A cost-effectiveness analysis of a novel algorithm to sequentially diagnose leprosy based on manufactured tests under the SUS perspective.

Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

Cost-Utility Model of Nirmatrelvir/Ritonavir in Brazil: Analysis of a Vaccinated Population.

OBJECTIVES: The aim of this study is to conduct a cost-utility analysis of the use of the antiviral nirmatrelvir/ritonavir, applied to a vaccinated Brazilian population against COVID-19, from the perspective of the Brazilian Public Health System (SUS). METHODS: A microsimulation model was created with individual-level data and daily cycles, with a 1-year time horizon, to compare the current scenario of standard care with a scenario in which nirmatrelvir/ritonavir is offered to the population. Adults of any age group that received ≥2 doses of the COVID-19 vaccine formed the investigated population. Direct medical costs of the outpatients and inpatients admitted to the ward or intensive care unit were included. The effectiveness of the model was measured in quality-adjusted life-years (QALYs). RESULTS: In all simulations, the use of nirmatrelvir/ritonavir resulted in incremental costs per patient of US dollar (USD)245.86 and incremental effectiveness of 0.009 QALY, over a year. The incremental cost-utility ratio was USD27 220.70/QALY. The relative risk of the vaccinated population was the factor that affected the outcome most, according to the univariate sensitivity analysis. The probabilistic sensitivity analysis resulted in 100% of the simulations being more costly and effective, but that only 4% of them were below the established cost-effectiveness threshold of USD24 000.00/QALY. In the scenario considering only the population over 60 years old and immunosuppressed (of any age), the incremental cost-utility ratio was USD7589.37/QALY. CONCLUSIONS: The use of nirmatrelvir/ritonavir in the treatment of COVID-19 in a vaccinated population was cost-effective only for immunosuppressed individuals and people over 60 years of age.

A cost-effectiveness analysis of a novel algorithm to sequentially diagnose leprosy based on manufactured tests under the SUS perspective / Análise de custo-efetividade de um novo algoritmo para exame sequencial de hanseníase baseado em testes fabricados sob a perspectiva do SUS / Análisis de costo-efectividad de un nuevo algoritmo para el examen secuencial de lepra basado en pruebas fabricadas bajo la perspectiva del SUS

Abstract: Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

Resumo: O Brasil tem o segundo maior número de casos de hanseníase (doença com carga significativa) do mundo. Apesar dos esforços globais e locais para eliminar esse problema de saúde pública, o diagnóstico inadequado ou tardio contribui para perpetuar sua transmissão, especialmente entre contatos intradomiciliares. Exames como o teste rápido de anticorpos IgM (RT) e a reação em cadeia da polimerase em tempo real (RT-PCR) foram desenvolvidos para superar as barreiras do diagnóstico precoce da hanseníase. Este estudo teve como objetivo analisar a relação custo-efetividade de um novo algoritmo de diagnóstico recomendado pelo governo brasileiro para diagnosticar a hanseníase em contatos domiciliares de casos confirmados de hanseníase, que inclui os testes RT e RT-PCR. Foi construído um modelo de árvore de decisão e adotada a perspectiva do Sistema Único de Saúde (SUS) considerando o período de um ano. Foram incluídos apenas os custos médicos diretos relacionados aos exames diagnósticos. A efetividade foi medida considerando o número de casos evitados de hanseníase. Diferentes cenários foram analisados. O uso sequencial de RT, baciloscopia e RT-PCR, conforme recomendado pelo Ministério da Saúde, foi comparado a um caso base (baciloscopia isolada), obtendo-se uma razão de custo-efetividade incremental de USD 616,46 por caso evitado de hanseníase. A análise de sensibilidade univariada mostrou que a prevalência de hanseníase entre contatos intradomiciliares foi a variável que mais influenciou o modelo. Este é o primeiro modelo econômico a analisar um algoritmo diagnóstico da hanseníase. Os resultados poderão auxiliar os gestores na definição de políticas e estratégias para a erradicação da hanseníase no Brasil.

