Brazilian Analytical Decision Model for Cardiovascular Disease: An Adaptation of the Scottish Cardiovascular Disease Policy Model.

INTRODUCTION: Despite the significant impact of cardiovascular disease (CVD), there is not yet an analytical decision tool for assessing efficiency of interventions to prevent primary CVD events in Brazil. Therefore, we sought to adapt a Scottish CVD Policy Model to be used in the proposed population. METHODS: Calibration consisted of identifying multiplicative factors for linear predictors of existing survival analysis models to produce predictions that closely match observed data (Life-table and Brazilian cohort study). Target data were life expectancy (LE) and cumulative incidence of coronary heart disease (CHD), cerebrovascular disease (CBVD), fatal CVD and fatal non-CVD. Root-Mean-Square-Error (RMSE) was used to estimate differences between predictions and observations. Acceptance criteria were defined as a fit of less than one year for LE and 1% for cumulative incidence. Male and female models were built separately. RESULTS: The original model underestimated LE (RMSE=2.85 for men and 1.91 for women), CHD and CBVD for women (RMSE=0.044 and 0.041, respectively). The calibration process identified multiplicative factors to reach acceptance criteria for the four target data mentioned above (RMSE=0.61, 0.21, 0.016 and 0.017, respectively). Over prediction was identified only for CHD events in men (RMSE=0.031) being further calibrated (RMSE=0.008). All other target data met the acceptance criteria. Overall, the calibrated model predicts properly to individuals aging 35-80 years old, diabetics or not, smokers or not, with or without family history of CVD, and presenting at least one of the risk factors uncontrolled: Systolic Blood Pressure, Total Cholesterol or HDL-Cholesterol. DISCUSSION: This is the first decision analytic model capable of assessing efficiency of interventions that prevent primary CVD events in Brazil. In future research, independent external validation should be carried out to corroborate the reliability of the model outputs.

Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections.

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil.

Análise de impacto orçamentário: uma revisão prática de conceitos e aplicações para o gestor / Budget impact analysis: a practical review of concepts and applications for the manager

Avaliações econômicas em saúde são essenciais para a tomada de decisão de gestores, visto que as inovações no setor nem sempre podem ser incorporadas conforme as expectativas dos usuários e da indústria. Logo, a análise de impacto orçamentário (AIO), uma das principais ferramentas da avaliação de tecnologias em saúde (ATS), permite aos gestores estimar o potencial número de indivíduos elegíveis para determinada tecnologia ao longo dos anos, prever quanto será necessário gastar para incorporar a tecnologia ou, eventualmente, se haverá economia nos cofres do pagador com a inclusão dela. Com a crescente publicação de artigos científicos sobre AIO no Brasil, surge a preocupação a respeito da qualidade metodológica desses estudos. O objetivo desta revisão é apresentar recomendações-chave para a elaboração de uma AIO adequada e expor a utilidade prática da AIO para a tomada de decisão de gestores de saúde por meio da análise de quatro estudos publicados. O formato de apresentação de uma AIO possibilita rápido entendimento e possui atributos que permitem evidenciar o maior valor de produtos e serviços de saúde junto aos tomadores de decisão em saúde, contribuindo para as melhores escolhas do ponto de vista clínico e econômico, nos sistemas público e privado. Porém, cabe ressaltar que alguns estudos ainda carecem de evidências de mundo real ou dados epidemiológicos para as estimativas e trabalham de maneira insuficiente as ferramentas para a redução de incertezas paramétricas.

Health economics evaluations are essential for decision makers, since innovations can not always be incorporated according to expectations of users and industry. Therefore, the Budget Impact Analysis (BIA), one of the main tools in Health Technology Assessment (HTA), allows managers to estimate the potential number of individuals eligible for a given technology over the years, to predict how much it will be necessary to spend for incorporate the technology or, eventually, whether there will be savings in the payer's coffers with the inclusion of the same. With the growing publication of scientific articles on BIA in Brazil, there is concern about the methodological quality of these studies. The objective of this review is to present key recommendations to elaborate an adequate BIA, commenting on four published studies, aiming to expose the practical utility of BIA for health managers. The presentation format of the BIA provides a quick understanding and has attributes that allows evidence of the highest value of health products and services among health decision makers, contributing to the best clinical and economic choices in public and private health systems. However, it should be noted in some studies there is still a lack of real-world evidence or epidemiological data for the estimates and insufficient using of tools to reduce parametric uncertainties.

