Insulin glargine in a Brazilian State : an assessment of drug utilization, effectiveness and value to provide future direction

The cost and utilisation of the insulin analogue (Insulin glargine) has grown appreciably in the State of Minas Gerais in Brazil in recent years, with costs growing on average by 291% per year. This growth has been driven by an increasing number of successful law suits and a 536% price differential between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One way forward to address concerns with its growing utilisation is to undertake a systematic review assessing the efficacy and safety of insulin glargine compared with NPH insulin in patients with Type I diabetes. As a result, provide published data to support future recommended activities by the State to limit its use

Clinical effectiveness and safety of analogue glargine in type 1 diabetes : systematic review and meta-analysis

INTRODUCTION: The use of insulin analogues for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given their higher costs. Objective: To evaluate the effectiveness and safety of Analogue Glargine (AG) compared to Recombinant DNA insulin (rDNA) in patients with DM1 in observational studies, building on previous reviews of RCTs comparing NPH insulin and AG. METHODS: A systematic review (SR) with meta-analysis. The SR included cohort studies and registries available on PUBMED, LILACS, and CENTRAL as well as manual and gray literature searches. The meta-analysis was conducted in Review Manager ® 5.2 software. The primary outcomes were: glycohemoglobin (Hb1Ac), weight gain and hypoglycemia. Methodological quality was assessed using the Newcastle-Ottawa scale. RESULTS: Out of 796 publications, 11 studies were finally included. The meta-analysis favored AG in Hb1Ac outcomes (adult patients) and hypoglycemic episodes (p <0.05), but without reaching glycemic control (Hb1Ac to approximately 7%). The methodological quality of the studies was moderate, noting that 45% of studies were funded by pharmaceutical companies. CONCLUSION: Given the high heterogeneity of the studies, the discrete value presented by the estimated effect on effectiveness and safety, potential conflicts of interest of the studies and the appreciable higher cost of AG, there is still no support for recommending first line therapy with analogues. The role of analogues in the treatment DM1 could be better determined by further observational studies of good methodological quality to assess their long-term effectiveness, safety as well as cost-effectiveness

Cost-effectiveness thresholds : methods for setting and examples from around the world

INTRODUCTION: Cost-effectiveness thresholds (CETs) are used to judge if an intervention represents sufficient value for money to merit adoption in healthcare systems. The study was motivated by the Brazilian context of HTA, where meetings are being conducted to decide on the definition of a threshold. AREAS COVERED: An electronic search was conducted on Medline (via PubMed), Lilacs (via BVS) and ScienceDirect followed by a complementary search of references of included studies, Google Scholar and conference abstracts. Cost-effectiveness thresholds are usually calculated through three different approaches: the willingness-to-pay, representative of welfare economics; the precedent method, based on the value of an already funded technology; and the opportunity cost method, which links the threshold to the volume of health displaced. An explicit threshold has never been formally adopted in most places. Some countries have defined thresholds, with some flexibility to consider other factors. An implicit threshold could be determined by research of funded cases. EXPERT COMMENTARY: CETs have had an important role as a “bridging concept” between the world of academic research and the “real world” of healthcare prioritization. The definition of a cost-effectiveness threshold is paramount for the construction of a transparent and efficient Health Technology Assessment system

Real world effectiveness of olanzapine and risperidone in the treatment of schizophrenia in Brazil over a 16-year follow-up period; findings and implications

Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits. Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up. Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After, patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyzes were performed. Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference. Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyzes

Pharmaceutical services in the primary health care of the Brazilian Unified Health System:: advances and challenges

This study is a synthesis of the main results of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines), Evaluation Component of the Basic Pharmaceutical Services. Based on the critical narrative of the elements of Brazil’s pharmaceutical policies, we discuss aspects related to the structure of the pharmaceutical services, the medicines’ sanitary state, human resources, access to medicines, rational use and management. Despite the advances that reflect the commitment of the group of actors involved, the results of the Survey indicate challenges, such as equitable access to medicines, the structuring of pharmaceutical services, the improvement of logistics and administration, and the implementation of actions directed to pharmaceutical care in the health unitsTrata-se de uma síntese dos principais resultados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos, componente de Avaliação dos Serviços de Assistência Farmacêutica Básica. Com base em narrativa crítica dos elementos das políticas farmacêuticas no Brasil, discutem-se aspectos relacionados à estrutura dos serviços farmacêuticos, situação sanitária dos medicamentos, recursos humanos, acesso a medicamentos, uso racional e gestão. Apesar dos avanços que refletem o empenho do conjunto de atores implicados, os resultados da Pesquisa apontam desafios, como o acesso equitativo dos medicamentos, a estruturação dos serviços farmacêuticos, o aprimoramento da logística e da gestão e a implantação de ações voltadas ao cuidado farmacêutico nas unidades de saúd

Consumer willingness to pay for dengue vaccine (CYD-TDV, Dengvaxia®) in Brazil : implication for future pricing considerations

Introduction and objective: Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur. However, given that the vaccine will potentially be paid via the public health system, information is need regarding consumers’ willingness to pay for the dengue vaccine in the country as well as discussions related to the possible inclusion of this vaccine into the public health system. This was the objective of this research. Methods: We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Results: 507 individuals were interviewed. These were mostly female (62.4%) had completed high school (62.17%), were working (74.4%), had private health insurance (64.5%) and did not have dengue (67.4%). The maximum median value of consumers’ willingness to pay for CYD-TDV vaccine is US$33.61 (120.00BRL) for the complete schedule and US$11.20 (40.00BRL) per dose. At the price determined by the Brazil's regulatory chamber of pharmaceutical products market (CMED) for the commercialization of Dengvaxia® for three doses, only 17% of the population expressed willingness to pay for this vaccine. Conclusion: Brazil is currently one of the largest markets for dengue vaccine and the price established is a key issue. We believe the manufacturer should asses the possibility of lower prices to reach a larger audience among the Brazilian population

Effectiveness of maintenance immunosuppression therapies in a matched-pair analysis cohort of 16 years of renal transplant in the Brazilian national health system

Maintenance of patients with renal transplant typically involves two or more drugs to prevent rejection and prolong graft survival. The calcineurin inhibitors (CNI) are the most commonly recommended medicines in combinations with others. While immunosuppressive treatment regimens are well established, there is insufficient long-term effectiveness data to help guide future management decisions. The study analyzes the effectiveness of treatment regimens containing CNI after renal transplantation during 16 years follow-up with real-world data from the Brazilian National Health System (SUS). This was a retrospective study with SUS patients after renal transplantion. Patients were propensity score-matched (1:1) by sex, age, type and year of transplantation. Kaplan-Meier was used to estimate the cumulative probabilities of survival. A Cox proportional hazard model was used to evaluate factors associated with progression to graft loss. 2,318 patients were included. Multivariable analysis, adjusted for diabetes mellitus and race / color, showed a greater risk of graft loss for patients using tacrolimus plus mycophenolate compared to patients treated with cyclosporine plus azathioprine. In conclusion, this Brazilian real-world study, with a long follow-up period using the matched analysis for relevant clinical features, and the representativeness of the sample, demonstrated improved long-term effectiveness for therapeutic regimens containing cyclosporine plus azathioprine. Consequently, we recommend that protocols and clinical guidelines for renal transplantation should consider cyclosporine plus azathioprine regimen as a potential first line option along with others

CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety

Introduction: Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia®) was the first vaccine to gain regulatory approval to try and address this problem. Aim: Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Method: Meta-analysis and systematic review. Results: The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2–16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. Conclusion: CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population. </jats:p