Is Science a self-correcting process? I (and the Institute of Medicine) think not.

For years, many scientists and doctors have argued that it was not necessary to police conflicts of interest and other irregularities in scientific research, Money, they argued, couldn't possibly taint their scientific judgment. And even if it did, science was essentially a "self-correcting" process. If some researchers allowed bias into their work and skewed their data as a result, the thinking went, other scientists would eventually expose them because they would not be able to reproduce their results.

Unfortunately, this long-held dogma turns out not to be true (if it ever was). As science becomes more complicated and specialized with dozens of authors weighing in on a single paper, no one has time to reproduce the vast amount of results reported in scientific papers. Nor do most scientists have the inclination to prove wrongdoing, especially when the results favor their own purposes or pocketbooks. In her fascinating new book, Plastic Fantastic, science writer Eugenie Samuel Reich explores the notorious case of Hendrik Schon, a young Bell Labs researcher from Germany who forged data on a number of significant papers detailing supposed breakthroughs in high-performance computer transistors. Reich concludes that in this case, the "self-correcting process" of science turned out to be far less systematic than many scientists think it is. Schon's forgeries were eventually caught in 2002 not by researchers in his own lab but by a few skeptical outliers in other labs who transformed themselves into whistle blowers and refused to accept the assurances of Schon's supervisors that his work was genuine.

Schon, Reich reveals, began fudging data as a graduate student and just dug himself deeper and deeper into a fantasy world in large part to please his supervisors and cover up his inadequacies as an original thinker. While Schon's work (if it had been authentic) certainly had commercial implications, he wasn't necessarily motivated by commercial pressures, she concludes.

The same, however, cannot be said of clinical drug research, where there are tremendous commercial pressures -- to report favorable results about a new drug or medical device. And that is why the national Institute of Medicine (IOM) has weighed in so decisively in its report on conflicts of interest in research and what needs to be done to ensure the integrity of the scientific process. A good overview of the IOM report and its conclusions can be found in this week's New England Journal of Medicine.

Basically, the IOM report calls for Congress to pass legislation (like Grassley's Physician Payment Sunshine Act) that would require pharmaceutical, medical device and biotechnology companies to publicly report payments to physicians and other health care professionals. But the IOM recommendations go beyond the Sunshine Act and call for legislation that would also require professional societies and patient advocacy groups, like NAMI, which have their own blatant conflicts of interest -- see here -- to publicly disclose them.

The IOM report also concludes, as I have argued in Side Effects, that disclosure is not enough. "Academic medical centers and research institutions should "restrict participation of researchers with financial conflicts of interest in research with human participants," the report says. That means if a particular researcher is getting lots of money in consulting and speaking fees from a drug or medical device company, he or she should not be involved in clinical trials of products made by that company. That would rule out the participation of many of the conflicted doctors I've written about here, including Martin Keller, Charles Nemeroff, Alan Schatzberg, Karen Wagner, Graham Emslie, Robert Robinson. The list goes on and on.

The IOM report also calls on medical societies to reform their continuing medical education programs so that they are "free of industry influence..." And it urges physicians to reject gifts or other "items of material value" from pharmaceutical, medical device and biotechnology companies. It also suggests that advisory groups that issue clinical guidelines about medical treatment restrict industry influence and conflicts of interest among panel members.

In sum, the nation's most respected medical body is acknowledging that financial conflicts of interest corrupt scientific research and harm public health in the process. And even in the absence of financial conflicts, scientists have to do more to ensure the integrity of the scientific process. Trust alone just doesn't cut it.

Conflicted psychiatrists strike back -- against the media

Anyone keeping up with the news knows that a number of prominent psychiatrists have been under seige of late after Congressional allegations that they failed to disclose lucrative payments from drug companies whose products they were studying and promoting on the medical circuit. Now comes evidence that some of these key opinion leaders (KOLs as they are known in the industry) are pushing back, accusing the press of launching a "witch-hunt" and trying to intimidate some of the media messengers.

