COMPAS Analytics: The industry’s most advanced suite
of QT analysis tools

iCardiac’s COMPAS platform maximizes the precision and decreases the cost of cardiac safety assessment from First-in-Human studies to Phase III studies. This suite of tools, which complies with the FDA’s ICH E14 QT/QTc guidance for Through QT Studies (TQT), was originally developed and validated at the University of Rochester’s Heart Research Follow Up Program (HRFUP), as well as in Pfizer’s Research and Development programs. iCardiac’s analytics have been used for over a decade in support of clinical trials.

Thorough QT Plus

iCardiac’s TQT Plus minimizes the effects of heart rate changes and increases the precision of QT analysis by selecting the optimal ECG periods for measurement. TQT Plus tools identify and flag periods of steady-state repolarization in the QT intervals of continuous ECG recordings. This computerized method provides reproducible, consistent and cost-effective measurements in cardiac safety studies.

High Precision QT (FDA ICH E14 Compliant)

High Precision QT (HPQT) improves analysis precision, reduces analysis time and increases the amount of data that can be analyzed per subject. As a result, it reduces cost by eliminating the need for cardiologists to manually review all ECG data.

The High Precision method has been shown to provide significant benefits for development teams in comparison to study methods utilized by traditional ECG core laboratories:

iCardiac’s HPQT method has been validated in numerous clinical QT studies, including a cross-validation against data from five leading ECG core laboratories, and has been used in submissions of QT data to the FDA. As part of the core validation studies, the University of Rochester independently performed the analysis of the ECGs and the results were sent to the FDA for statistical review. The extensive research and validation efforts have culminated in the High Precision QT method being recognized and accepted as equivalent to the manual evaluation of QT intervals by cardiologists in cardiac safety studies.

Dynamic QTbtb Analysis

iCardiac’s QTbtb analysis significantly improves the precision of the QT measurement and reduces the likelihood of false positives. It also dramatically reduces the number of subjects required for a study.

Dynamic analysis of Holter or continuous ECG data beat-to-beat (QTbtb) is an advanced cardiac safety assessment method that allows for quantification of QT interval changes under varying conditions of heart rate and autonomic tone, a measurement that cannot be obtained with Standard QT correction formulae. This advanced ECG biomarker relies on a set of sophisticated algorithms for dynamic data analysis, providing drug developers with an ability to visualize how a sequential series of QT-RR measurements or “cloud” of data moves over time at baseline and at the matched on-drug time period. This visualization ability allows for a more precise evaluation of pharmacokinetics in relationship to pharmacodynamic events that affect the ECG, such as behavioral or hemodynamic changes.

Advanced Biomarkers

The FDA has acknowledged the need for more precise and meaningful electrocardiographic markers than the QTc interval prolongation - currently the surrogate marker for arrhythmia liability identified by ICH E14 regulatory guidance. iCardiac has developed and implemented advanced ECG biomarkers that enable a comprehensive evaluation of repolarization morphology and dynamics.

These electrocardiographic markers provide complementary information to QT interval results, and have proven to be a more reliable measure than QT prolongation in validation studies with top pharmaceutical companies and academic institutions.

Unlike the current QTc prolongation measurement, iCardiac’s repolarization biomarkers enable measurement of the subtle differences in ECG signals that may indicate arrhythmia predisposition, thus enabling the sponsor to differentiate between “benign QT” prolongation and drugs posing actual risk.  

Restitution Analysis

iCardiac performs restitution analysis to help quantify arrhythmia liability, or to assess the efficacy of cardiovascular drugs with potential to improve cardiac restitution. Cardiac restitution is the ability of the heart to recover from one beat to the next. This can be measured by assessing the QT interval (working phase of the heart) relative to the previous TQ interval (resting phase of the heart). When the heart is not under stress, this ratio is less than 1, meaning the heart is resting more than it is working. However, as stress increases on the heart, for example during exercise or even eating, the heart works more than it rests, increasing this ratio to greater than 1. Sustained periods with inadequate recovery between beats would presumably lead to increased arrhythmia vulnerability as the QT/TQ ratio increases (i.e. R on T beats where TQ interval is zero are associated with increased arrhythmia liability).