A cost-effectiveness analysis of two different antimicrobial stewardship programs

Abstract There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective.

A cost-effectiveness analysis of two different antimicrobial stewardship programs.

There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective.

Cost-Effectiveness of Biologic Agents in the Treatment of Moderate-to-Severe Psoriasis: A Brazilian Public Health Service Perspective.

BACKGROUND: Psoriasis is a chronic disease that affects public health and budget payers. In Brazil, biologic therapy for psoriasis is mostly provided by means of lawsuit with no strategy for efficient allocation of resources. OBJECTIVE: This study aimed to identify which of the available biologic alternatives for psoriasis is the most efficient from the perspective of the Brazilian Public Health Service (SUS). METHODS: Direct costs and efficacy were expressed in Brazilian currency (real [R$]; US $1 = R$1.97) and Psoriasis Area Severity Index 75 (PASI75), respectively. The Markov model process included 12 cycles of 3 months each, comprising 3 years of horizon. Adalimumab (80 mg at week 0 followed by a maintenance dose of 40 mg at week 1 and then every other week), etanercept (50 mg twice weekly for 12 weeks followed by a maintenance dose of 25 mg weekly), infliximab (5 mg/kg at weeks 0, 2, and 6 and then every 8 weeks), and ustekinumab (45 mg at weeks 0 and 4 and then every 12 weeks) were assessed. One-way and horizon sensitivity analyses were performed. Moreover, probabilistic sensitivity analysis was applied to evaluate model robustness. The final result was interpreted as the cost for each patient who achieved and maintained PASI75 for at least 3 years. RESULTS: Adalimumab was the most cost-effective biologic therapy (R$120,981.45/PASI75) for moderate-to-severe psoriasis, followed by ustekinumab (R$126,336.67/PASI75), etanercept (R$225,074.71/PASI75), and infliximab (R$377,656.28/PASI75). One-way sensitivity analysis determined that the acquisition cost of biologics was the most sensitive parameter of the model. Horizon analysis suggests that the result was the same when the horizon was varied from 1 year to a lifetime. Probabilistic sensitivity analysis showed that adalimumab has 80% to 10% probability of being the most cost-effective biologic considering a willingness-to-pay value ranging from R$50,000 to R$500,000, whereas ustekinumab presented a probability of 20% to 90% for the same range. CONCLUSIONS: From the pharmacoeconomics point of view, adalimumab 80 mg at week 0 followed by a maintenance dose of 40 mg at week 1 and then every other week should be the first-line therapy for patients with plaque psoriasis concomitant or not to psoriatic arthritis or nail psoriasis. This study does not have the potential to evaluate the impact of incorporating a specific biologic agent on the final budget. Its goal is to point out which of the technologies is the most efficient, that is, the one that adds more value to the financial resource invested.

Efficacy and safety of biologics in the treatment of moderate to severe psoriasis: a comprehensive meta-analysis of randomized controlled trials / Eficácia e segurança de agentes biológicos no tratamento da psoríase moderada a grave: uma meta-análise de ensaios clínicos randomizados e controlados / Eficacia y seguridad de los agentes biológicos en el tratamiento de la psoriasis moderada a severa: un metaanálisis de ensayos aleatorios y controlados

We conducted a systematic review and metaanalysis of randomized placebo-controlled trials in moderate-to-severe psoriasis treated with biological agents, with a follow-up of 10-14 weeks. Overall, 41 studies, with mean Jadad score of 4.4, and 15,586 patients were included. For the efficacy outcomes PASI 50, 75 and 90 our findings are not conclusive to point what biological agent has the greatest response in short term follow-up. There were no statistical differences between placebo and biologics for the occurrence of infections and serious adverse events. Ustekinumab 45mg showed lower withdrawal due to adverse events compared with the placebo. Based on data available up to now, it is not possible to determine which biological agent is the best for PASI 50, 75 or 90 after 10-14 weeks of treatment. At the same follow-up, overall safety seems to be the same for all biological agents and Ustekinumab 45mg the most well tolerated drug. To better understand efficacy and safety, indirect meta-analysis comparing drug-to-drug is required since randomized placebo-controlled trials may not be feasible.

