Phase I QT Studies: Early Precision QT
The New Standard For Cardiac Safety
Assessing cardiac safety much earlier in the drug development process, by using data collected from routine Phase I studies, is now a strategy that is fully accepted by international regulatory agencies. In December 2015, the International Council for Harmonisation revised the guidance that defines and enables an alternative path to the conduct of a Thorough QT study. Likely the most significant regulatory shift in cardiac safety since the original E14 Guidance was adopted in 2005, the new revision emerged following the successful conduct of a prospective validation study in 2014 that was sponsored by iCardiac, using our personnel and technology to perform the critical data analysis. This alternative approach, which iCardiac calls “Early Precision QT,” provides significant benefit to drug developers – earlier, more precise, cost effective, cardiac safety assessment and informed decision making.
Early Precision QT Can Enable an FDA Thorough QT (TQT) Waiver
Per the December 2015 E14 Q&A document revision adopted by the International Council for Harmonisation, the FDA and other regulators will now review applications for TQT study waivers. iCardiac pioneered this alternative approach through its sponsorship of the 2014 IQ-CSRC validation study that demonstrated the feasibility and efficiency of exposure response analysis to characterize QT effect in routine Phase I clinical trials. iCardiac provides unparalleled expertise and experience to sponsors that are considering this strategy in their Phase I studies. By working with iCardiac and using Early Precision QT, sponsors can potentially save millions in TQT study costs while obtaining critical and actionable information about their compounds earlier in development.
iCardiac’s Quality Metric for Ensuring the Reliability of Phase I QT Assessment
As an innovator in the use of Phase I data for QT assessment, iCardiac recently introduced Method Bias Sensitivity (MBS), an advanced quality metric developed to provide certainty to regulators – and sponsors – as to whether the ECG core lab’s methodology for measuring QT intervals introduces relevant bias into the results. MBS serves a similar function in Phase I QT studies as the positive control arm in Thorough QT studies, in that they each help to minimize the possibility of a false negative result. Additionally, MBS provides information confirming the accuracy and consistency of a core lab’s ECG measurement method. It does this by comparing the QT measurements derived by the lab method to the automated measurements from each time point in the study. MBS is especially helpful in assessing studies where sufficiently high multiples of the clinically relevant plasma concentration are not reached, which often cannot be determined until later in the development program. iCardiac, which helped develop and test the new metric in collaboration with several regulatory and industry experts, offers MBS assessment in all new Phase I or other studies where QT is being measured for the purpose of characterizing QT effect or seeking a waiver of a TQT study.
Implementing Early Precision QT Across Your Drug Development Program
iCardiac offers training and certification processes for drug developers, as well as clinical pharmacology units, to help move development programs to this new standard. In order to ensure the reliability and accuracy of the results and reduce risks, iCardiac’s Early Precision QT needs to be administered by Certified providers. To learn more about training and certification please contact your iCardiac representative at 585-295-7610. Early Precision QT is only available through iCardiac and its Certified Partners.
About the IQ-CSRC Study
In December 2014 the FDA conducted a symposium to discuss the results of the IQ-CSRC (Cardiac Safety Research Consortium) study on the effectiveness of an advanced cardiac safety assessment methodology. The study used iCardiac’s High Precision QT analysis combined with Exposure Response (ER) modeling. Specifically, this methodology promises much higher precision in gauging the cardiac safety of compounds in Phase I human trials – much earlier than currently done and at a much lower cost. The study confirms this assumption.