Since the ICH E14 guidance was finalized in 2005, experiences implementing the guidance in the ICH regions have given rise to requests for clarification. This question and answer (Q&A) document is intended to facilitate implementing the E14 guidance by clarifying key issues.

This guidance is a revision of the ICH guidance titled E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs – Questions and Answers (November 2008). This Q&A document has been revised as follows:

  • In April 2012, added questions on Sex Differences, Incorporating New Technoloas recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not requiredgies, Late Stage Monitoring, and Heart Rate Correction
  • In March 2014, added questions on Concentration-Response Relationships, Combination Products, Large Targeted Proteins and Monoclonal Antibodies, and Special Cases
  • In December 2015, revised the question on Use of Concentration Response Modeling of QTC Data, to harmonize guidance on how concentration response modeling could be used for regulatory decision-making

This revised guidance incorporates the March 2014 and December 2015 changes. In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

Posted on the FDA website on 13 June 2017