New American Psychiatric Association Prez: We Want Money

In a recent speech, incoming American Psychiatric Association president Alan Schatzberg was quoted as saying:

"As the recent attacks on APA and leaders of the profession have occurred, it has struck me that some of the detractors in the press have voiced concern that some folks have earned too good a living, often by doing presentations," he said. "I have heard from colleagues and directly from one reporter asking me about one of my colleagues having too high an annual income. I can assure you these detractors would not ask the same question of a surgeon or radiologist earning 10 times the amount paid our colleagues. None of us do what we do for money. Yet, it is also time for us to realize that our members and residents have never taken vows of poverty, and the complexity of the work deserves to be recognized. We need to ask ourselves how we have contributed to our own devaluation with which others seem to resonate, and we need to reverse the course. The rewards for our dedication should not be limited to a sense of pride, but we are also entitled to be paid commensurate to the challenge.

So Schatzberg must be diving into dumpsters, begging at interstate off-ramps, and the like. Oh, wait a minute. This is the same Alan Schatzberg who in 2007 owned close to 5 million shares of Corcept (which translates into roughly 5 million dollars). I have no idea how many shares he owns currently. Corcept, in case you missed it, has shown its drug mifepristone (aka RU-486: "The Abortion Pill") is ineffective in relieving depression among patients with psychotic depression. Schatzberg, at one time, was the chief scientific officer of Corcept and was also the cofounder of the company. According to Corcept's website, he is still a scientific advisor. Despite the stuides of mifepristone showing negative results, the results were spun in a manner to make them sound as if they were positive (1, 2, 3, 4). In a press release, Schatzberg was quoted as saying that mifepristone "may be the equivalent of shock treatments in a pill." Right, with all of the negative studies, it's definitely shock treatment, meditation, and running a marathon all wrapped together in a capsule. Should he be paid "commensutate to the challenge" of trying to weave positive findings from negative results? I don't know what role, if any, he played in the misleading publications surrounding mifepristone. But in his role as chief of the scientific advisory board, I'd venture a guess that he had some involvement. But worry not, the negative results were not spun into positive findings for the sake of money, but for an altruistic love of patients with depression. I'm touched.

Schatzberg was also busted by yours truly putting his name on a duplicate publication that pimped Cymbalta, Lilly's antidepressant. The study presented data from the same set of patients who were involved in a previously published Cymbalta study. Scientific results are not meant to be published in nearly identical form in two different journals. But that didn't stop Schatzberg and his coauthors. If you've not read the lengthy post on this topic, please feel free to check it out in order to understand my cynicism regarding his recent speech.

Another quote from his talk:

We need to sit down with industry and come up with ways of interacting that are acceptable to both sides and fit with future guidelines. I have pledged to follow up on recent initiatives and work with Dr. Scully [APA's medical director] and our Board of Trustees to effect a new partnership—a partnership we can be proud of for what it contributes to the well-being of our patients and our profession.

I can only wonder what type of mutually agreeable interactions would meet Schatzberg's standards. Duplicate publication, serving as a scientific advisor for a company that writes scientifically dubious papers? And it appears that he's encouraging psychiatrists to be greedy -- take the money and don't feel bad about it. Taking industry money is perfectly acceptable in some instances, but it needs to be transparent, and there are plentiful examples of academics getting paid by industry and slanting science in a sponsor-friendly way.

And the clincher:

"The time has come," he said, "to be proud of what we do and to advocate for what we and our patients justly deserve."

Right, psychiatrists deserve to make as much money as possible bending science for corporate sponsors -- and they should be proud of it too. Am I being too cynical? Maybe. But when a guy with Schatzberg's record starts talking about psychiatrists needing to rake in more money from industry, it makes me think I'm living in Bizarro World. Get ready, APA memebers; it's going to be an interesting ride.

