{"id":67043,"date":"2016-07-24T19:34:08","date_gmt":"2016-07-24T23:34:08","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=67043"},"modified":"2016-07-24T20:09:15","modified_gmt":"2016-07-25T00:09:15","slug":"whats-it-going-to-take","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/07\/24\/whats-it-going-to-take\/","title":{"rendered":"what’s it going to take?…"},"content":{"rendered":"
At this summer’s American Psychiatric Association<\/font><\/em> meeting, Karen Dineen Wagner<\/font>, president elect of the American Academy of Child and Adolescent Psychiatry<\/font><\/em> discussed the treatment of depressed children and adolescents, saying:<\/div>\n
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…only two drugs are approved for use in youth by the Food and Drug Administration [FDA]: fluoxetine for ages 8 to 17 and escitalopram for ages 12 to 17, said Wagner. The youngest age in the clinical trials determines the lower end of the approved age range. So what do you do if an 11-year-old doesn’t respond to fluoxetine? One looks at other trials, she said, even if the FDA has not approved the drugs for pediatric use. For instance, one clinical trial found positive results for citalopram in ages 7 to 17…<\/font><\/strong><\/div>\n<\/blockquote>\n
She’s referring to a 2004 Citalopram study [in which she was the Principle Investigator and first author]:<\/div>\n
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A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.<\/a><\/div>\n
by Wagner KD, Robb AS, Findling RL, Jin J, Gutierrez MM, Heydorn WE.<\/div>\n
American Journal of Psychiatry<\/font><\/strong>. 2004 161[6]:1079-1083.<\/div>\n
[full text on-line<\/a>]<\/div>\n<\/blockquote>\n
Meanwhile, based on their recent deconstruction<\/a> of that same study, Jon Jureidini<\/font>, Jay Armstrong<\/font>, and Leemon McHenry<\/font> were waiting for word from the American Journal of Psychiatry <\/font><\/strong>[AJP<\/font><\/strong>] editor Robert Freedman<\/font> about their request that this same article be retracted. Dr. Freedman has now responded by email<\/a>: <\/div>\n
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RE: Am J Psychiatry 2004; 161:1079–1083 We are not retracting this article<\/font><\/strong>. Robert Freedman MD<\/div>\n<\/blockquote>\n
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Had I read this story in college while I was thinking about what comes next, I wonder if I might have been so disillusioned that I would’ve made other choices? Or later when I was thinking about switching my career direction from Internal Medicine to Psychiatry, would I have made the change? It involves the president of the main organization for child and adolescent psychiatry and the editor of the official journal of the professional organization for all of psychiatry. What if I knew then that this is not just an isolated incident, but rather something more like business as usual? I can’t answer those questions, but I know for sure it would’ve mattered, just like it matters now…<\/font><\/em><\/strong><\/sup><\/div>\n

The truth about this article has emerged more slowly than for its cousin Paxil Study 329<\/font>. Shortly after it was published, people noticed that it had a big error in reporting an effect size [see more Wagner et al<\/em>…<\/a>]. But in 2009 [shortly after this study was an essential ingredient in FDA Approval<\/a> for use in adolescents], in a suit alleging off-label marketing, discovery documents revealed it was ghost written, that the listed authors weren’t chosen until the study was over and the article was already drafted. Also, it failed to mention another completed study that was negative [see collusion with fiction…<\/a>]. That suit was settled for $149M. While the AJP<\/font><\/strong> published a stern note, they did not retract the article [see the jewel in the crown…<\/a>]. <\/p>\n

Now, in the wake of litigation for yet another legal suit, more internal documents make it abundantly clear that  just about everything about the study was jury-rigged – including the outcome switching<\/font><\/em> mentioned in wonky science…<\/a>. It’s all detailed in this recent publication by Jureidini et al: <\/div>\n
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The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance<\/a><\/div>\n
by <\/span>Jureidini, Jon N., Amsterdam, Jay, D, and McHenry, Leemon B.<\/font><\/div>\n
International Journal of Risk & Safety in Medicine<\/font><\/strong>, 2016 28[1]:33-43.<\/div>\n
[full text on-line<\/a>]<\/div>\n
[background notes<\/a>]<\/div>\n

<\/p>\n

OBJECTIVE<\/font><\/strong><\/em>: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. <\/div>\n
METHODS<\/font><\/strong><\/em>: Approximately 750 documents from the Celexa and Lexapro Marketing and Sales Practices Litigation: Master Docket 09-MD-2067-[NMG] were deconstructed. <\/div>\n
RESULTS<\/font><\/strong><\/em>: The published article contained efficacy and safety data inconsistent with the protocol criteria. Procedural deviations went unreported imparting statistical significance to the primary outcome, and an implausible effect size was claimed; positive post hoc measures were introduced and negative secondary outcomes were not reported; and adverse events were misleadingly analysed. Manuscript drafts were prepared by company employees and outside ghostwriters with academic researchers solicited as ‘authors’. <\/div>\n
CONCLUSION<\/font><\/strong><\/em>: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety. <\/div>\n<\/blockquote>\n

Their difficulties getting this paper published are discussed in the background notes<\/a>. And in addition to the internal emails, Dr. Wagner’s deposition in the case makes it clear that she never even personally reviewed the data or the statistical analyses that were published under her name [see author·ity…<\/a>]. So this article is just an advertisement, deceptively written by a drug company [Forest Laboratories], not a science-based report for physicians and their patients.<\/p>\n

Why would Dr. Freedman, editor of the AJP<\/font><\/strong>, send this hostile email with only six words ["We are not retracting this article<\/font><\/strong>"] instead of taking the mountain of information about this article seriously? Why does Dr. Wagner continue to quote this article as clinically meaningful [even promoting off-label use in children] in the face of it being so thoroughly discredited? What’s it going to take to put an end to this kind of irresponsible, deceitful behavior at the upper levels of psychiatry? Whatever it is, it’s way past due… <\/div>\n","protected":false},"excerpt":{"rendered":"

At this summer’s American Psychiatric Association meeting, Karen Dineen Wagner, president elect of the American Academy of Child and Adolescent Psychiatry discussed the treatment of depressed children and adolescents, saying: …only two drugs are approved for use in youth by the Food and Drug Administration [FDA]: fluoxetine for ages 8 to 17 and escitalopram for […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-67043","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/67043","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=67043"}],"version-history":[{"count":29,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/67043\/revisions"}],"predecessor-version":[{"id":67072,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/67043\/revisions\/67072"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=67043"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=67043"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=67043"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}