Thursday, June 12, 2014

Things that make you go hmmm! EMA policy on transparency is “strikingly” similar to deal struck with drug company, say experts

  1. Peter Doshi
A US drug company seems to have influenced the European Medicines Agency’s (EMA) draft policy on access to clinical trial data, which academics have claimed keeps too much information hidden.
Documents obtained by The BMJ under a freedom of information request showed a significant overlap between what the US drug giant AbbVie had agreed with the EMA could be released about its drug adalimumab (marketed as Humira) and the agency’s draft policy on providing public access to drug company data.
In 2012 the EMA announced a new, “proactive” transparency policy that would give full public access to clinical trial data about drugs authorised for marketing in the European Union from January 2014.1 But draft policy documents on how the system will work have been criticised for being overly restrictive. For example, the “view on screen only” policy will prohibit saving, downloading, or transferring data, limiting how the data can be analysed.2
Beate Wieseler, head of drug assessment at the German Institute for Quality and Efficiency in Health Care (IQWiG) and a vocal proponent of transparency, noted a “striking” similarity between the EMA’s redaction principles and particular elements that AbbVie and the EMA had agreed to redact in the adalimumab clinical study reports (CSRs).
CSRs are detailed reports of drug trials that companies submit to regulators as part of a marketing application. Since November 2010 the EMA has been releasing these documents in response to requests. By late 2012 it had released nearly two million pages of documents, 29% of which were released fully unredacted.
But in 2013 AbbVie took out an injunction to prevent the EMA releasing documents on adalimumab to a competitor. After more than a year of legal wrangling the lawsuits were withdrawn3—which, The BMJ has learnt, came after a series of negotiations between the EMA and AbbVie. During these consultations the EMA agreed a set of redactions in the adalimumab CSRs proposed by AbbVie, which were more extensive than the agency was originally willing to accept.
In a press release in April 2014 the EMA said that the resulting clinical study reports contained “very limited redactions.” But documents obtained by The BMJ have shown the extent of the redactions, which included the determination of trial sample size, exploratory efficacy subgroup analysis, and exploratory secondary endpoint results.
Wieseler said that “redaction of exploratory endpoints and analyses is a problem because these study results are often important for decision making outside regulatory agencies.” As had occurred with the released adalimumab CSRs, the EMA’s draft “redaction principles” document stated that safety and efficacy variables from exploratory analyses “may have to be redacted.”
“The similarity is striking,” said Wieseler, who challenged the notion that the proposed redactions constituted commercially confidential information. The EMA’s redaction “approach contradicts EMA’s own policy in other areas,” she wrote in a letter to The BMJ.4
Noting the quality of life as a prime example, she said, “We found that health related quality of life is often investigated as an exploratory endpoint. These data are very relevant for our benefit assessment; therefore, presentation of these study results should not be at the discretion of the study sponsors.” Wieseler and her colleagues recently studied 101 trials with CSRs and found that outcomes such as quality of life were often reported only in CSRs, not in journal publications.5
When asked about the purported similarities between its policy document and what it had agreed with AbbVie, the EMA said that “any observations concerning similarity are a direct result of having a single standard for what is considered CCI [commercially confidential information] regardless of access route.” But Trudo Lemmens, a professor of law at the University of Toronto, said that the EMA “seems to have returned very much to the former approach of giving companies a lot of leeway in deciding what they consider to be confidential.”
In 2012 Guido Rasi, executive director of the EMA, had said, “We are not here to decide if we publish clinical trial data, but how.” However, in their letter to The BMJ Wieseler and her colleagues wrote, “One and a half years later, the ‘if’ is at stake.”
The EMA rejected this characterisation. “The agency maintains that the vast majority of data within the CSR is not CCI and will be accessible to the public upon decision. The small remainder which may be CCI is open to a justification and review process which the agency controls,” a spokesperson said.
The BMJ asked AbbVie why it considered the redactions to its documents on adalimumab necessary and whether they undermined researchers’ ability to analyse the data. Dirk van Eeden, senior director of public affairs at AbbVie, responded, “AbbVie and the EMA agreed that a significant portion of data would be disclosed while protecting the information that is commercially sensitive. This allowed the EMA to revise its decision regarding AbbVie’s study reports.”


Cite this as: BMJ 2014;348:g3852


  • Competing interests: The BMJ has campaigned for more transparency at EMA, notably for oseltamivir data, and I am a member of the Cochrane review group that analysed these data. I also personally know Beate Wieseler and Trudo Lemmens and recently coauthored a blog with Trudo Lemmens on this topic.


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