To wit: One of the featured topics at the November 2009 conference of the International Forum on Mood and Anxiety Disorders in Monaco is Making sense of media attacks on experts: is this a wanton witch hunt?” According to my sources, the forum is essentially an "astroturf creation" of Pharma directed by two prominent psychiatrists with industry ties in Europe. The invited speaker list includes the usual list of KOL suspects, including our very own Alan Schatzberg, who is stepping down as chair of psychiatry at Stanford University.

Schatzberg and Stanford insist that his departure has nothing to do with the media blitz that occurred after a probe by Sen. Charles Grassley uncovered evidence that Schatzberg had failed to disclose he owned $4.8 million in stocks in a company he cofounded -- Corcept Therapeutics -- at a time when he was principal investigator of a NIH-funded study of Corcept's drug for treating depression. Stanford fully disclosed Schatzberg's stock ownership to Grassley's team only after The New York Times, Business Week and other media took note of the Congressional investigation, according to my sources. Shortly thereafter, Stanford asked Schatzberg to step down as principal investigator of the NIH study. And now it has come to light that Stanford is looking for a new chair of its psychiatry department. University officials insist Schatzberg decided to step down long before the conflict of interest contratemps. I'll leave it to you, dear reader, to decide if you believe them.

Schatzberg may be on his way out, but in the meantime, he and Stanford have been busy haranguing the likes of the New York Review of Books (for publishing Marcia Angell's article on medical corruption) in which she noted Schatzberg's conflicts;CBS, which reported on Stanford's problems, and the Corporate Crime Reporter, which recently published an interview with me here about conflicts of interest in medicine. Stanford media relations demanded corrections from all three media, insisting that Stanford fully disclosed Schatzberg's conflicts of interest. Last I heard, there have been no corrections issued.

Schatzberg, it turns out, is no stranger to litigation. A few years ago, he sued University of Massachusetts psychiatrist Anthony Rothschild alleging that Rothschild had libeled and defamed him. Among other juicy items, the lawsuit, which was filed in California Superior Court (Santa Clara County), alleges that Rothschild, using a fake email and name, reported on a Yahoo message board that Schatzberg was using his position at chair of psychiatry at Stanford to promote Corcept's drug and that he and his cofounder knew the drug didn't work (for depression) as far back as 2005 and were selling stock in the company.

There is a history here, of course: In the late 1980s, Rothschild and Schatzberg worked together at Harvard's McLean Hospital, where they came up with the idea of using a drug to block the stress hormone cortisol as a possible treatment for depression. Their brainstorm was to use the abortion drug RU-486, whose main ingredient is mifepristone, a chemical known to block cortisol. But then Schatzberg became chair of psychiatry at Stanford in 1991 and apparently took the idea with him, co-founding Corcept a few years later. At one point in this bizarre saga, Partners, which owns McLean Hospital, even sued Stanford over the patent for Corcept's drug (the case was settled in mediation from what I gather).

What all this shows is that Schatzberg is not afraid to throw lawyers at his critics. I wonder if that's the kind of aggressive action he'll advise at the wanton witch-hunt session in Monaco. What I want to know is: who's paying for his trip there?

Where's the conflict of interest here, Mr. Robinson?

Remember the flap a few weeks ago between researcher Jonathan Leo and the Journal of the American Medical Association, whereby JAMA's editors got egg all over their face after trying to intimidate Leo? Leo, a professor of neuroanatomy at Lincoln Memorial University in Harrogate, Tenn., had written a letter to the British Medical Journal, pointing out that the author of a study published in JAMA failed to disclose he had a financial relationship with the drug company whose product he was reporting on. As it turned out, Leo had first brought the undisclosed conflict of interest to the attention of JAMA, but when he didn't hear back from them for five months, he published it online in BMJ. JAMA editors then insisted they were about to issue the correction themselves (which they did here) and blasted Leo for acting precipitously (is waiting five months precipitous?). According to an article by David Armstrong in the Wall Street Journal, Catherine D'Angelis, editor in chief of JAMA, went so far as to call Leo "a nobody and a nothing."

