Assuntos
Ensaios Clínicos Fase I como Assunto/normas , Aprovação de Drogas/legislação & jurisprudência , Drogas em Investigação/farmacologia , Experimentação Humana não Terapêutica/normas , Guias de Prática Clínica como Assunto , Animais , Ensaios Clínicos Fase I como Assunto/ética , Ensaios Clínicos Fase I como Assunto/legislação & jurisprudência , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/normas , Europa (Continente) , União Europeia/organização & administração , Voluntários Saudáveis , Humanos , Modelos Animais , Experimentação Humana não Terapêutica/ética , Experimentação Humana não Terapêutica/legislação & jurisprudência , Projetos de Pesquisa/normasRESUMO
PURPOSE: To trace a profile of scientific publications, phase I, in order to know whether or not they show pre-clinical phase data, emphasizing bioethical aspects. METHODS: Sixty-one scientific articles, published in 2007, involving research in human beings using new drugs, medicines and vaccines during phase I were analysed. A schedule for data collection was elaborated in which it would be possible to analyse and evaluate those articles. The schedule included items related to the pre-clinical phase associated to the clinical phase, and items related to the sample characteristics. RESULTS: Most of research works were carried out in USA. Taking into consideration that a large number of works have been dedicated to oncologic affections, most of them were carried out in voluntary ill individuals. Information on the pre-clinical phase, phase I, was very poor or absent. Even though some authors consider the phase I research as a promising one and also suggest some future studies on phase II, the reader is not able to consider the same way, as long as there is a shortage of information on the pre-clinical phase. CONCLUSION: The profile of scientific publications showed that data deserve some reflections and analysis to better evaluate the publications on phase I.
Assuntos
Pesquisa Biomédica/ética , Ensaios Clínicos Fase I como Assunto/ética , Avaliação Pré-Clínica de Medicamentos/ética , Preparações Farmacêuticas , Animais , Brasil , Ensaios Clínicos Fase I como Assunto/legislação & jurisprudência , Modelos Animais de Doenças , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Projetos de Pesquisa , Pesquisadores , Estados UnidosRESUMO
This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.