ABSTRACT
Introduction No one can be expected to pay 100% attention to 100% of the issues
and data encountered in clinical pharmacology 100% of the time, so one should be forgiven for not recognizing immediately that QTc is a critical issue in drug development. My boss stepped in one day to alert me to the fact that I now had a
new project. We were developing a drug for anti-arrythmia. There were a number of ongoing clinical pharmacology trials that were delivering data, and results would be needed ‘Stat’ to enable the company to make an investment decision. I was used to this by this time. No one ever came by and said we
had plenty of time to get a job done, with no rush, and that senior management was happy to wait as long as we needed to get the job done at our convenience. I was hopeful at that time that maybe one day I would get a project like that, but now I have given up hope that such an event will ever happen. In any event, arrythmia denotes an irregular heartbeat. Some are be-
nign, but some are fatal, and the drug we were developing was intended to prevent its occurrence. To do so, my boss informed me that the drug would impact the ECG. I nodded sagely, and after she left I looked it up in my trusty medical dictionary. ECG denotes an electrocardiogram - a tracing of the electrical activity of the heart over time (we will see a typical one later in this chapter). What I was expecting when the data came in, therefore, was a lot of ECG tracings from which I would measure amplitude, trough to trough time intervals, and other summary measures to statistically describe the activity following dosing with our drug relative to placebo. These would obviously be related to the aortas and ventricles I remembered from 8th grade anatomy, so this should not have been too bad. What I received, however, was a data set of alphabet soup with num-
bers. There were measurements taken for PR, QRS, QT, RR, QTc, QTcB, QTcF, QTcI (to name a few) in addition to text fields describing T-wave morphology. All of these were measured in triplicate following dosing with placebo and our drug in a pretty large number of patients at many times over the course of a day. There was not an ECG to be seen,
nor any ventricles. It was a completely unidentifiable mass of unbelievable gobbledygook seemingly produced by a team of junior medics with slide rules, protractors, and way too much time on their hands. I found out later it was done by senior medics and had been done this way since the 1920s. My guess (which turned out later to be correct) was that these end-
points (PR, etc.) were measuring time relative to the voltage of the heart. But in this instance my medical dictionary let me down. QTc was not in there. This left me with three options to try to figure out what was going on:
1. Ask my statistical colleagues (they did not know, or said they did not).
2. Go downstairs and talk to Denny about what this stuff was (since the report was needed yesterday), but the problem with talking to Denny was that he would want to know about the data for a couple other projects I was working on, and I did not want to field twenty questions when all I needed was one answer.
