Reply letter to "response to article by Johnna Perdrizet et al." by Gomez and colleagues.

This communication seeks to address the questions and criticisms issued by Gomez and colleagues in their letter on our original study "Cost-effectiveness analysis of replacing the 10-valent pneumococcal conjugate vaccine (PCV10) with the 13-valent pneumococcal conjugate vaccine (PCV13) in Brazil infants." Gomez and colleagues are concerned that the assumptions used in our model may have unintended negative impacts for Brazil decision-making and we intend to clarify any potential misinterpretation of our assessment.

Cost-effectiveness analysis of replacing the 10-valent pneumococcal conjugate vaccine (PCV10) with the 13-valent pneumococcal conjugate vaccine (PCV13) in Brazil infants.

Brazil currently has a 10-valent pneumococcal conjugate vaccine (PCV10) pediatric national immunization program (NIP). However, in recent years, there has been significant progressive increases in pneumococcal disease attributed to serotypes 3, 6A, and 19A, which are covered by the 13-valent PCV (PCV13). We sought to evaluate the cost-effectiveness and budget impact of switching from PCV10 to PCV13 for Brazilian infants from a payer perspective. A decision-analytic model was adapted to evaluate the clinical and economic outcomes of continuing PCV10 or switching to PCV13. The analysis estimated future costs ($BRL), quality-adjusted life-years (QALYs), and health outcomes for PCV10 and PCV13 over 5 y. Input parameters were from published sources. Future serotype dynamics were predicted using Brazilian and global historical trends. Over 5 y, PCV13 could prevent 12,342 bacteremia, 15,330 meningitis, 170,191 hospitalized pneumonia, and 25,872 otitis media cases, avert 13,709 pneumococcal disease deaths, gain 20,317 QALYs, and save 172 million direct costs compared with PCV10. The use of PCV13 in the Brazilian NIP could reduce pneumococcal disease, improve population health, and save substantial health-care costs. Results are reliable even when considering uncertainty for possible serotype dynamics with different underlying assumptions.

Avaliação de custo-efetividade da vacina pneumocócica conjugada 13-valente comparada à vacina pneumocócica polissacarídica e não vacinação no Sistema de Saúde Suplementar Brasileiro / Cost-effectiveness evaluation of pneumococcal conjugate vaccine 13-valent compared to the polysaccharide pneumococcal vaccine and non-vaccination in the Brazilian Supplementary Health System

RESUMO Objetivo: As doenças causadas pela bactéria Streptococcus pneumoniae (pneumococo) são importantes causas de morbimortalidade no mundo, principalmente em indivíduos nos extremos de idade. O objetivo deste estudo foi avaliar os benefícios e custos incrementais associados à vacina pneumocócica conjugada 13-valente PCV13 (Prevenar® 13), comparada à não utilização de vacina e à utilização de vacina pneumocócica polissacarídica PPSV23 no Sistema de Saúde Suplementar, por meio de uma análise de custo-efetividade. Métodos: Foi realizado um estudo de custo-efetividade utilizando um modelo de Markov que englobou os estados de saúde saudável, doença pneumocócica e morte. Neste estudo foram incluídos dados clínicos de pacientes com doença pneumocócica (bacteremia, meningite, internações por pneumonia e pneumonias ambulatoriais), custos médicos diretos e indiretos, considerando um horizonte de tempo de três anos, com ciclos anuais e uma coorte hipotética de pacientes com 50 anos ou mais. Análises de sensibilidade univariada e probabilística também foram realizadas. Resultados: A utilização da vacina PCV13 se mostrou dominante em relação às demais estratégias nos pacientes com risco baixo, moderado e alto. A análise de sensibilidade probabilística indica que a chance de PCV13 ser a estratégia mais custo-efetiva é de 90%, quando um limiar de R$ 12.000 para cada ano de vida ganho é definido. Conclusões: Foi possível observar que a utilização da vacina PCV13 para a prevenção de doenças pneumocócicas em adultos com 50 anos ou mais, considerando o desfecho clínico "anos de vida salvos", pode ser a estratégia mais eficiente quando comparada à não vacinação ou à utilização da vacina PPSV23.

