9. Subject Considerations

9.1 Clinical trial subject recruitment: Are digital advertisements (including social media streams such as TikTok) allowed and, if so, what regulations govern them? 

We have not been able to determine any national regulations in this regard. Advertisement for the recruitment of patients seems to be permissible under the EU CTR 536/2014.

Please see Annex I – Pt. K-59 & K-60 of EU CTR 536/2014.

By way of case study (website of Pfizer’s Clinical Research Unit in Brussels - https://www.brusselscru.com), it appears that the following information may need to be provided in the advertisement:

1. Title/ Brief description of the study
2. Eligibility criteria for potential participants
3. What to expect – approximate duration of study, compensation payable, if any. 
4. Template of ICF
5. Contact details for finding more information
6. Details on how to participate
7. Advertisement in the language of the participant (English/French/Dutch)

9.2 Vulnerable Subjects

The Belgian law does provide for the protection of minors or vulnerable subjects, by allowing for a representative to be appointed on behalf of them. EU CTR has similar provisions.

Article 11, Law of 2017, states that “Without prejudice to the application of the [EU CTR], the "legally designated representative", within the meaning of Article 2, § 2, 20, of the Regulation is appointed, for the purpose of exercising the rights of the minor and incapacitated participant, in accordance with Articles 12 and 14 of the Act of 22 August 2002 on the rights of the patient.”

For easy reference:

1. “Legally designated representative” is defined in Article 2, § 2, (20) of EU CTR as “a natural or legal person, authority or body which, according to the law of the Member State concerned, is empowered to give informed consent on behalf of a subject who is an incapacitated subject or a minor”.
2. Article 12 of the Act of August 2002 (relating to the rights of the patient) reads as follows:
   • “§ 1. If the patient is a minor, the rights established by this law are exercised by the parents exercising authority over the minor or by his guardian. 
   • § 2. Depending on his age and maturity, the patient is associated with the exercise of his rights. The rights listed in this law can be exercised independently by the minor patient who can be deemed capable of reasonably assessing his interests.”
3. Article 14 of the Act of August 2002(relating to the rights of the patient) reads as follows:
   • “§ 1. The rights of an adult enshrined in this law are exercised by the person himself, provided that he is capable of expressing his will to do so. These rights are, however, exercised by a person whom the patient has previously designated to replace him, insofar as and for as long as he is unable to exercise his rights himself. The designation of the person referred to in paragraph 2 is made by a specific written mandate, dated and signed by this person as well as by the patient, a mandate by which this person gives his consent. This mandate may be revoked by the patient or by the representative designated by him in writing, dated and signed.
   • § 2. If the patient has not appointed a representative or if the representative designated by the patient does not intervene, the rights established by this law are exercised by the administrator of the person, designated by the judge of peace to do so, in accordance with Article 492/1, § 1, paragraph 4, of the Civil Code, insofar as and for as long as the protected person is unable to exercise his rights himself.
   • § 3. If no administrator is authorized to represent the patient under § 2, the rights established by this law are exercised by the cohabiting spouse, the legal cohabiting partner or the de facto cohabiting partner. If the person who can intervene by virtue of the first paragraph does not wish to intervene or if he defaults, the rights are exercised, in successive order, by an adult child, a parent, an adult brother or sister of the patient. If the person who can intervene by virtue of paragraph 2 does not wish to intervene or if he fails to do so, it is the professional practitioner concerned, if necessary within the framework of a multidisciplinary consultation, who looks after the interests of the patient. The same applies in the event of a conflict between two or more persons who may intervene under § 2 or paragraphs 1 and 2.
   • § 4. The patient is associated with the exercise of his rights as much as possible and taking into account his ability to understand.
   • § 5. The right of complaint referred to in Article 11 may, by derogation from §§ 1, 2 and 3, be exercised by the persons referred to in these paragraphs, designated by the King, by decree deliberated in the Council of Ministers, without must follow the order provided.”

