cost of fractures were obtained from Spanish sources (€ 2022). The utilities of patients with and without fracture (quality-adjusted life years [QALYs]) were obtained from the medical literature. Results: Compared with ALN, treatment with RIS-GR can avoid 79 fractures (between 75 and 82) every 1000 patients treated, and 0.0119 QALYs would be gained (between 0.0098 and 0.0140) per patient. Additionally, GR-RIS would generate a cost saving per patient of €1994 (€1437-2904) with a probability of 99.7%. The scenario analyses confirmed the stability of the base case results. Conclusion: According to this study, RIS-GR would be the dominant treatment (lower costs with QALY gain) compared with ALN.

Modified control variates method based on second-order saddle-point approximation for practical reliability analysis

Abstract. A novel method is presented for efficiently analyzing the reliability of engineering components and systems with highly nonlinear complex limit state functions. The proposed method begins by transforming the integral of the limit state function into an integral of a highly correlated limit state function using the control variates method. The second-order reliability method is then employed within the control variates framework to approximate the highly correlated limit state function as a quadratic polynomial. Subsequently, the probability of failure is obtained through the estimation of the saddle-point approximation and a small number of samples generated by Latin hypercube sampling. To demonstrate the effectiveness of the proposed method, four examples involving mathematical functions and mechanical problems are solved. The results are compared with those obtained using the second-order reliability method (SORM), control variates based on Monte Carlo simulation (CVMCS) with second-order saddle-point approximation (SOSPA), importance sampling (IS) and Monte Carlo simulation (MCS). The findings demonstrate that, while maintaining high-precision reliability results, the proposed method significantly reduces the number of evaluations of the limit state function through a small number of initial samples. The method is capable of efficiently and accurately solving complex practical engineering reliability problems.

Cost-effectiveness of apixaban and rivaroxaban in thromboprophylaxis of cancer patients treated with chemotherapy in Spain

BackgroundApixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points.MethodsA cost-effectiveness analysis was performed from the perspective of Spain’s National Health System (NHS) using an analytical decision model in the short-term (180 days) and a Markov model in the long-term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€2,021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted.ResultsIn the probabilistic sensitivity analysis, apixaban generated a cost per patient of €1,082 ± 187, with a 95% confidence interval (CI) of €713–1,442, while no prophylaxis produced a cost per patient of €1,146 ± 218, with a 95% CI of €700–1,491, with a saving of €64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of €993 ± 133, with a 95% CI of €748–1,310, while no prophylaxis produced a cost per patient of €872 ± 152, with a 95% CI of €602–1,250, with an additional expense of €121 per patient and a gain of 0.008 QALYs.ConclusionsIn thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar costs compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain.

Economic evaluation of third-line neratinib plus capecitabine versus lapatinib plus capecitabine with HER2+ metastatic breast cancer.

Breast cancer (BC) is one of the most common malignant tumors in women. In addition, human epidermal growth factor receptor 2-positive (HER2+) BC is overexpressed in 25% of BC patients, resulting in the predicament of poor prognosis. Although first- and second-line treatments have been established, optimum third-line treatment is still mired in controversies for HER2+ metastatic BC (mBC). Therefore, this study analyzes the cost-effectiveness of neratinib plus capecitabine (N+C) and lapatinib plus capecitabine (L+C) over a 5-year time horizon from a payer perspective. A half-cycle corrected four-state Markov model was established to simulate the course of BC events and deaths in N+C and L+C armed patients. The data of this model were derived from NCT01808573 trail and other published literatures. One-way deterministic sensitivity analysis (DSA) was conducted to investigate the impact of variables and probabilistic sensitivity analysis (PSA) was performed based on second-order Monte Carlo simulation. In addition, subgroup analysis was performed to verify its cost-effectiveness in China. The base-case results found that N+C was in dominant position in 82.70% of the generation scenarios, providing an improvement of 0.17 quality-adjusted life-years (QALYs) and a reduction of $1,861.28 compared with L+C. The ICER was $-1,3294.86/QALY, which did not exceed the willingness to pay (WTP) threshold, while in subgroup, the ICER decreased to $-2,448.17/QALY. This analysis indicated that the combination of neratinib plus capecitabine is likely to be cost-effective in comparison with lapatinib plus capecitabine in patients with HER2+ mBC who continues to progress during or after second-line HER2-targeted therapy. So neratinib plus capecitabine can become a third-line treatment option.

