{"id":64524,"date":"2016-04-08T12:42:54","date_gmt":"2016-04-08T16:42:54","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=64524"},"modified":"2016-04-08T13:02:45","modified_gmt":"2016-04-08T17:02:45","slug":"wolf-alert-wolf-alert","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/04\/08\/wolf-alert-wolf-alert\/","title":{"rendered":"wolf alert! wolf alert!&#8230;"},"content":{"rendered":"\n<p align=\"center\"><img decoding=\"async\" border=\"0\" width=\"100\" src=\"http:\/\/1boringoldman.com\/images\/wolf-sheeps-clothing.gif\" \/><\/p>\n<div align=\"justify\" class=\"small\">The wheels of progress turn very slowly, and about all one can really take heart from is that they keep turning. It seems as if what we call <em><font color=\"#200020\">Data Transparency<\/font><\/em> has been echoing around the Globe for several years but the yield so far has been sparse. In the version being worked out by the <font color=\"#0000ff\">European Medicines Agency <\/font>[<font color=\"#0000ff\">EMA]<\/font>, the focus of the first phase has been on the <font color=\"#200020\">CSRs <\/font>[<font color=\"#200020\">Clinical Study Report<\/font>s], covered by Tom Jefferson [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2015\/07\/01\/a-priori\/\"><em>a priori<\/em>&hellip;<\/a>]. The <font color=\"#200020\">IPD <\/font>[<font color=\"#200020\">Individual Participant Data<\/font>] policy is the next phase, still in discussion. In the US, there was a 290 page report from an <font color=\"#660033\">Institute of medicine Committee<\/font> released last year [linked here for reference]:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/www.nap.edu\/read\/18998\/chapter\/1#ii\">Sharing Clinical Trial Data<\/a>:<\/div>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/www.nap.edu\/read\/18998\/chapter\/1#ii\">MAXIMIZING BENEFITS, MINIMIZING RISK<\/a><\/div>\n<div align=\"center\" class=\"middle\">Committee on Strategies for Responsible Sharing of Clinical Trial Data<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES<\/font><\/strong>, pp. 290, 2015<\/div>\n<div align=\"center\" class=\"small\">[for reference]<\/div>\n<\/blockquote>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/journals.plos.org\/plosmedicine\/article?id=10.1371\/journal.pmed.1001946\" target=\"_blank\">Sharing Individual Participant Data [IPD] within the Context of the Trial Reporting System [TRS]<\/a><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#500050\">PLOS Medicine<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\"><font color=\"#200020\">National Library of Medicine, National Institutes of Health<\/font><\/div>\n<div align=\"center\" class=\"middle\">by Deborah A. Zarin and Tony Tse<\/div>\n<div align=\"center\" class=\"small\">January 19, 2016<\/div>\n<ul>\n<li>\n<div align=\"justify\">The role of individual participant data [IPD] sharing can best be understood as part of an overall three-level trial reporting system [TRS] framework.<\/div>\n<\/li>\n<li>\n<div align=\"justify\">Different &ldquo;types&rdquo; of IPD, which reflect varying degrees of information granularity, have different potential benefits and harms.<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><a href=\"http:\/\/www.bmj.com\/content\/351\/bmj.h4320\" target=\"_blank\">Study 329 of Paxil<\/a> [paroxetine] in children with depression is used as a case study to highlight the potential value of different components of the TRS.<\/div>\n<\/li>\n<\/ul>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">It&#8217;s a short article, easy to read laying out a stepwise program for <em><font color=\"#200020\">Data Transparency<\/font><\/em> that starts with the Registration of the Trial on ClinicalTrials.gov. The next step would be the Results Database on ClinicalTrials.gov. And then they move to IPD Sharing proper and they discuss various flavors of access &#8211; using our 329 rewrite as an example:<\/div>\n<p align=\"center\"><img decoding=\"async\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/trs.gif\" \/><\/p>\n<div align=\"justify\" class=\"small\">Reading this short benign article, I felt bothered but couldn&#8217;t put my finger on exactly why. When I came down this morning and saw it on my computer screen, I had a different response. I couldn&#8217;t find anything right about it. I haven&#8217;t read the whole IOM report, just skimmed it, but I had something of the same reaction. A few points:<\/div>\n<ul><span class=\"small\">           <\/p>\n<li>\n<div align=\"justify\"><u><strong><font color=\"#200020\">Index of Suspicion<\/font><\/strong><\/u>: The tone of the IOM Report and the article is very civil with talk of <font color=\"#200020\">Data Sharing<\/font> for other novel investigations, limiting the access by levels depending on what&#8217;s being looked for, using the <font color=\"#200020\">ClinicalTrials.gov Results Database<\/font>. etc. <\/div>\n<div align=\"justify\">We don&#8217;t want Data Transparency to look for novel anything. We want Data Transparency because it has been tampered with and distorted on a massive scale. We don&#8217;t want limited anything. We want to be able to look in every last nook and cranny. So I had a strong &quot;<em><font color=\"#200020\">con job<\/font><\/em>&quot; feeling [really strong].