Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAg-Positive and -Negative Chronic Hepatitis B.

INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (C, 2014) and utilities were obtained from literature. RESULTS: Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg-positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Treatment patterns, resource use and costs of idiopathic pulmonary fibrosis in Spain--results of a Delphi Panel.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a form of chronic fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function, with a poor prognosis. The objective of this study was to determine treatment patterns, resource use and costs of managing Spanish patients with IPF. METHODS: A three-round Delphi consensus panel of 15 clinical experts was held between December 2012 and June 2013 using questionnaires to describe the management of patients with IPF. A cost analysis based on Delphi panel estimates was made from the Spanish National Health System (NHS) perspective, including the direct costs of IPF diagnosis and management. Unit costs were applied to Delphi panel estimates of health resource use. Univariate sensitivity analyses were made to evaluate uncertainties in parameters. RESULTS: The Delphi panel estimated that 20, 60 and 20% of IPF patients presented with stable disease, slow and rapid disease progression, respectively. The estimated annual cost per patient with stable disease, slow and rapid disease progression was €11,484, €20,978 and €57,759, respectively. This corresponds to a weighted average annual cost of €26,435 with itemized costs of €1,184 (4.5), €7,147 (27.0), €5,950 (22.5), €11,666 (44.1) and €488 (1.9%) for the diagnosis of IPF, treatment, monitoring, management of acute exacerbations and end-of-life care, respectively. The parameter that varied the annual cost per patient the most was resource use associated with acute exacerbations. CONCLUSIONS: The management of patients with IPF in Spain, especially patients with rapid disease progression, has a high economic impact on the NHS.

Cost-effectiveness analysis of dabigatran and anticoagulation monitoring strategies of vitamin K antagonist.

BACKGROUND: Vitamin K antagonists are commonly used for the prevention of thromboembolic events. Patient self-monitoring of vitamin K antagonists has proved superior to usual care. Dabigatran has been shown, relative to warfarin, to reduce thromboembolic events without increasing bleeding. METHODS: We constructed a Markov model to compare vitamin K self-monitoring strategies to dabigatran including effectiveness and costs of monitoring and complications (thromboembolism and major bleeding). The model was used to project the incidence of these complications, life years, quality-adjusted life years, and health system costs with anticoagulant treatment throughout life. The analysis was conducted from the health system perspective and from the societal perspective. RESULTS: Low quality evidence suggests that self-monitoring is at least as effective as dabigatran for the outcomes of thrombosis, bleeding and death. Moderate quality evidence that patient self-monitoring is more effective than other forms of monitoring degree of anticoagulation with vitamin K antagonists, reducing the relative risk of thromboembolism by 41% and death by 34%. The cost per quality adjusted year gained relative to other warfarin monitoring strategies is well below 30,000 € in the short term, and is a dominant alternative from the fourth year. In comparison with dabigatran, the lower annual cost and its equivalence in terms of effectiveness made self-monitoring the dominant option. These results were confirmed in the probabilistic sensitivity analysis. CONCLUSIONS: We have moderate quality evidence that self-monitoring of vitamin K antagonists is a cost-effective alternative compared with hospital and primary care monitoring, and low quality evidence, compared with dabigatran. Our analyses contrast with the available cost analysis of dabigatran and usual care of anticoagulated patients.

[Cost-effectiveness analysis of dapagliflozin compared to DPP4 inhibitors and other oral antidiabetic drugs in the treatment of type-2 diabetes mellitus in Spain]. / Análisis de coste-efectividad de dapagliflozina en comparación con los inhibidores de la DPP4 y otros antidiabéticos orales en el tratamiento de la diabetes mellitus tipo 2 en España.