Resumen: Brasil tiene el segundo mayor número de casos de lepra (enfermedad con carga significativa) del mundo. A pesar de los esfuerzos globales y locales para eliminar ese problema de salud pública, el diagnóstico inadecuado o tardío contribuye a perpetuar su transmisión, sobre todo entre contactos intradomiciliarios. Los exámenes como la prueba rápida de anticuerpos IgM (RT) y la reacción en cadena de la polimerasa en tiempo real (RT-PCR) se desarrollaron para superar las barreras del diagnóstico precoz de la lepra. El objetivo de este estudio fue analizar la relación de costo-efectividad de un nuevo algoritmo de diagnóstico recomendado por el gobierno brasileño para diagnosticar la lepra en contactos domiciliarios de casos confirmados de lepra, que incluye las pruebas RT y RT-PCR. Se construyó un modelo de árbol de decisión y se adoptó la perspectiva del Sistema Único de Salud (SUS) teniendo en cuenta el periodo de un año. Solo se incluyeron los costos médicos directos relacionados con los exámenes diagnósticos. Se midió la efectividad teniendo en cuenta el número de casos de lepra evitados. Se analizaron distintos escenarios. Se comparó el uso secuencial de RT, baciloscopia y RT-PCR, conforme el Ministerio de Salud recomienda, con un caso base (baciloscopia aislada), y se obtuvo un cociente de costo-efectividad incremental de USD 616,46 por cada caso de lepra evitado. El análisis de sensibilidad univariante mostró que la prevalencia de lepra entre contactos intradomiciliarios fue la variable que más influyó el modelo. Este es el primer modelo económico que analiza un algoritmo diagnóstico de lepra. Los resultados podrán ayudar los gestores a definir políticas y estrategias para erradicar la lepra en Brasil.

Cost-effectiveness analysis of extended thromboprophylaxis with rivaroxaban versus no prophylaxis in high-risk patients after hospitalisation for COVID-19: an economic modelling study.

Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy. Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis. Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY. Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option. Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil.

Cost-effectiveness of ribociclib for premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer: a Brazilian public health care system perspective.

Introduction: The MONALEESA-7 trial compared ribociclib plus endocrine therapy (ET) with placebo as first-line treatment of advanced luminal/HER2-negative breast cancer (ABC) in premenopausal and perimenopausal women (age <50 years) and showed significant benefits to progression-free survival and overall survival. This study aimed to compare the cost-effectiveness of ribociclib + ET versus ET alone in patients with ABC from the perspective of the Brazilian public national health system. Methods: We calculated the incremental cost-effectiveness ratio (ICER) using a Markov model with progression-free survival, post-progression survival, and death states. We expressed ICER as incremental costs per progression-free life-year (PFLY) and quality-adjusted life-year (QALY) gained in a 10-year time horizon. We used parametric survival distributions fit to MONALEESA-7 data to generate survival distributions for progression-free and post-progression survival. The largest British preference study in breast cancer served as the basis to estimate health-state utilities. We estimated direct costs (ABC treatment, follow-up, monitoring, and adverse events) using Brazilian-specific values from public sources. An expert consensus panel determined the resource patterns required. We applied annual discounts of 5% to costs and QALYs. Results: Ribociclib + ET resulted in an incremental gain of 1.03 PFLYs and 0.80 QALYs at a cost of $37,319.31. The ICER of ribociclib + ET versus ET was $36,379.41 per PFLY gained and $46,590.79 per QALY gained. In deterministic sensitivity analysis, results were primarily affected by the annual discount rate, followed by the cost of ribociclib. In probabilistic sensitivity analysis, simulations agreed with the base-case. Conclusion: Ribociclib increased PFLYs and QALYs in patients with HR+/HER2- ABC when added to ET. Because Brazil does not have a formally defined cost-effectiveness threshold, other domains need to be considered for incorporation decisions, such as disease burden and humanistic impact on this young, economically active population. These findings may be useful in discussions for incorporation of ribociclib into the Brazilian public health system.

Cost-Utility of the CDK 4/6 Inhibitors for Postmenopausal Women With Luminal Advanced Breast Cancer in Brazil.

