{"id":5785,"date":"2011-03-11T22:21:18","date_gmt":"2011-03-12T03:21:18","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=5785"},"modified":"2011-03-12T23:31:45","modified_gmt":"2011-03-13T04:31:45","slug":"the-clinical-research-industry-something-to-change","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/03\/11\/the-clinical-research-industry-something-to-change\/","title":{"rendered":"the clinical research industry: an invisible empire&#8230;"},"content":{"rendered":"\n<div align=\"justify\">Back at the end of November, Paul Thacker, now at <strong><font><a target=\"_blank\" href=\"http:\/\/www.pogo.org\/pogo-files\/letters\/public-health\/ph-iis-20101129.html\"><strong><font color=\"#660033\">POGO<\/font><\/strong><\/a><\/font><\/strong>, wrote a letter to Dr. Francis Collins, Director of the NIH, about ghostwriting. His examples included a textbook by Drs. Charlie Nemeroff and Alan Schatzberg. Nemeroff I knew about from my years at Emory, but I didn&#8217;t know much about Schatzberg. I ended up spending some time looking into his drug, RU-486, Mifepristone. I was amazed at the low quality science behind the Clinical Trials involved in trying to get this drug approved. Then somebody sent me a couple of articles by <strong><font color=\"#200020\">Dr. Madhukar H. Trivedi<\/font><\/strong><font color=\"#200020\"> [<u><strong><a href=\"http:\/\/www.ps.psychiatryonline.org\/cgi\/content\/full\/55\/8\/879\" target=\"_blank\"><font color=\"#200020\">A Computerized Clinical Decision Support System as a Means of Implementing Depression Guidelines<\/font><\/a><\/strong><\/u> and <u><strong><a href=\"http:\/\/www.biomedcentral.com\/1472-6947\/9\/6\" target=\"_blank\"><font color=\"#200020\">Barriers  to implementation of a computerized decision support system  for  depression: an observational report on lessons learned in &quot;real  world&quot;  clinical settings<\/font><\/a><\/strong><\/u>]. He had developed a computer program to guide clinical decision making in treating Depression, but people didn&#8217;t use it. He was <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/01\/28\/evidence-based-medicine-i\/\" target=\"_blank\"><u><strong>perplexed<\/strong><\/u><\/a>:<\/font><\/div>\n<ul>\n<div align=\"justify\"><sup>Although state of the art evidence-based clinical guidelines have  been  available to clinicians for some time, it is now well understood  that  the implementation or adoption of research information in actual   clinical practices lags far behind, with limited potential to change   physician behavior.  Unfortunately to date, efforts to implement quality  improvement (QI)  research findings into practice have often proceeded  without insistence  on the same level of rigor required to establish  these QI targets as  worthy of implementation.  The capacity to base  treatment decisions on state-of-the-art knowledge  alone appears to be  insufficient to motivate behavior change among  clinicians.<\/sup><\/div>\n<\/ul>\n<div align=\"justify\">and he set out to try to understand why doctors were resistant to using his &quot;state-of-the-art&quot; algorithms. I must have had a violent reaction, because I launched into a two week rant about the modern use of the term <strong><font color=\"#200020\">evidence-based medicine<\/font><\/strong>. I thought people didn&#8217;t use his alogorhithm because it was simplistic and trivial at best, often off the mark. He was looking at what was wrong with the doctors rather than what was wrong with his algorithm based on Clinical Trials. He wrote as if Clinical Trials held the absolute truth. But back then, all I knew about Clinical Trials was that Industry funded them. Next, I started looking into how <strong><font color=\"#660099\">Seroquel<\/font><\/strong>, a drug I find to be pretty ineffective, got approved &#8211; so I looked at the <strong><font color=\"#660099\">Seroquel<\/font><\/strong> Clinical Trials. Pretty lame, at best. Then I got interested in how <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> got this weak sister of an Atypical Anti-Psychotic to be a major blockbuster on the market &#8211; Clinical Trials were a big part of the answer. So finally I ended up where I should have started, wondering about Clinical Trials in general and how they are conducted these days. What I found was a whole Industry, the <strong><font color=\"#200020\">Clinical Trials Industry<\/font><\/strong>, that I didn&#8217;t even know existed. And so for the last few weeks, I&#8217;ve been reading and writing about it. I was right the first time &#8211; simplistic and trivial at best, often way off the mark.