DISCUSSION DOCUMENT

Guidelines for the development of culturally sensitive approaches to obtaining informed consent for participation in HIV vaccine-related trials

Linda M Richter

Graham C Lindegger

Quarraisha Abdool Karim*

Nolwazi Gasa*

School of Psychology, University of Natal, Private Bag X01, SCOTTSVILLE, South Africa

richterl@psy.unp.ac.za

Phone: 09-27-331-2605016; Fax: 09-27-331-2605809

* Medical Research Council (Durban)

Commissioned by UNAIDS

Submitted February 1999

Revised May 1999

DISCUSSION DOCUMENT

Guidelines for the development of culturally sensitive approaches to obtaining informed consent for participation in HIV vaccine-related trials

Commissioned by UNAIDS

Submitted February 1999

Revised May 1999

CONTENTS

PART 1: OVERVIEW

1.1. INTRODUCTION ....................................................................................................... 1

1.2. LITERATURE REVIEW ............................................................................................ 1

1.2.1 Informed consent in the context of biomedical ethics

1.2.2 The interdependence of science and ethics

1.2.3 The moral and legal foundations of informed consent

1.2.4 Differences between treatment and research

1.2.5 Obstacles to informed consent

1.2.6 The role of culture in informed consent

1.2.7 Risks in HIV vaccine-related trials

1.2.8 Voluntariness and freedom from coercion

1.2.9 Summary

1.3 CONCEPTUAL FRAMEWORK FOR PROCEDURES TO OBTAIN

INFORMED CONSENT .......................................................................................10

1.3.1 The decision making process

1.3.2 Social desirability

1.3.3 Understanding

1.3.4 Freedom from coercion

1.4 REFERENCES ............................................................................................................12

PART 2: PRACTICAL GUIDE

2.1 PREPARATION FOR INFORMED CONSENT ..................................................1

2.1.1 Community preparation

2.1.2 Preparation of the scientific team

2.1.3 Researcher understanding

2.1.4 Staff preparation

2.1.5 Preparation of potential volunteers and significant others

2.2 INFORMED CONSENT MATERIAL PREPARATION ......................................2

2.2.1 Preparation of information for education of volunteers

2.2.2 Selection and training of staff for education and counselling

2.2.3 Methods of information transmission

2.2.4 Interactional aspects of education

2.2.5 Ongoing monitoring of information provided

2.3 UNDERSTANDING AND DECISION MAKING .................................................4

2.3.1 Assessment of understanding by volunteers

2.3.2 Research team understanding of volunteers' motivations

2.4 VOLUNTARINESS AND FREEDOM FROM COERCION ................................6

2.5 CONSENT ...............................................................................................................6

2.5.1 Phased consent

2.5.2 Ongoing right to withdraw

2.5.3 Multi-person consent

2.5.4 Agreement about compensation

2.6 EVALUATION OF THE CONSENT PROCESS AND CONDITIONS ................9

2.7 PROTOCOL FOR IMPLEMENTING A CULTURALLY

SENSITIVE INFORMED CONSENT PROCESS ................................................10

2.7.1 Pre-recruitment stage

2.7.2 Preparation for informed consent

2.7.3 Recruitment

2.7.4 Evaluation of recruitment procedures, including understanding

2.7.5 Obtaining consent

2.7.6 Ongoing counselling and evaluation

2.8 TASKS AND RESPONSIBILITIES FOR IMPLEMENTATION OF

INFORMED CONSENT PROCEDURES ............................................................15

2.9 TIMELINE ............................................................................................................17

2.10 BUDGET ................................................................................................................18

PART 1: OVERVIEW

1.1 INTRODUCTION:

This paper, Approaches to obtain informed consent, is one of three documents commissioned by UNAIDS to address some specific ethical, social and behavioural implications of HIV vaccine-related trials, with particular reference to potential study populations in Africa, Latin America and Asia. The other two documents are Monitoring risk behaviour in HIV vaccine trials and Explore willingness to participate in trials. The latter papers are preceded by other UNAIDS initiatives to address these implications, including a working document by Dr MJ Paris Spink entitled Social and behavioural dimensions of HIV vaccine trials, and regional workshops in Ouro Pretro, Bangkok and Entebbe to discuss ethical issues in preventive HIV vaccine trials.

