Assuntos
União Europeia , Organização do Financiamento/legislação & jurisprudência , Organização do Financiamento/organização & administração , Identidade de Gênero , Projetos de Pesquisa , Apoio à Pesquisa como Assunto/legislação & jurisprudência , Apoio à Pesquisa como Assunto/organização & administração , Sexo , Animais , Canadá , Ensaios Clínicos como Assunto/métodos , Feminino , Organização do Financiamento/economia , Aquecimento Global , Humanos , Masculino , Projetos de Pesquisa/legislação & jurisprudência , Projetos de Pesquisa/normas , Pesquisadores/educação , Pesquisadores/normas , Apoio à Pesquisa como Assunto/economia , Caracteres Sexuais , Fatores Sexuais , Razão de Masculinidade , Tartarugas/fisiologia , Estados UnidosAssuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Política de Saúde , Falência Renal Crônica/terapia , Nefrologia/legislação & jurisprudência , Medicina de Precisão , Terapia de Substituição Renal , Projetos de Pesquisa/legislação & jurisprudência , Tomada de Decisão Clínica , Difusão de Inovações , Previsões , Regulamentação Governamental , Política de Saúde/tendências , Necessidades e Demandas de Serviços de Saúde/legislação & jurisprudência , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Avaliação das Necessidades/legislação & jurisprudência , Nefrologia/tendências , Formulação de Políticas , Medicina de Precisão/tendências , Prognóstico , Parcerias Público-Privadas , Terapia de Substituição Renal/tendências , Projetos de Pesquisa/tendências , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologiaAssuntos
Diabetes Mellitus/terapia , Conhecimentos, Atitudes e Prática em Saúde , Implementação de Plano de Saúde , Política de Saúde , Grupos Populacionais/psicologia , Projetos de Pesquisa/legislação & jurisprudência , Comportamento de Redução do Risco , Austrália/epidemiologia , Canadá/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/psicologia , Humanos , Incidência , Grupos Populacionais/estatística & dados numéricosRESUMO
Using mobile health (mHealth) research as an extended example, this article provides an overview of when the Common Rule "applies" to a variety of activities, what might be meant when one says that the Common Rule does or does not "apply," the extent to which these different meanings of "apply" matter, and, when the Common Rule does apply (however that term is defined), how it applies.
Assuntos
Experimentação Humana/legislação & jurisprudência , Projetos de Pesquisa/legislação & jurisprudência , Telemedicina , Ciência do Cidadão/legislação & jurisprudência , Regulamentação Governamental , Humanos , Apoio à Pesquisa como Assunto , Estados UnidosRESUMO
Typhoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.
Assuntos
Recursos em Saúde , Experimentação Humana Terapêutica/ética , Febre Tifoide/terapia , Vacinas Tíficas-Paratíficas/administração & dosagem , Países Desenvolvidos/economia , Países em Desenvolvimento/economia , Voluntários Saudáveis , Humanos , Projetos de Pesquisa/legislação & jurisprudência , Salmonella typhi/imunologia , Salmonella typhi/patogenicidade , Experimentação Humana Terapêutica/economia , Experimentação Humana Terapêutica/legislação & jurisprudência , Febre Tifoide/economia , Febre Tifoide/microbiologia , Vacinas Tíficas-Paratíficas/efeitos adversos , Vacinas Tíficas-Paratíficas/economiaRESUMO
This editorial introduces articles in this Special Issue, which are based on presentations given at the 2017 meeting of the Global Forum of Bioethics in Research meeting. The main themes presented at the meeting were the use of cluster randomized trials, stepped-wedge cluster randomized trials, and controlled human infection models in research conducted in low-resource settings. The editorial sets out which ethical issues may arise in the context of alternative trial designs and describes the articles in this issue that addresses some or more of the ethical issues, such as justification of the research design, risk-benefit evaluations and consent.
