The association for the research-based pharmaceutical industry in Europe has challenged on ethical, legal and technical grounds the EMA’s draft policy on publication of, and access to, clinical-trial data. 

The European Federation of Pharmaceutical Industries and Associations (EFPIA) says it has “serious concerns” about the draft policy put out for consultation by the European Medicines Agency last June.

According to EFPIA, the policy as it stands “carries negative implications for public health in its failure to adequately protect the interests of patients and the research they benefit from”.

Under the EMA’s proposals, clinical-trial data, information or documents not subject to restrictions on access to commercially confidential information (CCI) or personal data would be available to download once the agency had published its European public assessment report on an application for centralised marketing authorisation.

Raw clinical-trial data that raised concerns about protection of personal data (PPD) would be subject to controlled access involving conditions such as a minimum standard of de-identification and a legally binding data-sharing agreement.

The EMA has also promised to “put in place measures to ensure the best-possible protection of public health (and regulatory decisions) against claims resulting from inappropriate analyses” of available clinical-trial data.  

Joint Principles

In July EFPIA and its US counterpart, the Pharmaceutical Research and Manufacturers of America (PhRMA), countered with a more restrictive set of joint Principles for Responsible Clinical Trial Data Sharing: Our Commitment to Patients and Researchers.

These involve sharing patient- and study-level clinical-trial data, full clinical-study reports, and protocols from trials approved in the US and the EU, with “qualified scientific and medical researchers upon request and subject to terms necessary to protect patient privacy and confidential commercial information”.

Under the joint Principles, synopses of clinical-study reports filed with the US Food and Drug Administration, the EMA or national authorities in EU member states will be made publicly available when a new medicine or indication is approved

Moreover, companies adhering to the Principles will seek to publish results from all Phase III clinical trials, as well as any results of “significant medical importance”, regardless of outcome. 

Full response

EFPIA has now filled in some of the detail behind its position by publishing a comprehensive response to the EMA’s draft policy on publication of, and access to, clinical-trial data.

The association’s three primary concerns are that the EMA’s approach to the data transparency issue will:

• Weaken safeguards intended to ensure the privacy of patients and other individuals identified in marketing authorisation application (MA) dossiers.                
• Undermine trust in the regulatory approval system for biopharmaceutical products and introduce into the process “risks of misinterpretation and misuse of clinical data”.  
• Weaken incentives for investment in biomedical research by disclosing companies’ CCI “without due consideration of the competing interests that may or may not justify disclosure”.

Patient protection

While industry has a vested interest in navigating concerns about data privacy to access electronic patient records, so that it can supplement conventional clinical trials (or design those trials more efficiently) using ‘real-world’ data, in this case it is laying the emphasis on patient protection.

Recent studies have “tested long-held assumptions that de-identifying data protects patient privacy and have shown that the risk of re-identification is particularly acute when de-identified data are made widely available”, EFPIA contends.

In ensuring that data de-identification measures were sufficient to protect patients, the EMA would need to consider “not only the clinical data themselves, but also all other public information that could be combined with study data to deduce subject identities, including discharge data, data in public study databases, claims data, US and EMA clinical trials databases, and even social media”, it says. 

In relation to ‘open access’ data, the EMA’s draft policy stipulates that marketing-authorisation applicants should provide an additional set of documents “appropriately de-identified to ensure protection of personal data”, EFPIA notes.

Notwithstanding “the efforts that would be required of MA applicants to de-identify documents”, it would be the EMA “making the actual disclosures from its website” in these circumstances, it adds.

As such, the agency would be legally responsible “for the publication of any information released”, the association warns.

Data Protection Regulation

EFPIA also cites the EMA’s obligations under the European Union’s Data Protection Regulation, claiming that without “the agreement of EU data protection authorities … on when data can be deemed ‘anonymised’, MA applicants would have to “comply with the most conservative national privacy laws, which could mean the marking of all data containing indirect identifiers as potentially personal data”.

Also imperative, the association insists, is “respect for the terms of the informed consent given by the patients participating in clinical trials, both in the EU and third countries, with regard to the subsequent or secondary use of their data (whether ‘anonymised’ or not), as a matter of ethics and a central tenet of good clinical practice”.

While the draft Policy refers to the “spirit of informed consent”, in reality “trial sponsors (and by definition, any other party handling the data, including the EMA) must respect the informed consent in its particular terms and according to the laws of the country where it was given”, EFPIA stresses. 

Secondary research

The association goes on to question the adequacy of the controls set out in the EMA’s draft policy to ensure that any secondary research/analyses using patient-level data from clinical trials would be “robust and scientifically credible”.

Essentially, EFPIA argues, any researchers requesting controlled access to patient-level data “should be held to the same standard as the clinical trial sponsor in terms of transparency, namely to (i) publicly register their research before initiation and (ii) post the results of their research within one year of completion”.

Moreover, the proposed mechanism for access “does not include any review of the purpose for which data will be used or the relevance of the proposed research to medical science or patient care”.

EFPIA believes that “a case-by-case assessment is necessary to determine whether access to ‘CT data with PPD concerns’ is justified in any given case”. Without such a review, it is “unclear how the proposed mechanism will meet the stated requirement that ‘analyses are in the interest of public health, in line with the spirit of informed consent’”.

CCI disclosure

The third strand of EFPIA’s objections to EMA’s draft policy relates to the agency’s assurances that commercially confidential information will not be divulged through the data-access mechanism – yet qualified by an assertion that “in general, however, CT data cannot be considered CCI; the interests of public health outweigh considerations of CCI”.

In the association’s view, this claim “is inconsistent with core protections afforded to MA applicants/holders under EU law”. Moreover, the EMA itself defines CCI in the draft policy as “any information that is not in the public domain or publicly available and where disclosure may undermine the legitimate economic interest of the owner of the information”.

Some information in certain marketing authorisation dossiers – depending on the sponsor, product at issue, therapeutic area, and value of the information to competitors – “may, indeed, meet the EMA’s definition of CCI”, EFPIA says.

Clinical-trial data within the dossier “may include commercially sensitive information, the protection of which helps incentivise companies to continue innovating and investing in medical and scientific research”, it adds.

“This appears to be evidenced by the fact that the majority of requests for disclosure are from pharmaceutical companies as opposed to healthcare professionals or members of the public.”

Robust procedure

As a consequence, the EMA should develop and implement “a robust procedure for the consultation of the marketing authorisation holder and review of the data proposed for disclosure, and for the MAH to appeal against the EMA’s decision to disclose, in advance of any disclosure of information (i.e., ‘open’ or ‘controlled’ access)”, EFPIA proposes.

A ‘stepwise analysis’ of whether the public interest might demand disclosure of CCI in a MA dossier “ is, in fact, required by EU law pursuant to Article (4)(2) of Regulation 1049/2001 Regarding Public Access to Documents”, it maintains.

Article (4)(2) “expressly states that EU institutions, including the EMA, will refuse public access to documents that would undermine the protection of the commercial interests of a natural or legal person unless there is an overriding public interest in disclosure”, the association insists.

Moreover, this view “is also consistent with Article 39(3) of the TRIPS Agreement, which obliges the EMA to protect against release of data submitted for MA purposes, ‘[e]xcept where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair commercial use’”.

EFPIA’s complete response to the EMA’s consultation can be found on the association’s website at http://transparency.efpia.eu/responsible-data-sharing.