Pharmalot: A Paroxetine study and retractation


Brown University, A Paxil Study And Retractions

For the past few years, an effort has been under way by a pair of academics to retract a study about the Paxil antidepressant in the Journal of the American Academy of Child and Adolescent Psychiatry that concluded the GlaxoSmithKline pill was “generally well tolerated and effective for major depression in adolescents.” Why? Since then, the 2001 paper has been discredited amid charges that primary and secondary outcomes were conflated, selective results were reported and ghostwriting was involved (see this).
The details became known more three years ago as documents emerged from investigations (look here) and lawsuits charging Glaxo hid various risks. By then, the FDA required Glaxo to place a Black Box warning about suicidality in youngsters and UK regulators recommended the drug not be given to those under 18 years of age. But by 2010, the paper had been cited in more than 200 other articles, many of which continued to point to the study as evidence that Paxil is effective in treating adolescent depression, according to BMJ.
The listed lead author of the paper, which was also known as study 329, was Martin Keller, a psychiatrist at Brown University (pictured to the right; background here). He was also among more than two dozen academics who were investigated by the Senate Finance Committee over alleged failures to properly disclose of federal grants to research drugs at the same time these professors had accepted payments from drugmakers (look here). Consequently, a pair of academics asked the JACAAP to issue a retraction, but were rebuffed. The editor told BMJ the paper does not contain any inaccuracies and negative findings are included in a results table and, as a result, there are no grounds for withdrawal (read here).
martin-kellerAnd so last October, the same two academics – Jon Jureidini, associate professor of psychiatry at the University of Adelaide, and Leemon McHenry, a lecturer in philosophy at California State University – were joined by two dozen others and wrote to Brown University officials to request that they seek a retraction (read the letter), but they were again rebuffed.
Last month, they received a letter from Ed Wing, who is the dean of the medical school, to say the university would not write the JACAAP to seek a retraction (here is the Wing letter). No explanation was given and he did not respond to a request for comment or The Brown Daily Herald, which first reported the official rejection (see here).
The controversy raised questions about if and when a journal article should be retracted. As BMJ noted in its coverage last year, the Committee on Publication Ethics expanded its own view and recommended retraction if journals “have clear evidence that the findings are unreliable.” The point is to “correct the literature and ensure its integrity” rather than to punish authors (here are the guidlines). And the International Committee of Medical Journal Editors urge retraction in the event of scientific fraud or if an error is “so serious as to vitiate the entire body of work (read here).
The Paxil study also underscored the ongoing dispute over ghostwriting, which has embroiled several drugmakers in scandal. The issue has become so contentious that, several months ago, a pair of University of Toronto academics suggested two legal remedies – pursuing class action lawsuits based on the Racketeer Influenced and Corrupt Organizations Act, or RICO, and filing claims of ‘fraud on the court’ against a drugmaker that uses ghostwritten articles in litigation (read here). And two other academics recently published a paper in which they suggested that all authors should be required to sign a statement guaranteeing that no ghostwriters participated in writing a submitted paper and that all medical writers should be listed as authors on the byline (see this).
However, the failure of universities to investigate instances where their professors may have engaged in ghostwriting has also generated criticism. Last year, Dalhouse University declined to examine allegations of ghostwriting and the involvement of psychiatry professor Stan Kutcher, who was listed as a co-author on Paxil study 329 (read here). “I find it very disturbing that a university that is suppose to be standing up for the highest academic values is unwilling to take any action when its faculty members violate those values,” Joel Lexchin, a professor of health policy at York University in Toronto and one of the academics who signed the letter to Brown University concerning a retraction, writes us.
The Department of Health & Human Services, by the way, was also reluctant to pursue the matter. In a letter last November to Jureidini, John Dahlberg, the director of the Division of Investigation Oversight in the Office of Research Integrity at the HHS, noted that Paxil effectiveness was “apparently exaggerated.” But he went on to say that his office was unable to pursue an investigation due to the statute of limitations.
Due to the statute, “…allegations of falsification, fabrication or plagiarism must be made within six years of the alleged misconduct… Further, given the significant lapse of time between the time the study was conducted and concerns raised, the likelihood of being able to conduct a fair and objective review, given the inevitable difficulties in locating records and relying on memories of events well over 10 years ago, seems remote” (here is the letter). Say Jureidini: “We are a bit stuck about where to take it from here.”

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Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis


Frontage of Heslington Hall, York, the adminis...Image via Wikipedia

Para los creyentes del Déficit de Atención, y que no se piense que hay sesgo de publicación. Lo que falta es tiempo para escribir. 