Assuntos
Recursos em Saúde , Projetos de Pesquisa/legislação & jurisprudência , Experimentação Humana Terapêutica/ética , Voluntários Saudáveis , Humanos , Experimentação Humana Terapêutica/economia , Experimentação Humana Terapêutica/legislação & jurisprudênciaRESUMO
Background Regulators increasingly rely on registries for decision making related to high-risk medical devices in the United States. However, the limited uniform standards for registries may create substantial variability in registry implementation and utility to regulators. We surveyed the current landscape of US cardiovascular device registries and chart the extent of inconsistency in goals, administration, enrollment procedures, and approach to data access. Methods and Results A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines identified studies (1995-2017) referencing cardiovascular device registries with a US-based institution. Registries were then evaluated by reviewing associated articles and websites. Extracted data included device type, primary scientific aim(s), funding, stewardship (eg, administration of registry procedures), enrollment procedures, informed consent process, and mechanisms to access data for research. The 138 cardiovascular device registries in the cohort covered devices addressing interventional cardiology (65.9%), arrhythmias (15.2%), heart failure (10.1%), and valvular disease (10.1%). While the majority (55.8%) were industry-funded, stewardship was predominantly overseen by academic centers (74.0%). Most registry participation was voluntary (77.5%), but a substantial minority (19.7%) were required as a condition of device implantation. Informed consent requirements varied widely, with written consent required in only 55.1% of registries. Registry data were primarily accessible only to stewards (84.1%), with 13.8% providing pathways for external applications. Conclusions The majority of cardiovascular device registries were funded privately under the auspices of academic institutions, which set the rules for data access. The substantial variation between cardiovascular device registries suggests a role for regulators to further strengthen guidelines to improve quality, consistency, and ethical standards.
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Doenças Cardiovasculares/terapia , Qualidade de Produtos para o Consumidor , Vigilância de Produtos Comercializados , Implantação de Prótese/instrumentação , Sistema de Registros , Projetos de Pesquisa , Acesso à Informação , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Humanos , Consentimento Livre e Esclarecido , Segurança do Paciente , Seleção de Pacientes , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Sistema de Registros/ética , Projetos de Pesquisa/legislação & jurisprudência , Apoio à Pesquisa como Assunto , Fatores de RiscoRESUMO
Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In "efficacy-to-effectiveness (E2E) trials," if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence. Yet more time could be saved by simultaneously addressing efficacy and effectiveness in an "efficacy and effectiveness too (EE2) trial." Additionally, hybrids of the E2E and EE2 approaches with differing degrees of overlap of the two components could allow flexibility for specific drug development needs. In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered. Although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.
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Ensaios Clínicos como Assunto/legislação & jurisprudência , Aprovação de Drogas/legislação & jurisprudência , Desenvolvimento de Medicamentos/legislação & jurisprudência , Projetos de Pesquisa/legislação & jurisprudência , Análise Custo-Benefício/legislação & jurisprudência , Humanos , Marketing/legislação & jurisprudência , Seleção de Pacientes , Resultado do TratamentoRESUMO
At the turn of the century, the pharmaceutical industry began a transition toward a focus on oncology, rare diseases, and other areas of high unmet need that required a new, more complex approach to drug development. For many of these disease states and novel approaches to therapy, traditional approaches to clinical trial design fall short, and a number of innovative trial designs have emerged. In light of these changes, regulators across the globe are implementing new programs to provide regular development program support, facilitate accelerated access, use real-world data, and use digital tools to improve patients' lives. Emerging market regulators are also focusing on simplifying their regulatory pathways via regional harmonization schemes with varying levels of ambition. These changes in the external environment imply that biopharma regulatory teams need to adapt and evolve, leveraging digital tools, data, and analytics, and positioning themselves as strategic advisors during development.
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Desenvolvimento de Medicamentos/legislação & jurisprudência , Indústria Farmacêutica/legislação & jurisprudência , Oncologia/legislação & jurisprudência , Ensaios Clínicos como Assunto/legislação & jurisprudência , Humanos , Doenças Raras , Projetos de Pesquisa/legislação & jurisprudênciaRESUMO
Importance: Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies. Objective: To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act. Design and Setting: A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications. Main Outcomes and Measures: Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models. Results: Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information. Conclusions and Relevance: Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.
