Guarded Response When my friend, Kelly, had a physical a few years ago, her doctor
asked how things were going in her life. Things weren't good.
Kelly's job was stressful, her marriage was on the rocks, and a
family member had recently died. She admitted that she felt pretty
blue most of the time. Her doctor asked her if she'd like to try
Prozac. The idea shocked her. She'd never thought of herself as someone
who would take an antidepressant drug. But she was also intrigued.
The idea of a mental boost to help get through the day was
appealing. So her doctor gave her a free sample pack of Prozac,
and wrote a prescription to start off on a low dose. Later Kelly told me that on the drive home from her doctor's office
her spirits were better than they'd been for months. She felt
empowered and hopeful - like a dark cloud had lifted. In short, she
didn't feel the least bit depressed. And at this point she hadn't
taken her first dose of the Prozac. What Kelly was experiencing was similar to a placebo effect. What
she needed most in her life was not a drug, but the feeling that
someone - or something - was in her corner, offering a helping
hand. And it's people like Kelly who have been messing up the
results of clinical trials for antidepressant drugs. In some cases the
positive results in these trials were stronger among placebo
subjects than those taking the drugs. Well… we can't have that! So now drug companies are devising
ways to weed out study subjects like Kelly - subjects known as
"placebo responders." Now, you know I'm not one to put a lot of stock in headlines, but
the recent headline of a Wall Street Journal (WSJ) article summed
up the situation in a nutshell: "Drug Makers Seek to Bar 'Placebo
Responders' From Trials" The WSJ article reports that Eli Lilly (maker of Prozac) and Pfizer
(maker of Zoloft) are funding research on brain imaging at the
University of California, Los Angeles. This research is designed to
identify disruptions in sleep and thought processes experienced by
depressed subjects. But some depressed patients don't experience
these disruptions, and it's these patients who are believed to be
placebo responders. According to WSJ, Pfizer researchers have also conducted studies
indicating that placebo responders may be identified through DNA
testing. It's an efficient plan: Spot the troublemakers, keep them out of the
trials, and the outcome will probably be much more in line with
desired results. The key word here is "desired." Accurate results
are secondary to desired results when an FDA approval of a cash
cow pharmaceutical is in the balance. Drug companies claim that the techniques designed to exclude
placebo responders would only be used for early trials - not for
FDA approval trials. Naaa! They wouldn't do that! They have too much integrity! But think about it: That very claim indicates an awareness that - at
worst - there may be something unethical about this practice,
while - at best - it corrupts the basic design of clinical studies.
Kay Dickersin, a professor at Brown University and the director
for the Center for Clinical Trials and Evidence-Based Healthcare at
Brown, told WSJ that placebo responder screening encourages bias
with a "subtle manipulation" of trial results. I think Professor
Dickersin is being charitable. This manipulation is not so subtle at
all. The gold standard for clinical trials calls for three elements: - Placebo-control (one group receives an active agent while
another receives a placebo) - Double-blinding (neither the subjects nor those who administer
the study are aware of which subjects receive placebo) - Randomization (once the group of study subjects are in place,
they are randomly assigned either placebo or active agent).
So when you're studying the effects of an antidepressant on mildly
depressed subjects, and you remove any subjects who qualify as
mildly depressed but who will probably respond to placebo, then
you're compromising the randomization. The results of your trial
will indicate how a drug works only on those subjects who are not
placebo responders. The implication: The drug won't be tested on
placebo responders, but it doesn't matter because, you know,
ANYthing works on them! Research that involves brain imaging and genetics doesn't come at
bargain prices. So the fact that two huge drug companies are
willing to underwrite such expensive research reveals to what
lengths companies will go to tip the balance of clinical trials in
their favor. Now, with new antidepressants in development for
both Pfizer and Lilly, just think how successful upcoming trials
might be if those pesky placebo responders simply get included
out. P.S.: Kelly did try the Prozac, but stopped using it after one month.
She said the drug made her feel woozy. So she started taking St.
John's Wort and that was enough to see her through a mild
depression during a tough time. To Your Good Health, Jenny Thompson
Health Sciences Institute Sources:
"Drug Makers Seek to Bar 'Placebo Responders' From Trials"
Leila Abboud, The Wall Street Journal, 6/18/04
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