Residential flood risk in Metro Vancouver due to climate change using probability boxes

ABSTRACT To enhance the decision-making process and reduce economic losses caused by future flooding, it is critical to quantify uncertainty in each step of flood risk analysis. To address the often-missing uncertainty quantification, we propose a new methodology that combines damage functions and probability bounds analysis. We estimate the likely direct tangible damage to 375,973 residential buildings along the Fraser River through Metro Vancouver, Canada, for a range of climate change driven flood scenarios, while transparently representing the associated uncertainties caused by sampling error, imprecise measurement, and uncertainty in building height and basement conditions. Furthermore, for the purposes of developing effective management strategies, uncertainties in this study are classified into two categories, namely aleatory and epistemic. According to our findings and absent significant action, we should expect an enormous increase in flood damage to the four categories of residential buildings considered in this study by the year 2100. Moreover, the results show that second-order Monte Carlo simulation cannot adequately represent epistemic uncertainty for small sample sizes. In such a case, we recommend employing a probability box to delineate the epistemic uncertainty.

Cost-effectiveness of cladribine tablets and dimethyl fumarate in the treatment of relapsing remitting multiple sclerosis in Spain.

Aim: To analyze the cost-effectiveness of treatment of relapsing remitting multiple sclerosis (RRMS) with cladribine tablets (CladT) and dimethyl fumarate (DMF) from the perspective of the Spanish National Health System (NHS). Methods: A probabilistic Markov model (second-order Monte Carlo simulation) with a 10-year time horizon and annual Markov cycles was performed. Results: CladT was the dominant treatment, with lower costs (-74,741 € [95% CI: -67,247; -85,661 €]) and greater effectiveness (0.1920 [95% CI: -0.1659; 0.2173] QALY) per patient, compared with DMF. CladT had a 95.1% probability of being cost-effective and a 94.1% chance of being dominant compared with DMF. Conclusion: CladT is the dominant treatment (lower costs, with more QALYs) compared with DMF in the treatment of RRMS in Spain.

Cost-utility of apixaban and rivaroxaban in the thromboprophylaxis of cancer patients treated with chemotherapy in Spain.

e24102 Background: Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy. The objective was to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. Methods: A cost-utility analysis was performed from the perspective of Spain´s National Health System (NHS) using an analytical decision model in the short term (180 days) and a Markov model in the long term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€ 2021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. Results: In the base case, apixaban was dominant (with a gain of 0.005 QALY, quality-adjusted life years, and a saving of €59.49 per patient) compared to no prophylaxis. Rivaroxaban would be cost-effective (with a gain of 0.006 QALY and an additional expense of €116.23 per patient) with a cost per QALY gained of €18,747 compared to no prophylaxis. For an willingness to pay of €25,000 per QALY gained, the probability that apixaban or rivaroxaban will be cost-effective would be 62.6% and 51.9%, respectively. Conclusions: VTE thromboprophylaxis with apixaban generates savings and with rivaroxaban it generates an additional cost vs. no prophylaxis. With both DOACs, a modest QALY gain would be obtained. The probability that prophylaxis with apixaban would be cost-effective is 10.7% higher than with rivaroxaban.

