Salmon Widens The Net, Significantly. . . .

In response to my post on the Wyeth ghostwriting docu-dump (or perhaps "liberation" would be more accurate), by the courts, the irrepressible Salmon has offered to explain how -- in fact -- it is all more related to Schering-Plough, generally, and asenapine, specifically -- than I imagined. Take a look (from his comments):

. . . .The nonprofit organization Alliance for Human Research Protection (AHRP) has some interesting things on their site.

First let me explain that AHRP is probably one of the foremost advocacy organizations regarding abuses by the pharmaceutical industry in the area of psychiatric drugs. In fact, the Alliance was a lead in a lawsuit regarding the distribution of the Zyprexa papers (papers that indicated that Lilly knew they had problems with Zyprexa and diabetes).

After reading an article at AHRP on asenapine (do go read it), I noticed an article on ghostwriting on the same page so I took a look at it since ghostwriting was in the news (PLoS, via the New York Times story). By the way, Sen. Grassley has also been focusing on pharmaceutical corruption with respect to antipsychotics and especially on pediatric bipolar medication regimens.

It seems that two days after the August 18 AHRP asenapine article ran (the ghostwriting article), AHRP ran one about ghostwriting, and Dr. Tom Laughren -- the FDA Psychiatry Division Director who wrote the approvable memo for asenapine -- do go read it all, but here is a snippet:

. . . ."For example, Dr. Laughren's name is penned to consensus statements recommending broadening the criteria for pediatric bipolar disorder. Such an endorsement by Dr. Laughren provides an authoritative green light to physicians to prescribe antipsychotics -- the most hazardous drugs in pharmacopoeia for children -- even as the drugs had not been approved for children.

Dr. Laughren not only co-authored major articles promoting industry's marketing goals but his name is penned to an apparently ghostwritten article [Ed Note: Per commenter TSC, below: "The contributions of Thomas Laughren and Robert Levin were made in their private capacity; no official support or endorsement by the Food and Drug Administration is intended or should be inferred. . . ."]:
"Mood Disorders in the Medically Ill: Scientific Review and Recommendations," published by the Journal of the Society of Biological Psychiatry, 2005.

The article promotes the notion that depression accompanies practically all patients with medical illnesses-e.g., cardiovascular disease, cancer, AIDS, Alzheimer's, Parkinson's, Diabetes, Osteoporosis, Obesity, and Pain. Dr. Laughren, a co-author, recommends the use of antidepressants for presumed underlying depression, even claiming that "SSRIs may be cardioprotective."

Dr. Laughren's name has lent the appearance of legitimacy of what is clearly industry propaganda that has no basis in science or evidence-based medicine. . . ."

I've also been doing some checking on others who are listed as reviewers on asenapine, and Robert Levin, the FDA medical reviewer, is a coauthor on an article with Laughren representing FDA views on proposed standards for approving drugs effecing neurocognitive (negative) and other negative symptoms of schizophernia. It's interesting since these begin in 2005 and mirror the timing of meetings the FDA held with Organon -- about standards for their trials looking at negative symptoms with schizophrenia (see page 194 in FDA's PDAC asenapine background package which discusses meetings the FDA had on this with Organon in 2004. I came across this serendipitously today since I still have not read through all the reviews for the first time yet.)

Also very interesting is that Gwen Zornberg the Psych Team Leader on asenapine wrote four articles on Neurontin in conjunction with key opinion leaders while she was employed with Pfizer. Neurontin has also been the subject of ghostwritten articles and is even discussed in a book Science in the Public Interest and articles in the New York Times (2002). I find it very interesting that she worked on asenapine at FDA -- as the overall FDA coordinator for asenapine -- a drug that was basically developed by Pfizer while she was employed by them working on Psych drugs.

I also found an article by her (while employed at Pfizer) discussing the relationship between neonatal hypoxia and development of schizophrenia later in life. Now neonatal hypoxia can be due to neonatal PAH, SIDS (which can be misdiagnosed PAH), and poor placental development which also appears to be due in certain to serotonin effects and drugs that effect serotonin systems.

What's most interesting is she wrote and article in December 2008 in the journal Drug Safety discussing the hypothetical risks of pediatric cardiovascular effects of drugs including effects of metabolites and took a "we need to monitor" attitude. Yet at FDA, she dismissed the clinical pharmacologist's concerns on this issue, with regard to asenapine in her review only six months earlier.

A very interesting set of circumstances indeed.

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LATER
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Going back and looking at it again I noticed another coincidence. The date of the End of Phase II meeting on asenapine where Organon and the FDA first discussed studies of negative symptoms was held on April 27, 2004.

That's only four days after the FDA-Pharma-academia meeting (discussing setting standards for approving antipsychotics for negative symptoms). Very interesting timing. N.B. Organon would have had to have requested the FDA meeting two months in advance -- and there would have also likely been a lead time for a meeting -- of a few months.

Zornberg -- in the abstract of her December 2008 article (on long term cardiovascular toxicities of drugs in children) ended with an indication to the effect that "let's not let it stand in the way of using drugs in children. . . ."

-- Salmon

August 22, 2009 9:56 PM