something really huge…

Posted on Thursday 10 April 2014

Something really huge just happened. Something that just might change medical science altogether. In medical school, we read some of the best mysteries you can imagine. Things like the story of Typhoid Mary and how they tracked her down. But this is one with a twist, and it happened just this week. It’s about Tamiflu, and here’s Ben Goldacre, a master story teller to tell you all about it…
  • The Guardian
    by Ben Goldacre
    April 9, 2014

    Today we found out that Tamiflu doesn’t work so well after all. Roche, the drug company behind it, withheld vital information on its clinical trials for half a decade, but the Cochrane Collaboration, a global not-for-profit organisation of 14,000 academics, finally obtained all the information. Putting the evidence together, it has found that Tamiflu has little or no impact on complications of flu infection, such as pneumonia.

    That is a scandal because the UK government spent £0.5bn stockpiling this drug in the hope that it would help prevent serious side-effects from flu infection. But the bigger scandal is that Roche broke no law by withholding vital information on how well its drug works. In fact, the methods and results of clinical trials on the drugs we use today are still routinely and legally being withheld from doctors, researchers and patients. It is simple bad luck for Roche that Tamiflu became, arbitrarily, the poster child for the missing-data story.

    And it is a great poster child. The battle over Tamiflu perfectly illustrates the need for full transparency around clinical trials, the importance of access to obscure documentation, and the failure of the regulatory system. Crucially, it is also an illustration of how science, at its best, is built on transparency and openness to criticism, because the saga of the Cochrane Tamiflu review began with a simple online comment… [click here to continue]

and here are the articles in the BMJ:
It’s a great story, and the reason we have to have Data Treansparency for all clinical trials…
Mickey @ 7:46 AM
Filed under: politics
“Munchausen’s by Proxy”…

Posted on Wednesday 9 April 2014

The post made in america… was about Peter Parry’s paper, Biologism in Psychiatry: A Young Man’s Experience of Being Diagnosed with “Pediatric Bipolar Disorder”. It’s a case study written as an interview of the patient himself about his lost adolescence as a Bipolar Child patient, with Peter’s thoughtful analysis of the case and the whole issue of Pediatric Bipolar Disorder. In the comments, Sandra Steingard and I were discussing the difficult topics of Projective Identification and “Munchausen’s by Proxy.” Then we we got some help from an unexpected source, the patient himself identified in the paper by the pseudonym Adam.  His comments are quite clarifying, located on-line here.
Mickey @ 6:12 PM
Filed under: politics
a graph…

Posted on Wednesday 9 April 2014

There is a SAMHSA [Substance Abuse and Mental Health Services Administration] Report now available for free download on-line [National Expenditures for Mental Health Services and Substance Abuse Treatment, 1986-2009] that is, in my opinion, a must-read for interested parties. That said, I hasten to add that it’s hard, because it’s written for policy wonks, and the graphs and tables are all corrected in unfamiliar ways – so one has to read what the scales are to see things accurately. The upper part of the figure below [my recoloring for clarity] is the relative overall US spending for each of the categories in per cent, regardless of the amount for each year – which has itself been a variable [from page 43]. Those big picture amount numbers are in the report in some mega-tables in the Appendices [page 67+ of the 108 page report] for the hearty. The middle piece of my figure was traced from rescaled graphs I had made of the patent life of the big named psychiatric drugs from various FDA  sites [so accuracy is more like the right year but nothing more]. The bottom graph is straight from the report [page 38]. Again, the ordinate scale can be deceptive. It’s the percentage growth. So the fall from 1999 to 2004 doesn’t mean less was spent, rather that spending was plateauing, no longer growing like a weed.
hat tip to Jamzo…     

A commenter recently mentioned she noticed a change in psychiatry [for the worse] around 1994. I said maybe a little earlier, but agreed that it was in the right ball park. Looking at these graphs, it looks as if the guesses were on the money [pun intended]. The bottom graph shows a five fold increase in the rate of spending from 1993 to 2001 and the upper graph shows the resulting three and a half fold increase in the drug share of overall spending. Looking at the last five years on the graph, it looks as if we’ve settled into a new equalibrium – a stability in a new system. From a cost perspective, these numbers will probably even fall as the drugs go generic and cost much less. But that doesn’t fix a thing because from the perspective of our system of delivering care, the damage has been done and is likely to be self perpetuating.

A friend of a friend called yesterday with a very sticky child custody problem. In trying to get the family the help they needed, I called a child advocacy lawyer I know in Atlanta  who mercifully agreed to try to help this woman through the thorniest mess I’ve heard in a long time. In talking to the lawyer, I said that if the child needed psychiatric care or evaluation and I could help her find someone suitable, to let me know. I was actually thinking of a psychologist who has spent her career amid the impossible situations that custody cases can be. But my lawyer friend understood my phrase "psychiatric care" as meaning "psychiatrist" and said, "Oh I doubt we’ll need a psychiatrist. They’re for medicines and …" adding "and they’re more expensive." I guess that’s the sad-but-true reputation of psychiatry these days, something that’s hard to add to the graph, but implied.

