Augusto Afonso Guerra Júnior

Federal University of Minas Gerais, Cidade de Minas, Minas Gerais, Brazil

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Publications (63)16.65 Total impact

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    ABSTRACT: INTRODUCTION: Prostate cancer is one of the most common prostatic diseases in adults and can compromise the longevity and quality of life of these individuals. The drug dutas-teride and abiraterone, according to the literature, could be used as alternative therapies for prevention and treatment of prostate cancer. Dutasteride inhibits the production of an androgen that is directly involved in the development of benign prostatic hyperpla-sia, while abiraterone is an inhibitor of the biosynthesis of hormones that stimulate the growth of prostate cancer cells. However, these drugs are not available in the Brazilian's Unified Health System (SUS). OBJECTIVES: Assess the available scientific evidence on the efficacy and safety of dutasteride and abiraterone for prevention and treatment of pros-tate cancer. METHODS: We searched Medline (via Pubmed), The Cochrane Library and LILACS databases for systematic reviews (SR) of randomized clinical trials (RCTs) that assessed the use of abiraterone and dutasteride for the treatment of prostate cancer. We searched Health Technology Assessments (HTA) in sites of international agencies and the Brazilian Network for Health Technology Assessment. Quality of the evidence and strength of recommendation were evaluated using the GRADE system. RESULTS: We identified 110 publications and included in the evaluation four complete studies, including two RCTs and two SR. The RCT showed that dutasteride reduced by 38-66% cancer progression compared to placebo, with a similar safety profile. Both RCTs have important limitations, such as funding by the manufacturer of dutasteride, considerable loss of follow up and no evaluation of survival. No HTA recommendations of dutasteride use in the treatment of prostate cancer were found. Regarding the prevention of prostate cancer, dutasteride was evaluated in a SR of moderate quality, which showed favorable efficacy results, but with possible increase of disease progression. This fact resulted in the withdrawal of the license by the manufacturer of this therapeutic indication. High quality SR showed that the use of abiraterone and prednisone promotes 26% higher survival and 45% lower disease progression compared to placebo combined with prednisone in the treatment of metastatic castration-resistant prostate cancer (CRPCm). However, abiraterone presented unfavorable safety profile. HTA recommend abiraterone for the treatment of CRPCm with disease progression during or after failed therapy with docetaxel. CONCLUSION: For the initial stages of prostate cancer, surgery, radiation therapy, brachytherapy, and in some cases, vigilant observation are indicated. The evidence evaluated is not sufficient to ensure a positive balance between the benefits and harms related in the use of dutasteride. For patients with symptomatic CRPCm, docetaxel generally is used as a first choice and in the case of failure of therapy, the abiraterone is a possible alternative. However, as recommended by HTA other drugs such as cabazitaxel and mitoxantrone could be used after failure with docetaxel, and it is difficult to choose one therapy over another, being necessary to conduct studies considering the impact of these drugs on patient's quality of life.
    II Simpósio Internacional de Farmacoeconomia no SUS, Belo Horizonte, Brazil; 07/2015
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    ABSTRACT: INTRODUCTION: Pregabalin is an anticonvulsant indicated for the treatment of neuro-pathic pain in adults. Its mechanism of action is the reduction of calcium influx to regulate transmission of excitatory messages between nerve cells. ETNA® is a combination of vitamin B12, uridine and cytidine nucleotides and it is indicated for the treatment of peripheral nerves diseases. OBJECTIVES: To evaluate if pregabalin and ETNA® are safer, more effective and more cost-effective than gabapentin and amitriptyline (available in SUS) to treat diabetic neuropathic pain. METHODS: a search for systematic reviews and economic studies was performed in the databases The Cochrane Library (via Bireme), Medline (via PubMed), LILACS and Centre for Reviews and Dissemination (CRD). Manual search was also conducted on the internet and in the references of the studies found. Health Technology Assessments (HTA) have been selected in international agencies and in Brazilian Network for Health Technology Assessment (REBRATS). Studies published in English, Portuguese or Spanish were selected. RESULTS: Nine studies were included, four systematic reviews, one clinical trial and four economic studies. Systematic reviews considering efficacy and safety of pregabalin evaluated the following outcomes: reduction in pain intensity, treatment response rate (≥50% on pain reduction), the Patient Global Impression of Change and adverse events. These reviews showed results in favor of pregabalin compared to placebo. The ETNA® clinical trial showed results in favor of the intervention but compared to vitamin B12 alone. The results of cost-effectiveness for pregabalin considered as a measure of effectiveness the number of days with no pain or mild pain, the number of days with 30% and 50% reduction in pain and QALY gains. Only one cost-effectiveness study has not favored pregabalin. CONCLUSION: The treatment for neuropathic pain is contemplated in the therapeutic guideline for chronic disease, which recommends the use of amitriptyline in monotherapy as first choice or its association with gabapentin in cases of therapeutic failure with the monotherapy. The evidences appraised here allow indicate the use of pre-gabalin in replacement of gabapentin only in cases of therapeutic failure of the schemes mentioned above, since no study included direct comparisons between pregabalin and amitriptyline or gabapentin, making it impossible to support the therapeutic superiority of pregabalin compared to other drugs already used in Brazil. The evidence does not support ETNA® use due to lack of studies with sufficient evidence of quality to ensure the efficacy and safety of this intervention and justify the expense.
