Abstract Background Refractory cardiogenic shock (CS) is associated with high mortality rates, and the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a therapeutic option has generated discussions. Therefore, its cost-effectiveness, especially in low- and middle-income countries like Brazil, remains uncertain.Objectives: To conduct a cost-utility analysis from the Brazilian Unified Health System perspective to assess the cost-effectiveness of VA-ECMO combined with standard care compared to standard care alone in adult refractory CS patients. Methods We followed a cohort of refractory CS patients treated with VA-ECMO in tertiary care centers located in Southern Brazilian. We collected data on hospital outcomes and costs. We conducted a systematic review to supplement our data and utilized a Markov model to estimate incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) and per life-year gained. Results In the base-case analysis, VA-ECMO yielded an ICER of Int$ 37,491 per QALY. Sensitivity analyses identified hospitalization cost, relative risk of survival, and VA-ECMO group survival as key drivers of results. Probabilistic sensitivity analysis favored VA-ECMO, with a 78% probability of cost-effectiveness at the recommended willingness-to-pay threshold. Conclusions Our study suggests that, within the Brazilian Health System framework, VA-ECMO may be a cost-effective therapy for refractory CS. However, limited efficacy data and recent trials questioning its benefit in specific patient subsets highlight the need for further research. Rigorous clinical trials, encompassing diverse patient profiles, are essential to confirm cost-effectiveness and ensure equitable access to advanced medical interventions within healthcare systems, particularly in socio-economically diverse countries like Brazil. (CS rates VAECMO VA ECMO (VA-ECMO discussions Therefore costeffectiveness, costeffectiveness cost effectiveness, effectiveness low middleincome middle income Brazil uncertain.Objectives uncertainObjectives uncertain Objectives costutility utility costs ICERs (ICERs qualityadjusted quality adjusted QALY (QALY lifeyear gained basecase base case Int 37491 37 491 37,49 results VAECMO, ECMO, 78 willingnesstopay willingness pay threshold that framework costeffective effective However research profiles systems socioeconomically socio economically 3749 3 49 37,4 7 374 4 37,

Resumo Fundamento O choque cardiogênico (CC) refratário está associado com altas taxas de mortalidade, e o uso de oxigenação por membrana extracorpórea venoarterial (VA-ECMO, do inglês venoarterial extracorporeal membrane oxygenation) como uma opção terapêutica tem gerado discussões. Nesse sentido, sua custo-efetividade, principalmente em países de baixa e média renda como o Brasil, continua incerto.Objetivos: Conduzir uma análise de custo-efetividade na perspectiva do Sistema Único de Saúde (SUS) para avaliar a custo-efetividade de VA-ECMO combinado com o tratamento padrão em comparação ao tratamento padrão isolado em pacientes adultos com CC refratário. Métodos Acompanhamos uma coorte de pacientes com CC refratário tratados com VA-ECMO em centros de assistência terciária do sul brasileiro. Coletamos dados de desfechos e custos hospitalares. Realizamos uma revisão sistemática para complementar nossos dados e usamos o modelo de Markov para estimar a razão de custo-efetividade incremental (RCEI) por ano de vida ajustado pela qualidade (QALY) e por ano de vida ganho. Resultados Na análise do caso-base, a VA-ECMO gerou uma RCEI de Int$ 37 491 por QALY. Análises de sensibilidade identificaram o custo de internação, o risco relativo de sobrevida, e a sobrevida do grupo submetido à VA-ECMO como principais variáveis influenciando os resultados. A análise de sensibilidade probabilística mostrou um benefício do uso de VA-ECMO, com uma probabilidade de 78% de custo-efetividade no limiar recomendado de disposição a pagar. Conclusões Nosso estudo sugere que, dentro do SUS, VA-ECMO pode ser uma terapia custo-efetiva para o CC refratário. Contudo, a escassez de dados sobre a eficácia e de ensaios clínicos recentes que abordem seus benefícios em subgrupos específicos de pacientes destaca a necessidade de mais pesquisas. Ensaios clínicos rigorosos, incluindo perfis diversos de pacientes, são essenciais para confirmar a custo-efetividade com uso de VA-ECMO e assegurar acesso igualitário a intervenções médicas avançadas dentro dos sistemas de saúde, especialmente em países com desigualdades socioeconômicas como o Brasil. (CC mortalidade VAECMO, VAECMO VA ECMO, ECMO (VA-ECMO oxygenation discussões sentido custoefetividade, custoefetividade efetividade, efetividade Brasil incerto.Objetivos incertoObjetivos incerto Objetivos SUS (SUS brasileiro hospitalares (RCEI QALY (QALY ganho casobase, casobase caso base, base caso-base Int 3 49 internação resultados 78 pagar custoefetiva efetiva Contudo pesquisas rigorosos saúde 4 7