This is all retrospective data, ending five years ago – now part of history. Like all of history, there were no road signs broadcasting these numbers, their meanings, or their ultimate outcome along the way. But even in my cloistered office, you could just feel it, like you can feel a front passing through before the rainstorm that will soon follow. And there’s one other important thing that’s not on those graphs, something once called transinstitutionalization, moving people from one institution to another – in this case from the mental institutions of the pre-1960s to the prisons of today. In my mind, this is the biggest tragedy in the story, because we have the where·with·all to do a lot better than that. And in this case, I don’t think the blame falls on psychiatry, or pharma, or any of the usual suspects. I blame whatever drives the attitudes in society as a whole, or at least American society, that avoids looking at and caring about the people we can’t "cure," but can damn sure do a better job of taking care of, mostly outside of any institutions, if the funds [and the will] were to be available…
Mickey @ 2:08 PM
Filed under: politics
if you’ve got a spare minute…

Posted on Wednesday 9 April 2014

A message from Carl Elliott:

In early December, we delivered a petition signed by over 3,500 of you to Minnesota Governor Mark Dayton, calling for an investigation of the death of Dan Markingson in a University of Minnesota psychiatric research study. That same week, the Faculty Senate at the university also overwhelmingly approved a resolution calling for an investigation.

Yet four months later, we still have seen no results. The president of the university, Eric Kaler, has indicated publicly that any review he commissions will not include an investigation of Dan Markingson’s death. Governor Dayton has not even acknowledged our petition.

In the meantime, evidence is accumulating that Dan Markingson was not the only patient who died or was seriously injured in psychiatric research studies at the university. Two investigative news reports have appeared with evidence of misconduct involving other patients. A confidential letter has emerged indicating that the Institutional Review Board was aware of ethical problems with psychiatric research at the University in 2009, and that it was concerned enough to request an external investigation. And for over six months, the university has stonewalled our open records requests for reports of deaths and serious injuries in psychiatric research studies.

You can find more information about these issues at:
So we need your help. We are organizing a series of actions beginning this week with a call-in campaign to Governor Mark Dayton and University of Minnesota Board of Regents Chairman Richard Beeson. We are asking you to make a phone call as soon as possible to the offices of Dayton and Beeson and leave a message asking for action. Here are phone numbers [and if you need it, a suggested script for your call.]

Please make your voice heard. And let us know that you called by leaving a comment at www.danmarkingson.com.

Thanks,

Carl Elliott

Richard Beeson
Office of the University of Minnesota Board of Regents
Phone: 612-625-6300

Gov. Mark Dayton
Phone 651-201-3437
Toll Free: 800-657-3717
[see also the academy itself…]. I’ve mused at times about why my radar lands on certain cases in the sea of stories about the misbehavior in psychiatry and the pharmaceutical industry. Paxil Study 329; The TMAP related cases; and this Dan Markingson case are always on my front burner. Each is a travesty that involves both psychiatrists who ought to know better, pharmaceutical companies manipulating things they ought to keep there noses clear of, and great big cover-up operations that need to see the light of day. But the Dan Markingson case is on top of the list, though it’s not the one I talk about the most, because it has a champion of its own that I could never equal for patience and single-mindedness, Carl Elliot.

Dan Markingson died by his own hand, a victim of an illness that dates to antiquity. He became a part of a study he should never have been enrolled in – a study that had no medical indication but was rather an experimercial. He was put on a maintenance dose of a blinded medication that wasn’t working. He languished in a treatment facility that did not adjust his treatment to his illness for six months as part of a legal double bind. And not long after hearing that his commitment was to be extended, he killed himself in a bizarre way – consistent with his untreated illness. All of that in a Trial that shouldn’t have been.

The kind of paranoid psychosis Dan had is a big time illness – it can be a lethal illness. Dan’s lethality was there the day he was admitted. He could have succumbed with the best of treatment, but we’ll never know because he didn’t get it. This may even be a case where, in spite of the dominant view of these medications, he may well have been grossly undermedicated, at least early on. But we don’t know that either. All we know is that he was adjudicated to a treatment he never received. Rather, he became a pawn in a marketing chess game.

Carl Elliot, Mary Weiss, and Mike Howard have been able to engage the Minnesota faculty and much of the mental health community in keeping this case on the front burner only to be repeatedly blocked by the very people who should be supporting their efforts. If you’ve got a spare minute tomorrow, leave a message or two to support Carl, Mary, and Mike in trying to make this thing go the right way…
Mickey @ 12:30 AM
Filed under: politics
kudus…

Posted on Tuesday 8 April 2014

While I have no business in the details of legal matters, I was really glad to read this article. It’s part of the fallout from the TMAP scam that has been dragging on now for ten long years:
The Associated Press
By Andrew Demillo
April 7, 2014

Arkansas Attorney General Dustin McDaniel asked the state Supreme Court on Monday to reconsider its decision tossing out a $1.2 billion judgment against drugmaker Johnson & Johnson, saying justices did "significant harm" to the state and broke from 170 years of precedent. McDaniel filed a petition for rehearing over the high court’s decision last month that the state misapplied the Medicaid fraud law in its lawsuit against New Jersey-based Johnson & Johnson and its subsidiary Janssen Pharmaceutical Inc. over the marketing of the antispyschotic drug Risperdal. McDaniel said last week that he would ask the court to revisit the ruling. "The court’s rejection of the state [Medicaid fraud] case does significant harm to the state and its citizens," McDaniel wrote in the filing. "It deprives the state of a critical tool to protect the integrity of the Arkansas Medicaid program and the vulnerable poor, sick and elderly who depend on Medicaid as a literal lifeline."