OBJECTIVE: To assess the efficiency of the combined therapy with metformin and dapagliflozin, a new oral anti-diabetic drug with an insulin-independent mechanism of action, in the treatment of type-2 diabetes mellitus (T2DM) compared to DPP4 inhibitors, sulphonylureas and thiazolidindiones, also combined with metformin. DESIGN: Cost-effectiveness analysis using a discrete event simulation model based on the results of the available clinical trials and considering patient's entire life as time horizon. SETTING: National Health System perspective. PARTICIPANTS: The model simulated the natural history of 30,000 patients with T2DM for each of the options compared. MAIN MEASUREMENTS: Quality-adjusted life-years (QALY) and economic consequences of managing the disease and its complications. The analysis considered direct costs updated to 2013. A discount rate of 3% was applied to costs and health outcomes. RESULTS: In the main analysis comparing dapagliflozin with DPP4 inhibitors, dapagliflozin resulted in a treatment option that would provide a slightly higher effectiveness (0.019 QALY) and lower overall associated costs (-€42). In the additional analyses, dapagliflozin was a cost-effective option compared with sulphonylureas and thiazolidinediones resulting in a cost per QALY gained of €3,560 and €2,007, respectively. The univariate and probabilistic sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The results of the analyses performed suggested that dapagliflozin, in combination with metformin, would be a cost-effective alternative in the Spanish context for the treatment of T2DM.

The association between asthma control, health care costs, and quality of life in France and Spain.

BACKGROUND: Current asthma management guidelines are based on the level of asthma control. The impact of asthma control on health care resources and quality of life (QoL) is insufficiently studied. EUCOAST study was designed to describe costs and QoL in adult patients according to level of asthma control in France and Spain. METHODS: An observational cost of illness study was conducted simultaneously in both countries among patients age greater or equal to 18 with a diagnosis of asthma for at least 12 months. Patients were recruited prospectively by GPs in 2010 in four waves to avoid a seasonal bias. Health care resources utilization of the three months before the inclusion was collected through physician questionnaires. Asthma control was evaluated using 2009 GINA criteria over a 3-month period. QoL was assessed using EQ-5D-3L®. RESULTS: 2,671 patients (France: 1,154; Spain: 1,517) were enrolled. Asthma was controlled in 40.6% [95% CI: 37.7%-43.4%] and 29.9% [95% CI: 27.6%-32.3%] of French and Spanish patients respectively.For all types of costs, the percentage of patients using health care resources varied significantly according to the level of asthma control. The average cost (euros/3-months/patient) of controlled asthma was €85.4 (SD: 153.5) in France compared with €314.0 (SD: 2,160.4) for partially controlled asthma and €537.9 (SD: 2,355.7) for uncontrolled asthma (p<0.0001). In Spain, the corresponding figures were €152.6 (SD: 162.1), €241.2 (SD: 266.8), and €556.8 (SD: 762.4). EQ-5D-3L® score was higher (p<0.0001) in patients with controlled asthma compared to partially controlled and uncontrolled asthma in both countries (respectively 0.88; 0.78; 0.63 in France and 0.89; 0.82; 0.69 in Spain). CONCLUSIONS: In both countries, patients presenting with uncontrolled asthma had a significantly higher asthma costs and lower scores of Qol compared to the others.

Cost-Effectiveness Analysis of Fracture Liaison Services Compared with Standard of Care in the Secondary Prevention of Fragility Fractures in Spain.

Purpose: To assess the cost-effectiveness of a Fracture Liaison Service (FLS) compared with standard care for the secondary prevention of fragility fractures in Spain. Methods: Patients with osteoporosis and an initial fragility fracture who were candidates to initiate osteoporosis treatment (mean age 65 years, 90.7% female) were included in the model. Disease progression was simulated with a Markov model through seven health states (with and without osteoporosis treatment, subsequent hip, vertebral, forearm and humerus fracture, and death). A time horizon of 10 years and a 6-month duration per cycle was set. Clinical, economic, and quality of life parameters were estimated from the literature and Spanish clinical practice. Resource use and treatment patterns were validated by an expert panel. The Spanish National Health System (SNS) perspective was adopted, taking direct costs (€; 2020) into account. Effectiveness was measured in life-years gained (LYG) and quality-adjusted life years gained (QALYs). A discount rate of 3% was applied to costs and outcomes. The uncertainty of the parameters was assessed using deterministic, scenario and probabilistic sensitivity analyses (1000 iterations). Results: Setting up a FLS for the secondary prevention of fragility fractures in Spain would provide better osteoporosis treatment initiation and persistence. This would reduce subsequent fragility fractures, disutilities and deaths. FLS would have greater clinical benefits (0.008 and 0.082 LYG and QALY gained per patient, respectively) and higher costs (€563.69 per patient) compared with standard care, leading to an incremental cost-utility ratio of €6855.23 per QALY gained over the 10 years horizon. The sensitivity analyses showed limited dispersion of the base case results, corroborating their robustness. Conclusion: From the SNS perspective and considering Spanish willingness-to-pay thresholds, the introduction of FLS for the secondary prevention of fragility fractures would be a cost-effective strategy.

