UPenn President is urged to resign as chair of Obama's bioethics commission for ignoring scientific misconduct allegations

The Project on Government Oversight (POGO) has called on President Obama to remove Amy Gutmann, University of Pennsylvania's president, as chair of his presidential commission for the study of bioethical issues. The reason: Gutmann did nothing to sanction the chairman of UPenn's psychiatry department for publishing an editorial under his name that was ghost-written by a medical company that worked for the drug industry. The editorial, published in Biological Psychiatry, called for the aggressive treatment of bipolar disorder on the grounds that it was linked to a number of serious diseases. In a letter to NIH Director Francis Collins last November, POGO had disclosed the ghost-writing allegation, among other egregious ghost-writing examples, and called on Collins to curb this widespread practice in scientific research.

Now, Dr. Jay Amsterdam, a psychiatrist at UPenn, has filed a new complaint with the federal Office of Research Integrity (ORI), charging that Dr. Dwight Evans, UPenn's psychiatry chair, and four colleagues (including then psychiatry kingpin Charles Nemeroff) engaged in scientific misconduct by allowing their names to be appended to a manuscript that was drafted by the same ghostwriter for GlaxoSmithKline that wrote the editorial for Evans. Amsterdam also alleges the ghost-written paper misrepresented information from a study on the use of Paxil in bipolar depression. The study in question was funded by GlaxoSmithKline and a grant from the NIMH and published in the American Journal of Psychiatry in June 2001.

In his complaint, which can be found here, Amsterdam, who was one of study 352's principal investigators, alleges that the published manuscript did not acknowledge the medical ghostwriter's contribution or the extent of Glaxo's involvement in preparing the paper. The study itself, he says, made unsubstantiated claims about Paxil's effectiveness and downplayed some serious side effects. For example, study 352 suggested that Paxil was beneficial in the treatment of bipolar disorder, when in fact it failed to show efficacy over an older antidepressant on at least one primary outcome measure. The manuscript also did not report that Paxil may have induced mania in some patients, which is a well-known side effect not only of Paxil but other SSRI antidepressants.

Dr. Amsterdam also alleges that even though he was a principal investigator of the study, he was excluded from the final data review, analysis and publication of the paper by the ghostwriter, Scientific Therapeutics Inc (STI). STI has a longstanding history of ghostwriting medical articles under contract to GSK and other drug companies. STI was the same company that ghost-wrote the notorious Paxil study 329, as detailed in Side Effects. Indeed, study 329 was included as one of the egregious examples of ghostwriting in POGO's letter to Collins last November, which I blogged about here.

Back in 2001, when Amsterdam repeatedly complained about not being included in the publication of his own study, one of the junior psychiatrists who had been named as an author in his place apologized to him, explaining that "control of the paper had been taken away from him and that GSK published the paper without circulating the draft to all the participants..." Amsterdam continued to assert that some sort of reprimand was necessary to ensure that "plagiarism" of a colleague's data didn't happen again. But his complaints were brushed off by Evans and other colleagues at UPenn.

In his letter to ORI, Amsterdam's attorney notes that even though study 352 was published 10 years ago, it continues to be referenced in medical journals, most recently as this year. He called on the Office of Research Integrity to conduct a thorough investigation to ensure that similar misconduct never happens again and to prevent further use of study 352 "to support the dangerous prescription of Paxil to patients diagnosed with bipolar depression."

And now back to Amy Gutmann. As chair of the presidential commission on bioethics, UPenn's president is supposed to be working to promote ethical behavior in scientific and medical research. Last November, when POGO released its letter to NIH citing the ghostwriting incident involving UPenn's psychiatry chair, the university student newspaper jumped on the story. At the time, a university spokesman was quoted in the student paper saying that allegations of ghostwriting in Evans' editorial were "unfounded." Yet documents unsealed in a lawsuit show evidence that STI prepared a draft of the editorial for Evans. Amsterdam's attorney sent Gutmann a copy of his official complaint last week; see here.