RESUMO Objetivo Avaliar a relação custo-utilidade do iStent inject® para o tratamento do glaucoma de ângulo aberto leve a moderado no Sistema Único de Saúde. Métodos Foi desenvolvido um modelo de Markov, no qual a medida de resultado de efetividade foi a razão custo-efetividade incremental (razão de custo-efetividade incremental: R$/ano de vida ajustado pela qualidade). Os custos médicos diretos foram obtidos por meio da perspectiva do Sistema Único de Saúde. O caso base foi composto de uma coorte hipotética de pacientes com glaucoma de ângulo aberto em uso de medicação tópica tratados de acordo com o Protocolo Clínico e Diretrizes Terapêuticas e um cenário do mundo real baseado em dados do Departamento de Informática do Sistema Único de Saúde. Foi testada a robustez do modelo por meio de análises de sensibilidade. Resultados No cenário base do Protocolo Clínico e Diretrizes Terapêuticas, o implante trabecular micro-bypass proporcionou ganhos de 0,47 ano de vida ajustado pela qualidade e razão de custo-efetividade incremental de R$7.996,66/ano de vida ajustado pela qualidade em relação ao tratamento com medicação tópica. No cenário real baseado em dados do Departamento de Informática do Sistema Único de Saúde, o implante trabecular proporcionou ganhos de 0,47 ano de vida ajustado pela qualidade e razão de custo-efetividade incremental de R$ 4.485,68/ano de vida ajustado pela qualidade em relação ao tratamento com medicação tópica. Os resultados foram robustos para análises de sensibilidade. Conclusão A incorporação do iStent inject® ao Sistema Único de Saúde proporciona melhora na qualidade de vida do paciente com um custo adicional que garante o benefício proporcionado a eles. Os resultados podem ser considerados custo-efetivos em comparação com a medicação tópica.

ABSTRACT Purpose To evaluate the cost-utility of the iStent inject® for the treatment of mild-to-moderate open-angle glaucoma (OAG) within the Brazilian Unified Health System (SUS). Methods A Markov model was developed, in which the effectiveness outcome measure was the incremental cost-effectiveness ratio (ICER: R$ / QALY quality-adjusted life-year). Direct medical costs were obtained from the SUS perspective. The base case comprised of a hypothetical cohort of patients with OAG using topical medication and being managed according to the Clinical Protocol and Therapeutic Guidelines (PCDT) and a real-world setting based on data from Datasus. The model’s robustness through sensitivity analyses was tested. Results In the PCDT base case setting, the trabecular micro-bypass implant provided gains of 0.47 QALYs and an ICER of R$7,996.66/QALY compared to treatment with topical medication. In the real-world setting based on data from Datasus, the trabecular micro-bypass implant, provided gains of 0.47 QALYs and an ICER of R$4,485.68/QALY compared to treatment with topical medication. The results were robust to sensitivity analyses. Conclusion Incorporating iStent inject® to SUS provides an improvement in the patient’s quality of life with an additional cost that warrants the benefit provided to patients. Results may be considered cost-effective compared to topical medication.

Abstract Aim: The study aimed to conduct a cost-utility analysis of traditional drug therapy (TDT) provided for hypertensive patients at primary care in comparison to the protocol based on combination with an exercise program (TDT+E) in real-life conditions, adopting a health system perspective. Methods: Longitudinal study based on enrollment of 49 hypertensive adults distributed into two groups, for 12 months. Quality-adjusted life years were estimated using health-related quality of life. Direct health care costs were calculated including inputs and human resources in primary care from medical records. Sensitivity analysis was performed based on multivariate and probabilistic scenarios. Results: Incremental cost-effectiveness ratios of TDT+E in comparison to TDT were +79.69. Sensitivity analysis showed that TDT+E presented advantages considering uncertainties. Conclusion: Our findings show that exercise programs may improve quality of life and life expectancy among hypertensive patients.

