Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain

[Abstract] Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective. Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018). Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/ Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA). Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS

Comparison of the design and methodology of Phase 3 clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir-based dual therapy (DTG) in HIV: a systematic review of the literature

Introduction: Current recommended antiretroviral regimens include a combination of two (dual; DT) or three (triple; TT) antiretroviral drugs. This study aims to determine whether the quality of evidence from clinical trials of dolutegravir (dolutegravir/lamivudine [DTG/3TC] or dolutegravir/rilpivirine [DTG/RPV]) is methodologically comparable to that of clinical trials conducted with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Areas covered: A systematic review of the medical literature was carried out in PubMed without date or language restrictions, following the PRISMA guidelines. All aspects of the methodological design of phase 3 randomized clinical trials (RCTs) of DT and TT, evaluated by the European Medicines Agency (registration trials), were reviewed. The quality of clinical trials was assessed using the Jadad scale. Expert opinion: The search identified 5, 3 and 2 phase 3 RCTs with BIC/FTC/TAF, DTG/3TC and DTG/RPV, respectively, that met the inclusion criteria. The designs would not be comparable due to differences in pre-randomization losses, blinding, patient recruitment, as well as differences in methodological quality, with the average score of the RCTs conducted with BIC/FTC/TAF, DTG/3TC and DTG/RPV being 4.2 (high quality), 3.0 (medium quality) and 3.0 (medium quality), respectively. Due to methodological differences between the BIC/FTC/TAF, DTG/3TC and DTG/RPV RCTs, the results of these are not comparable

Budgetary impact for the National Health System of Apixaban Prophylaxis of venous thromboembolism in patients undergoing yotal knee or hip replacement

Fundamentos: Debido al elevado coste sanitario del tromboembolismo venoso (TEV) es necesario realizar análisis económicos que determinen la eficiencia de sus diferentes tratamientos farmacológicos. El objetivo del trabajo es estimar el impacto presupuestario para el Sistema Nacional de Salud (SNS) de la prevención del tromboembolismo venoso (TEV) con apixaban en artroplastia total de cadera (ATC) o rodilla (ATR). Métodos: Se consideraron los costes de los diferentes fármacos para la prevención del TEV (apixaban, dabigatrán, enoxaparina, fondaparinux, otras heparinas, rivaroxaban y warfarina) y los de las complicaciones del TEV a corto plazo (90 días) y a 5 años (trombosis venosa profunda, embolismo pulmonar, sangrados y síndrome postrombótico). La eficacia de la prevención se estimó mediante un metaanálisis. Las tasas de TEV y muerte con apixaban fueron inferiores en ATC y ATR a las observadas con enoxaparina (-3,5% y -10,0%, respectivamente) y tuvo menos acontecimientos hemorrágicos (-0,7% y -1,6%, respectivamente). Los datos poblacionales y los costes se obtuvieron de fuentes españolas. Horizonte temporal: 5 años. Todos los costes se descontaron anualmente un 3,5%. Se estimó que a los cinco años de su comercialización el consumo de apixaban supondría el 23% de la prevención del TEV y el de enoxaparina descendería del 60% hasta el 33%. Resultados: La introducción de apixaban para la prevención del TEV produciría un ahorro para el SNS de 547.422 € en un periodo de 5 años. En el caso de considerar sin coste la administración ambulatoria de las heparinas, el ahorro quinquenal para el SNS ascendería a 270.068 €. Conclusiones: La introducción de apixaban podría reducir la tasa de TEV y sangrados en comparación con enoxaparina, reduciéndose el gasto del SNS en la prevención del TEVDue to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement. Methods: Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources. Time horizon: 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%. Results: Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of € 547,422 over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis € 270,068. Conclusions: According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxisEstudio financiado, sin restricciones, por Bristol-Myers Squibb y Pfize

Health and economic impact of the correct diagnosis of transthyretin cardiac amyloidosis in Spain

Objective: to estimate the health and economic impact of the reduction in mortality and cardiovascular hospitalizations, associated with correct diagnosis of cardiac transthyretin amyloidosis (ATTR-CM), from the Spanish National Health System (NHS) perspective. Methods: a costs and effects analysis were performed (probabilistic Markov model) with time horizons between 1 and 15 years, comparing the correct diagnosis of ATTR-CM versus the non-diagnosis. Transition probabilities were obtained from the ATTR-ACT study (placebo arm) and from the literature. Costs and healthcare resources were obtained from Spanish sources ( 2019) and from a panel of Spanish clinical experts. Results: after 1, 5, 10 and 15 years, the diagnosis of ATTR-CM would generate a gain of 0.031 (95%CI 0.025; 0.038); 0.387 (95%CI 0.329; 0.435); 0.754 (95%CI 0.678; 0.781) and 0.944 (95%CI 0.905; 0.983) life years per patient, respectively, with savings of 212 (95%CI -632; 633), 2,289 (95%CI 2,250; 2,517), 2,859 (95%CI 2,584; 3,149) and 2,906 (95%CI 2,669; 3,450) per patient, respectively, versus the non-diagnosis. Conclusions: just by correctly diagnosing ATTR-CM, years of life would be gained, cardiovascular hospitalizations would be avoided, and savings would be generated for the NHS, compared to the non-diagnosis of the disease

