The ICH E14 guidance requires pharmaceutical companies to conduct Thorough QT (TQT) studies to evaluate a new drug's cardiac safety. There have been discussions between regulatory agencies and pharmaceutical industries to improve the cost-effectiveness of TQT studies and to prevent the administration of the positive control, moxifloxacin, outside of its indication, which have led to the search for alternatives to the conventional TQT studies. The Concentration-QTc (C-QTc) modeling as an alternative approach to the TQT study was proposed.
The ICH E14 Q&A was revised in December 2015 and now enables pharmaceutical companies to use C-QTc modeling as the primary analysis for assessing QTc prolongation risk of new drugs. Because the C-QTc modeling approach is based on using all data from varying dose levels and time points, a reliable assessment of QTc prolongation can be based on smaller-than-usual TQT trials or based on single- and/or multiple- dose escalation (SAD/MAD) studies during early-phase clinical development in order to meet the regulatory requirements of the ICH E14 guideline.
This short course will describe E14 guidance & its regulatory history and discuss current good practices in designing studies to use C- QTc modeling as the primary analysis, conducting a C-QTc analysis, reporting the results of the analysis to support regulatory submissions. If time permitted, we will discuss some of the recent developments in C-QTc modeling.
An additional registration fee is required for all preconference short courses.
Who should attend?
At the conclusion of this course, participants should be able to:
- Appraise the ICH E14 guidance & its regulatory history and good practices in C-QTc modeling
- Design studies to use C-QTc modeling as the primary analysis
- Perform and report C-QTc modeling to support regulatory submissions