In its missive to President Obama, POGO writes:

We do not understand how Dr. Gutmann can be a credible Chair of the Commission when she seems to ignore bioethical problems on her own campus. Until the University concludes a sincere and transparent investigation of these charges and takes decisive action to deter future ghostwriting, we feel that Dr. Gutmann should be removed as Chair of the Commission.

Stay tuned...

Biederman and colleagues at Harvard get a slap on the wrist

Harvard Medical School finally wrapped up its three-year-old investigation of Dr. Joseph Biederman and two colleagues accused of failing to disclose extensive financial conflicts of interest, with essentially a slap on the wrist.

In 2008, Congressional investigators accused the three psychiatrists -- Biederman, Thomas Spencer and Timothy Wilens -- of failing to disclose more than $1 million each in payments from the drug industry. As I blogged about here, most of Biederman's financial ties were with the makers of anti-psychotic drugs at the very same time he was promoting the use of these drugs in the treatment of childhood bipolar disorder. According to documents released in a lawsuit, Biederman also courted funding from Johnson & Johnson by promising that his work at Mass. General would promote the use of its anti-psychotic Risperdal in children. Johnson & Johnson gave the hospital $700,000 for a Biederman-led research center that did studies promoting Risperdal. All of which raises the question of whether Biederman helped the drug company illegally market the off-label use of its anti-psychotic drug in children

But rather than suspend or fire him for such unethical and possibly criminal behavior, Harvard and Mass. General let him and his two colleagues off easy. According to The Boston Globe, they required the three physicians to refrain from all paid industry-sponsored activities for one year and undergo unspecified additional training. A letter Biederman and his colleagues wrote to co-workers about the remedial actions also mentioned that they might "suffer a delay of consideration for promotion and advancement."

Wow, that's tough. As Dr. Jerome Kassirer, a Tufts University professor and author of On the Take, notes in The Globe article, Biederman already is a full professor at Harvard so it's unclear how a delay in promotion would affect him. This strikes me as one more example of how hospitals and medical schools are so compromised by drug company money themselves that they no longer care to impose ethical standards on their own faculty.

On a sadly related note, the mother of Iris Chang, a bestselling author and historian who killed herself in 2004, reveals in a new memoir that her daughter was taking psychoactive drugs that may have caused her suicide. Iris Chang was the author of The Rape of Nanking, a critically acclaimed history of the massacre of Chinese men, women and children by Japanese soldiers in the run-up to World War II. She was only 36 when she died and the mother of a two-year-old boy.

In her memoir, The Woman Who Could Not Forget, Ying-Ying Chang, reveals that Iris was taking Risperdal and the antidepressant Celexa, when she killed herself. Chang's mother writes that she believes Iris' suicide was caused by her medications. She calls attention to the extensive literature showing that SSRI antidepressants cause suicidal behavior in some patients (often in the days after they first start the drugs), and she notes that Iris had begun taking Celexa right before she shot herself in October 2004.

Her mother writes:

"[Iris] represented a classic case in which psychiatric medications change one's personality. I do not need to repeat the huge number of bizarre cases documented, in which an originally ordinary mildly depressed patient becomes violent and destructive after taking antidepressants...The tragic violent way she ended her life was not characteristic of Iris."

Ying-Yang said she hopes her memoir "will help people become aware of the possible danger of psychiatric drugs and to think twice before taking them."

Everything you wanted to know about ghostwriting but were afraid to ask...

Two quick notes: the Project on Government Oversight (POGO) has posted a helpful FAQ on corporate-funded medical ghostwriting. As POGO investigator Paul Thacker writes:

"We hope this [FAQ] will answer any questions you might have on this very disturbing practice that corrupts the medical literature, drives up healthcare costs, and puts patient safety at risk."

Also, my blog was recently listed on a popular pharmacy website as one of the 50 best blogs about pharmaceuticals, right up there with Pharmalot and BNET Pharma. I'm honored.

The real reason biotech industry opposes Medicare advisory panel

A page-one story in The Boston Globe today spotlights the Massachusetts biotech industry's effort to block a key piece of President Obama's health care overhaul: the creation of an independent payment advisory board (IPAB) that would make recommendations on how to trim wasteful and counterproductive Medicare spending.

