Emicizumab prophylaxis for people with hemophilia A: Waste estimation and the Brazilian perspective.

Costs of hemophilia A treatment are increasing. Waste of clotting products should be avoided. To estimate the first-year waste of emicizumab prophylaxis for people with hemophilia A and inhibitors (PwHAi) who failed immune tolerance induction (ITI), in Brazil. We evaluated the manufacturer and the Brazilian Ministry of Health (MoH) protocol-recommended regimens in a budget impact model. The loading dose consisted of 3.0 mg/kg/Q1W for 4 weeks, for both recommendations. The manufacturer maintenance regimens comprised 1.5 mg/kg/Q1W, 3.0 mg/kg/Q2W, and 6.0 mg/kg/Q4W. The MoH protocol maintenance regimen encompassed a hybrid Q1W/Q2W administration, depending on the body weight. The Q4W regimen was not recommended by the MoH protocol. Analyses were performed to estimate waste given its expense based on the World Health Organization body weight range (percentiles [P] 15, 50, and 85). The first-year emicizumab waste was estimated individually and for the disclosed PwHAi who failed ITI (n = 114). The highest emicizumab waste was estimated for the lowest body weights and the Q1W regimen. The Q4W regimen resulted in the lowest emicizumab waste, followed by the MoH protocol regimen. The total reconstituted costs estimated for the PwHAi who failed ITI according to the hybrid MoH protocol ranged from US$32,858,777 (P15) to US$47,186,858 (P85), with emicizumab waste ranging from 7.9 % (US$2,594,515) to 3.7 % (US$1,738,750), respectively. Lost resources due to current protocols for emicizumab prophylaxis for PwHAi who failed ITI in Brazil are considerable. Waste was more pronounced due to lower body weight and shorter administration intervals.

Real-world evaluation of the impact of statin intensity on adherence and persistence to therapy: A Scottish population-based study.

AIM: To assess associations between statin intensity and adherence, persistence and discontinuation of statin therapy in Scotland. METHOD: Retrospective cohort study, using linked electronic health records covering a period from January 2009 to December 2016. The study cohort included adult patients (≥18 years) newly initiating statins within Greater Glasgow and Clyde, Scotland. Study outcomes comprised adherence, discontinuation and persistence to treatment, stratified by three exposure groups (high, moderate and low intensity). Discontinuation and persistence were calculated using the refill-gap and anniversary methods, respectively. Proportion of days covered (PDC) was used as a proxy for adherence. Kaplan-Meier survival curves and Cox proportional hazard models were used to evaluate discontinuation, and associations between adherence/persistence and statin intensity were assessed using logistic regression. RESULTS: A total of 73 716 patients with a mean age of 61.4 ± 12.6 years were included; the majority (88.3%) received moderate intensity statins. Discontinuation rates differed between intensity levels, with high-intensity patients less likely to discontinue treatment compared to those on moderate intensity (prior cardiovascular disease [CVD]: HR 0.43 [95% CI 0.34-0.55]; no prior CVD: 0.80 [0.74-0.86]). Persistence declined over time, and high-intensity patients had the highest persistence rates. Overall, 52.6% of patients were adherent to treatment (PDC ≥ 80%), but adherence was considerably higher among high-intensity patients (63.7%). CONCLUSION: High-intensity statins were associated with better persistence and adherence to treatment, but overall long-term persistence and adherence remain a challenge, particularly among patients without prior CVD. This needs addressing.

Confidentiality agreements: a challenge in market regulation.

