Clinical Trials Information System - CTIS

Implementation of the CTIS: Between harmonization and practical challenges

The introduction of the Clinical Trials Information System (CTIS) in January 2022 marked a milestone for European clinical research. The aim of EU Regulation 536/2014 was to replace fragmented national processes with a central platform that increases transparency and simplifies multinational studies. However, after more than three years of practical experience, the picture is ambivalent: While the system has conceptual strengths, technical shortcomings, prolonged approval procedures and organizational hurdles are hindering implementation.

Overview of changes

	Before CTIS	CTIS (Regulation EU 536/2014)
Legal framework	National law of the member states valid, e.g. GCP Regulation	Directly applicable EU regulation
Submission and amendments	National submission (via portals or paper-based), separately for each Member State	Central submission via CTIS for all participating Member States
Approval deadlines	Individual deadlines by country, in Germany, for example, 30 days with the authorities	Total duration with a theoretical maximum of 60 days
Transparency	Partially non-public study information	Automatic publication of relevant information (redacted and unredacted version required)
Communication	Personal contact with the responsible authorities and ethics committees	Communication exclusively digital via CTIS, no direct contact possible
Responsibilities	Fixed ethics committee according to the location of the LKP	Assignment of the responsible ethics committee is random
Administrative hurdles	Low-threshold submission process	Intensive familiarization with CTIS with sometimes complex role assignment
System dependency	Alternative submission methods possible, e.g. by post or e-mail	Submission exclusively via CTIS, technical stability is required
Tracking	Inconsistent tracking, partly paper-based	Uniform digital tracking through bundling in CTIS

Theoretical advantages vs. technical reality

CTIS should reduce duplication of work and strengthen cooperation between Member States by harmonizing the submission and evaluation processes. This is a step forward for multinational studies – instead of country-specific applications, a standardized set is sufficient. The integration of labels in the documentation and transparent approval requirements also improve traceability.

However, the technical implementation remains problematic:

System stability: Server overloads and errors in user administration (e.g. truncated organization names) delay applications.
Document management: The public website sometimes publishes outdated protocol versions, which misleads patients and researchers.
Workarounds: For non-substantial modifications, sponsors must use substantial modifications, although this is not intended.
Although the EMA is working on updates, fundamental shortcomings – such as the lack of support for platform studies – are hampering innovative research approaches.
The processing options are also limited from the perspective of the authorities: If, for example, the BfArM inadvertently enters an incorrect document as an authorization, this could not be exchanged in practice.

Approval deadlines: theory vs. practice

The CTR stipulates a maximum processing time of 45-60 days. In practice, however, approval procedures can sometimes take over 100 days if requests for information (RFIs) are made. What is particularly annoying in this context is that the time periods are often stretched to the limit, even for matters that are easy to process.

Countries such as Austria have introduced accelerated procedures (35 days) for mono-national studies in order to maintain locational advantages. Nevertheless, the industry criticizes the doubling of lead times compared to previous national processes:

Validation phase: RFIs extend the deadline by 15 days.
Assessment phase: Each request adds 31 days, even in the case of parallel RFIs. It should be noted that a shortened processing time by the applicant does not shorten the deadline.
Seamless responsiveness: Missed deadlines lead to the technical expiry of the application, which cannot be responded to with concessions from the authority.

These delays increase planning uncertainty and tie up additional resources, which is particularly problematic for IITs and studies with limited budgets.

Organizational adjustments: From theory to bureaucracy

The introduction of CTIS requires far-reaching process changes:

Personnel resources: Processing applications is 4-6 times more time-consuming than under the old system. Ethics committees and authorities have had to expand their teams in order to process RFIs within 8-12 days.
Training requirements: The complex role assignment and technical system logic require continuous training.
Substitution arrangements: Vacation or sick leave jeopardize compliance with rigid deadlines, as specialist knowledge is not easily transferable.
It is no longer possible to speak to a fixed contact person. Technical hurdles have to be processed via a ticket system that works inefficiently with processing times of several days in some cases.
Subsequent submissions are no longer possible without problems. In the previous system, it was possible to submit administrative matters such as signatures without any problems, which simplified and accelerated operational processes. This route has been completely eliminated and now requires a rigid wait to fulfill even minor formalities.

Large pharmaceutical companies can mitigate these challenges through CROs (Contract Research Organizations), while smaller research institutions reach their capacity limits.

Impact on the European research landscape

The CTIS problems jeopardize Europe’s attractiveness as a research location:

Emigration trends: Companies are considering relocating studies to Australia or Singapore in order to avoid longer approval times.
Academic research: Investigator-initiated trials (IITs) on rare diseases are conducted less frequently due to higher costs and complexity.
Transparency vs. data protection: The automatic publication of study documents requires complex redaction processes in order to protect business secrets and personal data.

Despite these challenges, successes are evident: 3,657 applications have been submitted via CTIS since 2022, 70% of which were for multinational studies. The average participation of six member states per study underlines the potential for transnational cooperation.