Benefits of Utilizing Early Precision QT and Artificial Intelligence-Powered Data Quality Assessments in Early Phase Trials

March 21, 2024
10:00 am
11:00 am
ET
Webinar Event

This webinar will review the opportunities provided by FIH trials to detect and manage the safety signals of a new drug entity. The advantage of using EPQT to leverage data from small FIH trials, along with specific results of how EPQT can assess the risk of QT interval prolongation will be discussed. Finally, an overview of how the AI-powered data quality tool was developed and its ability to assess data quality will be presented. The session will conclude with a live Q&A, providing participants with an opportunity to engage directly with the experts.

Session information:

The probability of success (POS) for developing a new drug is 10% to 15% but is as low as 3% in oncology and up to 33% in ophthalmology. Most new drug entities, ~70% fail in Phase I or the first-in-human (FIH) trial predominantly due to unmanageable toxicity or poor pharmacokinetics. These findings highlight the importance of the FIH trial in drug development where the main causes for failure are assessed and dictate if an asset progresses to late-phase development or the whole program fails.

Increased efficiency could be realized if cardiac safety data are generated from studies performed earlier in the clinical development program. In single ascending dose (SAD) or multiple ascending dose (MAD) FIH studies, escalating doses of the new drug entity are given to small cohorts of subjects, often up to the maximum tolerated dose. Plasma concentrations are often, therefore, achieved which will not be exceeded in patients. While some SAD or MAD studies include more rigorous assessments for changes from baseline in QT and other electrocardiogram (ECG) intervals, more common is a safety assessment based on the Principal Investigator’s read of 12-lead ECG printouts. This approach cannot confidently detect changes in the QT interval at the precision level of a TQT trial. In response, iCardiac Technologies, acquired by Clario in late 2017, introduced a transformative cardiac safety testing method. Expert Precision QT (EPQT), to improve the overall productivity of pharmaceutical development and, in collaboration with The Food and Drug Administration (FDA), has been tested successfully in a comprehensive clinical trial.

Given the critical position an early-phase trial has in determining the POS of a new drug entity, it is essential data generated at this phase are complete, usable and reliable. If manageable toxicity is detected in early-phase development, the steps taken to mitigate the toxicity in later-phase development can only be successful if the early-phase data are complete and reliable. For these reasons, assessing data quality after completion of the first dose cohort may help to identify errors in data collection or documentation. This provides an opportunity to determine the cause of the errors and implement corrective actions before more impactful data are collected from higher dose cohorts, during which toxicity is more likely to arise. Clario has developed an artificial intelligence (AI) powered tool to automatically check the quality of long continuous ECG recordings without the need for manual review of the recordings. Using an AI-powered tool will increase the overall quality of ECG analysis and reduce the risk of errors due to missing data or inappropriately misclassifying useful data.

Presented by Clario’s cardiac safety experts, Dr. Vic Patel and Dr. Jean Philippe Couderc, the webinar will review the opportunities provided by FIH trials to detect and manage the safety signals of a new drug entity. The advantage of using EPQT to leverage data from small FIH trials, along with specific results of how EPQT can assess the risk of QT interval prolongation will be discussed. Finally, an overview of how the AI-powered data quality tool was developed and its ability to assess data quality will be presented. The session will conclude with a live Q&A, providing participants with an opportunity to engage directly with the experts.

What you’ll learn:

  • Review the importance of the first-in-human trial and the opportunities it affords
  • Understand the advantage of leveraging EPQT and AI-powered data quality in early-phase QT assessment

Speakers

Vickas Patel headshot

Vic Patel, M.D., Ph.D.

Vice President and Chief Medical Officer, Cardiology at Clario

Dr. Patel is board-certified in cardiology with a Ph.D. in Biophysics and has done extensive research on mechanisms of cardiac arrhythmias. He was on faculty at U. Penn. School of Medicine for 11 years where he directed molecular arrhythmia research and practiced clinical electrophysiology. Dr. Patel then moved into drug development and cardiac safety as a clinical development leader and therapy area head across all phases. At Clario, Dr. Patel oversees cardiology consulting and ECG/Holter core lab services, while leading the biostatistics and medical writing groups. He works with our global customers to ensure they are satisfied and provided with robust, cost-effective solutions.

Alain Gay, M.D.

Senior Cardiologist, Cardiology at Clario

Dr. Alain Gay, M.D., is board-certified in cardiology. After completing his training as a cardiologist at the Hopital Cardiologique in Lille, France. Dr. Gay practiced for 10 years in a community hospital, completing his training in cardiac electrophysiology and cardiac pacing. Dr. Gay then moved into drug development and medical affairs studies for 15 years at Bayer. He contributed to establishing studies standards in heart failure and contributed to the prelaunch and launch of both Xarelto®️ and Kerendia®️. At Clario, Dr. Gay is a contributor to the ECG core lab, also reading Holters and other recording devices. He works with our global customers to ensure their needs are met with robust, cost-effective solutions.

Jean-Phillippe Couderc, Ph.D., MBA

Professor of Medicine & Electrical and Computer Engineering, University of Rochester

Jean-Philippe Couderc is a Scientist with experience in the development of groundbreaking technologies in the field of quantitative electrocardiography and cardiac safety. Internationally recognized authority in the development of computerized technologies related to cardiology. Scientific Founder and Chief Technology Officer of iCardiac Technologies Inc, Dr. Couderc is also the Founder and Director of the Telemetric and Holter ECG warehouse, an initiative developed with the US FDA under a private-public partnership and funded by the National Institute of Health. Characterized by a creative mind leading to translational scientific discoveries which have been highlighted by major media including the Wall Street Journal.