New analysis shows suicide link for teens on Paxil. 'Mischief' in old study claiming drug is safe.

[bananas]

Source: Washington Post

A reanalysis of data from a controversial study published in 2001 that opened the doors for doctors to write millions of prescriptions of an antidepressant to children and teens shows that the drug is not only ineffective but potentially unsafe. The new study, published Wednesday in The BMJ, details a number of issues with the original analysis that made paroxetine, marketed as Paxil by GlaxoSmithKline, look more favorable.

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The (original) study has been revealed to have been largely ghostwritten by a consultant on the drug maker’s payroll and has been investigated by both by both federal and state authorities.

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The team conducting the reanalysis -- led by Jon Jureidini, a professor at the University of Adelaide in Australia -- went back to the raw data and came to starkly different conclusions than the first paper. They found that the effect of the drug was no different than a placebo and that there was an increase in harms among study participants, the most alarming of which was an increase in suicidal thoughts and behavior.

Jureidini and his colleagues said that Study 329 contained numerous transcription errors and other problems that masked issues and violated the own company’s protocols for statistical analysis.

“It’s hard to think there wasn’t some mischief being done,” Jureidini said. He said it looked like there may have been "deliberate attempts to play down the adverse event profile."

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Read more: https://www.washingtonpost.com/news/to-your-health/wp/2015/09/17/mischief-in-old-study-showing-paxil-safe-for-teens-new-analysis-shows-increased-suicide-link/

[bananas]

1. Landmark Analysis of an Infamous Medical Study Points Out the Challenges of Research Oversight

http://chronicle.com/article/Landmark-Analysis-of-an/233179?cid=megamenu

Landmark Analysis of an Infamous Medical Study Points Out the Challenges of Research Oversight

By Paul Basken
September 17, 2015

One teenage patient taking the new antidepressant drug Paxil sliced about a dozen six-inch-long cuts into his arm over a period of several days. Another was hospitalized after threatening to kill herself.

Neither test subject participating in the clinical trial of Paxil two decades ago was classified by a team of university researchers as suicidal. The researchers, led by Martin B. Keller of Brown University, in a medical-journal article summarizing their findings, instead endorsed Paxil as "generally well tolerated and effective for major depression in adolescents."

In the years since then, Paxil — made by GlaxoSmithKline and generically known as paroxetine — has generated many billions of dollars in sales, and become a poster child for claims of poor medical ethics. The Keller study has provoked repeated calls for retraction by the journal that published it. Demands for universities to punish those involved. Protests that one of its authors was just chosen to head the leading association of adolescent psychiatrists. And, a few years ago, a key role in the nation’s largest-ever health-care-fraud settlement.

For those reasons, a small team of researchers donated hundreds if not thousands of hours over the past two years to pore through the 275 individual patient records and compile a virtual autopsy of Dr. Keller’s 2001 report, aimed at finding out exactly how and where he and more than a dozen other distinguished university authors could have gotten their conclusions so badly wrong.

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[bananas]

2. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depressio

Here's the new paper, free to read:

http://www.bmj.com/content/351/bmj.h4320

Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4320 (Published 16 September 2015) Cite this as: BMJ 2015;351:h4320

Abstract

Objectives To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine.

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Results The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group.

Conclusions Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

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[bananas]

3. No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions a

From a BMJ associate editor:

http://www.bmj.com/content/351/bmj.h4629

No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4629 (Published 16 September 2015) Cite this as: BMJ 2015;351:h4629

Peter Doshi, associate editor, The BMJ
pdoshi{at}bmj.com

As a new data analysis adds weight to calls for retraction of a paper on paroxetine in adolescents, Peter Doshi examines the resistance to action of a professional society, its journal, and an Ivy League university

A major reanalysis just published in The BMJ of tens of thousands of pages of original trial documents from GlaxoSmithKline’s infamous Study 329, has concluded that the antidepressant paroxetine is neither safe nor effective in adolescents with depression.1 This conclusion, drawn by independent researchers, is in direct contrast to that of the trial’s original journal publication in 2001, which had proclaimed paroxetine “generally well tolerated and effective.”2 The new paper, published under the restoring invisible and abandoned trials (RIAT) initiative,3 has reignited calls for retraction of the original study, putting additional pressure on academic and professional institutions to publicly address the many allegations of wrongdoing.
Troubled from the start

Few studies have sustained as much criticism as Study 329, a placebo controlled, randomized trial of paroxetine and imipramine carried out by SmithKline Beecham (which became GlaxoSmithKline (GSK) in 2000). In 2002, a US Food and Drug Administration officer who formally reviewed the trial reported that “on balance, this trial should be considered as a failed trial, in that neither active treatment group showed superiority over placebo by a statistically significant margin.”4 Yet this same year, according to the New York State Attorney General’s office, which sued GSK, over two million prescriptions were written for children and adolescents in the United States, all off-label, after a marketing campaign that characterized Study 329 as demonstrating “REMARKABLE Efficacy and Safety.”

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[Dont call me Shirley]

4. Big Crime Pharma, no problem killing people as long as they are making a killing.

[bananas]

5. Lot's of good comments in GD

"Researchers said a popular antidepressant was safe for teens. It was actually deadly."
http://www.democraticunderground.com/10027185982

[ChairmanAgnostic]

6. But there is a medical litigation crisis!

Actually, there is. They've protected the big pharma industry and bad doctors so well, that people are being hurt and dying with no chance of compensation.