{"id":50383,"date":"2014-10-03T07:35:06","date_gmt":"2014-10-03T11:35:06","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=50383"},"modified":"2014-10-03T14:30:11","modified_gmt":"2014-10-03T18:30:11","slug":"beyond-the-blind","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2014\/10\/03\/beyond-the-blind\/","title":{"rendered":"beyond the blind…"},"content":{"rendered":"\n
In the course of life, I had a hand in the later raising of an orphan, and I knew nothing of an orphan mentality. She hadn’t been abused, but she had been chronically deprived for much of her life. To my surprise, she was never satisfied. She had no concept of "enough" – so she always felt disappointed and was only comfortable in a somewhat deprived state. I had to learn that my natural inclination to be on the indulgent side [making up for the past] only made her sick, and that the right course of action was to provide only the "right amount" and accept her chronic state of disappointment as her necessary comfort zone. "Too much" was just as disastrous as "not enough." I’m pleased to report that it worked out in the end, but the path was slow and had more than its share of bumps. While it’s a trivial adage, "don’t go to the grocery store hungry" seems to apply.  Substitute the word "starved," and you’re close to understanding the orphan dilemma.<\/em><\/div>\n
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Publication of clinical reports<\/a><\/div>\n
EMA adopts landmark policy to take effect on 1 January 2015<\/font><\/strong><\/div>\n
Press release<\/font><\/strong><\/div>\n
October 2, 2014<\/div>\n

The European Medicines Agency [EMA] has decided to publish the clinical reports that underpin the decision-making on medicines. Following extensive consultations held by the Agency with patients, healthcare professionals, academia, industry and other European entities over the past 18 months, the EMA Management Board unanimously adopted the new policy at its meeting on 2 October 2014. The policy will enter into force on 1 January 2015. It will apply to clinical reports contained in all applications for centralised marketing authorisations submitted after that date<\/font><\/strong><\/em>. The reports will be released as soon as a decision on the application has been taken.<\/font><\/strong><\/em><\/p>\n

“The adoption of this policy sets a new standard for transparency in public health and pharmaceutical research and development,” said Guido Rasi, EMA Executive Director. “This unprecedented level of access to clinical reports will benefit patients, healthcare professionals, academia and industry.”<\/p>\n

The new EMA policy will serve as a useful complementary tool ahead of the implementation of the new EU Clinical Trials Regulation that will come into force not before May 2016. EMA expects the new policy to increase trust in its regulatory work as it will allow the general public to better understand the Agency’s decision-making. In addition, academics and researchers will be able to re-assess data sets<\/font><\/strong><\/em>. The publication of clinical reports will also help to avoid duplication of clinical trials, foster innovation and encourage development of new medicines.<\/p>\n

According to the policy’s terms of use, the public can either browse or search the data on screen, or download, print and save the information. The reports cannot be used for commercial purposes. In general, the clinical reports do not contain commercially confidential information<\/span>. Information that, in limited instances, may be considered commercially confidential will be redacted.<\/font><\/strong><\/em> The redaction will be made in accordance with principles outlined in the policy’s annexes. The decision on such redactions lies with the Agency.<\/p>\n

The policy will be implemented in phases. The first phase starts on 1 January 2015. Once a medicine has received a marketing authorisation, EMA will publish the clinical reports supporting applications for authorisation of medicines submitted after the policy’s entry into force. For line extensions and extensions of indications of already approved medicines, the Agency will give access to clinical reports for applications submitted as of 1 July 2015 after a decision has been taken.<\/p>\n

In future, EMA plans to also make available individual patient data.<\/font><\/strong><\/em> To address the various legal and technical issues linked with the access to patient data, the Agency will first consult patients, healthcare professionals, academia and industry. It is critically important for EMA that the privacy of patients is adequately protected before their data are released.<\/p>\n

The policy does not replace the existing EMA policy on access to documents. It will be reviewed in June 2016 at the latest.<\/div>\n<\/blockquote>\n
The decision of the EMA has been long awaited and is still incomplete. When it showed up yesterday, I scanned it and some of the reactions – then let it sit for a while. I realized that in this case, I’m in the orphan class ["been down so long it looks like up to me<\/em>"]. And reading worry…<\/a>, it’s easy to see that I’m primed to be disappointed. It’s not hard to see paranoia in others, but not nearly so simple in the mirror. Inserting some time is a good antidote. So if I can be allowed to revive my monotonous graphics:<\/div>\n

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There are four documents generated from a Clinical Trial: a Protocol<\/font><\/strong>, the CRFs<\/font> [Case Report Forms], the IPD<\/font><\/strong> [Individual Participant Data], the CSR<\/font><\/strong> [Clinical Study Report]. Oh yeah, I guess we could add the published [or maybe unpublished] journal article<\/font><\/strong>, bringing the total to five documents [see it matters…<\/a>]. In the absence of outright fraud, three of them come from "behind the blind," in other words, they are what the investigators [and sponsors] see when the "blind is broken." If you have those three things, the playing field is level. Someone evaluating the study from afar is in the same boat as those who did it. We’re talking about a gajillion pages [every piece of paper from every visit by every subject, the CRF<\/font><\/strong>s, AND the tables compiled into the IPD<\/font><\/strong> of everything that can be objectified and tabulated]. It’s an overwhelming stack of stuff.<\/p>\n

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After the blind is broken and the data is at hand, it is collated, analyzed, and turned into the CSR<\/font><\/strong> – a manageable report for regulators that will later be simplified further to become a journal article<\/font><\/strong> [or not]. While there are plenty of computers whirring at this point in the process, there are real live people with real live motives also in the mix, and this is where the problems have come from – beyond the blind<\/em>:<\/p>\n

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What the orphan in me wants is all of it. I want the Protocol<\/font><\/strong>, the CRF<\/font><\/strong>s, and the IPD<\/font><\/strong>. I want to to be level with the investigators\/sponsors. I’m understandably "starved.<\/em>" The CSR<\/font><\/strong> will contain the Protocol<\/font><\/strong> and in some cases, the IPD<\/font><\/strong> as Appendices, but that last part isn’t guaranteed, and I doubt it will continue under this policy. The raw CRF<\/font><\/strong>s won’t be in the CSR<\/font><\/strong>. So where does that leave us? The downside is that the CSR <\/font><\/strong>is prepared by those pesky, motivated humans. So the possibility of sleight of hand is there as it is with the messy journal article<\/font><\/strong>s we’ve lived with for too long. And, they<\/em> get to pick what’s in them. On the other hand, it puts us on the same level as the regulators who have the ultimate power – saying "No"<\/font><\/strong> to approving the drug. And that first paragraph up there has a key sentence, "The reports will be released as soon as a decision on the application has been taken.<\/font><\/strong><\/em>" And this promise sounds pretty good too, "In future, EMA plans to also make available individual patient data.<\/font><\/strong><\/em>" Not guaranteed, but at least an acknowledgement of the need. The piece that’s missing is the CRF<\/font><\/strong>s, necessary for a thorough vetting of the Adverse Events.So does it pass the Rolling Stones test:<\/div>\n