Economic evaluation of the personalisation of immunosuppressive therapy in kidney transplantation by means of an in vitro diagnostic test (Immunobiogram®) in Spain

Objective: Immunobiogram (IMBG) is an in vitro diagnostic immune function bioassay that evaluates the pharmacodynamic immune response profile of each patient to individual immunosuppressants (IMS) in renal transplant. The objective was to estimate the potential economic and health impact of the use of IMBG for the Spanish National Health System (NHS). Methods: The evolution of a cohort of patients with kidney transplantation at least 1 year after transplantation (time horizon of 5 years) was simulated using a second-order Monte Carlo simulation for two scenarios: renal failure in patients with high immunological risk (HR), and adverse events (AE) in stable patients (non-HR). The transition probabilities were obtained from a clinical study with IMBG and a systematic review. The cost associated with graft failure (dialysis, re-transplantation), IMS and AE management were obtained from Spanish sources. Results: IMS adjustment, according to the IMBG could contribute to a risk reduction of graft failure with a saving per HR patient of €20,263 (95% CI €17,520-23,678) (100% saving probability). The expected reduction in the AE rate would generate savings per non-HR patient of €1,409 (95% CI €41-3,316) (97.8% saving probability). Compared with the option of not using IMBG, 0.5256 (95% CI 0.3388, 0.7452) years of life and 0.0219 (95% CI 0.0115; 0.0356) quality-adjusted life years (QALY) would be gained in each patient evaluated with IMBG. Conclusions: IMBG could contribute to a risk reduction of graft failure and AEs related with IMS, with gain in years of life and QALY, as well as with considerable savings for the NHS. Key words: diagnosis; Immunobiogram; kidney transplantation; personalized medicine; rejection.

A second-order Monte Carlo simulation model to describe coagulase-positive Staphylococci growth in mayonnaise served in Algerian pizzerias

To bridge the data gap on food poisoning caused by coagulase-positive staphylococci (CoPS), especially related to mayonnaise sauce served at Algerian pizzerias, this study aimed to assess the concentration of CoPS in mayonnaise and the probability of exceeding a critical concentration of ≥ 5 log CFU/g. The city of Ain Témouchent in West Algeria was taken as a case study.A probabilistic assessment model was built, taking into account the initial contamination in freshly made mayonnaise and the potential growth before serving. Uncertainty and variability were integrated separately in the model. Uncertainty came from lack of data and model fitting error, variability from natural heterogeneity of biological materials (e.g., microbial strains) and temperature during cold storage.The second-order Monte Carlo procedure was implemented in R using the mc2d package. The following pieces of data were generated to populate the model: CoPS were enumerated and characterized from 57 samples of mayonnaise served at pizzeria in Ain Témouchent city; challenge tests at 23 °C were performed in mayonnaise using three CoPS isolates. The following existing data were also gathered: meteorological data from Ain Témouchent were analysed to build a realistic scenario of storage, while a set of 43 and 35 values of the minimal and maximal growth limits of CoPS, respectively, were collected from the literature and analysed to inform a secondary predictive model describing the growth rate at various storage temperature conditions. A sensitivity analysis was performed to facilitate the interpretation of the results.The results revealed a CoPS prevalence in freshly made mayonnaise of 25% [15%; 37%] with concentrations varying from 0.4 [0.3; 0.9] to 2.9 [2.4; 3.0] log CFU/g. The growth rates at 23 °C, based on challenge tests in mayonnaise, had a median value estimated to be 1.41 [1.17; 1.65] h − 1.Concentration levels according to various scenarios of temperature and serving conditions were calculated. For instance, the median contamination of CoPS in mayonnaise after storage in a refrigerated display counter for 14 h during the hottest months of the year was estimated to be zero. However, the 95th percentile was estimated to be 3.6 [2.9; 4.2] log CFU/g. In this scenario, the probability of exceeding a critical concentration of ≥ 5 log CFU/g was estimated to be 1% [0.3%; 2%], which is low but not negligible.These findings could be used to improve food safety policies and develop a risk management strategy to reduce the food poisoning associated with the consumption of ready-to-use foods in Algerian fast food restaurants.

A Veterans' Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysis.

