Thursday, August 27, 2009

"The (Accelerating) Placebo Effect" Examined -- In The Current Issue of Wired Magazine

This thought has long troubled me -- especially so, in the context of psych medications -- what to make of the so-called "placebo effect"? How much of the patients' response (in psych-med cases, at least) might be due to the fact that someone, somewhere, is finally showing enough of an interest -- to try and help them?

Moreover, what to make of study-measures (like those in psych-med trials) that are inherently expressed in shades of gray, and vary (even perhaps only minimally), from clinical assistant (reporter to reporter -- or even, among self-reporters -- patients)? How much of the placebo effect is the varying attentiveness of the observer/reporter? Are new generations of psych drugs growing less potent, or are study participants becoming more suseptible to a latent alternate potency -- inside the their own bodies? [Alternatively, are drug companies less easily-able to allegedly game the outcomes, these days?]

In a wonderful article-as-short-story format, Wired's Steve Silberman takes this on (do go read it all -- but here is a teaser):

. . . .Edward Scolnick, Merck's research director, laid out his battle plan to restore the firm to preeminence. Key to his strategy was expanding the company's reach into the antidepressant market, where Merck had lagged while competitors. . . . "To remain dominant in the future," he told Forbes, "we need to dominate the central nervous system."

His plan hinged on the success of an experimental antidepressant codenamed MK-869. Still in clinical trials, it looked like every pharma executive's dream: a new kind of medication that exploited brain chemistry in innovative ways to promote feelings of well-being. The drug tested brilliantly early on, with minimal side effects. . . .

Behind the scenes, however, MK-869 was starting to unravel. . . .

If, as early as 2002, Merck felt it needed to "own" the central nervous system-influencing drugs marketplace, per its science executives, generally, and Merck's Scolnick, specifically, it would be extremely interesting to learn where Whitehouse Station presently stands on William Potter's now-apparently quite-substantial body of work -- on the placebo effect -- in behavioral drugs, seven years into his efforting.

Will it continue, in the "New Merck" regime?

What will it mean, for the advancement of basic science, if it does not?
I know at least one regular commenter will have some cogent insights, and likely weigh in, here. [Blogging will be intermitent through Sunday evening, here -- on the West Coast, and more-than-occasionally off the grid.]

1 comment:

Anonymous said...

Wow, this is blast from the past!

Ed Scolnick left Merck after a stint as President of Merck Research Labs in 2002 to join the Broad Institute as the head of the psychiatry program and to work at the Stanley Center for Psychiaric Research. (Stanley as in the Danbury Mint Stanleys and founders of NAMI the National Alliance for the Mentally Ill.) The Broad Institute is a joint program between Harvard and MIT. This was of course after he arranged for Merck to give a $ 9 million grant to these institutions.

Around the same time his assistant Eve Slater (SVP of Clinical Research and Regulatory Affairs)because Undersecretary of HHS under Bush leaving a year or so later I believe to join Vertex's Board and take Marcia Angel's place at the NEJM. Also Merck's VP of Neuro and GI left to go to J&J to develop paliperidone.

(Interesting that the timing is I believe about when Vioxx toxicity was first being detected by Dave Graham or slightly before.)

MK-869 is a neurokinin 1 (NK-1) antagonist that in the late 1990s Merck reported in I believe Science as having a robust antidepressant effect in a phase II proof of concept study with minimal side effects. Thus setting off a race for 2nd for a new class of antidepressants. NK receptors were thought to be neuromodulators modulating the effects on things like dopamine and sertonin and people didn't think they would have more than modest effects on any CNS subsystem.

Up until that time Merck was primarily developing it as an antiemetic for chemotherapy, and although about 15 companies were looking at NK receptor antagonists no other company had been looking for antidepressant effects even though based on CNS receptor distribution it made sense that this might be a possiblity. (you need to read some pretty

However according to my sources the initial results couldn't be replicated. So the development program was dropped.

It's also interesting that Psych is promoted so heavily by Scolnick in the Wired article because except for MK-869 Merck's CNS research divisions hadn't come up with anything in years in spite of being probably the most productive CNS program in the industry in the distant past. Consequently the CNS research group on Canada was in danger of being shut down.

As for placebo effects with Psych Drugs. In the past several years several drugs have shown efficacy in ex-US but not at US sites and has resulted in several drugs being approved over FDA reviewer concerns over this.

One possibility is that there is so much overdiagnosis and or/diagnosis of milder forms in the US and also earlier diagnosis that perhaps we're not dealing so much with an increase in placebo effect but with a change in study populations as compared to the past (at least in the US).