1.2 LITERATURE REVIEW:

... ethical systems do not exist in order to eliminate ethical discourse, they provide a framework for such discourse.

Christakis (1992, p. 108)

2.1 INFORMED CONSENT IN THE CONTEXT OF BIOMEDICAL ETHICS

informed consent cannot be discussed in isolation from ethics in general, nor from other ethical issues in vaccine-related trials. This is because the informed consent document is an expression of a larger contract governing the relationship between science and society, and embodied in the relationship between the scientific team and the volunteer⁽¹⁾. As a result, obtaining written informed consent cannot compensate for comprises to the principles of respect for persons, beneficence, and justice in other respects of a trial. One of the problems with current approaches to informed consent is that consent has been reduced to a technical issue, often removed from wider ethical considerations.

The history of informed consent is well documented (Katz, 1972). Landmarks in its development from the time of its formulation in the 1947 Nuremberg Code are: the International Covenant on Civil and Political Rights (Article 7) adopted by the United Nations General Assembly in 1966; the Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research (1979); the World Medical Association Declaration of Helsinki (most recently revised in 1989); and the 1993 International Ethical Guidelines for Biomedical Research Involving Human Subjects proposed by the Council for International Organizations of Medical Sciences (CIOMS) and the World Health Organization (Beauchamp & Childress, 1983), a further revision of which was initiated in 1998.

The Belmont Report outlined three principles to guide the conduct of research - informed consent (embodying the ethical precept of respect for persons), the assessment of risks and benefits (beneficence and nonmaleficence), and the selection of subjects (justice). The report conceptualised informed consent as consisting of three elements: information, comprehension and voluntariness. Informed consent procedures in many senses thus represent the ethical stance adopted by scientists towards volunteers in a trial. It is from this perspective that we argue that the technicalities of informed consent are not separable from the conditions created in the trial to give meaning to the principles of respect for persons, beneficence and justice. For example, the access volunteers will have to treatments, compensation for research-related injuries, provisions for trial participants once the trial is completed, and the steps taken to counteract the stigma and discrimination that may be consequent on trial participation.

The early documents were based on an assumption of the universal applicability of the requirements to respect persons and protect their individual rights. And, while current requirements for consent continue to stress individual autonomy, understanding and freedom from coercion, there is a growing tendency to regard research in developing countries⁽²⁾ as presenting a set of special circumstances requiring difficult ethical interpretation and application. The prospect of large scale vaccine trials to control HIV/AIDS, designed for implementation among vulnerable groups, has increased debate around the issues of if, when and how deviations from standard requirements for informed consent are justified.

The Belmont Report emphasised the importance of consent requirements when research involved vulnerable persons, including minorities and economically disadvantaged groups. The CIOMS Guidelines pay particular attention to vulnerability, defined as the incapacity to protect one's own interests (for a number of reasons including unfamiliarity with modern medical concepts), as well as to research involving persons in underdeveloped communities (Guideline 8). This guideline reiterates that every effort should be made "to secure the ethical imperative that the consent of individual subjects be informed (p. 25), and advises researchers to "respect the ethical standards of their own countries and the cultural expectations of the societies in which research is undertaken" (p. 26). Other aspects of the guideline stress: the need for research to be responsive to the health needs of local communities, the reasonable availability to the community of tested products, the need for intermediaries to assist people to give informed consent when required, and the need for ethical review by persons with a thorough understanding of a community's customs and traditions.

... only the "authenticity of volunteering overcomes the depersonalizing effect of being treated as a token or sample in an experiment"

Jonas (1969, in Mackillop & Johnston, 1986; p. 181)

1.2.2 THE INTERDEPENDENCE OF SCIENCE AND ETHICS

Instead of seeing science and ethics being as separate and even opposing, a more sophisticated understanding recognises their essential interdependence.