Diseases caused by the bacteria Streptococcus pneumoniae are important sources of morbidity and mortality around the world, specially in regard to elderly people. We sought to assess costs and benefits inherent to 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar® 13) compared to pneumococcal polysaccharide vacine (PPSV23) and the policy of does providing vaccine in the perspective of Brazilian Private Health System. Methods: A cost-effectiveness analysis model was performed by means of a Markov modelling which comprised the health states healthy, pneumococcal disease and death. In this study were included clinical data of patients with pneumococcal disease (bacteremia, meningitis, hospitalization due to pneumonia and community acquired pneumonia) and direct and indirect medical costs. A three year time horizon and an annual cycle were set. The hypothetic cohort corresponds to patients aging 50 years or more. One-way and probabilistic sensitivity analyses were performed. Results: PCV13 is dominant over PPSV23 and non- -vaccination policy in low- moderate- and high-risk patients. Probabilistic analysis shows that PCV13 has a probability of being 90% more cost-effective when a threshold of BRL 12.000 is defined for each incremental life-year gained. Conclusions: Considering the outcome life-years gained PCV13 is the strategy that most promote value for money in patients aging 50 years or more, in the Brazilian Private Health System.

Qualidade de vida relacionada ao transplante de fígado em polineuropatia amiloidótica familiar: uma revisão sistemática / Quality of life related to liver transplantation in familial amyloidotic polyneuropathy: a systematic review

Objetivos: Avaliar o impacto do transplante de fígado sobre a qualidade de vida relacionada à saúde (QVRS) em pacientes com polineuropatia amiloidótica familiar (PAF). Métodos: Uma revisão sistemática da literatura foi realizada até dezembro de 2015 em bases de dados eletrônicas. Os desfechos avaliados referem-se às dimensões físicas e mentais analisadas nos questionários de QVRS. Resultados: Seis estudos foram selecionados para revisão. Antes e após o transplante de fígado, os pacientes com PAF apresentaram QVRS significativamente pior em comparação com a população geral, composta por pessoas com doenças crônicas ou de pacientes sem PAF transplantados. Quatro anos após o transplante, os domínios de bem-estar físico e emocional também foram significativamente menores para os pacientes com PAF. A comparação entre os períodos pré e pós-transplante mostrou uma melhora no componente mental de pacientes sem PAF e piora em PAF. O componente físico apresentou melhora para ambos os grupos, embora tenha sido significativamente maior no grupo sem PAF. Em comparação com pacientes com PAF que não receberam transplante, apenas o componente físico mostrou uma diferença significativa 12 meses após o transplante de fígado para o grupo com PAF que recebeu o transplante. Conclusão: Pacientes com PAF apresentaram piores escores de QVRS em comparação com os pacientes sem PAF que receberam transplante e a população controle. Dentre os pacientes com PAF (com e sem transplante), o transplante de fígado não apresentou impacto significativo sobre o componente mental da qualidade de vida.

Objectives: To assess the impact of liver transplantation on health-related quality of life (HRQoL) of patients with familial amyloidotic polyneuropathy (FAP). Methods: A systematic literature review was conducted until December 2015 in electronic databases. The outcomes assessed were physical and mental dimensions assessed in HRQoL questionnaires. Results: Six studies were selected for review. Before and after liver transplantation, patients with FAP showed a significantly worse HRQoL when compared to the overall control population, chronic diseases, and non-FAP transplanted patients. Four years after transplantation, the physical and emotional well-being domains were also significantly lower for patients with FAP. The comparison between pre- and post-transplantation periods showed an improvement in the mental component of non-FAP patients and FAP worsening. The physical component showed an improvement for both groups, although it was significantly higher in the non-FAP group. When compared to non-transplanted FAP patients, only the physical component showed a significant difference 12 months after liver transplantation for the transplanted FAP group. Conclusion: FAP patients showed worse HRQoL scores when compared to non-FAP transplanted patients and the control population. Among FAP patients (between transplanted and non-transplanted patients), liver transplantation did not show a significant impact on the mental component of quality of life.

