Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison.

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.

Public procurement of antineoplastic agents used for treating breast cancer in Brazil between 2013 and 2019.

BACKGROUND: Breast cancer is the most common cancer among women in Brazil and the country's public health care system is the main care provider. Timely treatment can increase the chance of cure, prevent metastasis and improve quality of life. Effective public procurement of antineoplastic agents can therefore improve access to drug therapy. This study investigates patterns in the procurement of selected antineoplastic agents used for treating breast cancer by public bodies and avoidable expenditure on these drugs between January 2013 and December 2019. METHODS: We selected antineoplastic agents used for adjuvant or preoperative chemotherapy listed in the 2018 Breast Cancer Diagnosis and Treatment Guidelines and included in category L of the WHO Anatomical Therapeutic Chemical classification system. We analyzed regular purchases of antineoplastic agents registered in the Integrated General Services Administration System (SIASG), considering purchased quantity, unit price, date of purchase and procuring entity. Prices were inflation-adjusted to July 2019 based on the National Consumer Price Index. RESULTS: A total of 10 antineoplastic agents were selected. Trastuzumab and tamoxifen accounted for the largest share of total spending and largest volume of purchases, respectively. The Ministry of Education was the largest purchaser in volume terms of all the drugs studied, except trastuzumab 440 mg, where the category "Other Institutions" accounted for most purchases, and vinorelbine 20 mg, where the Ministry of Health made most purchases. The category "Other Institutions" accounted for the largest share of total spending. Total avoidable expenditure was R$99,130,645. Prices paid for medicines and avoidable expenditure were highest in the Ministry of Defense. CONCLUSIONS: The differences observed in the performance of different categories of buyers as to amounts purchased and prices practiced for antineoplastic agents could be reduced by employing strategies to expand the centralization of purchases, resulting in expanded access to breast cancer medicines in the public sector.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Cancer care in Brazil: structure and geographical distribution.

BACKGROUND: The organisation and systematisation of health actions and services are essential to ensure patient safety and the effectiveness and efficiency of cancer care. The objective of this study was to analyse the structure of cancer care envisaged in Brazilian norms, describe the types of accreditations of cancer services and their geographic distribution, and determine the planning and evaluation parameters used to qualify the health units that provide cancer care in Brazil. METHODS: This observational study identified the current organisation of cancer care and other health services that are accredited by Brazil's national health system (SUS) for cancer treatment as of February 2017. The following information was collected from the current norms and the National Registry of Health Establishments: geographic location, type of accreditation, type of care, and hospital classification according to annual data of the number of cancer surgeries. The adequacy of the number of licensed units relative to population size was assessed. The analysis considered the facilitative or restrictive nature of policies based on the available rules and resources. RESULTS: The analysis of the norms indicated that these documents serve as structuring rules and resources for developing and implementing cancer care policies in Brazil. A total of 299 high-complexity oncology services were identified in facilities located in 173 (3.1%) municipalities. In some states, there were no authorised services in radiotherapy, paediatric oncology and/or haematology-oncology. There was a significant deficit in accredited oncology services. CONCLUSIONS: The parameters that have been used to assess the need for accredited cancer services in Brazil are widely questioned because the best basis of calculation is the incidence of cancer or disease burden rather than population size. The results indicate that the availability of cancer services is insufficient and the organisation of the cancer care network needs to be improved in Brazil.

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.

[Clinical trials and licensing of monoclonal antibodies and biological medicines for cancer treatment in Brazil]. / Os ensaios clínicos e o registro de anticorpos monoclonais e biomedicamentos oncológicos no Brasil.

Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, ClinicalTrials.gov and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA). Results Nine trials (eight phase III and one phase II) were selected. All had a randomized, controlled design. Two trials were double-blind and seven were open-label, and all recruited adults (≥ 18 years of age) of both sexes. The mean number of patients recruited per trial was 985.2. Seven trials had been completed and two had been terminated early. All trials were sponsored by non-Brazilian pharmaceutical companies and focused on renal, colorectal, gastric, and lung (non-small cell) cancer, non-Hodgkin lymphoma, and melanoma, and involved the use of cetuximab, figitumumab, ipilimumab, rituximab, bevacizumab and interferon alfa-2a. The FDA was the first agency to license the drugs, followed by EMA, except in the case of interferon alfa-2a, which was not approved by EMA. We were unable to determine the year of drug licensing by Anvisa in Brazil. Conclusions The participation of Brazil in clinical trials of monoclonal antibodies and biological medications for cancer treatment is insufficient. The quality of the available information on trials, history of licensing, and other relevant elements is a major weakness of the sources reviewed.