Assuntos
Pesquisa Biomédica/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Pediatria/legislação & jurisprudência , Vigilância de Produtos Comercializados/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Adolescente , Pesquisa Biomédica/normas , Pesquisa Biomédica/estatística & dados numéricos , Criança , Pré-Escolar , Rotulagem de Medicamentos/estatística & dados numéricos , Seguimentos , Humanos , Lactente , Recém-Nascido , Vigilância de Produtos Comercializados/normas , Modelos de Riscos Proporcionais , Projetos de Pesquisa/legislação & jurisprudência , Projetos de Pesquisa/normas , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos , United States Food and Drug AdministrationRESUMO
BACKGROUND: In recent years, experience on the application of adaptive designs in confirmatory clinical trials has accumulated. Although planning such trials comes at the cost of additional operational complexity, adaptive designs offer the benefit of flexibility to update trial design and objectives as data accrue. In 2007, the European Medicines Agency (EMA) provided guidance on confirmatory clinical trials with adaptive (or flexible) designs. In order to better understand how adaptive trials are implemented in practice and how they may impact medicine approval within the EMA centralised procedure, we followed on 59 medicines for which an adaptive clinical trial had been submitted to the EMA Scientific Advice (SA) and analysed previously in a dedicated EMA survey of scientific advice letters. We scrutinized in particular the submission of the corresponding medicines for a marketing authorisation application (MAA). We also discuss the current regulatory perspective as regards the implementation of adaptive designs in confirmatory clinical trials. METHODS: Using the internal EMA MAA database, the AdisInsight database and related trial registries, we analysed how many of these 59 trials actually started, the completion status, results, the time to trial start, the adaptive elements finally implemented after SA, their possible influence on the success of the trial and corresponding product approval. RESULTS: Overall 31 trials out of 59 (53%) were retrieved. Thirty of them (97%) have been started and 23 (74%) concluded. Nine of these trials (39% out of 23) demonstrated a significant treatment effect on their primary endpoint and 4 (17% out of 23) supported a marketing authorisation (MA). An additional two trials were stopped using pre-defined criteria for futility, efficiently identifying trials on which further resources should not be spent. Median time to trial start after SA letter was given by EMA was 5 months. In the investigated trial registries, at least 18 trial (58% of 31 retrieved trials) designs were implemented with adaptive elements, which were predominantly dose selection, sample size reassessment (SSR) and stopping for futility (SFF). Among the 11 completed trials including adaptive elements, 6 demonstrated a significant treatment effect on their primary endpoint (55%). CONCLUSIONS: Adaptive designs are now well established in the drug development landscape. If properly pre-planned, adaptations can play a key role in the success of some of these trials, for example to help successfully select the most promising dose regimens for phase II/III trials. Interim analyses can also enable stopping of trials for futility when they do not hold their promises. Type I error rate control, trial integrity and results consistency between the different stages of the analyses are fundamental aspects to be discussed thoroughly. Engaging early dialogue with regulators and implementing the scientific advice received is strongly recommended, since much experience in discussing adaptive designs and assessing their results has been accumulated.
Assuntos
Ensaios Clínicos Adaptados como Assunto/métodos , Aprovação de Drogas , Órgãos Governamentais , Marketing de Serviços de Saúde , Projetos de Pesquisa , Ensaios Clínicos Adaptados como Assunto/legislação & jurisprudência , Aprovação de Drogas/legislação & jurisprudência , Determinação de Ponto Final , Europa (Continente) , Órgãos Governamentais/legislação & jurisprudência , Regulamentação Governamental , Humanos , Marketing de Serviços de Saúde/legislação & jurisprudência , Projetos de Pesquisa/legislação & jurisprudência , Tamanho da Amostra , Fatores de TempoRESUMO
Cell transplantation therapy aspires to repair and restore lost function while minimizing the risk of harm. The potential for harm arises from cell instability, variability, inappropriate behavior, and/or transmission of adventitious pathogens. Quality assured and controlled assessment and production of human cells for clinical use ensures that the risk of harm is minimized. Application of quality standards requires thorough planning and consultation with regulatory authorities on process and product specifications, as early as possible at the research and development (R&D) stage. Here we outline considerations applicable to all human cells in relation to regulatory governance, the route to the clinic and Cell Therapy Product (CTP) characterization, with special emphasis on human pluripotent stem cells (hPSC).
