Is the Lady U-Turning?
Peter Doshi, Tom Jefferson
May 16, 2014
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 <tel:240810%2F2013>). The EMA
invited public comments on this document, and received more than 1,000
submissions from stakeholders (European Medicines Agency updates on development of its policy on publication and access to clinical-trial data | European Medicines Agency). 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).1?3
If the draft policy goes live on 12th of June as scheduled unchallenged,
working on clinical study reports to circumvent the problems of
reporting bias will become even more difficult. Remote viewing and
impossibility of analyzing and cross
checking (the kind of activity which is necessary) will be more
difficult and the constraints of screen shots will make navigation
well-near impossible. Is this the aim of the U-turn?
Peter Doshi, assistant professor, Department of Pharmaceutical Health
Services
Research, University of Maryland School of Pharmacy, Baltimore, MD 21201,
USA, pdoshi@rx.umaryland.edu <mailto:pdoshi@rx.umaryland.edu>
Tom Jefferson, Reviewer, Cochrane Acute Respiratory Infections Group, 00187,
Roma, Italy. jefferson.tom@gmail.com <mailto:jefferson.tom@gmail.com>
Disclosures
Both authors are co-recipients of a UK National Institute for Health
Research grant (HTA - 10/80/01 Update and amalgamation of two Cochrane
Reviews: neuraminidase inhibitors for preventing and treating influenza
in healthy adults
and children - http://www.nets.nihr.ac.uk/projects/hta/108001). In
addition: Dr Doshi received ?1500 from the European Respiratory Society
in support of his travel to the society?s September 2012 annual congress
in Vienna, where he
gave an invited talk on oseltamivir. Dr Doshi is an Associate Editor of
The BMJ. Dr Jefferson receives royalties from his books published by
Blackwells and Il Pensiero Scientifico Editore, Rome. Dr Jefferson is
occasionally interviewed by
market research companies for anonymous interviews about Phase 1 or 2
pharmaceutical products. In 2011-2013 Dr Jefferson acted as an expert
witness in a litigation case related to oseltamivir phosphate; Tamiflu
[Roche] and in a
labour case on influenza vaccines in health care workers in Canada. In
1997-99 Dr Jefferson acted as consultant for Roche, in 2001-2 for GSK
and in 2003 for Sanofi-Synthelabo for pleconaril (an anti-rhinoviral
which did not get approval
from FDA). Dr Jefferson was a consultant for IMS Health in 2013 and is
currently retained as a scientific advisor to a legal team acting on the
drug Tamiflu (oseltamivir, Roche).
References
1.Doshi P, Jefferson T. The first 2 years of the European Medicines
Agency?s policy on access to documents: secret no longer. JAMA Intern
Med. 2013 Mar 11;173(5):380?2.
2. Doshi P. Transparency interrupted: The curtailment of the European
Medicines Agency?s policy on access to documents. JAMA Intern Med
[Internet]. 2013 Aug 19 [cited 2013 Aug 20]; Available from:
http://dx.doi.org/10.1001/jamainternmed.2013.9989
3. Jefferson T, Doshi P. Multisystem failure: the story of
anti-??influenza drugs. BMJ. 2014;348:g2263.
El 16/05/2014 19:24, Juan G?rvas escribi?:
-se confirma, la Agencia Europea del Medicamento pretende limitar el
acceso a los datos de los ensayos cl?nicos hasta extremos que sea una
burla.
*EMA changed confirmed. European Ombudsman concerned about change of
policy at Medicines Agency as regards clinical trial data transparency.*
_El Defensor del Pueblo, Europa, preocupado por el cambio de rumbo de
la Agencia de Medicamtos, contra la transparencia de ensayos cl?nicos._
/European Ombudsman
-un saludo
-juan g?rvas
@JuanGrvas
2014-05-15 8:39 GMT+02:00 Juan G?rvas <jjgervas@gmail.com
<mailto:jjgervas@gmail.com>>:
*BE AWARE, EMA IS BACK PEDALLING
*
*There are signs the European Medicines Agency may be
backtracking on commitments to ensuring full access to
unpublished clinical trial data. *
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