Conduziu-se uma revisão sistemática e metaanálise de ensaios clínicos randomizados em pacientes com psoríase moderada a grave, tratados com biológicos ou placebo por 10 a 14 semanas. Foram incluídos 41 estudos, com escore de Jadad médio de 4,4, totalizando 15.586 pacientes. Para os desfechos de eficácia PASI 50, 75 e 90 os resultados não são conclusivos para definir qual é o melhor agente biológico no curto prazo. Não houve diferença estatística entre placebo e biológicos para ocorrência de infecções e eventos ad-versos sérios. Ustequinumabe 45mg foi o biológico com menor ocorrência de descontinuação por conta de eventos adversos. Baseado na evidência até então disponível, não é possível determinar qual agente biológico é o melhor para se atingir resposta PASI 50, 75 e 90 após 10-14 semanas de tratamento. Para o mesmo intervalo, a segurança global parece ser a mesma para todos os biológicos e ustequinumabe 45mg o tratamento melhor tolerado. Para melhor compreender a eficácia e segurança, meta-análise indireta comparando droga-a-droga são necessárias já que ensaios clínicos randomizados podem não ser viáveis.

Se realizó una revisión sistemática y metaanálisis de ensayos controlados aleatorios en pacientes con psoriasis moderada a severa tratados con biológicos o placebo por 10-14 semanas. Se incluyeron 41 estudios con una puntuación de Jadad de 4,4, un total de 15.586 pacientes. Para variables de eficacia PASI 50, 75 y 90, los resultados no son concluyentes para definir cuál es el mejor agente biológico en el corto plazo. No hubo diferencia estadística entre el placebo y la ocurrencia biológica de las infecciones y los eventos adversos graves. Ustequinumabe 45mg fue el biológico con una menor incidencia de la interrupción debido a eventos adversos. Basado en la evidencia disponible hasta el momento, no es posible determinar qué agente biológico es lograr la mejor respuesta PASI 50, 75 y 90 después de 10-14 semanas de tratamiento. Para el mismo período, la seguridad global parece ser el mismo para todos los tratamientos y ustequinumabe 45mg el mejor tolerado. Para comprender mejor la eficacia y seguridad, es necesario un metaanálisis indirecto comparando medicamento a medicamento.

Análise de custo-utilidade do tratamento adjuvante de câncer de cólon estádio III (Dukes C) / Análisis coste-utilidad del tratamiento adyuvante del cáncer de colon enestádio III (Dukes C) / Cost-utility analysis in adjuvant treatment of colon cancer staging III (Dukes C)

Introdução: O aumento do repasse financeiro ao tratamento adjuvante de câncer de cólon estádio II nos hospitaisintegrantes do Sistema Único de Saúde permite a utilização de quimioterápicos anteriormente não empregados.Entretanto, não há estudos farmacoeconômicos que norteiem gestores quanto à escolha da terapia. Objetivo: Avaliar a relação custo-utilidade das terapias adjuvantes Fluorouracil/Leucovorin (5FU/LV, Mayo Clinic Regimen) versusCapecitabina e 5FU/LV versus Fluorouracil/Leucovorin/Oxaliplatina (FLO X) para câncer de cólon em estádio II na perspectiva de um hospital público no Brasil. Método: Dados de eficácia foram extraídos da literatura e custos a partir do Sistema de Informação Hospitalar da referida instituição. Utilizou-se uma modelagem de Markov com dez ciclos de seis meses com quatro estados de saúde: terapia com antineoplásico, livre de doença, recidiva e morte. A taxa de desconto aplicada foi de 5%. Os custos foram expressos em Real (R$) e o desfecho em meses de vida ajustados pelaqualidade (QAL M). Realizou-se análise de sensibilidade univariada. Resultados: Capecitabina e FLO X proporcionam0,33 e 1,75 QALM a mais que 5FU/LV, respectivamente. A comparação Capecitabina e 5FU/LV mostrou relaçãocusto-efetividade incremental (RCEI ) de R$13.585,64/QALM, enquanto a comparação FLO X e 5FU/LV RCEIde R$1.007,92/QALM. A análise de sensibilidade sugere resultados robustos. Conclusão: O custo de aquisição da Capecitabina inviabiliza o uso em pacientes com câncer de cólon estádio III na perspectiva avaliada. O custo incremental de FLO X está compreendido pelo repasse financeiro do SUS, favorecendo sua incorporação como terapia adjuvante de câncer de cólon estádio II pelo hospital aos indivíduos elegíveis para esse protocolo