The EU CTR 536/2014 further states that in Article 10:

1. "Where the subjects are minors, specific consideration shall be given to the assessment of the application for authorization of a clinical trial on the basis of paediatric expertise or after taking advice on clinical, ethical and psychosocial problems in the field of paediatrics.
2. Where the subjects are incapacitated subjects, specific consideration shall be given to the assessment of the application for authorization of a clinical trial on the basis of expertise in the relevant disease and the patient population concerned or after taking advice on clinical, ethical and psychosocial questions in the field of the relevant disease and the patient population concerned.
3. Where the subjects are pregnant or breastfeeding women, specific consideration shall be given to the assessment of the application for authorization of a clinical trial on the basis of expertise in the relevant condition and the population represented by the subject concerned.
4. If according to the protocol a clinical trial provides for the participation of specific groups or subgroups of subjects, where appropriate, specific consideration shall be given to the assessment of the application for authorization of that clinical trial on the basis of expertise in the population represented by the subjects concerned.
5. In any application for authorization of a clinical trial referred to in Article 35, specific consideration shall be given to the circumstances of the conduct of the clinical trial."

9.3 Pediatrics (including whether consent from a single parent is sufficient vs. requiring both parents to sign)

According to the information provided under EMA's “Informed Consent for Paediatric Clinical Trials in Europe 2015 (last revision 06 June 2023), in Belgium, the general rule with respect to third parties acting in good faith is that consent is needed from one parent (deemed to act with the agreement of the other parent).

If there are indications of parental disagreement: both parents.

Additional information can also be found in the European Judicial Network- Parental Responsibility- child custody and contact rights.

9.4 Financial Disclosures 

The EU CTR 536/2014 requires the following information to be submitted at the time of submission of the dossier (please see - Annex I. P of EU CTR 536/2014): 

“69. A brief description of the financing of the clinical trial.

70. Information on financial transactions and compensation paid to subjects and investigator/site for participating in the clinical trial shall be submitted.

71. Description of any other agreement between the sponsor and the site shall be submitted.”

In addition, The European Federation of Pharmaceutical Industry Associations (EFPIA) Code provides for disclosures in relation to clinical studies, as follows (see Annex B on page 37 of the Code), in accordance with clauses 22 & 23.

Clause 23 provides that “Research and Development ToVs in each Reporting Period must be disclosed by each Member Company on an aggregate basis. Costs related to Events that are clearly related to activities covered in this section can be included in the aggregate amount under the “Research and Development Transfers of Value” category”.

Research and Development ToVs are defined in Section 15.01 of the HCP Code as: “Transfers of Value to HCPs or HCOs related to the planning or conduct of (i) non-clinical studies (as defined in OECD Principles on Good Laboratory Practice); (ii) clinical trials (as defined in Regulation 536/2014); or (iii) NIS that are prospective in nature and that involve the collection of patient data from or on behalf of individual, or groups of, HCPs specifically for the study”.

9.5 ICF translations – Are Certificates Required? 

The national law is silent on whether or not a translation certification is required. However, under normal practice, Certificates of Translations (CoTs) are not required to be submitted, but relevant CoTs should be filed within the Trial Master File.

9.6 Subject Compensation: Is there a need for a local sponsor to be listed on the insurance certificate, the insurance certificate to cover the duration of the study, and specific minimum amounts of coverage to be specified, both for individual events occurring and in aggregate?

The national legislation does not specifically provide for these matters, except that maintenance of insurance is mandatory. 

Please see the relevant provision of the Law of 2017 below:

“Article 12. § 1. The sponsor shall assume, even without fault, liability for damage caused to the subject or, in the event of death, to his successors in title, whether directly or indirectly related to the clinical trial. Any contractual stipulation aimed at restricting this liability is deemed null and void.
Where a clinical trial has more than one sponsor, all sponsors are jointly and severally liable.

§ 2. Prior to the clinical trial, the sponsor shall take out insurance covering this liability as well as that of any participant in the clinical trial, regardless of the nature of the links between the stakeholder, the sponsor and the subject.

In accordance with Article 74, § 1, of the [EU CTR], the sponsor or a legal representative of the sponsor is established in the European Union.

When a clinical trial has more than one sponsor, one of them is designated as responsible for taking out the insurance referred to in paragraph 1.

§ 3. For the purposes of this article, the participant or his successors in title may summon the insurer directly in Belgium, either before the judge of the place where the event giving rise to the damage occurred, or before the judge of the participant's domicile, or before the judge of the insurer's registered office.

Without prejudice to the possibility of fixing in the contract between the sponsor and the insurer maximum amounts in order to compensate the damages of the participant or, in the event of death, his successors in title, as well as to the possibility of fixing a maximum duration of coverage of the risk, no nullity, exception or forfeiture deriving from the law or the insurance contract may be invoked by the insurer against the participant or his successors in title, except in the cases provided for by the King.”

This is in line with the provisions of Article 76 of the EU CTR.

Furthermore, BAREC provides advice on the Insurance Coverage for clinical trials: