still on the books…

Posted on Thursday 4 April 2013

  1.  
    Bernard Carroll
    April 4, 2013 | 1:58 PM
     

    Here’s a virtual clone of Study 329.

    Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial.
    Geller DA, Wagner KD, Emslie G, Murphy T, Carpenter DJ, Wetherhold E, Perera P, Machin A, Gardiner C.
    J Am Acad Child Adolesc Psychiatry. 2004 Nov;43(11):1387-96.
    PubMed ID:15502598

    Same muting of the side effects through reporting sleight of hand.

  2.  
    April 4, 2013 | 3:29 PM
     

    I still do not get why the full court press on this matter. What you should be watching for are repeats by deceitful, disingenuous, and downright felonious behaviors by current and future study submissions that replicate what 329 did.

    Isn’t it inversely proportional that the louder a company touts their psychotropic newcomer, that responsible and attentive doctors should shun the sales reps for at least a year or more until the data from reality is then submitted?

    History is a bitch, eh?

  3.  
    Annonymous
    April 4, 2013 | 4:18 PM
     

    Part of why there should be a full court press on this matter:

    First.
    One of the two primary architects of this study, and the one who wrote the opaque and confrontational defense (the final word published in JAACAP on the matter), Dr. Neal Ryan, is now a primary person mapping out the next 10 years of research in child mental health.
    See
    http://1boringoldman.com/index.php/2012/12/13/a-formidable-opponent/#comment-232974
    and
    http://1boringoldman.com/index.php/2012/12/16/worth-pursuing/#comment-233704

    Second.
    Dr. Andres Martin’s judgment is that no editorial action whatsoever is required, not even publishing a letter.
    See:
    http://1boringoldman.com/index.php/2012/12/21/a-response-2/
    Since these JAACAP editors tend to serve 10 year terms he has 5 more years of being editor-in-chief of the most influential journal specialized in child mental health. And, this is his judgment.

    Third.
    Even if you think SSRIs are incredibly important for some adolescents with depression, this article acted to support that those adolescents getting paroxetine instead of fluoxetine. At the time Dr. Wagner spoke of paroxetine and in retrospect she appears to speak of SSRIs.

    Fourth.
    It is one of the most egregious cases. See the many posts from 1BOM. Most notably Dr. Neal Ryan’s defense in the 2003 author response is the most indefensible part of the story. There is no way to spin that letter when you combine it with the later revelation from court documents about the secondary endpoints. He bases his defense on the secondary endpoints and relies on the knowledge that no one else was ever supposed to have access to the data. Or, he wasn’t aware of it himself. Either way the main authors themselves realize that such a dichotomy would be extremely damaging to them.
    See:
    http://1boringoldman.com/index.php/2012/12/23/the-lesson-of-study-329-an-unfinished-symphony/

    Fifth.
    If simply pretending like this didn’t happen is consistent with being chosen a distinguished fellow of the AACAP, being chosen to sit on their ethics work group, and being chosen to be the key person planning the direction of the next 10 years of child psychiatry research, then what does that say? It’s clear that the approach taken by Drs. Ryan and Martin is working so far. Given how egregious an example Study 329 represents, that it is working sends a terrible message to anyone else in the field who might be facing a similar choice.

    Finally.
    It may mean nothing to those who think that research in child mental health has nothing to offer and should simply be universally opposed. But, it should mean a hell of a lot to those who think it does have something positive to offer.

    2/2 negative primary endpoints.
    6/6 negative preselected secondary endpoints.
    At least 15/19 post-hoc secondary endpoints.
    Then read the response letter from Dr. Ryan above.
    Then read the letter from Dr. Keller to Dr. Ryan and a few other coauthors above.
    Then read the response from Dr. Martin declining to publish Jureidini’s response.

    Is past behavior a good predictor of future behavior?

    Dr. Ryan is head of the research component of Back to Project Future of the AACAP that says it represents the 10,000 or so child psychiatrists in the U.S.
    Dr. Martin is the editor-in-chief of the JAACAP, their journal which is the major child mental health journal in the world.

    That is now. That is not history.

    I hope that clarifies why the matter deserves a full court press.

  4.  
    Annonymous
    April 4, 2013 | 4:24 PM
     

    Is past behavior a good predictor of future behavior?

    More specifically, if there is no acknowledgement of the original mistakes. This is NOT a matter of judging. It is that it seems absurd to expect fundamentally different behavior if there has never been any acknowledgement of the true original mistakes. And, as the Keller letter above makes clear, it is difficult to imagine how they could have signed off on the author responses published in JAACAP without either ignorance of information they should have had, or some level of intentional deception.

    Is this who people want at the helm guiding the research that is done ,and that can get published, that in turn guides the mental health care of children?

    I do not get the lack of a true full court press on this matter.

  5.  
    April 4, 2013 | 4:35 PM
     

    The question, “Is past behavior a good predictor of future behavior?” is almost rhetorical because the answer is “Yes, until proven otherwise.” And, as Annonymous points out, otherwise requires that the behavior be acknowledged as a first step. I ran across this in the APA brochure for the May meeting:

    APA Program

    Recall that Dr. Schulz is the psychiatrist at the center of the Dan Markingson case written about by Carl Elliot. Markingson was a first-episode Schizophrenic patient who committed suicide while in the CAFE trial [see fear and loathing in bioethics]. The irony in this title is obvious…

  6.  
    Fid
    April 4, 2013 | 8:25 PM
     

    “I still do not get why the full court press on this matter. ”

    Um… because it’s fraud that is still recognised as honesty.

  7.  
    April 4, 2013 | 9:13 PM
     

    The history of conventional psychiatry, as practiced today, has yet to be written…

    My best guess is that when it is written, it will be not only “be a bitch.”
    It will be a really mean and nasty bitch.
    One most of us would rather have never met.

    Get ready, conventional psychiatrists – “history” is on the way…

    Duane

  8.  
    Stan
    April 4, 2013 | 11:26 PM
     

    “I still do not get why the full court press on this matter. ” – WOW: must be nice living in a constant state of ignorant bliss….

    That above statement is coming from a practicing psychiatrist who is seeing patients and writing psychotropic drug prescriptions….I would have to take a wild stab & gander; that is more than reason enough…fraud is fraud after all…

    These drugs have shown & have been proven to have the potential to cause significant health damage and death not only to the users, but to other innocents within our society.

    These falsified studies & publications are no doubt high crimes perpetrated against humanity. There is no statute of limitations on these types of horrific crimes.

    There are no excuses, there is no more burying their heads in the sand…accountability is coming…it’s just a matter of how much blood is going to be spilled, and how many lives will be destroyed before that day finally arrives…

  9.  
    Annonymous
    April 5, 2013 | 9:00 AM
     

    The AACAP is the primary organization that represents child psychiatrists in the US.
    The JAACAP is the #1 ranked child mental health journal and #2 ranked pediatrics journal.

    Dr. Neal Ryan is currently head of the AACAP program entrusted with developing their 10-year roadmap for future child mental health research:

    Dr. Neal Ryan’s et al’s author response in JAACAP in 2003 about concerns about Study 329:

    Therefore since our two primary outcome measures did not reach a p<0.05 level of statistical significance, the more complex question that remains is whether or not we fairly interpreted the pattern of significant p values across a range of secondary endpoints as indicating that paroxetine is better that placebo for adolescent depression. . . . Surely a national regulatory body charged with approving or not approving a medication for a particular use might well simply say that if a study doesn’t show efficacy on the primary endpoint(s) it is a failed study and secondary outcome measures cannot then be used for approval. However, as scientists and as clinicians we must adjudge whether or not the study overall found evidence of efficacy and we do not have the convenience of falling back upon such simple rule. If we choose wrongly (in whatever direction) we don’t treat depressed children as well as the data would permit. Since we found a clear pattern of significant p values across multiple secondary analyses (recovery as assessed by HAM-D <8, Ham-D depressed mood item, and CGI score at endpoint) we thought and still think this provides significant evidence of efficacy of paroxetine compared to placebo in adolescent depression. Without established reliable measures that distinguish medication responder from non-responders at the time the study was designed, it is not surprising at all that the primary measures didn’t reach significance while other measures did. It still provides a strong “signal” for efficacy.”
    http://dida.library.ucsf.edu/pdf/zru38h10

    What was later learned was the true range of endpoints of Dr. Ryan’s study:

    2/2 negative primary endpoints.
    6/6 negative preselected secondary endpoints.
    At least 15/19 negative post-hoc secondary endpoints.
    Paroxetine separated from placebo on 4/19 post-hoc secondary endpoints

    Dr. Andres Martin is currently editor-in-chief of the JAACAP

    In the context of that new information, available through the originally confidential documents GSK had later released, wrote the following in 2012:

    After a comprehensive and extensive review, the Journal editors found no basis for retraction or other editorial action.” and “The inquiry is considered complete“.

    No one to this point has effectively addressed the question of how to simply make the target readership of JAACAP aware of the information above and let them make up their own minds.

    The key is how to simply make them aware of this.

    To this point no one has solved that problem.

  10.  
    Annonymous
    April 5, 2013 | 9:07 AM
     

    Until that problem is solved the AACAP and the JAACAP will do nothing.
    Until the constituencies they care about are aware of the information above and can make up their own minds.
    If you think that scientists don’t care about such things, I believe you’re wrong.

  11.  
    Annonymous
    April 5, 2013 | 9:18 AM
     

    And, if you think that pediatricians don’t care about such things, I also believe you’re wrong. There are many who know how to read a paper and know that saying, after multiple chances to recalibrate your position:

    Since we found a clear pattern of significant p values across multiple secondary analyses (recovery as assessed by HAM-D <8, Ham-D depressed mood item, and CGI score at endpoint) we thought and still think this provides significant evidence of efficacy of paroxetine compared to placebo in adolescent depression
    .

    when what you have is:

    2/2 negative primary endpoints.
    6/6 negative preselected secondary endpoints.
    At least 15/19 negative post-hoc secondary endpoints.
    Paroxetine separated from placebo on 4/19 post-hoc secondary endpoints

    but no one was supposed to know that because the information was confidential

    when you are pushing pediatricians to use one drug (Paxil) over another (Prozac) in teenagers

    is a big deal.

    Because a lot of them believe that the evidence base matters.

    And, I believe they would wonder if they should trust people who think that it is a problem not worthy of any action at all.

    No one is reaching out effectively and telling them.

  12.  
    Annonymous
    April 5, 2013 | 10:34 AM
     

    Without that, Drs. Ryan and Martin will apply this same scholarship to the research on prophylactic treatment of very young children. Educating the child mental health scientific and clinical counjty over this handling of Study 329 could make a difference.

    1BOM thank you for at least trying to keep the story alive if not that second piece.

  13.  
    April 5, 2013 | 2:32 PM
     

    I call this the “sorcerer’s apprentice effect.” The sorcerer (pharma) has left the scene but the apprentices are still hard at work getting people on chronic medications as early in life as possible, because that’s what the sorcerer wanted back when the apprentices were put into commission.

  14.  
    April 5, 2013 | 9:16 PM
     

    Glad some of you had a good time with my earlier comment here. Uh, did you read the rest of it? I’m not ignoring this happened, just advising watch what is coming out now with new meds. Oh, and by the way, I don’t write for Paxil, never liked it as the poisons seen early on, and SmithKlineBeechum was so disgusting in promoting it even before this study came out.

    But, hey, I’m a psychiatrist, so I am guilty and should be thrown to the curb. The next time a police officer is caught committing a crime, are all you antipsychiatry zealots going to take your next cause and picket your local police station? Yeah, let’s get rid of cops!

