A tale of censorship and secrecy starring the American Psychiatric Association

Psychiatry is supposed to be all about disclosure, disclosing the dark secrets of one's past to a professional in an effort to heal or, at the very least, figure out why one is in such psychic pain. But given the recent actions of the American Psychiatric Association, the largest trade group for psychiatrists in the U.S., one might get the impression that the profession is really all about censorship and obfuscation.

Remember when the Project on Government Oversight (POGO), as part of an effort to get the NIH to crack down on ghostwriting, released documents showing that a psychopharmacology handbook for primary care doctors, authored by then psychiatry kingpins Charles Nemeroff and Alan Schatzberg, had actually been ghost-written by a company hired by GlaxoSmithKline, the maker of the blockbuster antidepressant, Paxil? The New York Times broke the story last fall, relying on internal Glaxo documents obtained in the course of a lawsuit against the drug giant, and a number of other journalists, including myself, blogged about it -- see here. The documents showed that Glaxo hired Scientific Therapeutics Information (STI) to prepare a draft of the textbook with the understanding that Glaxo could review the initial drafts before publication. The handbook itself, which was published in 1999 by the APA, essentially promoted Paxil, among other drugs, as a safe and effective treatment for anxiety and depression.

Sound familiar? As Side Effects reveals, that's exactly how the initial drafts of the notorious Paxil study 329 were prepared -- by the same company, STI, again under contract to Glaxo. In a remarkably similar arrangement, the authors of the Paxil study did not object to the draft's positive wording and made only minor changes to the paper, which concluded that Paxil was safe and effective in treating depression in adolescents even though the actual data showed quite the opposite -- see back story here. (In its later review of Paxil and other antidepressants before attaching black box warnings to them, the FDA labeled study 329 a "negative finding" because the study did not show statistical evidence of the drug's effectiveness and did not accurately represent the extent of Paxil's suicidal side effects among adolescents in the trial).

To get back to the story at hand, after the Times article was published, Nemeroff, who was drummed out of Emory for failing to disclose myriad financial ties to the drug industry and is now chair of psychiatry at the University of Miami, and Schatzberg, the dethroned chair of psychiatry at Stanford and a past president of the APA, called in their lawyers who insisted on several corrections to the Times piece, which I append here:

A headline on Nov. 30 with an article about SmithKline Beecham’s role in the publication of a book about treating psychiatric disorders overstated SmithKline’s actions. While documents show that SmithKline (now known as GlaxoSmithKline) hired a writing company for the book, they do not indicate that the company wrote the book for the authors, Dr. Charles B. Nemeroff and Dr. Alan F. Schatzberg. The article also described incorrectly, in some editions, events outlined in a letter from the writing company to Dr. Nemeroff. The correspondence proposed a timeline for the writing company to furnish the doctors and SmithKline with draft text and final page proofs for approval; the letter did not say that the company had already provided those materials for final approval. And the article misstated the context under which Dr. David A. Kessler, the former commissioner of the Food and Drug Administration, commented about the book’s production. The letter and other documents were described to him; he did not personally review the documents.

All well and good, but then the APA, probably in response to outraged queries from its members, wrote a self-serving and inaccurate piece about the whole affair in its news bulletin, Psychiatric News. Its bromide said the corrections "seemed to throw into doubt the central premises of the original article" and "seriously overstated the role of the writing company." Neither of these allegations, of course, are true -- the corrections appended to the Times article do not change the basic fact that the handbook was largely ghost-written by a company hired by Glaxo to promote Paxil and other antidepressants to primary care doctors.

Indeed, two prominent psychiatrists pointed that very truth out in a letter to the editor of Psychiatric News. While Ron McMillen, a spokesman for the APA, argued in the PN article that Nemeroff and Schatzberg were actively involved "in every stage of the book's development," the letter's authors note that McMillen did not venture to say that Nemeroff and Schatzberg "wrote the initial drafts -- or indeed any drafts." The letter notes:

"The released 49-page sample chapter draft provided by Diane Coniglio and Sally Laden, employees of Scientific Therapeutics Information (STI), is largely reproduced verbatim in the Handbook.

In their January 28, 2011 letter to the editor, Dr. Bernard Carroll, professor and chairman emeritus of the department of psychiatry at Duke University Medical Center, Dr. Robert Rubin, professor and vice chair of the department of psychiatry at the University of California, Los Angeles, and Leemon McHenry, a researcher at California State University, also called on the APA to release internal documents that might shed light how much influence Glaxo did have on the context and tone of the book and its role in approving drafts. The letter writers concluded, "This case highlights the need for disclosure if we ever are to understand the scale of corporate influence on academic publishing."

