Análise descritiva da produção científica e sua correlação com os recursos financeiros públicos aplicados na pesquisa

A produção científica engloba o conjunto de pesquisas e publicações que são desenvolvidos por indivíduos e instituições, visando divulgar e propagar o conhecimento em diversas áreas do saber. Fatores como investimentos em pesquisa, infraestrutura disponível, políticas públicas de fomento e incentivo, além de perfil dos pesquisadores e suas redes de colaboração, exercem influência na produção científica. O recurso financeiro destinado à pesquisa é fundamental para garantir a produção científica de qualidade, uma vez que possibilita a contratação de pesquisadores, a aquisição de equipamentos e materiais de pesquisa, a realização de experimentos, bem como a divulgação e disseminação dos resultados obtidos, impactando diretamente no desenvolvimento científico, tecnológico e econômico do país e nos indicadores cientométricos. Estas são ferramentas utilizadas na avaliação da produção científica e do impacto de pesquisas, permitindo a análise em diversos aspectos, como a quantidade e qualidade de artigos publicados, livros e capítulos de livro, colaboração entre autores e instituições e produtos de inovação, entre outros. A presente tese visou analisar descritivamente indicadores de produção científica e a disponibilidade de recursos financeiros em um cenário regional e nacional, avaliando potenciais correlações entre diferentes tipos de produção científica e recursos financiados. Foram considerados nesta análise todos os pesquisadores com currículo Lattes cadastrado e que receberam 4 ou mais anos de bolsa de produtividade do CNPq, no período de 2000 a 2020 (n=22.058). A análise da correlação da produção científica versus fomento foi restrita aos recursos financeiros das agências de fomento nacionais (CNPq e CAPES) e das Fundações de Amparo à Pesquisa. Para análise de produção, foram considerados todos os indicadores da produção científica registrados no currículo Lattes do pesquisador, independente da fonte de financiamento. Os dados relacionados ao fator de impacto do periódico foram coletados no Journal Citation Report. Para análise da correlação dos recursos financeiros e da produção científica, estabeleceram-se grupos por área de atuação dos pesquisadores. Observou-se uma maior concentração de pesquisadores do sexo masculino (64,95%) na amostra total. Em relação ao financiamento, observou-se um investimento total de mais de US$6,6 bilhões no período, concentrado nas áreas de Ciências Biológicas e Exatas e da Terra (53,3$ 814,6 milhões). Ainda há desafios a serem enfrentados para promover uma distribuição mais equitativa de recursos e oportunidades para produção científica no Brasil, especialmente em áreas subfinanciadas ou negligenciadas. Observou-se que a FAPESP apresentou investimentos financeiros superiores à soma de recursos das demais fundações de amparo do país. Além disso, avaliamos os intervalos de tempo entre submissão e publicação de artigos em 72 periódicos em uma área de conhecimento específica, Genética e Hereditariedade, divididos em quartis de fator de impacto. Foram coletados e analisados dados de 46.349 artigos publicados entre 2016 e 2020, considerando os intervalos de tempo entre submissão e aceitação (SA), aceitação e publicação (AP) e submissão e publicação (SP). Os resultados mostraram que há diferenças significativas entre os quartis em relação ao tempo transcorrido entre a submissão e a publicação, tendo destaque para o Q4 que possuio menor tempo médio entre submissão e aceite, e maior tempo entre aceite e publicação, entretanto os tempos entre os quartis são tempos relativamente semelhantes. Não houve diferença significativa entre o tempo de publicação de artigos com autores de um ou mais continentes, mas foi observado que os artigos de autores da África e Oceania foram subrepresentados nas revistas de alto impacto. Os resultados destacam a necessidade de investimento contínuo em pesquisa e desenvolvimento no Brasil, com uma distribuição mais equitativa de recursos e oportunidades. Isso exigirá um esforço coordenado de agências de financiamento, formuladores de políticas e pesquisadores para identificar áreas prioritárias e desenvolver estratégias para fortalecer a capacidade de instituições de financiamento de pesquisa. Os achados podem também contribuir para o desenvolvimento de estratégias para acelerar o processo de publicação científica, direcionando esforços para diminuir os intervalos de tempo entre a submissão e publicação de artigos, visando a um processo mais eficiente de disseminação do conhecimento. O Brasil tem experimentado um crescimento significativo em sua produção científica, mas ainda há disparidades entre regiões e