The presidentially appointed board, to be comprised of representatives from hospitals, physicians, patients, drug and device companies and other health care constituencies, is supposed to recommend program changes that will hold Medicare spending increases to levels that are no greater than the pace of economic growth (GDP) plus one percent. As Merrill Goozner explains in gooznews, the board can recommend replacing fee-for-service with bundled payments or pay-for-performance schemes. It can penalize health care organizations for lousy care and give them incentives for higher quality care. Whatever the board recommends must be passed by Congress, which also has the option of substituting its own cost-cutting measures.

As Goozner, Paul Krugman and others note, the board will have much less power than comparable boards in Europe. Even so, the IPAB has come under attack from Republicans such as Paul Ryan (R-Wis.) and conservative columnists such as David Brooks. And now we see the biotech industry coming out against it.

Why? The Massachusetts biotech executive council says it's because the board would stifle innovation and hurt the state's economy. May I point out this is the same old canard the drug and medical device industry trots out whenever they don't like a particular regulation aimed at protecting American consumers? They trotted out the same argument when opposing Massachusetts' pioneering ban against gifts and free meals for doctors and then calling for its repeal -- see here. And they dusted it off again to pressure the FDA into backing down from its recent efforts to ensure that unsafe drugs and medical devices are kept from the market -- see here.

The real reason the biotech, drug and medical device companies are opposed to the creation of the independent board is because its recommendations that hospitals and doctors dispense effective but less expensive drugs and procedures would cut into industry's profit margins. Industry representatives don't seem to care that the board's decisions might actually improve the quality of patient care. Consider, for example, the metal-on-metal hip implants that Barry Meier wrote about in Sunday's New York Times. As it turns, these new implants, which were not fully vetted by the FDA, caused considerable pain and health problems for many patients.

If the independent payment advisory board had already been set up, it might have recommended that hospitals and doctors first consider older, safer hip implants for their patients. Likewise, as Meier points out, there are many older drugs that are just as effective, and in many cases, safer than the costly brand names. (Vioxx, Avandia, Seroquel and Zyprexa are just a few of the new drugs that were trumpeted as more effective and safer than existing meds but turned out to be the exact opposite). Yet the pharmaceutical industry does a masterful job -- through heavy marketing and lucrative doctor payments (some would call them kickbacks) -- of convincing physicians to prescribe costly new drugs instead of equally effective generic drugs. And as we can see from the soaring cost of health care, private insurers (the free market that Rep. Ryan is so fond of extolling) have done a lousy job of reining in these excesses.

The purpose of the independent advisory board is not only to cut such wasteful and counterproductive spending but to help doctors and hospitals reach more considered decisions about how to improve the quality of health care for Medicare patients. But the drug and medical device industry doesn't like that idea one bit.

New Pfizer deal with Boston-area medical schools dissected on WGBH-TV

I was planning to blog about Pfizer's new $100 million partnership with several Boston-area medical centers and its potential downsides. But before I could get around to doing that, I was invited to talk about the deal on WGBH-TV's Greater Boston show yesterday. If you're interested in what I have to say, you can watch here.

Is the credibility of Emory neurologist Helen Mayberg in question? You judge

A few weeks ago, I blogged about the strange case of Dr. Helen Mayberg, a neurologist at Emory University who has testified in more death penalty cases in recent years than almost any other doctor in the country. I highlighted Mayberg's lucrative and lethal (she always testifies for the prosecution who are pushing for the death penalty) sideline as an example of why the National Institutes of Health should adopt stricter conflict of interest guidelines that would require universities to more fully disclose the extent of their researchers' financial conflicts of interest.

At the time, I quoted a prominent neurologist who said that Mayberg goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process. Since then, I have received additional information about her testimony in one particular death penalty case that appears to buttress such accusations. Indeed, critics say that her testimony indicates a level of hypocrisy and willingness to dissemble that should concern officials at the NIH, where Mayberg is principal investigator of several major multi-million-dollar research grants.

