On 11 June 2020, the European Medicines Agency (EMA), during its Management Board meeting, has endorsed the methodology and next steps leading to the go-live of the Clinical Trials Information System (CTIS) which is now fixed for December 2021. A group consisting of representatives of the EU Member States and the European Commission has been set up to prioritise and coordinate all outstanding issues prior to go-live. The CTIS is the centralised EU portal and database for information storage foreseen by the Clinical Trials Regulation.
The Clinical Trials Regulation has entered into force in 2014 and its date of application is subject to the publication of a notification that the EU portal and database have achieved full functionality. The development of CTIS hosting the EU portal and database has proven to be a challenging task and its operation has been delayed several times, as outlined in previous posts.
This latest development is critical to the application of the Clinical Trials Regulation. This Regulation will replace the currently applicable Clinical Trials Directive and will apply directly to all EU Member States without national transposition measures.
The most important changes introduced by the Clinical Trials Regulation are summarised below.
Centralised EU portal and database
The EU portal and database expected, as discussed above, to go-live in December 2021, have been introduced by the Clinical Trials Regulation with the aim of streamlining and facilitate the flow of information between sponsors and EU national authorities and to increase transparency.
Clinical trials will be assigned with a unique EU trial number and the relevant data and information will be accessible to the public with the exception of personal data, commercially confidential information, confidential communication belonging to the EU Member States or data ensuring the effective supervision of the conduct of the clinical trial.
New authorisation procedures
The Clinical Trials Regulation simplifies the procedures for the submission of an application for authorisation of a clinical trial. Sponsors will be able to submit a single application dossier to the EU national authorities concerned through the EU portal. The evaluation of the application will be coordinated by a national authority, Reporting Member State (RMS), which will be designated either by the sponsor’s proposal or after agreement among the EU Member States concerned by the application. The same procedural requirements will apply for applications concerning clinical trials intended to be conducted only in one EU Member State.
The Clinical Trials Regulation significantly streamlines the procedural steps for the assessment of the single application and sets out clear deadlines for the RMS and the other EU Member States concerned to reach a single decision. These procedural rules are expected to reduce delays and increase the number of studies conducted within the EU.
Requirements for safety reporting
The Clinical Trials Regulation simplifies the rules concerning safety reporting. It contemplates that sponsors will be required to report suspected unexpected serious adverse reactions directly to the Eudravigilance database instead of reporting separately to every EU Member State. Moreover, annual reporting of clinical trials involving the use of more than one investigational medicinal product is simplified by submitting a single safety report on all the investigational medicinal products used in the clinical trial. Safety reporting by the investigators is not required if the adverse event is envisaged in the study protocol.
It is currently uncertain whether UK clinical trials would benefit from the CTIS. The latest guidance published by the MHRA states that, as the Clinical Trials Regulation would not apply at the time the UK left the EU on 31 January 2020 because the Regulation would not be incorporated into UK law on exit date for the purpose of the European Union (Withdrawal) Act 2018. Once the Clinical Trials Regulation starts to apply in the EU, the UK would seek to align its law with the Regulation “where possible”.
Clinical trials conducted outside the EU
Sponsors conducting clinical trials outside the EU but intending to submit an application for a marketing authorisation within the EU must conduct those clinical trials by following principles equivalent to the EU legislation.
The Clinical Trials Regulation will introduce rules that will greatly facilitate conduct of clinical trials to stimulate clinical research. There is a need for sponsors to align their respective internal procedure with the new requirements to ensure a successful transition to the new regulatory system.