<\/div>\n<h1><font color=\"#200020\">The Ghosts in the Machine<\/font><\/h1>\n<p align=\"justify\"><img loading=\"lazy\" decoding=\"async\" width=\"293\" hspace=\"4\" height=\"249\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/cro-15.gif\" \/>The Clinical Research Organizations are largely  invisible. Their main advertised function is to set-up and conduct  clinical trials <strong>quickly <\/strong>[and successfully]. The graph on the right is from www.clinicaltrials.gov and shows the time from submission to completion of all of <strong><font color=\"#660033\">Astrazeneca<\/font><\/strong>&lsquo;s <strong><font color=\"#660099\">Seroquel<\/font><\/strong> clinical trials in Schizophrenia. It demonstrates <strong><font color=\"#000099\">Parexel<\/font><\/strong>&lsquo;s success in shortening trial duration [and it shows &quot;globalization&quot; &#8211; mostly to Eastern Europe]. I thought it would be worth looking at the web sites of the top <strong><font color=\"#200020\">CRO<\/font><\/strong>s  to see how they bring off streamlining the process, but they&rsquo;re written too vaguely to nail down, so I&rsquo;ll only  mention a few notables: <\/p>\n<ul>\n<li>\n<div align=\"justify\"><strong><font color=\"#200020\">Mining Medical Records:<\/font><\/strong> When I was looking at the policies promoted by the industry professional organization [<strong><font color=\"#003366\">ACRO<\/font><\/strong>] in the <strong><a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/03\/08\/the-clinical-research-industry-cross-purposes\" target=\"_self\">last post<\/a><\/strong>, there were a couple I didn&rsquo;t understand:  <\/div>\n<ol>\n<div align=\"justify\">&bull; Ensure ease of access to data necessary to conduct research while considering patient privacy<\/div>\n<div align=\"justify\">&bull; Encourage health information technology policies that include consideration of medical research needs<\/div>\n<\/ol>\n<div align=\"justify\">They use <strong><a href=\"http:\/\/www.quintiles.com\/clinical-services\/atp-tools\/\" target=\"_blank\">data-mining<\/a><\/strong> of medical records to locate subjects [when they can] and would like to do a lot more of that in their recruiting.<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><strong><font color=\"#200020\">Prescreening:<\/font><\/strong> Several CROs mention having large databases of <strong><a target=\"_blank\" href=\"http:\/\/www.quintiles.com\/clinical-services\/patient-investigator-recruitment\/\">pre-screened<\/a><\/strong> subjects available to access when the right study comes along.<\/div>\n<\/li>\n<li>\n<div><strong><font color=\"#200020\">Globalization:<\/font><\/strong> They all mention some version of &quot;emerging&quot; or &quot;non-traditional&quot; countries. A <strong><a target=\"_blank\" href=\"http:\/\/www.quintiles.com\/clinical-services\/patient-investigator-nontraditional-regions\/\">quote<\/a><\/strong>:<\/div>\n<ol>\n<div align=\"justify\"> <sup>Different therapeutic indications tend to  cluster in different regions  of the world. Quintiles staff in  non-traditional regions includes  physician specialists in key  therapeutic areas to help fine tune study  design and protocols. <strong><font color=\"#990000\">Patients  in non-traditional regions have a high  rate of protocol compliance and  low dropout rates, because of the high  standards of medical care  available through clinical trials.<\/font><\/strong> This and  our  combination of global reach and local knowledge can result in speedy   recruitment of specific patient populations.<\/sup><\/div>\n<\/ol>\n<div>Overseas clinical trials are a <u>big deal<\/u> with each of the large <strong><font color=\"#200020\">CRO<\/font><\/strong>s.<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><strong><font color=\"#200020\">Communications:<\/font><\/strong> <a href=\"http:\/\/www.covance.com\/products\/clinical\/clinical-development\/clinical-development\/xcellerate.php?cid=Xcellerate_HP_BannerAd\" target=\"_blank\"><strong><font color=\"#200020\">Xcellerate&reg;<\/font><\/strong><\/a> [Covance]; <strong><font color=\"#200020\">Trial Enrollment Accelerator<\/font><\/strong>  [Quintilles]; Internet, email, social media, call centers, etc. They  have it all. And  it&rsquo;s ongoing, not study specific so they can begin  advertising and enrolling for a new  clinical trial the day the get the  contract. Most of them use sophisticated software to locate high yield  sites for a given study. <\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\"> There are a thousand <strong><font color=\"#200020\">CRO<\/font><\/strong>s in the world and many more <strong><font color=\"#200020\">CRC<\/font><\/strong>s [I can&#8217;t find a count, maybe like TNTC &#8211; <em>too numerous to count<\/em>], yet this vast empire is largely invisible. If you read a medical article, it may list the investigators at the CRCs, even their locations, but you can only figure out which <strong><font color=\"#200020\">CRO<\/font><\/strong> conducted\/managed the study if you know how to do it [see below]. The <strong><font color=\"#200020\">CRO<\/font><\/strong>s aren&#8217;t listed in www.clinicaltrials.gov either. The over-riding intelligence that organizes these large industry-funded multi-center trials just doesnt show&#8230;<\/div>\n<h1 align=\"justify<font\">Ghostwriters <font color=\"#999966\">and<\/font> <font color=\"#200020\">the Demigods<\/font>:<\/h1>\n<div align=\"justify\">As mentioned, <a target=\"_blank\" href=\"http:\/\/www.pogo.org\/pogo-files\/letters\/public-health\/ph-iis-20101129.html\"><strong><font color=\"#660033\">POGO<\/font><\/strong><\/a>  wrote the NIH Director, Francis Collins, about five instances of  &quot;ghostwriting.