The ICH E14 and ICH S7B Guidelines describe clinical and nonclinical risk assessment strategies to inform the potential risk for delayed depolarisation and proarrhythmia of a test substance and contribute to the design of clinical investigations. Emergent data over the past several years allow a more integrated nonclinical and clinical approach to evaluate delayed cardiac depolarisation.

The first combined E14/S7B Q&As, published in February 2022, provide information on how this integration may be approached. These Q&As have been replaced by E14/S7B Q&As (R1), which comprise the original Q&As plus new ones that provide clarity on making the testing framework sustainable and flexible enough to limit potential regional differences in the recommended approach to this important safety endpoint for existing and emerging modalities.