Book 5: Informed consent

Independent and informed consent for participation, based on complete, accurate, and appropriately conveyed and understood information as well as its consequences, should be obtained from each individual who is legally competent to give consent. Consent should be obtained for screening for eligibility for participation in an HIV preventive vaccine trial, and before a participant is actually enrolled in a trial. Throughout the trial efforts must be made to ensure that participants continue to understand the consequences of participation and that they participate freely as the trial progresses. Informed consent, with pre-and post-test counselling, should also be obtained for testing HIV status before, during, and after the research.

12.1 The purpose of informed consent is to foster considered decision-making by potential trial participants, including refusal to participate, based on respect for each person's autonomy and right to self-determination.

12.1.1 Investigators should facilitate decision-making for potential participants, who should be empowered to make decisions that are consistent with their values and preferences (see Book 1, 5.3.2.3).

12.1.2 Informed consent is a vital means of ensuring that trials are ethical, and should not be viewed primarily as legal indemnification for investigators.

12.2 Before the start of the research it is recommended that a process of consultation between community representatives, investigators, research ethics committees, regulatory bodies, and sponsor(s) be undertaken to design an effective informed consent strategy. Where appropriate, this consultative process should be supported by capacity building.

12.2.1 Issues affecting decision-making, such as illiteracy, language, cultural norms, and diminished personal autonomy should be addressed in this consultative process.

12.2.2 With vulnerable communities and participants, special efforts must be made to achieve adequate understanding of relevant technical concepts or procedures, such as 'placebo' or 'double blind', and the personal implications of trial participation.

12.2.3 Pre-trial consultations should provide for assistance to participants in the event of physical or psychological harm to themselves or their families as a result of trial participation (see Point 9).

12.3 Trial staff and counsellors should be sufficiently trained to ensure adequate informed consent (see Book 1, 9.6.2). 12.3.1 Trial staff and counsellors should:

1. Establish an optimal emotional context for the exploration of information;
2. Be sensitive to the interpersonal interaction between themselves and participants;
3. Facilitate participants' understanding of technical concepts and their consequences, and the personal, psychosocial implications of trial participation;
4. Facilitate considered decision-making by trial participants, including withdrawal or refusal to participate;
5. Assist with personal concerns arising from trial participation;
6. Evaluate the impact of the trial on participants; and
7. Provide feedback to investigators to adapt and improve consent procedures.

12.4 The disclosure duties of investigators are meticulously detailed in Book 1, 5.3.2.3.

12.4.1 In addition, each prospective participant must be counselled, using appropriate language and techniques, to understand the following specific information:

1. That they will receive counselling and access to the means of risk reduction but that in spite of these efforts, some may become infected with HIV;
2. That it is not known whether the experimental vaccine will prevent HIV infection or disease, and that some of the participants will receive a placebo instead of the candidate HIV vaccine (when such is the case). Therefore, they cannot assume that trial participation will afford them protection from HIV infection (see Points 9 and 14);
3. That participants in phase II and III trials have been selected because they are at relatively high risk of HIV infection;
4. The potential specific risks for physical, psychological and social harm; how these will be minimised, and the types of treatment, compensation and services that will be available should harm occur (see Point 9);
5. The nature and duration of care and treatment that is available if they become infected with HIV during the course of the trial, and any benefits to them personally or to their community that might be expected from participating in the trial (see Points 3, 10 and 16);
6. The confidential nature of their participation, and the limits of confidentiality where these apply (see Book 1, 6.6 and 7.2.3);
7. That they are free to participate, or to withdraw at any time without adverse consequences; and
8. The expected time when results will be made available to them.

12.5 Information transmission should be viewed as a bilateral process between investigators/ counsellors and prospective participants. Investigators and counsellors should make every effort to apprise themselves of the life circumstances, expectations and motivations of prospective participants.

12.5.1 Investigators and counsellors should attempt to understand the implicit and explicit expectations of participants, in order to pre-empt any misunderstanding or sense of exploitation (see Point 5.9).

12.5.2 Investigators should consult with community representatives to assess cultural issues relevant to the transmission of information, and to determine the best procedures for transmitting information (see Point 5).

12.6 Trial participants must have an adequate understanding of the aims, procedures, duration, potential risks, expected benefits, and personal implications of trial participation. They should also understand their rights as participants.

12.6.1 True understanding will require that trial information is understood in terms of the participant's personal, or religious and cultural values.

12.6.2 Participants' short-term recall of technical information about trials is not an adequate indication of understanding.

12.6.3 A range of procedures should be used to assess both understanding of technical terms (e. g. placebo) and understanding of the personal implications of participation (e. g. possible stigma or discrimination). Assessment procedures might include checklists of understanding of technical information, as well as responses to narratives or vignettes related to participation.

12.6.4 Procedures to assess understanding could be developed in consultation with community representatives.

12.6.5 Trial staff should be aware of the phenomenon of 'social desirability'; that is, the tendency for participants to act in order to win the favour of investigators. Social desirability may affect reported or expressed understanding. Trial staff should be sensitive to this phenomenon and to the unexpressed reservations of participants. Neutral advisors (see Book 1, 5.4) and appropriately trained counsellors (see Point 12.3) may play a role in promoting understanding among research participants.

