Registration pathways to accelerate regulatory assessment of innovative medicines in Latin America.

Countries worldwide have introduced new regulations to accelerate drug regulatory review to afford faster access to medicines, mainly for patients with no or limited therapeutic alternative without compromising the quality, efficacy, and safety of the drug. We mapped and analyzed accelerated regulatory pathways in 19 countries from Latin America (LATAM). Pathways included acceptance of Phase II studies, when justified, and requirement of a Certificate of Pharmaceutical Product (CPP) for regulatory submission or approval for a drug. We present a regional regulatory overview of innovative pathways to accelerate assessment of medicines by regulators to benefit patients in need. Most LATAM regulators we surveyed have implemented accelerated pathways. Adoption of good regulatory practices is key for success (World Health Organization, WHO, Good Regulatory Practices: guidelines for national regulatory authorities for medical products (World Health Organization, WHO, Good Regulatory Practices: guidelines for national regulatory authorities for medical products. World Health Organization QAS/16.686. WHO, 2016. https://www.who.int/medicines/areas/quality_safety/quality_assurance/GoodRegulatory_PracticesPublicConsult.pdf ).

Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach.

INTRODUCTION AND AIM: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). METHODS: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. RESULTS: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. CONCLUSION: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil.

In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4%) had cirrhosis and HCV genotype 1 predominated (64.3%). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4 percent) had cirrhosis and HCV genotype 1 predominated (64.3 percent). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6 percent of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8 percent; the SVR rate was 32.9 percent among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8 percent, whereas it was 37.5 percent in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95 percent: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95 percent: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95 percent: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95 percent: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

Reunião com expertos em hepatotoxicidade da Sociedade Brasileira de Hepatologia: analgésicos, antitérmicos, insumos vegetais, fitoterápicos, homeopáticos e AINEs / Meeting with Society's Hepatotoxic Experts Brazilian Institute of Hepatology: Analgesics, Antipyretics, Vegetable, Phytotherapic, Homeopathic and AINS

No dia 05 de agosto de 2010, no Hotel Blue Tree, no bairro do Morumbi em São Paulo, a Sociedade Brasileira de Hepatologia realizou uma reunião de expertos para discutir alguns assuntos importantes referentes à toxicidade hepática. Esta reunião foi de responsabilidade exclusiva da Sociedade Brasileira de Hepatologia (SBH), sem interferência de agências ou da indústria farmacêutica. Dentre os assuntos discutidos, três deles mereceram destaque pelo volume de solicitações de esclarecimentos encaminhadas diretamente à Sociedade Brasileira de Hepatologia. O site da SBH recebe com frequência tais solicitações de outras sociedades ou diretamente de colegas, assim como do público não-médico, por questões pertinentes a estes assuntos: 1. papel do acetaminofen/paracetamol nas alterações hepáticas da dengue; 2. eficácia e segurança da medicina alternativa (homeopatia, medicina natural, fitoterápicos); 3. alterações hepáticas induzidas por analgésicos, antitérmicos e anti-inflamatórios não-esteroides com foco no seu uso na dengue.Dentro deste contexto, a Sociedade Brasileira de Hepatologia organizou uma sessão durante todo o dia 05 de agosto para discutir unicamente estes temas.

Hepatitis B virus markers among teenagers in the Araguaia region, Central Brazil: assessment of prevalence and vaccination coverage.

The Brazilian hepatitis B (HBV) vaccination program for neonates was implemented in 1998 and broadened to include young people up to 20 years of age in 2001. However, HBV coverage of teenagers has not been systematically assessed in Brazil. A cross-sectional study was performed to estimate the magnitude of HBV infection and vaccine coverage among adolescent students regularly enrolled in the public schools of Barra do Garças, a city located in the state of Mato Grosso, Brazil. A representative sample was randomly obtained and participants were interviewed and had blood samples collected to test for HBV markers. The sample was composed of 576 subjects, 51% of which were females. The average age was 15, with the group ranging from 12 to 20 years of age. There were 29 anti-HBc reactive participants (5.0%). Four out of 29 were HBsAg positive (0.7%). Anti-HBs alone (vaccinated profile) showed in 323 (56.1%) students and 224 (38.9%) were negative for all HBV markers. Increasing age was associated with HBV exposure in a χ(2) for trend analysis (p=0.004). The prevalence of anti-HBs alone decreased as the subjects' age increased. Multivariate analysis showed independent association between HBV infection and the start of sexual activity. Another associated variable was the fact that the some students were enrolled in two low-income neighborhood schools. Our findings classify this area as low endemic for HBV and suggest that there is a progressive decrease in the spread of HBV in the region due to the introduction of universal vaccination of neonates. Approximately half of the adolescents 15 years or older were not immunized, which raises a concern in terms of the need to increase the vaccination rate for this segment of the population.

Pesquisa de anticorpos contra o vírus da hepatite C em pool de 5 soros: sua utilizaçäo em inquéritos soroepidemiológicos / Detection of antibodies against hepatitis C virus in a 5 sera pool testing: its use in seroepidemiological survey

Para avaliar reduçäo de custo da pesquisa de anticorpos contra hepatite C, por ELISA, em pool de cinco soros, realizou-se o teste em grupos de baixo e alto risco. Dois terços dos conjuntos de alto risco tiveram que ser repetidos. A reduçäo do gasto de reagente foi de 80 por cento na populaçäo de baixo risco e de 13 por cento na amostra de alto risco. Estes dados sugerem que a pesquisa do anti-VHC em pool reduz o custo do procedimento em populaçöes de baixo risco