The European Union (EU) implemented significant changes in the way clinical trials (CTs) are conducted where the EU Clinical Trial Regulation (EU CTR) (Regulation EU 536/2014) came into effect early this year, on 31st January 2022. The aim of the new regulation was to harmonize how clinical trials are supervised and assessed by enhancing collaboration and sharing important clinical trial data. The objectives of the new CTR are to protect participants and reliability of the data that is collected from the CTs; to encourage innovation, and to increase transparency between patients and innovation. Key changes include harmonized dossiers, coordination of CT assessment between Member States, single electronic submissions, simplifying reporting requirements, reinforcing CT supervision, implementing new provisions for informed consent among others [1].
As part of the EU CTRs initiative to enhance harmonization, the European Medicines Agency (EMA) implemented the Clinical Trials Information System (CTIS) that electronically integrates all stages of a CT application. This includes key stages such as submission to authorities, carrying out corrective measures and modifications as necessary, and publishing important documentation for public access. The single submission procedure will facilitate better sharing of data between Ethics Committees and competent authorities. The main benefits of the CTIS encompass increased transparency, digitalization & improved efficiencies, support to innovation & research, and enhanced patient safety [2].
CTIS users are assigned roles that determine the actions they can perform on the system. The roles are classified into High-level, Medium-level, and Business roles, and apply to Member State and Sponsors. High-level users include European Commission Administrators, Sponsors, and Member States that are able to manage users within their respective organizations. They, however, cannot perform business activities unless assigned to do so. Medium-level users are assigned within the CTIS who can assigned roles to different uses as needed, within their organization. These include CT administrators for Sponsors, and National organization administrators for Member States. Finally, Business roles include CT coordinators that are responsible for administration tasks, and other business roles that have permission associated with the activities they perform in a system such as reviewing, preparing, and submitting documentation.
Successful implementation of a new system requires thorough training. Thus, CTIS users were trained through the CTIS training programme, and equipped with the necessary skills and knowledge, to ensure that the user and the organization can use the CTIS efficiently. The training materials were produced in March 2020 that included a spectrum of guides, questions, e-learning materials, infographics, and videos that were made available in January 2021. Sponsors can choose between 2 different approaches: trial-centric and organization-centric and have been designed to address the requirements of different organizations [3]. EMA recommends adopting the organization-centric approach as it allows for quicker CT application process for first initial applications, is more secure since access to trials and data are managed by role assignment. While the trial-centric approach is less complex it since no validation process is required, it can be inconvenient in situations where organizations wish to run many trials. Furthermore, it can also impact data quality as users can create CT applications without sponsor administrator validation by EMA.
Though CT sponsors are able to use the CTIS from 31st January 2022, there is no obligation to do so as per the 3-year transition period that EMA has established. However, until 30th January 2023, CT sponsors can either choose to use the CTIS for CT application under the CTR or can choose to run a trial under the previous CT directive. After 31st January 2023, CT sponsors will be required to use the CTIS for CT application within the EU or EEA. From 31st January 2025, trials under the previous CT Directive will need to comply with the CTR, and their sponsors are required to record data of the CTs on the CTIS [4]. Sponsors are encouraged to make the most of the transition period to make sure that their information CT information is recorded in the CTIS in a timely manner to avoid any penalty.
-Akshita Srivastava, Senior Medical Writer at DDReg
References and further reading:
[1] Clinical Trials Regulation (EC) No. 536/2014
[2] CTIS Highlights, December 2020