McDaniel said justices broke with years of precedent by ruling on grounds not previously raised in filings. Justices ruled that the state Code Revision Commission "substantively altered" the meaning of the Medicaid fraud law when it was codified and that it was originally intended to regulate health facilities. The commission is responsible for making technical corrections to state code. McDaniel noted that the 1993 law remained unchanged for 21 years despite other amendments and attempted amendments by the Legislature over the years. "By improperly transforming a well understood and accepted interpretation of the law, this court has arrogated to itself powers not conferred by the Arkansas Constitution or the General Assembly," he wrote.

The drugmaker said in a statement Monday that it didn’t violate the Medicaid fraud law. "After a thorough review of the case, the Arkansas Supreme Court agreed with our position. We believe that the record speaks for itself and are prepared to vigorously defend our position," the company said. Risperdal was introduced in 1994 as a "second-generation" antipsychotic drug, and it earned Johnson & Johnson billions of dollars in sales before generic versions became available. The drug is used to treat schizophrenia, bipolar disorder and irritability in autism patients. An Arkansas jury found the New Jersey-based companies liable in 2012. Pulaski County Circuit Judge Tim Fox then ordered the companies to pay $5,000 for each of the 240,000 Risperdal prescriptions for which Arkansas’ Medicaid program paid during a 3 1/2-year span.
In champagne around…, I wrote:
After their settlement in Texas, J&J lost a number of similar suits – Louisiana, South Carolina, Arkansas. Having sat through the Texas trial, it’s hard for me to imagine how they could win. The off-label marketing, hiding side effects, giving out perks, etc. It was just rampant. I think they settled in Texas because they could tell [as could everyone in the courtroom] that if they let the trial proceed, they stood the chance of getting massacred. But in the other suits, they went to the end – losing the verdicts. Now, they’re neutralizing their losses one at a time on technicalities
To my way of thinking, the TMAP epidemic which had taxpayer money diverted into the J&J Bank Account based on an orchestrated fraud was the most cynical of the many underhanded marketing schemes in the world of psychopharmacology. To have hard won juried decisions thrown out on clever legal technicalities just adds insult to injury. I didn’t go to the Arkansas Trial, or to South Carolina, but I went to Texas, and what I heard there made me ashamed of medical care in general. Doctors, Administrators, Pharmaceutical Companies, and their paid sales force – everybody was behaving in a way I can only see as criminal, antisocial. These settlements are our only recourse, and I want them to stick instead of getting lost in the details of legalisms and clever argument. "… 240,000 Risperdal prescriptions for which Arkansas’ Medicaid program paid during a 3 1/2-year span!" Kudus to Arkansas Attorney General Dustin McDaniel!
Mickey @ 11:24 PM
Filed under: politics
the whole industry…

Posted on Monday 7 April 2014

Fierce PharmaMarketing
By Tracy Staton
April 7, 2014

GlaxoSmithKline [$GSK] says it’s rolling out sales and marketing reforms around the world. Apparently, the changes come none too soon. The British drugmaker opened another bribery investigation, this time in Iraq, to check out allegations that it paid government-employed physicians to promote its products. And Glaxo hasn’t yet finished working through the scandalous Chinese bribery allegations that kicked off an industry-wide corruption crackdown.

So, CEO Andrew Witty and his team sound a bit … conflicted. On the one hand, Witty sounds the perfectly contrite corporate leader. He apologized for the marketing allegations that ended with a $3 billion Department of Justice settlements. He’s promised good behavior and touted those worldwide sales reforms. But on the other, the company is digging into at least two sets of corruption accusations, and faces related repercussions at home and in the U.S. Two bribery probes in two different geographic divisions? That’s a systemic problem.

When the Chinese bribery scandal hit, Glaxo’s U.K. headquarters was quick to say that head-office executives didn’t know about any malfeasance in its China subsidiary. That may be so. But if HQ didn’t know, that means HQ was either turning a blind eye or failing to pay enough attention. Either way, that’s not a good thing for a company trying to clean up its image.

If Witty really wants to reform GSK, then he and his top managers need to move beyond plausible deniability. They can’t just launch new quota-free sales-rep compensation and promise to stop paying speaking fees to doctors in the U.S. and beyond. Painful follow-through has to happen.

