One-year Time Horizon Research Articles

Modeling the velocity of evolving lineages and predicting dispersal patterns

Accurate estimation of the dispersal velocity or speed of evolving organisms is no mean feat. In fact, existing probabilistic models in phylogeography or spatial population genetics generally do not provide an adequate framework to define velocity in a relevant manner. For instance, the very concept of instantaneous speed simply does not exist under one of the most popular approaches that models the evolution of spatial coordinates as Brownian trajectories running along a phylogeny. Here, we introduce a family of models-the so-called Phylogenetic Integrated Velocity (PIV) models-that use Gaussian processes to explicitly model the velocity of evolving lineages instead of focusing on the fluctuation of spatial coordinates over time. We describe the properties of these models and show an increased accuracy of velocity estimates compared to previous approaches. Analyses of West Nile virus data in the United States indicate that PIV models provide sensible predictions of the dispersal of evolving pathogens at a one-year time horizon. These results demonstrate the feasibility and relevance of predictive phylogeography in monitoring epidemics in time and space.

Cost-utility of sirolimus in the treatment of vascular malformations.

Sirolimus is being increasingly employed to manage specific vascular anomalies. We performed an exploratory cost-utility analysis to evaluate sirolimus as a treatment for vascular malformations from the Australian healthcare system perspective. Over a one-year time horizon, sirolimus treatment was associated with an increased expenditure of AU$2832.80 and a gain of 0.08 quality-adjusted life years (QALYs) when compared to supportive care, resulting in an incremental cost-effectiveness ratio of AU$35,410/QALY. By most metrics, sirolimus would be considered a cost-effective treatment for vascular malformations.

Enhancing Outcomes in Opioid Use Disorder Treatment: An Economic Evaluation of Improving Medication Adherence for Buprenorphine Through Blister-Packaging.

The opioid epidemic has severely impacted the US over the last 15 years. Buprenorphine is a partial opioid agonist indicated for the treatment of opioid use disorder (OUD) and is recognized as an effective treatment when taken as prescribed. However, adherence rates have been low in real-world settings. Blister-packaging has been shown to promote medication adherence across a variety of disease states, although it has never been studied in OUD. An economic analysis was conducted to assess the impact of increased adherence of blister-packaged buprenorphine on health care resource utilization (HCRU) and health care costs for 10,000 patients initiating therapy for OUD. The model analyzed a commercially insured population within the US over a one-year time horizon. Medication adherence was defined in the model as proportion of days covered (PDC) of at least 80%. Literature-based references were used to inform both the impact of blister-packaging on the number of patients who became adherent as well as the impact of medication adherence on HCRU and health care costs. Model input uncertainty was assessed in one-way sensitivity analyses. With the implementation of blister-packaging buprenorphine, adherence rates increased from 37.1% of patients in the pre-intervention period to 45.3%, resulting in an additional 818 patients becoming adherent post-intervention. The increase in adherence led to a reduction of medical costs of $12,138,757 (-$1,214 per-patient (PP)). Specifically, inpatient costs decreased by $7,127,073 (-$713 PP) while outpatient costs decreased by $5,013,319 (-$501 PP). Pharmacy costs increased by $3,432,705 ($343 PP). Despite the increase in pharmacy costs, total health care costs saw a reduction of $8,559,684 (-$856 PP). Blister-packaging buprenorphine for treatment of OUD has potential to improve medication adherence and health outcomes while reducing HCRU and health care costs. Future studies are necessary to assess the real-world application and impact of blister-packaging buprenorphine for OUD across various patient populations and health care settings.