instituições, tornando essencial promover uma cultura de diversidade, inclusão e excelência em ciência e tecnologia.Scientific production encompasses the set of research and publications developed by individuals and institutions, aiming to disseminate and propagate knowledge in various fields of knowledge. Factors such as investment in research, available infrastructure, public policies for promotion and incentive, as well as the profile of researchers and their collaboration networks, exert influence on scientific production. Financial resources allocated to research are essential to guarantee quality scientific production, as it enables the hiring of researchers, acquisition of research equipment and materials, conduct of experiments, as well as dissemination and dissemination of the results obtained, directly impacting the scientific, technological and economic development of the country and scientific metrics indicators. These are tools used in evaluating scientific production and the impact of research, allowing analysis on various aspects such as the quantity and quality of published articles, books and book chapters, collaboration between authors and institutions, and innovative products, among others. This thesis aimed to analyze descriptively indicators of scientific production and the availability of financial resources in a regional and national scenario, evaluating potential correlations between different types of scientific production and funded resources. All researchers with a registered Lattes curriculum and who received 4 or more years of productivity scholarship from CNPq, between 2000 and 2020 (n = 22,058), were considered in this analysis. The correlation analysis of scientific production versus funding was restricted to the financial resources of national funding agencies (CNPq and CAPES) and research support foundations. For the production analysis, all scientific production indicators recorded in the researcher's Lattes curriculum were considered, regardless of the source of funding. Data related to the journal impact factor were collected in the Journal Citation Report. To analyze the correlation of financial resources and scientific production, groups were established by the researcher’s field of expertise. A higher concentration of male researchers (64.95%) was observed in the total sample. Regarding funding, there was a total investment of over US$6.6 billion in the period, concentrated in the field of Biological Sciences and Exact and Earth Sciences (53.3$ 814.6 million). There are still challenges to be faced to promote a more equitable distribution of resources and opportunities for scientific production in Brazil, especially in underfunded or neglected fields. It was observed that FAPESP presented higher financial investments than the sum of resources from other research support foundations in the country. In addition, we evaluated the time intervals between submission and publication of articles in 72 journals in a specific field of knowledge, Genetics and Heredity, divided into impact factor quartiles. Data from 46,349 articles published between 2016 and 2020 were collected and analyzed, considering the intervals between submission and acceptance (SA), acceptance and publication (AP), and submission and publication (SP). The results showed significant differences between the quartiles regarding the submission to publication time, with Q4 standing out as having the shortest average time between submission and acceptance, and the longest time between acceptance and publication. However, the times between the quartiles are relatively similar. There was no significant difference between the publication time of articles with authors from one or more continents, but it was observed that articles by authors from Africa and Oceania were underrepresented in some high-impact journals. The findings highlight the need for continuous investment in research and development in Brazil, with a more equitable distribution of resources and opportunities. This will require a coordinated effort from funding agencies, policy makers, and researchers to identify priority fields and develop strategies to strengthen the capacity of research funding institutions. The findings may also contribute to the development of strategies to accelerate the scientific publishing process, by directing efforts towards reducing the time intervals between article submission and publication, aiming for a more efficient knowledge dissemination process. Brazil has experienced significant growth in its scientific production, but there are still disparities between regions and institutions, making it essential to promote a culture of diversity, inclusion, and excellence in science and technology

