Revisión sistemática de la implantación de prótesis de pene en cirugía mayor ambulatoria / Systematic review of the implantation of penile prosthesis in major ambulatory surgery

Introducción y objetivo La implantación de prótesis deZ pene (PP) es una alternativa eficaz para la disfunción eréctil. Aunque inicialmente la cirugía de PP se realizaba en régimen hospitalario, existe una tendencia creciente a realizar el implante de PP en un modelo de cirugía mayor ambulatoria (CMA). El objetivo de este estudio es realizar una revisión sistemática de la literatura para identificar la evidencia disponible sobre la implantación de PP en el marco de la CMA en comparación con el procedimiento realizado en régimen hospitalario. Material y métodos Se realizó una búsqueda en las bases de datos electrónicas PubMed, EMBASE, Cochrane Library y MEDES y en los suplementos no indexados de los congresos científicos para identificar artículos relacionados con la implantación quirúrgica de PP en CMA hasta febrero de 2021. Los términos de búsqueda incluyeron prótesis de pene, disfunción eréctil, cirugía ambulatoria, atención ambulatoria y cirugía. Resultados Entre las 171 publicaciones obtenidas (51 en PubMed, 73 en EMBASE, 3 en Cochrane, 2 mediante MEDES y 42 mediante búsqueda manual), se seleccionaron finalmente 5 estudios. No hubo diferencias significativas entre la CMA y el régimen hospitalario en términos del tipo de dispositivo, el abordaje quirúrgico o la ubicación del reservorio. Las tasas de complicaciones observadas en ambos grupos fueron similares. La implantación de PP en régimen de CMA supuso un menor coste que la cirugía en régimen hospitalario y se asoció con tasas aceptables de satisfacción de los pacientes y un adecuado control del dolor. Conclusiones Los estudios demostraron que la implantación de PP en régimen de CMA puede lograr resultados similares en términos de seguridad y satisfacción a la implantación de PP en el régimen hospitalario, pudiendo también reducir los costes y mejorar la eficiencia. Esta investigación podría ayudar a los responsables de la toma de decisiones a extender la cirugía de PP al régimen ambulatorio (AU)

Introduction and objective Penile prosthesis (PP) implantation is an effective option for erectile dysfunction. Although initially PP surgery was carried out in an inpatient setting, there is a growing trend to implant PP in a major ambulatory surgery (MAS). This study aimed to perform a systematic review of the literature to identify available evidence of the implantation of PP under MAS setting and go carry out a comparison between MAS and inpatient procedures. Material and methods PubMed, EMBASE, Cochrane Library and MEDES electronic databases and non-indexed supplements for scientific congresses were searched to identify articles related to the surgical implantation of PP in MAS up to February 2021. Key search terms included penile prosthesis, erectile dysfunction, ambulatory surgery, ambulatory care, and surgery. Results Among 171 publications retrieved (51 PubMed, 73 EMBASE, 3 Cochrane, 2 using MEDES and 42 manual searching), 5 studies were finally selected. There were no significant differences between MAS or inpatient setting in terms of the type of device, surgical approach, or location of reservoir. Complication rates observed in both groups were similar. Implantation of PP in MAS was less expensive than inpatient surgery and was associated with acceptable patient satisfaction rates and adequate pain control. Conclusions Studies demonstrated that outpatient PP surgery can achieve similar outcomes in terms of safety and satisfaction to implantation of PP in the inpatient setting, while it could reduce costs and improve the efficiency. This research could provide support decision makers to extend PP surgery into the ambulatory setting (AU)

Cost-effectiveness analysis of dyevert™ Power XT in patients with chronic kidney disease undergoing percutaneous coronary intervention procedures in Spain.

OBJECTIVE: To assess the efficiency of Dyevert™ Power XT compared to the standard clinical practice when used for percutaneous coronary interventions (PCI). METHODS: A Markov model was developed to estimate, over 3-month cycles and a lifetime time horizon, the cumulative costs and health outcomes (life years gained [LYG] and quality-adjusted life years [QALY]) in a hypothetical cohort of 1,000 patients with chronic kidney disease (CKD) 3b-4 and an average age of 72 years. The incidence of contrast-induced acute kidney injury for these patients is 18.89% in routine practice and 7.78% with Dyevert. QALYs were estimated by applying utilities by health state. Transitions between states and utilities were obtained from the literature. Overall all-cause and state-specific mortality were considered. The total cost (€2,022) estimated with the National Health System perspective included cost of the procedure and of CKD management. The parameters were validated by a panel of experts. A discount rate (3% per year) was applied to costs and outcomes. RESULTS: The use of Dyevert yielded more health benefits (34.60 LYG and 5.69 QALYs) compared to the current standard practice (33.11 LYG and 5.38 QALYs). Lifetime cost accumulated at the end of the simulation resulted €30,211/patient with Dyevert and €33,895/patient with current standard clinical practice. CONCLUSIONS: The use of Dyevert™ Power XT resulted dominant option, due to its higher effectiveness and lower cost as compared to standard clinical practice and, therefore, a preferred option in patients with CKD stages 3b-4 undergoing PCI in Spain.

Economic evaluations of radioembolization with yttrium-90 microspheres in liver metastases of colorectal cancer: a systematic review.

BACKGROUND: Transarterial radioembolization with yttrium-90 (Y-90 TARE) microspheres therapy has demonstrated positive clinical benefits for the treatment of liver metastases from colorectal cancer (lmCRC). This study aims to conduct a systematic review of the available economic evaluations of Y-90 TARE for lmCRC. METHODS: English and Spanish publications were identified from PubMed, Embase, Cochrane, MEDES health technology assessment agencies, and scientific congress databases published up to May 2021. The inclusion criteria considered only economic evaluations; thus, other types of studies were excluded. Purchasing-power-parity exchange rates for the year 2020 ($US PPP) were applied for cost harmonisation. RESULTS: From 423 records screened, seven economic evaluations (2 cost-analyses [CA] and 5 cost-utility-analyses [CUA]) were included (6 European and 1 USA). All included studies (n = 7) were evaluated from a payer and the social perspective (n = 1). Included studies evaluated patients with unresectable liver-predominant metastases of CRC, refractory to chemotherapy (n = 6), or chemotherapy-naïve (n = 1). Y-90 TARE was compared to best supportive care (BSC) (n = 4), an association of folinic acid, fluorouracil and oxaliplatin (FOLFOX) (n = 1), and hepatic artery infusion (HAI) (n = 2). Y-90 TARE increased life-years gained (LYG) versus BSC (1.12 and 1.35 LYG) and versus HAI (0.37 LYG). Y-90 TARE increased the quality-adjusted-life-year (QALY) versus BSC (0.81 and 0.83 QALY) and versus HAI (0.35 QALY). When considering a lifetime horizon, Y-90 TARE reported incremental cost compared to BSC (range 19,225 to 25,320 $US PPP) and versus HAI (14,307 $US PPP). Y-90 TARE reported incremental cost-utility ratios (ICURs) between 23,875 $US PPP/QALY to 31,185 $US PPP/QALY. The probability of Y-90 TARE being cost-effective at £ 30,000/QALY threshold was between 56% and 57%. CONCLUSIONS: Our review highlights that Y-90 TARE could be a cost-effective therapy either as a monotherapy or when combined with systemic therapy for treating ImCRC. However, despite the current clinical evidence on Y-90 TARE in the treatment of ImCRC, the global economic evaluation reported for Y-90 TARE in ImCRC is limited (n = 7), therefore, we recommend future economic evaluations on Y-90 TARE versus alternative options in treating ImCRC from the societal perspective.

Cost-Analysis of Subcutaneous vs Intravenous Administration of Natalizumab Based on Patient Care Pathway in Multiple Sclerosis in Spain.

INTRODUCTION: A subcutaneous (SC) formulation of natalizumab has been recently authorised for multiple sclerosis patients. This study aimed to assess the implications of the new SC formulation, and to compare the annual treatment costs of SC versus intravenous (IV) natalizumab therapy from both the Spanish healthcare system (direct health cost) and the patient (indirect cost) perspectives. METHODS: A patient care pathway map and a cost-minimisation analysis were developed to estimate SC and IV natalizumab annual costs over a 2-year time horizon. Considering the patient care pathway and according to natalizumab experience (IV) or estimation (SC), a national expert panel involving neurologists, pharmacists, and nurses provided information/data regarding resource consumption for drug and patient preparation, administration, and documentation. One hour of observation was applied to the first six (SC) or 12 (IV) doses, and 5 min for successive doses. The Day hospital (infusion suite) facilities at a reference hospital were considered for IV administrations and the first six SC injections. For successive SC injections, either a reference hospital or regional hospital in a consulting room was considered. Productivity time associated with travel (56 min to reference hospital, 24 min to regional hospital) and waiting time pre- and post-treatment (SC 15 min, IV 25 min) were assessed for patients and caregivers (accompanying 20% of SC and 35% of IV administrations). National salaries for healthcare professionals were used for cost estimation (€, year 2021). RESULTS: At years 1 and 2, total time and cost savings (excluding drug acquisition cost) per patient, driven by saving on administration and patient and caregiver productivity for SC at a reference hospital versus IV at a reference hospital, were 116 h (a reduction of 54.6%) and €3682.82 (a reduction of 66.2%). In the case of natalizumab SC at a regional hospital, the total time and cost saving were 129 h (a reduction of 60.6%) and €3883.47 (a reduction of 69.8%). CONCLUSIONS: Besides the potential benefits of convenient administration and improving work-life balance, as suggested by the expert panel, natalizumab SC was associated with cost savings for the healthcare system by avoiding drug preparation, reducing administration time, and freeing up infusion suite capacity. Additional cost savings could be derived with regional hospital administration of natalizumab SC by reducing productivity loss.

Cost-effectiveness of benralizumab versus mepolizumab and dupilumab in patients with severe uncontrolled eosinophilic asthma in Spain.

OBJECTIVE: To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. METHODS: Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), -0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. RESULTS: Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. CONCLUSIONS: Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.

Systematic review of the implantation of penile prosthesis in major ambulatory surgery.

INTRODUCTION AND OBJECTIVE: Penile prosthesis (PP) implantation is an effective option for erectile dysfunction. Although initially PP surgery was carried out in an inpatient setting, there is a growing trend to implant PP as a major ambulatory surgery (MAS). This study aimed to perform a systematic review of the literature to identify available evidence of the implantation of PP under MAS setting and go carry out a comparison between MAS and inpatient procedures. MATERIAL AND METHODS: PubMed, EMBASE, Cochrane Library and MEDES electronic databases and non-indexed supplements for scientific congresses were searched to identify articles related to the surgical implantation of PP in MAS up to February 2021. Key search terms included penile prosthesis, erectile dysfunction, ambulatory surgery, ambulatory care, and surgery. RESULTS: Among 171 publications retrieved (51 PubMed, 73 EMBASE, 3 Cochrane, 2 using MEDES and 42 manual searching), 5 studies were finally selected. There were no significant differences between MAS or inpatient setting in terms of the type of device, surgical approach, or location of reservoir. Complication rates observed in both groups were similar. Implantation of PP in MAS was less expensive than inpatient surgery and was associated with acceptable patient satisfaction rates and adequate pain control. CONCLUSIONS: Studies demonstrated that outpatient PP surgery can achieve similar outcomes in terms of safety and satisfaction to implantation of PP in the inpatient setting, while it could reduce costs and improve the efficiency. This research could support decision makers to extend PP surgery into the ambulatory setting.

Economic evaluations of radioembolization with Itrium-90 microspheres in hepatocellular carcinoma: a systematic review.

BACKGROUND: Transarterial radioembolization (TARE) with yttrium-90 microspheres is a clinically effective therapy for hepatocellular carcinoma (HCC) treatment. This study aimed to perform a systematic review of the available economic evaluations of TARE for the treatment of HCC. METHODS: The Preferred Reported Items for Systematic reviews and Meta-Analyses guidelines was followed by applying a search strategy across six databases. All studies identified as economic evaluations with TARE for HCC treatment in English or Spanish language were considered. Costs were adjusted using the 2020 US dollars based on purchasing-power-parity ($US PPP). RESULTS: Among 423 records screened, 20 studies (6 cost-analyses, 3 budget-impact-analyses, 2 cost-effectiveness-analyses, 8 cost-utility-analyses, and 1 cost-minimization analysis) met the pre-defined criteria for inclusion. Thirteen studies were published from the European perspective, six from the United States, and one from the Canadian perspectives. The assessed populations included early- (n = 4), and intermediate-advanced-stages patients (n = 15). Included studies were evaluated from a payer perspective (n = 20) and included both payer and social perspective (n = 2). TARE was compared with transarterial chemoembolization (TACE) in nine studies or sorafenib (n = 11). The life-years gained (LYG) differed by comparator: TARE versus TACE (range: 1.3 to 3.1), and TARE versus sorafenib (range: 1.1 to 2.53). Of the 20 studies, TARE was associated with lower treatment costs in ten studies. The cost of TARE treatment varied widely according to Barcelona Clinic Liver Cancer (BCLC) staging system and ranged from 1311 $US PPP/month (BCLC-A) to 71,890 $US PPP/5-years time horizon (BCLC-C). The incremental cost-utility ratio for TARE versus TACE resulted in a 17,397 $US PPP/Quality-adjusted-Life-Years (QALY), and for TARE versus sorafenib ranged from dominant (more effectiveness and lower cost) to 3363 $US PPP/QALY. CONCLUSIONS: Economic evaluations of TARE for HCC treatment are heterogeneous. Overall, TARE is a cost-effective short- and long-term therapy for the treatment of intermediate-advanced HCC.

Comparative cost analysis of cervical cancer screening programme based on molecular detection of HPV in Spain.

BACKGROUND: HPV cervical cancer screening (CCS) must use validated HPV tests based on the molecular detection of either viral mRNA (Aptima HPV Assay-AHPV) or DNA. AHPV has demonstrated the same cross-sectional and longitudinal sensitivity for the detection of HSIL/CIN2+ lesions but with greater specificity than HPV-DNA tests. The study aimed to estimate the total costs of a CCS with a primary HPV test based on the detection of mRNA compared to DNA in women aged 35-65 years for the National Health System. METHODS: A decision-tree-based model to estimate the cost of the CCS until the first colposcopy was designed based on Spanish CCS guidelines. The total cost (€, 2019) for CCS with AHPV or DNA tests (HC2 and Cobas) was calculated, including HPV test, liquid-based cytology (LBC) and colposcopy, for a population of 7,263,529 women aged 35-65 years (assuming 70% coverage). Clinical inputs derived from a literature review were validated by a multidisciplinary expert panel. Data from head-to-head studies between different HPV tests were selected. RESULTS: The use of AHPV showed reduction of 290,541 (- 35%) and 355,913 (- 40%) LBC compared to HC2 or Cobas, respectively. Furthermore, AHPV avoided 151,699 (- 47%) colposcopies versus HC2 and 151,165 (- 47%) versus Cobas. The total cost of CCS was € 282,747,877 with AHPV, € 322,587,588 with HC2 and € 324,614,490 with Cobas. Therefore, AHPV savings € - 39,839,711 versus HC2 and € - 41,866,613 versus Cobas. CONCLUSIONS: Assuming that 70% of women from 35 to 65 years attend the CCS programme, the cost of screening up to the first colposcopy using AHPV would provide cost savings of up to € 41.9 million versus DNA tests in Spain.

Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Systematic review of the evidence on the epidemiology of herpes zoster: incidence in the general population and specific subpopulations in Spain.

