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 (including the language/claims used and whether or not the mention of open-label products is permitted)?

Yes, recruitment using social media platforms and other traditional media is permitted. Patient-facing materials must be approved by the HREC.

9.2 Vulnerable Subjects

All Australian clinical trials that involve research participants selected from vulnerable populations must follow special processes for consent, as delineated in the National Statement.

The National Statement cautions that dependent or unequal relationships that might compromise the voluntary character of a participant’s decision should be considered. Examples of such relationships include caregivers and people with chronic conditions/disabilities; health care professionals and their patients; teachers and their students; prison authorities and prisoners; governmental authorities and refugees; employers/supervisors and their employees (including members of police and Defense Forces); and service-providers and especially vulnerable communities to whom the services are provided. Where potential participants are especially vulnerable or powerless, consideration should be given to the appointment of a participant advocate.

GCP characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation in a clinical trial, or of a retaliatory response for not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, residents of nursing homes, unemployed or impoverished persons, patients in emergency situations, homeless persons, nomads, refugees, minors, and those incapable of giving consent. People who may be involved in illegal activities, Aboriginal and Torres Strait Islander peoples, ethnic minority groups, and people in other countries are other groups for which specific ethical considerations are required.

Aboriginal and Torres Strait Islander People

Research involving Aboriginal and Torres Strait Islander Peoples must be reviewed and approved by an EC and include assessment and advice from: people who have networks with and/or knowledge of Aboriginal and Torres Strait Islander Peoples, and people familiar with the culture and practices of the relevant Aboriginal and Torres Strait Islander community(ies). In addition, the investigator should ensure the following:

Research methods are respectful and acknowledge the cultural distinctiveness of participating Aboriginal and Torres Strait Islander communities and groups.

There is evidence of support for the research project from relevant Aboriginal and Torres Strait Islander communities or groups and the research methodology engages with their social and cultural practices.

• The research methods provide for mutually agreed mechanisms for recruitment, the information provided about the research, notification of participants’ consent and of research progress, and final reporting.
• Procedures and actions have been taken to monitor and, where appropriate, minimize any potential negative consequences of the proposed research.

Children/Minors

Under Australian law, the age of majority is 18. The age of consent for medical treatment differs across jurisdictions.

When the research participant is a child or young person, it is not possible to attach fixed ages to their capacity to consent. The informed consent form (ICF) must be signed by the child or young person whenever he/she has the capacity to make this decision, and either one (1) parent, except when the ethics committee (EC) (known as Human Research Ethics Committee in Australia) decides that the risks require the consent of both parents or the child or young person’s legal representative(s) or guardian(s). Children and young people should be informed to the extent compatible with their maturity and understanding, and if capable, they should sign and personally date the ICF.

Children and young people who are not of sufficient maturity to consent should only participate in clinical studies when: the research is likely to advance knowledge about the health or welfare of, other matters relevant to, children and young people; or their participation is indispensable to the conduct of the research. When considering the inclusion of children and young people in research, the researchers and EC must consider their level of maturity to ensure adequate protection for his/her welfare.

If the child or young person has the capacity for consent, his/her affirmative consent is required to participate in a study according to his/her level of development and capacities. The following guidelines on maturity and corresponding capacity to consent are provided:

• Infants, who are unable to take part in the discussion about the research and its effects.
• Young children, who are able to understand some relevant information and take part in limited discussion about the research, but whose consent is not required.
• Young people of developing maturity who are able to understand the relevant information but whose relative immaturity means that they remain vulnerable; the consent of these young people is required, in addition to consent from a parent or guardian.
• Young people who are mature enough to understand and consent, and are not vulnerable through immaturity in ways that warrant additional consent from a parent or guardian.

The EC may approve research to which only the child or young person consents if it is satisfied that:

• He/she is mature enough to understand the relevant information and give consent.
• The research involves low risk.
• The research aims to benefit children or young people.
• The child or young person is estranged or separated from his/her legal representative(s) or guardian(s) and the researcher ensures his/her safety, security, and well-being in the research conduct; or it would be contrary to the best interests of the child or young person to seek consent from his/her legal representative(s) or guardian(s), and the researcher ensures his/her safety, security, and well-being in the research conduct.

Researchers must respect the dissent of a child or young person who has the capacity to give consent.

Pregnant Women, Fetuses and Neonates

Studies involving pregnant women, fetuses, and neonates require additional safeguards to ensure that the research assesses the risks to pregnant women, fetuses, and neonates.

Informed consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section. However, except for therapeutic innovative therapy cases, the process of providing information and obtaining consent for participating in research should be clearly separate from clinical care if the woman is pregnant and the fetus is in utero.

The well-being and care of the woman who is pregnant and of her fetus always takes precedence over research considerations. Research involving a fetus or fetal tissue should be conducted in a manner that maintains a clear separation between the woman’s clinical care and the research.

Further, the woman should be informed of the following:

• That she should consider whether to seek consent to the proposed research from any other person (e.g., the other parent).
• Whether it is possible to store the fetus or fetal tissues for later use in research.
• That she is free to withdraw her consent to the research at any time, whether before or after a termination or other loss of a fetus.
• Whether there is potential for commercial application of outcomes of the research, including the development of cell lines.
• That she will not be entitled to a share in the profits of any commercial applications.
• Whether fetal organs or stem cell lines developed from them will be exported to another country.

Prisoners

Prisoners are considered vulnerable because incarceration, which may create a dependent or unequal relationship, could affect their ability to make voluntary decisions regarding participation in research.

A research study involving prisoners should, wherever possible, invite prospective participants to discuss their participation with someone who is able to support them in making their decision. If prospective participants are especially vulnerable, researchers should consider appointing a participant advocate.

Mentally Impaired

The ethics committee (EC) (known as Human Research Ethics Committee in Australia) must approve the participation of research participants who are mentally incapable of giving consent. While the National Statement distinguishes cognitive impairment from intellectual disability and mental illness, the informed consent guidelines are similar. 

The mentally impaired participant must consent if he/she has the capacity, or the participant’s legal representative(s) or guardian(s) must consent on behalf of the mentally impaired participant. Where a legal representative(s) or guardian(s) has given consent, the researchers still must explain to the participant what the research is about and what participation involves. If the participant recovers the capacity to consent, the researcher should offer him/her the opportunity to continue participation or withdraw. Dissent will preclude the participation of a mentally impaired person.

If the participant’s mental impairment is temporary or episodic, researchers should seek consent when the condition does not interfere with his/her capacity to give consent. This consent should occur in the presence of a witness who is familiar with the participant, is independent of the research, and understands the research’s merits, risks, and procedures.

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

The informed consent form (ICF) must be signed by the child or young person whenever he/she has the capacity to make this decision, and either one (1) parent, except when the ethics committee (EC) (known as Human Research Ethics Committee in Australia) decides that the risks require the consent of both parents or the child or young person’s legal representative(s) or guardian(s).

9.4 Financial Disclosures

Researchers must disclose any financial activity which may be considered a real or perceived conflict of interest.

9.5 ICF translations – Are certificates required?

There may be occasions when participants may require documents translated into their native language as well as interpreters, when translation of participant-facing documents is required, the corresponding certificate of translation should be requested and kept for filing.

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?

Yes, the local Sponsor should be listed on the insurance. The duration and amount of coverage is study-dependent.