    II Simpósio Internacional de Farmacoeconomia no SUS, Belo Horizonte, Brasil; 07/2015
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    ABSTRACT: Strength of recommendations: Strong against the technology Technology: Rituximab Indication: Refractory systemic lupus treatment Characterization of the technology: Rituximab targets a specific protein known as CD20 on the surface of B-cells resulting in cell death. Question: Is the use of rituximabe as adjuvant treatment effective and safe for patients with refractory systemic lupus? Search and analysis of scientific evidence: We searched the Medline (via Pubmed), The Cochrane Library (via Bireme), Lilacs and the Centre for Reviews Dissemination (CRD). Systematic Reviews (SR) and Randomized Controlled Trials (RCT) of clinical trials comparing the use of rituximabe plus standard treatment with standard treatment at refractory systemic lupus treatment were included. The quality of evidence and strength of recommendation were assessed using the GRADE system and its variance. Summary of results of selected studies: Three SR with metanalysis and three RCT were included whose quality ranged from very low to moderate quality. Most of them showed no significantly superior efficacy to decrease the disease activity index of rituximabe in systemic lupus treatment when compared to standard treatments, despite the significant improved in serological markers of disease activity index (most of them with p value >0.05, against rituximab utilization). Unexpected adverse events, severe and non-severe, were not observed when compared to standard treatment. Recommendations: The strength of recommendation is strong against rituximabe for systemic lupus treatment, considering the quality of the evidence and the higher cost of treatment compared to standard treatment. However, more randomized controlled trials are needed to evaluate its effectiveness with higher precision. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: Strength of recommendations: Strong against the technology Technology: Rituximab Indication: Refractory systemic lupus treatment Characterization of the technology: Rituximab targets a specific protein known as CD20 on the surface of Bcells resulting in cell death. Question: Is the use of rituximabe as adjuvant treatment effective and safe for patients with refractory systemic lupus? Search and analysis of scientific evidence: We searched the Medline (via Pubmed), The Cochrane Library (via Bireme), Lilacs and the Centre for Reviews Dissemination (CRD). Systematic Reviews (SR) and Randomized Controlled Trials (RCT) of clinical trials comparing the use of rituximabe plus standard treatment with standard treatment at refractory systemic lupus treatment were included. The quality of evidence and strength of recommendation were assessed using the GRADE system and its variance. Summary of results of selected studies: Three SR with metanalysis and three RCT were included whose quality ranged from very low to moderate quality. Most of them showed no significantly superior efficacy to decrease the disease activity index of rituximabe in systemic lupus treatment when compared to standard treatments, despite the significant improved in serological markers of disease activity index (most of them with p value >0.05, against rituximab utilization). Unexpected adverse events, severe and non-severe, were not observed when compared to standard treatment. Recommendations: The strength of recommendation is strong against rituximabe for systemic lupus treatment, considering the quality of the evidence and the higher cost of treatment compared to standard treatment. However, more randomized controlled trials are needed to evaluate its effectiveness with higher precision. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective.
    Revista de saude publica 03/2015; 49(1):1-9. DOI:10.1590/S0034-8910.2015049005430 · 1.22 Impact Factor
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    ABSTRACT: Technologies: Medicines whose active ingredient is somatropin registered in Brazil. Indication: Hypopituitarism and Turner syndrome. Technologies characterization: Somatropin is human growth hormone produced by recombinant DNA technique. Question: What brand of recombinant human somatropin, currently incorporated by the Unified Health System (4 and 12 IU) and the general market (15, 16, 18, 30, 36 and 60 IU), presents itself more economically advantageous considering the indication, stability and the cost? Methods: The registered medicines in Brazil were obtained from the electronic database of the National Health Surveillance Agency (ANVISA). The stability of drugs and indications were obtained from the package inserts. The average body weight of patients with active process for somatropin was obtained in the Information System of the Pharmaceutical Assistance Management (SiGAF) and was used to calculate the consumption. To calculate the consumption and the wastage we considered the minimum and maximum dose recommended in Clinical Protocols and Therapeutic Guidelines of the Brazilian Ministry of Health. For the estimated cost of treatment analysis we considered the consumption and the Maximum Price of Sale to the Government with 0% tax obtained from the Drug Market Regulation Chamber on 11/20/2014. Results: Seven brands with 13 different presentations of human recombinant somatropin are currently available in the market. Aside from Eutropin® 4 IU that should be used right after reconstituted, all medicines have stability of 28 days. Hormotrop® is indicated only for Turner syndrome, but its formulation is similar to that of medicines indicated for hypopituitarism. Comparing all medicines, those incorporated by the SUS showed higher prices per IU (exception: Norditropin® 15 IU that showed the highest price). For children with hypopituitarism, the estimated average monthly somatropin wastage was 2.05 to 2.06 IU (4 IU stability of 28 days); 5.84 to 6.28 IU (IU 12); and 6.3 to 10.1 IU for presentations from 15 to 18 IU. For presentations of 30 IU or more the monthly average wastage was estimated to be 18.2 to 