We need to see Glaxo execs take out their brooms, and move into global operations to sweep out misbehavior. If they don’t, whistleblowers and government investigators will. And that makes all those the sales-and-marketing changes look like little more than window-dressing.
Just a fluff piece to fill a column? I don’t think so. I think Tracy Stanton is on to something that Sir Andrew Witty and others need to listen to carefully. I don’t think the time honored method of putting a few platitude band-aids on a problem and waiting for the news cycle to pass is going to work very well. We’re onto that maneuver – a lesson learned in the school of hard experience. I was looking over some old posts and ran across any number of excuses, press releases, and statements in response to accusations in years past, and most of them would be laughed at these days or at least send eyes rolling. And plausible deniability is on top of the list of worn out spinning wheels. Two early versions came from my favorite bad example, Dr. Charles Nemeroff, when he was busted for leaving out conflict of interest declarations:
New York Times
By MELODY PETERSEN
August 3, 2003

Two scientists are raising concerns about an article in a medical journal that described experimental treatments for depression because an author did not disclose his significant financial ties to three therapies that he mentioned favorably. The executive editor of the journal said it had not required disclosure of the potential conflicts, but was considering changing its policy in light of the criticism. The ties between pharmaceutical companies and researchers have come under increasing scrutiny in recent years.

The lead author of the article, Dr. Charles B. Nemeroff, chairman of the department of psychiatry and behavioral sciences at the Emory School of Medicine in Atlanta, said he would have reported the conflicts of interest, which include owning the patent on a treatment he mentioned, if the journal had asked him to. ”I have always been totally compliant, probably gone overboard, with disclosure,” Dr. Nemeroff said. ”If there is a fault here, it is with the journal’s policy.”
The Wall Street Journal
By David Armstrong
July 19, 2006

Charles Nemeroff, one of the nation’s most prominent psychiatrists, edits the journal Neuropsychopharmacology, which this month favorably reviewed a controversial new treatment for depression. But Tuesday, the journal said it plans to publish a correction because it failed to cite the ties of the article’s eight academic authors to the company that makes the treatment, including the article’s lead author: Dr. Nemeroff.

The journal’s nondisclosure of the financial ties of its own editor as well as those of the other authors highlights the failure of many respected medical journals to identify relationships between academic researchers and medical companies that may benefit from positive research reports. A spate of recent lapses is prompting calls for more journals to ban offending authors from publication. In addition, medical schools are being urged to regulate relationships between their researchers and industry more closely…
His excuse that second time – clerical error. It didn’t work so well as the first one and he decided to step down as editor shortly thereafter. We can thank Drs. Bernard Carroll and Bob Rubin for both of those exposures. They came early and got the ball rolling. The investigations of Senator Grassley and Paul Thacker came next, and then the epidemic of suits against the Pharmaceutical companies with the release of enough incriminating documents to convince any doubters. So we’re now veterans of ten years learning that plausible deniability simply equaled a lie, and we’re not likely to buy such things anymore, almost by reflex.

I was a retired person before I was capable of believing that Doctors, Academic Department Chairmen, and Pharmaceutical Companies named after long-dead men with handle-bar mustaches were capable of the kind of deceit we’ve all seen in recent decades – but our naivety has given way to, at the least, a careful suspiciousness, even paranoia about such matters. And GSK has placed itself in a goldfish bowl that’s going to be hard to escape.

So when Tracy says, "We need to see Glaxo execs take out their brooms, and move into global operations to sweep out misbehavior" she’s not just moralizing, she’s giving GSK an appropriate heads up they really need to hear – not just GSK, the whole industry. We’re veterans now…
Mickey @ 6:19 PM
Filed under: politics
made in america…

Posted on Monday 7 April 2014

by Peter Parry
Journal of Clinical Medicine. 2014 3:334-347.

Pediatric bipolar disorder is a diagnosis that arose in the mid 1990s in the USA and has mostly remained confined to that nation. In this article a young American man (under a pseudonym) describes his experience of having the diagnosis throughout his adolescent years. His story was conveyed via correspondence and a meeting with the author, an Australian child psychiatrist. The young American’s story reveals several issues that afflict contemporary psychiatry, particularly in the USA, where social and economic factors have contributed to the rise of a dominant biomedical paradigm—or “biologism”. This focus on the “bio” to the relative exclusion of the “psychosocial” in both diagnosis and treatment can have serious consequences as this young man’s story attests. The author explores aspects of his tale to analyze how the pediatric bipolar disorder “epidemic” arose and became emblematic of a dominant biologism. This narrative points to the need, depending on the service and country, to return to or retain/improve a balanced biopsychosocial perspective in child and adolescent mental health. Child psychiatry needs to advocate for health systems that support deeper listening to our patients. Then we can explore with them the full range of contextual factors that contribute to symptoms of individual and family distress.
While it’s refreshing to read a case study, the topic is anything but pleasant. Peter Parry, an Australian Child Psychiatrist, met an young American on-line who had spent his adolescence being treated for Childhood Bipolar Disorder. Later, on a visit to the US, Dr. Parry met and interviewed the young man in person. I’ll not even attempt to summarize what the former patient has to say. It’s on-line and he says it quite well for himself. Likewise for Dr. Parry whose commentary is a particularly clear outline of the damage that can be done when treatment is driven by ideology – in this case the biological mania that swept through psychiatry with the Bipolar Child diagnosis, part if a larger wave of what he calls "biologism." The child lost his adolescence in a medication fog. It’s an important developmental period for all of us, but particularly for a gay man coming into his identity. And Dr. Parry appropriately points out that this epidemic was Made in America.

This is one of those articles that keeps on giving. Back in my underlining days, I would’ve painted the whole thing yellow with my highlighter, but there’s one part that I thought was particularly important in the sea of importants:
3.5 Projective Identification and “Munchausen’s by Proxy”

It is traditional wisdom in child psychiatry that parents often project unresolved issues onto their offspring. The children may identify and act out accordingly. Some extreme versions of this can lead to “Munchausen’s syndrome by proxy”, where a parent , through having an ill child, vicariously gains desired attention from respected medical experts for unmet and disavowed dependency needs. It appears that once Adam left the home his mother produced spurious medical symptoms and diagnoses for herself, in other words her own likely case of Munchausen’s disorder.

An early critique of PBD noted that not only could parents have a psychological investment in the PBD diagnosis, but so too could a range of others including the pharmaceutical industry, academic child psychiatry, schools and cons umer advocacy groups. The authors speculated whether PBD may be a “variant on Munchausen’s syndrome”.

This is not to say that there need be any negligence or mal-intent at all. Factors operate at systemic and subconscious levels. Adam’s mother, his doctors and others no doubt acted with Adam’s best interests in mind. A dominant paradigm is hard to see when you’re living and working within it.
Again, it’s refreshing to hear someone talking about Projective Identification, something I consider one of the most powerful forces on the planet. Projection proper is easy. You walk into a room with a stranger and the first thing he says is, "I know that you and my mother have been plotting …" You immediately know that you are the placeholder for his fear. The case may be hard, but at least you’re not struggling wondering if he’s right, as you’ve met neither he nor his mother before. Projective Identification is much more difficult. The patient, whom you know [and knows you], comes for a session late in the day and says, "You’re tired. Listening to patients all day. You don’t want to hear my troubles." And she’s right, at least sort of. You are tired. It is the end of the day. Is the patient making an observation about you that’s true? or projectively identifying an internal sense of unimportance, or perhaps a rage at not being listened to, or something else? The point is that both is the probable answer – that’s the Identification part. The Projection lands on something that is at least partially true.

“Munchausen’s by Proxy” is one of the most difficult of things because all of the forces are unconscious, subjective, and as likely to effect the treaters as the treated. The case of Rebecca Riley should remain emblazened on all of our minds to remind us of the tragic possibilities. While it’s not Parry’s central point, it is an important point. Was the Bipolar Child epidemic largely an example of this phenomena? In the post about Rebecca, I quoted a piece from a deposition of Dr. Biederman:
"But the patients that come to me, and the families in tears and despair with these type of problems, I in good faith cannot tell them, ‘Come back in ten years until we have all the data in hand.’ I still need to use medicines that I am assuming that if they work in adults, with appropriate care and supervision, may also work in children."
Peter’s comments here are dead center:
This is not to say that there need be any negligence or mal-intent at all. Factors operate at systemic and subconscious levels. Adam’s mother, his doctors and others no doubt acted with Adam’s best interests in mind. A dominant paradigm is hard to see when you’re living and working within it.
[I would change hard to sometimes impossible]. And he’s also offering a hint at the correct solution, get an outside opinion [or two or three]. People who are otherwise rational and sane do crazy things when under the spell of Projective Identification. An outside person can often see it clearly. When it’s happening to you, it’s hard to see, but one of the hints is that you’re about to do something out of the ordinary [and rationalizing it]. Dr. Biederman’s comment is something that felt compassionate to him, I expect. But it’s still a crazy, unmedical assumption that, as we all know, mushroomed into an epidemic that became an affliction in its own right to people like Adam. And speaking of Projective Identification and spells, the recent reminders about SRA [satanic ritualized abuse] epidemic is another example, in my opinion [see un·retraction watch…]. The power of Projective Identification underlies my only rule for living:
Never accept an invitation to go crazy…
Mickey @ 11:37 AM
Filed under: politics
simply ‘fuel the fire’…

Posted on Sunday 6 April 2014

In the Fall of 2012, having had a chance to look at the raw numbers for the first time, I sent a series of posts to the Ethics Committee of the American Academy of Child and Adolescent Psychiatry along with a request that they consider retracting their article. I had written Dr. Andres Martin the year before [letter], but he hadn’t responded. Here’s my 2012 letter:

To: The American Academy of Child and Adolescent Psychiatry Ethics Committee
Date: September 22, 2012

In 2001, the JAACAP published an article on the use of Paroxetine [Paxil] in adolescent depression, now known as Study 329:

by MARTIN B. KELLER, M.D., NEAL D. RYAN, M.D., MICHAEL STROBER, PH.D., RACHEL G. KLEIN, PH.D., STAN P. KUTCHER, M.D., BORIS BIRMAHER, M.D., OWEN R. HAGINO, M.D., HAROLD KOPLEWICZ, M.D., GABRIELLE A. CARLSON, M.D., GREGORY N. CLARKE, PH.D., GRAHAM J. EMSLIE, M.D., DAVID FEINBERG, M.D., BARBARA GELLER, M.D., VIVEK KUSUMAKAR, M.D., GEORGE PAPATHEODOROU, M.D., WILLIAM H. SACK, M.D., MICHAEL SWEENEY, PH.D., KAREN DINEEN WAGNER, M.D., PH.D., ELIZABETH B. WELLER, M.D., NANCY C. WINTERS, M.D., ROSEMARY OAKES, M.S., AND JAMES P. MCCAFFERTY, B.S.
Journal of the American Academy of Child and Adolescent Psychiatry, 2001, 40[7]:762–772.

