{"id":40370,"date":"2013-09-28T14:43:49","date_gmt":"2013-09-28T18:43:49","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=40370"},"modified":"2013-09-28T15:09:19","modified_gmt":"2013-09-28T19:09:19","slug":"a-loophole-awaiting-exploitation","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/09\/28\/a-loophole-awaiting-exploitation\/","title":{"rendered":"a loophole awaiting exploitation…"},"content":{"rendered":"
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A few days ago, I was talking about a Venn diagram [in proxies…<\/a>] I’d sketched on the back of an envelope [left above]. A more accurate version of what it really looked like originally is on the right. What I was trying to get at is that in the Clinical Trial process, the motives of the pharmaceutical company and the motives of doctors and patients may differ somewhat, but the overall result is the same. The drug company moguls would be pleased as punch if the RCT blind was broken and revealed a new medication that was effective and non-toxic. So their motives and ours are similar in the top two bubbles, gathering and testing a subject cohort that has the right condition and is powered to show the desired result. Where things go haywire is when the study comes back with results that are tempting, but lacking robustness, safety, or both. So close and yet so far! That’s when the trouble starts. That’s where the temptation to "latch on to the affirmative, eliminate the negative, … and don’t mess with mister in-between<\/em>" too often comes into the picture. It’s in what happens in the green bubble, the space between breaking the blind and the published paper. That’s where the deceit lives and has flourished in epidemic proportions behind closed doors.<\/td>\n<\/tr>\n<\/table>\n

One way to deal with a negative or not quite positive study is to simply ignore it, not publish it. I hadn’t been aware of what a powerful tool that could be. With the FDA, you have to include it in the safety evaluation, but you can leave it out altogether in the efficacy submission. The FDA requirement is two positives. If you’ve got a bunch of negative trials, no matter. So if you get it through the FDA, the clinicians have no clue about the raft of failed attempts until Cochrane or someone else does a meta-analysis late in the patent life of the drug [if they can find out about the negative studies!]. This is where the AllTrials<\/font><\/strong> campaign shines. By insisting that something<\/em> be published from every trial, we’ll know about all the duds along the way up front. I gave an example recently from the Agomelatine studies [a breath of fresh air…<\/a>]:<\/p>\n

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Why bother to change the green bubble? The first time around, I populated it with the things that ought to protect us from the deceitful papers we’ve been inundated with, particularly in industry sponsored trials, particularly in psychiatry. But that’s obviously not enough, because they kept on coming. Recently, I’ve been looking back over some of those papers thinking about how to keep them out of the literature, or at least keep them out in the flavor they now come in. I guess I was wondering if there might be some way of adding regulations like we have with the other aspects of the process. But the things that are deceitful are subtle and have an almost infinite variety. And I’m not sure I’d want to routinize publications anyway. It’s stifling. So what to do? Thus, the big question mark… <\/td>\n<\/tr>\n<\/table>\n

Almost anything more than what we have would do something. If the data reports required by clinicaltrials.gov <\/font><\/strong><\/em>were really required, that would’ve been enough to stop a lot of the corruption. The study reports proposed in AllTrials<\/font><\/strong> would do the same thing. Those things work because the mechanisms of deceit are in what’s omitted or in the selective computation and presentation of what is shown. So why isn’t everyone dancing in the streets from the progress made already? Why does Dr. Healy keep writing these pesky doomsday articles like Neal Parker Avoiding Adverse Events<\/a>? Why does Johanna leave us comments like this one<\/a>? For that matter, why do I post something like the devil’s still<\/em> in the details…<\/a> every week or so? Even the nice guys like Ben Goldacre and Fiona Godlee go to parliamentary committees and can get a bit whiny on this topic [goldacre and godlee…<\/a>, a sticky wicket…<\/a>]? The answer is pretty simple. Anything [I mean any- and every-thing] that is prepared by the manufacturer is subject to the same manipulation as these ghost-written jury-rigged articles, no matter what the rules. That’s why. The stakes for them are too high. The temptations are too great. <\/p>\n

I’ve been looking over some of the older studies, ones I looked at back when I first developed this hobby of reading the psychiatric clinical trial literature several years ago. I’m amazed at how easy it is now to see the subtle ways they’ve been written to lean the truth, or omit it, even in some of the non-industry sponsored articles. I’m certainly no ace at spotting all the twists and turns possible, but I’m so much better at it now than I was just five years ago. And back then, I would’ve thought I should’ve been better than most, having been a research type in a former career. I’m still awed at some of the friends I’ve made along the way who have actually been involved in pharmaceutical research and clinical trials. They really do have "the gift" – a sixth sense. They smell deceit. I expect I’ll go through some of those older trials here as examples in the not distant future. <\/p>\n

But for the moment, the point is this. No matter how the AllTrials<\/font><\/strong> campaign or the EMA<\/font><\/strong> data transparency program comes out, there is a bottom line. There has to be a provision that allows access to the data as it came off the press at the last point when the goals of the pharmaceutical company and the needs of the patient who is going to be offered the medication are the same. And that moment is when the raw data as it stands when the blind is broken is revealed. As long as that information is in a safe place and there’s access for checking [for no other reason than it needs checking], we’ve done all we can do. Any program that falls short of that is a loophole awaiting exploitation<\/font><\/strong><\/em>. So everything we are doing right now will help, but without that essential piece, the job has not been completed and the question mark remains…<\/p>\n

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A few days ago, I was talking about a Venn diagram [in proxies…] I’d sketched on the back of an envelope [left above]. A more accurate version of what it really looked like originally is on the right. What I was trying to get at is that in the Clinical Trial process, the motives of […]<\/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":[1],"tags":[],"class_list":["post-40370","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40370","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=40370"}],"version-history":[{"count":19,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40370\/revisions"}],"predecessor-version":[{"id":40389,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40370\/revisions\/40389"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=40370"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=40370"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=40370"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}