51.2 IU. Considering all registered medicines, those incorporated by SUS emerged from the fifth position of lower estimated average cost. For adults with hypopituitarism, the estimated average monthly somatropin wastage was 1.00 to 2.00 IU (4 IU - 28 days); 6.00 to 9, 00 IU (12 IU); and from 0.00 to 21.00 IU for presentations from 15 to 18 IU. For presentations of 30 IU or more the monthly average wastage was estimated to be 30.00 to 105.00 IU. Considering all registered medicines, those incorporated by SUS appeared from the first position of lower average estimated cost for the minimum dose, and from the fifth position for the maximum dose. For patients with Turner syndrome the estimated average monthly somatropin wastage was 2.65 to 2.08 IU (4 UI - 28 days); 6.08 to 6.86 IU (12 IU); and from 7.18 to 10.18 IU for presentations 15-18 IU. For presentations of 30 IU or more the monthly average wastage was estimated to be 14.29 to 30.08 IU. In a ranking with 13 placements, the medicines incorporated by SUS appeared from the eighth place of lower estimated average cost. The medicine Eutropin® 4 IU showed the highest wastage and the highest cost estimates for both diseases. Recommendations: Strictly speaking the use of Hormotrop® for hypopituitarism is off label. We emphasize the similarity between the formulation of this medicine and that of the others, and the fact that the indication update process stars with a requested by the registry holder, and not only on the existence of scientific evidence. With the results obtained for hypopituitarism and Turner syndrome we know that: (i) IU prices of medicines incorporated by SUS were the highest among all registered medicines (except for Norditropin® 15 IU); (ii) less wastage with presentations incorporated by SUS did not translate into better results of estimated mean treatment cost (presentations 15, 16 and 18 IU had lower or similar cost); and that (iii) the stability of Eutropin® 4 IU was responsible for it worst results of treatment cost and wastage. Thus, in order to obtain the medicine with lower cost and wastage, we recommend that the purchase of somatotropin be made considering price per IU, and to allow the participation of presentations of up to 18 IU. We also recommend the inclusion of technical criteria for the purchase somatropin, such as stability of 28 days. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: INTRODUCTION: Pompe disease is a rare, inherited disease characterized by the deficiency of the production of acid alpha glucosidase. It manifests clinically in two forms: Infantile or late-onset Pompe disease. The enzyme replacement therapy (ERT) is the only available treatment for the disease, but is not currently provided by the Brazilian National Health System (SUS). OBJECTIVES: The aim this study was to evaluate the efficacy, safety and the cost of alglucosidase-alfa (Myozyme®) for ERT for Infantile and late-onset Pompe disease. METHODS: We searched for scientific studies in the electronic database PubMed, MICRO-MEDEX and in the website of the Brazilian National Health Surveillance Agency (ANVISA). The price of alglucosidase-alfa was obtained at the Regulatory Chamber of the Pharmaceutical Market (CMED) with 0% of Interstate Tribute for Services and Goods. Treatment costs were calculated considering every other week dose of 20 mg/kg for children (weight 10 kg) and adults (weight 70 kg). RESULTS: We included a clinical trial about Pompe disease in infants and three studies of Pompe disease in children or adults. The proportion of patients alive at 18 months of age was 100% in the group using ERT vs. 1.6% in the control group for Pompe disease in infants. Considering the live ones with non-invasive ventilation the ratio was of 72.2% vs. 0%, respectively. Regarding late-onset Pompe disease, a systematic review funded by the product manufacturer showed that 2/3 of patients had improvement or stabilization of their disease for most of the evaluated outcomes. However , the classification/presentation of outcomes did not allow evaluating if there was a significant clinical improvement. After two years of ERT there was a deterioration of the clinical status and patients developed antibodies against the enzyme, whose effects on the effectiveness of ERT still need to be further elucidated. The clinical trial included showed results in 78 weeks in favor of the use of ERT to the outcomes of distance walked during a 6-minute walk test; predicted forced vital capacity and maximal expiratory pressure. However , the authors considered the results modest. Only the observational study included evaluated the survival of patients with late-onset Pompe disease, and showed that up to nine years of follow-up patients treated with ERT have chances 59% lower to die. In further analysis the authors stated that eight years would be needed in ERT to obtain an extra year of life. The annual cost of treatment with ERT for infantile and late-onset forms were R$ 117,371.52 and R$ 821,600.64, respectively. Thus, eight years of ETR would correspond to a cost of more than R$ 6.5 million per patient with late-onset Pompe disease to obtain an extra year of life. CONCLUSION: ERT seems to have less effect in patients with late-onset Pompe disease than in infantile patients and results in high cost of treatment. Thus, further studies are needed to state on its efficacy and safety in patients with the late-onset form.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    ABSTRACT: Objective: To evaluate the lawful request of ziprasidone for treating trichotillomania and obesity. The drug is indicated, but it consists of a contingency measure, since social inclusion may have potencial to improve the overall state. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: INTRODUCTION: The draft Law 4,508/2013 of the Legislative Assembly of the State of Minas Gerais proposes the obligation of the State to ensure patients with diabetes mellitus (DM), through the State Department of Health, access to all the technologies available on the market, such as laboratorial exams, medicines, equipment and supplies for the application of insulin as well as the reimbursement by SUS to citizens who purchase these in the private market. OBJECTIVES: To estimate the budget impact for the State Treasury if the draft Law 4,508/2013 is approved in the Legislative Assembly of the State of Minas Gerais. METHODS: The estimated budget impact was calculated considering four scenarios for each type of DM, according to the prevalence of DM1 (477,407) and DM2 (4,057,961) in the population of Minas Gerais in 2013. We considered that 100% of patients with DM1 would use combined insulin therapy: intermediate-acting insulin and rapid-acting insulin, or insulin analog ultra-fast. Among patients with DM2 we considered that 40.7% were taking oral hypoglycemic and 7.9% were in use of combined insulin therapy. For each scenario we considered the minor and major values of each technology. We obtained the price of medicines and supplies in the Pharmaceutical Market Regulation Chamber and on the Minas Gerais or São Paulo banks prices and the annual cost of each therapy was calculated according to the Daily Defined Dose (DDD) of the World Organization Health. The health budget for the years 2013 and 2014 were consulted in the Secretariat of State for Planning and Management of Minas Gerais (SEPLAG/MG). RESULTS: The estimated budget impact on the Treasury of the State of Minas Gerais ranged from 895 million to 10 billion Reais per year for DM1, according to the scenarios (i) NPH and regular insulin + syringes, (ii) NPH and regular insulin + pen applicator, (iii) insulin analogues + pen applicator, and (iv) infusion pump and regular insulin. Regarding DM2, values ranged from 251 million to 2.1 billion Reais per year, according to the scenarios (i) monotherapy biguanide (metformin), (ii) biguanida in combination to sulphonylurea or dipeptidyl peptidase 4 (DPP-4), (iii) bigu-anide and sulphonylurea combination or DPP-4 and nocturnal insulin NPH, and (iv) insulin analogs therapy. The total estimate ranged, therefore, from 1.1 to 11.7 billion Reais per year. Data from SEPLAG/MG indicated that the total expenditure on health in Minas Gerais for the year 2014 will be of about 7.5 billion Reais. The most optimistic scenario in terms of forecast spending with the possible approval of the bill 4,508/2013 would result in an expense of 14.7% of the total health budget of Minas Gerais. CONCLUSION: It is estimated that with the possible adoption of the bill 4,508 of 2013, of the Legislative Assembly of the State of Minas Gerais, the impact on the budget of the Treasury of Minas Gerais State may vary from 1.1 to 11.7 billion Reais per year.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    Juliana De Oliveira Costa, Daniel Resende Faleiros, Augusto Afonso Guerra Júnior
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    ABSTRACT: EDITORIAL A Avaliação de Tecnologias de Saúde (ATS) fortificou-se nos últimos anos, tornando-se foco de grandes debates. É uma ferramenta essencial na garantia do acesso da população a medicamentos, dispositivos médicos e procedimentos de saúde que sejam efetivos, seguros e comercializados a um preço aceitável para o Poder Público e para a sociedade. Entretanto, diversos desafios surgem após a conclusão de um estudo de ATS. Como fazer com que os resultados obtidos sejam implantados na prática? Ou ainda, como traduzir este conhecimento à sociedade, aos médicos, gestores dos sistemas de saúde, ao Poder Judiciário e aos demais interessados? Neste sentido o Centro Colaborador do SUS para Ava-liação de Tecnologias e Excelência em Saúde (CCATES), em parceria com o Ministério da Saúde, promoveu o II Simpó-sio Internacional de Farmacoeconomia no SUS entre os dias 10 e 12 de novembro de 2014, na Faculdade de Farmácia da UFMG. O Simpósio teve como objetivo fomentar a discussão no campo da ATS, em especial, sobre as estratégias de disse-minação de evidências na tomada de decisão. A incorporação de tecnologias e a elaboração de Pro-tocolos Clínicos e Diretrizes Terapêuticas foram temas que permearam as discursões entre os representantes do Brasil, Argentina, Portugal, Escócia, Estados Unidos, Suécia, Aus-trália e do Banco Mundial, que na oportunidade traçaram o panorama internacional destas práticas. Outro ponto im-portante foi o debate acerca de tecnologias em saúde que se apresentam obsoletas ou que já não se apresentam mais vantajosas frente às alternativas terapêuticas. O desinves-timento, que pretende possibilitar realocação de recursos destas tecnologias para outras consideradas mais custo-efetivas, foi abordado pelo pesquisador do Karolinska Insti-tutet da Escócia. Os conflitos e as sinergias entre o mercado e as políticas de saúde e o acesso a novas tecnologias na vi-são da Justiça também compuseram a pauta de discussões, incluindo aspectos como o gerenciamento de pacientes de alto custo e a medicina personalizada. Representantes do National Prescribing Service (NPS) apre-sentaram as estratégias desta organização australiana sem fins lucrativos dedicadas à promoção do uso com qualidade de medicamentos. Como exemplo de uma destas estratégias foi apresentado o detalhamento acadêmico, que se constitui de visita face-a-face realizada por um profissional de saúde ao prescritor, objetivando a intervenção eficaz para melhorar os padrões de prescrição. Outra estratégia bem sucedida apre-sentada foi a campanha Resistance Fighter, estratégia direcio-nada à sociedade. Esta campanha conta com a participação de celebridades australianas na conscientização da população sobre o risco do uso indiscriminado de antibióticos. O II Simpósio Internacional de Farmacoeconomia no SUS permitiu a difusão dos avanços do conhecimento científico no âmbito da ATS e sua aplicação e a articulação em rede in-ternacional para realização e disseminação de avaliações de tecnologias. Aproximadamente 200 ouvintes participaram do evento, que contou com a presença de 11 convidados in-ternacionais e 23 nacionais, três minicursos e apresentação de 34 trabalhos aqui publicados. Os diapositivos e as fotos do evento estão disponíveis no site do Centro Colaborador do SUS (www.ccates.org.br). Boa leitura!