12.7 Legal requirements for capacity to consent must be met. Persons above the age of 18 years, who are of sound mind, are generally considered capable of giving independent informed consent for participation in research. If other requirements are met, when persons below the age of 18 years are to be involved in research, proxy consent must be secured from a parent or legal guardian. In certain circumstances persons below the age of 18 years are considered able to give their own consent. This is discussed in more detail under Point 18.

12.8 Respect for autonomy and self-determination are the foundation of informed consent. Consent must be voluntary and freedom of choice must be safeguarded (see Book 1, 5.3.2.4).

12.8.1 Investigators must make every effort to assess conditions that may threaten the autonomy of participants (see Book 1, 5.3.2.4.1; Points 7 and 13).

12.8.1.1 Participants may attempt to win the favour, and avoid the disapproval, of investigators because of real or perceived differences in power between investigators and participants, and the perceived advantages of trial participation. This 'social desirability' may lead participants to express socially desirable views rather than views based on personal needs and values, for example, about the acceptability of trial procedures.

12.8.2 Investigators must introduce measures to reduce potential threats to autonomy and free consent. These are discussed in Point 13. Trial counsellors (see Point 12.3.1) or community representational structures (see Point 5) might also play a valuable role in voicing the needs and concerns of trial participants.

12.8.3 Undue inducements, offers that persuade participants to volunteer against their better judgement or to assume risks that they would not otherwise have assumed, should be avoided (see Book 1, 9.13). Investigators should consult community representatives for assistance in making appropriate distinctions, with regard to local conditions, between legitimate benefits and undue inducements.

12.9 After careful consideration of the implications of trial participation, prospective participants will decide whether to participate or not. If they choose to participate, a record of their explicit consent should be obtained, through the signing of the informed consent form.

12.9.1 While the formal record of consent is important, it can never substitute for the process of informed consent.

12.9.2 Where participants are illiterate, alternative procedures may be negotiated, such as providing a thumbprint in the presence of approved witnesses.

12.9.3 Informed consent forms should contain sufficient information about the trial procedures, and their consequences for participants, to ensure a clear understanding of relevant considerations, without being complicated by excessive information.

12.9.4 In exceptional cases, prospective participants may refuse to have a formal record of participation. Book 1, 5.2 outlines that written informed consent may be waived only in certain compelling circumstances, and the necessary protections and regulatory requirements must be met.

12.9.5 An appropriate interval should be allowed between counselling and obtaining explicit formal consent.

12.10 HIV vaccine trials require informed consent at a number of stages. The first stage consists of screening candidates for eligibility to participate, which will involve, among other things, an assessment of the individual's risk-taking behaviour and a test for HIV status.

12.10.1 Informed consent should be obtained during screening, after the candidates have received all material information regarding the screening procedures and their consequences, as well as an outline of the vaccine trial in which they will be invited to enrol, if found eligible.

12.10.1.1 Informed consent should also be obtained for the test for HIV status. This should be accompanied by appropriate pre-test and post-test counselling, and referral to appropriate clinical and social support services, if found positive (see South African GCP Guidelines, 9.3 and 9.4.1).

12.10.1.2 Procedures should be set in place to protect people from possible breaches of confidentiality and negative consequences arising from exclusion from trials on the basis of HIV status.

12.10.2 The second stage at which informed consent is required occurs when a person is judged eligible for enrolment.

12.10.2.1 The nature and duration of the trial, potential risks and expected benefits, should be explored and discussed through appropriate methods (see Points 12.4 and 12.6).

12.10.2.2 Participants should understand that they are not obliged to participate and are entitled to withdraw from the trial at any time without suffering any loss of benefits to which they would otherwise have been entitled (see Point 12.4.1).

12.10.3 After enrolment, participants should give ongoing explicit assurance that their continued participation is based on free consent and understanding.

12.10.4 Informed consent, with pre-and post-test counselling, should be obtained for any repeated tests for HIV status.

12.11 A distinction should be drawn between the substantive ethical standard of informed consent and the procedures for the implementation of informed consent. The standard of informed consent should always apply, but the procedures for the most effective implementation of informed consent may vary. Investigators should be sensitive to local, culturally based norms that may affect procedures for obtaining informed consent, but these should not compromise fundamental substantive ethical standards.

12.11.1 In many South African communities it is customary to obtain the permission of community leaders or other designated authorities for investigators to enter the community to invite individual members to participate in research. Investigators should respect such norms and attempt to incorporate them in a spirit of collaboration (see Book 1, 11.4.1). Permission to enter communities should be distinguished from individual informed consent.

12.11.2 Local norms may require that prospective participants, especially women, obtain the approval of other persons (such as marital partners, heads of households) to participate in a trial (see Point 13). Practices based on such norms must never be used as a substitute for individual informed consent, which must always be obtained from the prospective participant.

12.11.3 Investigators should recognise that personhood in the African context is essentially defined by relationship, and that relationships will be important for many trial participants in South Africa. Explicit procedures should be in place to accommodate partners and family in the process of decision-making, if the participant so chooses. If the participant agrees, trial counsellors and staff should be available to the participant's partner or family, to discuss trial-related concerns and questions.

12.11.4 Investigators should also protect the right of individuals to choose not to involve partners or families in the process of decision-making. Care should be taken to consider and offset any potentially harmful social consequences of such a choice.

12.11.5 At times there may be conflict between respect for individual autonomy and regard for the participant's relationships with other individuals and the community. Every attempt should be made to protect both values; however, respect for individual consent should always receive priority.