Now there's a new twist to this saga: Robert Robinson, the researcher who originally failed to disclose his conflict of interest, published a letter yesterday in BMJ where he accuses Leo of having a conflict of his own. Leo, he said, was a board member of the International Center for the Study of Psychiatry and Psychology (ICSPP), a group "that is strongly opposed to the blanket use of psychopharmacological treatments." Neither accusation happens to be true: Leo is no longer a board member of ICSPP, and the ICSPP is not opposed to the use of drugs. Indeed, the group's website says, "we are not against the use of psychoactive drugs by competent adults who have been thoroughly informed of their value, potential side effects, and alternatives."

What Robinson seems not to understand is what a conflict of interest really consists of. According to Tufts University's Sheldon Krimsky and other experts, conflicts of interest are widely understood to be financial interests or ties to companies whose products you are studying. As Krimsky told me when I was researching my book, Side Effects, "The integrity of the scientific endeavor is tarnished by the quantity of the money [a particular researcher] is getting as well as the lack of disclosure." Research done by Krimsky and others shows that financial conflicts of interest do bias the recipients of such largesse and their work. And that's why JAMA and other leading medical journals require researchers to disclose financial conflicts of interest, which Robinson failed to do. (Robinson now acknowledges that he was getting personal payments from Forest Labs, the maker of Lexapro, which he should have disclosed in the JAMA study finding that Lexapro was effective in helping treat depression in stroke victims).

But where is financial conflict of interest with regard to Leo? Yes, he was once a board member of ICSSP, an unpaid position, but while that may shed light on where he stands about the indiscriminate use of powerful psychoactive drugs, it is not a conflict of interest. Get real, Robinson.

Full disclosure: I have been asked to speak at the ICSPP's annual meeting next fall (Oct. 9) in Syracuse. And while I am being reimbursed for my travel expenses, I am not being paid a speaker's fee. Would that I were!

Why didn't Brown axe Martin Keller years ago?

Brown University's student newspaper, The Daily Herald, reported this week that Martin Keller had announced his decision to step down as Brown's chair of psychiatry in August 2007. In a letter he apparently sent to faculty in his department, Keller said he would be stepping down in June 2009 to devote more time to research and allow the university to take the time to find a "world-class new chair."

However, according to sources, Keller was then asked to stay on as chair until Brown's affiliate hospitals could complete a merger with Lifespan Hospital. "The thinking was that they couldn't recruit a chair of psychiatry until the merger was decided," said a Brown faculty member who asked not to be named. The merger, of course, hasn't happened yet, and Brown officials apparently decided to revert to the original timetable for Keller's departure in the wake of publicity over Keller's misrepresentation of data in Paxil study 329 -- see back story here -- and Sen. Grassley's probe into his extensive financial ties to the pharmaceutical industry; see story here.

As several Brown faculty members note, it doesn't really matter when Keller was asked to step down as chair. What matters is the fact that the university let Keller stay on the faculty long after they were made aware of his scientific misconduct. Brown officials were first made aware of allegations about Keller's misrepresentation of data in Paxil study 329 when I was doing research for Side Effects in early 2007, and again in 2008, when David Egilman, a Brown faculty member, filed an ethics complaint against Keller, and Side Effects was published.

"[Keller] omitted evidence that showed that Paxil increased the risk of suicide attempts from his published papers," Egilman, a clinical associate professor at Brown, said in a recent interview. “He manipulated the data to show the drug was an effective treatment for depression when the data really showed it was no better than a sugar pill. GSK, the manufacturer of Paxil, wrote up the results and Keller claimed authorship." See back story here.

Egilman continues: "If my student does that, it’s called plagiarism and he gets thrown out; if a faculty member does it, the University runs a protection racket for him.”

Brown should have disciplined Keller as soon as they knew about his manipulation of data, Egilman says. "The fact that they cleared him of wrongdoing shows that the university relies on faculty to police themselves," he says. "Brown has no standards whatsoever for the work that the faculty does."

