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