Thursday, March 19, 2009

AstraZeneca Behaving Badly. Very, Very Badly.

Many bad things have been reported lately about Astra Zeneca’s efforts to bury negative data about Seroquel. This revolting story of data manipulation, deceit, and academics selling their opinions to the highest bidder is being covered widely. See these excellent stories in the Washington Post, the Minneapolis St. Paul Star Tribune, The St. Paul Pioneer Press, as well as incisive blogging at Clin Psych and BNET.

These days, we hear so much about drug companies behaving badly that “accusation fatigue” sets in. We’re tempted to throw up our hands and say, “All the drug companies do this, what else is new?”

Resist the temptation. Yes, Eli Lilly's behavior was wretched, and it recently pled guilty to off-label marketing of Zyprexa for treating agitation in dementia.

But AstraZeneca has truly grabbed the brass ring of subterfuge. The Seroquel documents are revealing a company-wide pattern of blatant deceit and manipulation that is astonishing, and should make any psychiatrist think twice before believing anything Astra Zeneca has to say about Seroquel, either in the past, the present, or the future.

I'll contribute to the discussion by adding yet another data point to the mix. Here is an AstraZeneca-supported CME article
which appeared as a supplement to Current Psychiatry. The title is “Issues associated with the use of atypical antipsychotic medications,” and it is dated December 2008. The identified authors are Henry A. Nasrallah, Donald W. Black, Joseph F. Goldberg,
David J. Muzina, Stephen F. Pariser, but presumably the text was written by ghost-writers at Dowden media.

Ultimately, you can most accurately think of the author as being AstraZeneca itself.
The article begins by trying to distract attention from the metabolic side effects of Seroquel by blaming the patients rather than the drug:

While the incidence of both obesity and diabetes is soaring among the general population, these conditions are more prevalent in patients with schizophrenia, even those who have no history of antipsychotic drug use.7 Prevalence rates for both diabetes and obesity are approximately 1.5 to 2 times higher in people with schizophrenia and other affective disorders than in the general population.4… Thus, it is difficult to predict which patients will be affected and the precise role drug treatment might play in this process.

The argument here is that these patients get fat because there are schizophrenic, not because they use Seroquel or similar obesity-promoting drugs.

Of course, AZ is forced to reference the well-known official statement co-published by the American Diabetic Association and the American Psychiatric Association which implicated Seroquel and other atypicals as causing weight gain and diabetes:

The ADA/APA statement ranked clozapine and olanzapine as being associated with the greatest risk of weight gain, diabetes, and dyslipidemia.4 Risperidone and quetiapine were put into an intermediate risk category for weight gain, while aripiprazole and ziprasidone were, at the time, too new to categorize. More recent data have shown ziprasidone and aripiprazole to be relatively weight-neutral.8

But check out how they go on to back-track, creating an alternative reality in which people are supposedly questioning this data:

However, the consensus statement must be interpreted with caution. Criticism has been leveled at the report from many corners, including the Division of Neuropharmacological Drug Products of the FDA, which argued that insufficient data were available to appropriately “rank” obesity/diabetes risks for the atypical antipsychotic agents.18

The criticism they are referring to was a one page letter from the FDA,
but it had nothing to do with weight gain. The letter cautioned that actual data connecting the atypicals to diabetes was minimal, and that more studies needed to be done to better characterize the relative ranking of each drug in terms of the potential to cause diabetes. But the FDA officials were clear that some drugs cause more weight gain than others: “The ADA correctly points out that SGAs have different weight gain liabilities.” Obesity, of course, is one of the main risk factors for diabetes—so you do the math.

Finally, the authors return to their main theme—insulting schizophrenics:

Other authors pointed out that efficacy considerations of these drugs are a critical and overlooked component of the discussion and that the data used to compare the agents did not adequately control for key lifestyle factors such as overreliance on “junk food.”19,20

That’s right—the problem isn’t Seroquel; the problem is that crazy people are junk food junkies!

Here is my modest proposal. Because of these documents, Astra Zeneca’s credibility is officially out the window. They should not be allowed to be involved in any medical education event. They should be banned from hiring promotional speakers and from supporting CME. AstraZeneca has lied to the medical community once too often.


10 comments:

therapyfirst said...

Amen! Couldn't have ended a post like this any better. And, for me, it is the validation I have been searching for this past year after I learned how these scumbags have been so inappropriately gunning for an indication for anxiety. Forget the crap about a first line indication for depression, as if that was appropriate in itself.

I don't know if AZ reps talk to you still, especially if you have interacted with them at all in the past 2 years after Seroquel XR came out, but when I asked about doses lower than 200XR, their reply was basically, " doses lower are not likely to be made as we see this formulation for schizophrenia and bipolar disorders." Well, I'll be darned, what did I find in the sample cabinet three weeks ago but 50 and 150XR samples and, while the reps did not talk to me, found out from the nurse who took them that these doses are intended for "patients with depression AND anxiety". And, imagine that, the indication for anxiety had not been finalized yet!

Again, thanks for this post!

Anonymous said...