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Saturday, June 20, 2009

Greedy and Ghostly Scientists

Story one: Zachary Stowe, psychiatrist at Emory University becomes Charles Nemeroff, Jr. Read all about it the Carlat Psychiatry Blog and University Diaries. And check out the WSJ Health Blog as well. The gist is that Stowe apparently did not report all of his external income from his many pharmaceutical industry gigs. Better yet, he was a frequent speaker for GlaxoSmithKline, which had the gall to cancel two of his commercial talks. He then wanted GSK to pay him even though he wasn't going to give the speeches. Read the relevant emails toward the bottom of this document. After reading about Stowe, refresh your memory about Golden Goblet Lifetime Achievement Award Winner, former Chair of Psychiatry at Emory University: Charles Nemeroff. Is there something in the water at Emory? Or is that just how we roll in modern academic psychiatry? Stowe is hereby nominated for a coveted Golden Goblet for his string of emails in which he attempted to shake down GlaxoSmithKline. Sometimes I think that the only thing worse than drug companies are the narcissistic academics who they employ as "key opinion leaders." Not all key opinion leaders are jerks; some are probably even able to reasonably balance their industry cash with being good scientists. But Stowe didn't really portray himself as Mr. Nice Guy in his string of soon to be infamous emails.

Oh, and this little gem:

"Especially disturbing is an email between employees at GSK and a public relations (PR) firm that the GSK hired. The email was titled “For your review/Paxil Breast Milk Press Release” and states:

"[P]lease review the attached press release and forward me any comments/edits.
As you may know, Dr. Stowe is on board for publicity efforts and NAME
REDACTED and I are coordinating time to meet with him next week to arm him
with the key messages for this announcement, which is slated for early February.
We are sending the release for your review at the same time in efforts to secure
distribution on Emory letterhead (as you know, would provide further credibility
to data for the media)."

In his testimony, Dr. Stowe confirmed that the press release was written by the PR
firm and concerned his research on Paxil and its presence in breast milk. He also
explained that placing the press release on Emory letterhead, as opposed to GSK letterhead, would make the data more credible to the public."

If I have this straight, Stowe was willing to place a press release written by a PR firm hired by GSK on official university letterhead to enhance its credibility. Apparently he wasn't concerned about his own credibility. Read the full document of Senator Charles Grassley's investigation of Dr. Stowe.

Part 2: Enter the Ghostwriters

One snippet, then go to Bloomberg for the rest:

Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents. To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as Progress in Neurology and Psychiatry, according to the unsealed documents. “The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,” Kerrie Mitchell, an employee of the public relations agency Cohn & Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files. “We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,” Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn & Wolfe, didn’t immediately return a call requesting comment.

The Bloomberg story is based on a recently released set of internal Lilly documents. That's right -- more Zyprexa documents are on the loose. And the first round of documents provided some good stuff (1, 2, 3), so I can't wait to see what kind of chicanery will be revealed by the latest round. In one sense, it's not exactly news that Lilly ghostwrote Zyprexa papers. We all know that ghostwriting is rampant. How else do key opinion leaders get their names on dozens of papers per year when they are also flying around the country pimping drugs, holding administrative meetings, and doing all sorts of other tasks? But it's nice to have it officially documented that Lilly was playing the ghostwriting game with Zyprexa.

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Friday, June 12, 2009

Leading Psychiatrist Slammed in Leading Journal

In the latest American Journal of Psychiatry appears a review of Allison Bass's book Side Effects. As many of my readers undoubtedly recall, the book details the saga of the antidepressant drug paroxetine (Paxil) and the troubled line of "research" used to support its use in children (among other points). The reviewer clearly liked the book, which is not necessarily newsworthy. What is notable is that a book review appearing in perhaps the world's leading psychiatry journal slams a leading member of the psychiatry profession. The reviewer, Dr. Spencer Eth, writes the following:

More recently, psychiatrists have been greeted in the morning with front-page newspaper exposés of huge sums being directed by these same drug companies to the physician leaders of our field. In Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial, journalist Alison Bass has written the powerful story of a leading medication, its manufacturer, and a favored psychiatrist, whose driving force was profit not treatment.

