OBJECTIVE:Chronic kidney disease (CKD) is the leading cause of kidney failure, end-stage kidney disease (ESKD), and cardiovascular (CV) events in patients with type 2 diabetes (T2D). The FIDELIO-DKD trial demonstrated that finerenone lowered the risk of renal and CV events in patients with CKD and T2D, regardless of cardiovascular disease history. This study evaluated the cost-effectiveness of finerenone added to background treatment (finerenone + BT) versus background treatment (BT) alone in patients with CKD and T2D from the perspective of the National Health Service in England and Wales. METHODS:A lifetime Markov model assessed the indicated usage of finerenone for the treatment of stage 3 or 4 CKD with albuminuria associated with T2D in adults, as per the relevant marketing authorization. The model structure considered kidney disease progression and CV risk, with health states encompassing patients' kidney disease stage and CV event profiles, using patient-level data from the FIDELIO-DKD trial. Model outcomes were life years, quality-adjusted life years (QALYs), per-patient costs, incremental costs, and incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analysis were performed, including an analysis exploring the impact of real-world data which suggests more frequent sodium-glucose co-transporter-2 (SGLT2) inhibitor use in the United Kingdom since FIDELIO-DKD. RESULTS:Patients receiving finerenone experienced kidney and CV benefits, including reduced rates of nonfatal CV events and CV deaths, translating to improvements in survival and quality-adjusted life years (QALYs) of 6.11 and 5.97 per patient for finerenone + BT versus BT, respectively. Total discounted per-patient costs were £48,940 for finerenone + BT and £47,716 for BT alone, resulting in an incremental cost-effectiveness ratio of £8,808 per QALY gained for finerenone + BT versus BT. CONCLUSION:Sensitivity and scenario analyses, including more frequent SGLT2 inhibitor use consistent with real-world data, indicate a robust ICER that remains within the bounds of what is typically considered cost-effective.

Randomized controlled trials (RCTs) are the gold standard when comparing treatment effectiveness, and Health Technology Assessment (HTA) agencies state a clear preference for such direct comparisons. When these are not available, an indirect treatment comparison (ITC) is an alternative option. The objective of this study was to assess the acceptance of ITC methods by HTA agencies across England, France, Germany, Italy, and Spain, using oncology cases for a homogeneous sample of HTA evaluations. The study was conducted on the PrismAccess database in May 2021 to retrieve HTA evaluation reports for oncology treatments for solid tumors, in which an ITC was presented. The analysis was restricted to HTA evaluation reports published between April 2018 and April 2021 in England, France, Germany, Italy, and Spain. Identified HTA evaluation reports were screened and reviewed by two independent reviewers. For each ITC presented, the methodology and its acceptance by the HTA agency were analyzed. Five hundred and forty-three HTA evaluation reports were identified, of which 120 (22

Background Previous economic evidence about interventions for schizophrenia is outdated, non-transparent and/or limited to a specific clinical context. Aims We developed a de novo discrete event simulation (DES) model for estimating the cost-effectiveness of interventions in schizophrenia in the UK. Method The DES model was developed based on the structure of previous models, populated with demographic, clinical and cost data from the UK, and antipsychotics' effects from recent network meta-analyses. We simulated treatment pathways for patients with first-episode schizophrenia including events such as relapse, remission, treatment discontinuation, cardiovascular disease and death and estimated costs (2020 ) pound taking the National Health Service perspective and quality-adjusted life years (QALYs) over ten years. Using the model, we ranked ten first-line antipsychotics based on their QALYs and costeffectiveness. Results Amisulpride was associated with the highest QALYs, followed by risperidone long-acting injection (LAI), aripiprazole-LAI (6.121, 6.084, 6.070, respectively) and others (5.947-6.058). The most cost-effective antipsychotics were amisulpride, olanzapine and risperidone-LAI, with total probability of rankings of 1, <= 2, <= 3, that is, 95%, 89%, 80%, respectively; meanwhile, the least costeffective were cariprazine, lurasidone and quetiapine, with total probability of rankings of 10, >= 9, >= 8, that is, 96%, 92%, 81%, respectively. Results were robust across sensitivity analyses and influenced primarily by relapse relevant parameters. Conclusions Our findings suggest amisulpride (or risperidone-LAI where oral treatment is inappropriate) as the best overall first-line option based on QALYs and cost-effectiveness. Our ranking may be used to guide decision-making between antipsychotics. Our model is open source and could be applied to the other settings.

