Clinical trials – Health, innovation and research institute

1. General information

1.1. Definition of a clinical trial

Under the scope of the Clinical Trials Regulation No. 536/2014:

A clinical study means any investigation in relation to humans intended:

to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; or
to identify any adverse reactions to one or more medicinal products; or
to study the absorption, distribution, metabolism and excretion of one or more medicinal products;

with the objective of ascertaining the safety and/or efficacy of those medicinal products.

A clinical trial is a category of a clinical study. A clinical trial means a clinical study which fulfills any of the following conditions:

the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within normal clinical practice of the Member State concerned; or
the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study; or
diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects.

For these clinical trials, approval from both the Independent Ethics Committee (IEC) and Competent Authority (CA) (which is the Federal Agency of Medicines and Health Products (FAMHP) for Belgium) is mandatory.

1.2. Legislation

The conduct of clinical trials in the EU used to be governed by the Clinical Trials Directive (2001/20/EC). The Clinical Trials Regulation (536/2014) replaced the Directive from 31 January 2022 onwards. Its aim is to ensure a greater level of harmonisation of the rules of conducting clinical trials throughout the EU.

Since the Clinical Trials Regulation (CTR) became applicable, it repealed the existing Clinical Trial Directive (CTD) and national legislation that was put in place to implement the Directive. It also applies to trials authorised under the previous legislation if they are still ongoing three years after the Regulation came into operation.

What does this mean?

All new clinical trials have to be submitted under the new CTR.
For ongoing clinical trials that were submitted under the old CTD, the CTR allowed for a transition period until 30 January 2025. From 31 January 2025, all these clinical trials have to follow the CTR and must have been transitioned to follow the Regulation.

For more information on this topic, please visit the website from the European Medicines Agency (EMA).

2. Submission under the Clinical Trial Regulation

2.1.1. Submission package

Before setting-up your submission package, we ask you to contact HIRUZ CTU (contact person for your department can be found here) to set-up a meeting to discuss your trial.

PART I

Cover letter (completed by HIRUZ CTU)
List of documents submitted (completed by HIRUZ CTU)
EU application form (completed by HIRUZ CTU in CTIS)
Study protocol
Synopsis of the study protocol (separate documents, in English and the local language(s) of the participants)
Participant facing documents: diary, questionnaire, interview topic list, etc.
Documentation about the IMP(s) and AxMP(s):
- Investigator’s Brochure (IB)
- SmPC / IMPD
- Study label
- GMP documentation, if applicable

PART II

Participant related documents:
- Informed Consent Form(s) (ICF(s))
- Recruitment materials: flyer, poster, etc.
- Description of the compensation for trial participants
Suitability/Feasibility documentation:
- Suitability of the investigator(s):
  - Declaration of interest of all participating PI’s
  - CV of all participating PI’s
  - GCP certificate of all participating PI’s
- Suitability of the facilities: site suitability form (written statement) of each participating center
Other documents:
- Data processing register (Ghent University Hospital studies | Ghent University studies)
- Insurance certificate (provided by HIRUZ CTU)
- Agreements (if applicable – a draft version is sufficient)
- Statement data protection
- Copy of the summary of scientific advice, if applicable

2.1.2. Submission procedure

2.1.2.1. Preparation of the submission package

In case of questions, please find the HIRUZ CTU contact person here.

2.1.2.2. Submission through the Research Portal

All trials must be submitted through the Research Portal of Ghent University (Hospital): https://onderzoeksportaal.uzgent.be/.
More information can be found here.

Once the applicant submits the trial in the Research Portal, approval of the Principal Investigator (PI), Head of Department (if applicable) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the trial is submitted to HIRUZ CTU for review.

After admissibility check, HIRUZ CTU will revise the information given in the Research Portal, as well as the documents that were submitted. Once the trial is reviewed, you will be informed (by email) that the review can be found in the Research Portal (in the tab ‘HIRUZ Remarks’).

2.1.2.3. Submission through the Clinical Trial Information System (CTIS)

Complete applications (after the review by HIRUZ CTU was implemented) are submitted by HIRUZ CTU through the CTIS. A CTIS submission applies to all EU Member States that are involved in the trial and contains their respective Competent Authority (CA) and Independent Ethics Committee (IEC) applications in one submission. All communication with the Member States (remarks/approval by CA/IEC) will be communicated to you by HIRUZ CTU.

Please note: HIRUZ Contract Unit or TechTransfer will be notified by HIRUZ CTU to review the draft agreement proposals or to set-up an agreement if necessary.

2.1.2.4. MEC and FAMHP approval

Information on the legal periods for advice by the FAMHP can be found here.

The trial can only start when a favorable consolidated opinion (from the Reporting Member State (RMS) for part I and the Member State Concerned (MSC) for part II) has been received and as soon as all agreements are finalized (if applicable). In addition (if HIRUZ CTU will be monitoring the trial), HIRUZ CTU will set-up a trial initiation visit at each participating site to discuss the practical aspects of the trial and provide the necessary training (ICH-GCP, protocol, ICF procedure, Investigator Site File, safety follow-up…). This initiation visit must take place before inclusion of the first patient at each site.

