Transparency in clinical trials: Revised transparency rules take effect

The revised transparency rules (“Revised Rules”) for the Clinical Trials Regulation (CTR) and its Clinical Trials Information System (CTIS), issued by the EMA in October 2023, took effect on June 28, 2024, with the launch of a new version of the dedicated portal.

The transparency rules implemented in the CTIS at the time of the system’s launch in January 2022 were established in a document adopted by the EMA in 2015 (the Appendix on disclosure rules to the Functional specifications for the EU portal and EU database to be audited – EMA/42176/2014). This document referred to the publication of the Clinical Trial Application (CTA) dossier uploaded to the CTIS portal and all information on a clinical trial submitted throughout the entire trial, excluding quality-control documents, financial agreements, and certain safety monitoring information.

The Revised Rules were issued after the system was in use for a period and take into account both that experience and feedback from 204 stakeholders, including sponsors, CROs, academics, national authorities, ethics committees, HCPs, and patient organizations. Feedback was submitted during the public consultation in May and June 2023.

Additionally, to help operators better understand the new rules, the following updated documents were issued on June 18, 2024:

• Guidance document on how to approach the protection of personal data and commercially confidential information while using the Clinical Trials Information System (CTIS), Version 2.0 (“Guidance”);
• Q&A on the protection of Commercially Confidential Information and Personal Data while using the CTIS, Version 2.0.

The Revised Rules do not affect individual requests for access to additional information or documents under the CTR that will be assessed by the EMA or requests for access to documents under Regulation (EU) No. 1049/2001.

The main changes

Major changes under the Revised Rules are as follows:

• the deferral mechanism for each category of trial was eliminated;
• published information is now limited to information deemed relevant for the public that meets the needs of patients and researchers in the EU;
• the public CTIS website was simplified to encourage understanding among the general public and facilitate searches in structured data fields.

These changes should lead to faster publication of key documents (including protocols) and should make the system easier to use.

Elimination of the deferral mechanism and impact on commercially confidential information (CCI)

Previously, sponsors had two tools they could use to protect CCI that they included in trial-relevant documents: the redaction mechanism, i.e., deleting CCI from documents intended for publication, and the deferral mechanism, i.e., seeking deferral of the publication of one or more documents.

With the latter, when submitting an application, the sponsor could request a deferral and provide justification if required. The extent of the deferral and the subsequent timing of publication depended on the trial category. During evaluation of an application, the reference Member State (RMS) could then ask the sponsor to make changes to the deferral settings via a Part I request. The deferral rules applied to certain documents, including the protocol, the investigator’s brochure, documents on the safety and efficacy of the investigational drug, summaries of the trial results (for certain studies), and key characteristics (for certain studies).

Deferral was conceived as an alternative to CCI. It was intended to reduce the amount of information excluded from publication and increase the amount of information that could be published at the end of the deferral period. However, in practice, sponsors found it difficult to predict which information would be considered confidential at the time of deferred publication. Indeed, most sponsors employed redaction similarly across all documents, regardless of deferral, which ran contrary to the intended purpose of the measure.

Eliminating the deferral mechanism may appear to weaken protection of CCI, but simultaneously limiting published information to information that is essential for patients and researchers will offset that.

Fewer documents subject to publication

To counterbalance elimination of the deferral mechanism, the Revised Rules have reduced the number of documents subject to public disclosure. Only those considered of fundamental public interest, all listed in Table II of Annex I, are now included.

Documents that often contain CCI, such as investigator’s brochures, investigational medicinal product documents, assessment reports, requests for information (RFI) and corresponding responses, and financial agreements, are not made public. A list of such documents can be found in Table VI of Annex I.

Unlike documents submitted to the CTIS, structured data fields cannot be redacted. Therefore, sponsors should refrain from entering personal data or CCI into these fields. Information available in structured data fields includes study title, study design, inclusion and exclusion criteria, clinical investigator sites in EU Member States, and sponsor contact details.

Tools to protect CCI

The Revised Rules decrease the number of documents subject to disclosure, and they also provide several tools that with proper management can protect CCI from risky disclosures.

As clarified by the recent Guidance, to allow sponsors to protect their confidential business information, the Revised Rules provide the following:

• for each document submitted, there can be a version for publication with CCI redacted (the Guidance devotes considerable space to the principles and rules for identifying information that falls under the definition of CCI and methods for redacting it without blocking more information than is strictly necessary to ensure that the remainder of the document remains intelligible);
• differing timelines for disclosure of data and structured documents depending on trial category and the age of the population (see Tables I and II of Annex I to the Guidance).

The new Guidance remains unchanged from the 2023 version with regard to data protection and CCI. It introduces a transitional regime specific to “historical” trials, meaning those whose procedures started before June 18, 2024, regardless of whether deferrals were requested for them.