Ouch. Though not naming the psychiatrist directly, it is clearly a reference to Martin Keller, bigwig at Brown University, whose work on one particular study regarding Paxil was the subject of a lengthy prior post. For the collection of my posts related to Dr. Keller, please click here.

Back to the review...

This well-told cautionary lacks the excitement of a novel but instead informs the reader with an actual case study with the real names of psychiatrists we know. We can see exactly how corporate greed, drug-company-sponsored clinical research, and mental health care become a toxic mix that inevitably damages our patients’ well being, our colleagues’ reputations, and our profession’s good name.

It was a refreshing surprise to see Martin Keller's goose get cooked in this review. I don't mean to sound vindictive or meanspirited. Keller has done a lot of work over the course of his career, much of which likely has some redeeming value. That being said, there can be little doubt that some of his "science" is quite dubious. And for a major psychiatry journal to run anything, even a book review, that directly goes after a "key opinion leader" who appears quite culpable in performing bad science -- that's a good sign.

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Friday, April 3, 2009

Seroquel, Haldol, and The Full Court Media Press

I was very pleased to have been acknowledged in a recent story in the St. Paul Pioneer Press. The reporter, Jeremy Olson, wrote the following in his story:

An Internet psychiatry blog first raised questions March 2 about the research Schulz presented at the APA conference and why it lacked any of the company's findings."It raises troubling questions when an independent academic author presents results that are in direct opposition to the underlying data," wrote the blogger, an anonymous academic.

He didn't cite my blog by name -- the unwieldy long name which I stupidly chose for the site may be responsible for that -- but I'm nonetheless grateful that my site was acknowledged for its work on this story. He is referencing my post in which I noted that a University of Minnesota psychiatry professor (Charles Schulz) had stated in a press release that Seroquel was "more effective" than Haldol. This was based upon his analysis of data comparing Seroquel to the much older antipsychotic drug Haldol in the treatment of schizophrenia. Yet an internal AstraZeneca analysis found that Haldol was actually more effective than Seroquel. Both the Pioneer Press and the Star Tribune, the two big papers in the Minneapolis-St. Paul area ran stories on the controversy.

When asked about his lavishing of praise on Seroquel in the press release, the Pioneer Press said:

In an interview with the Pioneer Press last week, Schulz defended his research and presentation of Seroquel as accurate and ethical. However, he acknowledged the corporate press release from his APA presentation might have exaggerated in calling Seroquel "significantly superior."

"You know," he said, "I can't disagree with that."

Schulz said the following in the Star Tribune:

In an interview this week, Schulz said the pharmaceutical company never shared its doubts about Seroquel, which went on to become a blockbuster, with annual sales of $4.5 billion today. "I don't recall anybody calling up and saying, oh my goodness, we have this problem," he said. At the same time, Schulz acknowledged that his own study did not really show that Seroquel was more effective than the older drug. "That's a bit of a misunderstanding," he said. "I think the overall message is that it works about the same."

Thanks to a helpful reader, I was able to track down what appears to be Schulz's presentation from 2000. It says "...quetiapine was clearly statistically significantly superior to placebo as well as to haloperidol..." This appears to contradict his statement that Haldol and Seroquel "work about the same." Again, the data from Schulz's presentation don't match AstraZeneca's internal analysis. Schulz is obviously backing away from his earlier praise for Seroquel, for which he deserves some credit. The problem was that Schulz, along with a laundry list of researchers in psychiatry were caught in a tidal wave of unbridled enthusiasm for the atypical antipsychotics, first as wonder drugs for schizophrenia, then as the Next Big Thing in bipolar, then moving into the world of depression and anxiety disorders in the absence of decent supportive evidence.

Interesting sidenote: While Schulz was presenting on the wonders of Seroquel, he was likely quite unaware that AstraZeneca has conducted a study (Study 15) which had found that Seroquel compared unfavorably to Haldol in preventing psychotic relapse among patients with schizophrenia who began the study in full or partial symptom remisison. Furious Seasons has some additional reporting on this study. It is a near certainty that Schulz was not informed about this study's results, as this could have changed his lofty opinion of Seroquel. This points to the problem of researchers relying on data collected by drug companies -- how are researchers to know they are receiving all of the data?

