top of page
  • Writer's pictureLighthouse

The New European Clinical Trials Information System

Updated: Mar 8, 2023

Summary in Thirty Seconds

  • The new Clinical Trials Information System (CTIS) was fully implemented on Tuesday, Jan. 31, 2023, with the goal of centralizing and standardizing all clinical trial documentation in the EU.

  • The roll-out of this system has been uneven although the intent of the CTIS is to make Europe more attractive as a site for clinical research through saving time and money by integrating all trial processes in a “one-stop shop” and focusing on patient needs.

  • The new system will require frequent use for familiarity and the updating of materials to meet new requirements; the CTIS is proving a number of resources for help in the adaptation process.

  • An additional part of the push for more trials and trial participation in Europe is the Accelerating Clinical Trials in the EU (ACT EU), which "seeks to transform how clinical trials are initiated, designed, and run” and support more large-scale multinational trials.

CTIS Roll-out

The European Medicines Agency (EMA) began mandatory use of the new Clinical Trials Information System (CTIS) as of Tuesday, Jan. 31, 2023, to streamline the EU trials process. The CTIS is intended to be a one-stop shop for all clinical trial documentation in up to 30 European countries (the 27 EU states, plus 3 EEA members—Iceland, Liechtenstein, and Norway—but importantly not the UK) with support for both sponsors and regulators. The CTIS handles all clinical trial applications submitted to EU/EEA member states (as well as to ethics committees), including registration of the trial, integrating everything into a single submission. The full roll-out of the CTIS has been slow, with delays, confusion, and technical challenges. Because of these issues, in a three-month trial period in 2022, only 56 clinical trial applications were submitted.[1] By comparison, about 4,000 new trials are authorized each year in Europe.[2] The challenges of the CTIS implementation process have made some pharma executives hesitant to start opening new trials in Europe in 2023.


EU Clinical Trial Directive to Clinical Trial Regulation

The EU Clinical Trial Directive (EU-CTD) has governed clinical trials since 2004, using standardized rules and enhanced patient protections. However, the EU-CTD had little weight because each EU member state had its own legal requirements, leaving clinical trial sponsors to face country-specific regulations and application processes. The Clinical Trial Regulation began (CTR) in 2014 with the goal of fully implementing the CTIS and repealing the EU-CTD (which took place on January 31, 2022). A significant advantage of the CTR is that it is binding to EU member states (unlike the CTD).[3] By Jan. 31, 2025, any ongoing trials originating under the EU-CTD will have to comply with and be transferred to the CTR and CTIS.[4] As a result of Brexit, the CTR does not apply in the UK, which means conducting a clinical trial in the UK will necessitate a separate submission process overseen by the Medicines and Healthcare products Regulatory Agency.[5]


The EU Clinical Trial Regulation

The EMA states, “The application of the CTR strengthens Europe as an attractive location for clinical research. The new regulation streamlines the processes for the application and supervision of clinical trials, and their public registration: all clinical trial sponsors will now use the same system and follow the same procedures to apply for the authorisation of a clinical trial, no matter where they are located and which National Competent Authority (NCA) or national ethics committee they are dealing with.”[6]


A European Pharmaceutical Review article[7] lists seven important advantages of the CTR:

  1. Use of coordinated assessments for multi-national applications;

  2. Use of the centralized CTIS;

  3. Increased transparency throughout the development process while protecting PHI and confidential commercial information;

  4. Adoption of new definitions, including for “low intervention trials” (minimal risk trials);

  5. Shorter, better-defined timelines (12 calendar days) for application queries and RFIs;

  6. Simplified safety reporting involving a single report for all unexpected events within 15 days;

  7. Enhanced patient protections reflected in more detailed informed consent guidelines.

Purpose of CTIS

The CTIS intends to save PIs and sponsors time and money. It also intends to make access to research studies easier for patients by putting patients at the center of CTIS focus. One way this is being done is by translating all materials into the 24 languages predominant in the CTR member countries. Presumably, the fully implemented CTIS will enhance what has recently been daily and effective communication and coordination between the EMA and FDA.[8]