Abstract Background: Implantable cardiac defibrillators (ICDs) therapy for primary prevention (PP) of sudden cardiac arrest (SCA) is well-established but underutilized globally. The Improve SCA study has identified a cohort of patients called 1.5 primary prevention (1.5PP), based on PP patients with the presence of documented risk factors: non-sustained ventricular tachycardia, frequent premature ventricular contractions, left ventricular ejection fraction < 25%, and pre-syncope or syncope. Objective: This study evaluated the cost-effectiveness of ICD therapy compared to no ICD among 1.5PP patients in the Brazilian public healthcare system. Methods: Modified inputs to a published Markov model were applied to compare costs and outcomes of ICD therapy to no ICD therapy from the Brazilian payer’s perspective. Mortality and utility estimates were obtained from the IMPROVE SCA trial. Additional effectiveness inputs were sourced from the literature. Cost inputs were obtained from the Brazilian Unified Health System and the Ministry of Health. Costs were discounted at 4.7%; quality-adjusted life years (QALYs) were discounted at 1.45%. This study applied a willingness-to-pay (WTP) value of three times Brazil’s gross domestic product (GDP) in 2017, R$105,723 (Brazilian Real). Results: The total discounted lifetime costs for ICD therapy were R$100,920 compared to R$43,866 for no ICD therapy. Total discounted QALYs for ICD therapy and no ICD therapy were 9.85 and 7.15, respectively. The incremental cost effectiveness ratio was R$21,156 per QALY and less than the R$105,723 WTP threshold. Results from sensitivity analyses were consistent with base case results. Conclusions: ICD therapy compared to no ICD therapy is cost-effective in the 1.5PP population in Brazil. (Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0) Background ICDs (ICDs (PP (SCA wellestablished well established globally 15 1 5 1. 1.5PP, 15PP , 5PP (1.5PP) factors nonsustained non sustained tachycardia contractions 25 25% presyncope pre syncope Objective costeffectiveness system Methods payers payer s perspective trial literature 4.7% 47 4 7 qualityadjusted quality adjusted (QALYs 145 45 1.45% willingnesstopay willingness pay (WTP Brazils Brazil GDP (GDP 2017 R105723 R 105 723 R$105,72 Real. Real . Real) R100920 100 920 R$100,92 R43866 43 866 R$43,86 985 9 85 9.8 715 7.15 respectively R21156 21 156 R$21,15 threshold results Conclusions costeffective effective Int Sci 2021 online.ahead onlineahead online .ahead ahead print PP.00 PP00 PP.0 0 PP.0-0 (1.5PP 2 4.7 14 1.45 201 R10572 10 72 R$105,7 R10092 92 R$100,9 R4386 86 R$43,8 98 8 9. 71 7.1 R2115 R$21,1 202 00 PP0 PP. PP.0- 4. 1.4 20 R1057 R$105, R1009 R$100, R438 R$43, 7. R211 R$21, R105 R$105 R100 R$100 R43 R$43 R21 R$21 R10 R$10 R4 R$4 R2 R$2 R1 R$1 R$

Resumen Este trabajo tiene por objetivo identificar los principales instrumentos de medición de estados de salud y las metodologías de valoración de preferencias que se utilizan para calcular los años de vida ajustados por calidad -AVAC-. A partir de una revisión de literatura con una estrategia de búsqueda equilibrada para la identificación de referencias bibliográficas relevantes, se presentan las características técnicas de los sistemas de clasificación en salud, como lo son los conceptos funcionales -sociales, mentales, físicos y sensoriales-, la combinación de atributos, el número de estados de salud diferentes, la duración de la encuesta y su administración. Asimismo, referente a las metodologías de valoración de preferencias, se resumen las particularidades sobre la consistencia con la teoría de los AVAC, la flexibilidad en la descripción de estados de salud, los estados peores que la muerte, entre otros aspectos. Se concluye que no existe un sistema de clasificación de estados de salud o método de valoración de preferencias mejor que otro, por lo que el investigador debe elegir la herramienta que mejor se adapte a la condición bajo análisis y al diseño de estudio en específico. JEL: I10, B41, D60.

Abstract The purpose of this research is to identify the main instruments for measuring health states and the methodologies for evaluating preferences, which are used to calculate quality-adjusted life years -QALYs-. From a literature review with a balanced search strategy to identify relevant bibliographic references, the technical characteristics of health classification systems are presented, such as functional concepts -social, mental, physical and sensory-, the combination of attributes, the number of different health states, the duration of the survey and its administration. Likewise, referring to the methodologies of valuation of preferences, the particularities on the consistency with the QALY theory, the flexibility in the description of health states, states worse than death, among other aspects, are summarized. It is concluded that there is no one better health status classification system or preference assessment method than another, so the researcher must choose the tool that best suits the condition under analysis and the specific study design. JEL: I10, B41, D60.