Abstract
It has been widely seen as the paradigm for a period in psychiatry when we were at our worst – an industry financed, ghost-written article that made claims of both efficacy and safety that were unsupported by its data. The article has been the centerpiece for numerous successful legal suits, the most recent being a $3 Billion settlement by GSK with the DOJ in which they admit all allegations. Calls for retraction of this article began a decade ago, but have been repeatedly rejected – at first by defending this indefensible article, then later for unclear reasons, likely political, related to a fear of embarrassing the Editor, the AACAP, and the "Authors" [many of whom remain active in the organization].

Psychiatry is in decline, largely because the increasing awareness of the extensive alliance between the pharmaceutical industry and academic psychiatry has undermined confidence in the traditional ethic of medicine. Fledgling moves to reform the extensive conflict of interest problems in our specialty, however, will have no traction if organized and academic psychiatry refuse to acknowledge the problem in need of reform. Child and Adolescent psychiatry is at the center of the growing storm of complaints about over-medication, particularly of children.

Your predecessors have refused to retract this article, saying it is factually correct, or that the Journal is not responsible for its distortions, or worse, saying nothing. It is not factually correct. It was published over the objections of peer reviewers. And saying nothing is tantamount to treating cancer by watchful waiting. It has earned its right to be retracted in courtroom proceedings and media across the land. If you’re not familiar with its history, I’ve appended a series of blog posts about it to the end of this email. Alison Bass’s Pulitzer Nominated book Side Effects is another good resource.

I urge you to familiarize yourself with this story if you don’t already know it, and implore the Ethics Committee to retract Study 329 from the literature. It’s the right thing to do and a right time to do it.

John M. Nardo MD
retired psychiatrist and psychoanalyst

I thought this letter had a chance of being well received. The 329 data was now public and I’d done my homework, The $3 B suit had just been settled by GSK. I used my long name and spell checked it several times. Looking back, rereading it, the "familiarize yourself with this story" part was a little cheesy, but otherwise not bad for a non-English Major. The letter was received warmly by the President of the AACAP, the President Elect, and the Chair of the Ethics Committee who assigned a member of the Committee to work with me, presumabely to present it at the meeting coming up in several months. We had several amicable exchanges. I sent her Alison Bass’s book. All very civilized.

The meeting came and went and I heard nothing. Somewhere down the road, I got a terse email. It was going to be handled by the editor. No action taken. It was a surprise – reading more like a second notice on an overdue water bill than the collegial  and professional emails earlier. That’s the last I heard from them. Now, in retrospect, I read this:

Tuesday, January 22, 2013 • 12:00–1:00 pm EDT/11:00 a.m. – 12:00 p.m. CDT

Conference Call Minutes

Council members in attendance: Martin J. Drell, M.D., President; Paramjit T. Joshi, M.D., President-Elect; David R. DeMaso, M.D., Secretary; Steven P. Cuffe, M.D., Treasurer; Louis J. Kraus, M.D., Assembly Chair; Laurence L. Greenhill, M.D., Steven Adelsheim, M.D., Mark Borer, M.D., Stephen Cozza, M.D., Deborah Deas, M.D., Joan Luby, M.D., Neal D. Ryan, M.D., Jennifer S. Saul, M.D., Margaret L. Stuber, M.D., Sourav Sengupta, M.D., M.P.H., Marika Wrzosek, M.D.

Council members absent: Warren Y.K. Ng, M.D., Harsh K. Trivedi, M.D.

Others participating: Andrés Martin, M.D. Staff: Heidi B. Fordi, Mary Billingsley, Jill Brafford, Larry Burner, Yoshie Davison, Colleen Dougherty, Genifer Goldsmith, Rob Grant, Earl Magee, Kristin Kroeger Ptakowski

Study 329: Andrés Martin, M.D., M.P.H

As an author of the JAACAP article, Keller et al 2001, Neal Ryan recused himself from this conversation. Dr. Martin briefly summarized the situation regarding Study 329. He and the JAACAP Action Editors [AEs] reviewed this issue over the past 6 months, and shared a letter outlining the situation, steps taken, and their determinations, with Academy leadership. In short, Study 329 and the article published in JAACAP about it, Keller et al 2001, was mentioned in a federal lawsuit against GlaxoSmithKline [GSK], but none of the criminal charges related to the article itself. This is the 4th time the Journal has conducted an inquiry into the circumstances surrounding Study 329 and Keller et al 2001 since its publication, and it has again been determined that while the article is not perfect, the ethical concerns raised by the GSK lawsuit are not substantiated. The AEs consulted with many individuals in making their determination, including several lawyers and editors of other academic journals, and have decided not to take any action against the paper. Both the Academy and the Journal received inquiries from the press about the situation and what was to be done, and Dr. Martin and the AEs believe that there is little to gain in responding and that doing so would simply ‘fuel the fire.’

