European and American regulatory authorities are now evaluating all new chemical entities to determine if these entities have any effect on cardiac repolarization. Pre-clinical cardiac repolarization data and precise measurements of the QT interval and other repolarization-related phenomena on the surface ECG are being used to define whether an effect is present. The proper balance between pre-clinical and clinical studies during Phases I, II and III will require careful consideration of the risks and utilities of the variety of tests available. The CPMP and FDA guidelines on these topics are general and are not a recipe of any kind for drug developers who have to consider these issues.
The science of cardiac repolarization is evolving rapidly, and a thoughtful approach is required to tackle the scientific, medical, drug development, and regulatory issues required to bring a safe and effective drug to market. In light of our long-term interest, experience and expertise in the area of cardiac repolarization, we are initiating a new service in Europe and the United States, QT..RESOLUTIONS, to provide drug developers with "one-stop" advisory, delivery, and consultation services focused on evaluating the potential of a drug to effect cardiac repolarization. Over the past decade, we have acquired a unique experience in the analysis of the repolarization effects of many drugs, including anti-histamines, anti-psychotics, prokinetics, and the conazole, macrolide and quinolone antibiotics. QT..RESOLUTIONS offers a menu of pre-clinical electrophysiologic, clinical and regulatory ECG, quantiative repolarization, and consultative services.
A word about our name, QT..RESOLUTIONS. Why the dots? The two dots symbolize that there is more to drug-related repolarization evaluation than just measurement of the QT interval, i.e., there are ion channel kinetics, static and dynamic T-wave phenomena, T-wave morphology, the U wave, etc., that can be affected by drugs. Changes in the QT interval are currently the gold standard for evaluating drug effects on ventricular repolarization. Important additional electrophysiologic parameters of ventricular repolarization can now be measured. Such parameters complement QT measurement in drug-safety testing and screening, and these measures are becoming increasingly utilized and relied upon by regulatory agencies in the drug approval process.
The RVRC is one of the activity of the Heart Research Follow-up Program (HRFUP) which has more than 20 years of research experience in quantitative analysis of ventricular repolarization involving animals, normal subjects, patients with genetic (Long QT Syndrome) and acquired (coronary disease and hypertension) cardiac disorders, and in patients exposed to drugs that affect the QT/U waves of the ECG.
Our group has an unique expertise in the non-invasive evaluation of ventricular repolarization. Our laboratory has published extensively in major journals on factors influencing ventricular repolarization.
Our group consists of physicians, pharmacologists, bio-engineers and technicians working together for a better understanding of the information recorded on the surface ECG. The RVRC service includes a Digital ECG Core Lab that has a long history of research in ECG signal processing. This Core Lab a large toolbox of customized-software has been designed for the analysis of the repolarization segment on the surface ECG for the analysis of repolarization segment based on electrocardiographic and vectocardiographic concepts equiped with various types of ECG devices (from the recorders to the software analysis).
Heart Research Follow-up Program ECG Core Lab is prepared to conduct analysis of all types of ECG recordings including a standard 12-lead ECG, signal-averaged ECG, digital high-resolution ECG and analog or digital long-term 24-hour Holter recordings. Over several years of conducting the NIH and industry sponsored large clinical studies and trials we have developed an expertise in the central coordination and analysis of ECG recordings. Our Digital ECG Core LAB is equipped with the a large set of ECG recorders and analyzer including digital devices from all the major american and European companies. The RVRC is fully prepared to conduct computer analyses of various high-resolution and long-term digital ECG recordings. We have in operation computer programs which interpret various aspects of ECG changes, including not only repolarization analysis in standard and long-term recordings,as descibed before but also P-wave, QRS signal-averaging, and heart rate variability analyses.
The above ECG-analytic facilities are merged with a central computer clinical data management that has been developed and validated over last 20 years.
Our ambulatory and hospital facilities at Strong Memorial Hospital, which is the only big university hospital in the metropolitan area with a broad referral network, provide an excellent opportunity to enroll patients in any kind of clinical study or trial. The best proof for the above is provided by the active involvement of our hospital group.