Abstract Objective In this study we conducted an economic evaluation of a surveillance programme to prevent hip dislocation in children with cerebral palsy. Method We developed a model that compared costs and health outcomes of children with cerebral palsy with and without a surveillance programme. Information from a number of sources was combined into a decision analytical model, primarily based on data from a comparative study with a 20-year follow-up. Effectiveness was measured using Quality-Adjusted Life Years (QALYs). The analysis took the perspective of the Spanish National Health Service. We undertook extensive sensitivity analyses including a probabilistic sensitivity analysis. Results The surveillance programme led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of 12,282€. The results were robust to model assumptions. The probability that the programme was cost-effective was estimated to be over 80% at the threshold of 25.000€/QALY recommended in Spain. Conclusion This study indicates that surveillance programmes to prevent hip dislocation in children with cerebral palsy are likely to be cost-effective.

Resumen Objetivo En este estudio se realiza una evaluación económica de un programa de vigilancia para prevenir la luxación de cadera en niños y niñas con parálisis cerebral. Método Se desarrolló un modelo que comparó los costes y los resultados en salud de niños y niñas con parálisis cerebral incluidas y no incluidas en un programa de vigilancia. Se combinó la información proveniente de diversas fuentes en un modelo analítico de decisión, principalmente basado en datos de un estudio comparativo con 20 años de seguimiento. La efectividad se midió empleando los años de vida ajustados por calidad (AVAC). El análisis tomó la perspectiva del Sistema Nacional de Salud de España. Se realizó un extenso análisis de sensibilidad, incluyendo un análisis de sensibilidad probabilístico. Resultados El programa de vigilancia estuvo asociado a más AVAC y mayores costes sanitarios, con un coste incremental por AVAC ganado estimado en 12.282 €. Los resultados fueron robustos a los supuestos del modelo. La probabilidad de que el programa fuera coste-efectivo se estimó en un valor por encima del 80% para el umbral de 25.000 € por AVAC recomendado en España. Conclusión Este estudio indica que es probable que los programas de vigilancia para prevenir la luxación de cadera en niños y niñas con parálisis cerebral sean coste-efectivos.

Abstract Objective In this study we conducted an economic evaluation of a surveillance programme to prevent hip dislocation in children with cerebral palsy. Method We developed a model that compared costs and health outcomes of children with cerebral palsy with and without a surveillance programme. Information from a number of sources was combined into a decision analytical model, primarily based on data from a comparative study with a 20-year follow-up. Effectiveness was measured using Quality-Adjusted Life Years (QALYs). The analysis took the perspective of the Spanish National Health Service. We undertook extensive sensitivity analyses including a probabilistic sensitivity analysis. Results The surveillance programme led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of 12,282€. The results were robust to model assumptions. The probability that the programme was cost-effective was estimated to be over 80% at the threshold of 25.000€/QALY recommended in Spain. Conclusion This study indicates that surveillance programmes to prevent hip dislocation in children with cerebral palsy are likely to be cost-effective.

Resumen Objetivo En este estudio se realiza una evaluación económica de un programa de vigilancia para prevenir la luxación de cadera en niños y niñas con parálisis cerebral. Método Se desarrolló un modelo que comparó los costes y los resultados en salud de niños y niñas con parálisis cerebral incluidas y no incluidas en un programa de vigilancia. Se combinó la información proveniente de diversas fuentes en un modelo analítico de decisión, principalmente basado en datos de un estudio comparativo con 20 años de seguimiento. La efectividad se midió empleando los años de vida ajustados por calidad (AVAC). El análisis tomó la perspectiva del Sistema Nacional de Salud de España. Se realizó un extenso análisis de sensibilidad, incluyendo un análisis de sensibilidad probabilístico. Resultados El programa de vigilancia estuvo asociado a más AVAC y mayores costes sanitarios, con un coste incremental por AVAC ganado estimado en 12.282 €. Los resultados fueron robustos a los supuestos del modelo. La probabilidad de que el programa fuera coste-efectivo se estimó en un valor por encima del 80% para el umbral de 25.000 € por AVAC recomendado en España. Conclusión Este estudio indica que es probable que los programas de vigilancia para prevenir la luxación de cadera en niños y niñas con parálisis cerebral sean coste-efectivos.

ABSTRACT Objectives: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. Material and method: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. Results: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. Discussion: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management.