Economic Evaluation of Rheumathoid Arthritis Monotherapy with Tocilizumab and Adalimumab

[Resumen] Fundamento: Tocilizumab (TCZ) fue superior a adalimumab (ADA) en monoterapia en la reducción de los signos y síntomas de la artritis reumatoide del adulto (AR) en pacientes intolerantes o con respuesta inadecuada a metotrexato (MTX). El objetivo del estudio fue analizar el coste-efectividad de TCZ vs ADA en estos pacientes. Métodos: Evaluación económica del coste por respuesta o remisión con TCZ vs ADA a partir del estudio ADACTA (horizonte temporal: 24 semanas). Criterios de respuesta clínica ACR o de remisión de la enfermedad, índice DAS28. Ámbito: Sistema Nacional de Salud. Los costes incluidos (adquisición, administración y monitorización de los medicamentos en € de 2012) se obtuvieron de fuentes españolas. Se efectuaron análisis de sensibilidad simples univariantes. Resultados: Las tasas de respuesta ACR20, ACR50 y ACR70 con TCZ y ADA se obtuvieron en el 65% y 49,4% (p <0,01); 47,2% y 27,8% (p <0,01); y en el 32,5% y 17,9% (p <0,01) de los pacientes, respectivamente. La remisión DAS28 se produjo en el 39,9% y 10,5%, respectivamente (p <0,0001). El coste por respuesta fue menor con TCZ que con ADA (ACR20: 8.105 y 11.553 €; ACR50: 11.162 y 20.529 €; ACR70: 16.211 y 31.882 €) respectivamente. El coste de la remisión DAS28 fue de 13.204 € y 54.352 € respectivamente. En todos los escenarios el tratamiento con TCZ tuvo mayor eficacia y menores costes que con ADA. Conclusiones: Según este análisis, en España la monoterapia con TCZ es una estrategia eficiente frente a ADA para el tratamiento de los pacientes con AR intolerantes o con respuesta inadecuada a MTX.[Abstract] Background: Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients. Methods: Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease remission criteria, DAS28. Perspective: National Health System. The costs included (acquisition, administration and monitoring of medicines; € 2012) were obtained from Spanish sources. Simple univariate sensitivity analyzes were performed. Results: ACR20, ACR50 and ACR70 response rates with TCZ and ADA were obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and 17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and 10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than with ADA (ACR20: € 8,105 and € 11,553; ACR50: € 11,162 and € 20,529; ACR70: € 16,211 and € 31,882) respectively. The cost of DAS28 remission was € 13,204 and € 54,352, respectively. Treatment with TCZ was dominant (more effective, with lower costs vs ADA) in all scenarios analyzed. Conclusions: According to this analysis, in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients intolerant to MTX or in which there is inappropriate response

¿Qué es una intervención sanitaria eficiente en España en 2020?

Hace más de 15 años que en Gaceta Sanitaria se publicó el artículo titulado «¿Qué es una tecnología sanitaria eficiente en España?». El creciente interés por fijar el precio de las nuevas tecnologías en función del valor que estas proporcionan a los sistemas de salud y la experiencia acumulada por los países de nuestro entorno hacen oportuno revisar qué es una intervención sanitaria eficiente en España en el año 2020. El análisis de coste-efectividad sigue siendo el método de referencia para maximizar los resultados en salud de la sociedad con los recursos disponibles. La interpretación de sus resultados requiere establecer unos valores de referencia que sirvan de guía sobre lo que constituye un valor razonable para el sistema sanitario. Los umbrales de eficiencia deben ser flexibles y dinámicos, y actualizarse periódicamente. Su aplicación debe estar basada en la gradualidad y la transparencia, considerando, además, otros factores que reflejen las preferencias sociales. Aunque la fijación de los umbrales corresponde a los decisores políticos, en España puede ser razonable utilizar unos valores de referencia como punto de partida que podrían estar comprendidos entre los 25.000 y los 60.000 euros por año de vida ajustado por calidad. No obstante, en la actualidad, más que la determinación de las cifras exactas de dicho umbral, la cuestión clave es si el Sistema Nacional de Salud está preparado y dispuesto a implantar un modelo de pago basado en el valor, que contribuya a lograr la gradualidad en las decisiones de financiación y, sobre todo, a mejorar la previsibilidad, la consistencia y la transparencia del proceso.Fifteen years ago, Gaceta Sanitaria published the article entitled “What is an efficient health technology in Spain?” The growing interest in setting the price of new technologies based on the value they provide to health systems and the experience accumulated by the countries in our environment make it opportune to review what constitutes an efficient health intervention in Spain in 2020. Cost-effectiveness analysis continues to be the reference method to maximize social health outcomes with the available resources. The interpretation of its results requires establishing reference values that serve as a guide on what constitutes a reasonable value for the health care system. Efficiency thresholds must be flexible and dynamic, and they need to be updated periodically. Its application should be based on and transparency, and consider other factors that reflect social preferences. Although setting thresholds is down to political decision-makers, in Spain it could be reasonable to use thresholds of 25,000 and 60,000 Euros per QALY. However, currently, in addition to determining exactfigures for the threshold,the key question is whether the Spanish National Health System is able and willing to implement a payment model based on value, towards achieving gradual financing decisions and, above all, to improve the predictability, consistency and transparency of the process

