Author Affiliations: Researcher, The Cochrane Collaboration, Rome, Italy (Dr Jefferson). Dr Doshi is a postdoctoral fellow at Johns Hopkins University School of Medicine, Baltimore, Maryland.
On November 30, 2010, the regulatory agency for medications in Europe, the European Medicines Agency (EMA), announced a policy on access to “any document originated, received or held by the Agency.”1 The policy made a wide range of regulatory documents potentially accessible to anyone who asks for them, including clinical study reports.2 Documents are released without charge, primarily in PDF format, and made available via a web-based download. We used this policy and received 25 000 pages of previously unreleased clinical study reports on Roche's oseltamivir phosphate (Tamiflu) trials, all unredacted. This formed the basis of our recent Cochrane review on neuraminidase inhibitors.3 The release of such documents contrasts with the approach of the US Food and Drug Administration (FDA), which similarly has a freedom of information policy but treats industry-sponsored clinical trial data as confidential and trade secret, denying public release on the grounds that disclosure could cause competitive harm to original study sponsors.4 We sought to inform discussion of access to clinical trial data by describing how the EMA's policy is being used.
We requested from the EMA a log of all requests for documents handled under the Agency's new policy (ie, since November 30, 2010) and received a table, dated November 19, 2012, of 457 requests containing details of each applicant's affiliation (categorized by the EMA), a brief description of documents requested, the date the request was received, the date of last response from the EMA, and the disposition of the request (eg, pending, open, or closed; full, partial, or no access granted; and total pages released)
(eAppendix). We summarized the information as follows: who requested information; what was requested; for partially fulfilled (part redacted) and fully fulfilled (unredacted) requests, how much was being released (as median number of pages per request and total per category of requestor's affiliation); and time to release of information (as median days per request) by the EMA. Because the request log represents a snapshot point in time, page counts in some cases represent only a partial fulfillment of a request. Time to first access of documents could not be determined because the information is not in the request log. We instead computed a time to access of the total number of pages thus far released. Institutional review board approval was not sought because no patients were involved in the study.
The EMA received 455 requests for information (2 separate requests were received prior to, but handled under, the new policy)—178 requests during the first year and 277 in the second (eFigure). No information was provided about the number of unique requestors. There were 31 requests that were pending after a median 28 days (interquartile range [IQR], 6-55 days [range, 4-110 days]). Approximately one-quarter (124 of 457) of all requests were closed with no documents released. Ten of these had time expired (owing to a lack of response to the EMA's request for clarification). Of the 302 requests that resulted in the release of documents, the median number of pages released per request was 81 pages (IQR, 17-825 pages [range, 1-254 251 pages]). Of 302 requests, 88 (29%) were released in full without redaction (304 876 pages). Median time to access of the total number of pages was 26 days (IQR, 16-60 days [range, 0-644 days]). Altogether, the EMA released 1 656 285 pages in the first 2 years of its policy. Requests made by the pharmaceutical industry, media, and legal affiliates were the majority of the 457 requests (Table). Requested materials varied widely, with at least 30 different types of EMA regulatory documents as well as data related to marketing authorization applications. The most frequently requested document types were assessment reports, dossiers, and clinical study reports. The largest releases were for clinical study reports for marketed, withdrawn, and never-approved medicines (at least 29 requests).
Since November 2010, the EMA has released many kinds of documents to a variety of applicants. Industry made the most requests and received the most pages (491 989). Health care professionals and the general public were far smaller beneficiaries, perhaps because of ignorance of the policy change and unfamiliarity with its use. Twenty-seven percent of requests were not granted access, sometimes simply because of nonapplicability (documents not held by the EMA) or time expiration (no response to the EMA's request for clarification). Limitations of this study include an inability to calculate the proportion of pages redacted. We only know that 71% of requests included at least 1 redaction, but in our experience with the release of clinical study reports, the redactions were minor and of no impact to interpretation of text, eg, redaction of patients' date of birth. Other limitations included possible misclassification of requests (eg, “industry” could request through “legal”); lack of knowledge of intended use of documents (the EMA is not legally allowed to query the purpose for which requests are made); and an inability to judge the long-term impact of EMA's policy (eg, competitive harm to trial sponsors). In the future, the EMA is likely to release more clinical trial data. While this study evaluated EMA's “reactive” disclosure policy, on January 1, 2014, the agency also intends to start a “proactive” policy on publication of clinical trial data.5
Published Online: December 19, 2012. doi:10.1001/jamainternmed.2013.3838
Correspondence: Dr Doshi, Johns Hopkins University School of Medicine, Reed Hall West, Room 201-C, 1620 McElderry St, Baltimore, MD 21205 (firstname.lastname@example.org).
Author Contributions: Dr Doshi had full access to the request logfile used in the study and takes responsibility for the accuracy of the data analysis. Study concept and design: Doshi and Jefferson. Acquisition of data: Doshi. Analysis and interpretation of data: Doshi and Jefferson. Drafting of the manuscript: Doshi and Jefferson. Critical revision of the manuscript for important intellectual content: Doshi and Jefferson. Statistical analysis: Doshi.
Conflict of Interest Disclosure: Dr Doshi received [euro]1500 from the European Respiratory Society in support of his travel to the society's September 2012 annual congress, where he gave an invited talk on oseltamivir. Dr Jefferson receives royalties from his books published by Blackwells and Il Pensiero Scientifico Editore, none of which are on clinical study reports. In 2011-2012, Dr Jefferson acted as an expert witness in a litigation case related to an antiviral (oseltamivir phosphate; Tamiflu [Roche]). Dr Jefferson is on a legal retainer for expert advice on litigation for influenza vaccines in health care workers. Drs Doshi and Jefferson also personally know some European regulators who share an interest in this topic.
Funding/Support: Both authors are co-recipients of a UK National Institute for Health Research grant to carry out a Cochrane review of neuraminidase inhibitors (http://www.hta.ac.uk/2352). Dr Doshi is funded by an institutional training grant from the Agency for Healthcare Research and Quality (#T32HS019488).
Additional Contributions: David Mackay, BVetMed, MSc, PhD, MRCVS, of the European Medicines Agency, closely reviewed the manuscript for accuracy and provided many clarifications about the EMA's policy. Dr Mackay received no compensation for his assistance.
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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.. Published online December 19, 2012. doi:10.1001/jamainternmed.2013.3838
eFigure. Number of requests submitted to the European Medicines Agency, per month (November 30, 2010, to November 19, 2012)
eAppendix. European Medicines Agency (EMA) request logfile (see Excel spreadsheet)
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