Silicone adhesive multilayer foam dressings to prevent hospital-acquired sacrum pressure ulcers: An economic evaluation based on a publicly funded pragmatic randomized controlled trial linked with real-world data

ObjectivesTo estimate the cost-effectiveness of sacrum multilayer silicone foam dressings as an adjuvant prophylactic therapy compared to standard pressure ulcer prevention in a hospital population at high risk for pressure ulcer development. MethodsAn economic evaluation is performed from a healthcare payer's perspective. This evaluation is based on a Belgian publicly funded pragmatic randomized controlled trial (RCT), linked with real-world data from administrative claims database and a Belgian cost analysis. A cost-consequences analysis with a one-year time horizon is performed. ResultsThe RCT has shown that the risk of developing a new pressure ulcer on the sacrum was statistically significantly reduced by 41 % in the treatment group (RR = 0.59, 95 % CI 0.35–0.98, p = 0.04). The absolute risk reduction of 2.0 % (95 % CI -0.1–4.1 %) coincides with a number needed to treat of 50.0 to prevent one new pressure ulcer of category II or worse. The evolution of quality of life is on average negative for patients who developed a pressure ulcer before day 3, while it is positive for patients without pressure ulcers. In a scenario with conservative assumptions, i.e. without inclusion of price discounts for the multilayer silicone foam dressings and only including costs during the hospitalization, pressure ulcer prevention with dressings on the sacrum was already cost-neutral. ConclusionsThe preventive use of silicone adhesive multilayer foam dressings on the sacrum for a population similar to the pragmatic trial population can be supported both from a clinical and economic point of view.

Cost-Effectiveness of Pediatric Conjunctivitis Management and Return to Childcare and School Strategies: A Comparative Study.

Infectious conjunctivitis affects 1 in 8 children annually, resulting in high ophthalmic antibiotic prescribing and absenteeism from childcare and school. We aimed to quantify the cost-effectiveness and annual savings of 3 evidence-based approaches to conjunctivitis management and return to childcare and school compared to usual care. Using a decision analytic model from a societal perspective over a 1-year time horizon, we conducted a cost-effectiveness analysis of 3 management strategies for children aged 6 months to 17 years with non-severe conjunctivitis compared to usual care in the United States. Strategies accounted for rate of transmission. Strategies included (1) refraining from prescribing ophthalmic antibiotics for non-severe conjunctivitis, (2) allowing children without systemic symptoms to attend childcare and school, (3) and the combined approach of refraining from prescribing ophthalmic antibiotics and allowing children without systemic symptoms to attend childcare and school. The estimated annual expenditure for pediatric conjunctivitis was $1.95 billion. Usual care was the most expensive ($212.73/episode), followed by refraining from ophthalmic antibiotic prescribing ($199.92) and allowing children without systemic symptoms to attend childcare and school ($140.18). The combined approach was the least costly ($127.38). Disutility was similar between approaches (quality-adjusted life days 0.271 vs 0.274). Refraining from antibiotic prescribing and the combination approach were dominant compared to usual care. The combined approach resulted in an estimated $783 million annual savings and 1.6 million ophthalmic antibiotic courses averted. Conjunctivitis poses an economic burden that could be reduced by refraining from ophthalmic antibiotic use and allowing children without systemic symptoms to remain at school or childcare.

A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation

IntroductionThree randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective.MethodsIndividual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis.ResultsFirst-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon.ConclusionFirst-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

Implementing teleophthalmology services to improve cost-effectiveness of the national eye care system