First some background. As I've blogged about here, Mayberg was recruited to Emory University by former psychiatry kingpin Charles Nemeroff and soon became involved in a major conflict of interest controversy with Nemeroff when they both failed to disclose significant financial ties to a medical device company in a positive paper they wrote about the company's patented technique. After Nemeroff was forced to step down as chief of psychiatry at Emory (for this and other failures to disclose), he departed Emory for the University of Miami. And lo and behold, Mayberg, who is not a psychiatrist and has never treated patients in clinical practice, became principal investigator of two major NIMH studies Nemeroff used to lead: the mood and anxiety disorders initiative, a collaboration between NIMH (which put up $2.1 million last year alone) and GlaxoSmithKline, to develop a new generation of antidepressants, and another $1.8 million study called predictors of antidepresssant treatment response.

As the principal investigator of such large, taxpayer-funded studies, Mayberg's credibility should be above reproach. However, according to transcripts, she has testified under oath in direct contradiction of her own statements in published research papers. In one particular death penalty case, a neurologist for the defense testified that PET scans taken of the defendant, a guy convicted of murder by the name of Erick Virgil Hall, showed that he had decreased functioning in an area of the brain associated with impulse control and aggressive behavior. Dr. James Merikangas, a clinical professor of psychiatry and at the George Washington School of Medicine, used the neuroimaging results, together with a comprehensive review of the defendant's social and medical history and a physical examination, to conclude that Hall had brain damage that should be allowed as mitigating evidence in his case. Merikangas was careful not to say that the decreased brain functioning found in the PET scan explained Hall's violent behavior, only that there was evidence of brain damage that may have impaired his judgment. (Such mitigating evidence is often introduced in an effort to take prisoners off death row and convert their sentence to a life in prison).

In her 2007 testimony in the Hall case, Mayberg derided the value of PET scans in showing brain damage, saying that "the use of PET scans for the clinical diagnosis and treatment of individual patients is extremely limited." She concluded that PET and functional neuroimaging scans cannot be used for diagnostic purposes or to quantify "residual effects of past traumatic brain injury."

However, Mayberg herself has used PET scans to diagnose depression and evaluate the response of depressed patients to deep brain stimulation, a surgical technique that she developed and patented and continues to promote as a valid treatment for depressed patients who have not responded to drugs; I've blogged about the controversial nature of her work here. In several papers Mayberg published about her research with deep brain stimulation, she discussed the value of using PET scans for this purpose. In one 1990 paper, for instance, she said that a PET scan "showed hypometabolism [decreased brain functioning] in the right lateral basotemporal region in all three patients." In another 2007 paper, she used PET scans to assert that "non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex." In yet another summary of one of her NIH-funded studies, she says she will use PET scans to assess the response of patients to different treatments. In these and other published articles, Mayberg herself is drawing cause and effect relationships between brain abnormalities and specific psychological conditions.

As Merikangas points out in his affidavit, Mayberg is well aware of the importance of neuroimaging in a forensic setting. In another 2007 paper, Mayberg concluded:

"In sum, neuroimaging evidence has become an increasingly important tool of proof in criminal and civil cases in the United States. Although subject to the constraints of reliability and relevance, results of neuroimaging scans can and do help courts to understand the nature, causes and behavior implications of injuries to the brain."

Indeed, a recent study cited in the New York Times affirmed that a highly sensitive functional type of magnetic resonance imaging found evidence of brain injuries in veterans injured in Iraq or Afghanistan that was too subtle to be detected by standard MRI scans.

To be fair, Mayberg testified in the Hall case three years before this new study came out. However, by 2007, plenty of research evidence existed showing that PET and other neuroimaging scans could detect key changes in brain functioning. In his affidavit, Merikangas cites three papers published in 2005 and 2007 indicating decreased brain functioning picked up by PET scans in areas implicated in aggressive and violent behavior.

Mayberg, Merikangas says, is simply ignoring the peer-reviewed literature on this subject. He concludes that her testimony in the Hall case is both misleading and deceptive. Now, Mayberg is at liberty to consult for and testify in whatever legal proceedings she elects to, as long as she fully discloses these conflicts of interest (which some would argue she hasn't). But as someone who is in charge of millions of dollars of taxpayer money, her word should be inviolate. It's kind of analogous to what's going on with Anthony Weiner and tweetgate. Given his sorry track record of lying to the American public, Rep. Weiner (NY) should probably resign his post in Congress, and in my view, we should hold federally funded researchers to the same high standard of credibility.