OBJECTIVES: Herpes zoster (HZ) is an important cause of morbidity around the world, especially among the adult population aged >50 years. STUDY DESIGN: A systematic review of the literature (up to October 31, 2016) was performed to identify available evidence on incidence of HZ in the general population and in a specific subpopulation in Spain. METHODS: PubMed and Embase databases were searched, combining the following search terms: 'herpes zoster', 'diabetes mellitus (DM)', 'chronic obstructive pulmonary disease (COPD)', 'chronic heart failure', 'mental disorders' and 'immunocompromised'. Supplements for local scientific congresses, non-indexed Spanish journals and official epidemiological reports, potentially HZ related, were also manually searched. The inclusion criteria were the following: English or Spanish publications reporting incidence of HZ in the Spanish general population and/or specific subpopulations. No restrictions were applied on the study design or population age. RESULTS: Among 269 references retrieved (48 PubMed, 148 Embase and 73 manual searching), 34 were finally included. Incidence of HZ in the general population ranged from 2.1 to 5.5/1000 person-years. HZ incidence ranged from 9.4 to 15.3/1000 patients with DM and from 11.0 to 11.4/1000 population with COPD or cardiovascular disease. In asthmatic patients, 6.9 HZ cases/1000 subjects were reported. The highest HZ incidence (1.3-400.0/1000 person-years) was in immunocompromised persons (10.0/1000 patients with cancer, 12.5/1000 patients with AIDS, from 5.0 to 240.0/1000 transplanted patients and from 6.6 to 27.0/1000 population with rheumatic diseases). Three studies estimated an increased risk of HZ in comparison with general population, for patients with DM (24%), COPD (39%) and COPD receiving inhaled corticosteroids (61%). CONCLUSIONS: The results suggest a high risk of HZ in certain age groups and specific subpopulations. This study could contribute to identify target age populations and at-risk groups if implementation of HZ vaccination programmes in Spain would be considered.

Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.

BACKGROUND: This study aimed at estimating the efficiency of palivizumab in the prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in preterm infants (32day 1-35day 0weeks of gestational age -wGA-) in Spain. METHODS: A decision-tree model was developed to compare health benefits (Quality Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32day 1-35day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15 mg/kg of palivizumab; 3.88 average number of injections per RSV season) was analysed. The model considered the most recent evidence from Spanish observational and epidemiological studies on RSV infection: the FLIP II study provided hospital admission and Intensive Care Unit (ICU) admission rates; in-hospital mortality rate was drawn from an epidemiological study from 2004 to 2012; recurrent wheezing rates associated to RSV infection from SPRING study were adjusted by the evidence on the palivizumab effect from clinical trials. Quality of life baseline value, number of hospitalized infants and the presence of recurrent wheezing over time were granted to estimate QALYs. National Health Service and societal perspective (included also recurrent wheezing indirect cost) were analysed. Total costs (€, 2016) included pharmaceutical and administration costs, hospitalization costs and recurrent wheezing management annual costs. A discount rate of 3.0% was applied annually for both costs and health outcomes. RESULTS: Over 6 years, the base case analysis showed that palivizumab was associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total costs were estimated in €2,110.71 (palivizumab) and €671.68 (non-prophylaxis) from the National Health System (NHS) perspective, resulting in an incremental cost utility ratio (ICUR) of €19,697.69/QALYs gained (prophylaxis vs non-prophylaxis). Results derived from the risk-factors population subgroups analysed were in line with the total population results. From the societal perspective, the incremental cost associated to palivizumab decreased to an €1,253.14 (ICUR = €17,153.16€/QALYs gained for palivizumab vs non-prophylaxis). One-way and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: The prophylaxis with palivizumab is efficient for preventing from RSV infections in preterm infants 32day 1-35day 0 wGA in Spain.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.

Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España / Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain

OBJETIVO: Realizar un análisis coste-efectividad y coste-utilidad de ingenol mebutato en el tratamiento de la queratosis actínica en España. MÉTODOS: Se realizó la adaptación de un modelo de Markov que simuló una cohorte de pacientes (73 años de media) con queratosis actínica en un horizonte temporal de 5 años. Los comparadores fueron diclofenaco 3% e imiquimod 5%. El análisis se desarrolló desde la perspectiva del Sistema Nacional de Salud, incluyendo costes directos sanitarios (PVPIVA con la deducción obligatoria, € 2015). La estimación de recursos se llevó a cabo por un panel de expertos y los costes unitarios se obtuvieron de bases de datos de costes nacionales. La tasa de descuento considerada fue del 3% anual. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. RESULTADOS: Ingenol mebutato fue más eficiente frente a diclofenaco, con 0,192 aclaramientos incrementales en la cara y el cuero cabelludo y 0,129 en el tronco y las extremidades. Los costes totales fueron de 551,50€ y 622,27€ comparados con 849,11€ y 844,93€ en diclofenaco (cara y cuero cabelludo y tronco y extremidades, respectivamente). Es decir, ingenol mebutato es una alternativa de tratamiento dominante frente a diclofenaco 3%. Ingenol mebutato también mostró una mayor eficacia frente a imiquimod 5%, con 0,535 vs. 0,503 aclaramientos ganados, y unos costes totales de 551,50€ vs. 527,89€, siendo la relación coste-efectividad incremental resultante de 728,64€/aclaramiento adicional. CONCLUSIONES: Ingenol mebutato resultó ser una estrategia dominante vs. diclofenaco, y eficiente, es decir, presentó mayor efectividad y mayores costes (relación coste-utilidad incremental inferior a 30.000€/AVAC) vs. Imiquimod

