Marketing, Lying, Geodon, Whatever...

Pharma Giles has a wonderful post about a fake antipsychotic and its dubious marketing which is similar to a real ad campaign for Geodon. The post on Pharma Giles is hilarious, and the FDA letter that slaps Pfizer for its false marketing of Geodon is worth a read as well. Geodon was featured in a medical journal ad that offended the sensibilities of the FDA. Here are some highlights...

Specifically, the journal ad fails to include the warnings for neuroleptic malignant syndrome, tardive dyskinesia, and hyperglycemia and diabetes mellitus. The journal ad does mention “movement disorders” and “low EPS,” and while we do not object to these claims, the presentations are insufficient to communicate the risk concepts associated with, and the seriousness of, tardive dyskinesia. Additionally, the professional journal ad fails to include important precautions, specifically, rash, orthostatic hypotension, and seizures. By omitting these risks, the journal ad misleadingly suggests that Geodon for Injection is safer than has been demonstrated.

The ad made a claim that:

Proven advantages over haloperidol IM
―twice the improvement as measured on the BPRS”

To which the FDA letter said:

This presentation is misleading because it implies that Geodon for Injection is more effective than haloperidol IM when this has not been demonstrated by substantial evidence or substantial clinical experience. The single study cited for this claim was an open-label study, which is not an appropriate study design to evaluate subjective endpoints, such as those measured by the Brief Psychiatric Rating Scale anchored version (BPRS), because of the potential for evaluator bias. In fact, FDA is not aware of any substantial evidence to support this claim.

Nice going Pfizer. Keep up the B.S. advertising and the shoddy science (1, 2, 3).

Rost Busts Pfizer and Journalists

Pfizer is proudly touting a new observational study which found that patients who switched from Lipitor to a generic medication had an increased risk of heart problems. Fantastic -- avoid the generic and use Lipitor. Oh, but wait, as Peter Rost points out...

There is only one teeny weeny problem. The most common reason for switching drugs is because the therapy doesn't work; when the drugs don't have the desired effect. So it is completely expected that patients who were forced to switch had a worse outcome. They may simply be treatment resistant.

And Pfizer knows this.

That's the reason they use a weasel-sentence in their press release, hidden deep inside the text, saying "As with all observational studies, the findings should be regarded as hypothesis generating."

But that has not stopped the so-called health media from running with the story from the Lipitor saves, generics kill angle (see several sources on Rost's site). Here's more fuel for the fire:

"The bottom line on this particular study is that the data tell us such switching may not be without consequences," said Michael Berelowitz, senior vice president of Pfizer's global medical division, in a phone interview.

With all due respect, Mr. Berelowitz, it would appear that you are either ignorant on this point or you are lying. An analogy in the mental health field would be if patients who tried Effexor and then switched to a generic tricyclic antidepressant (say, imipramine) were found to have worse depression outcomes than patients who stayed on Effexor. Duh! Again, maybe people who dropped Effexor are treatment-resistant and/or had more severe depression -- medications don't work as well for them. So it would be a pretty stupid comparison to say that those who switched antidepressants were acting dangerously by switching medications, wouldn't it?

Burying Data, Chapter 317

In the sad yet unsurprising category, Ed at Pharmalot has two reports (1, 2) on Pfizer burying negative data about Lipitor. How would they do such a thing? Well, Pfizer conducted a study comparing Lipitor to Zocor and found positive results. Naturally, a favorable press release was issued, which opened by stating...

A retrospective analysis of a large U.S. managed care database showed that patients who took Pfizer's cholesterol-lowering medicine Lipitor® (atorvastatin calcium) Tablets had a significant 14 percent reduction in the risk of cardiovascular events, including heart attacks and strokes, compared with patients who took simvastatin.

An "independent" academic was also featured in the press release, stating...

"This analysis is important for physicians, employers and formulary directors at managed care companies who are making real-world treatment decisions for patients," said Dr. Robert Vogel, an author of the study and professor of medicine at the University of Maryland. "This further supports the cardiovascular benefits previously seen with Lipitor."

Well, turns out the analysis was wrong. The difference between Lipitor and Zocor was not statistically significant -- someone made an error during data analysis. No big deal that someone screwed up the analysis in my book -- it happens from time to time. Ed noted that, of course, there was no press release accompanying the new, less favorable data analysis. Though Lie-Zer, er, Pfizer has issued platitudes regarding its commitment to transparency, this behavior does not exactly engender faith in their commitment to honesty, eh? Here's Ed Silverman's rant...

So Jeff [Kindler, Pfizer CEO], what happened? If the marketing team is no longer in charge of everything, why hasn’t Pfizer gotten around to issuing that bad news press release? Your company has had 11 days to correct its mistake. Will that happen, or are accountability and transparency just convenient buzzwords?

