another shot?…

Posted on Friday 6 July 2012

There is probably no single icon for the corruption of the modern psychiatric literature so paradigmatic as Glaxo-SmithKline’s Study 329 and its publication in 2001 by then Brown University’s Chairman of Psychiatry, Dr. Martin Keller:
Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial
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
Objective: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression.
Method: After a 7 to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine [20–40 mg], imipramine [gradual upward titration to 200–300 mg], or placebo. The two primary outcome measures were endpoint response [Hamilton Rating Scale for Depression [HAM-D] score <8 or >50% reduction in baseline HAM-D] and change from baseline HAM-D score. Other depression-related variables were [1] HAM-D depressed mood item; [2] depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version [K-SADS-L]; [3] Clinical Global Impression [CGI] improvement scores of 1 or 2; [4] nine-item depression subscale of K-SADS-L; and [5] mean CGI improvement scores.
Results: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score <8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects.
Conclusions: Paroxetine is generally well tolerated and effective for major depression in adolescents.
Like so many before me, in May 2011 I summarized the raft of reasons Study 329 should be retracted [retract study 329…], and in light of the recent GSK settlement, reiterated that call last week [“learnt from the mistakes that were made”…] pointing to the recent refusal of Brown University itself to request that the article be retracted [why not now?…]. Roy Poses covers this same ground at Healthcare Renewal [Giant GSK Settlement Provides Reminder of the Pervasiveness of Stealth Marketing] as does Howard Brodie at Hooked: Ethics, Medicine, and Pharma [Inside Paxil Study 329, Courtesy the Justice Department]. Earlier this year, Ed Silverman at Pharmalot summarized the whole tawdry affair [Brown University, A Paxil Study And Retractions] and Allison Bass, author of Side Effects, a book about Study 329, reacted to the Office of Research Integrity’s refusal to investigate [When it comes to scientific misconduct, should there be a statute of limitations?]. Whether this is a ghost-written, highly misleading, jury-rigged article is not among the questions swirling around this now decade old publication, nor is there any question about its scientific correctness. It stands on its own as a testimony to the lengths pharmaceutical companies and their colluding psychiatrists were willing to go to turn a sows ear into a silk purse for profit – exposed fully and penalized in both Civil and Federal actions.

Christina PaxsonRuth SimmonsRuth Simmons became President of Brown University in 2001, the same year Study 329 was published by Martin Keller, Chairman of Psychiatry at Brown’s Medical School. Simmons was Brown’s first female president and the first black president of an Ivy League School. When petitioned by Healthy Skepticism last year to retract Study 329, she passed the decision to  Dr. Edward Wing, Dean of the Medical School, who rejected the request without comment. This week, the popular Ruth Simmons stepped aside and was replaced by Christina Paxson, Dean of the Woodrow Wilson School of Public and International Affairs at Princeton. The blurb from the Princeton web-site says:
Christina Paxson is the Hughes Rogers Professor of Economics and Public Affairs and the Dean of the Woodrow Wilson School of Public and International Affairs. In 2000, she founded the Center for Health and Wellbeing [CHW], an interdisciplinary health research center in the Woodrow Wilson School. During her time as director of CHW, the center started undergraduate and graduate certificate programs in health and health policy, and took on the leadership of the University’s Health Grand Challenges program. Paxson is a Senior Editor of The Future of Children; a Research Associate of the National Bureau of Economic Research, where she is a member of the programs on Aging, Health, and Children; and a Research Associate of Princeton’s Office of Population Research. Her research is on health, economic development and public policy, with a current focus on economic status and health outcomes over the life course in both developed and developing countries. She has been the Principal Investigator of several NIH-funded studies, including "Economic Status, Public Policy, and Child Neglect", "Parental Resources and Child Wellbeing" and "College Education and Health", and was the founding director of an NIA Center for the Economics and Demography of Aging at Princeton.
With those child advocacy credentials, it’s hard to imagine that she would fail to see the issues involved in Study 329, particularly in light of the recent GSK settlement. I expect that she will be repetitioned to ask for retraction of Study 329 by Brown University. Let’s hope that she does the right thing…

The only discordant drum in her resume is the National Bureau of Economic Research. Remember them? They produced a report that attacked the FDA black box warning on antidepressants based on the 2004 suicide statistics [pretty loud coi…, tortured numbers…]. Let’s hope she wasn’t in that department.
  1.  
    July 7, 2012 | 4:02 PM
     

    Who is going to bring the issue up to Christina Paxson?

  2.  
    July 7, 2012 | 4:53 PM
     

    Alto,

    Somewhere I read that Jon Jureidini said that they would try again with a new president. But if Healthy Skepticism doesn’t, I guess it’s us…

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