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    ABSTRACT: INTRODUCTION: Renal transplantation is recognized as the best option for patients with end-stage renal disease, both in clinical and economic perspectives. Brazil has one of the largest public programs of organs and tissues transplantation of the world. The Brazilian National Health System (SUS) is responsible since the search for the donor until the post-transplant treatment. The success of transplantation is related to characteristics of the recipients and donors, among them the age and the type of donor (dead, living related, or living not related). It is necessary to know the profile of these individuals and their geographical distribution to guide the planning of specific actions for this population. OBJECTIVES: To describe the profile of kidney transplantation in Brazil according to demographic and clinical characteristics of recipients and donors. METHODS: Cohort from kidney transplanted (Jan/2000 to Dec/2009) developed from the deterministic-probabilistic linkage of Authorization for Hospital Hospitalization database-AIH/SUS. Information about donors was obtained for 106 patients transplanted in Belo Horizonte in the period of 2006-2009. RESULTS: In the 10 years of analysis, we identified 26.282 kidney transplants, an increase of 49.0% in the number of procedures, and decrease between 2003 and 2005, followed by a significant increase. The Brazilian Society of Nephrology saw a rise of 103.8% in the number of dialysis patients in these 10 years. Most of the recipients were male (59.6%), in which the most common type of transplant was living donor. In women the opposite was observed (p <0.01). The average age was 40 years. Kidney transplantation was more frequent in the 18-42 years old group (48.8%) and less in the ≥67 years old group (1.6%). The age of the living donors recipients was lower than that of the cadaver transplant recipients (p <0.01). 51.0% of the transplants were from living donors. It was observed that by the year 2006 most of the provided organs were from living donors (55.2%) and by 2009 most were from cadaveric donor (55.9%). From the 106 transplants with donor's information, 70.7% were cadaver, aged 32.95±13.87, and 50.6% were female. Among the living donors the average age was of 41.76±8.30 and 51.6% were men. Most were brothers (63.0%), followed by parents (16.6%). Transplant between individuals of different sex occurred in 64.5% of living donors and 51.3% in transplantation with cadaver organ. Overall, the highest number of transplants performed was in São Paulo State (38.6%), followed by Minas Gerais (10.7%) and Rio Grande do Sul (9.5%). CONCLUSION: Renal transplantation in Brazil occurs predominantly among men, aged between 18-42 years old, with organ from cadaver donors. The living donor transplant recipients were younger and major donors were siblings. In absolute numbers, São Paulo, Minas Gerais and Rio Grande do Sul are presented as major transplanters states. Over this period there was an increase in the number of kidney transplants , which did not follow the increase in the number of dialysis patients. This indicates that despite the recent advances and efforts in the area the number of kidney transplants is still insufficient.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    ABSTRACT: INTRODUCTION: Access to medicines of the Specialized Component of Pharmaceutical Assistance (CEAF) is carried out through opening of administrative proceedings in accordance with detailed rules and Clinical Protocols and Therapeutic Guidelines. The compliance of the medicines requests in Minas Gerais are evaluated by the Health Department of Minas Gerais State in partnership with the SUS Collaborating Centre (CCATES)/Federal University of Minas Gerais. Public information allows knowing the number of deferred requests. However, it is also necessary to understand the flow, the time to process the requests and the profile of the rejected and returned ones to provide a better service. OBJECTIVES: To assess the demand for medicines of the CEAF and the time spent to conduct the proceedings in Minas Gerais. METHODS: Analysis of all requests of CEAF medicines held in Minas Gerais, in 2013, by consultation to the Integrated Management System of the Pharmaceutical Assistance (SiGAF) and records of the CCATES. RESULTS: In the year 2013 we evaluated 85 thousand processes, of which 79% were granted, 13% returned and 5% refused. According to the 10th International Classification of Disease, most of the demands was for endocrine, nutritional and metabolic diseases (21.2%), followed by diseases of the skin and subcutaneous tissue (13.6%). Isotretinoin (26.0%) and the analog of insulin glargine (21.0%) were the most requested medicines. Insulin glargine is provided in Minas Gerais for the treatment of Diabetes Mellitus type 1. Isotretinoin is provided for Severe Acne Treatment, which occurs in 15% of patients with acne-skin disease. In the 2006 dermatological census 65% of the patients had acne-skin disease. The total average processing time was of 57.98 (± 30.89) days, and the average time spent on the compliance analysis was of 8.4 days (14.5%). The rest of time was spent on bureaucracy (49.5 days). CONCLUSION: Most of the requests came from patients with endocrine, nutritional and metabolic diseases, with emphasis on the request of insulin glargine, provided by State decision. The demand for isotretinoin was higher than the prevalence of severe acne reported in the literature. The total time of the conduct of proceedings decreased if compared to 2008, coinciding with the implementation of the SiGAF and the CCATES. It should be noted that analysis of compliance, key stage of the process, corresponded only to 14.5% (8.4 days) of the total time, and that can be further reduced with the electronic analysis and use of digital certification, such as already occurs with the federal revenue. It is recommended to optimize the processing time and transportation steps, as it represented more than 85% of the flow time.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    ABSTRACT: INTRODUCTION: New technologies have been developed and brought to market at a speed never seen before. Pressure on Public Health Systems to make available to the public new technologies resulted in clear and structured processes of incorporation, which, however, have " non substitutionary " /cumulative feature. Additionally, technologies already offered may have become obsolete, present safety issues or may not be cost-effective. These technologies are candidates for disinvestment, which is the reallocation of resources from the funding of technology for other purposes. Methods for divestment-since identification technologies until implementation of the decision-have not yet been defined. OBJECTIVES: Propose a guideline for divestment suitable for universal health care systems. METHODS: Integrative literature review and expert panel composed of managers and researchers in the fields of Public Health and Law. RESULTS: After consulting the international literature, we found that most publications on the subject did not address the implementation of the divestment decision. This may be due to the fact that in most countries, medicines, one of the most evaluated technologies, are financed through co-payment or reimbursement. In Brazil medicines are purchased and distributed by public