NAMI exposed: the drug money behind this supposedly grassroots group

Earlier this week, Senator Charles Grassley announced a probe into the nation's largest advocacy group for people with mental illness, the National Alliance for Mental Illness, asking the nonprofit group to disclose the funding it has received in recent years from the drug industry. The fact that NAMI is heavily dependent on drug company money is old news, but Grassley's investigation, first reported in Bloomberg News, may shed a welcome spotlight on an lobbying organization that masquerades as grassroots.

In Side Effects, I reveal that drug company contributions have always been a substantial portion of NAMI's revenues. I also tell the story of how Jim McNulty, president of NAMI from 2002 to 2004, failed to disclose the fact that he was being paid thousands of dollars from drug makers for promoting their products to NAMI members and others at various speaking engagements. In a particularly intriguing twist, McNulty laundered this drug company money through a state chapter of NAMI.

This is how the scheme worked, according to McNulty himself and others in the know. He would be paid thousands of dollars to speak about the benefits of various antidepressants -- McNulty himself suffered from depression -- and rather than pay him directly, companies such as Eli Lilly, the maker of Prozac, Pfizer, the maker of Zoloft, and GlaxoSmithKline, which made Paxil, would give his speaking fees to the Rhode Island chapter of NAMI, which would then cut McNulty a check. When I asked McNulty why he was paid this way, he said, "Paperwork. It was simpler that way."

McNulty, of course, never disclosed these conflicts to his constituents or to the NIH (which appointed him to sit on influential advisory boards that rendered opinions about the safety and efficacy of the drugs he was being paid to promote).

NAMI continues to receive hefty contributions from the drug industry but it no longer reveals the specific donors in its annual report, published online. So Grassley's team has asked the organization to disclose the specifics of its funding so that people with mental illness and their families can see for themselves how conflicted this advocacy group is. At FDA hearings over the years held to examine the safety and effectiveness of antidepressants like Prozac and Paxil, NAMI was always quick to come to the defense of these drugs. And NAMI opposed the black box warnings the FDA required drug makers to put on the labels of antidepressants in 2004 about their increased risk of suicidal thoughts and behaviors. Now that Grassley's team is looking into NAMI's books, perhaps the group's members -- people with mental illness and their families -- will cast a more skeptical eye on its credibility.

Brown psychiatry chief Martin Keller to step down in June...

Martin Keller is finally stepping down as the long time chief of psychiatry at Brown University. Brown University officials made the announcement in a Dear Colleagues letter dated today from Edward J. Wing, Brown's new Dean of Medicine and Biological Sciences.

Keller is the latest psychiatry kingpin to fall. In recent months, Emory University forced its psychiatry chief Charles Nemeroff to step down and Stanford is looking for a new head to replace Alan Schatzberg after reports that these two prominent psychiatrists, like Keller, failed to disclose years of lucrative financial payments from the pharmaceutical industry.

While Brown officials insist that the decision to step down was Keller's, my understanding from several sources is that the university has been under pressure to take action against him for months.

As I have reported in Side Effects and my blog here and here, Keller not only failed to disclose the millions of dollars he has received over the years from companies whose drugs he was studying and promoting in medical journals and at conferences. But there is evidence that Keller and his co-authors misrepresented data in a clinical trial of Paxil to make the antidepressant look safer and more effective than it really was. This trial, known as study 329 and funded by GlaxoSmithKline, was published in 2001 and used by the drug company to heavily market Paxil for off-label use in children and adolescents.

Yet as it turns out, the data in this trial do not corroborate the company's claims that Paxil was more effective than a placebo or sugar pill in treating depression in adolescents. The 2001 study also under-estimated the rate of suicidal thoughts and behaviors among participants taking Paxil in the study (in a 2006 paper, GlaxoSmithKline acknowledged that those taking the drug were five times more likely to be suicidal than those taking the placebo). GlaxoSmithKline is now under investigation by federal Department of Justice officials, and Keller himself has been deposed by attorneys in Boston's U.S. attorney's office, according to sources.

