Developing a Mechanistic Model-Based Approach to Assess Cardiac Safety of New Drugs
Thursday, Sept. 14, 2017
12:00 p.m. - 1:00 p.m., Eastern Daylight Time (EDT)
David Strauss, MD, PhD
Director, Division of Applied Regulatory Science
FDA’s Center for Drug Evaluation and Research
About the Presentation
This presentation addresses the public health and regulatory need for:
• a new paradigm to assess cardiac safety of new drugs;
• the cutting edge science that underpins that paradigm;
• the current status of ongoing validation studies; and
• expected impact of this novel mechanistic, model-informed approach.
In the 1990s to early 2000s, multiple drugs were removed from the market because they caused arrhythmias and sudden death. In response, regulatory guidelines were implemented that have successfully prevented such occurrences by focusing on detecting hERG potassium channel block in cells and QT prolongation on the electrocardiogram. However, this approach is not very specific because some drugs are flagged as posing a risk and thus can be dropped from development when they are actually safe.
A new model, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, aims to be a more accurate and comprehensive, mechanistic-based assessment of drug safety. It combines data that we get from multiple ion channels in the lab in a computer model to predict the risk in patients. The results are checked in an assay with human-induced pluripotent stem cell derived cardiomyocytes and using electrocardiographic biomarkers in standard phase 1 clinical trials.
Much of the development and validation work for CiPA has occurred in FDA labs, but this effort also involves our worldwide drug regulatory colleagues, academia, and industry through multiple public-private partnerships. In March 2017, this new model was presented to an FDA advisory committee, which endorsed this approach, pending ongoing validation studies.
About the Presenter
David Strauss, MD, PhD is a leader in translational sciences regulatory research. Before serving in his current role as Director of the Division of Applied Regulatory Science in FDA’s Center for Drug Evaluation and Research (CDER), Dr. Strauss was Senior Advisor for Translational and Experimental Medicine in CDER’s Office of Clinical Pharmacology and a medical officer and premarket medical device reviewer in the Center for Devices and Radiological Health. He earned a B.A. in chemistry and medical degree (M.D.) from Duke University, and a Ph.D. in clinical physiology from Lund University, Sweden. Dr. Strauss also completed a postdoctoral fellowship at Johns Hopkins University.
He has published over 100 peer-reviewed journal articles and book chapters related to assessing the safety and effectiveness of drugs and medical devices and predicting individualized response to therapies. He currently oversees research and review activities across the translational research spectrum, including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine and postmarket analyses.