Standing at the bedside in Phase 1

Most of the folks who visit this site work in health care, either as medical professionals or in the pharmaceutical development industry. If you have not yet heard, last week a Phase 1 trial in France was complicated by five subjects experiencing very serious adverse events. One subject has died, and four others have had serious neurologic events, reportedly involving deep brain bleeds.

I had the opportunity to serve as a study responsible physician in a Phase 1 trial. The fundamental compound was a human hormone, and we had experience with it using intravenous administration. Nonetheless, we conducted a very careful Phase 1 trial with first-in-human precautions because we were administering it in a novel formulation linked to another molecule.

I went to our clinical pharmacology unit, at a center in Belgium, to be present for the first in human dosing. The setting was hardly dramatic, just a healthy young man lying on a Gurney with an IV, an automatic BP cuff, and ECG telemetry electrodes in place. An experienced study nurse gave the subcutaneous injection, and…nothing happened.

Of course, one of the six subjects in the first series would receive placebo, so on the following morning, we did it all again. Another subject, in the same setting, with another injection and … again, nothing happened. Since the arithmetic demanded that at least one of the two subjects was assigned active drug, one of the two subjects had received the very first dose of this compound ever injected into a human being.

What do you think when you are the “responsible” physician standing at the bedside for such an event? F. Scott Fitzgerald captured the experience perfectly. He wrote, “The test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” One idea is, “my goodness, we are making such a fuss over something that we know is safe.” The other, not surprisingly, is “I hope and pray that nothing goes wrong, but if it does, I hope I my emergency plan works and he will be all right.”

Our subjects were all right. But the subjects in the Bial trial were not. This is the enormous responsibility that everyone involved in research involving human subjects shoulders. Unexpectedly, despite our best efforts, something goes off the tracks.

Instinctively, we all feel sympathy for the subjects. Let’s also feel sympathy for the researchers who had high hopes for a safe and effective new drug, and were terribly, terribly wrong. We cannot brush bad outcomes under the rug. We need to talk about them, and to make sure that the lay public understands that pharmaceutical research is not a strictly commercial activity. It is a very human, and occasionally very dangerous, effort to make life better.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s