Here's where things really get absurd. After sitting on the letter for two months, Psychiatric News decided not to publish it. In an email to Carroll et al dated March 22, Cathy Brown, executive editor for the publication, wrote that the issue has been covered extensively already and "therefore, we will not be printing additional information about it at this time."

How sad. Can it be that the APA is so fearful of its members' reactions (or more likely, legal threats by Nemeroff and Schatzberg) that it cannot even run a short and well-reasoned letter to the editor? For an organization that represents a profession whose very modus operandi is based on disclosure and transparency, the APA's track record of censorship and secrecy is unacceptable.

New study finds corrosive influence of industry money on cardiology practice guidelines

In a finding that may stun heart patients but surprise few others, researchers have found that more than half of the doctors who wrote key clinical practice guidelines in cardiology had financial ties to medical device and drug companies that stood to benefit from those guidelines. The study, published today in the Archives of Internal Medicine, raises serious questions about the reliability of such clinical guidelines in treating heart disease.

In recent years, much of the attention on conflicts of interest in medicine has focused on how lucrative financial ties can influence doctors' ability to carry out unbiased research or give patients sound medical advice. But as the researchers who did the study note, "improper bias in the production of clinical practice guidelines can have a potentially more widespread adverse effect on patient care than individual practitioners' conflicts of interest." That's because such guidelines, which range from how to treat patients with various types of heart disease and stroke to how to do coronary bypass surgery, are often adopted as the standard of care throughout the field and taught in medical training programs at all levels.

As Dr. Steven Nissen, a noted cardiologist at the Cleveland Clinic who commented on the study in an accompanying editorial, put it: To allow individuals with financial conflicts of interest to write clinical practice guidelines "defies logic."

The authors of the study, physicians and bioethicists at the University of Pennsylvania, Thomas Jefferson Hospital and Massachusetts General Hospital, found that more than half of the doctors who wrote clinical practice guidelines in cardiology between 2004 and 2008 served as promotional speakers on behalf of industry, and a substantial number actually held stock in companies affected by the guidelines they wrote. Again to quote Nissen:

"No conceivable logic can defend the practice of including promotional speakers and stockholders on CPG writing committees. Participants in speaker's bureaus essentially become temporary employees of industry, whose duty is the promotion of the company's products."

Even more worrisome, the study found that the chairs of these guideline writing committees are significantly more likely (81 percent) than committee members (55 percent) to have a potential conflict of interest. As Nissen says, "Such findings are disturbing and suggest that the decision-making process for selecting chairs for cardiovascular [clinical practice guidelines] is seriously flawed."

Proponents of the status quo often argue that such guidelines are merely a synthesis of scientific evidence derived from randomized clinical trials. But as Nissen notes, research shows that nearly half of these recommended guidelines are based on expert opinion. "The subjective nature of the [guidelines] makes it even more essential that these documents be free of commercial influence," he says.

Nissen then poses the question as to why professional societies have allowed "such extraordinary levels of commercial influence to infiltrate CPG committees?" His answer:

"Professional societies and their leadership are often plagued by the same commercial relationships as the [guideline] committees. Pharmaceutical and medical device companies provide large amounts of financial support for the education and advocacy efforts of professional societies. Such relationships have created a dependency that is difficult to terminate because the leadership of professional societies is reluctant to antagonize their financial benefactors."

I'm glad to see Nissen, who has consulted for drug companies and received research funding from some of them in recent years, lay it on the line like this. Hopefully, his plainspokenness is a sign that change is coming. It's past time for doctors in all fields, not just cardiology, to recognize the corrosive influence of industry money on the practice of medicine and stop taking the dough. Only then can patients truly trust their doctors' medical judgments.

NESW posts video of informative blogging panel

Here is a link to the newly posted video of a blogging panel sponsored earlier this winter by the New England Science Writers, a local chapter of NASW. I moderated the panel, which featured a stellar group of health and science bloggers: Gary Schwitzer, who writes the Healthnewsreview blog, Daniel Carlat, of the Carlat Psychiatry Blog, Rachel Zimmerman, who curates WBUR's Commonhealth blog, and Ivan Oransky, who writes Embargo Watch and Retraction Watch. About 60 local health and science writers turned out for the event at the Harvard Faculty Club, and as you can see for yourself, it was an informative and entertaining evening.