I also understand that the NIH recently refused to renew a long-term research grant submitted by Keller, in large part because of the allegations about Keller's scientific misconduct and his failure to disclose his conflicts of interest. Although Brown officials refused to confirm the NIH action, if you search the federal database for NIH grants (CRISP), you can see that Keller currently has three long-term research grants with National Institute of Mental Health; one of those grants, for a study comparing psychotherapy to drugs in treating depression, runs out this June. Another grant, for a long-term collaborative study of depression, ends in January.

Until recently, Keller was a major rainmaker for Brown, bringing in millions in research funding from the NIH and pharmaceutical companies to the university's medical school. Indeed, in a 2006 deposition, Keller said his department of psychiatry received $50 million in research funding, a significant hunk of change. Some have speculated that is why Brown has been reluctant to move against him. But now that NIH is no longer renewing Keller's research grants, one might speculate that his usefulness to Brown has diminished.

All of this may explain why come June, Martin Keller will join Nemeroff and Schatzberg on the growing roster of once-powerful psychiatry chiefs who have toppled from grace.

A new approach to treating mental illness?

When people exhibit signs of psychosis – they hear voices, they think someone is out to get them – more often than not, they are referred to psychiatrists who immediately put them on powerful drugs like Haldol, Depakote, Abilify or Seroquel. These drugs sometimes tamp down the voices and other psychotic symptoms (and sometimes they don’t). Such medications also make many people feel like zombies and carry a plethora of severe side effects such as excessive weight gain and an increased risk of diabetes and heart problems. Too often, their benefits are short-lived, and many people experiencing psychosis end up in a vicious cycle of hospitalization and isolation – unable to hold down a productive job and stigmatized by the world at large.

In her new book, Agnes’s Jacket, Gail Hornstein, a professor of psychology at Mount Holyoke College, offers an intriguing alternative to dealing with psychosis: support groups that allow people to discuss and deal with the voices they are hearing without medication, in a caring and empathetic environment. She explores this “psychiatric survivor movement” in great depth in her book, chronicling the Hearing Voices network and other support groups that have made this movement possible. She presents vivid examples of people who were previously labeled psychotic and slapped on drugs, but who, with the help of support groups, have learned how to live with and control the voices they hear inside their heads. Some of these people have gone on to live rich, productive lives without the need for medication or hospitalization. As Hornstein writes in her book, “Sharing experiences in peer support groups has led them to a whole different way of understanding their distress…Psychiatric survivor groups teach patients that emotional difficulties, no matter how severe, can coped with."

Hornstein makes a persuasive case for the power of peer support and the importance of understanding psychotic symptoms in the context of the trauma that many people with such symptoms have experienced in their lives. And she rightly points out that psychiatrists -- under the sway of the pharmaceutical industry and managed care – have been much too quick to put their patients on powerful drugs instead of exploring other therapeutic alternatives first.

Just one quibble. In her book, Hornstein seems to sweep all American psychiatrists into the same boat, ignoring those who remain committed to psychotherapy (despite inadequate reimbursement from insurers) and to developing the kind of positive, trusting relationships that put patients on the road to recovery.

Last year, for example, I had the opportunity to attend a meeting of the International Society for the Psychological Treatments of the Schizophrenias and other Psychoses (ISPS), where I heard a previously psychotic patient talk about how his relationship with his psychiatrist enabled him to recover from years of mental illness. As a young man, Mark had been labeled schizophrenic because he heard voices all the time. He was repeatedly hospitalized, put on Haldol and Clozaril, powerful anti-psychotics that made it difficult for him to function. For years, Mark couldn’t hold down a job or live on his own.

Over the past 10 years, however, Mark has been in therapy with the same psychiatrist, and they have developed such a strong relationship, one based on mutual respect and trust, that Mark is no longer psychotic. He now has a job, lives by himself and, judging by what he had to say at the ISPS meeting, is a thoughtful, articulate man. He credits the relationship he has developed with this particular psychiatrist for his recovery, noting: “When you feel good about the people you’re working with, you generally want to stay healthy.”

And that, of course, is precisely what makes the support groups that Hornstein extols so effective as well. Regardless of what experiences people are sharing and who they share it with, they are much more likely to recover from mental illness when they are surrounded by understanding, empathy and respect. And that’s not something you can get from a pill.