Assuntos
Pesquisa Biomédica/normas , Terapia Baseada em Transplante de Células e Tecidos/normas , Regulamentação Governamental , Células-Tronco Pluripotentes/transplante , Controle de Qualidade , Animais , Pesquisa Biomédica/legislação & jurisprudência , Pesquisa Biomédica/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Europa (Continente) , Humanos , Modelos Animais , Projetos de Pesquisa/legislação & jurisprudência , Projetos de Pesquisa/normas , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/normas , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normasRESUMO
BACKGROUND: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011. However, study start-up was significantly delayed and recruitment did not start until January 2013. METHOD: The FOR-DMD study is used as an example to identify systematic problems in the set-up of international, multi-centre clinical trials. The full timeline of the FOR-DMD study, from funding approval to site activation, was collated and reviewed. Systematic issues were identified and grouped into (1) study set-up, e.g. drug procurement; (2) country set-up, e.g. competent authority applications; and (3) site set-up, e.g. contracts, to identify the main causes of delay and suggest areas where anticipatory action could overcome these obstacles in future studies. RESULTS: Time from the first contact to site activation across countries ranged from 6 to 24 months. Reasons of delay were universal (sponsor agreement, drug procurement, budgetary constraints), country specific (complexity and diversity of regulatory processes, indemnity requirements) and site specific (contracting and approvals). The main identified obstacles included (1) issues related to drug supply, (2) NIH requirements regarding contracting with non-US sites, (3) differing regulatory requirements in the five participating countries, (4) lack of national harmonisation with contracting and the requirement to negotiate terms and contract individually with each site and (5) diversity of languages needed for study materials. Additionally, as with many academic-led studies, the FOR-DMD study did not have access to the infrastructure and expertise that a contracted research organisation could provide, organisations often employed in pharmaceutical-sponsored studies. This delay impacted recruitment, challenged the clinical relevance of the study outcomes and potentially delayed the delivery of the best treatment to patients. CONCLUSION: Based on the FOR-DMD experience, and as an interim solution, we have devised a checklist of steps to not only anticipate and minimise delays in academic international trial initiation but also identify obstacles that will require a concerted effort on the part of many stakeholders to mitigate.
Assuntos
Lista de Checagem , Ensaios Clínicos como Assunto/métodos , Estudos Multicêntricos como Assunto/métodos , Distrofia Muscular de Duchenne/tratamento farmacológico , Doenças Raras/tratamento farmacológico , Projetos de Pesquisa , Esteroides/administração & dosagem , Orçamentos , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/legislação & jurisprudência , Contratos , Humanos , Cooperação Internacional , Estudos Multicêntricos como Assunto/economia , Estudos Multicêntricos como Assunto/legislação & jurisprudência , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/economia , Seleção de Pacientes , Doenças Raras/diagnóstico , Doenças Raras/economia , Projetos de Pesquisa/legislação & jurisprudência , Apoio à Pesquisa como Assunto , Esteroides/efeitos adversos , Esteroides/provisão & distribuição , Fatores de Tempo , Resultado do TratamentoAssuntos
Prática Clínica Baseada em Evidências/economia , Pesquisa sobre Serviços de Saúde/economia , Projetos de Pesquisa/legislação & jurisprudência , Prática Clínica Baseada em Evidências/métodos , Guias como Assunto , Pesquisa sobre Serviços de Saúde/organização & administração , Humanos , Projetos de Pesquisa/normasRESUMO
AIMS: To review clinical and cost-effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series. METHODS: A systematic review of all new drugs evaluated in 2011-2016 within a health care profession-driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Agency (TLV). Public assessment reports from the European Medicines Agency, published pivotal studies, and TLV, Scottish Medicines Consortium and National Institute of Health and Care Excellence decisions and guidance documents were reviewed. RESULTS: Six drug cases were assessed (brentuximab vedotin, bosutinib, ponatinib, idelalisib, vismodegib, ceritinib). The validity of the pivotal studies was hampered by the use of surrogate primary outcomes and the absence of recruitment information. To quantify drug treatment effect sizes, the reimbursement agencies primarily used data from another source in indirect comparisons. TLV