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The potential of this effort to move the clinical http://www.selleck.cn/products/PLX-4720.html and regulatory assessment of the potential for QTc prolongation from phase 2 to early in phase 1 assessment could beneficially impact drug development by identifying or excluding a potential cardiovascular (CV) safety issue earlier, thus saving resources expended on a stand-alone TQT study. In addition, early signal detection might result in refocusing the drug toward patients with greater potential benefit. However, as the authors point out, http://www.selleckchem.com/products/avelestat-azd9668.html Concerns about a potential QT effect or bringing forward a drug in a class that has had safety signals, would likely strongly favor the FIM PK/PD approach. The relative cost implications of the various ECG strategies, integrating different risk scenarios, would need to be considered. For example, some companies might choose to perform the FIM study using appropriately designed protocols that permit the collection of high quality ECG data, but only analyze the ECG data when it is clear that the drug does not have significant noncardiac toxicity or adverse events that could derail development. There are several other issues that need to be further weighed. The PK/PD FIM approach as currently applied, does not assess assay sensitivity. It is not feasible to add an active control arm to a FIM study, and while statistical approaches can potentially be utilized to address this issue,[6] it remains to be seen if assay sensitivity is critical for the PK/PD approach to be used in lieu of the TQT study. The study described by Darpo et al.[3] has more subjects per dose group (nine receiving active drug and six receiving placebo compared to six and two, respectively). However, this is mitigated by the fact that only two doses are studied http://www.selleckchem.com/products/a-1331852.html and that a typical FIM study typically has ?5 dose groups. However, the PK/PD FIM approach may have reduced applicability for FIM studies that utilize smaller cohorts or fewer dose groups or those that do not truly explore supra-therapeutic exposures. Drugs with long half-lives may require multiple doses to reach sufficient exposures and this approach could be utilized in the multiple ascending dose study. Finally, the FDA has been involved in the development of this experimental approach. In order for positive results to meaningfully impact drug development, it is critical that other regulatory authorities accept the new approach and that ICH-E14 be revised.