Firstly, it is appreciated that poor science is unethical. It is unethical to ask people to participate in studies that have little or no likelihood, because of poor conceptualisation and/or design, of producing meaningful results or furthering scientific knowledge.

Secondly, inadequate attention to respect for persons, beneficence, and justice, can affect the scientific viability and validity of research. For example, conditions governing participation in trials affects recruitment, attrition, adherence and compliance, in ways that can introduce serious confounding, as well as threats to the internal and external validity of the data collected (Leventhal, 1991; Verheggen & van Wijmen., 1996).

Research conducted by humans on, or amongst, other humans is an essentially social activity. This necessitates responsibility for integrity in research relationships, as well as an awareness that there are always social consequences to research and that there are always impacts on a personal level (Mackillop & Johnston, 1986).

1.2.3 THE LEGAL AND MORAL FOUNDATIONS OF INFORMED CONSENT

Informed consent and related ethical requirements governing biomedical research have their origins in morality and in a shared revulsion towards the degeneracy of Nazi experimentation. However, subsequent developments in informed consent requirements have been strongly influenced by the litigious milieu in the United States of America and the necessity to develop legal criteria for consideration in criminal and civil cases (Alfidi, 1971; Hertz, Looman & Lewis, 1992; Kaufman, 1983; Meisel & Roth, 1983).

This legal history and context has, in the opinion of many authors, diminished the concept of informed consent. Informed consent is often, it is claimed, treated as a mere legalism (Baum, 1986; Finkelstein, Smith & Faden, 1993); a rite rather than a right; "... no more than an elaborate ritual, a device that, when the subject is uneducated and uncomprehending, confers no more than the semblance of propriety on human experimentation" (Ingelfinger, 1972).

This is one sense in which the claim is made that informed consent does not work. The scientists obliged to conform to informed consent requirements have to be convinced, as a scientific team, of both the moral right of human beings to decide what is to be done to them in research studies, and the scientific sense of not treating human beings as inert specimens. Otherwise, ethical requirements for informed consent can be manipulated into a cookbook approach to conform to the minimum bottom line. Rules can proliferate in an attempt to cover all possible gaps, yet still fail to achieve the purpose that concrete actions must be taken to demonstrate respect for persons by ensuring their autonomy.

1.2.4 DIFFERENCES BETWEEN TREATMENT AND RESEARCH

The Belmont Report distinguished between biomedical research and therapy on the basis that research involves greater risks for the patient-volunteer, and on the basis of the different intentions and motivations of the health professionals involved. The clinician is obliged to render "personal care" (Fried, 1974); care based entirely on considerations of the wellbeing of the patient. In contrast, the researcher is immediately intent on developing or testing new knowledge, even though the long-term goal of such investigations is to benefit patients. The altered intention of the investigator-physician potentiates a conflict of interests because the patient-volunteer becomes a means to an end (Lantos, 1993; Tuthill, 1997). In this situation, the interests of the investigator-physician and patient-volunteer may no longer be congruent. This conflict between the wellbeing of the patient and the goals of the investigating physician, is illustrated, for example, by placebos which are not meant to benefit the individual patient, and by randomisation which may conflict with clinical judgement about how to achieve maximum benefit available (Appelbaum, Lidz & Meisel, 1987).

Kaufman has argued that the distinction between therapy and research is simplistic, particularly when considered in the light of innovative or experimental therapy. However, it may also be simplistic when considered from the perspective of the patient-volunteer. Several studies, including in our local environment have found that one of the primary motivations for volunteering for participation in research is the belief that better care, better treatment, or other health benefits will accrue (Abdool Karim et al, 1997; Appelbaum et al, 1987; Tuthill, 1997). In many settings, but particularly in resource-poor environments, the same health professionals may function in respect of the community as both physicians and investigators. If the role of the health professional as an investigator is not made plain to the patient as a volunteer, the resulting role confusion, in the mind of the patient-volunteer, may constitute one of the most fundamental obstacles to voluntary entry into trials and thereby to informed consent. The problematic nature of this situation was well-recognised in the Belmont Report - "A continuum of such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion ends and undue influence begins"