Drug companies and psychiatry profession still singing the same old duet

The same drug giants paying millions of dollars to settle claims that they engaged in illegal and improper marketing of anti-psychotic drugs in the U.S. are even now looking for new worlds to conquer. Consider the study published today in the Archives of General Psychiatry. It surveyed more than 60,000 adults in 11 countries in Eastern Europe, Asia and South America and concludes that the treatment needs for people with bipolar disorder are "often unmet, particularly in low-income countries."

That may indeed be true. But I'd find this result a lot more believable if the study were not funded in large part by the same pharmaceutical companies who make the atypical anti-psychotics used to treat bipolar disorder: Eli Lilly (which makes Zyprexa), Janssen (the unit of Johndon & Johnson that brought us Risperdal), Pfizer (Geodon), Bristol Myers Squibb (Abilify), GlaxoSmithKline (Lamictal), and Novartis (Fanapt).

The fact that one of the study's primary authors is a long-time paid consultant for the drug industry also gives me pause, particularly since this researcher has been carrying water for the industry for years. I am referring to Ronald Kessler, an epidemiologist at Harvard Medical School, whose specialty is publishing alarmist studies about the increasing problem of mental illness among various populations -- a problem, of course, that can only be solved with drug treatment.

In 1999, for example, Kessler co-authored a widely publicized study showing that depression was afflicting more children than ever before; you may recall this was right around the time that Eli Lilly, Pfizer, GlaxoSmithKline and Forest Labs were ramping up their highly successful efforts to market antidepressants like Prozac, Zoloft, Paxil and Celexa to children and adolescents (and hiding the dangerous side effects of these drugs while doing so).

In 2001, Kessler (and coauthor Martin Keller of Brown University) struck again with a study purporting to show that a significant number of the world's population is plagued by chronic and excessive anxiety -- severe enough to require drugs. Like Keller, whose myriad conflicts I exposed in Side Effects, Kessler was a paid consultant at the time for GlaxoSmithKline and other companies who were also marketing their antidepressants as anti-anxiety agents. In 2007, he co-authored yet another finding declaring that one in four adults have symptoms of mental illness but only a third of them are receiving effective treatments (read drugs).

Then in 2008, in perhaps his most bizarre contribution, Kessler was among the authors of a controversial commentary in Nature that heralded a new era of "cognitive enhancement" -- the use of brain-stimulating drugs in healthy people. Kessler and his co-authors argued that competent adults should be able to freely indulge in such drugs and noted that this was already happening among undergraduate and graduate students trying to boost their academic performance with drugs like Adderall and Ritalin, which contain amphetamines. As one pediatrician who criticized the commentary told the San Francisco Chronicle, their arguments will only "fuel the fire of what we call prescribing pressure" even though the drugs in question have "very significant side effects." To its credit, the Chronicle article noted that Kessler and another co-author of the commentary were consultants to the same drug companies that stood to gain handsomely from their rhetoric.

Kessler currently serves on the board of an advocacy group for child mental disorders with none other than Joseph Biederman, the Mass General Hospital psychiatrist who was a major proponent of expanding the definition of childhood bipolar disorder so that more and more children could be diagnosed with it and treated with powerful anti-psychotic drugs. As I've blogged about here, Biederman came under fire from the Senate Finance Committee for failing to disclose his extensive financial ties to companies that make these anti-psychotics. (Biederman's failures to disclose have been under investigation for the past two years by Harvard Medical School, in what must be the longest investigation in that school's history).

But getting back to Kessler, if you read the fine print at the end of the latest Archives bipolar study, you can see for yourself the long list of drug companies whose generous payments have been padding his salary at Harvard over the years.

That list may help explain why I find the latest pronouncements about the unmet treatment needs of bipolar patients around the world so hard to swallow. What this study mainly indicates to me is that the psychiatry profession and its journal handmaidens are still singing the same tired old tune at the behest of drug companies.

To borrow a better tune (from Joan Baez), when will they ever learn, when will they ever learn?

New study dismantles myth of high drug development costs

I'm embarrassed to admit that when I was a medical reporter for The Boston Globe in the '90s, I (along with many other journalists) would unthinkingly use the $800 million that the pharmaceutical industry said it cost to develop a new drug product. Industry apologists routinely threw out that exorbitant figure whenever anyone complained about high drug prices, and they made sure to note that it was based on "real research," studies done by the Tufts Center for the Study of Drug Development.