BACKGROUND: Sustainability and the ability to maintain the right to health, with the guarantee of access to quality medicines and health services, have been a great challenge for countries with universal health systems. The great technological advances bring with it an expressive increase in the expenditures of the health systems, especially those directed towards the acquisition of high-cost drugs, which are still under patent protection, have a high cost and, in some cases, present uncertainties about their effectiveness and safety. As a way of maintaining the proper functioning of the systems and guaranteeing access to these medicines, some countries started to negotiate discounts with manufacturing companies. Pricing agreements have been adopted by developed countries with the objective of reducing their spending on high-cost medicines and, although they represent an opportunity for better negotiation with the industries, they violate the principle of transparency that regulates the world market. However, the existence of confidentiality agreements has meant that the declared prices are not the actual prices, unfairly harming the countries that use these price lists as beacons in their systems. METHODS: Representatives of health, judicial, legislative, patient organizations and academics from eight countries in Latin America and South Korea participated in a meeting in September 2017 in Chile to discuss price confidentiality agreements and the impact on public health policies. During the meeting, participants were presented with a hypothetical case to subsidize the discussion on the topic. Divided into groups, participants should propose recommendations for the problem by pointing out the pros and cons if each proposed recommendation was adopted. The groups were then confronted by a simulated jury and finally issued a single and final recommendation for the problem. RESULTS: The topic was widely discussed and recommendations were raised by the participants. Among them, it is worth noting the elaboration of norms that regulate the negotiations of prices between the countries bringing transparency and harmony in the adopted conducts. In addition, the possible consequences and potential impacts of confidentiality on drug prices and inputs, such as information asymmetry and inequity of access between countries, were pointed out. CONCLUSION: Despite there are efforts to make price negotiations more transparent, there is still no well-established standardization that promotes a well-functioning market. Confidentiality agreements hamper the fairness of access to essential health products.

HEALTH TECHNOLOGY PERFORMANCE ASSESSMENT: REAL-WORLD EVIDENCE FOR PUBLIC HEALTHCARE SUSTAINABILITY.

OBJECTIVES: Health technology financing is often based on randomized controlled trials (RCTs), which are often the same ones used for licensing. Because they are designed to show the best possible results, typically Phase III studies are conducted under ideal and highly controlled conditions. Consequently, it is not surprising that technologies do not always perform in real life in the same way as controlled conditions. Because financing (and price paid) decisions can be made with overestimated results, health authorities need to ask whether health systems achieve the results they expect when they choose to pay for a technology. The optimal way to answer this question is to assess the performance of financed technologies in real-world settings. Health technology performance assessment (HTpA) refers to the systematic evaluation of the properties, effects, and/or impact of a health intervention or health technology in the real world to provide information for investment/disinvestment decisions and clinical guideline updates. The objective is to describe the development and principal aspects of the Guideline for HTpA commissioned by the Brazilian Ministry of Health. METHODS: Our methods used include extensive literature review, refinement with experts across countries, and public consultation. RESULTS: A comprehensive guideline was developed, which has been adopted by the Brazilian government. CONCLUSION: We believe the guideline, with its particular focus on disinvestment, along with the creation of a specific program for HTpA, will allow the institutionalization and continuous improvement of the scientific methods to use real-world evidence to optimize available resources not only in Brazil but across countries.

Acceptability and consumers' willingness to pay for comprehensive medication management services in Brazil.

Aim: Comprehensive medication management (CMM) is a clinical service that aims to optimize the therapeutic results of patients at the individual level. Studies carried out in Brazil and in several parts of the world have found a positive impact of the service, mainly in the resolution of drug therapy problems and in improving clinical outcomes and patients' quality of life. This service is not widespread and its acceptability and willingness to pay were not defined by the population yet. Objective: This work aims to conduct a study with users of private health services to determine the acceptability and willingness to pay for CMM services. Methods: This is a cross-sectional survey conducted through face-to-face interviews, among residents over 18 years of age of the metropolitan region of Belo Horizonte, capital of Minas Gerais State, Brazil. Results: For this study, 563 individuals were interviewed. Most respondents were female (55.1%), had completed high school (46.8%) and were employed (62.5%). The acceptability for the service was 93,25%, and among all respondents, 37 would not accept the service even if it was free. The amount of consumers' willingness to pay for the CMM service was estimated at $17.75 (40.00 BRL). Conclusion: The research results show that most people are willing to pay for the CMM service. This study can contribute to the decision-making regarding the implementation and pricing of the service in Brazil.