Background The economic consequences of the recent COVID-19 pandemic were substantial. However, direct medical costs in France have not been determined.Objective To describe patient characteristics, intensity of care, mortality, and direct medical costs in patients hospitalised for COVID-19 infections in France.Study design A retrospective study of the French national hospital claims database for 2020.Setting Hospital care.Patients or other participants All patients hospitalised for COVID-19 in 2020 were included and classified by hospitalisation duration into acute phase and prolonged COVID-19.Intervention Stratification by intensity of care (Level 1: no or low-flow oxygen support; Level 2: non-invasive ventilation; Level 3: mechanical ventilation).Main outcome measure Cost of hospital care in 2020 Euros from a payer perspective.Results 199,455 patients were hospitalised for COVID-19 in France in 2020. 17,824 patients (8.9%) received mechanical ventilation and 32,602 patients (16.3%) died. Mean per patient cost was €5,510 ± 7,142. This cost was highest in patients receiving Level 3 care, patients aged >80 years and in those with prolonged COVID.Conclusion The economic burden of hospitalisations for COVID-19 infections in France during 2020 was substantial. The study provides robust baseline data to benchmark advances in the standard of care and to nurture epidemiological models.

In France, since 2013, pharmaceutical companies seeking reimbursement for innovative products claiming an improved medical benefit (ASMR) level III or higher and with significant impact on health expenditures (turnover > €20 million 2-year post-commercialization) are required to submit an economic analysis to the French National Authority for Health. The Economic and Public Health Assessment Committee (CEESP) evaluates the dossier and publishes efficiency opinions (EOs). This study aimed at synthesizing outcomes of these evaluations. We collected all the EOs released by CEESP until End June 2021. For each opinion, we extracted information including therapeutic area, methodological concern (MC), ICER (if multiple ICER were notified in the conclusion, the minimum was used), among other variables. We identified 144 EOs (including 43% in oncology, 10% for medical device and 8% in hematology), in which 1288 MCs were reported: 692 minor (54%), 507 important (39%) and 89 major (7%), 41% of the MCs referred to “modelling”. Among all EOs, 58 (40%) reported at least one major concern (40% in oncology, 16% for medical device, 12% in hematology), and 61 (42%) evaluations were considered as invalid; this was most frequently the case for medical devices (67%), hematology (64%) and oncology (45%). Between 2014 and 2017, the EO invalidation rate was 33%, and increased to 52% between 2018 and 2021 (increase by 57%). The mean ICER published in the EO conclusion was €271,060/QALY, varying from €12,648/QALY (virology) to €1,330,934/QALY (rare disease), and varying from €251,009/QALY in 2014-2017 vs. €326,424/QALY in 2018-2021 (increase by 30%). This analysis shows that in France, pharmaceutical companies present higher and higher ICERs over years, with economically evaluations are increasingly challenged by the CEESP.

Innovative medicines are defined as the medicines that contain an active substance or combination of active substances that have not been authorised before. Conducting health technology assessment (HTA) in silico may inform manufacturers of portfolio prioritisation and evidence generation strategy. This study aims to identify whether artificial intelligence algorithms may predict reimbursement decision for innovative drugs in Scotland.

La situation sanitaire causée par la COVID-19 est très dynamique, tant au niveau mondial qu'en France, avec à la fois l'arrivée de nouveaux variants et donc des changements de positionnement des traitements, mais une protection accrue contre les formes sévères par les vaccins. Dans ce contexte, il apparaît utile, voire nécessaire d'estimer le poids du fardeau sanitaire et économique de la COVID-19, pour soutenir les choix futurs des allocations de ressources et pour permettre la comparaison avec d'autres maladies. L'objectif de cette étude est d'apporter des premiers éléments de réponse, en présentant les résultats d'un modèle de simulation, simple mais flexible, permettant d'évaluer l'impact de santé publique de la COVID-19 chez les patients français traités en ambulatoire, présentant au moins un facteur de risque de forme sévère. La population d'intérêt est représentée par la population de la cohorte d'autorisation temporaire d'utilisation (ATU) de Ronapreve (moyenne de 63 ans). La première partie de ce modèle de simulation permet de refléter la phase aigüe de la COVID-19 (un mois), avec un arbre de décision. Les patients sont pris en charge soit en ambulatoire soit à l'hôpital, selon des probabilités dérivées de la même cohorte d'ATU. A l'issue de cette phase, les patients peuvent être « en vie sans forme longue », « en vie avec une forme longue traitée en ambulatoire », « en vie avec une forme longue ou prolongée traitée à l'hôpital », ou « décédé ». La seconde partie permet de simuler le devenir des patients sur 2 ans, à l'aide d'une chaîne de Markov. Dans chaque partie du modèle, les caractéristiques des séjours hospitaliers, que ce soit leur durée, la mortalité ou le coût associé, ont été documentées par une analyse de la base de données du PMSI. Plusieurs analyses de scénarios ont été réalisées. Sur 1 000 patients sont observées 382 hospitalisations, dont 258 au cours du premier mois, 407 formes longues ou prolongées de la COVID-19 et 37 décès. De façon générale, le modèle permet d'estimer le fardeau de la COVID-19 à 0,7 jours de vie perdu le premier mois, avec un coût associé de 1 578 €, et à 27 jours de vie perdus sur l'ensemble de l'horizon temporel, avec un coût associé de 4 280 €. La charge sanitaire et financière la plus élevée est observée pour les patients âgés de plus de 80 ans et pour les patients non vaccinés. Les scénarios menés avec un variant moins sévère, ou avec l'arrivée de nouveaux traitements efficaces permettent de documenter la réduction non négligeable du poids de ce fardeau. Cette étude permet de quantifier le fardeau considérable lié à la COVID-19 en France chez les patients infectés et traités en ambulatoire, présentant au moins un facteur de risque de forme sévère. Il semble indispensable de mettre en place des stratégies capables de réduire ce fardeau, en particulier chez les patients les plus vulnérables. Roche SA France

