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Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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February 12, 2004

The Cold Equations

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Posted by Derek

Here's a question for the folks at The New Republic: are you really sure that Gregg Easterbrook's blog is a good idea? Just checking. He's already stepped into so many steaming mudholes that I'm starting to think that he's one of those born-to-be-edited types. (Or would that help?)

I say this in response to today's entry, a diatribe against Eli Lilly over the suicide of one of their Phase I clinical volunteers. A 19-year-old student at a nearby Bible college with no known history of depression, she was one of one hundred normal subjects who were taking Lilly's new antidepressant, Cymbalta (duloxetine). She had completed the dosing protocol, which started early in January, going up in dosage and gradually back down to placebo. At the time of her suicide, she had been on placebo for four days.

Easterbrooks's upset about this, and on the face of it, who can blame him? The suicide of a young, apparently healthy person is disturbing to anyone. But he's even more upset at Eli Lilly:

"TRACI JOHNSON, 1985-2004: I've never read anything so heartless as the claim by the Eli Lilly drug company that its experimental anti-depressant Cymbalta has absolutely nothing to do with the fact that a healthy, apparently non-suicidal 19-year-old woman committed suicide while living in an Eli Lilly dormitory and serving as a subject in a trial of Cymbalta. No wait, I have read something still more heartless--Lilly's claim, to The New York Times, that although 5 of the 9,000 people who have taken Cymbalta, whose chemical name is duloxetine, have killed themselves, the company sees no connection. "We have not been able to discern any signal between duloxetine and suicide," an Eli Lilly spokesman told the Times."

This piece is the victim of a common fallacy - that is, taking what's in the New York Times as a mirror of reality. Let me recommend, in this case, the Indianapolis Star, which is at least out there on the ground in Indiana. There one might read that Michael Turek of Lilly attended chapel at the bible college on Sunday morning and spoke to the student body, quite possibly with enough heart to satisfy Gregg Easterbrook.

I just hate to add myself to the roll call of the heartless, but perhaps this Eli Lilly spokesman is actually telling the truth. Easterbrook isn't buying, though. Second paragraph, with my emphasis added:

Can this be anything other than a straight corporate lie? The suicide rate for all Americans is 10.8 per 100,000, according to the Surgeon General. This means 5 suicides would be expected in a group of 46,000 people, not in a group of 9,000. In a group of 9,000, one person would be expected to commit suicide, which suggests Lilly's own trials show that Cymbalta is causing subjects to kill themselves at five times the expected rate. The rates are suicides per 100,000 per year, but presumably Cymbalta trial subjects have not taken the drug for longer than a year. And some in the trials group may have symptoms of depression, which could put them at higher risk for suicide than the population as a whole. Still, five suicides in a group of 9,000 is way too high to be coincidence."

Bullshit. Some "may have had symptoms of depression"? Gregg, those other four deaths were all in phase II trials. They were in depressed patients. You can't compare those figures to the ones derived from the general population. And the suicide rate of those depressed patients taking Cymbalta is lower than those who are taking placebo - as it had damn well better be. It's actually ten times lower than the suicide rate of those taking existing antidepressants. The Indianapolis Star could have told you that.

It's true that such drugs may work differently in normal patients versus depressed ones, and it's also true that the effects may be different in younger patients (the subject of a lot of controversy in the field at the moment.) I can't deny any of that, and thus can't rule out that such an effect may have caused Traci Johnson's suicide. But neither can I rule it in. On the basis of the clinical data Lilly has, there's no way to know, and there's no reason to assume it. Their spokesman is correct.

Let's go back to Easterbrook for a wrap-up:

"Some people, including some young people, really do need anti-depressants, and society benefits from pharmaceutical companies researching such drugs. But pharmaceutical research isn't just a formality to win marketing approval--when trials show a drug has dangerous side effects, the research is supposed to stop. . .

Dr. Alan Breier, Lilly's chief medical officer, went so far as to make small of the young woman's death, telling the Times: "Most people who commit suicide in the general population leave people asking these kinds of questions. And just because this happens while someone is taking a drug doesn't mean the drug caused it."

What a malicious, cold-blooded thing for a corporation to say. Lilly has essentially just told the parents of a 19-year-old woman that it doesn't care that their daughter is gone. Physicians should fall to the floor and weep if they ask a completely healthy young person to take an experimental drug, and a month later she is dead. . ."

Dr. Breier is, I'm sorry to report, absolutely correct. Lilly has been told to stop enrolling patients in their latest studies on Cymbalta while the FDA studies this latest news. That's the right decision, too - but I think that they'll find that there's no way to know if there's a connection or not. Post hoc ergo propter hoc is the name of the fallacy that would tell you that we already know, but that's exactly what Breier is trying to say.

And he's not, as far as I can see, being malicious at all. And if he's being cold-blooded, well, then so am I. And so should everyone in clinical research. Does Cymbalta cause younger patients to become suicidal? We don't know, and we will never know until a lot of young people have taken it. I hate to put it that starkly, but it's true. You have to be willing to find the answers to questions like these, or you can't help anyone.

I am sorry that Traci Johnson is dead. But if we fall to the floor and weep, as Easterbrook recommends, we're neglecting our duty to the living. He's right - when trials show that a drug has dangerous side effects, the research is supposed to stop. But - excuse the cold-bloodedness - Traci Johnson's suicide does not establish this. Would we be walking away from a drug that could wind up preventing suicides instead of causing them?

"One owes respect to the living - to the dead one owes only the truth." - Voltaire.

Update: Check out this blog post, which begins: "I've been on anti-depressants for over two years now, so I feel qualified to offer some additional comments."

And I missed several Easterbrook/blogosphere dustups in my list above. Try this one, this one (also here), and this one (the January 13th post.)

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