On the Judicialization of Health and Access to Medicines in Latin America.

In a context of rapid technological innovation and expensive new products, the paper calls for the generation of real-world data to inform decision-making and an international discussion on the affordability of new medicines, particularly for low- and middle-income countries. Without these, the challenges of health judicialization will continue to grow.

Conventional Synthetic Disease-Modifying Anti-rheumatic Drugs for Psoriatic Arthritis: Findings and Implications From a Patient Centered Longitudinal Study in Brazil.

Background: Conventional synthetic disease-modifying antirheumatic drugs are the first-line treatment to inhibit the progression of psoriatic arthritis. Despite their widespread clinical use, few studies have been conducted to compare these drugs for psoriatic arthritis. Methods: a longitudinal study was carried out based on a centered patient national database in Brazil. Market share of drugs, medication persistence, drug costs, and cost per response were evaluated. Results: a total of 1,999 individuals with psoriatic arthritis were included. Methotrexate was the most used drug (44.4%), followed by leflunomide (40.6%), ciclosporin (8.2%), and sulfasalazine (6.8%). Methotrexate and leflunomide had a greater market share than ciclosporin and sulfasalazine over years. Medication persistence was higher for leflunomide (58.9 and 28.2%), followed by methotrexate (51.6 and 25.4%) at six and 12 months, respectively. Leflunomide was deemed the most expensive drug, with an average annual cost of $317.25, followed by sulfasalazine ($106.47), ciclosporin ($97.64), and methotrexate ($40.23). Methotrexate was the drug being the lowest cost per response. Conclusion: Methotrexate had the best cost per response ratio, owing to its lower cost and a slightly lower proportion of persistent patients when compared to leflunomide. Leflunomide had a slightly higher medication persistence than methotrexate, but it was the most expensive drug.

Acceptability and willingness to pay for a hypothetical vaccine against SARS CoV-2 by the Brazilian consumer: a cross-sectional study and the implications.

INTRODUCTION: The new coronavirus pandemic has appreciably impacted morbidity and mortality, as well as having an economic impact worldwide. New vaccines are a potential way forward to reduce transmission rates and subsequent infection. In Brazil, vaccines are being distributed via the public sector; however, in the future, they will be available in the private market. Information about consumers' willingness to pay (WTP) for a hypothetical vaccine against SARS CoV-2 can help future price setting discussions. METHODS: A cross-sectional study was conducted with consumers in the five regions of Brazil regarding the WTP for a hypothetical vaccine against SARS CoV-2 with a 50% efficacy. RESULTS: A total of 1402 individuals over 18 years of age who declared not having COVID-19 at the time of the survey were interviewed. The acceptability for this hypothetical vaccine was 80.7%. In addition, the amount of WTP by Brazilian consumers for a hypothetical SARS CoV-2 vaccine was estimated at US$ 22.18(120.00 BRL). CONCLUSION: This study can contribute to decision-making to inform potential pricing for a hypothetical SARS CoV-2 vaccine.

Prostate Cancer Survival and Mortality according to a 13-year retrospective cohort study in Brazil: Competing-Risk Analysis.