RESUMEN Objetivos: Evaluar, en presos con hepatitis C crónica (HCc) pendientes de tratamiento, el coste-efectividad de tratarlos con antivirales de acción directa (AAD) frente a no tratarlos, y analizar el impacto clínico y económico del tratamiento sobre las complicaciones hepáticas y la mortalidad. Material y método: Se desarrolló un modelo de Markov para simular el tratamiento y proyectar la progresión de la enfermedad de una cohorte estimada de 4.408 reclusos con HCc tratados con AAD en dos años (el 50% cada año) frente a ningún tratamiento. En los tratados, se asoció una respuesta viral sostenida del 95%. Las características de los pacientes, las probabilidades de transición, las utilidades y los costes (farmacológicos y estados de salud) se obtuvieron de publicaciones científicas. El modelo estimó costes y resultados en salud, la relación coste-utilidad incremental (RCUI), a partir de los costes totales y años de vida ajustados por calidad (AVAC) y los eventos clínicos evitados. La perspectiva fue la del Sistema Nacional de Salud (SNS) y se aplicó una tasa de descuento anual (el 3%) para costes y resultados en salud. La robustez de los resultados se evaluó mediante un análisis de sensibilidad. Resultados: En la población tratada, el modelo estimó una reducción del 92% de los casos de cirrosis descompensada y del 83% de carcinoma hepatocelular, se evitaron 132 trasplantes hepáticos y disminuyó el 88% la mortalidad hepática. El tratamiento consiguió 5,0/AVAC adicionales (21,2 frente al 16,2), con un coste incremental de 3.473 euros (24.088 € frente a 20.615 €) por paciente y una RCUI de 690 €/AVAC ganado. Discusión: Considerando el umbral de disponibilidad a pagar utilizado en España (22.000-30.000 €/AVAC), el tratamiento con AAD en los presos con HCc es una estrategia altamente coste-efectiva, reduce la transmisión, aumenta la supervivencia y reduce las complicaciones hepáticas, así como los costes asociado a su manejo.

RESUMO Objetivo: Estudar o custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade neovascular. Métodos: Utilizamos um modelo de árvore de decisão para analisar a relação custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade, sob a perspectiva do Sistema Único de Saúde. O ranibizumabe e bevacizumabe foram administrados a pacientes com o mesmo procedimento de tratamento, e a diferença nos custos do tratamernto foi calculada com base no custo dos medicamentos. Os custos diretos foram estimados utilizando as informações fornecidas pelo SUS. A efetividade foi determinada em anos de vida ajustados pela qualidade (QALY) baseados em valores de utilidade em deficiênciavisual. A razãoincremental custo-efetividadefoicalculada comparando os dois tratamentos. O horizonte analítico foi de um ano. Resultados: A análise da árvore de decisão mostrou que a diferença na efetividade do tratamento foi de 0,01 QALY. A razão incremental de custo-efetividade mostrou que o tratamento com ranibizumabe exigiu um custo anual incremental de R$ 2 milhões para gerar um QALY adicional, em comparação ao bevacizumabe. Conclusões: Do ponto de vista do SUS, o bevacizumabe é mais custo-efetivo que o ranibizumabe no tratamento da degeneração macular relacionada à idade neovascular. O seu uso poderia gerar uma grande economia anual para o orçamento em saúde.

ABSTRACT Purpose: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. Methods: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. Results: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. Conclusions: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

ABSTRACT Objective To carry out a cost-utility analysis of the application of the Oncotype genomic test to inform the decision to use or not to use chemotherapy in the Basque Country (Spain). Method The cost-utility study was carried out using a discrete event simulation model representing the natural history of breast cancer. The decision of treatment with chemotherapy based on Oncotype was compared with the standard of treatment based on clinical-pathological criteria. The model included clinical data from Basque hospitals and the literature and was processed by deterministic and probabilistic analysis to calculate the incremental cost-effectiveness ratio (ICER), the cost-effectiveness plane, the acceptability curve and the expected value of perfect information. The study adopted both a health and societal perspective. Results From a health perspective, the deterministic analysis estimated an ICER for Oncotype of 17,453 euros/quality-adjusted life year (QALY), discount included, and 9,613 euros/QALY without the discount. Eighty five percent (85%) of the simulations were below the efficiency threshold for Spain. The parametric variability associated with the Oncotype results was the main uncertainty factor in the decision. Conclusions Oncotype is a cost-effective intervention from a health system perspective since each QALY gained costs less than 25,000 euros. From a societal perspective, it is dominant since it provides greater health and is accompanied by cost savings.

