Cultural Variations in Public Beliefs about Mental Disorders: A Comparison between Tunisia and Germany.

BACKGROUND: In recent years there is a growing interest in public beliefs about mental disorders. Numerous representative population-based studies have been conducted around the globe, also in European countries bordering on the Mediterranean Sea. However, relatively little is known about public beliefs in countries in Northern Africa. OBJECTIVE: To fill this gap by comparing public beliefs about mental disorders in Tunisia and Germany, focusing on causal beliefs, help-seeking recommendations and treatment preferences. METHODS: Representative national population-based surveys have been conducted in Tunisia in 2012 (N = 811) and in Germany in 2011 (N = 1852), using the same interview mode and the same fully structured interview starting with a vignette depicting a person suffering from either schizophrenia or depression. RESULTS: In Tunisia, the public was more likely to adopt psychosocial and to reject biogenetic explanations than in Germany. Correspondingly, psychological treatments were more frequently recommended and biological ones more frequently advised against. There was also a strong inclination to share religious beliefs and to recommend seeking religious advice. Tunisians tended much more than Germans to hold moralistic views and to blame the afflicted person for his or her illness. In Tunisia, the public tended less to differentiate between schizophrenia and depression than in Germany. CONCLUSION: Marked differences between Tunisia and Germany exist in public beliefs about the causes of mental disorders and their treatment, which correspond to differences in cultural orientations prevailing in these countries. Mental health professionals need to be sensitive to the particular cultural context in which they operate, in order to be able to reach those they intend to care for.

Cultural differences in stigma surrounding schizophrenia: comparison between Central Europe and North Africa.

BACKGROUND: Exploring cultural differences may improve understanding about the social processes underlying the stigmatisation of people with mental illness. AIMS: To compare public beliefs and attitudes about schizophrenia in Central Europe and North Africa. METHOD: Representative national population surveys conducted in Germany (2011) and in Tunisia (2012), using the same interview mode (face to face) and the same fully structured interview. RESULTS: In Tunisia, respondents showed a stronger tendency to hold the person with schizophrenia responsible for the condition. At the same time they expressed more prosocial reactions and less fear than their German counterparts. In Germany, the desire for social distance was greater for more distant relationships, whereas in Tunisia this was the case for close, family-related relationships. CONCLUSIONS: Stigma differs between Tunisia and Germany more in form than in magnitude. It manifests particularly in those social roles which 'matter most' to people within a given culture.

Predictive models to estimate utility from clinical questionnaires in schizophrenia: findings from EuroSC.

OBJECTIVE: The clinical symptoms of schizophrenia are associated with serious social, quality of life and functioning alterations. Typically, data on health utilities are not available in clinical studies in schizophrenia. This makes the economic evaluation of schizophrenia treatments challenging. The purpose of this article was to provide a mapping function to predict unobserved utility values in patients with schizophrenia from the available clinical and socio-demographic information. METHODS: The analysis was performed using data from EuroSC, a 2-year, multi-centre, cohort study conducted in France (N = 288), Germany (N = 618), and the UK (N = 302), totalling 1208 patients. Utility was calculated based on the EQ-5D questionnaire. The relationships between the utility values and the patients' socio-demographic and clinical characteristics (Positive and Negative Syndrome Scale--PANSS, Calgary Depression Scale for Schizophrenia--CDSS, Global Assessment of Functioning--GAF, extra-pyramidal symptoms measured by Barnes Akathisia Scale-BAS, age, sex, country, antipsychotic type) were modelled using a random and a fixed individual effects panel linear model. RESULTS: The analysis demonstrated the prediction ability of the used parameters for estimating utility measures in patients with schizophrenia. Although there are small variations between countries, the same variables appear to be the key predictors. From a clinical perspective, age, gender, psychopathology, and depression were the most important predictors associated with the EQ-5D. CONCLUSION: This paper proposed a reliable, robust and easy-to-apply mapping method to estimate EQ-5D utilities based on demographic and clinical measures in schizophrenia.

Modelling the consequences of a reduction in alcohol consumption among patients with alcohol dependence based on real-life observational data.

BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.

A predictive microsimulation model to estimate the clinical relevance of reducing alcohol consumption in alcohol dependence.

