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Since the Clinical Trials Regulation (CTR) became applicable, it repealed the existing Clinical Trial Directive (CTD) and national legislation that was put in place to implement the Directive.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 for the future?

All new clinical trials have to be submitted under the new CTR.
For ongoing clinical trials that were submitted under the old CTD, the CTD still applies until the end of 2024. At the latest in January 2025, these 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 Directive

2.1. A new clinical trial

This is no longer possible since 31 January 2023

Please note this is no longer possible for trials for which Ghent University Hospital becomes the first Belgian participating site. This is only possible if other Belgian sites were already participating to the trial.

2.2.1. Submission package

Clinical Trial Application Form
Protocol
Protocol summary
Informed Consent Form(s)
All documents provided to the subjects (e.g. recruitement material, flyers, posters, diaries, questionnaires, interview topic list, patient trial cards, …)
IB, SmPC, IMPD of the IMP(s)
Secondary label(s) for the IMP(s)
GMP-certificate (if applicable)
Data processing register (Ghent University Hospital studies | Ghent University studies)
Agreements (a draft version is sufficient)
CV and GCP certificate of the PI at Ghent University (Hospital)
Insurance certificate
Letter of approval from the Federal Agency of Medicines and Health Products (FAMHP)
Letter of approval from the central Medical Ethics Committee (MEC)

2.2.2. Submission procedure

2.2.2.1. Preparation of the submission package

In case of questions regarding academic trials, please find the HIRUZ CTU contact person for your department here or contact the HIRUZ CTU advisor/monitor for your trial.

In case of questions regarding non-academic trials, please contact the Medical Ethics Committee of Ghent University (Hospital) directly.

2.2.2.2. Submission through the Research Portal

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

For commercial trials:
Once the applicant submits the request in the Research Portal, approval of the Principal Investigator (PI) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the request is directly submitted to the MEC of Ghent University (Hospital). All further communication with the MEC (remarks/approval MEC) will go via the Research Portal

Please note: If the amendment is also substantial for the FAMHP, the amendment must be submitted simultaneously to the FAMHP by the sponsor.

Please note: New agreements or changes to existing agreements should be submitted to hiruz.contracten@uzgent.be by email for review. In the near future, agreements will need to be submitted through the Research Portal.

For academic trials:
Once the applicant submits the request in the Research Portal, approval of the Principal Investigator (PI) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the request 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 request is reviewed, you will be informed (by email) that the review can be found in the Research Portal (in the tab ‘HIRUZ Remarks’).

Please note: the sponsor should submit the request simultaneously to the FAMHP.

Please note: When the request is submitted to the MEC, HIRUZ Contract Unit or TechTransfer will be notified to review the draft agreement proposals or to set-up an agreement if necessary.

2.2.2.3. MEC and FAMPH approval

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

The amendment can only be implemented when a favourable opinion from the central MEC and/or FAMHP has been received and as soon as all agreements are finalized (if applicable).

2.2.3. Trial follow-up

2.2.3.1. Start trial

Please register both the date of start of recruitment and the date of first inclusion in the Research Portal

2.2.3.2. During the trial

During the trial, Annual Progress Reports, Development Safety Update Reports (DSURs) and safety events must be submitted yearly to HIRUZ CTU (hiruz.ctu@uzgent.be) (only for academic trials) and the MEC of Ghent University (Hospital) (ethisch.comite@uzgent.be).

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

2.2.3.3. End of trial

Please register the end of the trial in the Research Portal and upload the final study report within one year after the end of the trial (as legally required)

2.3. Other amendment to a clinical trial

2.3.1. Submission package

All substantial changes compared to the original Medical Ethics Committee (MEC)/Federal Agency of Medicines and Health Products (FAMHP) application have to be approved by the MEC of Ghent University (Hospital) and/or the FAMHP through an amendment. This includes substantial changes to the trial design, trial protocol or other trial documents and the addition of other centers.

Documents to be submitted:

All modified trial documents in track-changes and clean version
All new documents that were created in light of the amendment
Substantial Amendment Notification Form (if Ghent University (Hospital) does not act as the sponsor of the trial; otherwise provided by HIRUZ CTU)

2.3.2. Submission procedure

2.3.2.1. Preparation of the submission package

In case of questions regarding academic trials, please find the HIRUZ CTU contact person for your department here or contact the HIRUZ CTU advisor/monitor for your trial.

In case of questions regarding non-academic trials, please contact the Medical Ethics Committee of Ghent University (Hospital) directly.

2.3.2.2. Submission through the Research Portal

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

For commercial trials:

Once the applicant submits the amendment in the Research Portal, approval of the Principal Investigator (PI) and Medical Manager of the biobank (if applicable) will be asked. When all approvals are given, the amendment is directly submitted to the MEC of Ghent University (Hospital). All further communication with the MEC (remarks/approval by MEC) will go via the Research Portal.

Please note: if the amendment is also substantial for the FAMHP, the amendment must be submitted simultaneously to the FAMHP by the sponsor.

Please note: new agreements or changes to existing agreements should be submitted to hiruz.contracten@uzgent.be by email for review. In the near future, agreements will need to be submitted through the Research Portal.

For academic trials:

If the MEC of Ghent University (Hospital) is the central MEC: after admissibility check, HIRUZ CTU will revise the information given in the Research Portal, as well as the documents that were submitted. Once the amendment is reviewed, you will be informed (by email) that the review can be found in the Research Portal (in the tab ‘HIRUZ Remarks’).

Complete applications (if applicable, after the review by HIRUZ CTU was implemented) are submitted by HIRUZ CTU to the MEC of Ghent University (Hospital) (also through the Research Portal) and/or to the FAMHP (if Ghent University (Hospital) is sponsor of the trial). All further communication with the MEC (remarks/approval by MEC) will go via the Research Portal. All communication with the FAMHP (remarks/approval by FAMHP) will be communicated to you by HIRUZ CTU (if applicable) through the Research Portal.

Please note: when the amendment is submitted to the MEC and/or FAMHP, HIRUZ Contract Unit or TechTransfer will be notified if new agreements are needed or if changes to existing agreements are necessary.

2.3.2.3. MEC and FAMHP approval

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

The amendment can only be implemented when a favourable opinion from the central MEC and/or the FAMHP has been received and as soon as all agreements are finalized (if applicable).

3. Submission under the Clinical Trial Regulation

3.1.1. 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 document, in English and the local language(s) of the participants)
Risk Assessment Plan
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

3.1.2. Submission procedure

3.1.2.1. Preparation of the submission package

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

3.1.2.2. 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’)

3.1.2.3. 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.

3.1.2.4. 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.

3.1.3 Trial follow-up

3.1.3.1. 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).

3.1.3.2. 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.

3.1.3.3. 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).

3.1.3.4. 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).

3.1.3.5. 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).

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 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;
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. The following documents should be provided:

The written statement, completed as agreed upon with (the department of) the PI
Confirmation 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.

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. Notification through the Research Portal of Ghent University (Hospital) is not applicable.