What I didn't realize then was that the $800 million was a highly inflated cost estimate produced by a center that received substantial industry funding and has very little credibility. The same goes for the latest cost estimate of $1.3 billion per new drug bandied about by the same folks.

Now, in a newly published report in Biosocieties journal, researchers at Stanford and the University of Medicine and Dentistry of New Jersey have taken apart both of these inflated cost estimates and shown exactly where they are wrong. Don Light and Rebecca Warburton note, for instance, that neither the $800 million or $1.3 billion estimate includes the substantial contributions made by taxpayers through tax write-offs for research and development. As it turns out, taxpayers indirectly pay for about 39 of drug company R&D. In addition, the industry-based figures are based on clinical trials (and number of participants) much larger than actual trials reported by the FDA and the National Institutes of Health.

Perhaps most disingenous, half of the industry estimates are not real costs, but exaggerated estimates of profits that companies might have made if they had not developed the drugs but just put their money into the stock market. As Light and Warburton note, "even if one were to accept the argument that profits foregone should be included as a 'cost' (which no other industry does), US government guidelines call for using three percent, not the 11 percent used by (the Tufts group). Light and Warburton argue that the pharm industry "cannot have it both ways."

They cannot treat R&D costs as if they are a long-term capital investment when tax authorities do the industry the favor of treating them as an ordinary business expense, fully deductible each year.

In their report, Light and Warburton attempt to reach a more realistic estimate for drug development, which, as they acknowledge, is hampered by the fact that the pharmaceutical industry is exceedingly secretive about its R&D data. But building on some of the data gathered by the Tufts Center and research done by Merrill Goozner of gooznews among others, they conclude that the real cost per "self-originated" drug product is closer to $180-231 million, a big reduction from the estimates that continue to be thrown out by industry spokesmen whenever they want regulatory concessions or more government spending. The latest example of this can be found in Christoph Westphal's op-ed in The Boston Globe, which I blogged about here.

The myth of high R&D costs not only exerts a destructive influence on state and federal policy, but it provides drug companies with an excuse for focusing on high-priced me too drugs (like Paxil and Seroquel), instead of developing lower priced drugs that might really save lives -- such as vaccines and treatments for disease. As Light and Warburton note:

The mythic costs of R&D are but one part of a larger, dysfunctional system that gives us mostly new medicines that have few or no advantages and serious side adverse reactions that have become a leading cause of hospitalization and death.

I couldn't have said it better.

Are we seeing a concerted drug industry campaign against the FDA?

There must be something in the air. Either that, or the drug and medical device industry has embarked on a concerted campaign to improve its tattered public image and bully the FDA into backing down from recent efforts to ensure that unsafe drugs and medical devices are kept from the market.

First appeared an op-ed piece in The Boston Globe early this week complaining that the average number of new drugs approved by the FDA since 2005 has dropped 33 percent and urging the FDA to once again speed up the process. The op-ed was penned by none other than Christoph Westphal, a biotech entrepreneur who made a mint when he sold his startup, Sirius, to GlaxoSmithKline in 2008 for a whopping $720 million.

Then comes a double whammy today in The New York Times: an op-ed piece by a former vice president at Merck calling for Congress to allow drug companies to work with other on joint direct to consumer advertising campaigns (as if the current barrage of television drug ads isn't bad enough), and an article in the business section decrying regulatory delays of medical devices and arguing that this slowdown is forcing some patients to go overseas. The article by Andrew Pollack raises the old canard that the pharm industry brings up whenever it wants concessions: that U.S. industry will lose its global competitive edge if the FDA doesn't relax its regulatory standards.

In his op-ed piece in The Globe, Westphal specifically criticizes the FDA's recent rejection of a drug to treat obesity, even though the agency had serious concerns about the drug's effectiveness and safety and its possible over-use as a treatment of first instead of last resort. He then goes on to urge $1 billion in additional funding by the federal government for early and late-stage drug development. The implication is that taxpayer money would be well-spent by supplementing research funding by the industry, which now pretty much controls drug testing and development with all the resulting conflicts of interest. Now, I would love to see the NIH take over control of clinical trials for new drugs if only to ensure less biased trial results and have blogged about that before. But somehow I don't think such independent research is what Westphal has in mind.