OBJECTIVE: To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. METHODS: We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. CONCLUSIONS: Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years)

Análisis coste-efectividad de celecoxib frente a antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis en España: una perspectiva actual / Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: a current perspective

OBJETIVO: Realizar un análisis coste-efectividad de celecoxib y antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis según práctica habitual en España. MÉTODOS: El análisis coste-efectividad se realizó mediante un modelo analítico tipo árbol de decisión utilizando la distribución, dosis y duración de los tratamientos y la incidencia de eventos gastrointestinales (GI) y cardiovasculares observados en el estudio pragmático «GI-Reasons». La efectividad se expresó en eventos evitados y años de vida ajustados por calidad (AVAC) ganados. Los AVAC ganados se calcularon a partir del coeficiente de utilidad asociado a cada tipo de evento GI o cardiovascular observados en el estudio GI-Reasons. La perspectiva fue la del Sistema Nacional de Salud para el cálculo de los costes de tratamiento usando precios actuales (€, noviembre de 2014) de los fármacos y eventos GI y cardiovascular. El análisis coste-efectividad se expresó como coste incremental por AVAC ganado y por evento evitado. Se llevaron a cabo análisis de sensibilidad probabilísticos y univariantes. RESULTADOS: En comparación con antiinflamatorios no esteroideos no selectivos, celecoxib, a su precio actual, mostró mayores costes sanitarios por paciente: 157 € versus 201 €. Sin embargo, se asoció con un aumento de la ganancia de AVAC y una incidencia significativamente menor de eventos GI (p < 0,001), mostrando un coste incremental de 13.286 € por AVAC ganado y 4.471 € por evento evitado. Los análisis de sensibilidad confirmaron los resultados. CONCLUSIÓN: Celecoxib a su precio actual puede ser considerado una alternativa coste-efectiva frente a los antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis en España

OBJECTIVE: To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. METHODS: A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. RESULTS: Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs € 201 and € 157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of € 13,286 per QALY gained and € 4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. CONCLUSION: Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS

Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain. / Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España.

OBJECTIVE: To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. METHODS: We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. CONCLUSIONS: Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years).

[Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective]. / Análisis coste-efectividad de celecoxib frente a antiinflamatorios no esteroideos no selectivos en el tratamiento de la artrosis en España: una perspectiva actual.

OBJECTIVE: To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. METHODS: A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons¼ trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. RESULTS: Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. CONCLUSION: Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS.

Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

OBJECTIVE: A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). METHODS: Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 µg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. RESULTS: Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. CONCLUSION: Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.

Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF / Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study

Antecedentes y objetivos: La terapia anticoagulante oral resulta compleja dadas las necesidades de control y el riesgo hemorrágico que conlleva. Este estudio pretende determinar la práctica clínica habitual del tratamiento para la prevención del ictus en pacientes con fibrilación auricular no valvular (FANV) en España. Pacientes y método: El Real Evidence of Anti Coagulation Treatment in AF es una cohorte multicéntrica, europea, multinacional, observacional, de seguimiento retrospectivo, de pacientes con FANV. En este estudio se incluye a los pacientes reclutados en España con al menos una visita en el periodo de inclusión (mayo 2010/abril 2012). Se evaluaron: a) la persistencia del tratamiento con anticoagulantes orales (tiempo hasta discontinuación); b) la tasa de persistencia (porcentaje de pacientes en tratamiento) a los 6, 12 y 24 meses, y 5 años; c) la adherencia terapéutica (tasa de posesión de medicación); d) la concordancia entre el tratamiento seguido y el recomendado según la Sociedad Europea de Cardiología; y e) la incidencia de ictus y eventos hemorrágicos. Resultados: Los pacientes tratados con anticoagulantes orales (n=7.526) presentaron un tiempo hasta discontinuación del tratamiento de 1,99 años (mediana) y una tasa de persistencia a 5 años del 26% (discontinuación ≥3 meses). La adherencia (tasa de posesión de medicación media) fue 0,54±0,36. La incidencia de ictus fue 0,3/100 personas-año y la de eventos hemorrágicos, 2,4/100 personas-año. El 58% de los pacientes con FANV (n=12.514) seguía las recomendaciones de la Sociedad Europea de Cardiología. Conclusión: El 42% de los pacientes con FANV no seguía las recomendaciones de la Sociedad Europea de Cardiología. Se detectó una baja persistencia y adherencia al tratamiento con anticoagulantes orales (AU)