entities or financed by co-payment, so the Guideline should address the implementation of the divestment in the aspects of logistics and distribution. With this in mind and based on the incorporation process adopted by the National Commission on Technology Incorporation in SUS (CONITEC), a flow that involves five steps was proposed: (1st) the identification, resulting of request by health professionals, industry, government entities or society; (2nd) prioritization to rank the priority requests for analysis; (3rd) evaluation according to the guidelines of Technology Assessment (HTA) of the Brazilian Network of HTA (REBRATS); (4th) disinvestment decision considering the existence of alternative/ substitute technology and the epidemiological assessment of the risk-benefit; (5th) development of an Action Plan to be agreed between the entities with the participation of the Health Councils and Committees. This plan should consider the time required for the consumption of stocks and to purchase the replacement technology and the spread of decision for managers, prescribers, judiciary and patients. CONCLUSION: Adopting a guideline of disinvestment after extensive debate in society may lead to the improvement of processes and steps. Disinvestment presents itself as an important tool for the reallocation of scarce public health resources, thus it is imperative to define a guideline that addresses the fundamental aspects of this process.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    ABSTRACT: INTRODUCTION: Acetylcholinesterase inhibitors (AChEI) are commonly used in the treatment of mild and moderate Alzheimer's disease (AD) and it is provided by the Brazilian National Health System (SUS). The treatment is available free of charge to eligible patients, according to criteria and norms established by the Clinical Protocol and Therapeutic Guidelines (CPTG), through the opening of an administrative request. The non-observance of the CPTG leads to delays in the process of drug dispensation, which may harm the patient in need for the treatment. OBJECTIVES: To describe prescriber's non-compliance to CPTG for Alzheimer's disease, assessing the frequency of AChEI requests not approved, as well as the reasons for that. METHODS: A cross-sectional study was conducted using 165 AChEI requests from Minas Gerais state, prescribed between October 2012 and May 2013 and selected randomly. The drug requests were available from the SUS/MG, which receives the request from the physician and sends it to an analyst to approve or deny the request. We estimated the frequency of not approved-requests and assessed patient's medical records included in the requests (i.e., differential diagnosis of dementia and cog-nitive tests, such as Mini-mental State Examination – MMSE and Clinical Dementia Rating – CDR) in order to investigate the reasons for non-compliance that led to non-approval of AChEI release. RESULTS: From the 165 AChEI requests included in this study, 38% were not approved and returned to the prescribers. The main reasons included: incongruence between cognitive tests (22%); high degree of dependence in basic activities of daily living , suggestive of score 3 at the CDR test (12%); cognitive tests applied wrongly (8%); and presence of untreated depression (7%). According to the CPTG for Alzheimer's disease, patients classified as CDR-3 are not eligible to AChEI treatment. Furthermore, the CPTG preconizes that depression should be treated in order to confirm the diagnosis of AD. CONCLUSIONS: The reasons presented suggest non-observance of the CPTG inclusion criteria and lack of knowledge in how to perform cognitive tests. Failure to comply with the CPTG generates an unnecessary cost to the State, regarding the analysis and reanaly-sis of requests by referees, expendable clinical examinations and ineffective treatment. Dissemination and clarification of clinical protocols and guidelines through educational interventions for prescribers, such as academic detailing, is important to ensure patient access to effective medication, in the corresponding stage of the disease.
    II Simpósio Internacional de Farmacoeconomia no SUS; 01/2015
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    ABSTRACT: INTRODUCTION: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder caused by the death of brain neurons and consequent decreased production of a neurotransmitter, dopamine. Pramipexole is a dopamine agonist that acts " replacing " dopamine. In Brazil, pramipexole is provided to the population by the Specialized Component of Pharmaceutical Assistance. In the market are available: reference medicine (Sifrol®); pramipexole immediate release generic; and similar medicine (brand-name non innovative). There are considerable differences in price. OBJECTIVES: Evaluate the interchange-ability between pramipexole generic, innovative and similar medicines, according to parameters of safety and efficacy. METHODS: A search was performed for Brazilian and other countries official documents and reports that addressed the standards for registration of generic and similar medicines on the websites of National Health Surveillance Agency (ANVISA), Food and Drug Administration (FDA), European Medicines Agency (EMA) and World Health Organization. Search for scientific studies was conducted in Medline (via PubMed), Centre for Reviews and Dissemination, The Cochrane Library, and LILACS. RESULTS: According to the Law and resolutions of ANVISA the interchangeability between reference and generic, or similar medicines, is expected as they have to demonstrate bi-equivalence for the registration of the medicine in the Ministry of Health. ANVISA resolutions regulated waiver from traditional bioequivalence studies for drugs considered to present high solubility and high permeability according to the Biopharmaceutics Classification System. In August 2014 pramipexole was included in the list of drugs eligible for biowaiver, as it is considered to present high absorption (greater than or equal to 85%) and wide therapeutic index, i.e., the therapeutic dose is far from the toxic dose. Furthermore , this drug has not been reported in human bioequivalence. In the United States of America, pramipexole is eligible for biowaiver since 2010. The European agency has not released the list of drugs, but as the World Health Organization considers drugs with high solubility and high permeability eligible for biowaiver. After applying the eligibility criteria one scientific study was included. This is a narrative review that concludes that patients with Parkinson's disease should be treated with brand name medicines. This study has important limitations regarding the fact that the authors can choose the ones that support their opinion. The peculiarities of patients with Parkinson's disease are presented as an argument , such as reduced gastric motility, affect the effectiveness of generic drugs, similar and reference in the same way. CONCLUSION: There is no normative support that point out to differences in safety and efficacy between brand name and generic drugs of prami-pexole, and the Brazilian and foreign regulations showed no evidence of bioinequivalence between different formulations of pramipexole dihydrochloride. In addition, scientific evidence of quality was not found, as precepts the evidence-based medicine, that pointed to differences in clinical effect between the presentations studied.