BACKGROUND: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. METHODS: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. RESULTS: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. CONCLUSION: The potential gains of reducing consumption in alcohol-dependent patients were considerable.

The Acceptance of Indirect Treatment Comparison Methods in Oncology by Health Technology Assessment Agencies in England, France, Germany, Italy, and Spain.

INTRODUCTION: 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. METHODS: 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. RESULTS: Five hundred and forty-three HTA evaluation reports were identified, of which 120 (22%) presented an ITC. This proportion was the highest in England (51%) and lowest in France (6%). The overall acceptance rate of ITC methods was 30%, with the highest in England (47%) and lowest in France (0%). Network meta-analysis (NMA; 23%) was the most commonly used ITC technique, with a 39% acceptance rate overall, followed by Bucher ITC (19%; 43% acceptance rate) and matching-adjusted indirect comparison (13%; 33% acceptance rate). The most common criticisms of the ITC methods from HTA agencies related to data limitations (heterogeneity and lack of data; 48% and 43%, respectively) and the statistical methods used (41%). CONCLUSIONS: The generally low acceptance rate of ITC methods by HTA agencies in oncology suggests that, whilst in the absence of a direct comparison ITCs may provide relevant evidence, this evidence is not widely considered sufficient for the purpose of HTA evaluations. The perception of ITC methods for the purpose of HTA evaluations varies substantially between countries. There is a need for further clarity on the properties of ITC techniques and the assessment of their results as ITC methods continue to evolve quickly and further techniques may become available in the future.

Quality of life is predictive of relapse in schizophrenia.

BACKGROUND: The objective of this study was to evaluate whether quality of life (QoL), as measured by the SF36 and the Quality of Life Interview (QoLI), is predictive of relapse for patients with schizophrenia. METHODS: Using data from a multicenter cohort study conducted in France, Germany, and the United-Kingdom (EuroSC), we performed Cox proportional-hazards models to estimate the associations between QoL at baseline and the occurrence of relapse over a 24-month period, with adjustment for age; gender; positive, negative and general psychopathology PANSS factors; functioning (GAF); medication; side-effects; and compliance measures. RESULTS: Our sample consisted of 1,024 patients; 540 (53%) had at least one period of relapse, and 484 (47%) had no relapse. QoL levels were the most important features predicting relapse. We found that a higher level of QoL predicts a lower rate of relapse at 24 months: HR = 0.82 (0.74; 0.91), p < 0.001 for the SF36-Physical Composite Score; and HR = 0.88 (0.81; 0.96), p = 0.002 for the SF36-Mental Composite Score. These results were not confirmed using the QoLI: HR = 0.91 (0.81; 1.01), p = 0.083. To a lesser extent, older age, better functioning, and a higher compliance score also predict a lower rate of relapse at 24 months (HRs from 0.97 to 0.98; p < 0.05). CONCLUSIONS: QoL, as assessed by the SF36, is an independent predictor of relapse at a 24-month follow-up in schizophrenia. This finding may have implications for future use of the QoL in psychiatry. Moreover, our findings may support the development and monitoring of complementary therapeutic approaches, such as 'recovery-oriented' combined with traditional mental health cares to prevent relapse.

Attitudes and beliefs of the French public about schizophrenia and major depression: results from a vignette-based population survey.

BACKGROUND: In their study 'Mental Health in the General Population: Images and Realities' Jean-Luc Roelandt et al. found a huge divide between the French public's conceptualizations of insanity and depression. The study aims to examine whether such differences can be replicated using modern operationalized diagnostic criteria for schizophrenia and major depressive disorder. METHODS: In 2012, an online survey was conducted using a representative sample drawn from the adult French population (N = 1600). After presentation of a case-vignette depicting a person with either schizophrenia or major depressive disorder a fully structured interview was carried out. RESULTS: Despite some similarities marked differences between both disorders emerge regarding beliefs and attitudes. While respondents presented with the schizophrenia vignette more frequently defined symptoms as the expression of an illness with a stronger biological component and a less favorable prognosis, demanding psychiatric treatment, respondents presented with the depression vignette considered the occurrence of symptoms more frequently as the consequence of current psychosocial stress, benefitting not only from established but also from alternative treatments. People with schizophrenia were more frequently perceived as unpredictable and dangerous, there was a stronger need to separate one-self from them, they were more frequently met with fear and less frequently reacted to with pro-social feelings, and they also faced more rejection. CONCLUSIONS: The French public draws a clear line between schizophrenia and major depressive disorder. This applies equally to beliefs about both disorders and to attitudes towards the persons afflicted. There is a need for interventions trying to reduce existing misconceptions in order to improve the care of patients.

Real-world evidence for steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease.

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.

A prospective study of health care resource utilisation and selected costs of schizophrenia in France.

BACKGROUND: Schizophrenia is among the most burdensome and costly illnesses worldwide. To estimate the cost of schizophrenia in France, a longitudinal study was carried out between 1998 and 2002. The main objective of this study was to describe and update the cost of schizophrenia in a longitudinal, representative sample of French patients. The second objective was to identify cost drivers in the treatment of schizophrenia. METHODS: Based on a cohort of 288 French schizophrenic patients during 2 years of prospective follow-up, this study collected clinical, patient reported outcomes, quality of life, functioning, patient management, care giver involvement and resource utilisation data every 6 months. For each service, information was collected on the type of service, the frequency of attendance and type of intervention provided to the patient. Unit costs were based on available French databases. Mean service use and costs over the five time points were estimated using between-effects regression models. RESULTS: In the total sample of 288 patients aged 18-64 years, the mean total cost (€ 3 534) was mainly accounted for by the cost of inpatient treatment (€ 1 390) and day care (€ 1 331). The estimate of the annual cost for direct medical health care for all French schizophrenic patients was € 1 581 million, including € 621 million for inpatient treatment and € 595 million for day care (77%). The costs for medication accounted for 16.1% of total annual costs. The remaining costs (6.9%) included visits to psychiatrists, general practitioners, other physicians and psychologists. The direct resource allocation showed inpatient treatment as the main direct cost. Unemployment was identified as a major indirect cost of schizophrenia treatment. Positive and depressive schizophrenia symptoms at baseline and relapse occurrence during the follow-up period were associated with a higher cost of treatment. Health satisfaction or negative symptoms of schizophrenia at baseline were associated with lower costs. CONCLUSION: Several cost drivers were identified. Based on the results obtained in France, we suggest further analysis of mechanisms that influence the service-specific costs for schizophrenia in other areas of the world.

Public health impact of COVID-19 in French ambulatory patients with at least one risk factor for severe disease.

Background: Quantification of COVID-19 burden may be useful to support the future allocation of resources. Objective: To evaluate the public health impact of COVID-19 in French ambulatory patients with at least one risk factor for severe disease. Study design: 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. The hospitalisation probabilities were derived from an early access cohort, and the hospitalisation stay characteristics were derived from the French national hospital discharge database. Several scenario analyses were conducted. Results: The number of hospitalisations reached 256 per 1,000 patients over the acute phase (first month of simulation), and 382 per 1,000 patients over 2 years. The number of deaths 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 first month, with an associated cost of €1,578, and a reduction of 27 days of life over the time horizon, with an associated cost of €4,280. The highest burden was observed for patients over 80 years old, and those not vaccinated. The scenarios with a less severe situation or new treatments available showed a non-negligible burden reduction. Conclusion: This study allowed us to quantify the considerable burden related to COVID-19 in infected patients, with at least one risk factor for severe form. Strategies with the ability to substantially reduce this burden in France are urgently required.

Validation of the FINE-CKD model for future health technology assessments for finerenone in patients with chronic kidney disease and type 2 diabetes.

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.

Real-world cost-effectiveness analysis of NOACs versus VKA for stroke prevention in Spain.

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.

Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis.

OBJECTIVE: To compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period. METHODS: Using data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy). RESULTS: Our sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505). CONCLUSION: After propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.

Targeted literature review of the burden of illness in patients with chronic kidney disease and type 2 diabetes.

OBJECTIVES: Chronic kidney disease (CKD) is increasingly prevalent among patients with type 2 diabetes (T2D). CKD is associated with increased mortality rates, clinical and humanistic burden, and substantial health care costs in the T2D population. The objective of this review was to summarize the burden of illness among patients with CKD and T2D, including the profile of patients, incidence, prevalence, mortality, progression, diagnosis and screening rates, and cardiovascular (CV) events. METHODS: A targeted literature review of published studies was conducted using Embase; Medline; Medline In-Process Citations, Daily Update, and Epub Ahead of Print; Igaku Chuo Zasshi databases; and 7 websites. Methods recommended by the Cochrane collaboration handbook, the Centre for Reviews and Dissemination, and the Joanna Briggs Institute critical appraisal checklist were employed. RESULTS: A total of 1290 full-text articles were reviewed for eligibility and 73 were included in this analysis. Patient profiles indicated older age was associated with more severe disease and number of comorbidities. The definition of kidney disease varied between studies reporting incidence and prevalence, with reported values up to 37.0% and 43.5% for incidence and prevalence, respectively. CKD among patients with T2D contributed to higher mortality rates. Higher disease progression rates were associated with higher albuminuria and lower estimated glomerular filtration rate levels. The available literature suggested annual screening rates for CKD declined over time. CV events were reported to have a substantial effect on morbidity and resource use. CONCLUSIONS: This review highlights the burden of CKD among patients with T2D and underscores a need for new treatment alternatives to reduce the burden of disease.

FINE-CKD model to evaluate economic value of finerenone in patients with chronic kidney disease and type 2 diabetes.

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.

Social Preferences for Orphan Drugs: A Discrete Choice Experiment Among the French General Population.

Objectives: While several authors have suggested using a multi-criteria approach for orphan drug assessment and proposed lists of determinants of orphan drug value, studies on social preferences regarding these determinants remain limited. The current study aimed to identify preferences of the French general population regarding attributes characterizing the value of orphan drugs in a discrete choice experiment. Methods: The list of attributes was formed based on a literature search and was refined through expert interviews, a focus group, and a pilot study. The final list included nine attributes: disease-associated disability, disease-associated mortality, number of patients, availability of alternative treatments, treatment impact on disease disability, treatment impact on mortality, treatment safety, uncertainty around therapeutic effect, and annual treatment cost per patient. Members of the General Public were presented with 12 choice sets containing two drug profiles described according to the attributes and an option to fund neither of these treatments. The questionnaire was disseminated online. A conditional logit model with random effects was used to estimate the weight of each attribute. Results: A total of 958 persons participated in the study (48.7% male, mean age: 47.5 years). All attributes except for disease-associated disability had a statistically significant influence on the choices made by participants. The attribute with the highest weight was treatment impact on mortality (p < 0.0001), followed by uncertainty around therapeutic effect (p < 0.0001). The direction of results was generally consistent with intuition: patients preferred a drug with a larger impact on mortality, a larger impact on disability, with mild or no adverse events, with less uncertainty. Although patients appeared to prefer drugs with a lower budget impact, the relationship between patient preferences and costs was more complex. Conclusions: Preferences of the general public between orphan drugs are mostly driven by the impact on mortality and the degree of certainty regarding the available evidence.

Real-world cost-effectiveness of rivaroxaban and apixaban vs VKA in stroke prevention in non-valvular atrial fibrillation in the UK.

BACKGROUND: Morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) imposes a substantial economic burden on the UK healthcare system. OBJECTIVES: An existing Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban and apixaban, each compared with a vitamin K antagonist (VKA), for stroke prevention in patients with NVAF from the National Health Service (NHS) and personal and social services (PSS) perspective. METHODS: The model considered a cycle length of 3 months over a lifetime horizon. All inputs were drawn from real-world evidence (RWE): baseline patient characteristics, clinical event and persistence rates, treatment effect (meta-analysis of RWE studies), utility values and resource use. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost per quality-adjusted life year was £14,437 for rivaroxaban, and £20,101 for apixaban, compared with VKA. The probabilities to be cost-effective compared with VKA were 90% and 81%, respectively for rivaroxaban and apixaban, considering a £20,000 threshold. In both comparisons, the results were most sensitive to clinical event rates. CONCLUSIONS: These results suggest that rivaroxaban and apixaban are cost-effective vs VKA, based on RWE, considering a £20,000 threshold, from the NHS and PSS perspective in the UK for stroke prevention in patients with NVAF. This economic evaluation may provide valuable information for decision-makers, in a context where RWE is more accessible and its value more acknowledged.