&quot; Two of the culprits, Charlie Nemeroff and Alan  Schatzberg denied the charge saying they had made edits to the galleys.  That&rsquo;s not ghostwriting, they claimed [<a href=\"http:\/\/1boringoldman.com\/index.php\/2010\/12\/10\/4546\" target=\"_blank\"><strong><u><font color=\"#200020\">enter the lawyers&hellip;<\/font><\/u><\/strong><\/a>]. In a way, I agree with them. What they did is an even worse than simple ghoswriting. <\/div>\n<ul>\n<div align=\"justify\">&bull; If I wrote my autobiography and gave it to my  wife to edit the grammar, my run-on sentences, and my stilted  phraseology, I&rsquo;d be an <strong><font color=\"#200020\">Author<\/font><\/strong> and she&rsquo;s be an <strong><font color=\"#200020\">Editorial Assistant<\/font><\/strong>.<\/div>\n<div align=\"justify\">&bull; If I want to write an autobiography but am a  lousy writer, so I hire someone who can write well to write my story  which I tell him-or-her &ndash; that&rsquo;s a <strong><font color=\"#200020\">Ghostwriter<\/font><\/strong> [my story, his-or-her writing]. I guess in this instance, I&rsquo;m a <strong><font color=\"#200020\">sort-of Author<\/font><\/strong>.                <\/div>\n<div align=\"justify\">&bull; If somebody else writes something and I sign on  as a prestigious author, but my only participation is maybe some editing  or tweaking along the way, I would be a <strong><font color=\"#200020\">Demigod<\/font><\/strong> &ndash; pretending I wrote something that I didn&rsquo;t write. I suppose that the real writer is still a <strong><font color=\"#200020\">Ghostwriter<\/font><\/strong>, just ghosting for another story-giver [Pharmaceutical Company, <strong><font color=\"#200020\">CRO<\/font><\/strong>], not the actual listed author.                <\/div>\n<\/ul>\n<div align=\"justify\">In the case in the Schatzberg and Nemeroff, the  real authors were the companies that paid and laid out the story for  Sally Laden and Donna Castiglio of <a href=\"http:\/\/www.stimedinfo.com\/\" target=\"_blank\"><u><strong><font color=\"#200020\">Scientific Therapeutic Information<\/font><\/strong><\/u><\/a> [STI], a Medical Writing Company. Schatzberg and Nemeroff were <strong><font color=\"#200020\">Demigods.<\/font><\/strong><\/div>\n<p>                                                                  <\/p>\n<table width=\"95%\" cellspacing=\"0\" cellpadding=\"3\" border=\"0\" align=\"center\">\n<tr>\n<td valign=\"top\" align=\"justify\"><sup>While I doubt the term <em><strong><font color=\"#200020\">Demigods<\/font><\/strong><\/em>  will achieve general usage to describe the Physicians who allow the  Pharmaceutical Companies to use their names as authors in the medical  literature to publish these quaesi-scientific &quot;<a target=\"_blank\" href=\"http:\/\/books.google.com\/books?id=cpJASw3ahhMC&#038;pg=PA157&#038;lpg=PA157&#038;dq=experimercials&#038;source=bl&#038;ots=ID4FoiMJA7&#038;sig=Y9MtlFF0fkGswtXSWnPDzmiiA9U&#038;hl=en&#038;ei=lr13Td3YGo6D0QHUkpTYBg&#038;sa=X&#038;oi=book_result&#038;ct=result&#038;resnum=2&#038;ved=0CBoQ6AEwAQ#v=onepage&#038;q=experimercials&#038;f=false\"><u>experimercials<\/u><\/a>,&quot; it works for me. <em><strong><font color=\"#200020\">Demigods<\/font><\/strong><\/em> [AKA <em><strong><font color=\"#200020\">Titans<\/font><\/strong><\/em>] comes from the <strong><font color=\"#200020\">Tibetan <u><a target=\"_blank\" href=\"http:\/\/www.buddhanet.net\/wheel1.htm\">Wheel of Life<\/a><\/u><\/font><\/strong>,  and describes people who aspire to be Gods, but have only made it  part-way. In this incarnation, they pad their resumes with publications,  jump on each new <em>break-through treatment<\/em>, and are vulnerable to engagement on the illusionary stage as <em>key opinion leaders<\/em>,  briefly experiencing the adoration they envy but can&rsquo;t quite attain on  their own. The Pharmaceutical Industry has had a field day capitalizing  on their unfullfilled aspirations. Like all personalities driven by  envy, they become quite defensive and &quot;prickly&quot; when confronted with  their deceit. It appears they actually believe their own mythology and  the compliments of their handlers.<\/sup><\/td>\n<td><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/images\/wheel_10.gif\"><img loading=\"lazy\" decoding=\"async\" width=\"200\" hspace=\"4\" height=\"224\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/demigods.gif\" \/><\/a><\/td>\n<\/tr>\n<\/table>\n<p align=\"justify\">The <strong><font color=\"#660033\">POGO<\/font><\/strong> examples are of <strong><font color=\"#200020\">Demigod\/Ghostwiter<\/font><\/strong> pairings from <a href=\"http:\/\/www.stimedinfo.com\/\" target=\"_blank\"><u><strong><font color=\"#200020\">Scientific Therapeutic Information<\/font><\/strong><\/u><\/a>, a medical writing company, not specifically a <strong><font color=\"#200020\">CRO<\/font><\/strong>. But in the unsealed documents and articles in the <strong><font color=\"#660099\">Seroquel<\/font><\/strong> story, there are a number of instances that suggest <strong><font color=\"#200020\">Demigod\/Ghostwiter<\/font><\/strong>&lsquo;s are at work in the Halls of the <strong><font color=\"#200020\">CRO<\/font><\/strong>s as well. All of the publications of the <strong><font color=\"#660099\">Seroquel<\/font><\/strong> trials have the same format: a lead academic author, multiple <strong><font color=\"#660033\">Zeneca<\/font><\/strong>\/<strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> authors, and somebody who probably did the writing in the acknowledgements. In the early preapproval articles, it was <strong><font color=\"#990000\">Suzanne Bristow-Marcalus<\/font><\/strong>, a pharmacy-type who either worked at or for<font color=\"#990000\"> <\/font><strong><font color=\"#660033\">Zeneca<\/font><\/strong>. After 2002 when <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> signed on <strong><font color=\"#000099\">Parexel<\/font><\/strong>, the probable writers were <strong><font color=\"#000099\">Parexel<\/font><\/strong> employees, <strong><font color=\"#990000\">Aruna Seth and Max Brady<\/font><\/strong> &ndash; recall the particularly incriminating episode with Dr. Nassir Ghaemi [<strong><a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/03\/01\/selling-seroquel-vii-indication-sprawl\" target=\"_blank\"><font color=\"#200020\">selling seroquel VII: indication sprawl&hellip;<\/font><\/a><\/strong>]. Later articles appear to have another medical writing company involved [<a target=\"_blank\" href=\"http:\/\/www.cnsspectrums.com\/aspx\/articledetail.aspx?articleid=2113\"><strong><font color=\"#200020\">Extended Release Quetiapine Fumarate Monotherapy for Major  Depressive Disorder:<\/font><\/strong><\/a> <a target=\"_blank\" href=\"http:\/\/www.cnsspectrums.com\/aspx\/articledetail.aspx?articleid=2113\"><strong><font color=\"#200020\"> Results of a Double-Blind, Randomized,  Placebo-Controlled Study<\/font><\/strong><\/a>]. They acknowledge <strong><font color=\"#990000\">Jocelyn Woodcock<\/font><\/strong> of <a href=\"http:\/\/www.complete-mc.com\/Default.aspx\" target=\"_blank\"><strong><font color=\"#200020\">Complete Medical Communications<\/font><\/strong><\/a> in that article. It most cases, we have to infer <strong><font color=\"#200020\">Demigod\/Ghostwiter <\/font><\/strong>pairings from the acknowledgements. They are difficult to prove  because they don&rsquo;t say <strong><font color=\"#200020\">Demigod: Dr. Richard Borison<\/font><\/strong>, <strong><font color=\"#200020\">Ghostwriter:<\/font><\/strong> <strong><font color=\"#990000\">Suzanne Bristow-Marcalus<\/font><\/strong> for obvious reasons.<\/p>\n<p align=\"justify\">I suspect that in practice, the <strong><font color=\"#200020\">CRO<\/font><\/strong>s  that actually do the Clinical Trials are heavily involved in writing up  the Approval Documents for the FDA. Likewise, I expect that the  published articles that make it into our literature are often written by the <strong><font color=\"#200020\">CRO<\/font><\/strong>s that do the studies in conjunction with the Pharmaceutical Companies. The role of the <strong><font color=\"#200020\">Demigods<\/font><\/strong>  is to legitimize the articles to Journal editors and general readers.  Of course they don&rsquo;t advertise such activities on their web-sites. Here  are representative pages for what they do say about their Medical  Writing departments:<\/p>\n<table cellspacing=\"0\" cellpadding=\"3\" border=\"0\" align=\"center\">\n<tr>\n<td align=\"center\" colspan=\"2\"><strong><font color=\"#200020\">Medical Writing<\/font><\/strong>                                                                   <\/p>\n<hr size=\"1\" \/>\n<hr size=\"1\" \/><\/td>\n<\/tr>\n<tr>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.quintiles.com\/clinical-services\/medical-writing\/\"><strong><font color=\"#200020\">Quintiles<\/font><\/strong><\/a><\/u><\/td>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.iconplc.com\/services\/phase-ii-iiib\/medical-safety-services\/medical-writing\/\"><strong><font color=\"#200020\">Icon<\/font><\/strong><\/a><\/u> <\/td>\n<\/tr>\n<tr>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.ppdi.com\/services\/phase_ii_iiib\/regulatory_affairs\/medical_writing.htm\"><strong><font