2.1.3 Trial follow-up

2.1.3.1. Start Trial

Please register both the date of start of recruitment and the date of first inclusion in the Research Portal. HIRUZ CTU will then notify the CA/IEC through CTIS.

Please note: the notification in CTIS has to be done within 15 calendar days from the start of the clinical trial and within 15 calendar days from the first inclusion, respectively. Please make sure you update the Research Portal as soon as possible.

In case of an international trial: please keep in mind the start of recruitment and the date of first inclusion need to be notified to each MSC in relation to that MSC (through CTIS).

2.1.3.2. During the trial

During the trial, Annual Progress Reports, Development Safety Update Reports (ASRs) and safety events must be submitted yearly to HIRUZ CTU (hiruz.ctu@uzgent.be).

Please note: for the time being, this still needs to be done by email instead of through the Research Portal.

2.1.3.3. End of recruitment of subjects

Please inform HIRUZ CTU about the end of the recruitment of subjects for the trial (via email). HIRUZ CTU will then notify the CA/IEC through CTIS.

Please note: the notification in CTIS has to be done within 15 calendar days from the end of recruitment. Please make sure you inform HIRUZ CTU as soon as possible.

In case of an international trial: please keep in mind the end of recruitment needs to be notified to each MSC in relation to that MSC (through CTIS).

2.1.3.4. End of trial

Please register the end of the trial in the Research Portal. HIRUZ CTU will then notify the CA/IEC through CTIS.

Please note: the notification in CTIS has to be done within 15 calendar days from the end of the trial. Please make sure you inform HIRUZ CTU as soon as possible.

In case of an international trial: please keep in mind the end of trial needs to be notified to each MSC in relation to that MSC (through CTIS).

2.1.3.5. Summary of results

Please upload the summary of the results to the Research Portal, within one year after the end of the trial, irrespective of the outcome of the trial. HIRUZ CTU will then notify the CA/IEC through CTIS.

All modifications to clinical trials under the CTR for which Ghent University (Hospital) acts as a sponsor must be registered through the Research Portal of Ghent University (Hospital): https://onderzoeksportaal.uzgent.be/.

More information can be found here.

After registration through the Research Portal, HIRUZ CTU helps with the official CTIS submission.

Please note that for clinical trials under the Clinical Trial Regulation (CTR) for which Ghent University (Hospital) does not act as sponsor of the trial, the trial should be submitted through CTIS to the relevant Member States. Please make sure the sponsor adds Ghent University Hospital as a participating site in the system with (SPOR/OMS) organisation ID ORG-100021542 and location ID LOC-100030233 (C. Heymanslaan 10, 9000 Gent). In case Ghent University is a participating site, make sure the sponsor adds Ghent University as a participating site in the system with (SPOR/OMS) organisation ID ORG-100022735 and ensure to select the correct location (6 addresses to choose from).

Submission through the Research Portal of Ghent University (Hospital) (https://onderzoeksportaal.uzgent.be) is only applicable in case Ghent University (Hospital) takes care of the insurance ((inter)nationally) and/or in case HIRUZ is providing monitoring services for the study. In all other cases, submission through the Research Portal is not applicable. Please refer to section 3.1.1. for more detailed submission guidance.

The following conditions must be met to start a clinical trial under the Clinical Trial Regulation (CTR) at Ghent University (Hospital) (as participating site):

Site suitability form (written statement), signed by the executive director / rector of Ghent University (Hospital)*;
Final clinical trial agreement(s) with the sponsor (i.e. signed by all parties): agreements will be reviewed by our Contract Unit / TechTransfer;
RMS/MSC (CA/IEC) approval of the trial in CTIS.

*The sponsor can request signing of the written statement by the executive director by emailing to hiruz.contracten@uzgent.be. (Ghent University Hospital) or by the rector by emailing to contracten@ugent.be (Ghent University).
The following should be provided:

The written statement, completed as agreed upon with (the department of) the PI
Confirmation (can be done through confirmation of all of the below via e-mail) of the PI (statement on honour) that he/she
- has received the following documents from the sponsor:
  - Protocol
  - IB, IMPD and/or SmPC of the IMP(s)
  - Budget proposal
- has read the abovementioned documents
- wishes to participate in the clinical trial, (if applicable) together with their study team
- believes that the clinical trial protocol can be performed by their department (adequate staffing, suitable patient population, adequate material and budget available, adequate expertise …)
- understands the responsibilities as local PI at Ghent University (Hospital).

Please note: Agreements should be submitted to hiruz.contracten@uzgent.be by email for review. In the near future, agreements and requests for written statements will need to be submitted to HIRUZ Contract Unit through the Research Portal.

Notification through the Research Portal of Ghent University (Hospital) (https://onderzoeksportaal.uzgent.be) is only applicable in case Ghent University (Hospital) takes care of the insurance ((inter)nationally) and/or in case HIRUZ is providing monitoring services for the study. In all other cases, notification through the Research Portal is not applicable.

Please note: that for clinical trials under the Clinical Trial Regulation (CTR) for which Ghent University (Hospital) does not act as sponsor of the trial, modifications should be submitted through CTIS.