<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><u><strong><font color=\"#200020\">CinicalTrials.gov<\/font><\/strong><\/u>: I love this site &#8211; visit it all the time &#8211; pour through the history of changes fequently. But it&#8217;s no panacea for Data Transparency. It describes the study, but it doesn&#8217;t have the a priori Protocol, and it doesn&#8217;t have the Statistical Analytic Plan, and it&#8217;s obviously easy to leave out important details. If the study is being done by a CRO, it diesn&#8217;t say which one. So it&#8217;s great in a general way, but specifics, not so much.<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><u><strong><font color=\"#200020\">CinicalTrials.gov<\/font><\/strong> <strong><font color=\"#200020\">Results Database<\/font><\/strong><\/u>: This is the most ignored requirement on the planet. The articles documenting how rarely it&#8217;s actually filled out are everywhere. It&#8217;s ignored by Industry and Academia alike. It&#8217;s improved some after all the attention its disuse gathered, but is hardly a reliable recource. And even if it is filled our, it rarely adds much to the published article. It&#8217;s as easy to jury-rig as the articles, maybe moreso because to my knowledge, it&#8217;s not reviewed. I hope the IOM Report will address this point.<\/div>\n<\/li>\n<li>\n<div align=\"justify\"><u><strong><font color=\"#200020\">The Horse&#8217;s Mouth<\/font><\/strong><\/u>: <strong><font color=\"#200020\">CinicalTrials.gov<\/font><\/strong> and the <strong><font color=\"#200020\">CinicalTrials.gov<\/font> <\/strong><strong><font color=\"#200020\">Results Database<\/font><\/strong> are secondary proxies for the actual data, and written by the sponsors. The other resource that are available are the <font color=\"#200020\">FDA Medical Reports<\/font> on <em><font color=\"#200020\">Drugs@FDA<\/font><\/em>. They&#8217;re also great, though often, the lag time can be excessive [the last one I went after took 18 months]. But all of these things are <em><font color=\"#200020\">about the data<\/font><\/em>, not the data itself. Even the <font color=\"#200020\">FDA Medical Reports<\/font> are <em><font color=\"#200020\">Drugs@FDA<\/font><\/em>. They&#8217;re too far from <strong><font color=\"#200020\">The Horse&#8217;s Mouth<\/font><\/strong>.          <\/div>\n<\/li>\n<li>\n<div align=\"justify\"><u><strong><font color=\"#200020\">Viva Europe!<\/font><\/strong><\/u>: The verdict is still out on how the <font color=\"#0000ff\">EMA<\/font> is going to deal with the IPD information, but they&#8217;re off to a good start so far. What they&#8217;re releasing with some CCI redactions is exactly what was sent to them in the application for approval. That&#8217;s going to be the Drug Company on it&#8217;s best behavior, the place where they&#8217;re least likely to do a lot of spinning because it&#8217;s going to be evaluated by experts who have the power to ask for more information. So it&#8217;s the highest level surrogate information available. As someone checking it over, you&#8217;re at an equal level with the regulators. What we can get from the <font color=\"#660033\">FDA<\/font> is <em><font color=\"#200020\">what they said about what they saw<\/font><\/em>. What we will be able to get from the <font color=\"#0000ff\">EMA<\/font> is also <font color=\"#200020\">what they saw<\/font>. Much better&#8230;          <\/div>\n<\/li>\n<p>         <\/span><\/ul>\n<div align=\"justify\" class=\"small\">And then there&#8217;s this from the report:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><strong><font color=\"#200020\">COMMITTEE ON STRATEGIES FOR RESPONSIBLE SHARING OF CLINICAL TRIAL DATA<\/font><\/strong><\/div>\n<ul>\n<div align=\"justify\">BERNARD LO (Chair), President, The Greenwall Foundation<\/div>\n<div align=\"justify\">TIMOTHY COETZEE, Chief Research Officer, National Multiple Sclerosis Society<\/div>\n<div align=\"justify\">DAVID L. DeMETS, Professor and Chair, Department of Biostatistics and Medical Informatics, University of