The Core Elements of Outpatient Antibiotic Stewardship provides a framework to improve antibiotic use, but cost-effectiveness data on implementation of outpatient antibiotic stewardship interventions are limited. We evaluated the cost-effectiveness of Core Element implementation in the outpatient setting. An economic simulation model from the health-system perspective was developed for patients presenting to outpatient settings with uncomplicated acute respiratory tract infections (ARI). Effectiveness was measured as quality-adjusted life years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug events (ADEs), and healthcare utilization were obtained from the literature. Probabilities for antibiotic treatment and appropriateness, ADEs, hospitalization, and return ARI visits were estimated from 16,712 and 51,275 patient visits in intervention and control sites during the pre- and post-implementation periods, respectively. Data for materials and labor to perform the stewardship activities were used to estimate intervention cost. We performed a one-way and probabilistic sensitivity analysis (PSA) using 1,000,000 second-order Monte Carlo simulations on input parameters. The proportion of ARI patient-visits with antibiotics prescribed in intervention sites was lower (62% vs 74%) and appropriate treatment higher (51% vs 41%) after implementation, compared to control sites. The estimated intervention cost over a 2-year period was $133,604 (2018 US dollars). The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared to usual care. In the PSA, the intervention was dominant in 63% of iterations. Implementation of the CDC Core Elements in the outpatient setting was a cost-effective strategy.

Clinical and economic benefit of 32 years of antiretroviral treatment for people living with HIV in Spain: Has it been an efficient intervention?

IntroductionAlthough antiretroviral therapy (ART) for HIV/AIDS was introduced in 1987, improvement in disease progression and reduction in mortality at a population level was not observed until 1996, with the combination of three or more drugs. The objective was to estimate the clinical and economic benefit of ART in Spain in the 32-year period between 1987 and 2018. MethodsA cost-benefit analysis was performed, using a second-order Monte Carlo simulation, from the societal (base case) and the National Health System (NHS) perspectives. New cases of HIV, AIDS and related deaths were obtained from the SINIVIH and UNAIDS registries, with population projections without ART using triple exponential smoothing. Expenditure on ART was obtained from the National AIDS Plan reports and market studies. ResultsThe NHS invested 6185 million euros in 32 years. In that period, 323,651 AIDS-related deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) is estimated at 35,812 million euros (societal) and 1032 million euros (NHS). For every euro invested in ART, a return on investment of € 6.79 and € 1.16 was obtained, respectively. ConclusionsThe use of ART over 32 years prevented a large number of deaths and cases of AIDS and HIV, providing significant economic savings for the NHS. ART is an efficient intervention for the NHS.

Beneficio clínico y económico de 32 años de tratamiento antirretroviral de personas que viven con VIH en España: ¿ha sido una intervención eficiente?

Although antiretroviral therapy (ART) for HIV / AIDS was introduced in 1987, improvement in disease progression and reduction in mortality at a population level was not observed until 1996, with the combination of three or more drugs. The objective was to estimate the clinical and economic benefit of ART in Spain in the 32-year period between 1987 and 2018. A cost-benefit analysis was performed, using a second-order Monte Carlo simulation, from the societal (base case) and the National Health System (NHS) perspectives. New cases of HIV, AIDS and related deaths were obtained from the SINIVIH and UNAIDS registries, with population projections without ART using triple exponential smoothing. Expenditure on ART was obtained from the National AIDS Plan reports and market studies. The NHS invested 6,185 million euros in 32 years. In that period, 323,651 AIDS-related deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) is estimated at 35,812 million euros (societal) and 1,032 million euros (NHS). For every euro invested in ART, a return on investment of € 6.79 and € 1.16 was obtained, respectively. The use of ART over 32 years prevented a large number of deaths and cases of AIDS and HIV, providing significant economic savings for the NHS. ART is an efficient intervention for the NHS.

Model and Empirical Research on Risk Assessment Based on Second-Order Monte Carlo Simulation

First order Monte Carlo simulation simplifies the processing of input variables, while the analysis results can not meet the needs of major decisions. Second order Monte Carlo simulation divides the input variables into uncertainty and variability, which can help decision makers understand the impact of different input variables on the results and the credibility of the evaluation results. On the basic of analysing the two methods, an enterprise’s investment project was taken as an example; using point estimation method, first-order Monte Carlo simulation and second-order Monte Carlo methods respectively for risk assessment and comparison. Finally, conclusions and recommendations are given for using second-order Monte Carlo simulation for risk assessment of Investment Project Decision-making.

