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

Area of Science:

• Pharmacology
• Clinical Safety
• Drug Development

Background:

• Emerging trends in cardiac safety were discussed, focusing on regulatory frameworks.
• Key guidelines including ICH S7A, S7B, and E14 were central to the discussions.

Framework:

• ICH S7A and S7B emphasize the necessity of hERG testing and non-rodent telemetric studies.
• ICH E14 mandates the FDA-required clinical 'thorough QT study' for all new drug applications.

Implementation:

• Physiological variability in QT interval, influenced by autonomic tone, requires careful consideration.
• Beat-to-beat QT variability and T-wave morphology are crucial components of integrated proarrhythmic risk assessment.

Implications:

• Preclinical data can predict human proarrhythmic risk, as demonstrated by a case study.
• Evaluating QT effects in patients is essential for establishing a drug's safety margin.