The Assessment of QT/QTc Interval Prolongation in Clinical Trials: A Regulatory Perspective
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Colrttr Strnodovo, PbD Therapeutic Products Directorate, Health Olnada, Ottawa, Ontario, Canada
INTERVAL PROLONGATION
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The Assessment of QT/QTc Interval Prolongation in Clinical Trials: A Regulatory Perspective*
Corrrspondrncr Addrrss Colette Stmadova, PhD, lhempeutic Products Directorate, Hdth Canada, 2nd Flow Hdland Cross. Tower B, 1600Scott Street, A.L. 3102C3, Ottawa, htario. Canada, KIA OK9 (email: cdette-stmad9hc-sc.gc.ca)
Kry Words Electrocardiograms (ECGs); QT/QTc prolongation; Twsade de p'ntes; Venticular repdarization: Cardiacsafety; Clinical trials; Design; Analysis; Interpretation; Drug regulation. 'T?te views expressed in this artide are those ofthe author and do not necessarily rej?ect the opinions of the International Conferenceon Hamonisation (JCH) Expert W&ng Gmups or Stern'ng Committee, Health Cunada. other regulatory authorities,or their advisory M i a . Ihe Drug Information Association is accredited by the Accreditation Councilfor ContinuingMedical Education to provide continuing medical educationfor physicians. The Drug Information Association designatesthis educational activity for a maximum of 1 category I credit toward the AMA Physician's Recognition Award. Each physician should only claim those credits that he/she actually spent in the activity.
m
nte Drug Information Assm'ation is accredited by the Accreditation Council for Phamacy Education as a provider of continuingphamacy education. This ptugram is designatedfora maximum of I contact hour or. 1 continuing education units (CEUs). 286-000QS-4U-HO4.
I f p would like to meive a statement ofcredit,p must m'ew the artide. answer the questionsto the posttest on the Posttest and Evaluation Form and submit it to the DlA. Participants must receive a passing score of 80% or better on the posttest in d e r to meive a statement ofcredit. Statements of a d i t will be mailed within 1 month ofreceipt ofthe Posttest and Evaluation Form. There is nofee to meiveyourstatementofcredit. RefeaseDate: November 200.5 Expimtion Date: November 30,2006 Estimated time to complete the activity: I hour
I NTRODUCTI 0 N The QT interval of the surface electrocardiogram (ECG) consists of the QRS complex,which represents depolarization within the His-Purkinje system and ventricles and the JT interval, which reflects ventricular repolarization. The QT interval is measured from the initiation of the QRS complex to the termination of the T wave. Because of its inverse relationship to heart rate, the measured QT interval is routinely transformed by various heart rate correction formulas into a variable known as the corrected QT interval (QTc),which is intended to be independent of heart rate. Excessive prolongation of the QT/QTc interval creates an electrophysiologicalenvironment that is conducive to torsade de pointes, a polymorphic ventricular tachyarrhythmia. Although
often asymptomatic,torsade de pointes can result in syncope or progress to ventricular fibrillation and sudden cardiac death. Torsade de pointes appears on the ECG as continuous twisting of the
