Overview

Following a consultation which began in November 2012, the European Medicines Agency (EMA) has recently adopted a new policy for the proactive disclosure of clinical reports which will make them more widely accessible to the public.

The new policy will apply to clinical reports submitted to the EMA as part of

  • applications for new marketing authorisations made under the centralised authorisation procedure on or after 1 January 2015; and
  • extension applications made under the centralised authorisation procedure on or after 1 July 2015.

This approach will result in data from clinical reports being published by the EMA following the grant, refusal or withdrawal of the relevant application. Applicants//Marketing Authorisation Holders (MAHs) will have a limited ability to redact data they consider to be commercial confidential information (CCI). Once published, the clinical data will be available for use for certain non-commercial purposes, subject to compliance with the EMA’s Terms of Use which will confer rights directly upon the applicant/MAH.

Applicants/MAHs will need to carefully consider what data in the clinical reports to be submitted they wish to redact and to clearly articulate their justifications for any proposed redactions. It will also be necessary for applicants/MAHs to understand what rights they have to challenge a decision of the EMA, their rights against the registered users of the data under contract and how they may be able to prevent misuse by any third party.

This briefing summarises the current disclosure approaches and the new proactive approach.

Current approaches to the release of clinical data

The current approaches of the EMA to transparency cover both the reactive and proactive release of clinical data.

The EMA’s current approach to the requested release of documents received or held by the EMA under ‘Policy on access to documents (related to medicinal products for human and veterinary use)' Policy 00431 has been in effect since 1 December 2010. This may include the release of clinical reports. Related EMA guidance states that:

“In general, the data included in clinical trial study reports is considered as data that can be released as such data is not considered either commercially confidential…that should be protected. In the case of exceptional and substantiated cases, particularly where innovative study designs and/or innovative analytical methods have been used, consideration will be given to the need for redaction.”2

The EMA is also involved in a separate process for the proactive release of clinical study result summaries on the EU Clinical Trials Register. These summaries will be generated from result-related data required to be entered into the EU’s EudraCT database by sponsors of clinical studies.

A comparative summary of the current and new approaches to release of clinical study data by the EMA is set out in the table below. A more detailed discussion about the EMA’s new policy follows.

Click here to view table.

The EMA’s new approach to the release of clinical reports - Policy 0070

After a detailed consultation process which began in November 2012, the final proactive ‘European Medicines Agency policy on publication of clinical data for medicinal products for human use’ Policy 0070 was adopted on 2 October 2014. Policy 0070 will be effective from 1 January 2015. A Q&A document has also been published by the EMA.

Policy 0070 will be implemented in two phases.

  • The first phase concerns the publication of clinical reports only on the EMA’s website.
  • A second phase, the EMA will find a way to make Individual Patient Data (IPD) available, in compliance with privacy and data protection laws. This will involve further consultation.

Policy 0070 does not replace the existing reactive Policy 0043. Nor will it limit the application if, or the rights to public access to documents of EU institutions and bodies given by Regulation (EC) No 1049/2001.

It is intended that there will be no difference in the EMA’s understanding of CCI in the assessment of documents requested through Policy 0043 or documents that will be proactively published under Policy 0070.

Scope and timings of Policy 0070

The scope of Policy 0070 relates to clinical data submitted after 1 January 2015 under the centralised authorised procedure10 including as part of marketing authorisation applications or certain post authorisation procedures. Policy 0070 does not cover clinical data:

  • held by the EMA for extension of indication applications and line extension applications submitted before 1 July 2015; or
  • which may be submitted to the EMA for non-centrally authorised medicines is not covered by the scope of Policy 0070 but access may be available to third parties in accordance with Policy 0043.

The EMA will publish clinical reports in accordance with arrangements for management of CCI and IPD and once the relevant authorisation/post-authorisation procedure has been finalised, i.e. following the Commission decision, scientific committee opinion or conclusion, or following receipt of the applicant’s/MAH’s letter notifying withdrawal of the submission.

Concerns about Commercially Confidential Information

One of the main concerns raised during the detailed consultation was the concept of CCI and the protection from its unfair commercial use. For the advice given to the EMA by the Clinical Trials Advisory Group on Legal Aspects (CTAG5) see here. The CTAG5 was unable to come to an agreed position on about CCI. Arguments objecting to proactive publication included:

  • damage to commercial interests by the disclosure of know-how, trade secrets and other intellectual property; and
  • undermining regulatory data protection; and
  • the prejudicing of later patent applications.