RESUMEN Objetivo Llevar a cabo un análisis de coste-utilidad del uso del test genómico Oncotype en el País Vasco (España) para informar la decisión de uso de quimioterapia. Método El estudio de coste-utilidad se realizó mediante un modelo de simulación de eventos discretos que representó la evolución natural del cáncer de mama. La decisión de tratamiento con quimioterapia basada en Oncotype se comparó con el estándar de tratamiento basado en criterios clínico-patológicos. El modelo incluyó datos clínicos de hospitales vascos y la literatura para calcular la ratio de coste-efectividad incremental (RCEI) mediante análisis determinista y probabilístico, el plano coste-efectividad, la curva de aceptabilidad y el valor esperado de la información perfecta. El estudio adoptó una perspectiva tanto sanitaria como social. Resultados El análisis determinista estimó una RCEI para Oncotype de 17.453 euros/año de vida ajustado por calidad (AVAC) con descuento y 9613 euros euros/AVAC sin descuento, desde la perspectiva sanitaria. El 85% de las simulaciones estuvieron por debajo el umbral de aceptabilidad para España. La variabilidad paramétrica asociada a los resultados de Oncotype fue el mayor factor de incertidumbre de la decisión. Conclusiones Oncotype constituye una intervención coste-efectiva, ya que cada AVAC ganado tiene asociado un coste inferior a 25.000 euros. El test es dominante desde una perspectiva social al lograr mayor salud acompañada de ahorros.

Abstract Objective To carry out a cost-utility analysis of the application of the Oncotype genomic test to inform the decision to use or not to use chemotherapy in the Basque Country (Spain). Method The cost-utility study was carried out using a discrete event simulation model representing the natural history of breast cancer. The decision of treatment with chemotherapy based on Oncotype was compared with the standard of treatment based on clinical-pathological criteria. The model included clinical data from Basque hospitals and the literature and was processed by deterministic and probabilistic analysis to calculate the incremental cost-effectiveness ratio (ICER), the cost-effectiveness plane, the acceptability curve and the expected value of perfect information. The study adopted both a health and societal perspective. Results From a health perspective, the deterministic analysis estimated an ICER for Oncotype of 17,453 euros/quality-adjusted life year (QALY), discount included, and 9,613 euros/QALY without the discount. Eighty five percent (85%) of the simulations were below the efficiency threshold for Spain. The parametric variability associated with the Oncotype results was the main uncertainty factor in the decision. Conclusions Oncotype is a cost-effective intervention from a health system perspective since each QALY gained costs less than 25,000 euros. From a societal perspective, it is dominant since it provides greater health and is accompanied by cost savings.

Resumen Objetivo Llevar a cabo un análisis de coste-utilidad del uso del test genómico Oncotype en el País Vasco (España) para informar la decisión de uso de quimioterapia. Método El estudio de coste-utilidad se realizó mediante un modelo de simulación de eventos discretos que representó la evolución natural del cáncer de mama. La decisión de tratamiento con quimioterapia basada en Oncotype se comparó con el estándar de tratamiento basado en criterios clínico-patológicos. El modelo incluyó datos clínicos de hospitales vascos y la literatura para calcular la ratio de coste-efectividad incremental (RCEI) mediante análisis determinista y probabilístico, el plano coste-efectividad, la curva de aceptabilidad y el valor esperado de la información perfecta. El estudio adoptó una perspectiva tanto sanitaria como social. Resultados El análisis determinista estimó una RCEI para Oncotype de 17.453 euros/año de vida ajustado por calidad (AVAC) con descuento y 9613 euros euros/AVAC sin descuento, desde la perspectiva sanitaria. El 85% de las simulaciones estuvieron por debajo el umbral de aceptabilidad para España. La variabilidad paramétrica asociada a los resultados de Oncotype fue el mayor factor de incertidumbre de la decisión. Conclusiones Oncotype constituye una intervención coste-efectiva, ya que cada AVAC ganado tiene asociado un coste inferior a 25.000 euros. El test es dominante desde una perspectiva social al lograr mayor salud acompañada de ahorros.

RESUMO Objetivo: O câncer de pulmão é um importante problema de saúde pela sua alta incidência e mortalidade. O tratamento da doença metastática melhorou após o conhecimento de vias moleculares tumorais. Contudo, a terapia-alvo está indisponível para muitos pacientes do Sistema Único de Saúde (SUS). Nosso objetivo foi avaliar a relação custo-efetividade de erlotinibe, gefitinibe e afatinibe vs. quimioterapia no tratamento do câncer de pulmão não pequenas células no contexto do SUS. Métodos: Foram desenvolvidos modelos analíticos distintos baseados em dados da literatura. Os desfechos foram apresentados em quality-adjusted life years (QALY, anos de vida ajustados pela qualidade) e incremental cost-effectiveness ratio (ICER, relação custo-efetividade incremental). Todos os custos relacionados ao tratamento e terapias de suporte foram incluídos nos modelos. Resultados: No primeiro modelo, dados de estudos retrospectivos apontaram 2,01 anos de vida salvos e uma média de ganho de QALY de 1,169. O ICER variou entre R$ 48.451,29 (gefitinibe) e R$ 85.559,22 (erlotinibe). No segundo modelo, dados de uma meta-análise evidenciaram −0,01 ano de vida salvos e uma média de ganho de QALY de 0,178. O ICER foi de R$ 27.028,30 (gefitinibe) a R$ 75.203,26 (erlotinibe). Conclusões: Não existe um modelo analítico ideal para o SUS. Contudo, diferentes cenários disponíveis na literatura mostram que a terapia-alvo com o uso dessas drogas é custo-efetiva. A adoção de descontos nos preços dos medicamentos melhorará a relação custo-efetividade do tratamento.

