{"id":41599,"date":"2013-11-14T21:53:19","date_gmt":"2013-11-15T02:53:19","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=41599"},"modified":"2013-11-15T07:32:18","modified_gmt":"2013-11-15T12:32:18","slug":"scarlet-bullets","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/11\/14\/scarlet-bullets\/","title":{"rendered":"scarlet bullets&#8230;"},"content":{"rendered":"<div align=\"justify\">Yesterday, I wrote about what we heard about the current goings-on with GSK and Paxil Study 329 [<a href=\"http:\/\/1boringoldman.com\/index.php\/2013\/11\/14\/how-that-should-work\/\" target=\"_blank\">how that should work&hellip;<\/a>, <a href=\"http:\/\/1boringoldman.com\/index.php\/2013\/11\/14\/grown-up-stuff\/\" target=\"_blank\">grown-up stuff&hellip;<\/a>]. Today we get yet a new puzzle piece from David Healy &#8211;<\/div>\n<ul>\n<li>\n<div align=\"justify\"><em><strong><font color=\"#990000\">an <\/font><a href=\"http:\/\/davidhealy.org\/wp-content\/uploads\/2013\/11\/021010_FDAApprovablePediatricPaxil.pdf\" target=\"_blank\"><font color=\"#990000\">FDA letter to GSK<\/font><\/a><font color=\"#990000\"> from 2003 approving Paxil for use in children and adolescents<\/font><\/strong><\/em>.<\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\">Yeah, you heard that part right. Here are the operative lines from that letter:<\/div>\n<div align=\"right\"><img decoding=\"async\" width=\"500\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/329-fda-ocd-letter.gif\" \/><\/div>\n<div align=\"justify\">Who knew? But speaking of new information, that second highlighted paragraph is something in its own right. It appears that GSK and the FDA had been chatting about the fact that <\/div>\n<ul>\n<li>\n<div align=\"justify\"><em><strong><font color=\"#990000\">Study 329 &quot;failed to demonstrate the efficacy of Paxil in pediatric patients with MDD&quot;<\/font><\/strong><\/em><\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\">[along with Studies 377 and 701].<\/div>\n<ul>\n<li>\n<div align=\"justify\"> <em><strong><font color=\"#990000\">And they were in agreement that there wasn&#8217;t any need to put that on the package label?<\/font><\/strong><\/em><\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\">Dr. Healy goes on to assemble some more pieces of the story into the timeline:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/davidhealy.org\/the-house-of-gsk\/?utm_source=feedburner&#038;utm_medium=email&#038;utm_campaign=Feed%3A+DrDavidHealy+%28Dr.+David+Healy%29\" target=\"_blank\">The House of GSK<\/a><\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">by Dr. David Healy <\/font><\/strong><\/div>\n<div align=\"center\" class=\"small\">November 14, 2013<\/div>\n<p align=\"justify\">&#8230;Study  329 began to unravel because a journalist, Shelley Jofre, working for  BBC&rsquo;s Panorama, accidentally left to her own devices, begin to dig.&nbsp;She  went to the American Psychiatric Association Meeting in Philadelphia in  May 2002, clutching the Keller-Laden paper. She was interested to  interview some of the &ldquo;authors&rdquo;.&nbsp;One of her questions was &ldquo;What is  emotional lability?&rdquo; There was a surprising number of children in 329  who became emotionally labile &ndash; what&rsquo;s this? she asked. No-one seemed to  know.<\/p>\n<p align=\"justify\">At APA, she approached one of the 329 authors Neal Ryan, <a href=\"http:\/\/davidhealy.org\/wp-content\/uploads\/2013\/11\/Emotional-Lability-Email.docx\" target=\"_blank\"><em><strong>who gave a non-answer<\/strong><\/em><\/a> and quickly got in touch with GSK to let them know a journalist was asking questions. A few weeks later in July and again in August, GSK send a dossier to FDA seeking approval for Paxil for children. A few weeks after that, on October 7th, to coincide with World Mental  Health day [October 10th], Newsweek hit the streets featuring a  depressed teenager on the front cover and a strapline Teen Depression: 3  million kids suffer from it. What you can do.&nbsp;The message inside was  that Prozac was already being marketing for children and Paxil and  Zoloft were about to be.&nbsp;What you can do &ndash; is get children on Prozac,  Paxil and Zoloft.<\/p>\n<div><em><strong><font color=\"#200020\">Celebrating World Mental Health Day<\/font><\/strong><\/em><\/div>\n<p align=\"justify\">Three days later, on October 10th, World Mental Health Day, and the  40th anniversary of the passage of the 1962 amendments to the Food and  Drugs Act, FDA sent GSK <a href=\"http:\/\/davidhealy.org\/wp-content\/uploads\/2013\/11\/021010_FDAApprovablePediatricPaxil.pdf\" target=\"_blank\"><em><strong>a letter saying Paxil was approvable<\/strong><\/em><\/a> for kids. Among other things, the letter notes that GSK had already told FDA  that Study 329 showed that&nbsp;Paxil doesn&rsquo;t work for depressed  children.&nbsp;FDA were happy to go along with GSK&rsquo;s suggestion that this  should not be mentioned in the labeling of the drug. Given that the  Study 329 publication majored on how effective Paxil was, it would have  been inconvenient if the label said otherwise. There are many notable things in this approvable letter.&nbsp;Perhaps the most interesting is FDA asking GSK to clarify just what <em>emotional lability<\/em> meant.<\/p>\n<div align=\"justify\">FDA have later spun this into a story that their reviewers detected there was an increase of emotional lability events in Study 329 that needed looking at. In fact this idea came on their radar after conversations between Jofre and third parties led to a visit to FDA on August 28th and a suggestion to FDA that they explore the issue of emotional lability.  FDA at the time had a few weeks to respond to GSK&rsquo;s request to market Paxil for children. Neither Jofre nor the third parties knew at the time that GSK were seeking pediatric approval for Paxil&#8230;<\/div>\n<\/blockquote>\n<div align=\"justify\">Pardon my heavy handed scarlet bullet formatting, but I wanted to convey outrage. Yesterday, I was reading that letter from GSK swatting away Jon Juriedini&#8217;s request for Study 329 to be withdrawn, saying &quot;<em><strong><font color=\"#200020\">GSK does not believe it appropriate to request retraction of the article<\/font><\/strong><\/em>&quot; &#8211; an article which had said &quot;<em><strong><font color=\"#200020\">paroxetine is generally well  tolerated and effective for major depression in adolescents<\/font><\/strong><\/em>.&quot; And now today I read that ten years ago, GSK and the FDA were openly talking about Paxil study 329 being a negative study that &quot;<strong><em><font color=\"#200020\">failed to demonstrate the efficacy of Paxil in pediatric patients with MDD<\/font><\/em><\/strong>,&quot; and that the FDA said &quot;<em><strong><font color=\"#200020\">we agree that it would not be useful to describe these negative trials in labeling.<\/font><\/strong><\/em>&quot; But it is apparently fine to leave the article that itself is a part of the proof that Paxil is not effective in pediatric patients with MDD but says the opposite intact in a major psychiatric journal for child psychiatrists around the world to read as if it is true? Scarlet bullets aren&#8217;t close to enough.<\/div>\n<p>   <\/p>\n<div align=\"justify\">We&#8217;re left dangling by Dr. Healy&#8217;s post because this revelation that the FDA was declaring Paxil &quot;approvable&quot; for OCD in Children and Adolescents is something I sure didn&#8217;t know. What happens next? And what about the biggest question of all. Whether it&#8217;s effective in OCD kids or not, there&#8217;s the question of akathisia, agitation, hostility, suicidality &#8211; those adverse effects that stay on the table with SSRIs in kids and adults, but particularly with kids. My crude analysis of Paxil Study 329 last year suggested that it was a real danger [<a href=\"http:\/\/1boringoldman.com\/index.php\/2012\/08\/29\/the-lesson-of-study-329-uh-oh\/\" target=\"_blank\">the lesson of Study 329: uh-oh!&hellip;<\/a>]. What was the FDA thinking about that? The FDA letter said:<\/div>\n<div align=\"right\"><img loading=\"lazy\" decoding=\"async\" width=\"500\" height=\"133\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/329-fda-ocd-letter-1.gif\" \/><\/div>\n<div align=\"justify\">To which Dr. Healy responded [above]:   <\/div>\n<blockquote>\n<div align=\"justify\">FDA  have later spun this into a story that their reviewers detected there  was an increase of emotional lability events in Study 329 that needed  looking at.&nbsp;In fact this idea came on their radar after conversations  between Jofre and third parties led to a visit to FDA on August 28th and  a suggestion to FDA that they explore the issue of emotional lability.<\/div>\n<\/blockquote>\n<div align=\"justify\">I expect we&#8217;ll hear more about this thread in the story [Healy leaves us with a crypyic &quot;to be continued&quot;]. I&#8217;ve chopped up Dr. Healy&#8217;s post and the FDA letter to make my own points, but there&#8217;s another thread in his narrative that I lost along the way. This story has a hero &#8211; journalist <strong><font color=\"#200020\">Shelley Jofre<\/font><\/strong>. I thought I&#8217;d make up for that omission by reposting her Panorama program for those of you that may not have seen it:<\/div>\n<p><\/p>\n<div align=\"center\"><iframe loading=\"lazy\" width=\"420\" height=\"315\" src=\"\/\/www.youtube.com\/embed\/_0ffzsrDkSQ\" frameborder=\"1\"><\/iframe><\/div>\n<p> <\/p>\n<div align=\"justify\">And here is Shelley&#8217;s later series &#8211; posted for American viewers who don&#8217;t know this part of the story:<\/div>\n<ul>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=99RWfNVJKlo\">Installment 1\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=SwEMDmHUnjI\">Installment 2\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=JqPDNbobDk8\">Installment 3\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=KMAtkRLgf9o\">Installment 4\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=T4nKd2Z8bro\">Installment 5\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=JZGIHMsDH70\">Installment 6\/7<\/a><\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/www.youtube.com\/watch?v=kIXHK0LFD2c\">Installment 7\/7<\/a><\/div>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Yesterday, I wrote about what we heard about the current goings-on with GSK and Paxil Study 329 [how that should work&hellip;, grown-up stuff&hellip;]. Today we get yet a new puzzle piece from David Healy &#8211; an FDA letter to GSK from 2003 approving Paxil for use in children and adolescents. Yeah, you heard that part [&hellip;]<\/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":[2],"tags":[],"class_list":["post-41599","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/41599","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=41599"}],"version-history":[{"count":29,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/41599\/revisions"}],"predecessor-version":[{"id":41652,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/41599\/revisions\/41652"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=41599"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=41599"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=41599"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}