Psychoactive substance consumption after the Fundão dam mine tailing disaster in Minas Gerais State, Brazil.

Disasters cause changes in morbidity, mortality, and medicine use. Brazil is one of the main producers of mineral ores at great environmental cost. Mine tailings are stored in dams and ruptures have led to major disasters. We investigated the consumption of psychoactive medicines in the municipalities affected by the Fundão dam disaster in Minas Gerais State. An ecological study was carried out on drug consumption, estimated using public purchases in Minas Gerais and dispensing data from private retail pharmacies. Consumption (in number of defined daily doses/100,000 inhabitants per day) was analyzed descriptively in eight municipalities, stratified according to consumption level during a 25-month period. Six comparisons of mean consumption values for both data sets were done for pre- and post-disaster periods. The means of medicine consumption before and after the event were plotted and linear trends were added. Public purchase data evinced high consumption levels. Only pharmaceutical retail showed significant differences between the strata in the pre-disaster versus two post-disaster periods. Smaller municipalities showed an increase in consumption 15 months after the disaster. Clonazepam led the way in pharmaceutical retail consumption, followed by fluoxetine. Medicines showed an upward trend after the disaster. The high public provision may have stifled significant consumption patterns of psychoactive drugs; however, peak consumption were observed in private retail, suggesting a modification in use patterns after the disaster. The decrease in consumption immediately after the event was probably related to lower care-seeking behavior on the part of the population, and significant peaks after the disaster may reflect economic consequences of it.

First use of antineoplastic agents in women with breast cancer in the state of Rio de Janeiro, Brazil.

Context: Breast cancer is the most common cancer, except for non-melanoma skin cancer, among women in Brazil and worldwide. Breast cancer treatment involves surgery, radiotherapy and chemotherapy, which is used in 70% of patients. This study analyzes the utilization of antineoplastic agents among women undergoing their first round of chemotherapy in Brazil's public health system (SUS) in the state of Rio de Janeiro. Methods: Data from the SUS Outpatient Information System's authorizations for high-complexity outpatient procedures (APACs) billed between January 2013 and December 2019 were extracted, and three datasets were created: all type 1 and type 2 APACs (including all chemotherapy procedures performed); all type 1 APACs; and first type 1 APACs (containing data only for the first round of breast cancer chemotherapy). Names of antineoplastic agents were standardized to enable the subsequent classification of therapy regimens, mitigating limitations related to data quality. Absolute and relative frequencies were used to describe sociodemographic, clinical and treatment characteristics, therapy regimen and supportive drugs. Results: We analyzed 23,232 records of women undergoing their first round of chemotherapy. There was a progressive increase in the number of procedures over time. Women were predominantly white, lived in the capital and close to the treatment center. Most had stage 3 cancer at diagnosis (50.51%) and a significant proportion had regional lymph node invasion (37.9%). The most commonly used chemotherapy regimens were TAC (docetaxel, doxorubicine, cyclophosphamide) (21.05%) and and cyclophosphamide (17.71%), followed by tamoxifen (15.65%) and anastrozole (12.94%). Supportive drugs were prescribed to 386 women and zoledronic acid was predominant (59.58%). Conclusion: The findings point to important bottlenecks and possible inequities in access to treatment and medicine utilization for breast cancer patients in Brazil. Efforts to improve breast cancer treatment and prevention should not only focus on interventions at the individual level but address the disease as a public health problem. The study focused on women undergoing their first round of treatment, providing valuable insight into patient and treatment characteristics to inform policy decisions.

