Cardiovascular Safety in Drug Development and Therapeutic Use : New Methodologies and Evolving Regulatory Landscapes

At a time when the field of cardiac safety is going through important changes, this unique book provides the rationale for, and cutting-edge explanations of, new regulatory landscapes that will likely govern cardiac safety assessments globally for the foreseeable future. Exposure-response modeling is already being accepted by regulatory agencies in lieu of the traditional Thorough QT/QTc Study, and the Comprehensive __in vitro__Proarrhythmia Assay initiative is well under way. Developments in the field of cardiovascular safety are also described and discussed in the book. These include the search for more efficient ways to exonerate new drugs for type 2 diabetes from an unacceptable cardiovascular liability, how best to address off-target blood pressure increases induced by noncardiovascular drugs, and the continued evolution of the discipline of Cardio-oncology. Front Matter....Pages i-xxvi Front Matter....Pages 1-1 The Central Role of Cardiovascular Safety in Drug Development and Therapeutic Use....Pages 3-20 Front Matter....Pages 21-21 Drug Structures and the Biological Basis of Drug Responses....Pages 23-49 Cardiovascular Structure, Function, and Pathophysiology....Pages 51-70 Front Matter....Pages 71-71 Analyzing and Reporting Efficacy Data....Pages 73-98 Analyzing and Reporting Safety Data....Pages 99-113 Meta-analysis, Group Sequential Study Designs, Centralized Endpoint Adjudication, and Composite Endpoints....Pages 115-133 Front Matter....Pages 135-135 The Proarrhythmic Cardiac Safety Regulatory Landscape Circa 2005–2015: Drug-Induced hERG Channel Block and the Thorough QT/QTc Study....Pages 137-163 QTc Exposure–Response Modeling as a Primary Methodology for Proarrhythmic Cardiac Safety Assessments....Pages 165-180 The Comprehensive In Vitro Proarrhythmia Assay Initiative....Pages 181-197 Front Matter....Pages 199-199 Oncology Drug Therapy: Cardiotoxicity and the Discipline of Cardio-oncology....Pages 201-221 Blood Pressure Responses to Noncardiovascular Drugs in Development and Therapeutic Use....Pages 223-238 The Genesis of Cardiovascular Safety Regulatory Landscapes for New Antidiabetic Drugs for Type 2 Diabetes....Pages 239-250 Satisfying the Regulatory Requirements for New Antidiabetic Drugs for Type 2 Diabetes Most Expeditiously....Pages 251-275 Front Matter....Pages 277-277 Postmarketing Cardiovascular Safety Considerations....Pages 279-304 A Safety Perspective on Additional Aspects of Drug Development and Therapeutic Use....Pages 305-330 Back Matter....Pages 331-333 With the advent of multiple new therapeutic agents for a variety of important diseases has come an increasing realization that many of these drugs can have adverse effects on the heart and vascular system. As this book so elegantly details the mechanisms by which harm occurs are highly complex, many times predictable, but always clinically relevant. Notable experts in the field of cardiovascular medicine, such as Drs. Turner, Karnad, and Kothari, have turned their attention to this thorny problem, and begun to dissect the diverse mechanisms by which cardiac harm can occur with a variety of non-cardiac drugs. This is no easy task, given the complexity of the diseases we treat, and the wide spectrum of new therapies we seek to apply. However, it is an issue with which all health care providers must become familiar in order to prescribe appropriate therapy while safeguarding patients against avoidable and life-threatening cardiac adverse effects. This compendium represents the state-of-the-art in the evolving field of cardiac safety and is vital reading for those interested in developing new chemical entities, as well as those who prescribe them and monitor patients for their hazard. As such, I recommend this book as essential reading for students, scientists, and health care providers at all levels of training. Peter R. Kowey, MD, FACC, FAHA, FHRS Lankenau Institute for Medical Research & Thomas Jefferson University At a time when the field of cardiac safety is going through important changes, this unique book provides the rationale for, and cutting-edge explanations of, new regulatory landscapes that will likely govern cardiac safety assessments globally for the foreseeable future. Exposure-response modeling is already being accepted by regulatory agencies in lieu of the traditional Thorough QT/QTc Study, and the Comprehensive in vitro Proarrhythmia Assay initiative is well under way. Developments in the field of cardiovascular safety are also described and discussed in the book. These include the search for more efficient ways to exonerate new drugs for type 2 diabetes from an unacceptable cardiovascular liability, how best to address off-target blood pressure increases induced by noncardiovascular drugs, and the continued evolution of the discipline of Cardio-oncology. "a resource that will likely serve as a standard for years to come" - Dr Jonathan Seltzer Therapeutic Innovation & Regulatory Science , 2017;51(2):180 "I have no hesitation in recommending this book as a valuable reference source" - Dr Rashmi Shah Journal for Clinical Studies , 2017;9(1):62-63 J. Rick Turner, Dilip R. Karnad, Snehal Kothari. Includes Bibliographical References.