ACTION: IF COUNCIL MEMBERS RECEIVE ANY INQUIRIES ABOUT STUDY 329, PLEASE DIRECT THESE TO ANDRÉS MARTIN.
hat tip to 1boringyoungman…
I don’t do moral outrage very well, but this would be a good place to practice if I wanted to learn. That report to the AACAP Council reads like they’re making a policy decision about pesky door-to-door salesmen. The Ethics Committee was  waved off from above, clearly. It’s hard to imagine him saying "but none of the criminal charges related to the article itself" and "the ethical concerns raised by the GSK lawsuit are not substantiated" with a straight face, much less to the committee. Then I remembered a peculiar episode that happened around the same time though I hadn’t connected the dots. In the fall of that year, the Chronicle of Higher Education published an article [Academic Researchers Escape Scrutiny in Glaxo Fraud Settlement] pointing out that the academics who signed on to Paxil Study 329, a prominent part of the $3 B settlement, had gotten off without a even a hand-slap [see the only enduring contract…]. In response, GSK’s lawyer wrote this letter to the Chronicle:
Chronicle of Higher Education
October 1, 2012

To the Editor:

As counsel for GlaxoSmithKline LLC in its recently concluded settlement with the United States government, I write to correct some significant factual inaccuracies in "Academic Researchers Escape Scrutiny in Glaxo Fraud Settlement" [The Chronicle, August 6]. The piece focuses on a peer-reviewed journal article published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry reporting the results of a clinical trial sponsored by Glaxo­SmithKline [Study 329] of Paxil® [paroxetine hydrochloride] for the treatment of major depressive disorder in adolescents [the article was "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial," by M.B. Keller et al., in the July 2001 issue]. Unfortunately, your piece incorrectly states that, as part of its government settlement, GlaxoSmithKline admitted that the journal article "was part of the fraud" and "constituted scientific fraud." In fact, GlaxoSmithKline made no such admission and vigorously disputes that the journal article was false, misleading, or fraudulent.

As part of its settlement with the government, GlaxoSmithKline pleaded guilty to a misdemeanor violation of federal law related to the marketing of Paxil for use by patients under 18, an unapproved, "off label" use for Paxil. While the law permits physicians to prescribe medications for such off-label uses, manufacturers are not permitted to market them for such purposes. The charging document filed by the United States, known as an information, contains many allegations that are either inaccurate or incomplete, that tell only part of the story, and that draw unwarranted conclusions from disputed facts. Throughout the investigation, the settlement process, and the guilty-plea proceeding, GlaxoSmithKline made clear to the government and to the court that it did not agree with all of the factual allegations made in the information. In particular, GlaxoSmithKline has consistently denied and disputed the allegations that the journal article was false or misleading. Nothing in the settlement or the guilty plea has changed Glaxo­SmithKline’s position on the journal article. Most important, Glaxo­SmithKline did not admit and has not admitted that the journal article was part of any fraud or that it was false or misleading.

Your piece also incorrectly states that the journal article "was actually written by Glaxo-hired authors to overstate the benefits and understate the risks of a highly profitable Glaxo drug." While GlaxoSmithKline did hire a medical writer to provide editorial assistance to the clinical investigators, a fact that the journal article itself acknowledged, control over the contents of the manuscript remained at all times with the clinical-investigator authors who provided substantial comments on and input into the manuscript. GlaxoSmithKline believed then and continues to believe that the journal article reflects the honestly held views of the clinical-investigator authors.

Thomas H. Lee II
Philadelphia


Editor’s note: The federal "criminal information" document in the Paxil case repeatedly describes the journal article as "false and misleading." It also notes that GlaxoSmithKline distributed the article to its marketing department and its sales representatives, who used it to promote the use of the drug for children and adolescents. In addition, the criminal information says that a contractor hired by Glaxo­SmithKline wrote the first draft of the article and incorporated changes made in the article by researchers and another GlaxoSmithKline employee. The plea agreement between GlaxoSmithKline and the U.S. Department of Justice states that GlaxoSmithKline "expressly and unequivocally admits that it committed the crimes charged in the information, and is in fact guilty of those offenses."
If you read the settlement agreement and the government complaint, their letter doesn’t hold water. Jon Juriedini and Leeman McHenry quickly responded [‘Any Reasonable Person’ Would See Glaxo Study as Fraud][see also the only enduring contract…]. Ever since I read that letter from GSK’s lawyer, I’ve wondered why he wrote it. It just makes him look silly to anyone who reads the settlement and complaint. Unlikely any reader of the Chronicle of Higher Education would see it as anything other that humorous. But now, coming when it did, I wonder if Andrés Martin was feeling a strong pressure to finally retract Paxil Study 329, and GSK wrote that letter cover the authors and the Journal against some kind of legal action, or maybe to justify not retracting it, or to make the authors and journal not ‘thrown under the bus’ by GSK. I even wonder if one of those lawyers Martin mentions consulting wasn’t Thomas Lee, the author of the Chronicle letter.