ContextCoronavirus disease (Covid-19) is an infectious disease caused by the SARS-CoV-2 virus. The disease can cause symptoms ranging from mild to very severe. People with risk factors as age, gender, medical conditions may be more likely to need hospitalization or intensive care if they have Covid-19, or to die of the infection. A retrospective study based on a national French hospitalized claims database (PMSI) over the year 2020 has been performed to support Covid-19 patient's description but also to describe the disease management with a dedicated focus on ventilation status and finally to describe the health care resource use and the economic impact for treatment of Covid-19 in outpatient patients with more than one risk-factor for severe Covid-19. –ObjectivesThe main objective was to describe patient's characteristics hospitalized for Covid-19. The secondary objectives were to describe the disease management of Covid-19 according to the ventilation status, the health care resource use for and economic impact of Covid-19 disease management in hospital.MethodThis retrospective observational study identified people with Covid-19 in the PMSI through hospitalisation diagnosis codes in 2020. 4 ventilation status were identified: without and with oxygen support (O2), with non-invasive ventilation (NIV), with mechanical ventilation (MV) based on CCAM acts. Due to underreporting of medical procedure related to oxygen support, status “without oxygen support” was combined to O2 status. In case of several status in the same stay, the most severe was kept. Risk factors were identified through ICD10 codes, DRG and age. Rehospitalizations were calculated for 1st wave stays (from January to June). A minimum delay of 14 days between 2 stays was applied (to not consider transfer as a rehospitalisation). Cost estimation was performed based on health insurance perspective.ResultsAbout 200,00 patients for 240,00 stays. 1% of stay were in NIV status, 8% in MV. Median age was 69 years and 54% of patients were men. Men were overrepresented in NIV and MV. 10% of people over 80 had MV. 34% of patients had no risk factor (11% of MV patients, 6% of NIV and 36% of O2). The length of stay increases with the requirement of ventilation support. From a mean of 7 days for O2 to 22 days for MV. 16% of patients died (14% of O2, 25% of NIV, 36% of MV). The mortality rate increase with the age, between 1 and 5% for patients younger than 60 years, 9% for 61-65 years, 13% for 66-70 years, 17% for 71-75, 23% for 76-80 years and 33% for patients older than 80 years old. 14% of 1st wave patients were rehospitalised in 2020. The mean cost of Covid-19 hospitalisation was €5,510 (€+/- 7,142) and the median is €3,800. The mean cost of hospitalisation increased with ventilation support intensity from €3,990 (€+/- 3,021) for O2, up to €10, 600 (€+/- 5,534) for NIV and €21,100 (€+/- 15,343) for MV.ConclusionAge, sex and risk factor increased the severity of ventilation support, cost and mortality rates. Elderly people had less MV support, shorter length of stay and lower cost. In this study, requirement for low-flow oxygen support was largely under-reported, due to many reasons: lack of impact of O2 support on stay valorisation, not specified in the registry, and overload of work leading to enter only the most valuable information in the database. This under-reporting could also apply, to a much lesser extent to non-invasive ventilation, as such procedure is associated with increased stay cost.Conflict of interestVM, KB and KLL are employees of Roche. CL, CB, ALM and AM are employees of Creativ-Ceutical, a contract research organisation under contract with Roche for the implementation and exploitation of this study.Financial supportThis study was funded by Roche.

