{"id":51586,"date":"2014-11-05T21:06:16","date_gmt":"2014-11-06T02:06:16","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=51586"},"modified":"2014-11-10T05:08:05","modified_gmt":"2014-11-10T10:08:05","slug":"something-else-2","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2014\/11\/05\/something-else-2\/","title":{"rendered":"something else&#8230;"},"content":{"rendered":"\n<p align=\"justify\">As some of you know, a group of us are on a RIAT [<a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f2865\" target=\"_blank\">restoring invisible and abandoned trials<\/a>] team that has spent the last year working on the first shot at an independent team analyzing and reporting on someone else&#8217;s Clinical Trial. It has been a great learning experience for me, and has been the reason for so many posts about how trials work and my monotonous slides: <\/p>\n<p align=\"center\"><img decoding=\"async\" border=\"0\" width=\"350\" src=\"http:\/\/1boringoldman.com\/images\/clinical-trial-11.gif\" \/><\/p>\n<p align=\"justify\">On the day there was a bruhaha in the comments, I had learned that there was much to do in a tight time-frame. Emails were buzzing across oceans and I was all caught up in those things, so I missed what was going on in my own back yard. When I say <em>tight time-frame<\/em>, I should say <em>tight time-frame for me<\/em>. My place in this hinges in part on my previous training in math and statistics [which ended the same year the first PC was built &#8211; 1974]. So every new task has a learning curve that&#8217;s long and tedious &#8211; catching up with newer statistical methodology and doing it using modern software [mainly the latter]. When I was doing it the first time, data was on punch-cards and software was something you wrote yourself [also on punchcards].   <\/p>\n<div align=\"justify\">Most of you don&#8217;t know this yet, but in retirement time can be infinite, or can fill up in ways you never imagined. I had already realized I needed to clear out some space for some intense learning time, so this is what I had planned to say:<\/div>\n<ul>\n<div align=\"justify\" class=\"small\"><em><font color=\"#200020\">Blogging is too much fun for me. I really enjoy having a piece of my day where I take something and research it a bit, then my dogs and I go out on the porch or one of those park benches in this beautiful Fall and compose what I want to say, write it down, then come back and format it as a post. It&#8217;s something a busy practitioner never really gets to do. But right now, I&#8217;m going to have to take something of a break and hit the books [AKA Internet] to learn some new stuff. I know what it is, and what it&#8217;s for, but I don&#8217;t know how to do it in practice or how to format the data or set up the equations, etc. If I keep having blogging fun, I won&#8217;t get the job done. So expect only occasional and brief content from me for the next month or so while I take a refresher course. Feel free to talk among yourself in the comments.<\/font><\/em><\/div>\n<\/ul>\n<div align=\"justify\">But that seems a really odd thing to say in the present moment without explanation, though it&#8217;s still the truth. I doubt I&#8217;ll be able to stop my pre-sunrise routine of looking at what&#8217;s going on. But I&#8217;m going to have to forgo the later fun part, mentioned above. So I may just post articles or links, without much comment or research. Envision me at the computer looking at screens with too many greek letters with my eyes trying to cross. It may not be as hard as I think, but I won&#8217;t know that until I know it. Here&#8217;s what I would&#8217;ve thought about today:<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/blogs.plos.org\/speakingofmedicine\/2014\/11\/03\/emas-release-regulatory-data-possible-fall-journals-research-synthesis\/\" target=\"_blank\">EMA&rsquo;s Release of Regulatory Data: Possible Fall out for Journals and Research Synthesis<\/a><\/div>\n<div align=\"justify\" class=\"small\"><strong><font color=\"#200020\">On 2 October the European Medicines Agency&rsquo;s [EMA] published the<\/font><\/strong> <a href=\"http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Other\/2014\/10\/WC500174796.pdf\">final version of its policy<\/a> <strong><font color=\"#200020\">  on prospective release of clinical study reports [CSRs] of trials   submitted by sponsors in support of Marketing Authorisation Applications   [MAAs] <\/font><\/strong><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#660033\">PLOS: Speaking of Medicine<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\">By Tom Jefferson<\/div>\n<div align=\"center\" class=\"small\">November 3, 2014<\/div>\n<div align=\"center\" class=\"middle\">[<a target=\"_blank\" href=\"http:\/\/blogs.plos.org\/speakingofmedicine\/2014\/11\/03\/emas-release-regulatory-data-possible-fall-journals-research-synthesis\/\">full text on-line<\/a>]<\/div>\n<p align=\"justify\">I have summarized its content and made preliminary comments <a href=\"http:\/\/blogs.bmj.com\/bmj\/2014\/10\/07\/tom-jefferson-emas-release-of-regulatory-data-trust-but-verify\/\" target=\"_blank\">here<\/a> <\/p>\n<p align=\"justify\"><strong><font color=\"#200020\">The policy<\/font><\/strong><br \/>   In brief, from 1 January 2015 the proactive policy will join the  current reactive policy and allow prospective access to incomplete CSRs  at two levels: a &ldquo;viewer&rdquo; level of access and a &ldquo;researcher&rdquo; level. The  former will allow on-screen viewing only with a simple registration  procedure, while the latter will require proof of identity but allow  download and OCR searches to be carried out on CSRs. Prospective seems  to mean two things: after a regulatory decision has been taken, pharma  will format and write CSRs for direct web posting, and once you have  obtained access credentials, you will not have to ask every time you  want a CSR and wait some months [and in some cases be turned down].