OBJECTIVES: Several trials have demonstrated the benefit of the CDK 4/6 inhibitors for postmenopausal women with luminal advanced breast cancer. This research aims to compare the cost-utility of the CDK 4/6 inhibitors in patients with no history of resistance to endocrine therapy. METHODS: A Markov model was constructed to estimate the incremental cost per quality-adjusted life-years (QALYs) of treatments from the Brazilian public health system perspective over a lifetime horizon (30 years) with 5% annual discount rate for both benefits and costs. Efficacy parameters were extracted from the pivotal studies. Costs were based on open data from the Brazilian Ministry of Health. The utilities were calculated according to the overall population preferences from a British study. Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results. RESULTS: The most cost-effective drug was ribociclib (US$50 748/QALY), followed by abemaciclib (US$64 052/QALY) and palbociclib (US$65 289/QALY). The univariate analysis showed that the incremental cost-utility ratio (ICUR) was mainly sensitive to the overall survival hazard ratio. The one thousand-probabilistic simulation showed that all ICUR values were above classical thresholds such as 1 to 3 gross domestic product (GDP) per capita per QALY. CONCLUSIONS: Even though there is no established willingness to pay threshold in Brazil, the estimated ICUR for CDK 4/6 inhibitors is >6 times the Brazilian GDP per capita (GDP per capita = US$5694.73), which might be a barrier to their inclusion in the Brazilian public health system.

Cost Utility of Prasugrel in Postangioplasty Diabetic Patients.

OBJECTIVES: To prevent thrombotic events after angioplasty, current guidelines recommend dual antiplatelet therapy with aspirin and thienopyridine. Clopidogrel is the only thienopyridine currently available in the Brazilian National Health System. The purpose of this study was to determine the cost-effectiveness of prasugrel, an alternative thienopyridine, compared with clopidogrel in patients with acute coronary syndrome and diabetes mellitus who underwent angioplasty. METHODS: A state-transition Markov model was created to simulate the progression of diabetic patients after angioplasty. The model had a lifetime horizon and discounted outcomes at a 5% annual rate. The risks of myocardial infarction and death were calculated using data from the diabetes subgroup, and the risks of bleeding were calculated using data from the overall group from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38 trial. Direct costs were estimated using official Brazilian open data. Quality of life values were obtained through literature search. Univariate and multivariate sensitivity analyses were performed. RESULTS: Prasugrel was associated with more quality-adjusted life-years (QALYs) (5.03 vs 4.94) and higher costs (US$975.11 vs US$575.97), resulting in an incremental cost-utility ratio (ICUR) of US$4303.86/QALY. In one-way sensitivity analysis, the costs of prasugrel had the greatest impact on ICUR, followed by the initial age entering the cohort. In the probabilistic sensitivity analysis, all ICUR values simulations were less than one Brazilian gross domestic product per capita/QALY (US $5802.86). CONCLUSIONS: Given the appealing economic profile, the clinical debate between reducing the risk of myocardial infarction and increasing the risk of bleeding may overcome economic concerns in the Brazilian National Health System.

Statements about hemophilia A in Brazil: an expert Delphi panel / Consensos em hemofilia A no Brasil: painel Delphi de especialistas

Objective: Understanding unmet needs related to hemophilia A management in Brazil is critical for supporting decision-making. Methods: A modified Delphi consensus panel was conducted. Hematologists with extensive experience treating hemophilia in the Brazilian Public Health System were invited to answer questions regarding indicators of severe hemophilia prophylaxis effectiveness, emicizumab treatment indications, and bypassing agents used to reduce bleeding in patients with inhibitors, immune tolerance induction (ITI) use, and adherence. The consensus was defined as ≥75% of votes in Round 1 or using a 5-point Likert-type scale (1 = strongly disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = strongly agree) in Round 2, which included questions not reaching minimum cut-off in the first step. Results: Nine expert panelists with extensive experience in the Brazilian Public Health System participated. The panel reached an agreement on recommendations about prophylaxis, bleeding treatment patterns, and bleeding sites. From patients' perspectives, venous access and infusion frequency were the most significant barriers to improving patient treatment. According to most experts, emicizumab will not replace ITI or long-term factor VIII therapy. Still, emicizumab was thought to be a good therapeutic option for patients with difficult venous access, patients requiring central venous access, in the presence of inhibitors, or patients experiencing infusion-related pain. Conclusion: The information gleaned from this study may be helpful to both decision-makers and those in charge of developing healthcare economic models for the treatment of hemophilia A in Brazil.

