What will be the fate of the Thorough QT Study in a post-CiPA world? Stay tuned as the field re-defines preclinical CVS risk assessment.
With the advent of CiPA (Comprehensive in vitroProarrhythmia Assay) the intention is to do away with the clinical Thorough QT (TQT) study as a costly and largely ineffective effort for most molecules. CiPA, coupled with suitable preclinical in vivo studies, certainly promises to provide a relevant and reasonably translatable cardiovascular risk assessment, including human, animal, and in silico components. However, the talk of elminating the TQT study and possibly re-writing ICH S7B (2005) seems predicated on the premise that test articles will traverse CiPA unscathed, or only incur a QT prolongation that can then be excused as not likely to cause arrhythmia or sudden cardiac death based on a specific constellation of CiPA results. There are certain to be exceptions to this apparent binary classification of test articles, and those molecules are likely to still need the more thorough human studies to advance. This will at least be a variation on TQT and not a mere addition of ECG interval analysis to smaller-scope first-in-human studies. Therefore, although we are almost certain to see the TQT study no longer be a staple in drug development, we may see an iteration of it become an alternate route to approval for candidate drugs that pick up flags along the way in CiPA. This will certainly be a topic to follow in 2016 as the field re-defines preclinical cardiovascular risk assessment.
—Robert Kaiser, Safety Pharmacology, Charles River Labs