<\/p>\n<p align=\"justify\"><strong><font color=\"#200020\">Its meaning<\/font><\/strong><br \/>   The practical importance of the policy hinges on the dawning  realization of the difference in accuracy, completeness and  trustworthiness of published versions of trials compared to their CSR  counterparts. Trials may not be published, some may not even be  registered [especially the older ones] posing decades-old problems for  readers, users and, from my point of view, evidence synthetisers.  Reporting bias [cherry picking] is the broad term which encompasses the  scores of different types of bias present in publications. The range  from the well-known publication bias to the less known swamping bias  [when important information on a trial is missed amidst a sea of other  information]. CSRs in theory cut through all this by presenting  exhaustive structured narratives and results of trials. This is  essentially part of what regulators see.<\/p>\n<p align=\"justify\">The policy has some as yet unclear legal aspects and sets out equally  unclear rules for redaction of CSRs [based on the preservation of  commercial interests and protection of participant privacy]. It also  does not explain why some parts of the CSRs will not be released.<\/p>\n<p align=\"justify\">The proactive EMA policy will provide an easily accessible window to  look at CSRs. When you read the statements &ldquo;placebo controlled&rdquo; or  &ldquo;matching placebo&rdquo; or &ldquo;double blind&rdquo; in a journal article you can now go  and check if that is really the case. And if, for example, the  certificate of analysis<sup>1<\/sup> is missing from the CSR that you are  accessing, you can ask EMA why that is so, introducing an unheard of  degree of accountability.<\/p>\n<p align=\"justify\">An ever growing body of scientific evidence shows that journals do  not give the whole story [although some go to extraordinary lengths].&nbsp;  This point reflects simple arithmetic: the ratio of CSR pages to  publication pages for the same trial can be as much as 8000 to 1.&nbsp; To  maintain their credibility journals will have to either provide access  to CSRs, or stop publishing trials altogether and offer commentaries on  trials only. One further option, that of asking for the complete CSR to  be made available for each trial on submission, is also at present  unrealistic, as current peer reviewers are unskilled in making sense and  reviewing a CSR, especially if time constrained. My experience also  tells me that every trial should be looked at in the context of the  whole trial programme, for example to avoid a piecemeal approach to the  assessment of potential harms.<\/p>\n<p align=\"justify\">There may be other scenarios such as slowing the rate of publication  of trials to allow thorough review of the linked CSR, the growth of a  skilled cohort of well-paid peer reviewers or the publication of  structured summaries linked to CSRs on the EMA webpage or a combination  of these.<\/p>\n<p align=\"justify\"><strong><font color=\"#200020\">Evidence synthesis<\/font><\/strong><br \/>   Accessibility of CSRs, although not a panacea for reporting bias,  should also improve the reliability of research synthesis. As more  information on the planning, intended and real conduct of the trial will  be available, a good review will be the one that searches regulatory  and pharma websites, reconstructs and presents the whole trial programme  of interest and includes and reviews CSRs. A good review will also  contact the trials sponsors to obtain confirmation that there are no  invisible trials and trawls through registers, black and grey literature  to check that this is so.<\/p>\n<p align=\"justify\">But all this will take a lot of time and require skills and tools to  be developed. Businesses which produce reviews in months will require  years to do the same, or fall behind.<\/p>\n<p align=\"justify\">It is likely that the whole infrastructure to produce synthesis  studies will have to change and become much more professional, flexible  and intensive, or fall behind. For the record, I don&rsquo;t believe in  automatic methods of data extraction to facilitate dealing with CSRs,  but perhaps I am too old-school and will be proved wrong.<\/p>\n<div align=\"justify\">So, increased accountability should work for everyone and should keep  CSR writers on their toes, open regulators to being quizzed,  revolutionise publishing and produce better synthesis assessments.<\/div>\n<\/blockquote>\n","protected":false},"excerpt":{"rendered":"<p>As some of you know, a group of us are on a RIAT [restoring invisible and abandoned trials] team that has spent the last year working on the first shot at an independent team analyzing and reporting on someone else&#8217;s Clinical Trial. It has been a great learning experience for me, and has been the [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","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-51586","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/51586","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=51586"}],"version-history":[{"count":4,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/51586\/revisions"}],"predecessor-version":[{"id":51609,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/51586\/revisions\/51609"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=51586"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=51586"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=51586"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}