Wisconsin&ndash;Madison<\/div>\n<div align=\"justify\"><strong><font color=\"#990000\">JEFFREY DRAZEN, Editor-in-Chief, New England Journal of Medicine<\/font><\/strong><\/div>\n<div align=\"justify\">STEVEN N. GOODMAN, Professor, Medicine &amp; Health Research &amp; Policy, Stanford University School of Medicine<\/div>\n<div align=\"justify\">PATRICIA A. KING, Carmack Waterhouse Professor of Law, Medicine, Ethics and Public Policy, Georgetown University Law Center<\/div>\n<div align=\"justify\">TRUDIE LANG, Principal Investigator, Global Health Network, Nuffield Department of Medicine, University of Oxford<\/div>\n<div align=\"justify\">DEVEN McGRAW, Partner, Healthcare Practice, Manatt, Phelps &amp; Phillips, LLP<\/div>\n<div align=\"justify\">ELIZABETH NABEL, President, Brigham and Women&rsquo;s Hospital<\/div>\n<div align=\"justify\">ARTI RAI, Elvin R. Latty Professor of Law, Duke University School of Law<\/div>\n<div align=\"justify\">IDA SIM, Professor of Medicine and Co-Director  of Biomedical Informatics of the Clinical and Translational Science  Institute, University of California, San Francisco<\/div>\n<div align=\"justify\">SHARON TERRY, President and CEO, Genetic Alliance<\/div>\n<div align=\"justify\">JOANNE WALDSTREICHER, Chief Medical Officer, Johnson &amp; Johnson<\/div>\n<\/ul>\n<\/blockquote>\n<div align=\"justify\" class=\"small\"><strong><font color=\"#200020\">In my mind, this brings Dr. Jeffrey Drazen&#8217;s recent comments about Data Sharing into much sharper focus, and I smell danger, danger all around this whole story! <\/font><\/strong><\/div>\n<p align=\"center\"><img decoding=\"async\" border=\"0\" width=\"140\" src=\"http:\/\/1boringoldman.com\/images\/wolf-sheeps-clothing.gif\" \/><\/p>\n<div align=\"justify\" class=\"small\">Give it another read&#8230; <\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMe1516564\" target=\"_blank\">Data Sharing<\/a><\/div>\n<div align=\"center\" class=\"small\">by Dan L. Longo, and Jeffrey M. Drazen<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#000001\">New England Journal of Medicine<\/font><\/strong>. 2016&nbsp;  374:276-277.<\/div>\n<div align=\"center\" class=\"middle\">[<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMe1516564\" target=\"_blank\">full text on-line<\/a>] <\/div>\n<p align=\"justify\">The  aerial view of the concept of data sharing  is beautiful. What could be  better than having high-quality  information carefully reexamined for the  possibility that new nuggets  of useful data are lying there, previously  unseen? The potential for  leveraging existing results for even more  benefit pays appropriate  increased tribute to the patients who put  themselves at risk to  generate the data. The moral imperative to honor  their collective  sacrifice is the trump card that takes this trick&#8230; <\/p>\n<div align=\"justify\">    <strong><font color=\"#990000\">A second concern held by some is that a new class of research person will emerge &mdash; people who had nothing to do with the design and execution of the study but use another group&rsquo;s data for their own ends, possibly stealing from the research productivity planned by the data gatherers, or even use the data to try to disprove what the original investigators had posited. There is concern among some front-line researchers that the system will be taken over by what some researchers have characterized as &ldquo;research parasites&rdquo;&#8230;<\/font><\/strong><\/div>\n<\/blockquote>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" border=\"0\" width=\"180\" height=\"151\" src=\"http:\/\/1boringoldman.com\/images\/wolf-sheeps-clothing.gif\" \/><\/div>\n","protected":false},"excerpt":{"rendered":"<p>The wheels of progress turn very slowly, and about all one can really take heart from is that they keep turning. It seems as if what we call Data Transparency has been echoing around the Globe for several years but the yield so far has been sparse. In the version being worked out by the [&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":[5],"tags":[],"class_list":["post-64524","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64524","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=64524"}],"version-history":[{"count":35,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64524\/revisions"}],"predecessor-version":[{"id":64564,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/64524\/revisions\/64564"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=64524"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=64524"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=64524"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}