Topics in the design and analysis of Thorough QT Studies
Regulatory requirements for the licensing of new drugs necessitate the conduct of a Thorough QT Study, in which healthy volunteers will be administered the drug over 24 hours in order to determine whether there is any effect on cardiac rhythm. In particular, volunteers are normally treated with the test drug, placebo and an active control. The last is known to have effects on the heart, which should be picked up in the study. Output from electrocardiograms is studied, and such items as the QT interval and the RR interval are determined at various times after administration of the drug. Of particular interest is whether the QT interval is lengthened, when put into the context of the RR interval, as this might suggest an undesirable effect on cardiac activity. This project concerns the design and analysis of Thorough QT studies, focussing on questions such as appropriate allowance for the RR interval and for the changing concentration of the drug over time as well as considerations of sample size and interim analyses.