Note to key opinion leaders: If you don't realize it by now, you are pawns. You are being used to place an academic veneer on the marketing of drugs. The drugs that you are marketing as major breakthroughs typically offer little to no benefit over existing treatment and may cause a slew of nasty side effects. Decide if you want to be a scientist or a marketer. Don't try to do both at the same time, because the odds are pretty good that your scientific credentials will end up being tarnished. Just ask this guy. Now that the media are paying much closer attention to the conflicted interests and skewed science that sadly underlie much of psychiatry these days, it would be a good idea to maintain appearances.

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Friday, March 20, 2009

Internal Documents Suggest that Seroquel Data Were Not Presented Accurately

A document dated March 9, 2000 titled "BPRS meta-analysis" shows that AstraZeneca, maker of the antipsychotic drug quetiapine (Seroquel), knew fully that its drug did not relieve schizophrenia symptoms to the same extent as its older, generic competitor haloperidol (Haldol). The document provides results of a meta-analysis, a statistical analysis that combines the results of several individual studies. The authors used the Brief Psychiatric Rating Scale (BPRS) as their main measure of efficacy. The BPRS rates a variety of psychiatric symptoms relevant to schizophrenia. More details on the BPRS can be seen here. A total of ten clinical trials were included in the meta-analysis, which variously compared Seroquel to placebo, Haldol, and several other antipsychotic medications. Four trials compared Seroquel to Haldol. Several subscales of the BPRS were included in the analysis.

When examining the amount of change on the BPRS, Seroquel consistently outperformed placebo, both on the BPRS total score and on several of the BPRS subscales. However, in several analyses, Seroquel was outperformed by Haldol and by risperidone (Risperdal; Janssen's antipsychotic). The document states: "Against 'all doses' of Seroquel, each of the three significant p-values generated was in favour of Haloperidol (Total BPRS, Factor V, and Hostility Cluster). There was no evidence of significant differences between the treatments when Haloperidol was compared to high-dose Seroquel." This is a plain admission that Haldol outperformed Seroquel on several outcomes, but that high dose Seroquel yielded approximately equivalent results to Haldol. Only one trial compared risperidone to quetiapine and the results clearly favored risperidone. The document stated: "Comparisons against Risperidone using all doses of Seroquel showed significant improvements for Risperidone on total BPRS, Factor V scores, and the Hostility Cluster. Against high-dose Seroquel only, the Anxiety item, Factor I, and Mood cluster scores were also significantly in favor of Risperidone." Risperidone beat Seroquel, and did so by a wider margin when a high doses of Seroquel was used.

The author of the document, Rob Hemmings, summarizes the results in a table, which appears below. It is described as such: "The following table is an attempt to simplify the claims that could be obtained from these results. A ✔ is entered for those comparisons where we have a statistically significant benefit, be it with 'all doses' or with high dose Seroquel... A x marks those comparisons where a comparator has demonstrated significant superiority compared to Seroquel."

The table demonstrates that according to an analysis by AstraZeneca employees, Seroquel is only shown to outperform placebo, whereas Seroquel is shown to demonstrate poorer efficacy than several other medications.

Under the heading "Conclusions," the document states, in part:

In terms of generating positive claims for Seroquel, these analyses seem somewhat disappointing. Although some trends in favour of Seroquel were observed in the Factor I and Mood cluster items, there was no evidence in these analyses of a significant benefit for using Seroquel over any of the active agents assessed."

The internal analysis clearly indicates that, based on several clinical trials, Seroquel offered no benefits over the competition in terms of reducing schizophrenia symptoms. Indeed, other drugs tended to outperform Seroquel.