Speaking of possible conflicts, Westphal seems to have become a regular guest contributor to The Globe's op-ed page, which is interesting because his wife, Sylvia Pagan Westphal also is a regular op-ed contributor to the paper on medical issues. (I'll give Westphal this much: he's a brilliant marketer. He sold Sirius to GlaxoSmithKline on the promise that its one product, resveratrol, a basic ingredient in red wine, would become an anti-aging bullet. Yet just last year GlaxoSmithKline had to stop a clinical trial of resveratrol after a number of patients taking it developed kidney failure).

The Times' op-ed piece, disingenuously headlined "Better Drug Ads, Fewer Side Effects," essentially argues for weakening anti-trust regulations to allow the drug companies to work together on joint advertising campaigns that, in my mind, would be even more misleading than the television ads now dominating the air waves. The author of this piece, the former Merck exec who now works for law firms that represent drug companies, argues that these joint ads would inform consumers about diseases and treatment options (including drugs) and spare viewers "the assault of promotional messages, often unintelligible warnings about side effects and cloying images..." Yes, we could all do without the cloying images, but I guess I'd rather have unintelligible warnings than no warnings at all. Better yet, as I've blogged about before, what would really protect consumers is if Congress passed legislation prohibiting all direct to consumer advertising by pharmaceutical companies, period.

Why is the industry mounting what looks like a carefully orchestrated campaign to sway public opinion now? Perhaps because its lobbyists smell blood in the water. The House is now under the control of pro-business Republicans, and in recent weeks, even President Obama has gone out of his way to cozy up to big business interests. So industry officials must think this is the time to put pressure on regulatory agencies like the FDA, which in the last few years has shown an increased willingness to hold new drug and medical device approvals up to a higher level of scrutiny for safety and effectiveness. I just hope that, in the interest of public health and safety, the FDA stays strong.







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Psychiatric journal refused to retract flawed antidepressant study

The Journal of the American Academy of Child and Adolescent Psychiatry has refused to retract a study finding that the antidepressant Paxil was safe and effective in adolescents despite evidence of fabrication, plagiarism and failure to disclose conflicts of interest on the part of its authors, according to two academic researchers.

In a paper published yesterday in the journal Accountability in Research, Jon Jureidini and Leemon McHenry recount the myriad flaws of study 329, the same clinical trial that prompted a New York State Attorney General's lawsuit against Paxil's maker, GlaxoSmith Kline, in 2004. The story of that lawsuit and how it helped propel reforms in the way drugs are tested and marketed is the subject of Side Effects. In that book, I exposed how the authors of study 329 failed to fully disclose their lucrative financial ties with GlaxoSmithKline and how they misrepresented the data in the study to make Paxil look safer and more effective than it really was. I've also written about the study's extensive flaws in my blog here and here.

In this week's paper, Jureidini and McHenry concluded that study 329 violated JAACAP's written policy in several ways:

1. Failure to disclose conflicts of interest of "authors."
2. GSK concealed commercially damaging data (about the study).
3. Fabrication (creation of a strong false impression that one primary outcome measure was positive by deliberately confusing it with another measure).
4. Falsification (post hoc changes to secondary outcome measures and misrepresentation of severe adverse effects).
5. Plagiarism (submittting a ghostwritten manuscript).

The two researchers said they brought evidence of these clearcut violations to the attention of the journal's current editor, Andres Martin, but he has so far refused to retract the study. In their paper, Jureidini and McHenry said this case makes them wonder how many industry-sponsored publications of clinical research are equally flawed. As they note:

It is unclear to what extent one can extrapolate from Study 329 since relatively few industry-sponsored clinical trials have been exposed to this level of scrutiny. Given, however, the vast operations of "publication planning" conducted by pharmaceutical marketing, there is little doubt about the degree to which industry-sponsored research is suspect.

As a result, they reach the conclusion that other researchers have: that publication of industry trials should be banished from the journals. Instead, "pharmaceutical companies should be obliged to post results of their trials on websites, leaving journals to independently and critically examine the raw data and conclusions," they argue.

That's one solution. Here's another, long espoused by Dr. Marcia Angell, the author of The Truth about Drug Companies: prohibit pharmaceutical companies from funding randomized clinical drug trials and instead have those trials funded by the National Institute of Health and conducted by independent researchers who are not on the drug companies' payroll.