European Medicines Agency's (EMA's) Clinical Trial Regulation (CTR) & Clinical Trial Information System (CTIS): Trial Sponsor and CRO Frequently Asked Questions & Regulatory Announcements

What may be considered CCI when redacting CTA documents for submission to CTIS and how should I go about redacting this information? 

Some examples of confidential information may be names of manufacturers, details of the manufacturing process, future development plans, innovative analytics methods and equipment used at the clinical sites.

Once you confirm the information that is confidential with your IP Legal, Regulatory, Clinical and non-Clinical teams, the redactions in the CTA document should be limited only to the specific information that is deemed confidential. This means that full paragraphs and pages will not be redacted while specific content or syntax within a sentence, table or figure will be redacted.

Prior to finalizing your CCI decisions, remember to double check applicable public sources such as global trial registries, publications and abstracts to confirm the information indeed remains confidential and has not already been made public.
Link to EMA Guidance document on how to approach the protection of personal data and commercially confidential information in documents uploaded and published in the Clinical Trial Information System (CTIS).

How can I streamline my internal review and approval process of redacted CTIS CTA documents?

To optimize and streamline your internal approvals, consider using a log to capture each proposed redaction and the associated justification. This information will assist reviewers and approvers and help mitigate potential questions and delays. Further, by building a list, you can repurpose the information for other documents and studies, as applicable.

An example log may include a column for each of the following:

  1. Document type e.g.; Investigator Brochure
  2. Document filename e.g.; IB_9301_redacted_draft
  3. Document version: v2.1
  4. Page reference e.g.; page 7
  5. Non-redacted syntax e.g.; 3 mg
  6. Proposed redacted syntax e.g.; 3
  7. Justification category: e.g.; proprietary manufacturing technique or method
  8. Justification: e.g.; text justification of why this information is proposed to be redacted
  9. Transparency Redactor: e.g; Jane Smith
  10. Redaction date: 15 Oct 2023

Which studies are required to transition to the CTR and what is the deadline to complete this?

Since the launch of the CTR in 2022, the timescales and expectations for transition studies from EudraCT have been socialized by EMA. The authorization of transition studies in CTIS requires advanced planning to prepare and submit the necessary documents prior to the deadline of 30 January 2025.

The EMA is estimating up to 6,000 studies under the Clinical Trials Directive (CTD) will require transition and approval in CTIS prior to the deadline of 30 January 2025. To date, approximately 320 studies have completed the transition.

Trials authorized under the CTD with at least one active site in the EU must be transitioned by 30 January 2025. Trials that have ended locally in all EU member states but have active sites in other regions of the world do not need to transition. Key to achieving the deadline of 30 January 2025 is not just submitting the necessary information and documents into CTIS but receiving the authorization itself.

There are specific considerations and deliverables for each transition study as outlined in the following documents that are made available by EMA.

Guidance for the transition of clinical trials

CTCG’s best practice guide and cover letter template

New EMA announcement 06 Oct 2023 explains planned changes to Transparency Rules for 2024. Revisions to EMA’s CTIS Transparency rules will impact all trial sponsors

Following a public consultation period in May and June 2023, on 06 October 2023, the EMA announced upcoming changes to CTIS Transparency Rules that will become effective in 2024.

To be implemented in 2024, changes include removal of the deferral mechanism for all trials, an abbreviated list of ‘for publication’ documents and simplification of required data fields in CTIS.

With these changes, EMA aims to simplify and streamline the transparency of information for patients and healthcare professionals while balancing protection of commercial confidential information and personal data for trial sponsors.

Trial sponsors will need to continue to manage their CTIS projects under the current rules while anticipating the changes for mid-year 2024.

EMA Announcement

Revised CTIS Transparency Rules

What happens if I receive an RFI regarding redacted version ‘for publication’ documents submitted to CTIS and how can I avoid this?