ABSTRACT Objective: Lung cancer is an important health problem due to its high incidence and mortality. The treatment of metastatic disease improved after the molecular pathways of cancer came to be known. However, targeted therapy is unavailable to many patients treated within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). Our objective was to assess the cost-effectiveness of erlotinib, gefitinib, and afatinib versus that of chemotherapy for the treatment of non-small cell lung cancer in the context of the SUS. Methods: Different analytical models were developed based on data in the literature. The outcomes were presented in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) per QALY gained. All costs related to treatment and supportive therapies were included in the models. Results: In one model, data from retrospective studies showed 2.01 life-years saved and a mean QALY gain of 1.169. The ICER per QALY gained ranged from R$48,451.29 (for gefitinib) to R$85,559.22 (for erlotinib). In another model, data from a meta-analysis showed −0.01 life-years saved and a mean QALY gain of 0.178. The ICER per QALY gained ranged from R$27,028.30 (for gefitinib) to R$75,203.26 (for erlotinib). Conclusions: There is no ideal analytical model for the SUS. However, targeted therapy with EGFR-tyrosine kinase inhibitors has been shown to be cost-effective in various scenarios. The adoption of drug price discounts will improve the cost-effectiveness of treatment.

Resumo Objetivo: Avaliar a relação custo-utilidade do tratamento inicial com laser ou medicamentos do glaucoma primário de ângulo aberto (GPAA) no Brasil, considerando de um lado os custos totais e de outro lado o impacto na qualidade de vida dos pacientes. Métodos: O estudo foi realizado com base em um modelo de Markov, onde uma coorte teórica de portadores de GPAA em estágio inicial foi gerada. Os parâmetros usados no modelo foram obtidos na literatura e incluíram: custos médicos diretos (consultas, exames, tratamento); custos não médicos diretos (gasto com hospedagem, transporte, alimentação, acompanhante); custos indiretos (relacionados à incapacidade para o trabalho); valores de utilidade (qualidade de vida medida em QALY - quality-adjusted life year); e probabilidade de transição entre os estágios de saúde. Três estratégias de tratamento foram testadas no modelo: (1) sem tratamento; (2) tratamento inicial com colírios; (3) tratamento inicial com trabeculoplastia a laser. A medida de desfecho foi a razão de custo-utilidade incremental (RCUI). A robustez do modelo foi testada através de análise de sensibilidade. Resultados: As estratégias (2) e (3) de tratamento inicial do GPAA geraram ganhos em qualidade de vida em relação à (1) no Brasil. Iniciar o tratamento com laser gerou ganho médio de 1 QALY, enquanto que com medicamentos propiciou um ganho de 2 QALYs em média. Dentre as três estratégias testadas, a estratégia (2) foi a custo-efetiva e foi dominante sobre as demais, pois foi ao mesmo tempo a mais barata e a mais efetiva. Conclusão: Tanto a trabeculoplastia a laser quanto os medicamentos como tratamentos primários do GPAA inicial geraram ganhos significativos de qualidade de vida. A estratégia de se iniciar o tratamento com medicações foi custo-efetiva, quando se considera os custos totais. A alternativa de tratamento inicial através de trabeculoplastia a laser não foi custo-efetiva.

