1 Boring Old Man

The EMA appears poised to make a major U-turn on its transparency initiatives, reversing its principle of public access to clinical trial data as its sets up a system of controlled access similar to those independently established by industry. This is a stunning and surprising reversal, particularly as it comes after AbbView dropped its lawsuit against EMA and after the passing of the European clinical trials legislation which will require public access to clinical study reports. If finalized, the EMA’s new policy will prohibit a data requestor from even printing out a redacted clinical study report: they must instead read it in a so-called “view on-screen-only” mode. In the first half of 2013, the EMA held a series of teleconferences with its five advisory committees to obtain guidance on developing a policy for the draft policy on proactive publication of and access to clinical-trial data. Individuals serving on the advisory committees came from academia, industry, and other sectors. The process was open, transparent, and inclusive. We served on some of these advisory committees. The process culminated in the publication, on June 24, 2013, of a draft policy document titled “Publication and access to clinical-trial data” [EMA/240810/2013]. The EMA invited public comments on this document, and received more than 1,000 submissions from stakeholders [http://tinyurl.com/k9a2plb].

This week, the EMA is discussing the finalization of its policy. Documents distributed prior to the meeting indicate that a major U-turn is about to occur.  Under the draft Terms of Use policy document: “ the User [data requestor] acknowledges that the Information [meaning Clinical Study Reports as well as other types of documents] will be made available to the User in a “view-on-screen-only” mode, after completing the registration process. The User agrees that the User is not permitted to download, save, edit, photograph print, distribute or transfer the Information. The User agrees not to access the Information using a method other than the interface provided by the EMA, or remove, bypass, circumvent, neutralise or modify any technological protection measures which apply to the Information.”

The EMA’s June 2013 draft policy document suggested that clinical study reports were largely “open access” documents, with only those sections containing individual participant data necessitating a “controlled access” scheme [See Annex II of the June 2013 draft policy]. However, the new Terms of Use document indicates that EMA now plans to treat clinical study reports as “controlled access” documents. Taking the “public” out of “publication.” While the draft policy is titled “Publication and access to clinical-trial data,” it is no longer clear what—if any—data will be published i.e. made public. The draft Terms of Use make clear that Clinical Study Reports will not be published, but instead only made accessible [but not downloadable, printable, photographable, or salvable] to those granted access.

Redacting Clinical Study Reports

A separate draft “Redaction principles” policy document sets forth a framework for redacting Clinical Study Reports. “In general, much of the information in CSRs pertaining to study designs, statistical analyses, and study results would not be considered CCI [commercial confidential information],” the EMA writes. The document however outlines the “limited circumstances where such information could constitute CCI,” leading to redactions. For example, the EMA writes that “statements/descriptions relating to objectives that are not supportive of a label claim and do not contribute to the overall benefit/risk evaluation” may be considered commercial confidential information, and therefore redacted. This would appear to suggest that trials for off-label uses of drugs will not be made available. However the vague wording of the text leaves the door open to a variety of interpretations, as the cook said the proof will be in the pudding, but by the time proof is available it will be too late. The document also suggests that “there may be occasions” when the Clinical Study Report’s description of the sample size calculation will be redacted. This could occur, the EMA writes, when information used in the calculation “is considered CCI,” but it is unclear who would make this determination. CSR[a] and CSR[b]

Perhaps most surprising is the concept of “CSR [a]” and “CSR [b]”. Under thisscheme, sponsors submitting Clinical Study Reports as part of their marketing authorization application would submit two Clinical Study Reports for each trial: a standard one [CSR[a]] and one redacted one [CSR[b]]. The scheme puts primary responsibility for redacting in the hands of sponsors. “If EMA disagrees” with some of the redactions, “the Consultation Process is initiated,” presumably until the sponsor and EMA agree. How close CSR[a] is to CSR[b], and what parts are missing, may never be known to third party data requestors.

Irony

The irony of EMA’s apparent U-turn is that since late 2010, while the EMA has been deliberating over its “prospective” policy, there was a separate “reactive” policy in place. This was to release the “legacy” clinical study reports not covered by their “prospective” policy. Under this the agency has released 2 million pages of clinical study reports and other internal documents. These documents were released electronically, with no restrictions on use, re-use, or distribution, and at no-cost. Clinical study reports were often completely unredacted, such as the over 20,000 pages of Clinical Study Reports we received for oseltamivir [Tamiflu].