Impact of regulatory assessment on clinical studies in Brazil / Impacto da avaliação regulatória em estudos clínicos no Brasil

SUMMARY Introduction: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. Objective: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. Method: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. Results: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. Conclusion: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country’s scientific development.

RESUMO Introdução: apesar da recente expansão de estudos clínicos alocados para o Brasil, a demora dos prazos regulatórios locais impacta diretamente em sua realização. Objetivo: este artigo analisa o processo de alocação de estudos clínicos para o Brasil em comparação a outros países, bem como o impacto financeiro dos estudos não realizados em decorrência da interrupção pela demora no processo regulatório. Método: foram comparados os processos de alocação de estudos em nove países com estágios semelhantes de desenvolvimento econômico e países da América Latina através dos siteshttp://data.worldbank.org/data-catalog/GDP-ranking-table, http://worldpopulationreview.com e clinicaltrials.gov, que engloba 185 países. Os 46 estudos patrocinados pela indústria farmacêutica tiveram o processo de avaliação regulatória analisado. Resultados: foram analisados 46 estudos patrocinados pela indústria submetidos no país entre junho de 2007 e junho de 2013; 18 (39%) foram descontinuados pelo atraso na obtenção das aprovações necessárias. Para os estudos aprovados, o recrutamento de pacientes começou, em média, aos 11 meses após os demais países. Estima-se que 530 pacientes brasileiros não tiveram a oportunidade de participar desses estudos. As perdas financeiras foram da ordem de 14,6 milhões de dólares para o país, incluindo custos com paciente, medicação, suprimentos e despesas administrativas. Conclusão: o Brasil tem um enorme potencial para a realização de estudos clínicos. Investigadores, associações de deficientes e pacientes portadores de doenças crônicas, patrocinadores e autoridades devem trabalhar juntos para desenvolver um processo de aprovação eficiente, previsível e antes de tudo transparente. O atual ambiente regulatório deve e pode ser melhorado e aperfeiçoado, caso contrário não resultará em benefícios tangíveis para o paciente, para a sociedade e a evolução médico-científica do país.

Impact of regulatory assessment on clinical studies in Brazil.

INTRODUCTION: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. OBJECTIVE: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. METHOD: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. RESULTS: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. CONCLUSION: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development.

AMI is associated with polymorphisms in the NOS3 and FGB but not in PAI-1 genes in young adults

Background: We investigated the relationship between NOS3, FGB and PAI-1 polymorphisms and endothelial dysfunction and risk factors for acute myocardial infarction (AMI) in young adults.Methods: Endothelial function was measured by response to flow mediated vasodilation (FMV) and induced by nitrate (FMN). Biochemical parameters were measured by standard enzymatic methods and plasma total nitrate was analyzed by the NOA™system. NOS3 (T-786C, G894T and intron 4A/B STR), FGB (C-148T and G-455A) and PAI-1 (4G/5G) polymorphisms were determined by PCR-RFLP.Results: Concentrations of total and LDL cholesterol, apo B, triglycerides, nitrate, PAI-1 and fibrinogen were higher and apo AI, HDL cholesterol and FMVwere lower in AMI patients than in controls ( pb0.001). PAI-1 ( pb0.001) but not nitrate was higher in AMI patients with low response toFMV. NOS3 T-786C and FGB C-148T polymorphisms were associated with AMI ( pb0.050). NOS3 T-786C was also related to hypertension ( p=0.049).NOS3 intron 4A/B STR was associated with increased concentrations of total cholesterol and apo B. NOS3-786TT/894GT haplotype was associated with increased FMV ( p=0.018) than the other haplotypes. Conclusions: Our data suggest NOS3 and FGB polymorphisms are associated with AMI. NOS3 is also related to hypertension, endothelialdysfunction and variation on serum cholesterol in young adults with AMI.

AMI is associated with polymorphisms in the NOS3 and FGB but not in PAI-1 genes in young adults.

BACKGROUND: We investigated the relationship between NOS3, FGB and PAI-1 polymorphisms and endothelial dysfunction and risk factors for acute myocardial infarction (AMI) in young adults. METHODS: Endothelial function was measured by response to flow mediated vasodilation (FMV) and induced by nitrate (FMN). Biochemical parameters were measured by standard enzymatic methods and plasma total nitrate was analyzed by the NOA system. NOS3 (T-786C, G894T and intron 4A/B STR), FGB (C-148T and G-455A) and PAI-1 (4G/5G) polymorphisms were determined by PCR-RFLP. RESULTS: Concentrations of total and LDL cholesterol, apo B, triglycerides, nitrate, PAI-1 and fibrinogen were higher and apo AI, HDL cholesterol and FMV were lower in AMI patients than in controls (p<0.001). PAI-1 (p<0.001) but not nitrate was higher in AMI patients with low response to FMV. NOS3 T-786C and FGB C-148T polymorphisms were associated with AMI (p<0.050). NOS3 T-786C was also related to hypertension (p=0.049). NOS3 intron 4A/B STR was associated with increased concentrations of total cholesterol and apo B. NOS3-786TT/894GT haplotype was associated with increased FMV (p=0.018) than the other haplotypes. CONCLUSIONS: Our data suggest NOS3 and FGB polymorphisms are associated with AMI. NOS3 is also related to hypertension, endothelial dysfunction and variation on serum cholesterol in young adults with AMI.