    II International Symposium on Pharmacoeconomics in SUS - Dissemination of HTA for decision-making; 01/2015
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    ABSTRACT: INTRODUCTION: Sunitinib is an antineoplastic, protein kinase inhibitor, inducing apop-tosis and reducing proliferation to malignant cell. It is indicated for the treatment of renal cell carcinoma, gastrointestinal stromal tumors after disease progression, imatinib contra-indication, and unresectable Pancreatic Neuroendocrine Tumor (PNET). OBJECTIVES: To review the available scientific evidence on sunitinibe use in the treatment of unresectable PNET and evaluate its safety and effectiveness for treating of this tumor type. METHODS: The databases The Cochrane Library (via BIREME), Medline (via PubMed), LILACS and Centre for Reviews and Dissemination (CRD) were searched. Manual search of references in the studies found was performed. Health Technology Assessments (HTA) was searched in the Brazilian Network for Technology Assessment and Health (REBRATS) and international agencies as Agencias y Unidades de Evaluación de Tecnologías Sanitarias (AUnETS/Spain), Canadian Agency for Drugs sites and Technologies in Health (CADTH/Canada), National Institute for Health and Clinical Excellence (NICE/UK), Health Technology Assessment Programme (NIHR/UK) and Pharmaceutical Benefits Advisory Committee (PBAC/Australia). Cohort studies and clinical trials, systematic reviews and economic evaluations conducted in any geographic region, with patients of either sex, older than 18 years, with unresect-able PNET were eligible. Studies comparing the use of sunitinib any other therapeutic intervention, placebo or no treatment intervention groups were selected. Progression-free survival, overall survival, time to response, objective response rate, duration of response and adverse events were evaluated. RESULTS: The search returned 665 studies and five were selected: a phase III clinical trial, two phase II clinical trials, a matching-adjusted indirect comparison of two phase III clinical trials and a cost-effectiveness analysis. Compared with placebo, sunitinib provided improved overall survival (11.4 months vs. 5.5 months), progression-free survival (71.3% vs. 43.2% in six months of treatment) and response to treatment (9.3% vs. 0.0%, p-value = 0.007). Compared to everolimus, no significant differences were observed in overall survival (HR = 0.81, IC95% = 0.49-1.31; p-value = 0.383). However, neutropenia (OR = 0.15; p-value = 0.049) and hypertension (OR = 0.19, p-value = 0.021) were significantly associated with sunitinib compared with the everolimus. Furthermore , the Incremental Cost-Effectiveness Ratio tends to discourage sunitinib compared with the everolimus (ICER = US$ 41.702,00 per QALY with everolimus). CONCLUSION: Considering the evaluation of the safety and cost-effectiveness, sunitinib is recommended only in everolimus contraindication. Considering the methodological quality and the available scientific evidence, this recommendation is weak. Other clinical trials are needed to strengthen the evidence.
    II Simpósio Internacional de Farmacoeconomia no SUS, Belo Horizonte; 11/2014
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    ABSTRACT: Strength of recommendations: Weak against the technology Technology: Valganciclovir Indication: Prevention of cytomegalovirus disease in solid organ transplant recipients Characterization of the technology: Valganciclovir is an antiviral drug, L-valyl ester (prodrug) of ganciclovir. It acts by inhibiting the viral DNA synthesis by a competitive inhibition of deoxyguanosine triphosphate incorporation to the viral DNA. Question: Is valganciclovir more effective and safer than other available therapies for cytomegalovirus prevention in solid organ transplant patients? Search and analysis of scientific evidence: We searched the Medline (via Pubmed), The Cochrane Library (via Bireme), Lilacs and the Centre for Reviews Dissemination (CRD). Systematic Reviews (SR) of clinical trials comparing valganciclovir to other antiviral drugs were included. Health Technologies Assessment (HTA) reports of international agencies were also searched. The quality of evidence and strength of recommendation were assessed using the GRADE system. Summary of results of selected studies: Seven SR were included and most of them presented low quality. None showed significantly superior efficacy of valganciclovir in cytomegalovirus prevention in solid organ transplants patients, when compared to therapeutic alternatives. In addition, its use, especially in 900mg/day dose, was statistically associated with the risk of leucopenia or neutropenia. We did not include any HTA. Recommendations: The strength of recommendation is weak against valganciclovir for cytomegalovirus prevention in solid organ transplants patients, considering the quality of the evidence and the higher cost of treatment compared to therapeutic alternatives. However, more transplant-specific studies are needed to evaluate its effectiveness in each type of solid organ transplant. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: Technologies: Generic immediate release formulation of pramipexole Indication: Treatment of motor symptoms of Parkinson's disease. Technologies characterization: Pramipexole is a dopamine agonist that acts "replacing" dopamine, a neurotransmitter that is in decreased concentration in Parkinson's disease. Question: The generic drug pramipexole is safe and effective in the treatment of the motor symptoms of Parkinson's disease in comparison to the reference medicine (Sifrol®) and the similar medicine (Stabil®)? Search and analysis of scientific evidence: We performed a search for Brazilian official documents and reports that addressed the standards for registration of generic and similar medicines in the electronic sites of the National Health Surveillance Agency (from the Portuguese Agência Nacionald e Vigilância Sanitária - ANVISA) and international documents of the Food and Drug Administration (FDA), European Medicines Agency (EMA) sites and the World Health Organization (WHO). We conducted a search for scientific studies in Medline (via Pubmed), Centre for Reviews and Dissemination, The Cochrane Library, and LILACS. Summary of results of the selected studies: According to Law and resolutions of ANVISA the interchangeability between reference and generic, or similar medicines, is expected as they have to demonstrate biequivalence for the registration of the medicine in the Ministry of Health. ANVISA Resolutions regulated waiver from traditional bioequivalence studies for drugs considered to present high solubility and high permeability according to the Biopharmaceutics Classification System. In August 2014 pramipexole was included in the list of drugs eligible for biowaiver as it is considered of high absorption (greater than or equal to 85%) and of broad therapeutic index, i.e., the therapeutic dose is distant to the toxic dose. Furthermore, this drug has no reports of human absence of bioequivalence. In the United States of America pramipexole is eligible for biowaiver since 2010. The European