[Data processing of the Brazilian National System of Controlled Product Management for drug utilization research with antimicrobials]. / Tratamento de dados do Sistema Nacional de Gerenciamento de Produtos Controlados para estudos de utilização de medicamentos com antimicrobianos.

The Brazilian National System of Controlled Product Management (SNGPC) stores data on the dispensing of manufactured and compounded drugs and pharmaceutical inputs, whether controlled and antimicrobial, based on the records of private pharmacies and drugstores. This study assessed the quality of SNGPC data from the dispensing records of manufactured antibiotics, aiming to propose their use in drug utilization researchs (DURs), with a descriptive and retrospective design, analyzing the raw dataset of the SNGPC from January 2014 to December 2020. A total of 475,805,207 drug-dispensing records were collected. On average, antibiotics corresponded to 54.5% of the total records. The quality dimension "unreported" was systematically identified in the variables "active ingredient", "sex", "age" and "ICD-10". The amount of vials/bottles and packages ranged from one to 536 units and the amount of pharmaceutical inputs dispensed, from one to 7,500 units. Results show that 25% of the records exceed an individual therapy and the SNGPC has no critical mechanism to avoid dispensations outside the therapeutic standard for the class. Despite vulnerabilities due to data quality, which can be overcome, the SNGPC allows for the construction of different analytical plans, involving time and other aggregations, in the analysis of community use of antimicrobials and controlled drugs, which makes it a powerful source of data for DUR.

O Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC) armazena dados de dispensação de medicamentos industrializados, manipulados e insumos farmacêuticos sob controle especial e antimicrobianos, a partir dos registros de farmácias e drogarias privadas. Este trabalho explorou a qualidade dos dados inseridos no SNGPC, a partir dos registros de dispensação de antibióticos industrializados, com o objetivo de propor seu emprego em estudos de utilização de medicamentos (DUR). A pesquisa foi desenvolvida por meio de desenho descritivo e retrospectivo, examinando o conjunto dados brutos do sistema, para o período de janeiro de 2014 a dezembro de 2020. Um total de 475.805.207 registros de dispensação de medicamentos foi coletado. Os antibióticos corresponderam em média a 54,5% do total de registros. A dimensão de qualidade "não informado" foi identificada, sistematicamente, nas variáveis "princípio ativo", "sexo", "idade" e "CID-10". As quantidades de frascos e caixas variaram de 1 a 536 unidades, e as quantidades de formas farmacêuticas dispensadas de 1 a 7.500 unidades. Os resultados mostram que 25% dos registros extrapolam uma terapia individual e que o sistema não apresenta um mecanismo de crítica para evitar dispensações não conformes ao padrão terapêutico para a classe. Apesar das vulnerabilidades decorrentes da qualidade dos dados, que podem ser superadas, o SNGPC possibilita construir diferentes planos analíticos, envolvendo tempo e outras agregações, na investigação de uso comunitário de antimicrobianos e medicamentos sob controle especial, o que faz dele uma potente fonte de dados para DUR.

El Sistema Nacional de Gestión de Productos Controlados (SNGPC) almacena datos sobre la dispensación de medicamentos industrializados, manipulados, insumos farmacéuticos bajo control especial y de antimicrobianos con base en los registros de farmacias y de boticas privadas. Este trabajo analizó la calidad de los datos ingresados en el SNGPC relacionados a los registros de la dispensación de antibióticos industrializados, para proponer su posible aplicación en estudios sobre el uso de medicamentos (DUR); para ello, realizó un análisis descriptivo y retrospectivo del conjunto de datos brutos para el periodo de enero de 2014 a diciembre de 2020. Se recogieron un total de 475.805.207 registros de dispensación de medicamentos. Los antibióticos correspondieron en promedio al 54,5% del total de los registros. La dimensión de calidad "no informado" se identificó sistemáticamente en las variables "principio activo", "sexo", "edad" y "CIE-10". Las cantidades de viales y cajas oscilaron entre 1 y 536 unidades, y las cantidades de formas farmacéuticas dispensadas entre 1 y 7.500 unidades. Los resultados muestran que el 25% de los registros exceden una terapia individual y que el sistema no tiene un mecanismo crítico para evitar la dispensación que no se ajusta al patrón terapéutico de la clase. A pesar de las vulnerabilidades derivadas de la calidad de los datos, que pueden ser superadas, el SNGPC permite la construcción de diferentes planes analíticos, involucrando tiempo y otras agregaciones, en la investigación del uso comunitario de antimicrobianos y medicamentos bajo control especial, lo que hace que el Sistema sea una potente fuente de datos para DUR.