color=\"#200020\">Pharmaceutical Product Development<\/font><\/strong><\/a><\/u><\/td>\n<td><a target=\"_blank\" href=\"http:\/\/www.kendle.com\/MW_Publications.php\"><u><strong><font color=\"#200020\">Kendle<\/font><\/strong><\/u><\/a><\/td>\n<\/tr>\n<tr>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.covance.com\/products\/commercialization\/periapproval\/phase-3b-phase-4\/statistical-analysis-reporting.php\"><strong><font color=\"#200020\">Covance<\/font><\/strong><\/a><\/u><\/td>\n<td><a target=\"_blank\" href=\"http:\/\/www.pharmanet.com\/phase2-4\/html\/medwriting.html\"><u><strong><font color=\"#200020\">PharmaNet      Development Group<\/font><\/strong><\/u><\/a><\/td>\n<\/tr>\n<tr>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.criver.com\/en-us\/prodserv\/bytype\/clinical\/support\/pages\/protocol_development_and_medical_writing.aspx\"><strong><font color=\"#200020\">Charles River Laboratories<\/font><\/strong><\/a><\/u><\/td>\n<td><strong><u><a target=\"_blank\" href=\"http:\/\/www.prainternational.com\/Our%20Services\/Product%20Registration%20Services\/Analysis%20%20Reporting\"><font color=\"#200020\">PRA      International<\/font><\/a><\/u><\/strong><\/td>\n<\/tr>\n<tr>\n<td><u><a target=\"_blank\" href=\"http:\/\/www.parexel.com\/services-and-capabilities\/clinical-research\/medical-writing-and-submission\/\"><strong><font color=\"#200020\">Parexel<\/font><\/strong><\/a><\/u><\/td>\n<td><a target=\"_blank\" href=\"http:\/\/www.incresearch.com\/Services\/Clinical-Trial-Services.aspx#Regulatory\"><u><strong><font color=\"#200020\">INC Research<\/font><\/strong><\/u><\/a><\/td>\n<\/tr>\n<\/table>\n<div align=\"center\"><sup>The secret code word is &quot;manuscripts.&quot;<\/sup><\/div>\n<p align=\"justify\">It&rsquo;s equally frustrating trying to run down who manages the recruitment,  scheduling, communications with, and presentations by, the <strong><font color=\"#200020\">Key Opinion  Leaders<\/font><\/strong> &ndash; the Physicians who ride the circuit giving talks at meetings,  dinners, and CME presentations that are essentially stealth drug  advertisements. This slide show from <strong><font color=\"#200020\">Quintiles<\/font><\/strong> is an example of the involvement of the <strong><font color=\"#200020\">CRO<\/font><\/strong>s with the <strong><font color=\"#200020\">KOL<\/font><\/strong> networks [<a target=\"_blank\" href=\"http:\/\/www.quintiles.com\/elements\/media\/case-studies\/stakeholder-network-mapping.pdf\"><em><strong><font color=\"#660033\">Improved Commercialization Strategy through Stakeholder Network Mapping<\/font><\/strong><\/em><\/a>]. Here&rsquo;s another approach from <strong><font color=\"#000099\">Parexel<\/font><\/strong> [<u><a target=\"_blank\" href=\"http:\/\/www.parexel.com\/files\/1012\/7518\/6884\/Reach_KOLs_Online_2_11_08-63750-1.pdf\"><strong><em><font color=\"#000099\">Reach KOLs On-Line<\/font><\/em><\/strong><\/a><\/u>]. My impression is that the <strong><font color=\"#200020\">KOL<\/font><\/strong>s are connected with the Pharmaceutical  Companies, but that the <strong><font color=\"#200020\">CRO<\/font><\/strong>s are heavily involved in creating  presentations, and maintaining communication networks. I can&rsquo;t penetrate further [because they don&#8217;t want us to know how all  this works].<\/p>\n<h1 align=\"justify\"><font color=\"#200020\">Practical Ghostbusting for Rookies<\/font><\/h1>\n<div align=\"center\"><img decoding=\"async\" vspace=\"7\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-16.gif\" \/><\/div>\n<div>I guess I have the enthusiasm of a recovering rookie, and would like to go through an article to demonstrate the ghosts. I&#8217;ve used this article before because the complete text is on-line. It&#8217;s a study using <strong><font color=\"#660099\">Seroquel XR<\/font><\/strong> to treat <strong><font color=\"#200020\">Major Depressive Disorder<\/font><\/strong>:<\/div>\n<blockquote>\n<div align=\"center\"><a href=\"http:\/\/www.cnsspectrums.com\/aspx\/articledetail.aspx?articleid=2113\" target=\"_blank\"><strong><font color=\"#200020\">Extended Release Quetiapine Fumarate Monotherapy for Major  Depressive Disorder:<\/font><\/strong><\/a><\/div>\n<div align=\"center\"><a href=\"http:\/\/www.cnsspectrums.com\/aspx\/articledetail.aspx?articleid=2113\" target=\"_blank\"><strong><font color=\"#200020\"> Results of a Double-Blind, Randomized,  Placebo-Controlled Study<\/font><\/strong><\/a><br \/>                                              by Richard Weisler, <strong><font color=\"#0000ff\">J. Mark  Joyce<\/font><\/strong>, <strong><font color=\"#0000ff\">Lora McGill<\/font><\/strong>, <strong><font color=\"#6600cc\">Arthur Lazarus<\/font><\/strong>, <strong><font color=\"#6600cc\">Johan Szamosi<\/font><\/strong>, and <strong><font color=\"#6600cc\">Hans Eriksson<\/font><\/strong><\/div>\n<\/blockquote>\n<div>Since most studies are not directly on line, even if you don&#8217;t have access to something like OVID through a university affiliation, you still have some research abilities:<\/div>\n<ul>\n<div><strong><font color=\"#990000\">Resource Number 1<\/font><\/strong>:<strong><font color=\"#200020\"> <u><a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/advanced\">pubmed.gov<\/a><\/u><\/font><\/strong>. PubMed is a database of scientific articles maintained by the NIH. Enter the title and you&#8217;ll get an abstract of the article.