Análise descritiva da produção científica em um hospital universitário e sua relação com os recursos financeiros aplicados na pesquisa

Entre 2000 a 2013 o governo federal disponibilizou por meio de editais competitivos mais de R$150 bilhões para pesquisa e desenvolvimento. As agências de fomento nacionais e internacionais, por meio do sistema de avaliação, buscam, essencialmente, embasar o investimento do recurso a partir de indicadores qualitativos e quantitativos da produção científica. Neste contexto, um hospital geral público e universitário inova há mais de três décadas investindo recursos de forma não competitiva, a partir de seu fundo de pesquisa institucional, para estimular o desenvolvimento da produção científica na instituição. Em cenário de escassez de recursos públicos, é importante avaliar, a partir de indicadores, o impacto de recursos financeiros institucionais ofertados de forma não competitiva sobre o impulso observado na produção científica. O presente estudo visa analisar descritivamente a alocação de recursos institucionais para pesquisa e os indicadores de produção científica dos pesquisadores contemplados em um período de 15 anos em um hospital geral público e universitário no Sul do Brasil. Foram considerados nesta análise todos os pesquisadores com currículo Lattes cadastrado e que tiveram dois ou mais projetos de pesquisa aprovados pelos Comitês de Ética institucionais independente da fonte de financiamento, no período de 2000 a 2014 (n=646). A análise da produção científica versus fomento foi restrita aos recursos do Fundo de Pesquisa institucional. Para análise de produção, todos os artigos incluídos no CV Lattes do pesquisador, independente da fonte de financiamento, foram coletados. Os dados relativos à pós-graduação foram coletados junto à CAPES, os de impacto do periódico, no Journal Citation Report. Para análise da distribuição dos recursos financeiros, os pesquisadores foram agrupados conforme o aporte de recursos. Os dados foram analisados descritivamente. Observou-se que há, na amostra, predomínio de pesquisadores do sexo feminino, com graduação em medicina e com doutorado, sendo que somente metade destes tem vínculo com programas de pós-graduação. O grupo de pesquisadores nas maiores faixas de recurso investido pelo fundo institucional aumentou ao longo dos 15 anos de estudo, enquanto o número de pesquisadores que não receberam nenhum financiamento diminuiu no mesmo período. Em relação à produção, houve aumento no número de artigos a partir de 2006 atingindo um platô em 2010. Da mesma forma, houve aumento na mediana do fator de impacto das produções até 2009, quando se observou estabilização. Foi observada, ainda, uma relação direta entre concessão e produtividade científica. Pesquisadores sem financiamento do fundo institucional apresentaram mediana do fator de impacto de publicações próxima àquela dos grupos de maior aporte. Publicações com maiores fatores de impacto foram observadas para pesquisadores do sexo masculino, com doutorado, vinculados a programas de pós-graduação notas 6 e 7 da CAPES e detentores de bolsas de produtividade do CNPq. Embora ao longo dos anos tenha se observado uma evolução positiva no número das publicações de pesquisadores da instituição, e pareça haver uma relação positiva entre investimento de recursos financeiros institucionais e maior produtividade, esta relação não é uniforme e não há um reflexo significativo sobre o fator de impacto da produção. A produção de pesquisadores que não receberam recursos financeiros institucionais não difere significativamente dos demais grupos e os pesquisadores que receberam as maiores quantias de financiamento não são necessariamente os mais produtivos. Por outro lado, foram fornecidos recursos do fundo de investimento em pesquisa institucional para o desenvolvimento de projetos de pesquisa independente de vínculo com a pós-graduação. Este grupo correspondeu a 50,8$150 billion in research and development funding available through competitive tenders. National and international funding agencies seek to support their investment in research through qualitative and quantitative indicators of scientific output. Within this context, for the past three decades, a public, university-affiliated general hospital in Brazil has provided noncompetitive funding through an institutional research incentive fund to encourage intramural scientific output. In a scenario of scarce public resources, the use of indicators to assess the impact of noncompetitive funding initiatives on scientific output is particularly important. To conduct a descriptive analysis of institutional allocation of research funding at a public, university-affiliated general hospital in Southern Brazil and scientific output indicators for the recipients of such funding over a 15-year period. All investigators with a curriculum vitae (CV) posted in the Lattes platform and who had two or more research projects approved by the institutional Research Ethics Committee from 2000–2014, regardless of funding source, were included (n=646). Comparison of scientific output vs. funding was restricted to resources from the institutional Research Incentive Fund. For analysis of scientific output, all articles included in each investigator’s Lattes CV, regardless of funding source, were considered. Data on affiliation with graduate programs were collected from CAPES, while the impact factors of journals were collected from the Journal Citation Report. For analysis of distribution of financial resources, investigators were clustered by the amount of funding received. Descriptive analyses were carried out. The sample was predominantly composed of female MDs with a doctoral degree. Only half of investigators were affiliated with a graduate program. The group of investigators who received the largest amounts of funding increased over the 15-year study period, while the number of investigators who did not receive any funding decreased over the same period. Regarding output, the number of articles published increased from 2006 and plateaued in 2010. Likewise, the median impact factor of the journals in which papers were published increased before stabilizing in 2009. A positive association was found between provision of funding and researcher productivity, especially regarding the mean number of publications and median impact factor of the journals in which they were published. However, investigators who received no resourced from the institutional Fund published in journals with a median impact factor similar to those in which investigators from the higher funding groups did. Male investigators, those with a doctoral degree, those affiliated with CAPES grade 6 and 7 graduate programs and recipients of CNPq Research Productivity Scholarships were more likely to publish in journals with higher impact factors. Although institutional research output at the study hospital increased over the years, and there appears to be a positive association between institutional funding and increased productivity, this association was not uniform and was not reflected in the impact factor of the investigators’ output. The output of investigators who did not receive institutional funding did not differ significantly from that of other groups of investigators, and those who received the largest amounts of funding were not necessarily the most productive. On the other hand, our findings confirmed that resources from the institutional Fund were provided to research projects regardless of affiliation with institutional graduate programs. Unaffiliated investigators accounted for 50.8% of the overall sample and 13% of its research output. In this study, the scientific production was analyzed in a public, tertiary and university hospital and its potential relation with the granting of funds from the Research Incentive Fund (FIPE), in a non-competitive format. The results allow to delineate the scientific production scenario in the institution and to implement future decisions about the continuity and / or adjustments of this unique model of promotion to health research