Cost-effectiveness of sacral neuromodulation compared to botulinum neurotoxin a or continued medical management in refractory overactive bladder.

OBJECTIVES: This study assessed the cost-effectiveness and health-care budget impact of sacral neuromodulation (SNM) in refractory idiopathic OAB-wet patients in Spain. METHODS: A 10-year Markov analytic model was developed to estimate quality-adjusted life-years (QALYs) gained and incontinence episode avoided associated with SNM therapy compared with botulinum neurotoxin A (BoNT-A) or continued optimized medical treatment (OMT). RESULTS: At 10 years, the cumulative costs of SNM, BoNT-A, and OMT were €29,166, €29,458, and €29,370, respectively, whereas the QALYs for SNM, BoNT-A, and OMT are 6.89, 6.38, and 5.12, respectively. Consequently, incremental cost-effectiveness ratios (ICERs) for SNM demonstrate that although the initial costs for SNM are higher than those for the other treatments, decreasing follow-up costs coupled with consistently greater effectiveness in the long term make SNM the economically dominant option at 10 years. Sensitivity analyses suggest that 99.7% and 99.9% (for SNM vs. BoNT-A and OMT, respectively) of the 1000 Monte Carlo iterations fall within the €30,000 cost-effectiveness threshold, considered to be acceptable in Spain. The 10-year incremental cost per incontinence episode avoided for SNM also makes this therapy the dominant option compared to BoNT-A or OMT. Additionally, the estimated budget impact of the gradually increased referral for SNM for the management of OAB patients in Spain is small. CONCLUSIONS: As a treatment option for refractory idiopathic OAB, at 10 years, SNM provides a considerable possibility of symptom and quality-of-life improvement and is cost-effective compared to BoNT-A or continued OMT.

[Analysis of the evolution in the access to orphan medicines in Spain]. / Análisis de la evolución en el acceso a los medicamentos huérfanos en España.

OBJECTIVE: To assess the access to orphan medicines in Spain, focusing on those with an active "orphan" designation, as of 31st December 2017; and for those orphan medicines in the Spanish market, estimate the time between being assigned a National Code (NC) by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) and being approved for launch. METHOD: We used the European Commission's Public Register of orphan medicines to identify the orphan medicines authorised by the European Medicines Agency (EMA), as of 31 December 2017, while we sourced expired orphan indications from the EMA's website. Dates when NCs were assigned were sourced from the AEMPS, and commercialisation dates from Bot PLUS. A descriptive analysis of the study variables was done. The quantitative variables were described using means and medians, as well as standard deviations and ranges. The qualitative variables were described according to absolute and relative frequencies. The comparison of results was performed by parametric and non-parametric contrasts according to the applicability, at a 5% significance level. RESULTS: The EMA has approved 100 orphan medicines (with designation as of 31/12/2017) between 2002-2017. Eighty-six have a NC assigned by the AEMPS. Fifty-four have been launched in Spain (representing 54% of the full sample; 63% with NC). For the 53 orphan drugs with launch date in Spain, the median time between receiving its NC and its launch is 13.4 months (standard deviation: 17.0; minimum: 2.1; maximum: 91,7). The median time is 12.4 months and 14.0 months for those medicines launched in Spain between 2002-2013 and 2014-2017 respectively (p = 0.46). This difference is not statistically significant, which is what could be expected given the low numbers of orphan medicines in the "population". CONCLUSION: Complex factors determine the access to orphan drugs in Europe. The centralised procedure to obtain marketing authorisation at European level is a success. However, access is more limited, given the complexities of the evaluation of the available evidence for pricing and reimbursement decisions. It is therefore necessary to implement new policies that reduce inequalities in access and help achieve sustainable healthcare systems. To achieve this, they will need to offer the possibility of allowing earlier access, and using payment by results when there is high uncertainty.

Modeling the cost-effectiveness of different oral antiviral therapies in patients with chronic hepatitis B.

BACKGROUND/AIMS: Chronic hepatitis B (CHB) is a common disease associated with high morbidity, mortality and impact on healthcare costs. Several oral antiviral therapies can lead to complete virologic response, which is associated with prevention of disease progression. The aim of this study was to estimate the cost-effectiveness of the oral antiviral treatments lamivudine, adefovir, telbivudine, entecavir and tenofovir, in patients with CHB. METHODS: A Markov model was used to project the lifetime complications and costs in cohorts of both HBeAg-positive and HBeAg-negative CHB patients treated with one of the above drugs or no treatment. Rescue therapy with two different combination therapies (adefovir plus lamivudine or tenofovir plus entecavir) with their corresponding costs and efficacy rates was also considered. The probabilities of disease progression were based on serum HBV DNA levels. Disease and complication costs were assessed using the perspective of the Spanish National Health System. RESULTS: The highest rate of virologic response was obtained with tenofovir, and this translated to its higher life years saved (LYS) and quality adjusted life years (QALY) compared with the rest of the alternatives in HBeAg-positive and HBeAg-negative patients. Tenofovir is associated with lower costs and higher efficacy over entecavir, telbivudine and adefovir in HBeAg-positive patients, and telbivudine and entecavir in HBeAg-negative patients. The incremental cost-effectiveness ratios with respect to the rest of the alternatives are below the common reference efficiency threshold of 30,000 euro per LYS/QALY. CONCLUSION: In chronic HBV infected patients, tenofovir is a cost-effective or even cost-saving strategy compared with other available treatment options for CHB.

[Cost-reduction analysis for oral versus intravenous fludarabine (Beneflur) in Spain]. / Análisis de minimización de costes de fludarabina (Beneflur) oral vs. vía intravenosa en España.

INTRODUCTION: Various international studies have shown that fludarabine is effective, safe, and efficient for treating B-cell chronic lymphocytic leukemia (B-CLL). The purpose of the present study was to carry out a cost-minimization analysis for two alternative forms of fludarabine (oral and intravenous) used to treat B-CLL in Spain. METHODS: The presence of clinical evidence about the treatment equivalence of the two options being compared (oral fludarabine vs. intravenous fludarabine) led us to carry out a cost-minimization analysis. A pharmacoeconomic model was constructed to compile data from the literature and experts' opinions in order to determine the use of health resources associated with the treatment; unit costs were obtained from Spanish databases. The analysis contemplated two perspectives: that of the national health service, which includes only direct health costs, and the social perspective, which also includes the indirect costs that result from loss of productivity. RESULTS: Although fludarabine in its oral form has a higher purchase price than generic intravenous fludarabine does, increased administration costs for the latter, which is used in hospitals, mean that oral fludarabine use produces total savings of euro1,908 and euro1,292 for single-drug therapy and combined therapy with cyclophosphamide, respectively. Including indirect costs increased the savings associated with the oral form of the drug. CONCLUSIONS: In B-CLL patients, treatment with oral fludarabine has a lower cost than treatment with intravenous fludarabine, in both single-drug therapy and combined therapy. Various sensitivity analyses confirmed these results and showed that oral fludarabine should be the treatment of choice for B-CLL in Spain, unless contrain.

Estimating the future health burden of chronic hepatitis B and the impact of therapy in Spain.

BACKGROUND: Chronic hepatitis B virus (HBV) infection can lead to fatal complications and death. Only a relatively small proportion of patients actually receive medication, and the majority requires long-term antiviral therapy that can result in the emergence of resistant strains of HBV. The study aimed to estimate the future burden of chronic hepatitis B in Spain over the next 20 years, the impact of current lamivudine treatment and the emergence of drug-resistant HBV. METHODS: We constructed a hypothetical cohort of people with active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20 years. The cohort was stratified with respect to factors that affect prognosis (i.e. hepatitis B e-antigen and histology-defined status). To estimate the burden, Markov mathematical simulation was performed based on three scenarios: natural history, treatment with antiviral drug (lamivudine) and treatment with a hypothetical drug with identical profiles to lamivudine but to which there is no resistance. RESULTS: We estimated that in 2005 there were around 111,000 individuals suffering from active chronic HBV infection. If the cohort is not treated, by the year 2025 there will be about 60,000 events of morbidity and 40,000 cases of liver-related deaths, with 1.84 billion euro expected to be consumed in providing care for the cohort. Treating 35% of the cohort with lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively; whereas the hypothetical drug will reduce the morbidity and mortality by 27 and 24%. The cumulative cost savings resulting from the use of lamivudine and the hypothetical drug, respectively, are 160 and 300 million euro. Antiviral resistance accounts for a reduction of about one-third in the potential benefit of treatment, and almost a half of the potential cost saving. CONCLUSION: Chronic hepatitis B will pose a great burden in the future if the individuals with active disease are left untreated. Effective antiviral therapy and treatment coverage have substantial impact in reducing the future burden; however, antiviral resistance decreases treatment benefit considerably.

Comparative economic study of the use of corifollitropin alfa and daily rFSH for controlled ovarian stimulation in older patients: Cost-minimization analysis based on the PURSUE study.

This study presents an economic assessment of controlled ovarian stimulation in assisted reproductive technology procedures in Spain, comparing the use of corifollitropin alfa and various forms of recombinant follicle-stimulating hormone (rFSH) in women of advanced maternal age. A cost-minimization analysis (CMA) was performed to assess the cost per cycle of controlled controlled ovarian stimulation, including only direct costs associated with the stimulation phase. The CMA was based on the population characteristics, the protocol, and the results obtained from the PURSUE study, taking into account 9 days of controlled controlled ovarian stimulation and 300 IU rFSH/day. The primary analysis included pharmacological costs alone. Different scenarios were evaluated including various doses and possible additional days (0-5) for rFSH. For the alternative analyses, the total costs (direct pharmacological costs, costs of visits and follow-up tests, and any additional pharmacological costs) were considered in both the private and public sectors. Treatment with corifollitropin alfa resulted in a lower pharmacological cost compared with rFSH (€757.25 and €950.30, respectively), creating a saving of approximately -20%. The results of the scenario analyses showed that corifollitropin alfa reduced the pharmacological cost of controlled ovarian stimulation in comparison with daily administration of doses ≥ 250 IU rFSH (considering same daily dose for all days), regardless of the additional days required (7-12 days) (average -€223; range -€488 to -€44). In conclusion, in addition to the efficacy shown in the PURSUE study, the use of corifollitropin alfa results in a decrease in the direct costs associated with controlled ovarian stimulation in older women in Spain.

[Clinical efficacy of moxifloxacin in the treatment of exacerbations of chronic bronchitis: a systematic review and meta-analysis]. / Eficacia clínica del moxifloxacino en el tratamiento de las agudizaciones de la bronquitis crónica. Revisión sistemática y metaanálisis.

OBJECTIVE: As the research undertaken to date on the efficacy of the new antibiotics in the treatment of exacerbations of chronic bronchitis has taken the form of trials designed to demonstrate equivalence, we have no data on the advantages associated with the use of these new drugs with greater bactericidal activity. Our objective was to compare the clinical efficacy of moxifloxacin to that of the antibiotic regimens routinely used to treat such exacerbations by a systematic review of the literature and a meta-analysis. METHODS: A manual and electronic search was performed to identify all clinical trials carried out between January 1997 and July 2005 to compare moxifloxacin and the antibiotics that are currently the first line treatment for exacerbations of chronic bronchitis. Once it had been established that the designs of the trials included were acceptable, a meta-analysis of clinical outcomes was performed. RESULTS: Of the 45 studies identified, 9 met the inclusion criteria. Of these, 5 were double-blind randomized trials and 4 were randomized open trials. The 9 trials comprised a total of 3905 patients. The aggregate standardized mean difference in clinical success rate was 1.5% (95% confidence interval, -0.4 to 3.4%). Bacterial eradication rates ranged from 68.4% to 96% for the standard regimens, and from 87.7% to 96% for moxifloxacin. No intergroup differences in the percentages of patients lost to follow-up were observed in any of the studies. CONCLUSIONS: Although the trials reviewed were designed to demonstrate equivalence, meta-analysis revealed that the clinical success rate achieved with moxifloxacin tended to be higher than that obtained in the groups that received standard antibiotic treatment.