The incorporation of the 3HP regimen for tuberculosis preventive treatment in the Brazilian health system: a secondary-database nationwide analysis.

Introduction: The recommendation of rifampin-based shorter - and safer - regimens for tuberculosis preventive treatment (TPT) is progressively replacing monotherapy with isoniazid by different countries. The Brazilian Ministry of Health (MoH) approved the incorporation of the Rifapentine + isoniazid regimen (3HP) at the end of 2020, with free distribution in the Brazilian Unified Health System (SUS) started from the last quarter of 2021. The objectives were to describe the implementation of the IL-TB System (Information System of TPT Notification) and uptake of Rifapentine + isoniazid (3HP) and Isoniazid (6H or 9H) in Brazil. Methods: A quantitative observational and descriptive was performed using the IL-TB National System as the main data source, from January 2018 to December 2022. Results and discussion: There was a steady increase of the number of TPT prescription quarterly throughout the period, which reflects the implementation of the system itself and the progressive adherence of the health system to the non-compulsory notification of new TPT. The substitution of isoniazid (6H or 9H) by 3HP is progressing. The 3HP regimen represented less than 4% of the total administered by the end of 2021, reaching around 30% in the second half of 2022 and 40% in the last quarters of 2022. The study points not only to the need to expand TPT in the country, but also to accelerate 3HP uptake and to encourage the municipalities to notify to the IL-TB system, since there is still a high level of underreporting.

[Strategies adopted to ensure the rights of people with cancer in the Brazilian Unified Health System (SUS)]. / Estratégias adotadas para a garantia dos direitos da pessoa com câncer no âmbito Sistema Único de Saúde (SUS).

This study was based on Giddens' Structuration Theory and aimed to analyze strategies adopted to ensure the rights of people with cancer in five Brazilian municipalities, anchored on the experience of managers and health professionals within the Brazilian Unified Health System (SUS). A multiple-case study design was conducted. The municipality was the unit of analysis and oncology care-certified facilities were established as analytical sub-units. We analyzed the strategic behavior of ten managers and 15 health professionals from interviews. The results were systematized according to care, legal and social dimensions. The relevant elements expressed were the need to expand and organize the diagnostic and therapeutic cancer care network; the concern with the large number of lawsuits, both in light of economic sustainability of the health system and because of the promotion of inequalities; and the low resoluteness of social benefits, as they do not meet all people's needs. The adopted measures are considered insufficient to ensure the rights of people with cancer in the Brazilian Unified Health System.

Este estudo, fundamentado na Teoria da Estruturação de Giddens, buscou analisar as estratégias adotadas para garantir os direitos das pessoas com câncer em cinco municípios brasileiros, a partir da experiência de gestores e profissionais de saúde no contexto do Sistema Único de Saúde. Foi conduzido um estudo de casos múltiplos. A unidade de análise foi o município e a subunidade foi a unidade habilitada de atenção oncológica. Foi realizada a análise de conduta estratégica de dez gestores e 15 profissionais de saúde, a partir de entrevistas. Os resultados foram sistematizados em três dimensões: assistencial, judicial e social. Destacaram-se: a necessidade de expansão e organização da rede assistencial diagnóstica e terapêutica; a preocupação com o grande número de demandas judiciais, tanto pela sustentabilidade econômica do sistema de saúde, quanto pela promoção de iniquidades; a pouca resolutividade dos benefícios sociais, uma vez que não atendem a todos aqueles que necessitam. A percepção é de que as medidas adotadas são insuficientes para garantir os direitos da pessoa com câncer no sistema de saúde brasileiro.

Knowledge and risk perception of vulnerable women on Zika virus infection at primary health care level in Brazil.