Esparza Olcina MJ. Comparación de la eficacia de los estimulantes para el TDAH en niños y
 adolescentes según un metaanálisis. Evid Pediatr. 2011;7:102.
Traducción autorizada de: Centre of Reviews and Dissemination (CRD). Comparing the efficacy 
of stimulants for ADHD in children and adolescents using meta-analysis. University of York
Database of Abstracts of Review of Effects web site (DARE).
 Documento número: 12010003072 [en línea] [fecha de actualización: 2011; 
fecha de consulta: 9-6-2011]. 
Disponible en:

Documento en Castellano
Document in English           

Harvard docs disciplined for conflicts of interest


Published  by Ed Silverman

joseph-biedermanThree years after they were fingered in a US Senate probe into the interplay between academics who receive grant money from both pharma and the National Institutes of Health, three prominent psychiatrists from Harvard Medical School and Massachusetts General Hospital have been sanctioned for violating conflict of interest rules and failing to report the extent of their payments.
In a mea culpa addressed to their colleagues, Joseph Biederman, Thomas Spencer and Timothy Wilens wrote that “we want to offer our sincere apologies to HMS and MGH communities…We always believed we were complying in good faith with the institutional polices and our mistakes were honest ones. We now recognize that we should have devoted more time and attention to the detailed requirements of these policies and to their underlying objectives.”
And what is their punishment? They must refrain from “all industry-sponsored outside activities” for one year; for two years after the ban ends, they must obtain permission from the med school and the hospital before engaging in any of these activities and they must report back afterward; they must undergo certain training and they face delays before being considered for promotion or advancement (you can read their letter here).
The hospital had this to say: “A committee at Massachusetts General Hospital that has been looking into conflict-of-interest questions involving three MGH child psychiatrists has completed its review. Appropriate remedial actions have been taken by the hospital to address specific issues (read the statement). And a Harvard Med School spokesman sent us this: “We confirm that the review of their compliance with the Harvard Medical School Policy on Conflicts of Interest and Commitment has concluded, and appropriate actions have been taken.” He added that the conflicts policy was revised last year.
The sanctions result from a long-standing controversy over the explosive use of antipsychotics in children. Biederman, in particular (see photo), had been one of the most influential researchers in child psychiatry. Although his studies were small and often financed by drugmakers, his work helped fuel a 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder.
For more than a decade, Biederman and his colleagues aggressively promoted the diagnosis and use of antipsychotics to treat childhood bipolar disorder, a problem that once was largely believed to be confined to adults. But the docs maintained thisr was underdiagnosed in kids and the meds could be used for treatment, even though they had not been approved for most pediatric use at the time. Meanwhile, the relationships with drugmakers were never properly disclosed (back story).
doctorsandmoney11And for years, payments they received from drugmakers were not thoroughly reported to university officials. Yet, millions of dollars in NIH grants, which were administered by the hospital, were awarded to the docs at the same time they were receiving money from various drugmakers that make and sell antipsychotics and antidepressants. Which ones? Eli Lilly, Johnson & Johnson, Pfizer, GlaxoSmithKline and Bristol-Myers Squibb.
At one point, Biederman pushed J&J to fund a research center at MassGen that would focus on the use of its Risperdal antipsychotic in children, well before the med was approved for pediatric use. He was then placed in charge of the institute and began a study of 40 children between 4 and 6 years old who were given Risperdal and Lilly’s Zyprexa, another antipsychotic. At the time, Harvard and MGH rules forbid researchers from running trials with drugmakers if they receive more than $10,000 from a company that makes the drug (back story).
But in June 2008, US Senator Chuck Grassley made a far-reaching statement before Congress that pulled the curtain back on the money involved. The statement is memorialized in the Congressional Record. Referring to the three docs, he said “they are some of the top psychiatrists in the country, and their research is some of the most important in the field. They have also taken millions of dollars from the drug companies.”
“Out of concern about the relationship between this money and their research, I asked Harvard and Mass General Hospital last October to send me the conflict of interest forms that these doctors had submitted to their institutions. Universities often require faculty to fill these forms out so that we can know if the doctors have a conflict of interest. The forms I received were from the year 2000 to the present. Basically, these forms were a mess. My staff had a hard time figuring out which companies the doctors were consulting for and how much money they were making.”
How much were they making? At first, maybe a couple of hundred thousand dollars combined. But at his behest, the med school and hospital asked the docs to take a second look. “And this is when things got interesting. Dr. Biederman suddenly admitted to over $1.6 million dollars from the drug companies. And Dr. Spencer also admitted to over $1 million. Meanwhile, Dr. Wilens also reported over $1.6 million in payments from the drug companies.
“The question you might ask is: Why weren’t Harvard and Mass General watching over these doctors? The answer is simple: They trusted these physicians to honestly report this money.” And as Grassley then noted, there was still more money that went unreported (click on ‘payments to physicians’ here to read the complete statement and the chart showing payments to each doc).
pic thx to jerome kassirer

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