On 2 March 2016, the European Medicines Agency (EMA) published guidance on aspects of the Agency’s proactive disclosure policy for clinical reports (Policy 0070).  The latest Proactive Disclosure Guidance can be found here and focuses on:

  • Procedural aspects of submitting clinical reports.
  • The anonymisation of clinical reports.
  • The identification and redaction of commercially confidential information (CCI) in clinical reports, i.e. the disclosure of information that is not in the public domain and may undermine the legitimate economic interest of the applicant.

The Guidance is accompanied by a number of annexes, including template cover letters, template anonymisation reports and process flowcharts.

Policy 0070

The EMA Management Board adopted Policy 0070 in October 2014.  Under Policy 0070, the EMA will proactively publish clinical reports on its website following the approval of medicines.  Policy 0070 applies to clinical reports submitted to the EMA as part of a marketing authorisation application from 1 January 2015 or extension of indication applications from 1 July 2015 for centrally authorised products.

The EMA expects to publish the first wave of clinical reports in mid-September 2016 and the Agency will start reaching out to those companies who will be affected by the first wave of publication.

Submission Process for Clinical Reports

According to the Guidance, after the Committee for Medicinal Products for Human Use has reached opinion on the marketing authorisation or extension application dossier, applicants will be required to submit a “Redaction Proposal Version” of the clinical reports.  The applicant should identify each proposed CCI redaction in the “Redaction Proposal Version” of the reports together with a justification table explaining the proposed redactions.  The justification table is used as communication tool through the redaction process by both the applicant and the EMA.  Before submitting the justification table, the applicant is required to tick a box confirming that the company has performed all the necessary searches to check whether information in the report is in the public domain.

On receipt of the “Redaction Proposal Version” of the reports, a dedicated team in the EMA will co-ordinate the redaction consultation process:

  • Validation process – The EMA will first check that the justifications are complete and will contact the company for additional clarification if the justifications are incomplete or too general.
  • Assessment of CCI – The EMA will then review the justifications to check that the justifications reflect the principles in Policy 0070. The EMA will contact the company if further clarifications are needed with applicants sending back clarified/revised justifications within 5-7 calendar days.  A maximum of one round of consultation is permitted, which includes separate correspondence/exchanges between the applicant and EMA.  At the end of the EMA’s assessment phase, the EMA will inform the applicant of its conclusion for the entire set of clinical reports.  Within 7 days of the EMA’s conclusion, the applicant should provide written agreement to the conclusion and apply the redactions.  The applicant must then submit a “Final Redacted Version” of each clinical report.

Anonymisation of Clinical Reports

Policy 0070 places on the onus on the applicant to ensure that no personal data of trial participants is included in clinical reports published on the EMA’s website.  The Guidance explains that when information is made public and published to the world at large, the risk of re-identification needs to be very low.

The latest Proactive Disclosure Guidance highlights processes and techniques that an applicant can use to ensure that clinical reports submitted to the EMA for publication are sufficiently anonymised.  Anonymisation is the process of turning data into a form that does not identify individuals and where identification is unlikely to take place.  The Guidance recognises that particular care must be taken when anonymising clinical reports concerning rare diseases and small populations.

Applicants must submit an anonymisation report demonstrating the technique used, the outcome of the process and how the risk of re-identification has been measured or managed.

Identification of CCI in Clinical Reports

The Guidance emphasises that the EMA considers that the majority of clinical information in clinical reports is not CCI.  The Guidance explains that Annex 3 to Policy 0070 identifies certain exceptions that potentially may be considered CCI.

The EMA advises that all justifications should be specific and relevant and that the proposed redaction should be limited to specific words, figures or sections of text rather than entire pages.  The applicant must also identify the relevant section of Annex 3 of Policy 0070 on which the redaction is based.  Justifications should also highlight the innovative features of the redacted information, indicate which on-going development programme the proposed redactions relates to (if applicable) and explain exactly how disclosure of the information would undermine the company’s legitimate economic interest.

The Guidance explains that the EMA will use five rejection codes to explain why the Agency does not consider that information is CCI:

  • Rejection Code 01 – Information already in the public domain or publicly available, for instance on the company’s own website, the EMA’s and other regulators websites and clinical trial registries.
  • Rejection Code 02 – Information that is common knowledge and does not bear any innovative features because it has already been revealed to an extent or can be inferred from scientific literature and guidance.
  • Rejection Code 03 – Disclosure of the information would be in the public interest, such as unit measurements, study identification numbers, countries where a study was conducted, excipient batch numbers, quantification ranges for PK/PD tests, primary and second endpoints, and statistical and bioanalytical methods amongst others.
  • Rejection Code 04 – Insufficient justification. The EMA may request additional clarifications from the company.
  • Rejection Code 05 – Irrelevant justification. The Guidance provides a number of examples of irrelevant justifications.

Publication of Clinical Reports

The Guidance explains that the EMA will publish redacted and anonymised clinical reports on its website within 60 days of the Commission’s decision on a marketing authorisation application or line extension or 150 days after withdrawal of a marketing authorisation application.  Each page of the published clinical report will include the watermarked text that “This document cannot be used to support any marketing authorisation application and any extensions or variations thereof”.

Challenging the EMA’s conclusion on redactions

The Guidance explains that if an applicant does not agree with the EMA’s conclusion on some of the proposed redactions to a document and challenges the EMA’s decision in the General Courts, the applicant must submit a partial “Final Redacted Version” containing any agreed redactions.  The EMA will publish the partial “Final Redacted Version” and replace the partial version with a final version after a final decision on interim relief is issued by the General Court.

Where an applicant does not submit a complete “Redaction Proposal Document” or “Final Redacted Document”, the EMA will publish a non-compliance notice.