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?

Digital advertising and social media advertising are regulated by the same resolution that regulates other forms of advertising (ANVISA’a Resolution RDC No. 96/2008). There are only a few specific provisions in this resolution focused on Internet advertising (e.g., in relation to how warnings must appear).

9.2 Vulnerable Subjects

As per GSP and ethics guidelines in all Brazilian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations are characterized as those who are relatively (or absolutely) incapable of protecting their own interests due to a lack of autonomy, intelligence, education, resources, strength, or other necessary attributes. These participants may include those with incurable diseases, people in convalescent homes, the unemployed or indigent, patients in emergency situations, ethnic minorities, homeless people, seasonal workers, refugees, minors, and those who cannot give their consent.

All individuals, including healthy research participants, should be seen as intrinsically vulnerable. These participants may currently be exposed to or are at risk of being exposed to an investigational product of unknown safety and efficacy, or one that is not fully understood, which could affect their overall health. In addition, other social, cultural, economic, psychological, or medical factors may adversely affect a participant’s ability to make rational and objective decisions that protect their own interests. However, these factors may not be easily perceptible to the investigator.

The guidelines specify that ethics committees (ECs) (known as Comitês de Ética em Pesquisas (CEPs)) must pay special attention to protecting participants who are from vulnerable populations. If the EC (CEP) regularly evaluates studies involving vulnerable populations, it should consider including members or consultants who know or have had experience working with the group in question. Vulnerable groups should not be included unless the research is necessary to promote the health of the population represented, and this research cannot instead be performed on legally competent participants.

INDIGENOUS PEOPLE

According to Resolution No. 304, special attention should be paid when conducting a study involving indigenous people in Brazil. Studies involving this population should comply with ethical requirements while also considering the unique qualities of each community. The benefits and advantages resulting from conducting a study with indigenous people must also meet the needs of individuals or groups targeted by the study or of related societies, and/or the country as a whole. Investigators should take into account the need to promote and maintain the well-being of participants while protecting and preserving their biological, cultural, individual, and collective health while also contributing to the development of the participant’s knowledge and abilities.

CHILDREN/MINORS

The applicable regulatory requirements do not specify the age of minors. According to Resolution No. 466, when the research participant is a child, the child’s legal representative(s) and/or guardian(s) must sign the informed consent form. However, all pediatric participants should be informed to the fullest extent possible about the study in language and terms that they are easily able to understand.

Children should only participate in clinical studies when their participation is necessary to promote the health of the population represented.

Assent Requirements

An assent form should be used to obtain informed consent from children. The form should be prepared in a language that is accessible to minors or those legally incapable of giving their own consent. After the form is explained and the research study is clarified, the children participants shall provide their consent to participate in the study, without the influence of their legal representative(s) or guardian(s).

Consent for Processing Personal Data

In the context of complying with data protection requirements, the processing of personal data of children and adolescents must be carried out in their best interest with specific and highlighted consent given by at least one (1) of the parents or the legal guardian. However, the sponsors (known as “controllers” in LawNo13.709) are permitted to collect personal data from children without the consent of a parent or legal guardian when collection is necessary to contact the parent or legal guardian, used only once and without storage, or for their protection, and in no case may be passed on to a third party without the consent of at least one (1) parent or the legal guardian.

The sponsor must make all reasonable efforts to verify that the consent was given by the individual responsible for the child, considering the available technologies. Additionally, the information on the processing of the personal data of children and adolescents must be provided in a simple, clear, and accessible manner, considering the physical-motor, perceptual, sensory, intellectual, and mental characteristics of the user, using audiovisual resources when appropriate, in order to provide the necessary information to the parents or legal guardian, and that is appropriate to the child's level of understanding.

PREGNANT WOMEN, FETUSES, AND NEONATES

Any Brazilian clinical studies involving women of childbearing age or who are pregnant, require additional safeguards to ensure that the participants are fully aware of the risks and that the research assesses the risks and benefits as well as any potential impact on fertility, pregnancy, the embryo or fetus, labor, lactation, and the newborn. Resolution No. 466 further states that research on pregnant women should be preceded by research on women outside the gestational period, except when pregnancy is the fundamental purpose of the study. The investigator(s) should also ensure that female participants have the right to participate in the research without the use of compulsory contraceptives—if they have expressly indicated that they are free from the risk of pregnancy and sexual practices, or they are sexually active in a non-reproductive way.

PRISONERS

Prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. Freedom of consent must be guaranteed to those research participants who are fully competent but are exposed to specific constraints or have restricted autonomy. These participants must have the freedom to decide whether or not to participate without any fear of reprisal.

MENTALLY IMPAIRED

The CEP must approve the participation of research participants who are mentally or physically incapable of giving consent, and sufficient justification must be provided for involving this population in a study. Consent should only be provided once the participant is informed about the study, to the extent that he/she is able to understand it, and if able, should sign and date the written informed consent in person. The participant’s legal representative(s) or guardian(s) must also be present during the informed consent process and sign and date the informed consent form.

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

When the research participant is a child, consent is required from both parents.

9.4 Financial Disclosures

Investigators must disclose all financial arrangements and any other perceived or actual conflicts of interest.

9.5 ICF translations – Are Certificates Required?

No, certificates are not required.

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?

There is no specific detail on this matter - the guidelines do not comment on what details should be included in the insurance certificate. Guidelines only specify that insurance certificates are required as specified in Section 2.18 of this guidebook.