1.2.5 OBSTACLES TO INFORMED CONSENT

There is a comprehensive literature on informed consent. Over 1 000 references are listed in Medline since 1989 in which informed consent is the focus of the paper (Kent, 1996). A good part of this literature, in one way or another, refers to or documents difficulties in obtaining informed consent. This is as true in the United States of America and the United Kingdom, as anywhere else in the world (Alfidi, 1971). It is hard to imagine that it could be otherwise. As Beecher (1966, p. 1355) noted, more than 30 years ago, "all so-called codes are based on the bland assumption that meaningful or informed consent is readily available for the asking".

The difficulties in obtaining informed consent include:

1. The problems lay people have in remembering and understanding the details of scientific design and biomedical treatment comparisons (Cassileth et al, 1980);

2. Defensive psychological forgetting of threatening information, especially about risks (Verheggen & van Wijmen, 1996);

3. Barriers to communication emerging from cultural and class differences; these include illiteracy, language differences, competing models of disease, presumed differences in the construction of personhood, etc (Schoepf, 1991);

4. Situational pressures, including a feeling of obligation, as volunteers get caught up in several processes with different people, so that they can no longer distinguish between treatment and research, nor do they feel able to exert their right to withdraw (Meisel & Roth, 1983);

5. Implicit forms of coercion which threaten voluntariness and the right to withdraw (Abdool Karim et al, 1997; Levine, 1991), and

6. The resistance of health professionals which arises from the challenge that informed consent requirements pose to their assumed beneficence (Kaufman, 1983; Lidz et al, 1983; Meisel & Kuczewiski, 1996; Taylor & Kelner, 1987).

Informed consent is by all accounts an ideal not easily accomplished. This is the second sense in which the criticism is heard that informed consent does not work. However, the fact that informed consent is difficult to attain, in no way justifies dispensing with it or relegating it to a formality.

Formalistic consent requirements can become a way of delegating the entire burden of medical decisions to the patient, thus isolating him or her from physician and family support and limiting medical responsibility.

(Gostin, 1995; p. 845)

1.2.6 THE ROLE OF CULTURE IN INFORMED CONSENT

A lengthy debate has been waged concerning the role of cultural differences in significantly altering either the requirements or methods for obtaining informed consent from individual volunteers. This debate is summarised by the opposing accusations of "ethical imperialism" on the one hand, and advocating "double standards" on the other (Angell, 1992; Barry, 1992; Benatar, 1998; Ijsselmuiden & Faden, 1992; Olivier, 1995).

Sometimes the question is formulated as to whether American ethical standards should be everywhere applied? This question involves several complex issues and the arguments can be interpreted in different ways. Another way the debate is approached is by asking whether ethical principles are relative or universal, and whether informed individual consent, based on notions of individual autonomy, should be imposed by Western researchers on collectivist cultures as occur, for example, in parts of Africa and Asia, and which are assumed to place little value on personal autonomy.

It stands to reason that because morals are social constructions, that ethical standards, in general, are likely to differ from culture to culture and are in this sense, relative (Christakis, 1992). However, this does not mean that the ethical principles generated specifically to govern the conduct of biomedical research are relative and therefore amenable to adjustment or compromise. Ethical principles were articulated to restrain biomedical research regardless of where it occurs. Therefore, the ethical principles under discussion are specific to the activity (biomedical research) and not determined by the setting (for example, a society based on collectivist values) (Christakis, 1992; Gostin, 1995).

In addition, the anthropological literature articulating differences between societies characterised by collectivist and individualist values, does not support the conclusion that collectivist societies are uniformly devoid of concepts relating to individuality and personal autonomy, and that individuality is unconditionally rejected (Gasa, 1999; Ijsselmuiden & Faden, (1992).