Footnote: Erich Hall is still on death row.

Helen Mayberg: A case study in why we need greater transparency about conflicts of interest

A year ago, the Department of Health and Human Services proposed new rules governing the disclosure and handling of financial conflicts of interest by medical researchers who receive federal funding. The more stringent rules were prompted by Congressional findings that prominent NIH-funded researchers had failed to disclose significant consulting and other income, violating the agency's own regulations. The new rules would, among other things, require universities to post on a publicly available website information describing the specific financial conflict of interests of their federally funded researchers, according to Sheldon Krimsky, the Tufts University ethicist who wrote about the new rules in an article for Ethics in Biology, Engineering & Medicine last year.

Why is this so important? Because the current system of disclosure has proven woefully inadequate in providing consumers with information about financial conflicts that can skew medical research and adversely affect patient care. According to a 2008 Inspector General's report, the vast majority (93 percent) of institutions reporting conflicts of interest to the NIH did not describe the nature of their researchers' conflicts; in addition, 90 percent of the universities relied solely on the researchers' discretion in reporting conflicts, which is why there was so much failure to disclose in the first place.

Here's an interesting case in point. Dr. Helen Mayberg, a neurologist at Emory University School of Medicine, has testified in more than 50 death penalty cases, always for the prosecution in an attempt to discredit any mitigating evidence of brain damage in defendants on death row. Indeed, in a 2009 transcript (State of Connecticut vs Richard Roszkowski), Mayberg acknowledged that she has probably testified exclusively for the prosecution in more recent death penalty cases than any other doctor in the country, except perhaps Park Dietz, known by some as Dr. Death for his decades of testifying on behalf of the prosecution in high-profile cases.

While Emory officials say Mayberg has reported her expert witness work to them, they are under no obligation to disclose the full range of her extra-curricular activities to the public under existing federal rules. As a result, very few of Mayberg's colleagues or patients know of her extensive testimony in death penalty cases. And Mayberg goes to some lengths to keep her lucrative sideline out of the public eye.

For example, she had a friend (David Dobbs)* scrub her Wikipedia page of any reference to her death penalty work or her previous failures to disclose other conflicts of interest; here's a more comprehensive earlier version of her wikipedia page pre-scrubbing. I blogged here about Mayberg's collaboration with former psychiatry kingpin Charles Nemeroff and her previous failure to fully disclose conflicts of interest involving her work with deep brain stimulation, a controversial technique for treating depression.

Also missing from Wikipedia is the fact that she has so angered other neurologists with her death penalty testimony that they tried to get her drummed out of the American Neuropsychiatric Association. As one prominent neurologist says, it's not just that Mayberg always testifies for the prosecution in death penalty cases -- in effect, "trying to kill people" -- but that she goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process.

"She uses a lot of maneuvers to say that [defense] findings in brain scans are not valid, yet at the same time, she's written articles saying the brain scans are valid," says the neurologist in the Washington, D.C. area who has written extensively about brain damage. "In fact, she uses the same brain scans that she says are invalid in the courtroom to diagnose depression in people whom she then treats with deep brain stimulation."

According to Krimsky, Mayberg's death penalty work is considered a significant financial conflict of interest under both the old and new NIH rules. And if the new rules are adopted, she would not only be forced to disclose the extent of her death penalty work but also the money she makes from it. According to lawyers who do for this kind of work, Mayberg makes as much as $500 an hour testifying for the prosecution in death penalty cases. And since she travels all over the country to testify, including to notorious death penalty states like Texas and Alabama, those hefty hourly fees add up.

In response to my query about how many death penalty cases Mayberg has disclosed since she came to Emory in 2004 and how much money she's made from this sideline, all Emory officials would tell me is that "she reported five instances of expert witness activity in 2009." You do the math.

*Correction: David Dobbs did not scrub Mayberg's wikipedia page; he merely added a link to a feature he had written about her for the New York Times magazine.