Background and purposeOptometrist-assisted and teleophthalmology-enabled referral pathway (OTRP) for community optometry referrals has the potential to improve the capacity and efficiency of eye care delivery systems through risk stratification and limiting the number of improved referrals. This study investigates the expected future costs and benefits of implementing OTRP under various possible organizational set-ups relevant to a Danish context.MethodsA decision-analytic model (decision tree) with a one-year time horizon was constructed to portray alternative future patient referral pathways for people examined in optometry stores for suspected ocular posterior segment eye disease. The main outcomes were total healthcare costs per patient, average waiting time from eye examination in store until the start of treatment or end of referral pathway, and quality-adjusted life-years (QALY) gained. The economic evaluation compares the general ophthalmologist referral pathway (GO-RP) with a potential reimbursement model for the optometrist-assisted teleophthalmology referral pathways (R-OTRP) and a procurement model for the optometrist-assisted teleophthalmology referral pathways (P-OTRP).ResultsThe cost per individual with suspected ocular posterior segment eye disease was estimated to be £116 for GO-RP and £75 and £94 for P-OTRP and R-OTRP respectively. The average waiting time for diagnosis or end of referral pathway was 25 weeks for GO-RP and 5.8 and 5.7 for P-OTPR and R-OTPR respectively. QALY gain was 0.15 for P-OTRP/R-OTRP compared to 0.06 for GO-RP.ConclusionOTRP is effective in reducing unnecessary referrals and waiting times, increasing patients’ HRQoL, and decreasing the costs of diagnosing individuals with suspected ocular posterior segment eye disease.

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a Danish healthcare perspective

Abstract Background As demonstrated in three randomized clinical trials (RCTs), initial rhythm control with first-line pulmonary vein isolation (PVI) using cryoballoon ablation decreases atrial arrhythmia recurrence compared to antiarrhythmic drug (AAD) therapy in patients with symptomatic paroxysmal atrial fibrillation (PAF). Purpose To assess the cost-effectiveness of first-line cryoablation versus first-line AADs in a Danish healthcare setting. Methods Data from 703 participants with symptomatic PAF enrolled into Cryo-FIRST, STOP AF First and EARLY-AF RCTs were used to estimate risk equations (rate of ablation, AF recurrence and resolution, AF-related hospital attendance in addition to health-related quality-of-life (HRQoL) utilities). These were then incorporated into a cost-effectiveness model (CEM) . The Danish cost data was derived from published Danish literature, DRG tariffs and pharmaceutical list prices in Denmark. Where parameters could not be derived, inputs were sourced from published literature or expert opinion. The CEM consisted of a decision tree (one-year time horizon) and a Markov model (three-month cycle length) hybrid, with a lifetime (40 years) time horizon. The CEM is from the perspective of the Danish healthcare system. Health benefits were expressed in quality-adjusted life-years (QALYs), and all costs and benefits were discounted at 3%. As there is no official cost-effectiveness threshold in Denmark, the UK threshold of £20,000 (~€23,200) was assumed. Input uncertainty within the CEM was explored using probabilistic sensitivity analysis. The results presented include data from the initial 12-week blanking period for all studies. Results The three-monthly rate of AF symptom recurrence had a reduction, on average, of 46.7% (p<0.001) in those treated with cryoablation. In addition, the cryoablation arm had a 72.8% (p<0.001) reduction in the monthly rate of receiving an ablation following initial treatment. The average cryoablation patient was also associated with a 4.3% (p=0.025) increase in their HRQoL. Finally, there was no difference in the rate of AF symptom resolution in those who failed initial treatment. Base case results per patient are presented in Table 1. Cryoablation was shown to be dominant when compared to AADs (0.159 more QALYs and €2,519 less costly), with a 99.96% probability of being cost-effective at a willingness-to-pay threshold of ~€23,200 per QALY gained. Individuals in both arms of the model were also expected to receive ~1.2 ablations over a lifetime horizon. Nonetheless, there was a 45% relative reduction in time spent in symptomatic AF states for individuals who were initially treated with cryoablation. Scenario analysis results are presented in Table 2. Cryoablation remained cost-effective over AADs in all scenarios conducted. Conclusions Initial rhythm control with cryoballoon ablation is cost-effective (dominant) when compared to AADs in the Danish healthcare system.Table 1:Key results (per patient)Table 2.Deterministic scenario analysis

The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.

A short-term economic evaluation of early insulin therapy compared to oral anti-diabetic drugs in order to reduce the major adverse events in type 2 diabetes patients in Iran

Objective While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy’s cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. Methods In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran’s healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. Results The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. Conclusion In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

Improving Adherence and Reducing Health Care Costs Through Blister-Packaging: An Economic Model for a Commercially Insured Health Plan.