Use of real-world evidence in meta-analyses and cost-effectiveness models.

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial data with valuable information on patient behaviors and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges. The objectives of this communication were to (1) summarize all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses. No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results. RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines.

Cost-Effectiveness of Coronary and Peripheral Artery Disease Antithrombotic Treatments in Finland.

INTRODUCTION: Currently, 15-20% of individuals with coronary artery disease (chronic coronary syndrome [CCS]) or peripheral artery disease (PAD) receiving routine treatment experience cardiovascular events (CVEs) within 3-4 years. Using PICOSTEPS (Patients-Intervention-Comparators-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis) reporting, we evaluated the cost-effectiveness of recently approved rivaroxaban 2.5 mg twice daily in combination with acetylsalicylic acid 100 mg daily (RIV + ASA) for the prevention of CVEs among Finns with CCS or symptomatic PAD. METHODS: Myocardial infarction, ischemic stroke, intracranial hemorrhage, acute limb ischemia, amputations, major extracranial bleeding, venous thromboembolism, and cardiovascular deaths were modeled in a Markov model examining a cohort of patients with CCS or symptomatic PAD. Relative effects of the intervention (RIV + ASA) and comparator (ASA) were based on the COMPASS trial. The primary outcome was 3%/year discounted incremental cost-effectiveness ratio (ICER), defined as cost (2019 euros) per quality-adjusted life year (QALY) gained in the Finnish setting over a lifetime horizon. In addition to nonfatal and fatal CVEs, the effects factored Finnish non-CVE mortality, quality of life, and direct costs from a public payer perspective. Disaggregated costs and QALYs, costs per life year gained (LYG), and ischemic strokes avoided, net monetary benefit (NMB), expected value of perfect information (EVPI), economic value-added (EVA), cost-effectiveness table, and acceptability frontier were examined. Probabilistic and deterministic sensitivity analyses were conducted. RESULTS: In the deterministic comparison with ASA over a lifetime horizon, RIV + ASA resulted in a benefit of 0.404 QALYs and 0.474 LYGs for an additional cost of €3241, resulting in an ICER of €8031/QALY. The probabilistic ICER was €4313/QALY (EVPI €1829/patient). RIV + ASA had positive NMB (€8791/patient), low EVPI (€88/patient), high EVA (€8703/patient), and 91% probability of cost-effectiveness using the willingness-to-pay of €25,254/QALY. The primary result was conservative and robust for RIV + ASA. CONCLUSION: RIV + ASA was a cost-effective treatment alternative compared with ASA in patients with CCS or symptomatic PAD in Finland.

Finland lacks published evidence on the cost-effectiveness of approved interventions for the prevention of cardiovascular events among individuals with chronic coronary syndrome (stable coronary artery disease) or symptomatic peripheral artery disease at risk of cardiovascular complications. Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid 100 mg once daily is indicated and reimbursed in Finland for the prevention of cardiovascular events for patients with stable coronary artery disease or symptomatic peripheral artery disease. We assessed the effectiveness and costs of treatment with rivaroxaban plus acetylsalicylic acid in comparison with treatment with acetylsalicylic acid. That is, we examined whether rivaroxaban is cost-effective when prescribed in combination with acetylsalicylic acid.Cardiovascular events with their associated costs and impact on quality of life were modeled over the lifetime of patients. The main effectiveness outcome was quality-adjusted life years (modeled survival multiplied by the expected quality of life), and costs included those relevant to the Finnish public payer in 2019. Extensive sensitivity analyses were carried out to evaluate the impacts of different model inputs and rationale.Rivaroxaban plus acetylsalicylic acid had high probability of being cost-effective, compared with acetylsalicylic acid. By valuing quality-of-life benefit with a plausible willingness-to-pay, net cost savings of €8791 per patient could be gained or economic value added by €8703 per patient if rivaroxaban was used.