Vulnerable low-income groups were most affected by Zika virus (ZIKV)-related neurologic syndrome during the 2014-2016 outbreak in Brazil. Major ZIKV infection response took place in Primary Health Care (PHC), including prevention strategies and risk communication. We aimed to detect knowledge and beliefs, as well as knowledge gaps among vulnerable women at the PHC level. A cross-sectional study was carried out in two low-income urban community settings: a small municipality with few ZIKV infection cases and a large municipality hard-hit by the epidemic. An open-ended data collection instrument centred on ZIKV infection knowledge, sources of information, possible causes, symptoms, risk perception, consequences for pregnant women and PHC point-of-care communication was developed. Interviews were recorded, transcribed and content coded for thematic analysis. Most of the seventy-nine respondents had some knowledge of the disease, acknowledging the vector as the source of infection and associating microcephaly with the disease, but distanced themselves from possible ZIKV infection and related risk. PHC services in both communities did not adequately communicate risk for women and children. In an uncertain future scenario as to disease re-emergence, awareness may be diminished and acquired knowledge lost, configuring a public health challenge that must be overcome.

Consumption of antidepressants and economic austerity in Brazil.

OBJECTIVE: To describe consumption of antidepressants in Brazil through dispensing data from pharmacy retail outlets, in between 2011 and 2017, and explore the relationship between consumption patterns and changing economic context during this period. METHODS: A time-series analysis of dispensing data from pharmacy retail outlets was carried out considering 10 commonly used antidepressants. DDDs/1000 inhabitants/year for each drug were calculated for each quarter. Ttime-series graphs were constructed to analyze the volumes of drugs purchasedRelationship between economic context and consumption was assessed using the following indicators: annual percent change in Gross Domestic Product (GDP), public debt (% of GDP), and annual net savings (in billions of Brazilian reais - BRL). RESULTS: Overall consumption of antidepressants increased over the study period despite a sharp fall of -3.55% in annual percent change in GDP, negative net annual savings of -53.568 BRL, and an increase in public debt exceeding 32% of the GDP during the economic crisis of 2015. CONCLUSION: Consumption of antidepressants from pharmacy retail outlets increased even within a context of economic crisis, which may be a reflection of the disease burden in Brazil. Health budget cuts due to the economic crisis may be directing users to out-of-pocket expenses, deepening social inequalities.

[Essential drugs and pharmaceutical care: reflection on the access to drugs through lawsuits in Brazil]. / Essencialidade e assistência farmacêutica: considerações sobre o acesso a medicamentos mediante ações judiciais no Brasil.

The guarantee of pharmaceutical care as a legal right established by the Brazilian federal constitution of 1988 led to an increase in lawsuits to put that right into practice. This phenomenon has been dubbed the judicialization of pharmaceutical care. Studies on this topic have revealed, on the one hand, deficiencies in the access of Unified Health Care (SUS) users to drugs included in Ministry of Health pharmaceutical care lists, and, on the other hand, limitations of the legal system to deal with the situation. The present article addresses these issues in the context of the conceptual framework that supports the Brazilian drug policy and pharmaceutical care policy, especially the notions of essential drugs and allocation of scarce resources.

COVID-19 and the medicines regulation challenges in times of pandemic. / COVID-19 e os desafios para a regulação de medicamentos em tempos de pandemia.

The SARS-CoV-2 pandemic has brought challenges related to prevention, protection and care. Coping strategies, such as social distancing, individual protection for the population and workers, increase in the number of intensive care beds, provision of human resources and equipment are necessary actions. However, there are yet no specific effective and safe medicines that justify their use. The challenge imposed on the regulatory framework for medicines is aimed at providing timely access to medicines capable of modifying the course of the disease and leading to better treatment outcomes, with health safety. Regulatory agencies must protect the health by assessing the actual benefits and harms of the medicines under these specific conditions. The article discusses the main regulatory challenges and response of regulatory agencies to the demands imposed by the COVID-19 pandemic, especially, drug development strategies and regulatory strategies related to off-label use. Emergency drug use authorization and alternatives for extended/compassionate use are addressed, as well as clinical trials, safety assessment and monitoring of adverse events.

