Electrocardiographic assessment for therapeutic proteins—scientific discussion

• Published in: The American heart journal 2010-10, Vol.160 (4), p.627-634
• Main Authors: Rodriguez, Ignacio, MD, Erdman, Andrew, MD, Padhi, Desmond, PharmD, Garnett, Christine E., PharmD, Zhao, Hong, PhD, Targum, Shari L., MD, Balakrishnan, Suchitra, MD, PhD, Strnadova, Colette, PhD, Viner, Norman, MD, Geiger, Mary Jane, MD, PhD, Newton-Cheh, Christopher, MD, MPH, Litwin, Jeffrey, MD, Pugsley, Michael K., PhD, Sager, Philip T., MD, Krucoff, Mitchell W., MD, Finkle, John K., MD
• Format: Article
• Language: English
• Subjects: Arrhythmias, Cardiac - diagnosis; Arrhythmias, Cardiac - physiopathology; Arrhythmias, Cardiac - therapy; Biological and medical sciences; Biomedical Research - methods; Cardiology. Vascular system; Cardiovascular; Critical path; Electrocardiography; Electrocardiography - methods; Humans; Medical sciences; Molecular weight; Pharmaceutical industry; Practice Guidelines as Topic - standards; Proteins; Proteins - therapeutic use; Risk assessment
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2010.07.001

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.