Objetivo: É fundamental entender as necessidades não atendidas relacionadas ao manejo da hemofilia A no Brasil. Métodos: Foi conduzido um painel Delphi modificado. Foram convidados hematologistas com vasta experiência no tratamento de hemofilia no SUS para responder a perguntas sobre indicadores de eficácia da profilaxia, indicações de tratamento com emicizumabe, uso de agentes de bypass, uso de indução de tolerância imunológica (ITI) e adesão. O consenso foi definido como ≥75% dos votos na rodada 1 ou usando uma escala do tipo Likert de 5 pontos (1 = discordo totalmente, 2 = discordo, 3 = não concordo nem discordo, 4 = concordo e 5 = concordo totalmente) na segunda rodada, que incluiu questões que não atingiram o corte mínimo na primeira etapa. Resultados: Nove especialistas participaram e houve consenso sobre recomendações para profilaxia, padrões de tratamento de sangramento e locais de sangramento. O acesso venoso e a frequência da infusão foram identificados como as barreiras mais significativas para melhorar o tratamento do paciente. De acordo com a maioria, emicizumabe não substituirá a ITI ou tratamento com fator VIII de longo prazo. Emicizumabe foi considerado uma boa opção terapêutica para

Cost Utility of Vaccination Against COVID-19 in Brazil.

OBJECTIVES: The objective of this study was to evaluate the cost-utility of the Oxford, CoronaVac, and Janssen COVID-19 vaccines from the perspective of the Brazilian public health system. METHODS: A total of 3 microsimulation models were constructed with individual data to evaluate the 3 vaccines. The simulation contains 7 transition states that are related to the natural history of the disease. The model with a daily cycle has a time horizon of 1 year and uses data from 289 days of the pandemic. The analysis was conducted from the perspective of the Brazilian public health system considering direct medical costs. For the model inputs, outpatient and hospital databases were used with information on treated patients stratified by age. Information on mortality was also stratified based on patients' age in the mortality database (SIM). The efficacy of vaccines to reduce the likelihood of patients becoming ill was evaluated independently for each vaccine. Information on the quality of life of patients in outpatient or hospital treatment and the sequelae resulting from the disease were extracted from the literature. The main outcome of the analysis was quality-adjusted life-years (QALYs). RESULTS: The vaccines showed incremental cost-utility ratios ranging from R$-23 161.3/QALY (Oxford) to R$17 757.85/QALY (CoronaVac). The older the population, the lower was the incremental cost-utility ratio. Given a willingness-to-pay threshold of R$17 586/QALY, all the vaccines were considered cost-effective in the probabilistic sensitivity analysis. CONCLUSIONS: The results of the analysis by age group can help in the preparation of a vaccination prioritization plan.

Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável / Cost-Effectiveness Analysis of CCTA in SUS, as Compared to Other Non-Invasive Imaging Modalities in Suspected Obstructive CAD

Resumo Fundamento Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. Objetivos Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. Métodos Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. Resultados Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. Conclusão Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.

Abstract Background The Brazilian public health system does not include computed tomography angiography (CTA). Objective Rank, according to the Brazilian public health system, the cost-effectiveness of different strategies for the diagnosis of coronary artery disease (CAD), combining exercise tests (ET), myocardial scintigraphy (MS), stress echocardiography (SE), and CTA in a hypothetical intermediate pre-test probability cohort of patients. Methods This study implemented a cost-effectiveness analysis through a decision tree. The incremental cost-effectiveness ratio (ICER) and net benefit were analyzed by adopting multiple thresholds of willingness to pay, from 0.05 to 1 GDP per capita per correct diagnosis. In sequential tests, a second confirmatory test was performed only when the first was positive. Results After excluding dominated or extended dominance diagnostic strategies, the efficiency frontier consisted of three strategies: ET, ET followed by SE, and SE followed by CTA, the last being the most cost-effective strategy. Through the net benefit, the ranking of the most cost-effective strategies varied according to willingness to pay. Conclusions Using current concepts of health technology assessment, this study provides a ranking for decision-making concerning which diagnostic strategy to use in a population with an intermediate pre-test risk for CAD. With a feasible cost estimate adopted for CTA, the impact of including this to the list of the diagnostic arsenal would represent a cost-effective strategy in most of the evaluated scenarios with broad variations in the willingness to pay.

Cost-Effectiveness Analysis of CCTA in SUS, as Compared to Other Non-Invasive Imaging Modalities in Suspected Obstructive CAD. / Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável.