Indicadores de qualidade na condução de estudos clínicos

Introdução: A geração, análise e difusão de indicadores pertinentes é uma das estratégias fundamentais do processo de gestão de qualidade. Indicadores são mensurações que avaliam direta ou indiretamente os processos e desfechos da assistência ao participante de pesquisa. Padrões rigorosos de qualidade  garantirão a validade dos dados obtidos nos estudos clínicos. Métodos: Estudo transversal descritivo e analítico, com dados coletados no Centro de Pesquisa Clínica de um Hospital Universitário, durante Novembro/2016 a Fevereiro/2019 quanto ao tempo de inclusão de dados no e-CRF (IID), tempo de comunicação de desvios de protocolo ao CEP-Comitê de Ética em Pesquisa (ICD), tempo de resposta aos feasibilities recebidos (IRF) e tempo de resposta às pendências de monitoria (IRP). Resultados: Variações substanciais foram encontradas entre os escores de qualidade ao longo de 27 meses. O desempenho geral da equipe do EP alcançou a classificação excelente ou satisfatória em 61,40% das observações: 50,87% e 10,52% respectivamente. Entre 38,59% de observações críticas, 17,54% foram expressas pelo IRP, seguido de 12,28% por ICD e 7% atribuído ao IID que não atingiram a meta proposta. Conclusão: O Escritório de Projetos em Pesquisa em Pesquisa elencou dois indicadores de qualidade: IID e IRP que podem melhorar o tempo e a eficácia das entregas propostas da equipe.Palavras-chave: Projetos de pesquisa; protocolos clínicos; avaliação da pesquisa em saúde; indicadores de projetos de pesquisa e desenvolvimento; integridade em pesquis

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2 : an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine : a pooled analysis of four randomised trials

Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5×10¹⁰ viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2×10¹⁰ viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAATpositive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24422 participants were recruited and vaccinated across the four studies, of whom 17178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]). Interpretation The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose