{"id":11386,"date":"2011-07-12T16:11:03","date_gmt":"2011-07-12T20:11:03","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=11386"},"modified":"2011-07-12T16:14:18","modified_gmt":"2011-07-12T20:14:18","slug":"trial-93-a-very-bad-penny","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/07\/12\/trial-93-a-very-bad-penny\/","title":{"rendered":"trial 93: a <u>very<\/u> bad penny&#8230;"},"content":{"rendered":"\n<div align=\"justify\"><sup><em><font color=\"#999933\">I had assumed that the version of the Biederman documents I was using was all that was available. That was wrong as EP pointed out. <strong>psychrights<\/strong> had the complete release. When I located it before, I thought it was &#8216;broken,&#8217; not realizing that it was just a huge file that took its time traveling to Georgia [14+ Mb].<\/font><\/em><\/sup><\/div>\n<p>               <\/p>\n<div align=\"justify\">Here is a more complete piece of the RISPERDAL 2002 Business Plan Summary added as an update to the end of the last post:              <\/div>\n<ul>\n<div>\n<div align=\"justify\"><strong><sup>The clinical development program for RISPERDAL has yielded important new efficacy and safety data in the child and adolescent area. <\/sup><font color=\"#000080\"><sup><em>These efforts have previously been focused in the area of Disruptive Behavior Disorders and Subaverage IQ. Several trials, RI5-U5A-93 and RI5-CAN- 19 (as well as the open label 48 week follow up trials, USA-97 and CAN-20), initially designed to support filing for an FDA indication, have been completed and have yielded an impressive volume of new efficacy and safety data. Unfortunately, the FDA determined that Disruptive Behavior Disorder lacks the diagnostic specificity necessary to receive an approved indication<\/em>.<\/sup><\/font><\/strong><strong><sup> Nevertheless, these studies have contributed significantly to the clinical knowledge of RISPERDAL in the child and adolescent population, and provide a basis for ongoing medical education activities. Going forward, regulatory and clinical development efforts will include the evaluation of the NIMH RUPP Risperidone in Autism database to support filing for potential autism indication, adolescent schizophrenia indication, and the fulfillment of the FDA Written Request requirement for additional 6 month patent exclusivity. It is expected that the request will include the following requirements:<\/sup><\/strong><\/div>\n<div>\n<div align=\"justify\"> <\/div>\n<ol>\n<div align=\"justify\"><strong><sup>&bull; Pediatric PK trial;<br \/> &bull; Adolescent schizophrenia trial; and<br \/> &bull; Pediatric bipolar trial.<\/sup><\/strong><\/div>\n<\/ol>\n<div align=\"justify\"><strong><sup>The child and adolescent market offers several unique challenges not found in other areas where RlSPERDAL is used. <\/sup><em><font color=\"#800000\"><sup>First and foremost, the sensitivity towards medications and their use in children shapes this segment. This Issue is prominent in medical as well as lay press and public discussions regarding pediatric psychopharmacology. This results in many stereotypes and stigmas that prevent some children from receiving appropriate treatment. Additionally, the child and adolescent market is not driven by diagnosis, but rather by treatment of symptoms such as aggression, agitation, self-injurious behavior, and explosive rage. This lack of consistent diagnosis stems from a reluctance to &quot;label&quot; children at an early age, as well as a fundamental lack of consensus regarding the actual underlying disease states causing this symptomatic behavior. As a result, multiple diagnoses and comorbidities are the rule, rather than the exception in this area.<\/sup><\/font><\/em><\/strong><strong><sup> These issues have influenced the clinical development process and limited the ability to achieve an FDA approved indication for RISPERDAL in children&#8230;<\/sup><\/strong><\/div>\n<\/div>\n<\/div>\n<\/ul>\n<div align=\"justify\">&quot;&#8230; <em><font color=\"#800000\">many stereotypes and stigmas that prevent some children from receiving appropriate treatment<\/font><\/em>.&quot; I&#8217;ve never been in the business world and know nothing of marketing, but I expect this is pretty much standard fare &#8211; knowing your market or something like that. If they were discussing washday detergents or toothpaste, it would sound much the same and it wouldn&#8217;t bother anybody. But they&#8217;re not. They&#8217;re talking about big drugs for small children, so it takes on another dimension. And we probably wince at the statement that these &quot;<em><font color=\"#800000\">stereotypes and stigmas<\/font><\/em>&quot; are interfering with &quot;<em><font color=\"#800000\">appropriate treatment<\/font><\/em>.&quot; Who are they to define what is appropriate treatment?             <\/div>\n<p align=\"justify\">&quot;&#8230; <font color=\"#800000\"><em>the child and adolescent market is not  driven by diagnosis, but rather by treatment of symptoms such as  aggression, agitation, self-injurious behavior, and explosive rage<\/em><\/font>&quot; actually seems an accurate description of prescribing practices to me. It comes from their marketing research which they show in a slide that goes with their Business Plan:<\/p>\n<p align=\"center\"><img decoding=\"async\" width=\"400\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/ris-1.gif\" \/><\/p>\n<p align=\"justify\">It&#8217;s no wonder that they started where they did: &quot;<em><font color=\"#000080\">These efforts have previously been focused in the area of Disruptive  Behavior Disorders and Subaverage IQ. Several trials &#8230; initially designed to support filing for an FDA indication,  have been completed&#8230;<\/font><\/em>&quot; It&#8217;s what their marketing research said to do.They seemed surprised the FDA didn&#8217;t approve it: &quot;<em><font color=\"#000080\">Unfortunately, the FDA determined that   Disruptive Behavior Disorder lacks the diagnostic specificity necessary   to receive an approved indication<\/font>.<\/em>&quot; It continues:<\/p>\n<ul>\n<div align=\"justify\"><strong><sup>The bulk of RISPERDAL use in the child and adolescent market is for mood and anxiety related diagnoses [keeping in mind the limitation previously mentioned regarding diagnosis vs. symptomatic treatment]. <\/sup><em><font color=\"#008000\"><sup>Bipolar Disorder with 18% of uses leads the way<\/sup><\/font><font color=\"#008000\"><sup> in this area<\/sup><\/font><\/em><\/strong><strong><sup> followed by Depression with 10% and Anxiety with 3%. This represents an overall mood and anxiety use of 31% of the total atypical drug use for children. ADHD\/Conduct Disorder makes up the next largest market segment with 20% of total drug uses, followed by schizophrenia\/psychosis at 15%, and autism at 14%. These usage patterns are consistent with those for all atypical antipsychotics in aggregate.<\/sup><\/strong><\/div>\n<\/ul>\n<div align=\"justify\">Reading this business plan, you can see what&#8217;s coming. They wanted to market their drug to Children and Adolescents so they initially went for <strong><font color=\"#200020\">Disruptive Behavior Disorder<\/font><\/strong>, which is hardly a diagnosis &#8211; it&#8217;s more like a &#8216;complaint.&#8217; How that one made it into the DSM-IV is beyond me. In the DSM-III, they moved from a &#8216;disease&#8217; model to a &#8216;descriptive model&#8217; &#8211; lists of symptoms. But <strong><font color=\"#200020\">Disruptive Behavior Disorder<\/font><\/strong> isn&#8217;t even that, because it doesn&#8217;t describe the symptoms of the patient [child]. It describes the symptoms of the teacher or parent. It&#8217;s about the &#8216;impact&#8217; of the child on others [Disruptive]. The FDA is [wisely] not about to approve a medication as efficacious because someone other than the person taking the medicine has a decreased symptom burden. So even if the medication is being prescribed for &quot;<strong><font color=\"#200020\">Aggression \/ Hostility<\/font><\/strong>&quot; and &quot;<strong><font color=\"#200020\">Behavior dyscontrol \/ Impaired impulse control<\/font><\/strong>&quot; &#8211; that&#8217;s not an <em>indication<\/em>. It&#8217;s a medication usage that should be carefully considered in every individual case where its contemplated, and carefully monitored when used. Some think the medication should never be used in this way. Some use it way too much in this way. But wherever one falls on that spectrum, it&#8217;s never a routine matter.<\/div>\n<p align=\"justify\">So the marketing department takes a second look and sees: &quot;<font color=\"#008000\"><em>Bipolar Disorder with 18% of uses leads the way in this area<\/em><\/font>.&quot; Is it any wonder that they suddenly decided to respond to Dr. Biederman&#8217;s&nbsp; requests that they fund a Center at Harvard\/Mass General? Dr. Biederman was the primo Bipolar Child guru who had already given bipolar disorder in children a dose of steroids and was already an advocate for treating them with Atypical Antipsychotics. <strong><font color=\"#990000\">No one would question giving the medication for a <em>disease<\/em>.<\/font><\/strong> Why they could even recycle their earlier studies under the new label [&quot;<font color=\"#000080\"><em>Several trials, RI5-U5A-93 and RI5-CAN- 19  (as well as the open label 48 week follow up trials, USA-97 and CAN-20),  initially designed to support filing for an FDA indication, have been  completed and have yielded an impressive volume of new efficacy and  safety data<\/em><\/font>&quot;]. All they had to do was reanalyze the data and get Dr. Biederman to present it for them, and then later publish it [<u><strong><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/07\/10\/trial-93-a-bad-penny\"><font color=\"#200020\">trial 93: a bad penny&hellip;<\/font><\/a><\/strong><\/u>]. <strong><font color=\"#200020\">And he did it!<\/font><\/strong> <\/p>\n<p align=\"justify\">In the <a href=\"http:\/\/www.windhover.com\/pdf\/biedermanday2.pdf#page=31\" target=\"_blank\"><u><strong><font color=\"#200020\">deposition<\/font><\/strong><\/u><\/a>, the lawyer takes Dr. Biederman apart on the topic of this study [the one I called the <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/07\/10\/trial-93-a-bad-penny\/\" target=\"_blank\"><u><strong><font color=\"#200020\">bad penny<\/font><\/strong><\/u><\/a>]. Biederman didn&#8217;t admit it was ghost-written, but he might as well have. The paper claimed that Risperidone was effective on the Affective Symptoms [disruptive retarded kids]. As it turned out, the abstract mis-stated the results. It was actually more effective on the Non-Affective Symptoms!<\/p>\n<p align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"120\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/ris-4.gif\" \/><\/p>\n<p align=\"justify\">Here&#8217;s the lawyer pointing out the error:<\/p>\n<p align=\"center\"><img decoding=\"async\" width=\"450\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/ris-5.gif\" \/>&nbsp;<\/p>\n<div align=\"justify\">But if you think about it, what does the result of a Risperidone Trial in disruptive retarded kids have to do with bipolar disorder in children, even if it had shown what they claimed [which it didn&#8217;t]? Stay tuned&#8230;  <\/div>\n","protected":false},"excerpt":{"rendered":"<p>I had assumed that the version of the Biederman documents I was using was all that was available. That was wrong as EP pointed out. psychrights had the complete release. When I located it before, I thought it was &#8216;broken,&#8217; not realizing that it was just a huge file that took its time traveling to [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","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_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-11386","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/11386","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=11386"}],"version-history":[{"count":52,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/11386\/revisions"}],"predecessor-version":[{"id":11445,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/11386\/revisions\/11445"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=11386"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=11386"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=11386"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}