QT Prolongation & Beyond

Venue l Registration

Post-Conference Workshop - 24th November 2005

Good Science Principles in ECG analysis: Correctly assessing the repolarisation risk

ABOUT THE WORKSHOP
With recent regulatory opinions emphasizing preclinical imprecision in the assessment of repolarization risk, there has been no better time to highlight the importance of adopting the most accurate methods for in-vivo QT interval analysis. Robust preclinical risk assessment is not possible unless the potential for false-negative and false-positive results have been effectively eliminated. This workshop will cover step-by-step analysis of the canine and cynomolgus ECG to assess drug-mediated changes in repolarization. The derivation and use of a novel, and demonstrably accurate, individual QT rate-correction method will be demonstrated. Methodology will be introduced which effectively removes the critical impact of QT hysteresis. The sessions will include detailed in-vivo preclinical data obtained with reference compounds such as moxifloxacin.

WORKSHOP AGENDA
09.30	Delegate registration and coffee
10.00	Workshop leader: Henry Holzgrefe Principal Scientist Safety Pharmacology BRISTOL MYERS SQUIBB	Good science principles in ECG analysis to assess repolarization risk Characteristics of the canine and cynomolgus ECG Effective removal of rate and hysteresis components Derivation of a stable QTc Design of in-vivo repolarization studies In-vivo QT assessment in a GLP environment
12.30	Lunch
13.45	Workshop leader: Marek Malik Professor of Cardiac Electrophysiology ST GEORGE’S, UNIVERSITY OF LONDON	Practicalities of clinical thorough QT studies The recent scientific development as well as the new E14 guidelines put into light the need to optimise the design of thorough QT studies. Although the scientific background is covered during the main meeting, many practical aspects and feasibility suggestions need to be discussed in more detail. This half-day session will look at the practicalities of design and conduct of thorough QT studies through interactive discussions. Topics covered: Organisation of ECG collection including serial and consecutive monitoring Selection of suitable ECG measurement technology Practice of ECG measurement including distinction between measurable and non-measurable recordings Testing heart rate stability of selected time-points Definition of QT/RR relationship and its formal description in study population and individuals Design of heart rate correction formula Design of QT/RR hysteresis model and of hysteresis correction formula Selection of study time-points and the prospective design of the analytical plan Compilation of ECG database and digital data submission
16.00		Close of Workshop
16.15	Close of Workshop

ABOUT YOUR WORKSHOP LEADERS
Mr. Henry Holzgrefe		Mr. Henry Holzgrefe is presently a Principal Scientist in the Department of Safety Pharmacology at Bristol-Myers Squibb. He has 24 years of diverse drug-development experience within the pharmaceutical industry. His scientific career has been dedicated to the development of preclinical models of cardiovascular disease, with emphasis of the in-vivo assessment of repolarization and ventricular function.
Dr Marek Malik		Dr Marek Malik graduated from both mathematics and medicine, and has PhD and Doctor of Science degrees from mathematics and computer science, and MD and Doctor of Science degrees from medicine and cardiology. He is presently Professor of Cardiac Electrophysiology at University of London and the head of Noninvasive Electrophysiology Unit at St George’s Division of Cardiac and Vascular Sciences. His scientific interests include acquired long QT syndrome, electrocardiology and computerised electrocardiography, cardiac autonomic status, and cardiac risk stratification. He has authored 11 monographs and textbooks and more than 350 articles in peer review journals.

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