In the fight against the pandemic, it was essential to join forces with professionals to better understand the resources involved in the care ecosystem. A public health impact model was developed to estimate the health and economic burden of COVID-19, to support future choices of resource allocations and to allow comparison with other diseases. A Markov model was used to estimate life years, costs, number of hospitalisations, number of deaths and long/prolonged COVID forms over a time horizon of 2 years. Data from the literature suggest that the age of patients can affect the risk of hospitalisation and the risk of death during hospitalisation, hence the model was stratified by age group. The hospitalisation probabilities were derived from a Temporary Use Authorisation cohort, and the hospitalisation stays characteristics were derived from the French national hospital discharge database. Several scenarios were conducted. Over the model time horizon and in a situation where patients were not treated, the number of hospitalisations reached 256 per 1,000 patients in the acute phase and 382 per 1,000 patients overall. The number of deaths in the acute phase was 37 per 1,000 patients, and the number of long/prolonged COVID forms reached 407 per 1,000 patients. These translated into a reduction of 0.7 days of life per patient in the acute phase (versus the maximum lifetime during the acute phase: 30.4 days), with an average cost of €1,578, and a reduction of 27 days of life over the time horizon (versus the maximum lifetime during the whole simulation considering natural mortality: 2 years and 15.8 days), with an average cost of €4,280. This study shows that the health and economic burden is considerable especially for the elderly and/or unvaccinated and goes beyond the acute phase because of the effects and consequences of the long/prolonged COVID forms.

Aims A Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban, dabigatran and apixaban. Each of these non-vitamin K antagonist oral anticoagulants was compared with vitamin K antagonist for stroke prevention in patients with non-valvular atrial fibrillation in Spain. Methods All inputs were derived from real-world studies: baseline patient characteristics, clinical event rates, as well as persistence rates for the vitamin K antagonist treatment option. A meta-analysis of real-world studies provided treatment effect and persistence data for rivaroxaban, dabigatran and apixaban, each compared with vitamin K antagonist therapy. The model considered 3-month cycles over a lifetime horizon. The model outcomes included different costs, quality-adjusted life years and life-years gained. Sensitivity analyses were performed to test the robustness of the model. Results When compared with vitamin K antagonist, rivaroxaban incurred incremental costs of €77 and resulted in incremental quality-adjusted life years of 0.08. The incremental cost per quality-adjusted life year was €952. For the same comparison, the incremental cost per quality-adjusted life year for dabigatran was €4,612. Finally, compared with vitamin K antagonist, the incremental cost per quality-adjusted life year for apixaban was €32,015. The sensitivity analyses confirmed the robustness of the base case results. The probabilities to be cost-effective versus vitamin K antagonist were 94%, 86% and 35%, respectively, for rivaroxaban, dabigatran and apixaban, considering a willingness-to-pay threshold of €22,000 per quality-adjusted life year gained, based on a cost-effectiveness study of the Spanish National Health System. Conclusion These results suggest that rivaroxaban and dabigatran are cost-effective versus vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation, from the Spanish National Health System perspective.

Background Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria. Objective We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients. Results A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting. Conclusions Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.

BACKGROUND: The FINE-CKD model was developed to estimate the cost-effectiveness of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). OBJECTIVE: To perform internal and external validation by comparing the model estimates with trial results and outcomes from other models. METHODS: Incidence rates from trials were compared with the model predictions. Statistical tests were then performed to assess whether modeled event rates aligned with trial observations. A cross-validation was also performed using the online version of the SHARP CKD-Cardiovascular Disease (SHARP CKD-CVD) model, with population characteristics from the finerenone trials analyzed. Where no finerenone data were available, the default SHARP CKD-CVD values were used. Comparison of the results considered the ranges from both models. RESULTS: The outcomes of the FINE-CKD model reflect the event rates observed in the trials. Based on the results of the statistical tests, the hypothesis of no difference between observed and modeled events cannot be rejected for any of the outcomes. The results of the FINE-CKD model are within the ranges from the SHARP CKD-CVD model. Disease progressions align across the models; however, incident kidney failure events in the SHARP CKD-CVD model were higher. This can be explained by simulation of more severely affected patients in the SHARP CKD-CVD model. CONCLUSIONS: This study demonstrates that the FINE-CKD model adequately reflects the clinical data and provides reliable extrapolation relative to the existing predictive tools while also being conservative in its approach.