To model the potential clinical and economic impact of blister-packaging medications for chronic conditions on medication adherence and healthcare costs in a commercially insured population. A health economic model was developed to evaluate the potential impact of blister-packaging chronic medications for a commercially insured population. The chronic medication classes assessed were renin-angiotensin-system (RAS) antagonists, statins, non-insulin oral antidiabetics, and direct oral anticoagulants (DOACs). The model was designed to reflect the perspective of a hypothetical commercially insured health plan with 100,000 members, over a one-year time horizon. Literature-based or best available epidemiologic references were used to inform the number of patients utilizing each medication class, the impact of blister-packaging on the number of patients who become adherent, as well as the impact of medication adherence in a commercially insured population on healthcare costs for each medication class assessed. Impact on costs was measured in total net healthcare costs, as well as being stratified by medical costs and medication costs. Following the blister-packaging intervention, there were an additional 591 patients adherent to RAS antagonists, 1196 patients adherent to statins, 169 patients adherent to oral antidiabetics, and 25 patients adherent to DOACs. While pharmacy costs increased, these costs were more than offset by the reduction in medical costs. Overall, the increase in patients adherent to therapy due to blister-packaging led to a reduction in total healthcare costs of $879,312 for RAS antagonists (-$0.73 per-member per-month (PMPM)), $343,322 for statins (-$0.29 PMPM), $78,917 for oral antidiabetics (-$0.07 PMPM), and $120,793 for DOACs (-$0.10 PMPM). Blister-packaging chronic medications in a commercially insured population has the potential to reduce healthcare costs. Future research is needed to confirm these findings in real-world settings and to fully understand the clinical and economic implications of blister-packaging chronic medications.

Budget Impact Analysis of Minimally Invasive versus Open Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disease: A European Hospital Perspective.

When traditional therapies fail to provide relief from debilitating lower back pain, surgeries such as transforaminal lumbar interbody fusion (TLIF) may be required. This budget impact analysis (BIA) compared minimally-invasive (MI)-TLIF versus open (O)-TLIF for single-level fusion from an Italian hospital perspective. The BIA compared costs of 100 MI-TLIF and 100 O-TLIF procedures from an Italian hospital perspective over a one-year time horizon. The base case included costs for length of hospital stay (LOS), blood loss, and sterilizing surgical trays. The scenario analysis also included operating room (OR) time and complication costs. Base case inputs were from the Miller et al meta-analysis; scenario analysis inputs were from the Hammad et al meta-analysis. The device costs for MI-TLIF and O-TLIF procedures were from Italian tender prices for Viper Prime™ System and Expedium™ Spine System, respectively. Base case deterministic analysis results showed cost savings of €207,370 for MI-TLIF compared with O-TLIF. MI-TLIF costs were lower for LOS (€215,277), transfusion for blood loss (€16,881), and surgical tray sterilization (€28,232), whereas device costs were lower for O-TLIF (€53,020). The probabilistic result was similar, with MI-TLIF resulting in savings of €211,026 (95% credible interval [CR]: €208,725 - €213,327). All 1000 base case probabilistic sensitivity analysis runs were cost saving. Deterministic scenario analysis results showed cost savings of €166,719 for MI-TLIF. MI-TLIF costs were lower for LOS (€190,813), transfusion for blood loss (€16,881), surgical tray sterilization (€28,232), and complications (€2076), whereas O-TLIF costs were lower for OR time (€18,263) and devices used (€53,020). Despite the increase incremental cost for medical device innovation and OR time, this study demonstrates the economic savings of MI-TLIF compared to O-TLIF from a European hospital perspective. The findings will be useful to policy and hospital decision makers in assessing purchasing, funding and reimbursement decisions.

Cost-effectiveness of intravascular ultrasound-guided percutaneous intervention in patients with acute coronary syndromes: A UK perspective.