agency has not released the list of drugs eligible for biowaiver, but considers drugs with high solubility and high permeability eligible for biowaiver, as well as the World Health Organization. After applying the eligibility criteria a scientific study was included. It is a narrative review in which the authors indicate that patients with Parkinson's disease should be treated with the brand name medicines. This study has important limitations regarding the method, as narrative reviews do not use a structured and reproducible search for studies, the authors can choose the ones that support their opinion. The peculiarities of patients with Parkinson's disease presented as an argument, such as reduced gastric motility, affect the effectiveness of generic, similar and reference medicines the same way. Recommendations: There is no legal and scientific support to justify the preference for brand name medicines with respect to pramipexole, since the Brazilian and foreign regulations point to the fact that there is no evidence of absence of bioequivalence between different formulations of immediate release pramipexole dichloridrate. In addition, we did not find high quality scientific evidence, according to the precepts of evidence-based medicine, which could point to differences in clinical outcomes between the formulations studied. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: Intensity of recommendations: Weak in favor of the technology. Technology: Fluoxetine, sertraline and citalopram. Indication: Moderate or major depression. Characterization of the technology: Selective serotonin reuptake inhibitor (SSRI) antidepressants increase the amount of serotonin in the synaptic cleft, thus increasing synaptic stimulation and serotonergic activity in the body. Question: Are citalopram and sertraline more effective than fluoxetine for the treatment of major depression in adults? Search and analysis of scientific evidence: We searched Medline (via Pubmed), Centre for Reviews and Dissemination (CRD), The Cochrane Library and LILACS databases for systematic reviews (SR) of clinical trials that compared the efficacy and safety of fluoxetine, sertraline and citalopram for moderate or major depression. Quality of the evidence and strength of recommendation were evaluated using the GRADE system. We searched for Health Technology Assessments and therapeutic guides in international agencies and websites in the Brazilian Network for Health Technology Assessment. Summary of results of selected studies: We included seven SR, six with meta-analysis and one without. Assessing the effectiveness, the results of RS demonstrated a slight superiority of sertraline and fluoxetine front no statistically significant differences were observed between fluoxetine and citalopram. As for safety, most studies proved inconclusive or slightly favorable to fluoxetine. Compared to rates of noncompliance, the results were not statistically significant, we conclude that there is no difference between the drugs. Most RS showed evidence of low quality and all contributed to a weak recommendation in favor of sertraline. Four treatment guidelines were included. Their authors made no distinction between the SSRI medicines. Recommendations: Considering that most of the results had limitations and inconclusive data, it is recommended that further research is made, focusing on the comparison of SSRI drugs among themselves, expecting that new publications increase the strength and quality of evidence available for decision making. FULL CONTENT IN PORTUGUESE
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    ABSTRACT: Technologies: Dutasteride and Abiraterone Indication: Prevention (dutasteride) and treatment (dutasteride or abiraterone) of prostate cancer. Characterization of the technologies: Dutasteride inhibits the conversion of testosterone to dihydrotestosterone, an androgen that is directly involved in the development of benign prostatic hyperplasia. Abiraterone is an inhibitor of androgens biosynthesis, which are hormones that stimulate the growth of prostate cancer cells. Question: Are dutasteride and abiraterone safe and effective for the prevention and treatment of prostate cancer? Search and analysis of scientific evidence: We searched Medline (via Pubmed), The Cochrane Library, LILACS and Centre for Reviews and Dissemination (CDR) databases for systematic reviews (SR) of clinical trials that assessed the use of abiraterone and dutasteride for the treatment of prostate cancer. We searched Health Technology Assessments (HTA) in sites of international agencies and the Brazilian Network for Health Technology Assessment. Quality of the evidence and strength of recommendation were evaluated using the GRADE system. Summary of results of selected studies: Four studies, two RS and two RCTs were selected. The RCT showed that dutasteride reduced by 38-66% cancer progression compared to placebo, with similar safety profile. Both RCTs have important limitations, such as funding by the manufacturer of dutasteride, considerable loss of follow up and no evaluation of survival. No ATS recommendations of dutasterida use in the treatment of prostate cancer were found. Regarding the prevention of prostate cancer, dutasteride was evaluated in a RS moderate quality, which showed favorable efficacy results, but with possible increase of disease progression. The fact resulted in the withdrawal of the license by the manufacturer of this therapeutic indication. High quality RS showed that the use of abiraterone and prednisone promotes 26% higher survival and 45% lower disease progression compared to placebo combined with prednisone in the treatment of metastatic castration-resistant prostate cancer. However the abiraterone presented unfavorable safety profile. ATS recommend abiraterone for the treatment of metastatic castration-resistant prostate cancer who had disease progression during or after failed therapy with docetaxel. However, other drugs such as cabazitaxel and mitoxantrone could be used after failure with docetaxel, and there is difficulty in choosing one therapy over another. Recommendations: For the initial stages of prostate cancer, surgery, radiation therapy, brachytherapy, and in some cases, vigilant observation are indicated. Dutasteride should not be used for prevention or treatment of prostate cancer, since the evidence evaluated is not sufficient to ensure a positive balance between the benefits and harms related to the technology use. Chemotherapy is indicated in more advanced stages of the disease and should be initiated quickly in patients with castration-resistant and metastatic cancer who are symptomatic, usually using docetaxel as first choice. After failure of first-line therapy, we weakly recommend the use of abiraterone and prednisone. For the treatment of patients who have resistant metastatic prostate cancer to castration, asymptomatic or mildly symptomatic who failed hormonal therapy and are chemotherapy-naive, we weakly recommend against the use of abiraterone and prednisone, due to lack of sufficient evidence to ensure greater effectiveness of abiraterone compared with docetaxel.