Cardiac safety strategies. 25-26 October 2005, the Radisson SAS Hotel, Nice, France.

摘要

This meeting was organised by IIR Life Sciences. It was chaired by Brian Guth, (head of General Pharmacology at Boehringer Ingelheim Pharma) and brought together scientists and clinicians from the pharmaceutical industry, university and regulatory agencies. The meeting presented emerging trends in cardiac safety, including its regulatory context pertaining to ICH S7A, S7B and E14. ICH S7A and S7B highlight the importance of the hERG test and telemetric studies in non-rodents. ICH E14 describes the clinical 'thorough QT study' that is required by the FDA for any new drug. Marked physiological variability in QT interval over time can be observed, partly as a result of fluctuation in autonomic tone. Beat-to-beat QT variability and T-wave morphology should be considered as a part of an integrated estimate of proarrhythmic risk. A case study illustrated the predictivity of preclinical data for proarrhythmic risk in humans, showing the importance of evaluating QT effects in patients to establish a safety margin.