I’m not so grandiose as to think that my letter was the impetus for all that wheeling and dealing, for the GSK Chronicle letter, for the AACAP to go silent and dig in its heels even further. Because the call for retraction was coming from everywhere at that time [and ever since]. And I have no notion of the potential legal ramifications of JAACAP retraction the article. But I do feel sorry for the members of the AACAP Ethics Committee. It must be mighty disillusioning to be preparing to debate a thorny ethical issue like this one and to essentially be taken off the case and have its domain simplified down to "the ethical concerns raised by the GSK lawsuit are not substantiated" by a decree from above. What’s an Ethics Committee for if it’s not to deal with such matters?

Whatever all of this means in the end, the American Academy of Child and Adolescent Psychiatry and it’s Journal have lost sight of the reason they exist – to take care of the needs of mentally ill kids, and to do no harm. Neither the accepting editor, Mina Dulcan, nor her successor, Andres Martin, seem to have grasped these fundamentals. They’ve had numerous opportunities to make things right, and they’ve declined those chances, even now blocking anyone else from taking a look [like their own Ethics Committee]…
Mickey @ 3:52 PM
Filed under: politics
a sunny day…

Posted on Thursday 3 April 2014

And so I’m at a coffee house in Black Mountain, NC on a beautiful sunny day and I pull out my iPhone for a bit of free WiFi, after a morning visiting with relatives, and I’m stunned. Yesterday’s article on Paxil Study 329 was pretty great [Controversial Paxil paper still under fire 13 years later], but today’s news is more substantial. Today, the EU voted [Europe votes for clinical trial transparency]:
It’s soon going to be the law in Europe that drug clinical trials are publicly registered and results reported. MEPs have today voted by a huge majority to adopt the Clinical Trials Regulation, 547 in favour and 17 against.
AbbVie, one of the two U.S. companies trying to stop Europe’s drugs regulator from releasing previously secret clinical trials data, said on Thursday it had withdrawn lawsuits against the watchdog. The decision follows a move by the London-based European Medicines Agency [EMA] to accept a new set of redacted documents submitted by AbbVie, along with the company’s rationale for removing certain commercially confidential information. "A significant portion of data will be disclosed while protecting the information that is commercially sensitive," AbbVie said in a statement. "As a result, AbbVie has withdrawn its lawsuits." The EMA said the "very limited redactions" would have no significant impact on the readability of the clinical study reports that were at the centre of the litigation.
It is, indeed, a sunny day…
Mickey @ 5:57 PM
Filed under: politics
parsing “some”…

Posted on Thursday 3 April 2014

Some say former U. professor Martin Keller’s paper was ghostwritten and should be retracted
The Brown Daily Herald
By Isobel Heck
April 2, 2014

Former University Professor Martin Keller published a 2001 paper on the drug Paxil that has allegedly been ghostwritten by GlaxoSmithKline.

Two weeks ago, Edmund Levin and George Stewart, members of the American Academy of Child and Adolescent Psychiatry, sent a letter to the editor of the Academy’s journal, requesting an explanation as to why a controversial study led by former Brown Professor Emeritus of Psychiatry and Human Behavior Martin Keller has not been retracted.

The paper — which details the findings of Study 329 and focuses on the effects of the drug Paxil on adolescent depression — has been continually criticized since its publication in 2001.

While Levin and Stewart have worked to get the paper retracted, Jon Jureidini, a professor at the University of Adelaide in Australia and a member of the nonprofit Healthy Skepticism, has been working with his team to reanalyze the original data and republish the results…
"some say" is a bold statement. In the case of Paxil Study 329, "some" means anyone who looks into the study [and is not a listed author]. It has become the symbol of an era when ghostwritten, industry funded studies were the rule for psychiatric drugs, and science and its methods were things to be played with rather than tools for knowledge.

There are a number of reasons study 329 percolated to the top of the pile as an example of the widespread scientific misbehavior in clinical trial reporting. It was about using medication in children. It is an obviously jury-rigged report on first reading. It was authored by an army of top level child psychiatrists and published in a first line journal. One wonders why the authors, the company [GSK], and the Journal [Journal of the American Academy of Child and Adolescent Psychiatry] hasn’t  simply retracted it and  moved on. Instead, they persist in their denial.

Were it not for the persistence of people like Dr. Levin, Dr. Stewart, Dr. Juriedini, and the Healthy Skepticism group, it might have just faded away, as I think the authors, the Journal, GSK, the American Academy of Child and Adolescent Psychiatry, and Brown University hoped. But that’s not going to happen. It’s too important to acknowledge, not just to "some," but to "all" the level of corruption that had filtered into academic psychiatry and its literature. It’s important for one simple reason – they are traditionally good things, and tolerating this kind of corruption will destroy them for the future.
Mickey @ 9:54 AM
Filed under: politics