Cardiac Safety of Noncardiac Drugs: Practical Guidelines for Clinical Research and Drug Development

ISBN-13: 9781588295156 / Angielski / Twarda / 2004 / 362 str.

Joel Morganroth; Ihor Gussak; Joel Morganroth

Opis

It is generally easy to define the efficacy of a new the- peutic agent. However, what is even more difficult and more challenging yet more important is to define its safety when administered to millions of patients with multi-faceted d- eases, co-morbidities, sensitivities and concomitant medi- tions. The commonest cause of new drug discontinuations, cause for disapproval from marketing and removal from the market after approval is a drug's effect on cardiac repolari- tion which is essentially identified by increasing the duration of the QTc interval duration on the standard 12-lead elect- cardiogram (ECG). Cardiac Safety of Noncardiac Drugs: Practical Guide- Joel Morganroth, MD lines for Clinical Research and Drug Development is designed to present the current preclinical, clinical, and re- latory principles to assess the cardiac safety of new drugs based primarily on their effects on the ECG. Practical gu- ance to define cardiac safety at all stages of clinical research and drug development are featured and discussed by inter- tionally recognized experts with academic, industrial, and regulatory experience. Each chapter contains the best ava- able evidence, the author's personal opinions, areas of c- troversy, and future trends. Although some of the areas are highly specialized, this book has been designed for a broad audience ranging from medical and graduate students to cli- cal nurses, clinical trial coordinators, safety officers, data managers, statisticians, regulatory authorities, clinicians, and Ihor Gussak, MD, PhD scientists.

Recenzje

"...excellent and timely...an extremely readable and handy guide to the subject." - BTS Newsletter

Spis treści

Part I. Introduction Cardiac Safety of Noncardiac Drugs: Historical Recollections Raymond John Lipicky Part II. Preclinical and Pharmacogenomic Cardiac Safety Evaluations Molecular Physiology of Ion Channels That Control Cardiac Repolarization Jeanne M. Nerbonne and Robert S. Kass Cellular, Molecular, and Pharmacologic Mechanisms Underlying Drug-Induced Cardiac Arrhythmogenesis Charles Antzelevitch hERG Assay, QT Liability, and Sudden Cardiac Death Arthur M. Brown Pharmacogenomics in Drug Development: When and How to Apply Richard Judson and Arthur J. Moss Part III. Clinical Methodologies and Technical Aspects of Assessing Cardiac Safety of Investigational Drugs: Focus on Cardiac Repolarization Assessment of Ventricular Repolarization From Body-Surface ECGs in Humans Jean-Philippe Couderc and Wojciech Zareba ECG Acquisition and Signal Processing: 12-Lead ECG Acquisition Justin L. Mortara Digital 12-Lead Holter vs Standard Resting Supine Electrocardiogram for the Assessment of Drug-Induced QTc Prolongation: Assessment by Different Recording and Measurement Methods Nenad Sarapa Holter Monitoring for QT: The RR Bin Method in Depth Fabio Badilini and Pierre Maison-Blanche\ Part IV. Application of Electrocardiology in Clinical Research Fundamentals of ECG Interpretation in Clinical Research and Cardiac Safety Assessment Ihor Gussak, Robert Kleiman, and Jeffrey S. Litwin Design and Conduct of the Thorough Phase I ECG Trial for New Bioactive Drugs Joel Morganroth Use of ECGs in Support of Cardiac Safety in Phase II and III Clinical Trials Martin P. Bedigian Cardiac Arrhythmia Assessment in Phase IV Clinical Studies Gerald A. Faich and Annette Stemhagen Statistical Analysis Plans for ECG Data: Controlling the Intrinsic and Extrinsic Variability in QT Data Alan S. Hollister and Timothy H Montague Interpretation of Clinical ECG Data: Understanding the Risk From Non-Antiarrhythmic Drugs Rashmi R. Shah Part V. Regulatory Considerations The FDA's Digital ECG Initiative and Its Impact on Clinical Trials Barry D. Brown Quality Control and Quality Assurance for Core ECG Laboratories Amy M. Annand-Furlong ECG Digital Communities and Electronic Reporting of Cardiac Safety Data: New Technologies for Reporting Digital ECG Data in Clinical Research Settings Scott Grisanti and Robert Brown Index

Blurb

Although it is relatively easy to determine the efficacy of a new drug, it is difficult to establish its safety when administered to millions of patients with multifaceted diseases, co-morbidities, sensitivities, and multiple drug use. In Cardiac Safety of Noncardiac Drugs: Practical Guidelines for Clinical Research and Drug Development, 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 from their effects on the electrocardiogram (ECG). 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 electrocardiology in clinical research, demonstrating 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 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.
Authoritative and up-to-date, Cardiac Safety of Noncardiac Drugs: Practical Guidelines for Clinical Research and Drug Development offers clinical researchers in industry and academia expert practical advice on establishing their product's cardiac safety, predicting regulatory actions, and getting it successfully to market.