Use of intravascular ultrasound (IVUS) during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes over angiography alone. Despite this, the adoption of IVUS in clinical practice remains low. To examine the cost-effectiveness of IVUS-guided PCI compared to angiography alone in patients with acute coronary syndromes (ACS). A one-year decision tree and lifetime Markov model were constructed to compare the cost-effectiveness of IVUS-guided PCI to angiography alone for two hypothetical adult populations consisting of 1,000 individuals: ST-elevation myocardial infarction (STEMI) and unstable angina/ non-ST-elevation myocardial infarction (UA/NSTEMI) patients undergoing drug-eluting stent (DES) implantation. The UK healthcare system perspective was applied using 2019/20 costs. All-cause death, myocardial infarction (MI), repeat PCI, lifetime costs, life expectancy and quality-adjusted life-years (QALYs) were assessed. Over a lifetime horizon, IVUS-guided PCI was cost-effective compared to angiography alone in both populations, yielding an incremental cost-effectiveness ratio of £3,649 and £5,706 per-patient in STEMI and UA/NSTEMI patients, respectively. In the one-year time horizon, the model suggested that IVUS was associated with reductions in mortality, MI and repeat PCI by 51%, 33% and 52% in STEMI and by 50%, 29% and 57% in UA/NSTEMI patients, respectively. Sensitivity analyses demonstrated the robustness of the model with IVUS being 100% cost-effective at a willingness-to-pay (WTP) threshold of £20,000 per QALY-gained. From a UK healthcare perspective, an IVUS-guided PCI strategy was highly cost-effective over angiography alone amongst ACS patients undergoing DES implantation due to the medium- and long-term reduction in repeat PCI, death, and MI.

An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a German healthcare service payer perspective

Abstract Background Three recent randomized controlled trials demonstrated that, in patients with symptomatic paroxysmal atrial fibrillation (PAF), first-line pulmonary vein isolation (PVI) with cryoballoon ablation reduces atrial arrhythmia recurrence when compared to initial antiarrhythmic drug (AAD) therapy. Purpose To evaluate the cost-effectiveness of initial rhythm control therapy from a German healthcare service payer perspective. Methods The cost-effectiveness model (CEM) structure consisted of a hybrid decision tree and Markov model, where the decision tree informed the initial health state allocation in the first cycle of the Markov model and had a one-year time horizon. The Markov model had a 40-year time horizon using a three-month cycle length. Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% p.a. Individual patient-level data from 703 participants with untreated PAF enrolled into Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518) and EARLY-AF (NCT02825979) were used to estimate efficacy, resource use and health-related quality of life parameters. Cost inputs were sourced from diagnosis-related groups and the Institute for the Hospital Remuneration System (InEK). Where parameters could not be derived, inputs were sourced from available published literature or determined through clinical expert opinion. Probabilistic sensitivity analyses were conducted to explore the impact of any assumptions on model outputs. Results In those treated with cryoablation, the three-month rate of AF recurrence was reduced by 46.7% (p<0.001) on average. Similarly, the average monthly rate of receiving an ablation following initial treatment was reduced by 72.8% (p<0.001). Cryoablation was also associated with a 4.3% (p=0.025) increase in health-related quality of life at 12 months, assessed through the standard EQ-5D-3L instrument. There was no difference in the rate of AF resolution in those who failed initial treatment. CEM results are shown in Table 1. Analysis shows that cryoablation is cost-effective, incurring a cost of ∼€1,000 per patient over a lifetime compared to AADs, while offering an increase in QALYs. Cryoablation attains an average ICER of ∼€5,500, with a 94.1% probability of being cost-effective at a willingness-to-pay threshold of €35,000 per QALY gained. Through 5,000 iterations, the probabilistic sensitivity analysis indicates that cryoablation has ∼20% probability of being cost-saving. Individuals are expected to receive a total of ∼1.2 ablations over a lifetime, regardless of initial treatment. Although, those initially treated with cryoablation as opposed to AADs experience a 45% reduction in time spent in AF health states. Conclusion Initial rhythm control with cryoballoon ablation in PAF is a cost-effective treatment option in a German healthcare setting.Table 1:Key results (per patient)