OBJECTIVE: To analyze cancer-specific mortality (CSM) and other-cause mortality (OCM) among patients with prostate cancer that initiated treatment in the Brazilian Unified Health System (SUS), between 2002 and 2010, in Brazil. METHODS: Retrospective observational study that used the National Oncological Database, which was developed by record-linkage techniques used to integrate data from SUS Information Systems, namely: Outpatient (SIA-SUS), Hospital (SIH-SUS), and Mortality (SIM-SUS). Cancer-specific and other-cause survival probabilities were estimated by the time elapsed between the date of the first treatment until the patients' deaths or the end of the study, from 2002 until 2015. The Fine-Gray model for competing risk was used to estimate factors associated with patients' risk of death. RESULTS: Of the 112,856 studied patients, the average age was 70.5 years, 21% died due to prostate cancer, and 25% due to other causes. Specific survival in 160 months was 75%, and other-cause survival was 67%. For CSM, the main factors associated with patients' risk of death were: stage IV (AHR = 2.91; 95%CI 2.73 - 3.11), systemic treatment (AHR = 2.10; 95%CI 2.00 - 2.22), and combined surgery (AHR = 2.30, 95%CI 2.18 - 2.42). As for OCM, the main factors associated with patients' risk of death were age and comorbidities. CONCLUSION: The analyzed patients with prostate cancer were older and died mainly from other causes, probably due to the presence of comorbidities associated with the tumor.

Sixteen Years of Heart Transplant in an Open Cohort in Brazil: Analysis of Graft Survival of Patients using Immunosuppressants. / Dezesseis Anos de Transplante Cardíaco em Coorte Aberta no Brasil: Análise de Sobrevivência de Pacientes em Uso de Imunossupressores.

BACKGROUND: Heart transplant is the main therapeutic alternative for advanced heart failure patients. Several risk factors affect these patients' survival; however, few studies about the topic are available in Brazil. OBJECTIVES: To review the survival rates of heart transplant patients in the Brazilian Public Health System (Sistema Único de Saúde - SUS) between 2000 and 2015. METHODS: This is a non-concurrent, open cohort study, involving cardiac transplant patients in Brazil. The cumulative survival probability was estimated by the Kaplan-Meier curve, and the curve comparison was done using the Log-Rank test. The Cox model was used to calculate the Hazard-Ratio (HR). Analyses were conducted at the 95% confidence level. RESULTS: The heart transplant survival rate median in Brazil, during the period, was 8.3 years. Each additional year in the recipient's age, the occurrence of infections, and the performance of the surgical procedure in the South Region were associated with a higher risk of graft loss. A higher use ratio of immunosuppressants mycophenolate and azathioprine acted as a protection factor. CONCLUSIONS: The analyses conducted provide the first information about the median survival time in heart transplant patients in Brazil. The difference noticed among the geographical regions may be related to the different treatment protocols adopted in the country, especially in the early 2000s. The rate of mycophenolate and azathioprine use as a protection factor suggests that, despite the absence of differences among therapeutic strategies, use of these drugs may favor survival of certain patients. The study provides robust epidemiological data, which are relevant for public health.

FUNDAMENTO: O transplante cardíaco é a principal alternativa terapêutica para pacientes com insuficiência cardíaca avançada. Diversos fatores de risco influenciam a sobrevivência desses pacientes, entretanto, poucos estudos acerca do tema estão disponíveis no Brasil. OBJETIVOS: Analisar a sobrevivência de pacientes transplantados cardíacos pelo Sistema Único de Saúde no Brasil entre 2000-2015. MÉTODOS: Trata-se de uma coorte não concorrente, aberta, de pacientes transplantados cardíacos no Brasil. A probabilidade acumulada de sobrevivência foi estimada por Kaplan-Meier e a comparação entre as curvas realizada pelo Teste de Log-Rank. O modelo de Cox foi utilizado para calcular o Hazard-Ratio (HR). As análises foram realizadas ao nível de 95% de confiança. RESULTADOS: A mediana de sobrevivência do transplante cardíaco no Brasil no período foi 8,3 anos. Cada ano adicional na idade do receptor, a ocorrência de infecções e a realização do procedimento cirúrgico na região Sul relacionaram-se ao maior risco de perda do enxerto. Maior proporção de uso dos imunossupressores micofenolato e azatioprina atuou como fator protetor. CONCLUSÕES: As análises realizadas fornecem a primeira informação quanto ao tempo de sobrevivência mediana do transplante cardíaco no Brasil. A diferença observada entre as regiões pode estar relacionada aos diferentes protocolos de tratamento adotados no país, principalmente no início dos anos 2000. A proporção de uso de micofenolato e azatioprina como fator protetor sugere que, apesar de não haver diferença entre as estratégias terapêuticas, o uso desses medicamentos pode favorecer a sobrevida de determinados pacientes. O estudo apresenta dados epidemiológicos robustos e importantes para a saúde pública.

