Friday, September 25, 2009

Huzzah! -- Just As Salmon Has Been Writing -- Right Here, For Months!

Tonight, The New York Times weighs in on the improper influence Dr. von Eschenbach more than occasionally (allegedly) exerted on what should have been solely independent agency science decisions (this time, as to a medical device, but as Salmon has shown, this pattern occasionally also carried over to drug candidates, at FDA, during the Bush years):

. . . .The agency’s scientific reviewers repeatedly and unanimously over many years decided that the device, known as Menaflex and manufactured by ReGen Biologics Inc., was unsafe because the device often failed, forcing patients to get another operation. . . .

"The message here is that there were problems with the integrity of F.D.A.’s decision-making process that have solutions," Dr. Joshua Sharfstein, the agency’s principal deputy commissioner, said in a conference call with reporters. . . .

The report, written by top agency officials, said that Dr. von Eschenbach, who resigned as F.D.A. commissioner in January, became as a result of political pressure "personally engaged in the details of a process usually coordinated" by scientific staff. One agency manager concluded that Dr. von Eschenbach "was demanding not only an expedited process but also an outcome in favor of ReGen," the report stated. . . .

Dr. David R. Schmidt, the knee surgeon for the San Antonio Spurs, said he was involved in the original clinical trial of ReGen’s Menaflex device and concluded that patients did not benefit. He said he was surprised that the F.D.A. approved it. . . .

Click the following links, to read of prior reports of the same sort of conduct, alleged by Salmon, most recently here (as to some device approvals), and here (as to Schering-Plough's drug Saphris), also here, here, here (more generally, on the FDA's recently-amended drug approval process), as well as here (cancer drugs), and here (as to Merck's Vioxx).

Salmon only "scooped The Gray Lady" by about eleven months, right here, on this blog -- overall. . . .


Anonymous said...

Thanks but actually I don't think I've scooped anybody except on the zyprexa/asenapine/other serotonin drugs. The reports with the medical devices has actually been coming out for quite a while.

On April 2, 2009 there was a letter from a group of 9 CDRH device reviewers to President Obama outlining a number of reports of problems with device approvals reported in the press and going back to 2005. See also

Even earlier on November 29, 2007 there was an article in Pharmalot that the Congress was having the Inspector General’s office take back over investigation of criminal complaints of FDA employees since the Office of Internal Affairs which had been handling it since 1997 under a MOU had instead been investigating and harassing the reviewers who made the complaints.

Shortly after this Janet Woodcock gave an interview trying to build support to get Congress to back off, claiming people were scared and couldn’t do their work because of Congressional scrutiny. Who do you think she’s talking about. I’m pretty sure it’s not the staff reviewers who are afraid of congressional scrutiny.

It’s fairly well known about investigations of reviewers by OIA from what occurred with Andy Mosholder the psych reviewer who reported the suicidality with antidepressants in children. But it goes back much further to Leo Lutwak and others with Troglitazone which was pulled for causing hepatotoxicity, ( Lutwak was also the reviewer who raised concerns about phen-fen but was overruled. He also apparently felt there was some hanky-panky going on with the advisory committee (sound familiar).

There’s another article in Pharmalot from November 2008 with another letter of complaint to congress from device reviewers. In addition to the letter I think the attached comments from FDA staffers about what is happening to various reviewers speaks for themselves. There even appears to be a comment about the asenapine reviewer, see

Let’s of course not forget the Reagan-Udall Institute and Congressional concern, I could go on but this is what I found in simply doing some quick google searches on things

Getting back to asenapine a few days ago I was googling some stuff and and I came across some slides from Larry Lesko the head of the FDA’s Division of Clinical Pharmacology.

From the title slide:

Pharmacogenomics, Personalized Medicine and the Role of FDA
Lawrence J. Lesko, Ph.D., FCP
Bio-IT World Conference
Boston, Massachusetts
May 18, 2004

Then later on:

“Poisons and medicines are often times the same substance given with different intents”
Peter Latham (1789-1875)

Boy that sure sounds like a drug we’ve been talking about.

Then there’s the following slide:
Dealing with the Failure of Prediction: Drug/Test Co-Development
“Certain new therapies will be developed along with genetic or phenotypic tests that can identify an appropriate treatment population and detect patients who need different doses or are prone to certain toxic effects. Development of these test and therapy combinations must be facilitated because they have the potential to maximize drug benefits while minimizing toxicity.”
Mark McClellan, M.D., FDA Commissioner, Washington Drug
Letter, April 13, 2003

Looks like the asenapine reviewer wasn’t suggesting anything so different than the ex-FDA Commissioner was saying 5 years earlier only he was pointing out a specific example.


Anonymous said...

Actually the question should be if the FDA is this dirty and Congress simply keeps sending letters and there are news reports every so many months how can anyone expect FDA management to take Congress seriously that anything will ever happen to them.


Anonymous said...

I should point out these are only selected examples of Congressional letters and press reports. I've found many many others. Some letters from Durbin, some from Stupak, some from Dingle, and so on. These are typically posted on congressional websites but there are simply so many that I don't keep track. Ed from Pharmalot or Dickinson's FDAView or something like the pink sheet probably has records of many of them.


Anonymous said...

See the excerpts from Alicia Mundy's book on phen-fen and Leo Lutwak. She also talks about Fred in the book but not in these excerpts.


Anonymous said...

Found an interesting opinion piece by Fred Hassan on the PhRMA website.

What I find interesting is the discrepancy in Cardiovascular health in civil war soldiers and us presently and Fred's interest in it. (I saw almost the exact same piece on SP's website but it was from a speach Fred gave to I believe the American Heart Association several years ago.)

Fred states that Civil War soldiers were small and sickly by their 20's, if they lived to their 40's they were chronically ill, and heart disease struck 10-20 years earlier than today with 80% having heart disease by age 60 compared with 50% today.

Simply amazing. This got me thinking what could cause this. It's got to be an environmental factor. Small and sickly by 20 might mean poor diet but the US was an agarian society and presumably people had enough to eat (except of course during the war due to logistics and other things). Plus it shouldn't have this effect on heart disease years later, it anything the opposite.

So what environmental factor could be so widespread and is not due to today's current industrialization.

One possibility is something in the diet that was widespread.

Well back then if you wanted flour you took it to or got it via your local mill. We know that if wheat or rye is not stored properly that the grain can become infected with certain fungi that contain ergot poisons. These compounds effect serotonin receptors and in acute or subacute toxicity cause psychosis and intense vasoconstriction causing gangrene of the hands and feet with an intense burning sensation. This is called St. Anthony's Fire.

Ergots are used for migraines and for parkinson's disease and a modern ergot derivative is pergolide which was recently removed from the market for causing PULMONARY ARTERIAL HYPERTENSION.

You've got to wonder what Fred was thinking that this history of cardiovascular illness made such an impression on him.


Anonymous said...

Oh. By the way. The early symptoms in the labeling for pergolide that eventually turned out to be predictive for PAH. Under the new FDA labeling criteria of 5% and double placebo they wouldn't even be listed in the labeling today. They're also the same symptoms that we are seeing with asenapine, the other atypical antipsychotics, the SSRIs, and a number of other drugs that effect serotonin receptors.