ABSTRACT
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.
Subject(s)
Cardiovascular Diseases/diagnosis , Data Collection/standards , Endpoint Determination/standards , Stroke/diagnosis , Clinical Trials as Topic , Humans , United States , United States Food and Drug AdministrationSubject(s)
Cardiomyopathy, Dilated/etiology , Muscular Dystrophy, Duchenne/complications , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/etiology , Biological Specimen Banks/organization & administration , Cardiomyopathy, Dilated/drug therapy , Cardiomyopathy, Dilated/therapy , Clinical Trials as Topic , Combined Modality Therapy , Diagnostic Techniques, Cardiovascular , Disease Models, Animal , Genotype , Glucocorticoids/therapeutic use , Heart-Assist Devices , Humans , Male , Muscular Dystrophy, Duchenne/genetics , Phenotype , Registries , Respiration Disorders/etiology , Respiration Disorders/therapy , Respiration, Artificial , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/therapyABSTRACT
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.
Subject(s)
Arrhythmias, Cardiac , Biomedical Research/methods , Electrocardiography/methods , Practice Guidelines as Topic/standards , Proteins/therapeutic use , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , HumansSubject(s)
Cardiology/standards , Cardiovascular Diseases/therapy , Clinical Trials as Topic/standards , Endpoint Determination/standards , American Heart Association , Cardiology/legislation & jurisprudence , Cardiovascular Diseases/diagnosis , Common Data Elements , Confidentiality , Databases, Factual , Health Insurance Portability and Accountability Act , Humans , Quality Assurance, Health Care , Quality of Health Care , Reproducibility of Results , Research Design , Societies, Medical , Terminology as Topic , Translational Research, Biomedical , Treatment Outcome , United StatesABSTRACT
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.
Subject(s)
Drugs, Investigational/adverse effects , Long QT Syndrome/chemically induced , Animals , Controlled Clinical Trials as Topic/methods , Drug Approval/organization & administration , Drug Evaluation, Preclinical/methods , Electrocardiography/drug effects , Humans , International Cooperation , Long QT Syndrome/physiopathologyABSTRACT
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.