ICH E14 - Clinical Evaluation of QT/QTc Interval Prolongation

What it says

E14 gives recommendations on designing, conducting, analyzing and interpreting clinical studies to assess the potential of a drug to delay cardiac repolarization, measured as prolongation of the QT/QTc interval. It describes the thorough QT study, positive controls, and expectations for evaluating QT effects during later development.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• QT prolongation can be linked to a risk of serious arrhythmia, so most new drugs are evaluated for it.
• The study must be sensitive enough to detect a small effect, which is why a positive control is included.
• Concentration-response analysis from earlier studies can in some cases replace a dedicated study.

What inspectors look for

• Whether the study design has assay sensitivity.
• Whether ECG measurements follow a consistent method.
• Whether results are analyzed according to the plan.

Related regulations