Abstract Objective: To evaluate the cost-utility relation of the initial treatment with laser or primary open-angle glaucoma medications (PLA) in Brazil, considering on the one hand the total costs and on the other side the impact on patients’ quality of life. Methods: The study was performed based on a Markov model, where a theoretical cohort of early-stage GPAA carriers was generated. The parameters used in the model were obtained in the literature and included: direct medical costs (consultations, examinations, treatment); direct non-medical costs (accommodation, transportation, meals, companions); indirect costs (related to incapacity for work); utility values (quality of life measured in QALY - quality-adjusted life year); and probability of transition between stages of health. Three treatment strategies were tested in the model: (1) without treatment; (2) initial treatment with eye drops; (3) initial treatment with laser trabeculoplasty. The measure of outcome was the incremental cost-utility ratio (RCUI). The robustness of the model was tested through sensitivity analysis. Results: The strategies (2) and (3) of the initial treatment of POAG generated gains in quality of life in relation to (1) in Brazil. Initiating the laser treatment generated an average gain of 1 QALY, whereas with medication it gave a gain of 2 QALYs on average. Among the three strategies tested, strategy (2) was cost-effective and was dominant over the other strategies, since it was at the same time the cheapest and the most effective strategy. Conclusion: Both laser trabeculoplasty and medications as primary treatments of early-stage POAG have generated significant gains in quality of life. The strategy of starting treatment with medications was cost-effective, whereas laser trabeculoplasty strategy was not cost-effective, when non-medical costs (direct and indirect) are included.

Objective: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer’s disease (AD) from the perspective of the Brazilian Unified Health System. Method: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. Results: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. Conclusions: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Resumen Introducción. La reconstrucción mamaria inmediata o diferida hace parte del tratamiento del cáncer de mama. Cada país y sistema de salud costea y evalúa estos procedimientos de forma diferente. Es importante determinar cuál estrategia resulta de mayor costo-utilidad en Colombia. Objetivo. Evaluar la costo-utilidad del tratamiento del cáncer de mama con reconstrucción inmediata, comparada con la reconstrucción diferida. Materiales y métodos. Se utilizó un modelo de árbol de decisiones con un plazo previsto de un año desde la perspectiva del tercer pagador. Los datos de costos se tomaron del manual tarifario del Instituto de Seguros Sociales de 2001 más un ajuste del 30 % según la metodología del Instituto de Evaluación Tecnológica en Salud y el modelo de facturación del Centro Javeriano de Oncología del Hospital Universitario San Ignacio. Las probabilidades de transición y las utilidades se obtuvieron de médicos especialistas, de las pacientes y de la literatura médica. Se hicieron los análisis univariado y probabilístico de sensibilidad. Resultados. Los costos esperados per cápita fueron de COP$ 26’710.605 (USD$ 11.165) para la reconstrucción inmediata y de COP$ 6’459.557 (USD$ 11.060) para la diferida. La reconstrucción inmediata generó un costo incremental de COP$ 251.049 (USD$ 105), así como 0,75 años de vida ajustados por calidad (AVAC), en tanto que la diferida generó 0,63 AVAC, con una relación de costoutilidad incremental de COP $2’154.675 por AVAC (USD$ 901). Conclusiones. El costo por AVAC no superó el umbral de aceptabilidad del producto interno bruto (PIB) per cápita. Los costos durante el primer año resultaron similares y ambas técnicas son favorables para el sistema de salud colombiano, pero la utilidad de la reconstrucción inmediata reportada por los pacientes y en la literatura médica, es mayor.

Abstract Introduction. Breast reconstruction, either immediate or delayed, is part of the treatment of breast cancer. Each country and health system pays for and evaluates these procedures in different ways. Thus, it is important to determine which strategy is most cost-effective in Colombia. Objective: To evaluate the cost-utility of breast cancer treatment with immediate reconstruction compared with delayed reconstruction. Materials and methods: We used a decision tree model and a one-year time horizon from the perspective of the third-party payer; the cost data were taken from the Colombian Instituto de Seguros Sociales 2001 rate manual plus a 30% adjustment according to the methodology of the Instituto de Evaluación Tecnológica en Salud, IETS, and the billing model of the Centro Javeriano de Oncología at the Hospital Universitario San Ignacio. The transition probabilities and profits were obtained from medical specialists, patients, and the medical literature. We also conducted univariate and probabilistic sensitivity analyses. Results: The expected costs per capita were COP$ 26,710,605 (USD$ 11,165) for the immediate reconstruction and COP$ 26,459,557 (USD$ 11,060) for the deferred reconstruction. Immediate reconstruction generated an incremental cost of COP$ 251,049 (USD$ 105) and 0.75 quality-adjusted life years (QALY), while deferred reconstruction generated 0.63 QALYs, with an incremental cost-utility ratio of COP$ 2,154,675 per QALY (USD$ 901). Conclusions: The cost per QALY did not exceed the acceptability threshold of the Gross Domestic Product (GDP) per capita. The costs for the first year were similar. Both techniques are favorable for the Colombian health system, but the utility reported by patients and the literature is greater with the immediate reconstruction.