BACKGROUND: The Brazilian public health system does not include computed tomography angiography (CTA). OBJECTIVE: Rank, according to the Brazilian public health system, the cost-effectiveness of different strategies for the diagnosis of coronary artery disease (CAD), combining exercise tests (ET), myocardial scintigraphy (MS), stress echocardiography (SE), and CTA in a hypothetical intermediate pre-test probability cohort of patients. METHODS: This study implemented a cost-effectiveness analysis through a decision tree. The incremental cost-effectiveness ratio (ICER) and net benefit were analyzed by adopting multiple thresholds of willingness to pay, from 0.05 to 1 GDP per capita per correct diagnosis. In sequential tests, a second confirmatory test was performed only when the first was positive. RESULTS: After excluding dominated or extended dominance diagnostic strategies, the efficiency frontier consisted of three strategies: ET, ET followed by SE, and SE followed by CTA, the last being the most cost-effective strategy. Through the net benefit, the ranking of the most cost-effective strategies varied according to willingness to pay. CONCLUSIONS: Using current concepts of health technology assessment, this study provides a ranking for decision-making concerning which diagnostic strategy to use in a population with an intermediate pre-test risk for CAD. With a feasible cost estimate adopted for CTA, the impact of including this to the list of the diagnostic arsenal would represent a cost-effective strategy in most of the evaluated scenarios with broad variations in the willingness to pay.

FUNDAMENTO: Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. OBJETIVOS: Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. MÉTODOS: Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. RESULTADOS: Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. CONCLUSÃO: Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.

Impacto econômico da adoção de denosumabe em pacientes com metástases ósseas ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro / Economic impact of denosumab adoption in cancer patients with bone metastases or multiple myeloma from the Brazilian private healthcare system's perspective

Objetivo: Estimar o custo por evento relacionado ao esqueleto (ERE) e o impacto econômico anual da adoção de denosumabe em pacientes com metástases ósseas secundárias ao câncer de mama, próstata e outros tumores sólidos ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro. Métodos: Um modelo econômico foi desenvolvido para comparar os custos relacionados com denosumabe versus ácido zoledrônico na prevenção de EREs. O modelo incluiu os seguintes custos: medicamento, administração, monitoramento e manejo de ERE. O custo anual foi apresentado em reais (BRL) para 100 pacientes. Os custos do manejo de ERE [fratura vertebral (FV), fratura não vertebral (FNV), radiação óssea (RO), cirurgia óssea (CO) e compressão da medula espinhal (CME)] foram estimados a partir dos recursos e procedimentos coletados da revisão de literatura, bases de dados e painel Delphi. Dados coletados dos estudos clínicos randomizados relacionados com cada tipo de tumor na análise e de um estudo prospectivo observacional foram utilizados para estimar a eficácia clínica de denosumabe versus ácido zoledrônico. Resultados: O custo por cada tipo de ERE variou de BRL 27.246 a BRL 28.035 para FV, BRL 18.023 a BRL 18.811 para FNV, BRL 42.750 a BRL 43.538 para RO, BRL 18.023 a BRL 18.811 para CO e BRL 12.472 a BRL 13.260 para CME. A introdução de denosumabe foi estimada em economia anual por 100 pacientes de até BRL 1.072.043,14 para câncer de mama, BRL 1.212.822,79 para outros tumores sólidos, BRL 1.929.660,67 para câncer de próstata e BRL 77.965,07 para mieloma múltiplo. Conclusão: Esta análise sugere que EREs adicionam custos substanciais no manejo de pacientes com metástases ósseas. Dessa forma, o uso de denosumabe pode prevenir e retardar EREs em pacientes com câncer e pode possivelmente levar à redução do impacto econômico associado aos EREs sob a perspectiva dos pagadores de saúde privada brasileira.