A pandemia de SARS-CoV-2 trouxe desafios relacionados à prevenção, proteção e cuidado. Estratégias de enfrentamento, como distanciamento social, medidas de proteção individual da população e trabalhadores, ampliação dos leitos de terapia intensiva, disponibilização de recursos humanos e equipamentos são ações necessárias. Não há, ainda, medicamentos específicos com eficácia e segurança que justifiquem sua utilização. O desafio imposto ao marco regulatório de medicamentos volta-se para o acesso tempestivo a medicamentos capazes de modificar o curso da doença e conduzir a melhores desfechos no tratamento, com segurança sanitária. Cabe às agências reguladoras a proteção da saúde com a atribuição de avaliar os reais benefícios e malefícios dos medicamentos nestas condições especificas. O artigo apresenta as ações das agências reguladoras e discute os desafios na implementação da política regulatória de medicamentos frente às exigências impostas pela pandemia de COVID-19. São abordadas, especialmente, estratégias de desenvolvimento de fármacos e estratégias regulatórias sobre a indicação de uso off label, do uso emergencial de medicamentos e das alternativas de uso extendido/compassivo, bem como da realização de ensaios clínicos e da avaliação da segurança e monitoramento de eventos adversos.

Data Sources for Drug Utilization Research in Brazil-DUR-BRA Study.

Background: In Brazil, studies that map electronic healthcare databases in order to assess their suitability for use in pharmacoepidemiologic research are lacking. We aimed to identify, catalogue, and characterize Brazilian data sources for Drug Utilization Research (DUR). Methods: The present study is part of the project entitled, "Publicly Available Data Sources for Drug Utilization Research in Latin American (LatAm) Countries." A network of Brazilian health experts was assembled to map secondary administrative data from healthcare organizations that might provide information related to medication use. A multi-phase approach including internet search of institutional government websites, traditional bibliographic databases, and experts' input was used for mapping the data sources. The reviewers searched, screened and selected the data sources independently; disagreements were resolved by consensus. Data sources were grouped into the following categories: 1) automated databases; 2) Electronic Medical Records (EMR); 3) national surveys or datasets; 4) adverse event reporting systems; and 5) others. Each data source was characterized by accessibility, geographic granularity, setting, type of data (aggregate or individual-level), and years of coverage. We also searched for publications related to each data source. Results: A total of 62 data sources were identified and screened; 38 met the eligibility criteria for inclusion and were fully characterized. We grouped 23 (60%) as automated databases, four (11%) as adverse event reporting systems, four (11%) as EMRs, three (8%) as national surveys or datasets, and four (11%) as other types. Eighteen (47%) were classified as publicly and conveniently accessible online; providing information at national level. Most of them offered more than 5 years of comprehensive data coverage, and presented data at both the individual and aggregated levels. No information about population coverage was found. Drug coding is not uniform; each data source has its own coding system, depending on the purpose of the data. At least one scientific publication was found for each publicly available data source. Conclusions: There are several types of data sources for DUR in Brazil, but a uniform system for drug classification and data quality evaluation does not exist. The extent of population covered by year is unknown. Our comprehensive and structured inventory reveals a need for full characterization of these data sources.

Public financing of human insulins in Brazil: 2009-2017.

BACKGROUND: From 2006 to 2017, the Brazilian federal government provided free of charge traditional insulins for diabetes treatment. This involved public tendering by the Department of Health Logistics of the Ministry of Health (DLOG-MOH) and the reimbursement after direct contracting for supply with commercial private retailers (Brazilian Popular Pharmacy Program - PFPB). OBJECTIVE: We aim to describe the budget of the Brazilian federal government committed to for the acquisition of insulin, as well as corresponding prices and treatment availability from 2009 to 2017. METHODS: Insulin volume and expenditure data were obtained in official administrative databases and in the Electronic System of the Information Service to Citizens. Data were analyzed according to the total provision by the federal government, DLOG-MOH and PFPB. Moreover, data were presented according to insulin type. Volumes were calculated in number of defined daily doses (DDD)/1,000 inhabitants/day. RESULTS: Budgetary commitments due to insulin over nine years amounted to U$1,027 billion in 2017, with an approximate average of U$114.1 million per year. DLOG-MOH was the main insulin provider, despite the increase in PFPB provision along period. DLOG-MOH and PFBP together provided an average of 6.08 DDD/1000 inhabitants/day for nine years. Average prices in PFPB were higher than those in the DLOG series, with a downward trend over the years, narrowing to 2.7 times in 2017, when compared to 2009. CONCLUSIONS: Brazil evidenced a moderately sustainable and effective, albeit imperfect, policy for public provision of traditional insulins in the period preceding mandatory free supply of insulin analogues. Future studies must address treatment availability and financial sustainability in the new scenario.