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 analyses 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 analyses.

Comorbidities and in-hospital death of viral pneumonia adults admitted to SUS (2002-2015).

OBJECTIVE: To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS: This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS: Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS: Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

Cost-minimization analysis of teledermatology versus conventional care in the Brazilian National Health System.

Aims: Cost-minimization analysis (CMA) comparing the teledermatology service of the State of Santa Catarina, Brazil with the provision of conventional care, from the societal perspective. Patients & methods: All costs related to direct patient care were considered in calculation of outpatient costs. The evaluation was performed using the parameters avoided referrals and profile of hospitalizations. The economic analysis was developed through a decision tree. Results: Totally, 40% of 79,411 tests performed could be managed in primary care, avoiding commuting and expanding the patients' access. The CMA showed the teledermatology service had a cost per patient of US$196.04, and the conventional care of US$245.66. Conclusion: In this scenario, teledermatology proved to be a cost-saving alternative to conventional care, reducing commuting costs.

Lay abstract Diagnosis and treatment of skin diseases through teledermatology avoid patient referrals, improves accessibility to specialized care, as well as the skin care provided by physicians. This study compared the costs of the teledermatology service of the State of Santa Catarina, Brazil with the costs of the provision of conventional care, to check which of them was more efficient. All costs related to direct patient care were considered in the calculation of costs. Totally, 40% of 79,411 dermatological tests performed could be locally managed in primary care, avoiding commuting, and expanding the patients' access to care. The teledermatology service had a cost per patient of US$196.04, compared with the cost of conventional care of US$245.66. In this evaluation, teledermatology proved to be cheaper than conventional care, reducing commuting costs.

Use of medicines by adults in primary care: Survey on health services in Minas Gerais, Brazil. / Uso de medicamentos por adultos na atenção primária: inquérito em serviços de saúde de Minas Gerais, Brasil.

INTRODUCTION: Inappropriate use and increase of health care spending reinforce the need to extend our knowledge about the quality of medication use. OBJECTIVES: To describe and evaluate the profile of medication use in a representative sample of adult users of primary care services in the Unified Health System (SUS) of Minas Gerais. METHOD: Cross-sectional study, with 1,159 interviewees in 104 municipalities and 253 health care services. Data on sociodemographic characteristics, health conditions and use of medicines were collected, and these variables were stratified by age group. Univariate and multivariate analyses, using logistic regression, were conducted to identify predictors of self-medication. We set a significance level of 5% for all tests. RESULTS: The prevalence of medication use was 81.8%, with an average of 2.67 medicines per user, which increased with age. The most used drugs were losartan, hydrochlorothiazide and simvastatin, which differed between age groups. Significant self-medication was observed not only in young adults but also in the elderly. The predictors of self-medication were: being a young adult, having a higher level of education, not having chronic diseases, having worse self-perception of health and not adhering to prescription drugs. Young and elderly adults showed characteristics that made them more vulnerable in relation to the rational use of medicines. CONCLUSION: This study can contribute to improving primary care, where it identified problems related to the extent of medication use, especially among young adults and the elderly in Minas Gerais.

Funding and Service Organization to Achieve Universal Health Coverage for Medicines: An Economic Evaluation of the Best Investment and Service Organization for the Brazilian Scenario.