A cost-utility analysis on a multicomponent intervention for fibromyalgia syndrome in Spain

Abstract Background Fibromyalgia is a chronic musculoskeletal condition associated with widespread pain, fatigue, and other somatic symptoms that reduce functionality and quality of life. Its significant economic burden for society urges improving the usual clinical practice. Methods This study presents a trial-based cost-utility analysis on a multicomponent intervention programme (MCI) for patients with fibromyalgia compared to the usual clinical care in Catalonia's primary care centres. This economic evaluation was conducted from a societal perspective, a human capital approach, and a one-year time horizon. The study outcomes included direct medical costs, productivity losses, and quality of life. Quality-adjusted life years (QALYs) were calculated using the SF-6Dv2 metric algorithm. Subsequently, crude and adjusted incremental cost-utility ratios (ICUR) were estimated to compare the treatment strategies and one- and two-way deterministic sensitivity analyses were performed. Results The complete case analysis comprised 297 individuals (161 in the intervention group / 136 controls). The obtained crude ICUR of €1,780.75 per QALY gained, and the adjusted ICUR of €851.67 suggested that the increase in participants’ quality of life outweighed the cost increase as they fell below the cost-effectiveness threshold. Furthermore, the sensitivity analyses supported the robustness of the results when variating large cost components and increasing therapeutic adherence, which endorsed the implementation scheme. Conclusions Given its cost-utility for society, the study's results support including the proposed MCI as part of the standard regional practice for patients with fibromyalgia. These findings provide decision-makers with evidence to enhance the healthcare approach to fibromyalgia syndrome, reduce its social burden and improve patients’ quality of life in a context of medical uncertainty. Key messages • The usual clinical practice for fibromyalgia syndrome urges improving its therapeutic approach in a scenario of medical uncertainty. • Patients with fibromyalgia syndrome can benefit from multicomponent intervention programmes that cover physical, psychological and health education needs reducing the economic burden for society.

Reducing Nervousness in Master Production Planning: A Systematic Approach Incorporating Product-Driven Strategies

Manufacturing companies face a significant challenge when developing their master production schedule, navigating unforeseen disruptions during daily operations. Moreover, fluctuations in demand pose a substantial risk to scheduling and are the main cause of instability and uncertainty in the system. To address these challenges, employing flexible systems to mitigate uncertainty without incurring additional costs and generate sustainable responses in industrial applications is crucial. This paper proposes a product-driven system to complement the master production plan generated by a mathematical model. This system incorporates intelligent agents that make production decisions with a function capable of reducing uncertainty without significantly increasing production costs. The agents modify or determine the forecasted production quantities for each cycle or period. In the case study conducted, a master production plan was established for 12 products over a one-year time horizon. The proposed solution achieved an 11.42% reduction in uncertainty, albeit with a 2.39% cost increase.

A Two-Stage Stochastic Linear Programming Model for Tactical Planning in the Soybean Supply Chain

Background: The soybean market is representative of the world. Brazil is the largest producer and exporter of this crop and has low production costs but high logistical costs, which are influenced mainly by transport costs. Added to these characteristics, the disputed grain supply, the possibility of crop failure, and the randomness of some parameters that influence the soybean supply chain make decisions even more challenging. Methods: To mathematically model this problem, we carried out an analysis of the scientific production related to grain supply chain and the models used to address the problem, as well as a document analysis and a case study. Results: This paper proposes a new two-stage stochastic linear programming model with fixed recourse for tactical planning in the soybean supply chain from the perspective of the shipper under take or pay contracts over a one-year time horizon. The first-stage variables are the grain purchasing decisions and the volumes of rail and road transportation hired in advance. The model addresses 243 scenarios derived from four uncertainty sources: the purchase and sale prices of raw agricultural products on the spot market, the probability of crop failure, and the external demand. Conclusions: The model is successfully applied to a soybean trade firm in Brazil with expected gain of US$4,299,720 when using the stochastic model instead of the deterministic model. The stochastic model protected the firm from take or pay fines and crop failures, contracting a smaller volume of rail transport than what the company does.