granted reimbursement in five cases, compared with five in five cases for Scottish Medicines Consortium and four in five cases for National Institute of Health and Care Excellence. Decision modifiers, contributing to granted reimbursement despite hugely uncertain cost-effectiveness ratios, were, for example, small population size, occasionally linked to budget impact, severity of disease, end of life and improved life expectancy. CONCLUSION: For drugs whose authorization is based on prospective case series, most applications for reimbursement within public health care are granted. The underlying evidence has limitations over and above the design per se, and decision modifiers are frequently referred to in the value-based pricing decision making.
Assuntos
Aprovação de Drogas/métodos , Custos de Medicamentos , Medicina Baseada em Evidências/métodos , Reembolso de Seguro de Saúde/economia , Projetos de Pesquisa , Seguro de Saúde Baseado em Valor/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Aprovação de Drogas/legislação & jurisprudência , Custos de Medicamentos/legislação & jurisprudência , Determinação de Ponto Final , Medicina Baseada em Evidências/legislação & jurisprudência , Feminino , Política de Saúde , Humanos , Reembolso de Seguro de Saúde/legislação & jurisprudência , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Formulação de Políticas , Estudos Prospectivos , Projetos de Pesquisa/legislação & jurisprudência , Suécia , Resultado do Tratamento , Incerteza , Reino Unido , Adulto JovemRESUMO
The OECD TG 215 method (2000) (C.14 method of EC Regulation 440/2008) was developed on the rainbow trout (Oncorynchus mykiss) to assess chronic toxicity (28d) of chemicals on fish juveniles. It contemplates to use other well documented species identifying suitable conditions to evaluate their growth. OECD proposes the European sea bass (Dicentrarchus labrax, L. 1758) as Mediterranean species among vertebrates recommended in the OECD guidelines for the toxicity testing of chemicals. In this context, our study is aimed to proposing the adaptation of the growth test (OECD TG 215, 2000) to D. labrax. For this purpose toxicity tests were performed with sodium dodecyl sulfate, a reference toxicant commonly used in fish toxicity assays. The main aspects of the testing procedure were reviewed: fish size (weight), environmental conditions, dilution water type, experimental design, loading rate and stocking density, feeding (food type and ration), test validity criteria. The experience gained from growth tests with the sea bass allows to promote its inclusion among the species to be used for the C.14 method.
Assuntos
Bass/crescimento & desenvolvimento , Projetos de Pesquisa , Dodecilsulfato de Sódio/toxicidade , Testes de Toxicidade/métodos , Animais , Peso Corporal , Organização para a Cooperação e Desenvolvimento Econômico , Projetos de Pesquisa/legislação & jurisprudência , Projetos de Pesquisa/tendências , Especificidade da EspécieRESUMO
Understanding how to improve decision makers' use of scientific information across their different scales of management is a core challenge for narrowing the gap between science and conservation practice. Here, we present a study conducted in collaboration with decision makers that aims to explore the functionality of the mechanisms for scientific input within the institutional setting of the National Protected Area Network of Peru. First, we analyzed institutional mechanisms to assess the scientific information recorded by decision makers. Second, we developed two workshops involving scientists, decision makers and social actors to identify barriers to evidence-based conservation practice. Third, we administered 482 questionnaires to stakeholders to explore social perceptions of the role of science and the willingness to collaborate in the governance of protected areas. The results revealed that (1) the institutional mechanisms did not effectively promote the compilation and application of scientific knowledge for conservation practice; (2) six important barriers hindered scientific input in management decisions; and (3) stakeholders showed positive perceptions about the involvement of scientists in protected areas and expressed their willingness to collaborate in conservation practice. This collaborative research helped to (1) identify gaps and opportunities that should be addressed for increasing the effectiveness of the institutional mechanisms and (2) support institutional changes integrating science-based strategies for strengthening scientific input in decision-making. These insights provide a useful contextual orientation for scholars and decision makers interested in conducting empirical research to connect scientific inputs with operational aspects of the management cycle in other institutional settings around the world.