[Distribution of the public healthcare budget of Catalonia (Spain) for 2005 among the 17 ICD-9-CM categories]. / Distribución del presupuesto sanitario público de Cataluña del año 2005 entre las 17 categorías CIE-9-MC.

OBJECTIVES: To describe the distribution of the Catalan public healthcare budget for 2005 among the 17 ICD-9-CM (International Classification of Diseases, Ninth revision, clinical modification) categories. MATERIAL AND METHOD: The methodology comprised 2 phases: an initial phase in which the global budget was distributed by type of healthcare (hospital, outpatient or pharmacological care), and a second phase in which the expenditure was distributed by the type of care among the ICD-9-CM categories. In the first phase, this distribution was based on information enabling the various budget items to be assigned to the different types of care. Various elements were used for the distribution by categories, depending on each type of care: hospital stay, outpatient visit or consumption by therapeutic subgroup. RESULTS: Distribution of the budget was as follows: 46.6% for specialized care, 27.5% for pharmacological care, and 20.0% for primary care; 5.9% was not distributed. Of the 17 categories, that accounting for the largest percentage (17.3%) was "diseases of the circulatory system" (VII), followed by category VIII, "diseases of the respiratory system" which totaled 10.9%. The budget was concentrated in 5 categories, the 2 mentioned above plus category V "mental disorders" (9.4%), category II "tumors" (9.1%) and category IX "disorders of the digestive system" (7.7%), which accounted for 54.4% of the total budget. The internal composition of each category showed major variations. CONCLUSION: The distribution of the budget offers a point of reference for health planning and management.

Percutaneous coronary intervention reduces mortality in myocardial infarction patients with comorbidities: Implications for elderly patients with diabetes or kidney disease.

BACKGROUND: Percutaneous coronary intervention (PCI) reduces mortality in most myocardial infarction (MI) patients but the effect on elderly patients with comorbidities is unclear. Our aim was to analyse the effect of PCI on in-hospital mortality of MI patients, by age, sex, ST elevation on presentation, diabetes mellitus (DM) and chronic kidney disease (CKD). METHODS: Cohort study of 79,791 MI patients admitted at European hospitals during 2000-2014. The effect of PCI on in-hospital mortality was analysed by age group (18-74, ≥75years), sex, presence of ST elevation, DM and CKD, using propensity score matching. The number needed to treat (NNT) to prevent a fatal event was calculated. Sensitivity analyses were conducted. RESULTS: PCI was associated with lower in-hospital mortality in ST and non-ST elevation MI (STEMI and NSTEMI) patients. The effect was stronger in men [Odds ratio (95% confidence interval) 0.30 (0.25-0.35)] than in women [0.46 (0.39-0.54)] aged ≥75years, and in NSTEMI [0.22 (0.17-0.28)] than in STEMI patients [0.40 (0.31-0.5)] aged <75years. PCI reduced in-hospital mortality risk in patients with and without DM or CKD (54-72% and 52-73% reduction in DM and CKD patients, respectively). NNT was lower in patients with than without CKD [≥75years: STEMI=6(5-8) vs 9(8-10); NSTEMI=10(8-13) vs 16(14-20)]. Sensitivity analyses such as exclusion of hospital stays <2days yielded similar results. CONCLUSIONS: PCI decreased in-hospital mortality in MI patients regardless of age, sex, and presence of ST elevation, DM and CKD. This supports the recommendation for PCI in elderly patients with DM or CKD.

[Controversial issues in economic evaluation (I): perspective and costs of Health Care interventions]. / Cuestiones controvertidas en evaluación económica (I): perspectiva y costes de intervenciones sanitarias.

Economic evaluation of health care interventions has experienced a strong growth over the past decade and is increasingly present as a support tool in the decisions making process on public funding of health services and pricing in European countries. A necessary element using them is that agents that perform economic evaluations have minimum rules with agreement on methodological aspects. Although there are methodological issues in which there is a high degree of consensus, there are others in which there is no such degree of agreement being closest to the normative field or have experienced significant methodological advances in recent years. In this first article of a series of three, we will discuss on the perspective of analysis and assessment of costs in economic evaluation of health interventions using the technique Metaplan. Finally, research lines are proposed to overcome the identified discrepancies.

Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

OBJECTIVE: The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. METHODS: An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. RESULTS: The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. CONCLUSIONS: Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.

Análisis de la evolución en el acceso a los medicamentos huérfanos en España / Analysis of the evolution in the access to orphan medicines in Spain

OBJETIVO: Evaluar el acceso al mercado de los medicamentos huérfanos en España que a fecha de 31 de diciembre de 2017 tuvieran vigente su designación, y para aquellos comercializados en España estimar los tiempos entre la asignación de código nacional (CN) por parte de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) y la fecha de comercialización efectiva. MÉTODO: La base de datos para identificar los medicamentos huérfanos autorizados por la Agencia Europea de Medicamentos (EMA), a fecha 31 de diciembre de 2017 (n = 142), es su Registro Comunitario publicado por la Comisión Europea. La EMA publica los medicamentos huérfanos que han perdido la designación. Las fechas de asignación de CN provienen de la AEMPS, y las de comercialización, de Bot PLUS. Se llevó a cabo un análisis descriptivo de las variables de estudio. Las variables cuantitativas se describieron utilizando la media y mediana, así como la desviación estándar y su rango. Las variables cualitativas se describieron según frecuencias absolutas y relativas. La comparación de resultados se realizó mediante contrastes paramétricos y no paramétricos en función de la aplicabilidad, con un nivel de significación del 5%. RESULTADOS: Entre 2002 y 2017, la EMA autorizó (con designación vigente a 31 de diciembre de 2017) 100 medicamentos huérfanos. De ellos, 86 tienen CN asignado, y de estos, 54 se han comercializado en España (54% de los medicamentos huérfanos vigentes y 63% de aquellos con CN). Para todos los medicamentos huérfanos con fecha de comercialización (53), el tiempo (mediana) desde la asignación del CN hasta su comercialización en España es de 13,4 meses (desviación estándar: 17,0; mínimo: 2,1; máximo: 91,7). La mediana para los comercializados en 2002-2013 y 2014-2017 es de 12,4 meses y 14,0 meses, respectivamente (p = 0,46). Esta diferencia no es estadísticamente significativa, lo que cabría esperar dado el número limitado de medicamentos huérfanos en nuestra «población». CONCLUSIÓN: Numerosos factores determinan el acceso a los medicamentos huérfanos. La autorización centralizada de comercialización en Europa es un éxito; su acceso es más limitado, dadas las complejidades de evaluación de la evidencia disponible en los procesos de financiación y precio. Es necesario implementar nuevas políticas que reduzcan las desigualdades en el acceso y permitan la sostenibilidad del sistema. Para conseguir estos objetivos, podrían contemplar un proceso acelerado en la decisión de financiación y precio, y el pago por resultados con incertidumbre alta

OBJECTIVE: To assess the access to orphan medicines in Spain, focusing on those with an active "orphan" designation, as of 31st December 2017; and for those orphan medicines in the Spanish market, estimate the time between being assigned a National Code (NC) by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) and being approved for launch. METHOD: We used the European Commission's Public Register of orphan medicines to identify the orphan medicines authorised by the European Medicines Agency (EMA), as of 31 December 2017, while we sourced expired orphan indications from the EMA's website. Dates when NCs were assigned were sourced from the AEMPS, and commercialisation dates from Bot PLUS. A descriptive analysis of the study variables was done. The quantitative variables were described using means and medians, as well as standard deviations and ranges. The qualitative variables were described according to absolute and relative frequencies. The comparison of results was performed by parametric and non-parametric contrasts according to the applicability, at a 5% significance level. RESULTS: The EMA has approved 100 orphan medicines (with designation as of 31/12/2017) between 2002-2017. Eighty-six have a NC assigned by the AEMPS. Fifty-four have been launched in Spain (representing 54% of the full sample; 63% with NC). For the 53 orphan drugs with launch date in Spain, the median time between receiving its NC and its launch is 13.4 months (standard deviation: 17.0; minimum: 2.1; maximum: 91,7). The median time is 12.4 months and 14.0 months for those medicines launched in Spain between 2002-2013 and 2014-2017 respectively (p = 0.46). This difference is not statistically significant, which is what could be expected given the low numbers of orphan medicines in the "population". CONCLUSION: Complex factors determine the access to orphan drugs in Europe. The centralised procedure to obtain marketing authorisation at European level is a success. However, access is more limited, given the complexities of the evaluation of the available evidence for pricing and reimbursement decisions. It is therefore necessary to implement new policies that reduce inequalities in access and help achieve sustainable healthcare systems. To achieve this, they will need to offer the possibility of allowing earlier access, and using payment by results when there is high uncertainty

Orphan drugs revisited: cost-effectiveness analysis of the addition of mifamurtide to the conventional treatment of osteosarcoma.

INTRODUCTION: Mepact(®) (mifamurtide) is the first drug approved for the treatment of high-grade resectable non-metastatic osteosarcoma in patients aged 2-30 in the last 20 years. It follows a randomized clinical trial showing a statistically-significant and clinically-relevant decrease in the risk of death without compromising safety. AIM: This study assessed the cost-effectiveness and budget impact of mifamurtide. METHODS: The economic evaluation was done on a hypothetical cohort of young patients under the age of 30 with high-grade, non-metastatic, resectable osteosarcoma. Standard chemotherapy without mifamurtide was used as comparator. A Markov model was adapted using Spanish costs and the results of the INT-0133 Phase III study. The analysis has been carried out from the perspective of the Spanish National Health Service, with a time horizon of up to 60 years in the base analysis. RESULTS: The observed greater efficacy of mifamurtide in the trial translates into a gain of 3.03 (undiscounted) and 1.33 (discounted) quality-adjusted life years at an additional cost of €102,000. The estimated budgetary impact of using mifamurtide in 10-100% of the potential population would cost €671,000 and €6.7 million respectively. CONCLUSION: The cost per quality-adjusted life years gained with mifamurtide in Spain is in the low band (<€100,000) of the iCERs obtained by other orphan drugs and would have a limited and affordable cost in Spain.

PREDyCES study: The cost of hospital malnutrition in Spain.

OBJECTIVES: The aim of this study was to analyze the economic effects of hospital malnutrition and the cost of longer hospital stays according to the Prevalence of Hospital Malnutrition and Associated Costs in Spain (PREDyCES) study data. METHODS: This was a nested case-control study in a prospective cohort of patients (n = 114) who were at nutritional risk at admission and controls (n = 354) who were not at risk at admission. The total cost of hospital stay was the cost of the bed plus the cost of drugs administered during the stay. Hospital costs were extrapolated to Spanish National Health System admissions for 2009. RESULTS: The mean hospital length of stay for patients at risk (cases) was significantly longer (11.5 ± 7.5 versus 8.5 ± 5.8 d; P < 0.001) than for the controls. The cost of patients at risk at admission was significantly higher than that of those not at risk (€8590 ± €6127 versus €7085 ± €5625; P = 0.015). The most significant difference in the cost of the hospital stay was observed between controls at nutritional risk at discharge and controls who remained not at risk throughout the hospital stay (€13 013 ± €9086 versus €6665 ± €5091; P < 0.001). Extrapolation of the study findings to Spanish National Health System hospital admissions showed that the potential cost of hospital malnutrition in Spain was at least €1.143 billion per year. CONCLUSION: Hospital malnutrition in Spain is associated with substantial costs, suggesting the need to establish procedures for screening, diagnosing, and treating malnutrition.