Avoiding an RFI is critical to your study timelines. RFI’s require a short turnaround time. Awareness of the CTR and its guidance are critical to mitigating the risk of an RFI. Read on to learn more about avoiding RFIs due to CCI redactions and examples of acceptable CCI.

RFI’s related to ‘for publication’ documents have recently been noted bay several study sponsors. In these cases, the Member State has noted dense redactions in these documents and the RFI has indicated the sponsor needs to resubmit a revised version of the document that adheres to Section 1.3 Legal Framework in EMA’s CCI Guidance document (including references to Article 81.4 of the CTR).

Avoiding an RFI is critical to your study timelines. RFI’s require a short turnaround time and therefore the operational considerations of turning a revised document in an expedited fashion are often challenging. 

Awareness of the CTR and its guidance are critical to mitigating the risk of an RFI. Per the CTR guidance, when deferring publication of documents, redactions should be minimal. Further, sponsors should be redacting ‘for publication’ documents based on what is anticipated to be confidential at the time of publication (not at the time of upload to CTIS).

Examples of information that may be deemed acceptable to redact as CCI are listed below (note: this is not an exhaustive list). It is recommended you check the guidance to confirm your suggested CCI data for your study meet the necessary criteria.

  • Exploratory endpoints
  • Biomarkers
  • Manufacturing site and vendor details
  • 3rd party questionnaires 
  • Formulations and unique processes 

Link to more information: EMA CCI CTIS Guidance

Are Member States reviewing public version documents in CTIS and could my ‘for publication’ document redactions result in an RFI?

The guidance from EMA has been consistent: if you are deferring, ‘for publication’ version documents should contain minimal if any redactions upon upload to CTIS. Further, the guidance states that Sponsors should not defer and redact.

At the start of the CTIS launch in 2022 it became clear that Member States were not reviewing ‘for publication’ documents to ensure conformance to this expectation - although it was expected that study sponsors adhere to the guidance at all times. However, more recently, multiple study sponsors have begun to receive RFIs as a result of heavy redaction in ‘for publication’ documents. It is important for all study sponsors to remember that when deferring, only commercially sensitive information at the time of publication (following the deferral period, if applicable) should be redacted. EMA is expecting all ‘for publication’ documents to be meaningful for the public.

Link to Sponsor Handbook with guidance regarding deferral and ‘for publication’ document redaction.
Link to EMA
CTR Questions & Answers Version 6.5, see Question 6.5, paragraphs 259-261.

My organization considers the dosing information for my CTIS project as Confidential (CCI). However, CTIS requires metadata fields be populated with dosing information. How can a Sponsor approach the protection of this information?

Depending on the phase of the trial, Sponsors can protect this information from becoming public despite certain CTIS fields requiring an input. Below is EMA’s guidance from section 3.3 “Q&A on the protection of Commercially Confidential Information and Personal Data while using CTIS”:

How can dose details be protected from disclosure from CTIS for certain trials category falling within category 2?
The main characteristics of medicinal products used in clinical trials falling under category 2 are subject to publication rules after a decision on the clinical trial application is issued by the first Member State concerned.

These main characteristics also include structured data fields on daily dose allowed and maximum dose allowed for the medicinal product under investigation. In some instances, depending on the trial development phase, dose details may be considered to be CCI. In such instances, sponsors can include ‘dummy data’ (e.g. 00 digits) in the related structured data field(s) of CTIS.

The full information on the posology should, however, be provided to the Member States for assessment in the document version ‘not for publication’ and can be redacted in the corresponding documents to be published.

This approach would be acceptable only on justified grounds, i.e. when the sponsor proves that the specific information on the posology is not in the public domain and constitutes patentable matter, the disclosure of which before a patent application is filed (typically, after the completion of the trial and during the trial readout) would jeopardize its protection.

This might be applicable for example to integrated phase I/phase II trials that are to be marked in CTIS as category 2 trials. The grounds for considering dose details as CCI should be clearly documented in the cover letter of the application. Link to additional Guidance


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