We are working on the website in phases. We are consantly adding new information to the website. Please check our website regularly for the most recent information. Also consult the CCMO website.

A brochure published by the Dutch Clinical Research Foundation (DCRF) describes the changes in a nutshell.
English: DCRF+brochure+CTR+EN
Dutch: DCRF-Folder-ECTR-Wetgeving-NL-Online

European Clinical Trial Regulation (ECTR)

The new Clinical Trials legislation has taken the legal form of a Regulation (Clinical Trial Regulation (EU) no 536/2014, CTR) and will replace national law. The rules for clinical trial applications, assessments and conduct are identical throughout the European Union (EU). The Regulation applies to all clinical trials (national and multinational) conducted in the European Economic Area (EEA).

Transition period

The CTR will apply from 31 January 2022 as published in the Official Journal of the European Union on July 31, 2021 (EU commission decision 2021/1240). The Directive 2001/20/EC will be repealed on the day of application of the CTR. Paragraph 5a of the Dutch Act on Research Involving Human Subjects (WMO) will also be repealed. There is, however, a transition period of three years starting from that day for clinical trials authorised under Directive 2001/20/EC legislation.

This transition period is as follows (see also questions 1.2 and 11.2 of the Q&A CTR):

1st year: initial application according to old (Directive 2001/20/EC) and new legislation (CTR EU no 536/2014) is allowed
2nd and 3rd year: all initial applications according to Clinical Trial Regulation
4th year and later: all ongoing clinical trials should comply with the requirements of the Clinical Trial Regulation

During the three years transition period, substantial modifications of clinical trials approved under Directive 2001/20/EC can be submitted according to this old legislation. Clinical trials not authorised under the regime of the CTR and still ongoing in EEA (Last Visit Last Patient has not taken place yet) at the end of the transitional period have to be ended or should switch before the end of this period into the regime of the CTR. If the duration of the clinical trial is expected to be more than two years at the date of the primary application in the first year of the transitional period it is strongly recommended to apply for an authorisation under the regime of the CTR.

Clinical trial application (CTR): from start to finish

The timeline below describes a clinical trial application under the EU Clinical Trial Regulation (CTR) from start to finish. See for a full overview the website of the CCMO.

National or multinational: general information

The CTR is applicable to national and multinational clinical trials.

National

For a national clinical trial, the reporting Member State (rMS) is the MS to which the clinical trial application is submitted.

Multinational

For multinational clinical trials there will be a coordinated and consolidated assessment by the Member States where the trial is intended to be carried out. For multinational trials, the sponsor proposes a rMS but it is up to the concerned Member State (cMS) to express their willingness to become rMS during the first 3 days of the application.

Research file: full, staggered or mixed applications

The sponsor is allowed to submit a full initial application (part I and part II at the same time), a staggered initial application (first part I followed by part II) or a mixed initial application (full, staggered or mixed applications).

Mixed initial applications in a multinational clinical trial: The sponsor can submit a whole application (Part I and II) to some Member States concerned (on the basis of article 5 CTR) and at the same time an application limited to Part I only (on the basis of article 11 CTR) to other Member States concerned.

Full or staggered application in the Netherlands

These committees will be responsible for the Part I and Part II assessment including ethical review. This means one integrated assessment by one committee within the timelines set. It is therefore advised to submit Part I and Part II in parallel.

Clinical Trials Information System (CTIS)

A main characteristic of the CTR is an application procedure via a single entry point- an EU portal and database (CTIS), for all clinical trials to be conducted in the EU/EEA.

Research dossier Part I and Part II

See for more information about the Research dossier Part I and Part II the CCMO website.

Submission

The sponsor proposes a Member State to act as reporting Member State (rMS).

Deadlines

The CTR foresees strict and in some cases fatal deadlines. The clock starts running the day after the application is submitted and follows the Central European Time (CET). The Netherlands uses CET.

Each phase, from validation, assessment and decision, has its own maximum deadline for MSs and sponsors. The deadlines are set in calendar days and follow the rules as set in Regulation 1182/71. This means that the due date can never fall on a weekend day or an official holiday. Neither can a time period be shorter than two consecutive working days. For multinational trials, official holidays of rMS and/or MSc are taken into account depending on the hard task of rMS/MSc . The deadlines are visible in CTIS.

Christmas clock stop

There is an informally agreed Christmas clock stop between 23 December and 7 January for all clinical trials, i.e national and multinational. The sponsor must indicate any objections against this clockstop to the rMS in time. There are no other clock stops within the procedures.

Notifications

The following submissions are for notifications:

Foundation BEBO

General information CTR