[Profile of antineoplastic medication among indigenous people treated in the Brazilian Unified National Health System]. / Perfil de utilização de medicamentos antineoplásicos entre indígenas atendidos pelo Sistema Único de Saúde.

Brazil has an estimated 900,000 indigenous people (0.4% of the country's population), belonging to more than 300 different ethnic groups. However, information is scarce on cancer epidemiology and the antineoplastic drugs used in treatment of these individuals. The study's objectives are to identify the antineoplastic drugs used and to describe the profile of use of these drugs in the indigenous population treated in Brazil, as well as to describe the patients' epidemiological profile. An ecological study was performed involving outpatient chemotherapy care from January 2014 to December 2018 throughout Brazil. The data source was the Outpatient Information System of the Brazilian Health Informatics Department, considering only Authorizations for High-Complexity Chemotherapy Procedures. We identified 2,425 authorizations for chemotherapy procedures for treatment of indigenous patients. Of these, 2,292 authorizations for a total of 210 individuals were analyzed. We found an increase in the number of authorizations and of indigenous persons receiving chemotherapy over the period, with a higher concentration of individuals living in and receiving treatment in the South of Brazil, plus a wide diversity in the types of diagnosed tumors (n = 63) and of treatment regimen used during the treatment (n = 107). The current study provided a new overview of the epidemiological profile of indigenous patients receiving chemotherapy in the Brazilian Unified National Health System. The findings help fill a current knowledge gap on indigenous people's health in Brazil.

Estima-se que no Brasil existam cerca de 900 mil indígenas (0,4% da população do país) pertencentes a mais de 300 etnias diferentes. Porém, informações sobre a epidemiologia do câncer e sobre os medicamentos antineoplásicos utilizados no tratamento desses indivíduos são escassas. Os objetivos do presente estudo são identificar os medicamentos antineoplásicos utilizados e descrever o perfil de utilização deles na população indígena tratada no Brasil, além de descrever o perfil epidemiológico dos usuários. Foi realizado um estudo do tipo ecológico que envolveu os atendimentos ambulatoriais de quimioterapia, realizados no período de janeiro de 2014 e dezembro de 2018, em todo o Brasil. A fonte de coleta dos dados utilizada foi o Sistema de Informação Ambulatorial, do Departamento de Informática do SUS, considerando apenas as Autorizações de Procedimentos de Alta Complexidade para Quimioterapia. Foram identificadas 2.425 autorizações para procedimentos de quimioterapia destinadas ao tratamento de pacientes indígenas. Um total de 2.292 autorizações, para um total de 210 indivíduos, foram analisadas. Observou-se um aumento do número de autorizações e de indígenas em uso de quimioterapia ao longo do período, maior concentração de indivíduos residentes e em tratamento na Região Sul do país, diversidade de tipos de tumores diagnosticados (n = 63) e de esquemas terapêuticos utilizados durante o tratamento (n = 107). O presente estudo trouxe um novo panorama sobre o perfil epidemiológico dos usuários indígenas sob tratamento quimioterápico no Sistema Único de Saúde. Os achados contribuem para o preenchimento da atual lacuna de conhecimento a respeito da saúde indígena no Brasil.