Cost-effectiveness Analysis of Rituximab Maintenance Treatment in Patients With Follicular Lymphoma who Respond to First Line Induction Therapy in Portugal

Introduction: To perform a cost-effectiveness analysis of follicular lymphoma maintenance treatment after first-line induction with rituximab compared to observation in Portugal. Methods: A Markov follicular lymphoma model was developed with four health states: progression free survival on first and second lines, progression and death. The transition probabilities between health states were obtained from the PRIMA and EORTC20981 clinical trials and the health states utilities from the literature. The analysis considered the Portuguese National Health Service perspective and includes only direct costs. Resource consumption was estimated by a Portuguese clinical expert panel. The unit costs (€ in 2014) were estimated using Portuguese official databases. Deterministic and probabilistic analyses were performed. Results: In the base case, for a time horizon of 10 years, the cost per life year gained and per quality-adjusted life-year were € 10,634 and € 10,664, respectively. The sensitivity analyses confirmed the stability of the base case for time horizons of 20 and 30 years, varying between € 7,430 and € 7,155. Maintenance with rituximab is cost-effective for a time horizon of 5.5 years (cost per quality-adjusted life-year gained of € 23,616). Conclusion: According to the present model rituximab maintenance treatment of follicular lymphoma patients that respond to first line induction therapy in comparison with observation is cost-effective in Portugal

Coste de la diarrea asociada a Clostridium difficile en España

Background: There are not available adequate studies of the costs of Clostridium difficile-associated diarrhea (CDAD) in Spain. The aim of the study is to estimate the cost of CDAD for the National Health Service (NHS). Methods: an economic model was carried out to calculate the cost per episode of CDAD (due to antimicrobials, prolonged hospitalization, surgical procedures, measures to control the infection, recurrences of infections treated) and the CDAD annual cost. Resources use in clinical practice was obtained through a Delphi panel of Spanish clinicians with expertise in CDAD and unit costs (€ 2012) from Spanish Sources. Results: An estimated 7,601 episodes of CDAD occur annually in Spain (incidence of 17.1 episodes/year/10,000 hospital discharges) with an annual cost to the NHS of € 32,157,093. Cost per episode of CDAD: € 3,901 (initial infection), € 4,875 (first recurrence) and € 5,916 (second recurrence). Total cost of recurrences: € 10,426,750 annually. The 95.6% of spending is due to the prolonged hospitalization, 0.5% to antibiotic treatment, 2.8% for surgery and 1.1% for measures of control infection. Study results are sensitive to incidence and case fatality rate of CDAD in Spain and the prolongation of duration of hospital stay due to CDAD. Conclusions: According to this study, the expense associated with CDAD is primarily due to the prolongation of hospitalization and has a great economic impact on the NHS.Fundamentos: No se dispone de estudios adecuados del coste de las diarreas asociadas a Clostridium difficile (DACD) en España. El objetivo del estudio es estimar el coste de las DACD para el Sistema Nacional de Salud (SNS). Métodos: Se realizó un modelo económico para calcular el coste por episodio de DACD (por antibióticos, prolongación del ingreso hospitalario, procedimientos quirúrgicos, medidas de control de la infección, recurrencias de las infecciones tratadas) y el coste anual de la DACD. El uso de recursos en la práctica clínica se obtuvo mediante un panel Delphi de clínicos españoles con experiencia en la DACD y los costes unitarios (€ 2012) de fuentes españolas. Resultados: Se estimó que anualmente se produjeron 7.601 episodios de DACD en España (incidencia de 17,1 episodios/año/10.000 altas hospitalarias) con un gasto anual para el SNS de 32.157.093 €. Coste por episodio de DACD: 3.901 € (infección inicial), 4.875 € (primera recurrencia) y 5.916 € (segunda recurrencia). Coste total de las recurrencias: 10.426.750 € anuales. El 95,6% del gasto se debería a la prolongación de la duración de la estancia hospitalaria, el 0,5% a tratamientos antibióticos, el 2,8% a intervenciones quirúrgicas y el 1,1% a las medidas de control de la infección. Los resultados del estudio fueron sensibles a la incidencia y tasa de letalidad de la DACD en España y a la duración de la prolongación de la duración de la estancia hospitalaria debida a la DACD. Conclusiones: Según este estudio, el gasto asociado a la DACD se debe fundamentalmente a la prolongación de los ingresos hospitalarios y tiene un gran impacto económico en el SNS

Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR-TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS). METHODS: The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation. RESULTS: The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57-881.29) per patient. CONCLUSION: In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system