Tom Jefferson: The EMA’s policy 0070 is live

Yesterday the European Medicines Agency’s (EMA’s) long awaited policy 0070 went live. I have previously described the policy, its aims, advantages, possible limitations, and potential impact on everyone here and here and here. Briefly, the first phase of the policy sees the release of fundamental components of clinical study reports (CSRs) of randomised controlled trials and other pharmaceutical studies. These complex documents provide a wealth of detail and a chance to minimise the effects of reporting bias, which plagues large swathes of contemporary pharmaceutical trial literature.

I have also shown and discussed the limits of the current 0043 retrospective policy here and here. The release of documents under policy 0043 is slow, inefficient, and cumbersome, but it offers access to reports of trials of pharmaceuticals that are in use today, so it is very much more real than policy 0070, although in time its day to day importance will wane.

Yesterday’s launch provides “only” a quarter of a million pages of reports on two medicines: Kyprolis (carfilzomib), an orphan cancer medicine for multiple myeloma, and Zurampic (lesinurad), an anti-gout compound.

I went on the EMA’s website and, after a simple registration procedure as a researcher (I was asked my passport number), I downloaded a huge compressed file containing 104 reports and appendices on carfilzomib (0.5 giga in size).

The download is straightforward, although we shall have to see how data on other compounds add comprehension and depth to what we currently know (the EMA estimates that it offers access to 4500 reports a year, although it is not clear whether this is a running total or new accesses). For example, out of curiosity I pulled down the main body of carfilzomib study 2011-002 and found that 204 pages out of 748 were completely redacted. This is strange as the attendant anonymisation report grades the risk of re-identification as “low to very low.” Without a review of the whole trial programme, it is not possible to assess the impact of particular redactions, but now such an endeavour is possible for those who are willing to graft.

Here lies one of the conundrums of the present situation.

So far academics have by and large failed to make use of the EMA’s policy of releasing data, something which has puzzled industry. One survey reported that only 7% of Cochrane reviewers considered looking for unpublished data (which includes regulatory data) in their reviews.

As the EMA policy unfolds and more studies comparing trial reports in regulatory submissions with their journal counterparts are published, I would warn users to stay away from trial publications in journals, especially when they do not offer linked access to regulatory submissions. I would also warn all users to stay away from synthesis studies, such as Cochrane reviews, which do not even make an effort to look at regulatory data. “Too difficult” will cost lives, as it already has.

Tom Jefferson, honorary research fellow, the Centre for Evidence Based Medicine, Oxford.

Competing interests: TJ was a recipient of a UK National Institute for Health Research grant for a Cochrane review of neuraminidase inhibitors for influenza. In addition, TJ receives royalties from his books published by Il Pensiero Scientifico Editore, Rome and Blackwells. TJ is occasionally interviewed by market research companies about phase I or II pharmaceutical products. In 2011-13, TJ acted as an expert witness in litigation related to the antiviral oseltamivir, in two litigation cases on potential vaccine related damage and in a labour case on influenza vaccines in healthcare workers in Canada.

He has acted as a consultant for Roche (1997-99), GSK (2001-2), Sanofi-Synthelabo (2003), and IMS Health (2013). In 2014 he was retained as a scientific adviser to a legal team acting on oseltamivir. TJ has a potential financial conflict of interest in the drug oseltamivir. In 2014-16, TJ was a member of three advisory boards for Boerhinger Ingelheim. He is holder of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews. TJ is a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial on an influenza vaccine. Between 1994 and 2013, TJ was the coordinator of the Cochrane Vaccines Field. TJ is a co-signatory of the Nordic Cochrane Centre Complaint to the European Medicines Agency (EMA) over maladministration at the EMA in relation to the investigation of alleged harms of HPV vaccines and consequent complaints to the European Ombudsman.

 

  • jhnoblejr

    Tom,
    I agree with your conclusion, ” . . . I would warn users to stay away from trial publications in journals, especially when they do not offer linked access to regulatory submissions. I would also warn all users to stay away from synthesis studies, such as Cochrane reviews, which do not even make an effort to look at regulatory data. ‘Too difficult’ will cost lives, as it already has.” Nonetheless, I find it a dismal commentary on existing and future guidelines based on so-called “evidence-based medicine.”

    Shouldn’t physicians conspicuously post in their office a sign warning their patients about the uncertainty of the information that guides their practice. Is there not a common law duty to discover and warn consumers about anticipated dangers of use. Travel agencies and tourist guides are in the United States are subject to such law. See: Dickerson, T.A. (1981). Travel Law. New York, NY: Law Journal Seminars-Press, ©1981- Retrieved from http://www.nycourts.gov/courts/9jd/TacCert_pdfs/Dickerson_Docs/Duty_To_Warn_Of_Danger_The_Chinese_Tick_Case4.pdf.

    Should not physicians be held to the same standard? If not, why not?!