RESUMO
This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.
Assuntos
Doenças Cardiovasculares/diagnóstico , Coleta de Dados/normas , Determinação de Ponto Final/normas , Acidente Vascular Cerebral/diagnóstico , Ensaios Clínicos como Assunto , Humanos , Estados Unidos , United States Food and Drug AdministrationAssuntos
Cardiomiopatia Dilatada/etiologia , Distrofia Muscular de Duchenne/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Bancos de Espécimes Biológicos/organização & administração , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Técnicas de Diagnóstico Cardiovascular , Modelos Animais de Doenças , Genótipo , Glucocorticoides/uso terapêutico , Coração Auxiliar , Humanos , Masculino , Distrofia Muscular de Duchenne/genética , Fenótipo , Sistema de Registros , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/terapia , Respiração Artificial , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapiaRESUMO
Electrocardiographic monitoring is an integral component of the clinical assessment of cardiac safety of all compounds in development. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline recommends a dedicated study to evaluate drug-induced effects on cardiac repolarization ("thorough QT/QTc study"). There has been limited published information on QT interval changes secondary to therapeutic proteins; however, in theory, biologic therapies may affect cardiac electrical activity either directly or indirectly. This article summarizes scientific discussions of members of the Cardiac Safety Research Consortium and includes possible approaches to consider for the clinical evaluation of drug-induced QT prolongation in development programs of therapeutic proteins.
Assuntos
Arritmias Cardíacas , Pesquisa Biomédica/métodos , Eletrocardiografia/métodos , Guias de Prática Clínica como Assunto/normas , Proteínas/uso terapêutico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , HumanosAssuntos
Cardiologia/normas , Doenças Cardiovasculares/terapia , Ensaios Clínicos como Assunto/normas , Determinação de Ponto Final/normas , American Heart Association , Cardiologia/legislação & jurisprudência , Doenças Cardiovasculares/diagnóstico , Elementos de Dados Comuns , Confidencialidade , Bases de Dados Factuais , Health Insurance Portability and Accountability Act , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes , Projetos de Pesquisa , Sociedades Médicas , Terminologia como Assunto , Pesquisa Translacional Biomédica , Resultado do Tratamento , Estados UnidosRESUMO
Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.
Assuntos
Drogas em Investigação/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Animais , Ensaios Clínicos Controlados como Assunto/métodos , Aprovação de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos/métodos , Eletrocardiografia/efeitos dos fármacos , Humanos , Cooperação Internacional , Síndrome do QT Longo/fisiopatologiaRESUMO
This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.