{"id":67326,"date":"2016-08-13T07:00:40","date_gmt":"2016-08-13T11:00:40","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=67326"},"modified":"2016-08-13T18:09:46","modified_gmt":"2016-08-13T22:09:46","slug":"the-wrong-tree","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/08\/13\/the-wrong-tree\/","title":{"rendered":"the wrong tree…"},"content":{"rendered":"\n
On my trip, I was thinking about the years of the abuse of the clinical trial system – wondering what could be done to put a stop to it? What creative reform would finally save the day? There have been so many attempts, and yet it goes on and on, at least with the psychiatric drugs I’m familiar with. And it dawned on me that I might be asking the wrong question. There’s nothing wrong with the reforms that have already been instituted, nothing except for one not-so-minor detail – they’ve been largely ignored<\/font><\/em>.<\/div>\n

Take for example preregistration. An essential element of any credible clinical trial is a declaration of the outcome variables prior to beginning the study. The elements of the design are Randomization<\/font><\/em>, Double Blinding<\/font><\/em>, Preregistration of Outcomes<\/font><\/em> followed by Replication<\/font><\/em> of positive results with a follow-up study. Here’s a contemporary snapshot of what actually happens: <\/p>\n\n\n\n\n\n\n
outcome switching – The COMPare Project<\/font><\/strong><\/em> <\/td>\n<\/tr>\n
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rules<\/font><\/strong><\/em><\/sup><\/td>\nIt is imperative that a trial sponsor declare the outcome variables before<\/u> the trial begins <\/font><\/em><\/strong>[see The Meaning of “Significance” for Different Types of Research<\/a>, the hope diamond…<\/a>, Why we need pre-registration<\/a>, For Preregistration in Fundamental Research<\/a>].<\/sup><\/td>\n<\/tr>\n
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reality<\/font><\/strong><\/em><\/sup><\/td>\n\n

Ben Goldacre has been a tireless campaigner against the secrecy afforded the pharmaceutical industry with their clinical trial data. His AllTrials campaign has alerted us all to the problem, but it has been stymied and undermined by industry every step of the way. It’s still viable, but disappointing in that we still don’t have the data access we need. But he’s got another trick up his sleeve that seems to be moving right along in his campaign. He’s looking at how closely recent Clinical Trials adhere to preregistration, something he calls Outcome Switching:
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The COMPare Trials Project.<\/font><\/strong><\/em><\/sup><\/div>\n
by Ben Goldacre, Henry Drysdale, Anna Powell-Smith, Aaron Dale, Ioan Milosevic, Eirion Slade, Philip Hartley, Cicely Marston, Kamal Mahtani, Carl Heneghan.<\/sup><\/div>\n
www.COMPare-trials.org<\/a>, 2016.<\/sup><\/div>\n

Here again, the rule is to report on the a priori<\/em> declared outcome variables. This is what Goldacre’s group reports finding on recently reported trials [major journals]:<\/sup><\/p>\n\n\n\n
TRIALS
CHECKED<\/font><\/strong><\/sup><\/td>\n		TRIALS WERE
PERFECT<\/font><\/strong><\/sup><\/td>\n		OUTCOMES NOT
REPORTED<\/font><\/strong><\/sup><\/td>\n		NEW OUTCOMES
SILENTLY ADDED<\/font><\/strong><\/sup><\/td>\n<\/tr>\n
67<\/font><\/strong><\/sup><\/td>\n9<\/font><\/strong><\/sup><\/td>\n354<\/font><\/strong><\/sup><\/td>\n357<\/font><\/strong><\/sup><\/td>\n<\/tr>\n<\/table>\n

After the data is in hand, one can do all kinds of statistical tests on the results, thumbing through all the possible outcome variables until you find something that gives you the p-value you want. This is probably the most abused rule of them all in the jury-rigging of clinical trial results. <\/sup><\/p>\n

9 ÷ 67 = 13%<\/font><\/strong>. That’s pitiful…<\/sup><\/div>\n<\/td>\n<\/tr>\n<\/table>\n

And looking at the multiple attempts to insist on preregistration, compliance with the rules [some of which are actual laws] mirrors these findings… <\/p>\n\n\n\n\n\n\n
clinicaltrials.gov – preregistration\/results<\/font><\/strong><\/em> <\/td>\n<\/tr>\n
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rules<\/font><\/strong><\/em><\/sup><\/td>\n\n
Since 2007, the rules have been crystal clear – actual law. Trials are to be registered before they’re begun, and the results published within the first year following completion. There’s no ambiguity in what’s supposed to happen.
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reality<\/font><\/strong><\/em><\/sup><\/td>\n\n
If I ever have to justify the name of this blog [1boring<\/u>oldman<\/em>], I will probably present a monotonous list of my posts pointing out how the pharmaceutical companies [AND NIMH grant recipients] have been noncompliant with the mandates for timely PRE-registration and later posting results on clinicaltrials.gov. There’s no rational reason for their ignoring this requirement. They already have the data, and the system is simple. They’re given plenty of time. But they’ve just ignored it. This is a partial listing of my posts on this point: transparency!…<\/a>, studying the studies…<\/a>, what dreamer?…<\/a>. non·random missing·ness…<\/a>, speaking of about time!…<\/a>, Beware of Shiny Objects!…<\/a>, back on track…<\/a>, never been imposed…<\/a>, a dreamer…<\/a>, wolf alert! wolf alert!…<\/a>, etc. And an exempler article [among many] available on-line:.<\/sup><\/div>\n