Clinical and economic outcomes associated with use of anti-arrhythmic drugs versus ablation in atrial fibrillation.

Aim: To evaluate the clinical and economic impact of antiarrhythmic drugs (AADs) compared with ablation both as individual treatments and as combination therapy without/with considering the order of treatment among patients with atrial fibrillation (AFib). Materials & methods: A budget impact model over a one-year time horizon was developed to assess the economic impact of AADs (amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, and as a group) versus ablation across three scenarios: direct comparisons of individual treatments, non-temporal combinations, and temporal combinations. The economic analysis was conducted in accordance with CHEERS guidance as per current model objectives. Results are reported as costs per patient per year (PPPY). The impact of individual parameters was evaluated using one-way sensitivity analysis (OWSA). Results: In direct comparisons, ablation had the highest annual medication/procedure cost ($29,432), followed by dofetilide ($7661), dronedarone ($6451), sotalol ($4552), propafenone ($3044), flecainide ($2563), and amiodarone ($2538). Flecainide had the highest costs for long-term clinical outcomes ($22,964), followed by dofetilide ($17,462), sotalol ($15,030), amiodarone ($12,450), dronedarone ($10,424), propafenone ($7678) and ablation ($9948). In the non-temporal scenario, total costs incurred for AADs (group)+ablation ($17,278) were lower compared with ablation alone ($39,380). In the temporal scenario, AADs (group) before ablation resulted in PPPY cost savings of ($22,858) compared with AADs (group) after ablation ($19,958). Key factors in OWSA were ablation costs, the proportion of patients having reablation, and withdrawal due to adverse events. Conclusion: Utilization of AADs as individual treatment or in combination with ablation demonstrated comparable clinical benefits along with costs savings in patients with AFib.

P-457 A biosimilar FSH is a cost-effective option for women undergoing IVF/ICSI treatment in France