Assuntos
Conservação dos Recursos Naturais/métodos , Tomada de Decisões , Política Ambiental/tendências , Pesquisa Interdisciplinar/organização & administração , Formulação de Políticas , Projetos de Pesquisa/tendências , Conservação dos Recursos Naturais/legislação & jurisprudência , Conservação dos Recursos Naturais/tendências , Política Ambiental/legislação & jurisprudência , Regulamentação Governamental , Pesquisa Interdisciplinar/legislação & jurisprudência , Pesquisa Interdisciplinar/tendências , Peru , Projetos de Pesquisa/legislação & jurisprudênciaRESUMO
BACKGROUND: Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. METHODS: We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. RESULTS: The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential. CONCLUSIONS: The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.
Assuntos
Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Pragmáticos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Atitude do Pessoal de Saúde , Confidencialidade , Comportamento Cooperativo , Equipamentos e Provisões , Europa (Continente) , Medicina Baseada em Evidências , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Multicêntricos como Assunto/economia , Estudos Multicêntricos como Assunto/legislação & jurisprudência , Terapia Nutricional , Ensaios Clínicos Pragmáticos como Assunto/economia , Ensaios Clínicos Pragmáticos como Assunto/legislação & jurisprudência , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/legislação & jurisprudência , Doenças Raras/terapia , Projetos de Pesquisa/legislação & jurisprudência , Pesquisadores , Apoio à Pesquisa como AssuntoAssuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Aprovação de Drogas , Neoplasias/tratamento farmacológico , Projetos de Pesquisa/tendências , Antineoplásicos/efeitos adversos , China/epidemiologia , Ensaios Clínicos como Assunto/legislação & jurisprudência , Aprovação de Drogas/legislação & jurisprudência , Previsões , Regulamentação Governamental , Humanos , Neoplasias/epidemiologia , Formulação de Políticas , Projetos de Pesquisa/legislação & jurisprudência , Fatores de Tempo , Fluxo de TrabalhoRESUMO
BACKGROUND: Ecological momentary assessment (EMA)-which often involves brief surveys delivered via mobile technology-has transformed our understanding of the individual and contextual micro-processes associated with legal and illicit drug use. However, little empirical research has focused on participant's perspective on the probability and magnitude of potential risks in EMA studies. OBJECTIVES: To garner participant perspectives on potential risks common to EMA studies of illicit drug use. METHODS: We interviewed 38 persons who inject drugs living in San Diego (CA) and Philadelphia (PA), United States. They completed simulations of an EMA tool and then underwent a semi-structured interview that systematically explored domains of risk considered within the proposed revisions to the Federal Policy for the Protection of Human Subjects or the "Common Rule." Interviews were transcribed verbatim and coded systematically to explore psychological, physical, social, legal, and informational risks from participation. RESULTS: Participants perceived most risks to be minimal. Some indicated that repetitive questioning about mood or drug use could cause psychological (i.e., anxiety) or behavioral risks (i.e., drug use relapse). Ironically, the questions that were viewed as risky were considered motivational to engage in healthy behaviors. The most cited risks were legal and social risks stemming from participant concerns about data collection and security. IMPORTANCE: Improving our understanding of these issues is an essential first step to protect human participants in future EMA research. We provide a brief set of recommendations that can aid in the design and ethics review of the future EMA protocol with substance using populations.