Background and objectives: Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. Patients and method: The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. Results: The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Conclusion: Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants (AU)

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study. / Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF.

BACKGROUND AND OBJECTIVES: Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. PATIENTS AND METHOD: The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. RESULTS: The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. CONCLUSION: Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants.

[Cost-minimization analysis of subcutaneous abatacept in the treatment of rheumatoid arthritis in Spain]. / Análisis de minimización de costes de abatacept subcutáneo en el tratamiento de la artritis reumatoide en España.

OBJECTIVE: To compare the cost of treating rheumatoid arthritis patients that have failed an initial treatment with methotrexate, with subcutaneous abatacept versus other first-line biologic disease-modifying antirheumatic drugs. METHOD: Subcutaneous abatacept was considered comparable to intravenous abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab, based on indirect comparison using mixed treatment analysis. A cost-minimization analysis was therefore considered appropriate. The Spanish Health System perspective and a 3 year time horizon were selected. Pharmaceutical and administration costs (Euros 2013) of all available first-line biological disease-modifying antirheumatic drugs were considered. Administration costs were obtained from a local costs database. Patients were considered to have a weight of 70 kg. A 3% annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Subcutaneous abatacept proved in the base case to be less costly than all other biologic antirrheumatic drugs (ranging from Euros -831.42 to Euros -9,741.69 versus infliximab and tocilizumab, respectively). Subcutaneous abatacept was associated with a cost of Euros 10,760.41 per patient during the first year of treatment and Euros 10,261.29 in subsequent years. The total 3-year cost of subcutaneous abatacept was Euros 29,953.89 per patient. Sensitivity analyses proved the model to be robust. Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity analysis simulations versus adalimumab, certolizumab, etanercept and golimumab, in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3% versus infliximab. CONCLUSIONS: Treatment with subcutaneous abatacept is cost-saving versus intravenous abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis patients initiating treatment with biological antirheumatic drugs.

OBJETIVO: Comparar, desde la perspectiva del Sistema Sanitario, el coste del tratamiento con abatacept subcutáneo en pacientes con artritis reumatoide tras fracaso a metotrexato, frente al resto de fármacos antirreumáticos modificadores de la enfermedad disponibles en España con indicación en primera línea de terapia biológica. MÉTODOS: Una comparación indirecta demostró eficacia y seguridad de abatacept subcutáneo comparables a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab, por lo que se optó por una minimización de costes. El análisis incluyó costes farmacológicos y de administración (, 2013) para un paciente "tipo" de 70 kg y un horizonte temporal de tres años. Se aplicó una tasa anual de descuento del 3%. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. RESULTADOS: Abatacept subcutáneo tuvo un coste anual de 10.760,41 durante el primer año, 10.261,29 en los años siguientes, y un coste total de 29.953,89 a los tres años, generando ahorros (rango -831,41 versus infliximab a -9.741,69 versus tocilizumab) frente a los demás antirreumáticos modificadores de la enfermedad. Las mayores diferencias entre fármacos se observaron durante el primer año de tratamiento. Abatacept subcutáneo se asoció a ahorros en el 100% de las simulaciones del análisis de sensibilidad probabilístico versus adalimumab, certolizumab, etanercept y golimumab, en más del 99,6% versus abatacept intravenoso y tocilizumab y en el 62,3% versus infliximab. CONCLUSIONES: En base a los resultados, el tratamiento con abatacept subcutáneo genera ahorros frente a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab en pacientes con artritis reumatoide que inician tratamiento con fármacos antirreumáticos biológicos.