Objective: To estimate the cost per SRE and annual economic impact of denosumab adoption in patients with bone metastases (BM) secondary to breast cancer, prostate cancer, other solid tumors or multiple myeloma from the Brazilian private healthcare system's perspective. Methods: An economic model was developed to compare the cost outcomes associated with denosumab instead of zoledronic acid for SRE prevention. The model included the following costs: drug, administration, monitoring and SRE management. Annual costs per 100 patients were reported in 2019 Brazilian currency (BRL). The SRE management costs (vertebral fracture (VF), non-vertebral fracture (NVF), radiation to bone (RB), surgery to bone (SB) and spinal cord compression (SCC)) were estimated from the resources and procedures collected from literature review, official database, and a Delphi panel. Data collected from randomized clinical trials related to each tumor type in the analysis and from a prospective observational study was used to estimate the clinical efficacy of denosumab vs zoledronic acid. Results: The cost per each type of SREs across all tumors ranged BRL 27,246 ­ BRL 28,035 for VF, BRL 18,023 ­ BRL 18,811 for NVF, BRL 42,750 ­ BRL 43,538 for RB, BRL 18,023 ­ BRL 18,811 for SB and BRL 12,472 ­ BRL 13,260 for SCC. The introduction of denosumab was estimated to result in annual savings per 100 patients of up to BRL 1,072,043.14 for breast cancer, BRL 1,212,822.79 for other solid tumors, BRL 1,929,660.67 for prostate cancer and BRL 77,965.07 for multiple myeloma. Conclusion: This analysis suggests that SREs add substantial costs to the management of patients with bone metastases. In this way, the use of denosumab would prevent and delay SREs in cancer patients and might possibly lead to reduce the economic burden associated with SREs, borne by Brazilian private healthcare payers.

The Assessment for Disinvestment of Intramuscular Interferon Beta for Relapsing-Remitting Multiple Sclerosis in Brazil.

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-ß-1a-IM) was inferior to the other beta interferons (IFN-ßs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-ß-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-ß-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-ß-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-ß-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-ß-1a-IM was inferior to the other IFN-ßs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-ß-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-ß from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.

Health-related quality of life in elderly: a review of the EQ-5D use / Qualidade de vida relacionada à saúde em idosos: uma revisão do uso do EQ-5D

Objective: To systematically identify and review studies that used EQ-5D to assess health-related quality of life (QoL) in elderly. Methods: Relevant literature was searched in MEDLINE and Lilacs databases and the EuroQol Plenary Meetings Proceedings (June/2003 to June/2013). The inclusion criteria were subjects aged 60 years or more and the use of the EQ-5D questionnaire. Two independent reviewers screened title, abstract, full text and performed data extraction. The country where the study had been conducted, demographic characteristics of the population, objectives, common criteria used by the studies to the exclusion of patients/participants and presentation of the data were the variables analyzed. Results: A total of 90 studies were included with 34,449 subjects, the mean age was 75.6 ± 4.3 years. The majority of the studies were from Europe (66.7%). Studies in Africa and South America were not identified. The main diseases investigated were orthopedic (20.0%) and cardiovascular diseases (15.5%). The study's results were most frequently based on personal interviews (41.1%) involving directly the elderly (92.2%). The most common exclusion criteria were health conditions that could result in bias or confounding on the study protocol (61.1%) and low cognitive level (50.0%). The EQ-5D results were presented in different ways: means (82.2%) or medians (5.6%) associated with measures of dispersion as standard deviation (61.1%) and confidence interval (22.2%), or according to the answers in the descriptive system (22.2%). Conclusions: The lack of standardization in the exhibition of the results limits a direct comparison among different interventions.

Objetivo: Identificar sistematicamente e revisar os estudos que utilizaram o EQ-5D para avaliar a qualidade de vida relacionada à saúde em idosos. Métodos: Foram realizadas buscas nas bases MEDLINE e Lilacs e nos arquivos do encontro anual do grupo EuroQol (Junho/2003 a Junho/2013). Os critérios de inclusão dos estudos foram: população com idade ≥ 60 anos e uso do questionário EQ-5D. Dois revisores independentes avaliaram os títulos, depois os resumos e o texto completo e extraíram os dados. As variáveis estudadas foram: país de origem do estudo, características demográficas da amostra, objetivos do estudo, critérios para a exclusão dos pacientes e forma de apresentação dos resultados. Resultados: Foram incluídos 90 estudos, totalizando 34.449 indivíduos, cuja média de idade foi de 75,6 ± 4,3 anos. A maioria dos estudos foi conduzida na Europa (66,7%). Não foram identificados estudos na África ou na América do Sul. As principais doenças investigadas foram ortopédicas (20,0%) e cardiovasculares (15,5%). Os resultados dos estudos basearam-se em entrevistas presenciais (41,1%) realizadas com o próprio idoso (92,2%). Os critérios de exclusão mais comumente utilizados foram condições de saúde que poderiam inserir viés ou confundimento durante o estudo (61,1%) e baixo nível cognitivo do paciente (50,0%). Os resultados do EQ-5D foram apresentados de diferentes maneiras: médias (82,2%) ou medianas (5,6%) associadas com medidas de dispersão, como desvio-padrão (61,1%) e intervalo de confiança (22,2%), ou distribuição das respostas no sistema descritivo (22,2%). Conclusões: A ausência de padronização na apresentação dos resultados limita a comparação direta entre diferentes intervenções.