Well said. I'd like to ask similar questions regarding the convenient release of study results that found Zoloft was ineffective for posttraumatic stress disorder ten years after the study was conducted, yet positive trials for Zoloft in PTSD took much less time to get published. How Pfizer handled other data regarding Zoloft is also dubious.

Reality Impresonates Art

For those of you who have seen The Constant Gardener, you are now allowed to wonder if the movie was really fictional. Criminal charges have been filed against Pfizer for allegedly setting up a clinical trial in which they misled African child participants badly and used a very weak comparison drug, which may have led to the demise of some participants. Here's one piece from the lawsuit, courtesy of Pharmalot...

“The families of the children who [Pfizer] used as laboratory guinea pigs were led to believe and in fact understood that the Defendants were providing their children with volunteer relief, clearly focused humanitarian medical intervention and nothing more,” the lawsuit says. Parents were not told that alternative treatments were available, it adds.

UPDATE: Please see comments.

Advertising as Education: CME Part Deux

I had the good fortune to read the Journal of Clinical Psychiatry supplement which featured Dr. Henry Nasrallah (the author) sneaking in some friendly messages about ziprasidone (Gedon), the antipsychotic from Pfizer that has been dwarfed by its competitors such as Zyprexa, Seroquel, and Risperdal. The piece discusses the findings of the CATIE study, which compared several newer antipsychotics to an older medication, perphenazine, and generally found that the newer and older drugs were of roughly equal effectiveness and that olanzapine had the worst safety profile. I thank an alert reader for passing the article along.

CME Overview: The good news is that physicians can read this article and take a quiz as part of the continuing medical education (CME) that helps them maintain their licenses. The bad news is that these articles are often thinly veiled advertisements for a product or a message that supports a product.

Highlights: It is stated that the difference favoring olanzapine (Zyprexa) over ziprasidone in terms of efficacy was not significant after a statistical adjustment (granted, this seems like a legitimate argument). It then mentions that olanzapine had the worst metabolic profile in terms of effects on weight, blood glucose, glycosylated hemoglobin, cholesterol, and triglycerides. It then states “In contrast, patients treated with ziprasidone had the best overall metabolic profile.” It places some numbers in a table regarding the metabolic effects of the various drugs in the CATIE study but provides not a single statistical analysis (or reference to an analysis on CATIE data) backing its assertion that it is significantly better than all other drugs in terms of metabolic profile.

The piece then turns to a secondary phase of the CATIE study, in which patients who discontinued their medications in the first phase of CATIE were assigned to other medications. It mentions olanzapine weight gain then mentions that patients on ziprasidone lost weight. It then discusses weight loss on ziprasidone again, then moves on to ziprasidone being associated with decreases in cholesterol and triglycerides, whereas olanzapine was associated with gains in both of these measures.

In case readers have been sleep-reading through this piece, it then moves to state that “except for clozapine, olanzapine clearly caused the heaviest burden of metabolic side effects. Ziprasidone, on the other hand, was consistently associated with the most benign side effect profile.”

Then, the piece moves to scare the reader about older antipsychotics and their risk of inducing extrapyramidal symptoms [EPS]. “The clinician must carefully decide whether the lower cost of the typical antipsychotic is worth the potential striatal neurotoxicity manifested by acute extrapyramidal side effects and long-term TD [tardive dyskinesia].” Of course, he must be assuming that atypical antipsychotics never or rarely induce EPS, which appears to be wrong and that all older medications induce EPS at the same rate as Haldol, which is likewise incorrect (1, 2).

Overall Message: The bottom line message of the piece is clear. Geodon is safe; Zyprexa is unsafe. Don’t use older meds because they’ll cause EPS – ziprasidone won’t. In fact, Geodon is the safest of the second generation antipsychotics.

Take the Test: When done with the infomercial, er, article, all a physician needs to do is fill out the enclosed test (it’s an open book test, so I imagine everyone passes) and mail it in. Physicians can even complete the test online. [this section was taken directly from an earlier post]

Ghostwriter Watch. Who wrote the article? You tell me – I’m confused. Here’s what is written in the article…

This article is derived from the planning teleconference “Evaluating the Evidence: Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and Beyond,” which was held on May 10, 2006, and was independently developed by the CME Institute of Physicians Postgraduate Press, Inc., and Health and Wellness Education Partners (HWeP) pursuant to an educational grant from Pfizer and addition support from HWP Publishing

Dr. Nasrallah is a consultant for, has received honoraria from, and been on the speakers/advisory boards for Abbott, AstraZeneca, Janssen, Pfizer, and Shire and has received grant/research support from AstraZeneca, Janssen, and Pfizer.