    I’ll go out on a limb here and bet most of the most strident critics of psychiatry are Obama supporters. If so, you must love what that man is doing for health care with that legislative assault. Well, you do get the electorate you deserve…

  15.  
    April 5, 2013 | 11:01 PM
     

    Uh–Bama supporter? NOT. Btw Joel, do you still write for Seroquel? knowing that scandal and AstraZeneca’s buring of Study 15? Why dose it out at all? it’s no better than Paxil for that matter–same shame, buried data, cooked data, corrupt doctors, pharma sponsored studies Shultz is still getting away with it–not one person has said a word about how you are a psychiatrist. The discussion is about TRUTH AND EVIDENCE BASED MEDICINE, don’t we all want that.

  16.  
    Stan
    April 5, 2013 | 11:35 PM
     

    So nice of you Joel to finally admit in a public forum that what you do with such mercenary zeal, is a crime…of course your spot on dirty cop/psychiatrist comparison was just so damned precious & felicitous that I was consumed in a delirious state of temporary beguilement.

    Oh yes, you are correct that it is far past time that your kind were thrown off the “Medical Bus” out into the charlatan gutter where they belong….

    Of course good old Dr. Unhinged once more goes off on one of his legendary tirades of nonsensical retort….

    Just maybe Dr. Unhinged needs to add a small dose of Seroquel to take his internet addiction rough edge off… 🙂 LMAO

  17.  
    Annonymous
    April 6, 2013 | 12:17 AM
     

    I am reminded of this:
    http://1boringoldman.com/index.php/2011/08/22/about-comments/

    And this:
    “not one of the novelists who releases a polished sheaf of words once in a blue moon, but one of the writers whose voices you are accustomed to hearing every day.
    It is strange to have that supply cut off.
    There are not many people whose voices you hear every day. Even your best friends, separated by distance or whatever the quaint hesitancy is that dogs us when it comes to the telephone these days, devolve into lines of text on a screen. Even your nearest and dearest are just people whose words you read every day, if you are lucky, inquiring what you did and wanting to know what you know and telling you what they have heard and thought and seen.”
    http://www.washingtonpost.com/blogs/compost/wp/2013/04/05/thank-you-roger-ebert/

    We all can exhibit contentiousness. I certainly exhibit more than my share on this site. At the same time we all come here because we find the writing of the psychiatrist who authors this site to be of value to us in one way or another.

  18.  
    Nick Stuart
    April 6, 2013 | 4:21 AM
     

    ‘I’ll go out on a limb here and bet most of the most strident critics of psychiatry are Obama supporters. ‘

    Thomas Szasz and his followers maybe? Ha! Don’t think so… What kind of limb are you thinking with?

  19.  
    Fid
    April 7, 2013 | 6:35 PM
     

    Can I vote for Obama if I’m a Brit living in New Zealand?

    Joel, you criticize folk for bunching psychiatrists altogether yet your style of argument does exactly the same.

    Paxil 329 should never be forgotten – I agree that there are newer drugs/studies to discuss. Steph has pointed out Seroquel as one but hey, we don’t write this blog, BOM does – we just make the comments.

    PS – Did you ever complain about any of the ‘disgusting’ SmithKline Beecham reps? If so, who to? If not, why?

  20.  
    April 8, 2013 | 2:17 PM
     

    Straw person alert!

  21.  
    April 8, 2013 | 9:53 PM
     

    Joel,

    Obama supporter?
    No way in hell.
    Try consitutional conservative, with strong libertarian tendencies.

    http://discoveandrecover.wordpress.com/freedom

    Duane

  22.  
    April 8, 2013 | 9:56 PM
     

    By the way, Joel.

    I’m in good company, with Dr. Peter Breggin.
    He sent me an autographed copy of this book –

    http://breggin.com/index.php?option=com_content&task=view&id=256&Itemid=120

    Duane

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