<\/div>\n<\/ul>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"213\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-17.gif\" \/><\/div>\n<div align=\"justify\">Click the + next to Publication Types:<\/div>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"281\" height=\"194\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-18.gif\" \/><\/div>\n<div align=\"justify\">This tells you that it was not a government funded Clinical Trial, and gives you the Clinical Trial ID Number:<\/div>\n<ul>\n<div align=\"justify\"><strong><font color=\"#990000\">Resource Number 2<\/font><\/strong>:<strong><font color=\"#200020\"> <u><a target=\"_blank\" href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/a><\/u><\/font><\/strong>. This is a database of Clinical Trials maintained by the NIH. Enter the Clinical Trial ID Number and you&#8217;ll get the data on the Trial referenced by the article.<\/div>\n<\/ul>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"73\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-19.gif\" \/><\/div>\n<ul>\n<div align=\"justify\">and further down the page:<\/div>\n<\/ul>\n<div align=\"center\">&nbsp;<img loading=\"lazy\" decoding=\"async\" width=\"224\" height=\"48\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-20.gif\" \/><\/div>\n<div align=\"justify\">While there&#8217;s lots of information there, it doesn&#8217;t name the CRO, but it does tell you that it was funded by <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>, maker of the tested drug, and that the Investigator was <u>not<\/u> the listed first author &#8211; but probably an <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> employee. Without the whole article, the only thing further would be to look up the first author to see if he\/she is being paid by Pharma: <\/div>\n<ul>\n<div align=\"justify\"><strong><font color=\"#990000\">Resource Number 3<\/font><\/strong>:<strong><font color=\"#200020\"> <u><a target=\"_blank\" href=\"http:\/\/projects.propublica.org\/docdollars\/\">probublica.org<\/a><\/u><\/font><\/strong>.  ProPublica has a database of payments to physicians from eight major Pharmas. Enter the  author&#8217;s name:<\/div>\n<\/ul>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"476\" height=\"112\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/cro-21.gif\" \/><\/div>\n<div align=\"justify\"><strong><font color=\"#200020\">So, with only the name of the article, you can deduce quickly that it is a Clinical Trial funded by the maker of the drug, managed by the drug-maker, and has a first author that is being paid by the drug-maker. That goes a long way towards suggesting unacceptible bias.<\/font><\/strong> If you have a copy of the whole article, you can go much further:<\/div>\n<ul>\n<div align=\"justify\"><strong>Faculty Affiliations and Disclosures:<\/strong> Dr. Weisler is Adjunct Professor of Psychiatry in the Department of Psychiatry at the University of North Carolina, Chapel Hill, and Adjunct Associate Professor of Psychiatry at Duke University, in Durham, North Carolina. Dr. Joyce is Principal Investigator at <strong><font color=\"#000099\">CNS Healthcare<\/font><\/strong> in Jacksonville, FL. Dr. McGill is Lead Principal Investigator at <strong><font color=\"#000099\">CNS Healthcare<\/font><\/strong> in Memphis, TN.  Dr. Lazarus is Senior Director, Clinical Research at <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> Pharmaceuticals LP in Wilmington, DE. Mr. Szamosi is Principal Statistician at <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> in S&ouml;dert&auml;lje, Sweden. Dr. Eriksson is Medical Science Director at <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> in S&ouml;dert&auml;lje, Sweden.