Content development and writing support for this article was provided in part by an independent writer contracted by HWeP: Martin Korn, M.D., a psychiatrist in private practice in New York.

I may be piecing this together wrong, but here goes… Pfizer writes a check to the CME Institute and HWeP. Nasrallah and a few other bigwigs engage in a conference call and are reimbursed (likely quite well) for their time. HWeP hires Martin Korn to write the piece, which then is reviewed, likely in a cursory manner at most, by Dr. Nasrallah. The piece is then reviewed by a member of the CME Advisory Board. These "reviews" appear to be consist of a race to grab the rubber stamp as quickly as possible.

I’m not sure if Pfizer provided the talking points directly to Dr. Korn, but it seems he got the message that Zyprexa and older meds should be slammed while Geodon should come across looking angelic. The CME Institute then stamps their approval and we call all be assured that doctors are being “educated” about the latest and greatest treatments in a purely objective fashion.

Please also feel free to read my earlier piece on CME. I recall seeing Dr. Korn's name on an earlier CME piece similar to this, but I can't seem to track it down.

Don't be confused -- I'm not defending Zyprexa. Geodon appears to be a safer drug than Zyprexa, but this quite thinly veiled advertisement that masquerades as independent education is ludicrous -- how does reading or watching commercials passing for "education" help physicians make better decisions for their patients?

Convenient Honesty and Zoloft

Recently, a study was published which cast doubt on the efficacy of sertraline (Zoloft) for PTSD, finding that the drug was no better than a placebo.

The kicker is that the patent has expired for Zoloft, which is why the data are now flowing more freely. I’ll make the case here that data were buried until they would no longer hurt sales to any meaningful extent, at which point data were published, at least partially as a public relations move to show just how “honest” the companies are with sharing both positive and negative results with the psychiatric community.

The Research: The latest study, which appears in the May 2007 Journal of Clinical Psychiatry, showed no benefit for drug over a 12-week period. Placebo tended to outperform Zoloft on the majority of outcome measures, though the differences were of a small and statistically insignificant degree. Patients were significantly more likely to drop out of treatment on Zoloft. It was unclear if there were any serious adverse events (e.g., suicide attempts, notable aggression, etc.) because the article did not mention them at all. Patients started this study between May 1994 and September 1996. The original draft of the study was received by the journal in March 2006. Nearly 10 years passed between study completion and writing up the data for publication.

Two prior studies found positive results found positive results for Zoloft and were published quickly, while these negative results languished until the Zoloft patent had expired. One earlier positive study did not list the dates during which the study occurred, but it seems clear that it was rushed to publication much quicker than the negative study. Another positive study was conducted between May 1996 and June 1997 and was published in 2000. It’s quite obvious why the positive studies were rushed to press and the negative study languished, is it not?

Do keep in mind that the magnitude of positive effect for Zoloft over placebo, even in the positive studies, was small to moderate. When even the positive news for antidepressants in treating PTSD show only modest improvement relative to placebo, one should tread cautiously.

Change of Heart: Drug companies have been criticized widely for failing to disclose clinical trial data (1, 2). In an effort to shore up the support of the medical community and the public at large, what could possibly make more sense than publishing negative trial results? Gee, look at how honest we are – we share the good news and the bad news! Of course, when the positive results are published as quickly as possible and the negative results are published after a 10 year delay, well after the negative results can pose any threat to corporate profits, I’m not impressed by their newfound dedication to transparency.

Note: If you are a journalist, this is the kind of story that would merit a broad audience. The plot is pretty simple to follow and it reeks of corporate malfeasance, a subject that is not new to Pfizer and its former cash cow antidepressant.

Rost Busts Pfizer... Again and Again and Again

Rost continues to bring the hammer down on Pfizer. I won't even bother to summarize his work, suffice to say that it involves a combination of...

• Spying
• Bribery
• Money laundering
• Retaliation toward a Pfizer whistleblower
  
• VOODOO

The investigation is up in three parts and you're a fool to not read it.
Part one. Part two. Part three.

Enjoy.

Pfizer Girls Got Back

The first part is okay (the bipolar Krusty is a bit too stereotypical for my liking) but then it gets really funny toward the end.


Hat Tip: The Last Psychiatrist.

Rost Vindicated, Pfizer Slapped

Jim Edwards of Brandweek NRX called it. Peter Rost has talked about it for years. Pfizer pushed their human growth hormone product, Genotropin off-label, and has now settled a lawsuit for the sum of about $35 million. Big props to Rost for his excellent whistleblowing on this issue. I expect he'll have celebratory T-shirts and coffee mugs released by the end of the week!