Arguments made in the CTAG5 for proactive publication included benefits to safety and efficacy, the public interest in identifying deficiencies, the reliability of data and accountability to the regulatory system. The compromise made by the EMA to take into account all stakeholders’ competing interests was:

  • the management of CCI in clinical reports by redaction and a process for publication of clinical reports; and
  • a publication process through Terms of Use which govern the access to and use of clinical data.

Approach to redactions of Commercially Confidential Information

Policy 0070 defines CCI as “any information contained in the clinical reports submitted to the EMA by the applicant/MAH that is not in the public domain or publicly available and where disclosure may undermine the legitimate economic interest of the applicant/MAH.”

Whilst it is a stated objective to protect CCI, Policy 0070 also states: “In general,[…]clinical data cannot be considered CCI. The EMA acknowledges that there are limited circumstances where information could constitute CCI.”

The only specific guidance in Policy 0070 on what might constitute CCI is contained in Annex 3 of Policy 0070. Annex 3 sets out specific elements contained in the common technical document which may be considered CCI together with appropriate justifications for redaction. The EMA’s Q&A also highlights in its Annex 1, as an example, parts of the CSR which may contain CCI.

The common technical dossier modules which constitute the clinical reports and the relevant titles or parts of them which may contain CCI are summarised in the table below.

Click here to view table.

Where redaction of CCI is proposed, the EMA will scrutinise the proposed redaction and justification made for it with regard to various factors including the:

  • nature of the medicine concerned;
  • competitive situation of the relevant therapeutic market;
  • approval status in other jurisdictions;
  • novelty of the clinical developments; and
  • any new developments by the same company.

If the EMA disagrees with the proposed redaction, a consultation will be undertaken with the applicant/MAH. It is for the EMA to take the final decision on what will be redacted. In case of disagreement with the EMA’s final decision on redaction, the applicant/MAH will have a defined period prior to the publication to seek an interim injunction from the General Court which is part of the Court of Justice of the EU. In this case, the EMA will only publish the undisputed parts of the clinical reports.

The application for an interim injunction must be made after or at the same time as an application to the General Court for the annulment of the EMA decision. An applicant/MAH may appeal a decision of the General Court not to grant an interlocutory injunction within two months of notification of the decision.

Potetially relevant grounds of appeal include:

  • a breach of procedure before the General Court which adversely affects the interests of the applicant/MAH; or
  • an incorrect application of EU law. an incorrect application of EU law.

Terms of Use governing access to and use of clinical reports

There are two sets of Terms of Use (ToU) set out in the Annexes to Policy 0070 which will govern the access to and use of published clinical reports.

The ToU seek to address concerns about damage to commercial interests and the undermining of regulatory data protection by granting only limited rights of use to the user and imposing specific contractual restrictions on unfair commercial use and submission to regulators by the user in support of relevant applications. An applicant/MAH will have the right to enforce the ToU directly against a user but the ToU will not be enforceable in contract against a third party that may have been disclosed information by the user in breach of its terms. An applicant/MAH will need to enforce its rights in confidential information, copyright or other intellectual property rights to prevent use of the information by any third party.

The key terms of the two sets of ToU are summarised in the table below.

Click here to view table.

Comment

The EMA reports that under Policy 0043 it has released over 1.9 million pages of clinical data in response to safety-related requests between November 2010 and April 2013. Whilst the EMA has been required to balance the public and private interests of disclosure, industry has been concerned about the concept of CCI and its protection from unfair commercial use by persons requesting the data.

These concerns have been considered by the EMA as it extends its approach on transparency11 to proactive release of clinical data under Policy 0070. Unfortunately there was no agreement between stakeholders on how to address the concerns. The processes for management of CCI and the adoption of Terms of Use therefore represent a compromise by the EMA between public and private interests.

As a result of the process for management of CCI, applicants/MAHs will have certainty about the clinical data which will now be more widely accessible to the public. They will also now have the ability to enforce in contract the Terms of Use directly against users including in respect of unfair commercial use or submission to regulators.

However, the EMA’s understanding of what constitutes CCI has not changed and the EMA remains of the view that clinical reports do not “in general” contain CCI. Their ability to prevent the disclosure of data in clinical reports by the EMA will be limited. The ability of applicants/MAHs to prevent misuse of the clinical data by any third party which may have obtained it from the registered user will also be limited to enforcing any intellectual property rights in the reports or data.