The objectives of the study were to describe the characteristics of Covid-19 patients hospitalised, the level of intensity of care that was required for their management and in particular the ventilation status, and to estimate the direct medical costs of these hospitalisations to the French national health insurance. The study included all patients hospitalised with an ICD-10 diagnostic code for Covid-19 between 1st January 2020 and 31st December 2020 and stratified into 4 ventilations: status without and with oxygen support (O2), with non-invasive ventilation (NIV), with mechanical ventilation (MV) based on medical procedure. Due to underreporting of procedures related to oxygen support, status "without O2" was combined to O2 status. Risk factors for complications were identified based on the list defined by the French National Health Authority. Cost estimation of hospitalisation was determined from the DRG. 199,455 patients were included for 238,582 stays. 1% of stays were in NIV status, 8% in MV. Median age was 69 years and 54% of patients were men. Men were overrepresented in NIV and MV. 10% of people over 80 had MV. 34% of patients had no risk factor (11% of MV, 6% of NIV and 36% of O2). 16% of patients died (14% of O2, 25% of NIV, 36% of MV). The mortality rate increased with the age, between 1 and 5% for patients younger than 60 years to 33% for patients older than 80 years old. The mean cost of Covid-19 hospitalisation was €5,510 (€+/- 7,142) and the median €3,800. It increased with ventilation support intensity from €3,990 (€+/- 3,021) for O2, €10, 600 (€+/- 5,534) for NIV, €21,100 (€+/- 15,343) for MV. Age, sex and risk factor increased the severity of ventilation support, cost and mortality rates. Elderly people had less MV support, shorter length of stay and lower cost.

BACKGROUND:Chronic kidney disease (CKD) is a progressive and irreversible disease often associated with type 2 diabetes (T2D). CKD is associated with an elevated risk of cardiovascular (CV) events, increased mortality, and diminished quality of life. Finerenone is a new treatment for patients with CKD and T2D that delays CKD progression and reduces CV complications.OBJECTIVE:To describe the approach and structure of a costeffectiveness model for finerenone for patients with CKD and T2D and compare it with existing economic models in CKD.METHODS:A de novo cost-effectiveness model (FINE-CKD model), reflective of FIDELIO-DKD results, was developed for finerenone. The FINE-CKD model was designed and implemented in accordance with published guidance on modeling and was developed with input from economic and clinical experts. The final model approach was evaluated against existing modeling structures in CKD identified through a systematic literature review.RESULTS AND CONCLUSIONS:The FINE-CKD model structure follows recommended modeling guidelines and has been designed in accordance with the best practices of modeling in CKD, while also incorporating important features of the FIDELIO-DKD design and results. The approach is consistent with the published literature, ensuring transparency and minimizing uncertainty that can arise from unnecessary complexity. The FINE-CKD model allows for reliable assessment of benefits and costs related to the use of finerenone in patients with CKD and T2D, and it is a reliable assessment of cost-effectiveness.

Background Patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD) are at substantial risk of atherothrombotic events. The COMPASS trial showed that patients with stable CAD or PAD experienced significant benefits after treatment with rivaroxaban in combination with acetylsalicylic acid (ASA) compared with ASA alone. This paper aims to provide insight into the clinical and economic consequences of treatment with rivaroxaban from a Dutch societal perspective. Methods The clinical and economic implications of rivaroxaban in terms of the number of events prevented, costs, the incremental cost per life-years gained (LYG), and incremental cost per quality-adjusted life-years (QALYs) were determined based on a cost-effectiveness model for patients with stable CAD or PAD and in high-risk subgroups (i.e. patients with CAD and PAD, CAD and prior myocardial infarction and renal impairment, CAD and heart failure) using results from the Cardiovascular OutcoMes for People Using Anticoagulation Strategies (COMPASS) trial. Results Patients treated with rivaroxaban have an expected increased discounted life expectancy of 0.67 years. In high-risk groups discounted incremental life expectancy ranged from 1.33 to 1.90 years. The incremental cost-effectiveness ratio for the full COMPASS population was euro9,760/LYG and euro12,033/QALY, whereas, for high-risk subgroups of patients with underlying conditions, incremental cost-effectiveness ratios ranged from euro2,966/LYG to euro5,052/LYG and from euro3,940/QALY to euro6,815/QALY. Results from the sensitivity analyses revealed that the model results were robust to variations in single or multiple input parameters at once. Conclusions The cost-effectiveness analysis showed that rivaroxaban in combination with ASA is a cost-effective treatment option in stable CAD or PAD patients. Rivaroxaban in combination with ASA is even more cost-effective in high-risk subgroups.