Se estima que en Brasil existan cerca de 900 mil indígenas (0,4% de la población del país) pertenecientes a más de 300 etnias diferentes. No obstante, la información sobre la epidemiología del cáncer y medicamentos antineoplásicos utilizados en el tratamiento de esos individuos es escasa. Los objetivos del presente estudio son identificar los medicamentos antineoplásicos utilizados, y describir el perfil de utilización de esos medicamentos en la población indígena tratada en Brasil, así como describir el perfil epidemiológico de los usuarios. Se realizó un estudio de tipo ecológico, implicando la atención ambulatoria con quimioterapia, realizada en el período de enero de 2014 y diciembre de 2018 en todo Brasil. La fuente de recogida de datos utilizada fue el Sistema de Información Ambulatoria, del Departamento de Informática del SUS, considerando solamente las Autorizaciones de Procedimientos de Alta Complejidad para Quimioterapia. Se identificaron 2.425 autorizaciones para procedimientos de quimioterapia, destinadas al tratamiento de pacientes indígenas. Se analizaron 2.292 autorizaciones para un total de 210 individuos. Se observó un aumento del número de autorizaciones y de indígenas en el tratamiento de quimioterapia a lo largo del período, con una mayor concentración de individuos residentes y en tratamiento en la región sur del país, con una diversidad de tipos de tumores diagnosticados (n = 63) y de esquemas terapéuticos utilizados durante el tratamiento (n = 107). El presente estudio presentó un nuevo panorama sobre el perfil epidemiológico de los usuarios indígenas bajo tratamiento quimioterápico en el Sistema Único de Salud. Los hallazgos contribuyen a llenar la actual laguna de conocimiento con respecto a la salud indígena en Brasil.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health.

OBJECTIVES: This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS: Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS: All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION: Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

Demographics, deaths and severity indicators in hospitalizations due to drug poisoning among children under age five in Brazil. / Demografia, óbitos e indicadores de agravamento nas internações por intoxicações medicamentosas entre menores de 5 anos no Brasil.

INTRODUCTION: In Brazil, drugs are the main causative agents of poisonings, and children under age five are the group with the highest number of cases. The objective of the present study was to describe hospitalizations due to drug poisoning in this population regarding demographics, deaths and worsening indicators in hospitalizations. METHODS: The frequency of hospitalizations for drug poisoning between 2003 and 2012 was verified using data from the Hospital Information System. The study variables were year, gender, age, place of residence and hospitalization, patient follow-up, main diagnosis, secondary diagnosis, nature of the health establishment and amount related to Intensive Care Unit expenses. RESULTS: There were 17,725 hospitalizations due to drug poisoning in children under five, predominantly two-year-old male children. The hospitalizations outside the city of residence occurred in 25% of the cases, with predominance in the Northeastern region. The proportion of deaths in hospitalizations was 0.4%, with a higher number of deaths in the Southeastern region. CONCLUSION: Despite the decrease in the number of hospitalizations in the period, regional disparities remained, which could be attenuated with the provision of specialized attention to drug poisonings in municipalities, expanding the access to a more complex care.

INTRODUÇÃO: No Brasil, os medicamentos são os principais agentes causadores de intoxicação, e o maior número de casos desse problema envolve menores de 5 anos. Assim, o objetivo deste estudo foi descrever as internações por intoxicação medicamentosa nessa população quanto a sua demografia, óbitos e indicadores de agravamento. MÉTODOS: Verificou-se a frequência das internações por intoxicação medicamentosa entre 2003 e 2012, utilizando os dados do Sistema de Informação Hospitalar. As variáveis utilizadas foram ano, sexo, idade, município de residência e de internação, evolução do paciente, diagnóstico principal, diagnóstico secundário, natureza do estabelecimento de saúde e valor referente aos gastos de unidade de terapia intensiva. RESULTADOS: Ocorreram 17.725 internações por intoxicação medicamentosa em menores de 5 anos de idade, com o predomínio do sexo masculino e de crianças de 2 anos. As internações fora do município de residência deram-se em 25% dos casos, com predomínio da Região Nordeste. A proporção de óbitos nas internações foi de 0,4%, com maior número de óbitos na Região Sudeste. CONCLUSÃO: Apesar da diminuição do número de internações no período, permaneceram disparidades regionais que podem ser atenuadas com a oferta de atenção especializada às intoxicações medicamentosas nos municípios, ampliando o acesso a cuidados de maior complexidade.