Abstract Study question Is Bemfola® a cost-effective treatment option compared to Gonal-f® for women undergoing IVF/ICSI treatment in France based on real-world evidence? Summary answer Bemfola® is a cost-effective treatment option, based on real-world evidence, demonstrating lower gonadotropin costs per live-birth following one ovarian stimulation cycle compared to Gonal-f®. What is known already Since Bemfola®’s first launch in 2015, real-world data has been collected in France, comparing it with the originator Gonal-f®, in the REOLA study (Barriere P, et al., J Gynecol Obstet Hum Reprod. 2023;52:102510). This study demonstrated comparable clinical outcomes according to follicle stimulating hormones (FSH) starting dose between the two FSH, in terms of oocytes retrieved, cumulative live-birth rate (CLBR), and total FSH dose per cycle. Previous health economic studies comparing the cost-effectiveness of Bemfola® against Gonal-f® utilise clinical trial data and therefore leave ambiguity over the cost-effectiveness as the results may not reflect what happens in clinical practice. Study design, size, duration We developed a decision-tree cost-effectiveness model with a one-year time horizon based on the gonadotropin costs and CLBR per ovarian stimulation for Bemfola® and Gonal-f®. The output was gonadotropin cost per live-birth following one ovarian stimulation cycle. CLBR per ovarian stimulation data were taken from the REOLA real-world study while acquisition costs were taken from publicly available databases in France. Model structure and methodology were based on previous publications and validated by clinical experts. Participants/materials, setting, methods The model used clinical data from REOLA, a non-interventional, retrospective, real-world study conducted in 17 French Assisted Reproductive Technology (ART) centres including data from 2,319 Bemfola® and 4,287 Gonal-f® ovarian stimulation cycles for IVF/ICSI grouped according to starting dose. Data was collected for ovarian stimulations between the dates of 01/01/16 and 28/02/17 and CLBR included a follow-up to live-birth of all pregnancies following both fresh and frozen embryo transfer within 12 months of oocyte retrieval. Main results and the role of chance The REOLA study data utilised within the model comparing Bemfola® vs Gonal-f® grouped according to FSH starting dose (< 150 IU, 150 - 224 IU, 225 −299 IU and ≥ 300 IU) are the median total FSH used - 1100 IU, 1500 IU, 2250 IU and 3300 IU vs 1008 IU, 1500 IU, 2250 IU and 3300 IU, and the CLBR - 30.5%, 25.4%, 21.4% and 12.3% vs 27.0%, 27.3%, 19.6% and 12.0%, respectively. The gonadotropin cost per live-birth for Bemfola® was €2,302.12 compared to €2,856.26 per live-birth for Gonal-f®, saving €554.15 per live-birth. The main reasons for this cost saving was the lower acquisition costs of Bemfola® of €489.01 compared with Gonal-f® costs of €597.36 on average per ovarian stimulation. As this analysis is based on real world data as opposed to results from clinical studies it can be used to estimate potential gonadotrophin cost savings in clinical practice in France. With 27,861 babies born annually in France using ART it can be estimated that if all had been born following Gonal-f® usage then a change to all being born following Bemfola® usage could result in savings sufficient to fund gonadotrophins for an additional 31,572 ovarian stimulation cycles. Limitations, reasons for caution The model assumed equal distribution of Bemfola® and Gonal-f® across the starting dose categories and have assumed that the number of fresh and frozen cycles required following ovarian stimulation would be equivalent irrespective of the gonadotropin used. Wider implications of the findings Bemfola® is cost-effective compared to Gonal-f® for IVF/ICSI treatment which would potentially enable more women to be treated with the same healthcare budget for the French health system. This might apply for other countries where Bemfola® is available and benefit from lower acquisition costs than Gonal-f®. Trial registration number not applicable

Cost-effectiveness of routine annual influenza vaccination by age and risk status

BackgroundThe epidemiology of circulating seasonal influenza strains changed following the 2009 pandemic influenza A(H1N1). A universal influenza vaccination recommendation has been implemented and new vaccine types have become available post-2009. The objective of this study was to evaluate the cost-effectiveness of routine annual influenza vaccination in the context of this new evidence. MethodsA state transition simulation model was constructed to estimate the health and economic outcomes of influenza vaccination compared to no vaccination for hypothetical US cohorts stratified by age and risk status. Model input parameters were derived from multiple sources, including post-2009 vaccine effectiveness data from the US Flu Vaccine Effectiveness Network. The analysis used societal and healthcare sector perspectives and a one-year time horizon, except permanent outcomes were also included. The primary outcome was the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life years (QALYs) gained. ResultsCompared to no vaccination, vaccination yielded ICERs lower than $95,000/QALY for all age and risk groups, except for non-high-risk adults 18–49 years ($194,000/QALY). Vaccination was cost-saving for adults ≥50 years at higher risk for influenza-related complications. Results were most sensitive to changes in the probability of influenza illness. Performing the analysis from the healthcare sector perspective, excluding vaccination time costs, delivering vaccinations in lower-cost settings, and including productivity losses improved the cost-effectiveness of vaccination. Sensitivity analysis revealed that vaccination remains below $100,000/QALY for older persons ≥65 years at vaccine effectiveness estimates as low as 4 %. ConclusionsCost-effectiveness of influenza vaccination varied by age and risk status and was less than $95,000/QALY for all subgroups, except for non-high-risk working-age adults. Results were sensitive to the probability of influenza illness and vaccination was more favorable under certain scenarios. Vaccination for higher risk subgroups resulted in ICERs below $100,000/QALY even at low levels of vaccine effectiveness or circulating virus.