Cardiac Safety Of Noncardiac Drugs

by Morganroth, Joel; Gussak, Ihor

• ISBN13: 9781588295156
• ISBN10: 158829515X
• Format: Hardcover
• Copyright: 2004-11-30
• Publisher: Humana Pr Inc

Summary

Basic and clinical researchers from industry and academia detail the preclinical, clinical, and regulatory principles currently used to assess the cardiac safety of new drugs. The authors explain the parameters of cardiac safety at all stages of clinical research and drug development, including both the preclinical and pharmacogenomic aspects generally and the clinical methodologies and technical aspects for investigational drugs based on cardiac repolarization, as defined by the duration of the QTc interval. Additional chapters comprehensively review the application of electrocardiography in clinical research, the fundamentals of ECG interpretation in clinical trials, the statistical analysis plans for ECG data obtained in formal clinical trials, and the practical interpretation of the ECG results. Highlights include practical guidance on how to conduct a thorough ECG Trial in New Drug Development, how to use new ECG and web based technology in clinical research, and how to follow the new FDA requirements for ECG submissions.

Table of Contents

Dedication	v
Preface	vii
Contributors	xi
Part I. Introduction
Chapter 1. Cardiac Safety of Noncardiac Drugs: Historical Recollections	3	(10)
Raymond John Lipicky
Part II. Preclinical and Pharmacogenomic Cardiac Safety Evaluations
Chapter 2. Molecular Physiology of Ion Channels That Control Cardiac Repolarization	13	(24)
Jeanne M. Nerbonne and Robert S. Kass
Chapter 3. Cellular, Molecular, and Pharmacologic Mechanisms Underlying Drug-Induced Cardiac Arrhythmogenesis	37	(30)
Charles Antzelevitch
Chapter 4. hERG Assay, QT Liability, and Sudden Cardiac Death	67	(16)
Arthur M. Brown
Chapter 5. Pharmacogenomics in Drug Development: When and How to Apply	83	(24)
Richard Judson and Arthur J. Moss
Part III. Clinical Methodologies and Technical Aspects of Assessing Cardiac Safety of Investigational Drugs: Focus on Cardiac Repolarization
Chapter 6. Assessment of Ventricular Repolarization From Body-Surface ECGs in Humans	107	(24)
Jean-Philippe Couderc and Wojciech Zareba
Chapter 7. ECG Acquisition and Signal Processing: 12-Lead ECG Acquisition	131	(16)
Justin L. Mortara
Chapter 8. Digital 12-Lead Holter vs Standard Resting Supine Electrocardiogram for the Assessment of Drug-Induced QTc Prolongation: Assessment by Different Recording and Measurement Methods	147	(20)
Nenad Sarapa
Chapter 9. Holter Monitoring for QT: The RR Bin Method in Depth	167	(22)
Fabio Badilini and Pierre Maison-Blanche
Part IV. Application of Electrocardiology in Clinical Research
Chapter 10. Fundamentals of ECG Interpretation in Clinical Research and Cardiac Safety Assessment	189	(16)
Thor Gussak, Robert Kleiman, and Jeffrey S. Litwin
Chapter 11. Design and Conduct of the Thorough Phase I ECG Trial for New Bioactive Drugs	205	(18)
Joel Morganroth
Chapter 12. Use of ECGs in Support of Cardiac Safety in Phase II and III Clinical Trials	223	(6)
Martin P. Bedigian
Chapter 13. Cardiac Arrhythmia Assessment in Phase IV Clinical Studies	229	(10)
Gerald A. Faich and Annette Stemhagen
Chapter 14. Statistical Analysis Plans for ECG Data: Controlling the Intrinsic and Extrinsic Variability in QT Data	239	(20)
Alan S. Hollister and Timothy H Montague
Chapter 15. Interpretation of Clinical ECG Data: Understanding the Risk From Non-Antiarrhythmic Drugs	259	(42)
Rashmi R. Shah
Part V. Regulatory Considerations
Chapter 16. The FDA's Digital ECG Initiative and Its Impact on Clinical Trials	301	(28)
Barry D. Brown
Chapter 17. Quality Control and Quality Assurance for Core ECG Laboratories	329	(10)
Amy M. Annand-Furlong
Chapter 18. ECG Digital Communities and Electronic Reporting of Cardiac Safety Data: New Technologies for Reporting Digital ECG Data in Clinical Research Settings	339	(16)
Scott Grisanti and Robert Brown
Index	355