Adapting to the CTIS

As various entities in pharma development use the CTIS, system users will need to frequently log in to gain familiarity with CTIS as well as to ensure that users understand the specific tasks necessary to them and respond to RFIs in a timely manner. Specific patient-related materials will need to be updated to reflect the new system as well as to meet the CTIS requirements. The CTIS will require learning and adapting to a new system of compliance, regulatory, and transparency requirements.[9]


KIVO.io recommends three key steps for sponsors to adapt to the new CTIS:

  1. Align internal processes—have the different clinical trial teams collaborate on clinical trial processes with guidance from the EMA guidebook;[10]

  2. Define CTIS responsibilities and assign roles accordingly—decide who within a company will fill which role in the application, alert, RFI, and communications process;

  3. Utilize technology to maximize efficiency and maintain compliance—streamline workflow through technology for a sponsoring organization throughout the entire clinical trial process.

The CTIS has developed a number of resources and references to help sponsors adapt to the new system. First is a “quickguide” flowchart[11] that begins with a decision on which of two user management approaches a sponsor wishes to use: “organization-centric” (for those usually running multiple trials) or “trial-centric” (for organizations, such as academia, that typically start one trial). Second is a Sponsor Handbook[12] comprised of guidance, technical information, recommendations, and references for sponsors.


The European Pharmaceutical Review notes that “Sponsors must be aware of stricter transparency and reporting obligations, new safety and patient protection provisions, updated definitions, and shorter deadlines. Communication with regulatory and regulatory intelligence teams will be valuable, as EU-CTR encourages sponsors to think more proactively and more frequently about their regulatory strategy.”[13]


Accelerating Clinical Trials in the EU (ACT EU)

An additional part of the push for more trials and trial participation in Europe is a new initiative, the Accelerating Clinical Trials in the EU (ACT EU), which was announced in conjunction with the CTIS rollout on January 31, 2022. ACT EU "seeks to transform how clinical trials are initiated, designed, and run," and to "develop the EU as a focal point for clinical research; promote the development of high-quality, safe, and effective medicines; and better integrate clinical research in the European health system."[14] The ACT EU includes in its objectives the need to support more large-scale multinational trials “with broader geographical scope,” “reducing administrative burden and increasing efficiency,” and “strengthening clinical trials that deliver decisional evidence for unmet medical needs, rare diseases, and on vaccines…”.[15]


The Bottom Line

Many clinical trials suffer from a lack of patient pool diversity.[16] Extending trials into Europe can increase such diversity while also increasing enrollment. In the past, European trials were complicated by the complex, varied regulations and requirements across European countries. With the implementation of the CTIS, the CTR aims to overcome the problems of the CTD (most notably the decentralization of functions across the EU members). While adapting to the new system will be challenging, the CTIS should result in greater efficiency for clinical trial submissions and assessments leading to more patients receiving treatments that have been tested on study participants more like themselves.

[2] EU clinical trials: ‘Application process is now simplified’ (biopharma-reporter.com) [3] https://www.europeanpharmaceuticalreview.com/article/168043/understanding-the-new-eu-clinical-trial-regulation-seven-things-sponsors-should-know [4] Clinical Trials Regulation | European Medicines Agency (europa.eu) [5] Medicines and Healthcare products Regulatory Agency - GOV.UK (www.gov.uk) [6] Use of Clinical Trials Information System becomes mandatory for new clinical trial applications in the EU | European Medicines Agency (europa.eu) [7] https://www.europeanpharmaceuticalreview.com/article/168043/understanding-the-new-eu-clinical-trial-regulation-seven-things-sponsors-should-know [8] Clin. Pharmacol. Thera. (2020); 107(3):507-513 [9] CTIS Blog Series Part I: 3 Ways to Prepare your Organization (kivo.io) [10] Key principles for sponsor organisation modelling for CTIS V2 (europa.eu) [11] Getting started with CTIS - Sponsor quick guide (europa.eu) [12] CTIS Sponsor Handbook 2022_v.3.01 (europa.eu) [13] https://www.europeanpharmaceuticalreview.com/article/168043/understanding-the-new-eu-clinical-trial-regulation-seven-things-sponsors-should-know [14] Accelerating Clinical Trials in the EU (ACT EU) (europa.eu) [15] ibid [16] New Federal Incentives for Diversity in Clinical Trials | NEJM



bottom of page