PIN39 Thirty Two YEARS of Antiretroviral Therapy (ART) for People Living with HIV in Spain: HAS IT Been an Efficient Intervention?

The aim of this study is to estimate the clinical and economic impact of ART in Spain over a 32-year period (1987-2018). A cost-benefit analysis was performed, using a second-order Monte Carlo simulation model, from a societal (base case) and National Health Service (NHS) perspective. New cases of HIV, AIDS and associated deaths in Spain were obtained from SINIVIH registry and UNAIDS. Local projections of new HIV cases, AIDS cases, and AIDS related deaths in a scenario without ART were estimated by triple exponential smoothing. HIV and AIDS cases averted and deaths prevented, were estimated. ART expenditure and the benefits of avoiding HIV infections and AIDS cases were obtained from National HIV plan assessment reports and Market Research data. The monetary value of a life was estimated as the local annual GDP per capita. The model’s assumptions and data were validated by a panel of 4 Spanish experts. The NHS invested 6,185 million euros on ART over 32 years. In that period, 323,651 AIDS deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) associated with these results is estimated at 35,812 million euros (social perspective) and 1,032 million euros (NHS perspective). ART is a profitable investment as it would render benefit/cost ratios of 6.79 (95%CI 5.39-8.35) and 1.17 (95% CI: 1.16; 1.18) from a social and NHS perspective, respectively. Subanalysis of ART drugs marketed by Gilead Sciences (2002-2018), brought out a net benefit of 8,361 million euros, 23% of the total (benefit/cost ratio of 3.2 from a social perspective). The use of ART over 32 years in Spain has highly limited the amount of deaths from AIDS as well as new cases of both HIV and AIDS, while simultaneouly providing significant economic savings.

VA Antibiotic Stewardship Intervention to Improve Outpatient Antibiotic Use for ARIs: A Cost-Effectiveness Analysis

Background: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use, but cost-effectiveness data on interventions to improve antibiotic use are limited. Beginning in September 2017, an antibiotic stewardship intervention was launched in within 10 outpatient Veterans Healthcare Administration clinics. The intervention was based on the Core Elements and used an academic detailing (AD) and an audit and feedback (AF) approach to encourage appropriate use of antibiotics. The objective of this analysis was to evaluate the cost-effectiveness of the intervention among patients with uncomplicated acute respiratory tract infections (ARI). Methods: We developed an economic simulation model from the VA’s perspective for patients presenting for an index outpatient clinic visit with an ARI (Fig. 1). Effectiveness was measured as quality-adjusted life-years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug reactions (ADRs), and healthcare utilization were obtained from the published literature. Probability parameters for antibiotic treatment, appropriateness of treatment, antibiotic ADRs, hospitalization, and return ARI visits were estimated using VA Corporate Data Warehouse data from a total of 22,137 patients in the 10 clinics during 2014–2019 before and after the intervention. Detailed cost data on the development of the AD and AF materials and electronically captured time and effort for the National AD Service activities by specific providers from a national ARI campaign were used as a proxy for the cost estimate of similar activities conducted in this intervention. We performed 1-way and probabilistic sensitivity analyses (PSAs) using 10,000 second-order Monte Carlo simulations on costs and utility values using their means and standard deviations. Results: The proportion of uncomplicated ARI visits with antibiotics prescribed (59% vs 40%) was lower and appropriate treatment was higher (24% vs 32%) after the intervention. The intervention was estimated to cost $110,846 (2018 USD) over a 2-year period. Compared to no intervention, the intervention had lower mean costs ($880 vs $517) and higher mean QALYs (0.837 vs 0.863) per patient because of reduced inappropriate treatment, ADRs, and subsequent healthcare utilization, including hospitalization. In threshold analyses, the antibiotic stewardship strategy was no longer dominant if intervention cost was >$64,415,000 or the number of patients cared for was <3,672. In the PSA, the antibiotic stewardship intervention was dominant in 100% of the 10,000 Monte Carlo iterations (Fig. 2). Conclusions: In every scenario, the VA outpatient AD and AF antibiotic stewardship intervention was a dominant strategy compared to no intervention.Funding: NoneDisclosures: None