If the FDA can levy billion dollar penalties against drug companies for perceived unscrupulous marketing practices, why not have an additional penalty, as you suggest, barring them from CME-sponsored activity? Brilliant! I hope the FDA is reading your blog. Perhaps the greatest blow to a market-driven drug company is to be excluded from all CME-related activity at the APA meeting, for example. This would take money out of the pockets of the APA (which gets its vig from the drug company-supported symposia), so I wonder if it would be supported by the association and its members.

That is the big question. Is the APA and the FDA willing to support "alternative" penalties other than money fines, which might benefit the field overall, but could reduce sponsorship funds to the association and multi-million dollar penalties that go to the FDA coffers? Good work here.

insider said...

Great Job!

There's much more to come.....

Anonymous said...

What is emerging as the common element in big business is that the only consideration in management's quest for profit is whether or not they can get away with it. The banks will happily risk our money, and the drug companies gladly risk our lives. And what is worse, they all walk off into the sunset with their ill-gained winnings. What have we come to?

Anonymous said...

Our field is so corrupt. It is sickening. It's like you can't trust any psychiatric research directly or indirectly funded by pharma for the past 20 years or so. Which is most of the research! Oh, and yes, the NY Times had a wonderful article on Biederman this morning -- wherein he basically compared himself to God! Wow!

Michael S. Altus, PhD, ELS said...

Dr. Carlat,
You wrote in part, "...but presumably the text was written by ghost-writers at Dowden media."

1. What do you mean by "ghost-writers" (or "ghostwriting")?

2. Why do you presume that the text was written by ghostwriters?

Daniel Carlat, M.D. said...

Michael,

I may have used sloppy terminology--and I'm sure you'll correct me. By "ghostwriters" I meant employees of Dowden Media or contractors they paid who may have actually written the first draft of this article. Their names are not mentioned, therefore the "ghost."

I assume ghostwriters were involved because this article includes the typical industry soundbites regarding the atypical antipsycotic and obesity issue. I've read the same drivel in dozens of other industry-supported CME articles.

I may be wrong. I invite Dowden media to chime in here.

Anonymous said...

My brother has Schizophrenia and his drug Clozorill has changed his life. He went on it during some sort of experimental time when the drug first came out. (like 20 years ago). It isn't the safest drug as newer atypicals are safer, but the slightest change to his drug regime impacts his life, and health so much that its difficult to know if he would be better off with a newer drug. He is so much more normal, less fearful, more content, more independent then he ever was when on prior drugs. I am not sure why the author is so negative on atypicals when they are so lifechanging for shizophrenics. I am not sure if he is suggeting patients would be better off on Haldol or Risperdol or something else??? My brother must be more careful about his diet and has made some good changes and he now weighs about 225 (he is like 6'2 or so). I would rather have a brother who must manage diabetes and schizphrenia with an atypical than to not have diabetes and have to be forced to take haldol or other drugs that seems far more dangerous and less effective than an atypical.

Iowa Doc said...

Sadly, many of the "authors" of that article are relentless and unapologetic in their defense of Pharma. I would love to see how many dollars they have accepted over the past ten years.

insider said...

Here's the AZ sidewiki (written by yours truly) in full:

Welcome to the blogosphere!
Question 1. How much did Dave Brennan know about "The Seroquel Issue" at the time?

http://pharmagossip.blogspot.com/2009/10/astrazeneca-to-pay-520-million-to.html

The pharmaceutical company AstraZeneca said Thursday (29/Oct/09) that it had reached a $520 million agreement to settle two federal investigations and two whistle-blower lawsuits over the sale and marketing of its blockbuster psychiatric drug Seroquel.

One of the investigations related to “selected physicians who participated in clinical trials involving Seroquel,” AstraZeneca disclosed in a government filing. The other case related to off-label promotion of the drug.

H. Waxman's letter:

http://oversight.house.gov/Documents/20070305175741-03469.pdf

The Zoladex issue:

http://www.justice.gov/opa/pr/2003/June/03_civ_371.htm

Question 2

What do you think Corporate Integrity Agreements are?

http://oig.hhs.gov/fraud/cia/agreements/AstraZeneca06042003.PDF

This might help.

http://peterrost.blogspot.com/2007/04/secret-astrazeneca-audio-tapes.html

http://peterrost.blogspot.com/2007/04/open-letter-to-oig-from-astrazeneca.html

Question 3

Is Dr Michael Reinstein one of the Seroquel investigators under investigation by the DoJ?

http://pharmagossip.blogspot.com/2009/11/dr-michael-reinstein-clozaril-king-is.html

Today's question (4):

Was Geoff Birkett the "man behind the curtain" in the Seroquel Scandal?

Someone has to take the fall Dave!

http://www.chicagotribune.com/health/chi-drugs-seroquel-reinsteinnov11,0,6067737.story


Last question, for now:

http://pharmagossip.blogspot.com/2009/11/astrazeneca-seroquel-fao-marketing-and.html

If you or AZ or anyone have any issues of fact about any of this then please say and it will be changed/removed. If not, the so be it!