<\/div>\n<\/ul>\n<div align=\"justify\"> Dr. Lazarus and Mr. Szamosi, two of the authors, are employees of the drug-maker. Two of the authors are Investigators with <strong><font color=\"#000099\">CNS Healthcare<\/font><\/strong>. A simple Google Search of <u><a target=\"_blank\" href=\"http:\/\/www.cnshealthcare.com\/\"><strong><font color=\"#000099\">CNS Healthcare<\/font><\/strong><\/a><\/u> shows you it is a CRO-like group of CRCs [who did the study]. Only Dr. Weisler is not part of the drug-makers system, and we already know he is a paid affiliate of the drug-maker [from ProPublica]. Reading further:<\/div>\n<ul>\n<div align=\"justify\"><strong>Faculty Disclosures:<\/strong> Dr. Weisler is a  consultant to Abbott, the Agency of Toxic Substances and Disease  Registry\/Centers for Disease Control and Prevention, <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>,  Biovail, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly, Forest,  GlaxoSmithKline, Johnson &amp; Johnson, Organon, Otsuka America  Pharmaceutical, Pfizer, Pharmacia, Sanofi, Sanofi-Synthelabo, Shire,  Solvay, Validus, and Wyeth; is on the speaker&rsquo;s bureau of Abbott, <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>, Biovail, Bristol-Myers Squibb, Burroughs Wellcome,  Cephalon, Ciba Geigy, Eli Lilly, Forest, GlaxoSmithKline, Janssen,  Johnson &amp; Johnson, Novartis, Organon, Pfizer, Sanofi,  Sanofi-Synthelabo, Shire, Solvay, Validus, and Wyeth; has received  grant\/research support from Abbott, <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>, Biovail, Bristol-Myers  Squibb, Burroughs Wellcome, Cenerx, Cephalon, Ciba Geigy, CoMentis,  Dainippon Sumitomo Pharma America, Eisai, Eli Lilly, Forest,  GlaxoSmithKline, Janssen, Johnson &amp; Johnson, Lundbeck , McNeil  Pharmaceuticals, Medicinova, Merck, National Institute of Mental Health,  Neurochem, New River Pharmaceuticals, Novartis, Organon, Pfizer,  Pharmacia, Repligen, Saegis, Sandoz, Sanofi, Sanofi-Synthelabo,  Schwabe\/Ingenix, Sepracor, Shire, Synaptic, Takeda, TAP, UCB Pharma,  Vela, and Wyeth; and owns stock in Bristol-Myers Squibb, Cortex, Merck,  and Pfizer.<\/div>\n<\/ul>\n<div align=\"justify\">we find numerous Pharma connections for Dr. Weisler. Finally, we find:<\/div>\n<ul>\n<div align=\"justify\"><strong>Acknowledgments:<\/strong> The authors would like to thank Jocelyn Woodcock, MPhil, from<strong> Complete Medical Communications<\/strong>, who provided medical writing support funded by <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>&#8230;<\/div>\n<\/ul>\n<div align=\"justify\">Googling <u><a target=\"_blank\" href=\"http:\/\/www.complete-mc.com\/Default.aspx\"><strong>Complete Medical Communications<\/strong><\/a><\/u>, we see that it is a Medical Writing Company. <strong><font color=\"#200020\">So, with the whole article, we can deduce that it is an industry funded and managed study. All five authors are connected to the drug-maker and the first author is a heavily connected to Pharma in general. The study was conducted by a CRO. Finally, the acknowledgment of the Medical Writing Company makes us heavily suspect that it is ghostwritten. <\/font><\/strong>Though we can&#8217;t prove the last connection conclusively, this certainly looks like one of those <strong><font color=\"#200020\">Demigod\/Ghostwriter<\/font><\/strong> pairings all too common these days.<\/div>\n<h1 align=\"justify\"><font color=\"#200020\">The Clinical Trial &#8211; A Ghost of its Former Self<br \/>      <\/font><\/h1>\n<p align=\"justify\"><img loading=\"lazy\" decoding=\"async\" width=\"260\" hspace=\"4\" height=\"336\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/sell-seroquel-15.gif\" \/>I criticized this article earlier as an example of a <strong><font color=\"#200020\">CRO-Chart<\/font><\/strong> article that may [or may not] have achieved significance, but was irrelevant, based on the reported data [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/02\/19\/selling-seroquel-iii-the-data-factories\"><strong><font color=\"#200020\">selling seroquel III: the data factories&hellip;<\/font><\/strong><\/a>]. Here, I am suggesting more &#8211; that this article <u>in the medical literature<\/u> is little more than a stealth ad, a way to advertise <strong><font color=\"#660099\">Seroquel XR<\/font><\/strong> [extended release and<em> patent extending<\/em>] as an off-label first-line treatment for Major Depressive Disorder. The article reeks of bias and deliberate obfuscation of the primary data.&nbsp; <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> did <u>not<\/u> get <strong><font color=\"#660099\">Seroquel XR<\/font><\/strong> approved as monotherapy in MDD, but not because of the likely bias and inadequacy of this study. They were turned down because the FDA saw the side effects as too dangerous to approve it for this indication as a primary treatment.       <\/p>\n<div align=\"justify\">The privatization of Clinical Research has created a lucrative Invisible Empire of CRCs and CROs, employed by the Pharmaceutical Industry that often uses Physicians [KOLs] as Demigod Authors for the largely ghostwritten articles that have populated our Psychiatric literature. The articles don&#8217;t belong there. These jury-rigged Clinical Trials don&#8217;t belong in FDA applications. One shouldn&#8217;t have to vet an article for signs of ghosts. The Clinical Trial is the last step before a drug is approved for actual use by sick patients and deserves to be conducted under pristine scientific conditions &#8211; should be an example of <strong><font color=\"#200020\">evidence-based medicine<\/font><\/strong> at its best. This is not <u>anything<\/u> at its best. It&#8217;s something we ought to be ashamed of. It&#8217;s something to change&#8230;<\/div>\n<hr width=\"95%\" size=\"1\" \/>\n<div><strong><font color=\"#200020\">UPDATE:<\/font><\/strong> Just in [hat tip to <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/03\/08\/the-clinical-research-industry-cross-purposes\/#comment-194309\" target=\"_blank\"><strong><font color=\"#300030\">Nancy<\/font><\/strong><\/a>]:<\/div>\n<blockquote>\n<div align=\"center\"><strong><font color=\"#200020\"><a href=\"https:\/\/www.oag.state.tx.us\/oagNews\/release.php?id=3661\" target=\"_blank\">Texas and 37 States Reach $68.5 Million Settlement With AstraZeneca<\/a><br \/>    Attorney General of Texas<\/font><\/strong><br \/>    &nbsp;<sup>Settlement comes after three-year investigation into marketing of Seroquel<\/sup><br \/>    March 11, 2011<\/div>\n<p align=\"justify\"><strong>AUSTIN<\/strong> &ndash; Texas Attorney General Greg Abbott and 37 other state  attorneys general today reached a record-breaking agreement with <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong>, which the states investigated for improper marketing  practices. The states&rsquo; $68.5 million settlement resolves a three-year  investigation into <strong><font color=\"#660033\">AstraZeneca <\/font><\/strong>Pharmaceutical&rsquo;s efforts to market the  antipsychotic drug <strong><font color=\"#660099\">Seroquel<\/font><\/strong>. Under today&rsquo;s settlement, the State of  Texas will receive $3.8 million. Today&rsquo;s multistate agreement stems from a complaint in federal court  charging <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> with unlawfully marketing <strong><font color=\"#660099\">Seroquel<\/font><\/strong> for unapproved &ndash;  or off-label &ndash; uses. The states also charged <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> with failing  to disclose <strong><font color=\"#660099\">Seroquel<\/font><\/strong>&rsquo;s harmful side effects and concealing scientific  data that revealed safety concerns&#8230;<\/p>\n<div align=\"justify\">Under  the settlement, <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> agreed to comply with state and federal  laws governing its marketing &ndash; including legal requirements that  prohibit manufacturers from promoting their products for off-label uses  not approved by the U.S. Food and Drug Administration [FDA]&#8230; The states&rsquo; legal action explained that <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> targeted Alzheimer&rsquo;s patients at nursing homes, as well as  patients who suffered anxiety, depression, sleep disorders and post  traumatic stress syndrome. The settlement also imposes injunctive provisions that require <strong><font color=\"#660033\">AstraZeneca<\/font><\/strong> to:<\/div>\n<ul>\n<div align=\"justify\">&bull;\tPublish any payments it makes to physicians on the Internet;<\/div>\n<div align=\"justify\">&bull;\tImplement policies that ensure its marketing and sales personnel are not financially compensated for marketing off-label uses;<\/div>\n<div align=\"justify\">&bull;\tEstablish polices to ensure that its sales personnel will refrain from  marketing Seroquel to health care providers who are unlikely to  prescribe it for an FDA-approved use; and <\/div>\n<div>&bull;\tCite <strong><font color=\"#660099\">Seroquel<\/font><\/strong>l&rsquo;s FDA-approved indicators when referencing selected symptoms.<\/div>\n<\/ul>\n<div align=\"justify\">  Atypical antipsychotics, including <strong><font color=\"#660099\">Seroquel<\/font><\/strong>, can produce dangerous side  effects, including weight gain, hyperglycemia, diabetes, cardiovascular  complications, an increased risk of mortality in elderly patients with  dementia and other severe conditions.<\/div>\n<\/blockquote>\n","protected":false},"excerpt":{"rendered":"<p>Back at the end of November, Paul Thacker, now at POGO, wrote a letter to Dr. Francis Collins, Director of the NIH, about ghostwriting. His examples included a textbook by Drs. Charlie Nemeroff and Alan Schatzberg. Nemeroff I knew about from my years at Emory, but I didn&#8217;t know much about Schatzberg. I ended up [&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_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-5785","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/5785","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=5785"}],"version-history":[{"count":67,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/5785\/revisions"}],"predecessor-version":[{"id":5909,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/5785\/revisions\/5909"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=5785"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=5785"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=5785"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}