BACKGROUND: There are many health benefits since 31 years after the foundation of the National Health Service (NHS) in Brazil, especially the increase in life expectancy. However, family-income inequalities, insufficient funding, and suboptimal private sector-public sector collaboration are still areas for improvement. The efforts of Brazil to achieve universal health coverage (UHC) for medicines have resulted in increased public financing of medicines and their availability, reducing avoidable hospitalization and mortality. However, lack of access to medicines still remains. Due to historical reasons, pharmaceutical service organization in developing countries may have important differences from high-income countries. In some cases, developing countries finance and promote medicine access by using the public infrastructure of health care/medical units as dispensing sites and cover all costs of medicines dispensed. In contrast, many high-income countries use private community pharmacies and cover the costs of medicines dispensed plus a fee, which includes all logistic costs. In this study, we will undertake an economic evaluation to understand the funding needs of the Brazilian NHS to reduce inequalities in access to medicines through adopting a pharmaceutical service organization similar to that seen in many high-income countries with hiring/accrediting private pharmacies. METHODS: We performed an economic evaluation of a model to provide access to medicines within public funds based on a decision tree model with two alternative scenarios public pharmacies (NHS, state-owned facilities) versus private pharmacies (NHS, agreements). The analysis assumed the perspective of the NHS. We identified the types of resources consumed, the amount, and costs in both scenarios. We also performed a budget impact forecast to estimate the incremental funding required to reduce inequalities in access to essential medicines in Brazil. FINDINGS: The model without rebates for medicines estimated an incremental cost of US$3.1 billion in purchasing power parity (PPP) but with an increase in the average availability of medicines from 65% to 90% for citizens across the country irrespective of family income. This amount places the NHS in a very good position to negotiate extensive rebates without the need for external reference pricing for government purchases. Forecast scenarios above 35% rebates place the alternative of hiring private pharmacies as dominant. Higher rebate rates are feasible and may lead to savings of more than US$1.3 billion per year (30%). The impact of incremental funding is related to medicine access improvement of 25% in the second year when paying by dispensing fee. The estimate of the incremental budget in five years would be US$4.8 billion PPP. We have yet to explore the potential reduction in hospital and outpatient costs, as well as in lawsuits, with increased availability with the yearly expenses for these at US$9 billion and US$1.4 billion PPP respectively in 2017. INTERPRETATION: The results of the economic evaluation demonstrate potential savings for the NHS and society. Achieving UHC for medicines reduces household expenses with health costs, health litigation, outpatient care, hospitalization, and mortality. An optimal private sector-public sector collaboration model with private community pharmacy accreditation is economically dominant with a feasible medicine price negotiation. The results show the potential to improve access to medicines by 25% for all income classes. This is most beneficial to the poorest families, whose medicines account for 76% of their total health expenses, with potential savings of lives and public resources.

Effectiveness of Maintenance Immunosuppression Therapies in a Matched-Pair Analysis Cohort of 16 Years of Renal Transplant in the Brazilian National Health System.

The 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 of follow-up with real-world data from the Brazilian National Health System (SUS). This was a retrospective study of 2318 SUS patients after renal transplantion. Patients were propensity score-matched (1:1) by sex, age, type and year of transplantation. Kaplan-Meier analysis 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. 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 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 the cyclosporine plus azathioprine regimen as a potential first line option, along with others.

Comparative persistence of anti-tumor necrosis factor therapy in ankylosing spondylitis patients: a multicenter international study.

Objective: To evaluate persistence on conventional DMARDs (cDMARDs) and anti-TNF therapies, and to identify potential determinants of discontinuation among individuals with ankylosing spondylitis (AS) living in Brazil and Quebec, Canada.Methods: We conducted a cohort study of AS patients using health administrative data (2010-2015). One-year and 2-year persistence rates were assessed. Cox regression was used to identify potential determinants of therapy discontinuation.Results: One-year persistence was less likely in Brazil for both anti-TNF and cDMARDs (Brazil: 62.1 and 30.7%, Quebec: 66.9 and 67.0%). The 2-year persistence rates were lower for both anti-TNF and cDMARD, but remained higher in Quebec (Brazil: 47.9 and 18.1%, Quebec: 51.5 and 53.5%). In multivariate Cox regression analysis, age, sex and comorbidities were associated with persistence in both countries. In Quebec, persistence did not differ between rural and urban regions or with socioeconomic status. While in Brazil, patients in regions with higher Human Development Index and those in cities with lower Gini index were less likely to discontinue therapy.Conclusions: Canadian AS patients were more likely to persist on therapy compared to Brazilian patients, although rates were lower at 2 years in both countries. Socioeconomic disparity in persistence was found in Brazil, but not in Quebec.