Custo-efetividade do uso associado de estabilizadores de humor e antipsicóticos atípicos na terapia de manutenção do transtorno bipolar no Sistema Único de Saúde / Cost-effectiveness of mood stabilizers and atypical antipsychotics in maintenance therapy of bipolar disorder in the Brazilian Unified Health System

RESUMOObjetivo: Avaliar a custo-efetividade da associação de antipsicóticos atípicos e estabilizadores de humor na terapia de manutenção do transtorno bipolar no Sistema Único de Saúde (SUS). Métodos: Assumindo os custos diretos na perspectiva do SUS, construiu-se um modelo de Markov com as transições entre eutimia, mania, depressão, descontinuação e morte. Dados foram obtidos de ensaios clínicos, coortes prospectivas e bases assistenciais do SUS (valores correntes de 2015). Com uma coorte hipotética (n = 2000, idade = 40 anos), foram simulados ciclos trimestrais no horizonte de até 30 anos (ou efetividade < 1 dia em remissão). Adotaram-se taxas de desconto, correção de meio de ciclo e análises de sensibilidade. Resultados: Os dados de eficácia permitiram apenas a análise da associação com a quetiapina. No horizonte temporal de 12 anos (48 ciclos), ocorreram 512 episódios agudos (depressão: 285, mania: 227) com a monoterapia de lítio ou valproato e 306com associação de quetiapina (depressão: 166, mania: 139). A razão de custo-efetividade incremental (RCEI) da associação com a quetiapina foi de R$ 807,95 por mês adicional em remissão. A análise de sensibilidade demonstrou robustez do modelo, sendo a variação da dose e do preço da quetiapina seus maiores modificadores (amplitude da RCEI de R$ 541,60 a R$ 1.770,05). Conclusões: A terapia de manutenção com a associação da quetiapina ao lítio ou valproato demonstrou ser potencialmentecusto-efetiva. Considerando que o uso de antipsicóticos atípicos não é desprovido de riscos, a estratégia estudada pode ser uma alternativa terapêutica em populações específicas do SUS

ABSTRACTObjective: To evaluate the cost-effectiveness of the combination of atypical antipsychotic and mood stabilizers in maintenance treatment of bipolar disorder in the Brazilian Unified Health System (SUS). Methods: Taking direct costs, from the perspective of SUS, we built a Markov model withtransitions between the states: euthymia, mania, depression, discontinuation and death. Data were extracted from clinical trials, prospective cohorts and SUS databases (current values of 2015). In a hypothetical cohort (n = 2,000, age = 40 years), maintenance therapy was simulated over quarterly cycles through a timeframe up to 30 years (until effectiveness < 1 day in remission). Discount rates and half-cycle correction were applied and sensitivity analyses were run. Results: The efficacy data enabled to include only a combination with quetiapine in the analysis. After twelve years (48 cycles), there were 512 acute episodes (depression: 285, mania: 227) for monotherapy with lithium or valproate against 306 (depression: 166, mania 139) for the quetiapine combination. The incremental cost-effectiveness ratio (ICER) for the quetiapine combination was R$ 807.95 per additional month in remission. The sensitivity analysis demonstrated the model?s robustness, while dosage and quetiapine-price variations had most impact in ICER (ranging from R$ 541.60 to R$ 1,770.05 per additional month in remission). Conclusion: Maintenance therapy with the combination of quetiapine andlithium or valproate seems to be cost-effective. As the use of atypical antipsychotics is also associated with risks, the studied strategy can be a therapeutic alternative for specific populations in SUS.

An Estimate of the Cost of Hepatitis C Treatment for the Brazilian Health System.

OBJECTIVES: Hepatitis C therapy in Brazil is expensive due to the cost of antiviral drugs and demands on medical resources. The objective of this study was to estimate the direct costs per patient of chronic hepatitis C therapy in a Brazilian setting. METHOD: A microcosting study from a public health system perspective. The costs included were those of antiviral drugs, secondary medicines, diagnostic tests, visits to physicians and other professionals, hospitalization, nurse, and pharmaceutical care. All costs were priced in 2010. The values were converted to US $ (2010). RESULTS: The total direct cost of hepatitis C treatment per patient with interferon alpha (IFN) plus ribavirin (RBV) was US $982.25, with peginterferon alpha (PEG) 2a 180 µg plus RBV was US $10,658.08, and with PEG 2b 120 µg plus RBV was US $12,597.63, taking into account entire treatment according to Brazilian guidelines and assuming that all patients completed full treatment. The antiviral drugs are the most expensive element of the cost of treatment, totaling more than 40% of the medical costs of IFN plus RBV therapy and more than 88% of PEG plus RBV therapy. Calculating an average of 10,000 treatments per year, the total direct cost is US $90,346,772.39. According to the Ministry of Health, 90% of the annual total cost of hepatitis C treatment is accounted for by antiviral drugs. CONCLUSIONS: In Brazil, antiviral drugs are the most expensive component of hepatitis C treatment. The cost of follow-up and support to patients is minimal compared with the cost of antiviral drugs.