Parecer técnico científico e análise de custo-efetividade Mitraclip para insufciciencia mitral / Scientific technical advice and cost-effectiveness analysis mitraclip for mitral insufficiency

INTRODUÇÃO: A insuficiência mitral (IM) é caracterizada pela regurgitação sanguínea para o átrio esquerdo durante a sístole ventricular. Pode ser decorrente de anormalidades em diferentes locais do aparato valvar, tais como folhetos, ânulo, cordas tendíneas e músculos papilares. Etiologicamente, a insuficiência mitral é classificada em primária ou degenerativa quando existem anormalidades estruturais da valva e como funcional ou secundária quando a regurgitação não ocorre por problemas na valva, mas como resultado de outros problemas. Dentre as causas primárias, destacam-se a febre reumática, o prolapso valvar mitral, a endocardite infecciosa, traumas e as deformidades congênitas. As etiologias secundárias estão relacionadas à isquemia miocárdica, cardiomiopatia hipertrófica e dilatação ventricular esquerda. A IM secundária tem pior prognóstico por associar-se a outras doenças. TECNOLOGIA: O dispositivo percutâneo MitraClip® (Abbott Vascular, Menlo Park, CA) surgiu como uma possível alternativa à cirurgia convencional de plastia ou troca valvar mitral. Publicado no diário oficial em 24 de março de 2014, o dispositivo foi aprovado para utilização no Brasil pela ANVISA sob o número 25351.099555/2013-99. Nome comercial: clip delivery system ­ MitraClip system. PERGUNTA CLÍNICA: O uso do MitraClip® deve ser considerado em dois grupos distintos: 1. substituto da cirurgia aberta; 2. opção para pacientes cujo alto risco cirúrgico contraindique a cirurgia aberta. Abordaremos as evidências de acordo com as perguntas: 1. O uso do MitraClip® é eficaz, seguro e custo-efetivo em pacientes com insuficiência mitral e indicação de cirurgia de correção mitral quando comparado à cirurgia? 2. O uso do MitraClip® é eficaz, seguro e custo-efetivo em pacientes com insuficiência mitral grave e alto risco cirúrgico, considerados inoperáveis, quando comparado ao tratamento clínico padrão? ANÁLISE DA EVIDÊNCIA: Embora muitas intervenções percutâneas estejam em desenvolvimento, apenas duas encontram-se atualmente disponíveis no mercado internacional; MitraClip® e Carillon®. A MitraClip® possui uma base de evidências mais desenvolvida, embora ainda limitada, com apenas 1 ensaio clínico randomizado, o EVEREST II. DISCUSSÃO: O MitraClip® tem demonstrado boa segurança e eficácia em pacientes selecionados adequadamente através da ecocardiografia transesofágica. Porém, é necessário refinar a seleção dos pacientes, em relação a etiologia da IM, se funcional ou degenerativa, presença de hipertensão pulmonar, disfunção ventricular direita e presença de arritmias como a fibrilação atrial. Apesar dos resultados clínicos promissores, os custos e a custo-efetividade da MitraClip® limitam sua utilização. O benefício clínico é inferior ao obtido com o tratamento cirúrgico, e com um custo muito superior, sendo assim contraindicada a utilização do MitraClip® em substituição à cirurgia aberta. O custo/benefício de um procedimento como MitraClip® pode ser menos significativo em pacientes com IM funcional devido a comorbidades que limitam significativamente sua expectativa de vida. PARECER FINAL: -Recomendação forte contrária à incorporação na rotina hospitalar; -Frente a eficácia e segurança, a tecnologia pode ser utilizada em contexto de pesquisa ou ensino.