Integrative Review of Managed Entry Agreements: Chances and Limitations.

BACKGROUND AND OBJECTIVE: Managed entry agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high-priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective of this article is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high- and middle-income countries. METHODS: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior-level co-authors including key South American markets. It also involved senior-level decision makers and advisers providing guidance on the potential advantages and disadvantages of MEAs and ways forward. RESULTS: Twenty-five studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%) and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. CONCLUSIONS: We are likely to see a growth in MEAs with the continual launch of new high-priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome-based MEAs could be an important tool to improve access to new innovative medicines, there are critical issues to address. Comparing knowledge, experiences, and practices across countries is crucial to guide high- and middle-income countries when designing their future MEAs.

The Price of Substitute Technologies.

BACKGROUND: Only a small share of new drugs is truly innovative; 85% to 90% of all new health technologies have little or no advantage over existing therapeutic alternatives. Health economic evaluations can be used to induce acceptable prices for new technologies through threshold pricing. OBJECTIVE: This work discusses a cost-effectiveness threshold (λ) to be applied to the price regulation of substitute technologies. METHODS: Considering that substitute technologies add only small marginal benefits in terms of innovation or ethical considerations to the system, it does not make sense to allow a loss of efficiency to list them. It has been postulated that the threshold calculated from opportunity costs (κ) represents its maximum possible value and that there must be a threshold (ß) that maximizes consumer surplus. For a substitute technology to be listed, the cost of treatment associated with it must be lower than the cost of treatment of the incumbent technology added to the difference in effectiveness priced at the threshold. RESULTS: There is no reason for us to believe that the oligopolistic pharmaceutical market is currently charging prices at the cost of production. That way, the cost-effectiveness ratio of the incumbent technology, when lower than κ, is shown through a deductive process to be a plausible estimate for λ that fulfills the objective of maximizing consumer benefit, granting producers a part of the combined surplus to stimulate research and development; that is, it would be between ß and κ. CONCLUSION: In conclusion, the price of substitute technologies should be limited by the cost-effectiveness ratio of the incumbent technology.

Consumer willingness to pay for a hypothetical Zika vaccine in Brazil and the implications.

ABSTRACT  Background: Zika virus is a newly emerging infection, associated with increasingly large outbreaks especially in tropical countries such as Brazil. A future Zika vaccine can contribute to decreasing the number of cases and associated complications. Information about consumers' willingness to pay (WTP) for a hypothetical Zika vaccine can help price setting discussions in the future in Brazil, starting with the private market. METHODS: A cross-sectional study conducted among residents of Minas Gerais, Brazil, regarding their WTP for a hypothetical Zika Vaccine. The mean effective protection was 80%, with the possibility of some local and systemic side- effects. RESULTS: 517 people were interviewed. However, 28 would not be vaccinated even if the vaccine was free. Most of the resultant interviewees (489) were female (58.2%), had completed high school (49.7%), were employed (71.2%), had private health insurance (52.7%), and did not have Zika (96.9%). The median individual maximum WTP for this hypothetical Zika vaccine (one dose) was US$31.34 (BRL100.00). CONCLUSION: Such discussions regarding WTP can contribute to decision-making about prices once a Zika vaccine becomes available in Brazil alongside other ongoing programs to control the virus.