How Can These Data be Managed? Shortly after the internal meta-analysis was completed, AstraZeneca employees discussed how to handle the negative results. An AstraZeneca publications manager, John Tumas, wrote in an email

The data don't look good. I don't know how we can get a paper out of this. My guess is that we all (including Schulz) saw the good stuff, ie the meta-analysis of responder rates that showed we were superior to placebo and haloperidol and then thought further analyses would be supportive and that a paper was in order. What seems to be the case is that we were only highlighting the good stuff and that our own analysis support the "view out there" that we are less effective than haloperidol and our competitors.

It would appear that an earlier analysis provided positive results which did not hold up during the internal meta-analysis. "Schulz" almost certainly refers to Dr. Charles Schulz, a psychiatrist at the University of Minnesota. In a press release from the year 2000, Dr. Schulz was quoted:

I hope that our findings help physicians better understand the dramatic benefits of newer medications like SEROQUEL because, if they do, we may be able to help ensure patients receive these medications first. The data suggest that SEROQUEL is an effective first- choice antipsychotic.

This press release was based on Schulz's presentation at the American Psychiatric Association convention in May 2000. The email from John Tumas discussed earlier noted that a group at AstraZeneca needed to meet soon "because Schulz needs to get a draft ready for APA and he needs any additional analyses we can give him well before then." It is unclear if Schulz ever received the analyses that showed Seroquel was less effective than Haldol. Regardless, in the press release, he was also quoted as saying: "Almost 50 years later, however, many patients are still taking these medications [such as Haldol], even though more effective treatments like Seroquel exist." While he was stumping for Seroquel in a press release, AstraZeneca's internal data painted a completely different picture.

Schulz, in his role as primary author, would typically be expected to demonstrate a solid understanding of the data underlying his presentation. It raises troubling questions when an independent academic author presents results that are in direct opposition to the underlying data. Such issues have been mentioned previously on this site.

The documents regarding Seroquel are available at Furious Seasons. Reporting on other facets of the documents can be found at the St. Petersburg Times, Bloomberg, New York Times, and the Wall Street Journal.

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Monday, March 2, 2009

What's Next for Schatzberg?

An advertisement in the Psychiatric Times (page 34 of .pdf) calls for applicants for the Chair of the Department of Psychiatry and Behavioral Sciences at Stanford University, a position now filled by Dr. Alan Schatzberg. The Stanford Psychiatry Department webpage currently states, in part:

Under the direction of the Chairman and Chief Alan F. Schatzberg, M.D., the Stanford University Department of Psychiatry and Behavioral Sciences, a center for the advancement of psychiatric practice, research and education, has three goals:

• To advance the understanding of the etiologies of psychiatric or sleep disorders and to lay the foundation for new treatment development.
• To develop innovative treatments and to deliver comprehensive services on a continuum of care to patients in a high quality efficient and compassionate manner.
• To train medical students, residents and clinical and research fellows in the science and practice of psychiatry and sleep medicine.

Looks like Schatz is out. I have noted previously that Schatzberg was deeply involved with a duplicate publication that pimped Cymbalta. Schatzberg's close involvement with Corcept, maker of mifepristone (Corlux), has also raised eyebrows. Mifepristone has been an utter failure in clinical trials, but the manufacturer has attempted to spin the data in ways that should be obvious to anyone with a smidgen of critical thinking skills. Charles Grassley has hit Schatzberg as part of the investigation into the tangled web of conflicted interests involving psychiatrists and drugmakers. There is also some evidence that Schatz was involved in the launch of Zyprexa for bipolar disorder.

Schatz is apparently out as department chair. I wonder who will take his place...

Thanks to an alert reader for the tip.

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Saturday, February 14, 2009

KOL Continues to Vanish

Charles Nemeroff, about whom I have written much, continues to disappear. His latest vanishing act: From a psychiatric research gathering in Berlin in late November 2008. Their website now reads: "Dr. Charles B. Nemeroff (Atlanta, the USA) called his participation off in the congress and its scientific contributions." We can only hope that they had another key opinion leader of his stature to replace him.

Back story.

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Saturday, January 3, 2009