There is almost no support in the literature for the idea that individual informed consent can be replaced by the proxy consent of local leaders, government officials, husbands, fathers or other traditional male authorities. In fact, cogent arguments have been advanced by several authors (Adityanjee, 1986; Angell, 1992; Barry, 1992; Benatar, 1998; Ijsselmuiden & Faden, 1992; Olivier, 1995) for strict adherence to the requirement that individual volunteers give informed consent for their participation in clinical trials. Among other things, there are no guarantees that proxy authorities have the best interests of all potential participants in mind with respect to a particular endeavour; in addition to which, their decisions are likely to replicate and entrench traditional age, gender and status differentials to the detriment of individual rights.

The uncompromising adherence to the principle of informed consent does not exclude sensitivity to local customs and expectations. It is polite and anticipated that any major research endeavour, such an HIV vaccine-related trial, will make contact with local authorities and seek their consent and cooperation before approaching citizens to volunteer for a study with potential personal, economic and political ramifications for the society. This is not a custom peculiar to Africa, Asia or Latin America - it would be as much expected and appreciated in Cambridge, Massachusetts. Undue interpretations of differences between societies can function to objectify others, and care should be taken not to see all cultural differences as indicating extreme incompatibilities between social values and practices.

Similarly, the notion that an individual approached for recruitment into a trial, especially a trial with considerable personal ramifications, might want to discuss the issue with family and friends is not unusual (Nelson, 1992). However, the consent of such people cannot replace the individual informed consent of the volunteer (Gostin, 1995). Rather than seeking the proxy consent of such people, scientific teams should ensure that recruits and volunteers feel free to share decisions with their families or not, depending on the idiosyncratic circumstances of each potential volunteer.

The idea that people in resource-poor countries - who are likely to be culturally distant from Western researchers and also technocratic elites from their own society - cannot understand the basics of research design or biomedical treatment options because they have little education, speak languages devoid of the technical terms of biomedical research, or have different views about health and illness, appears to be exaggerated. It may be difficult to communicate the purposes, conditions and risks of research, but the difficulty of doing so should not be used to detract from the importance of obtaining individual informed consent. In any case, several researchers (Abdool Karim et al, 1997; Preziosi et al, 1997) have recounted experiences to indicate that, with sufficient care, acceptable levels of understanding can be communicated to volunteers in Africa. In our own research (Gasa, 1999), for example, we have found that largely illiterate rural people can understand randomization when illustrated with coins; but, like Westerners, they seem to show defensive denial when the idea of randomisation is personalised

The foregoing arguments for the necessity of obtaining individual informed consent do not invalidate the assertion that important social and cultural differences are likely to exist between scientific teams and volunteers, whether the scientific teams are foreign or local. Sometimes what are called cultural differences reflect also differences in power, prestige and resources. For example, we have found (Gasa, 1999) that largely illiterate rural women find it extremely difficult to respond to questions with an Agree or Disagree format. It is very difficult for them to engage in a personalised discourse of conflict or disagreement with people they consider to be authorities or in a superior position.

On a macro level, issues raised in connection with culture are frequently associated with two assumptions: firstly, that vaccine trials will involve a binational or international agreement where a more resourced country from the North will finance and provide intellectual leadership for the conduct of the HIV vaccine trial based on a product developed in the North; and secondly, that the host country involvement and contribution occurs only at the stage of an efficacy trial. Developments during the last year have radically altered this model of assumed vaccine development and testing. Several governments from the South (including China, Cuba, India, South Africa and Pakistan) have made a commitment to and become actively involved in vaccine development. This shift in initiative places new imperatives on the need to understand and come to grips with the interplay between culture and power. There may be an unwarranted assumption that the role of cultural differences will be negligible and therefore also the threats to understanding and voluntariness when the product and trial are conducted by local researchers involving local participants. Power differentials between researcher elites and local communities will continue to exert effects previously attributed also to the influence of cultural differences.

1.2.7 RISKS IN HIV VACCINE-RELATED TRIALS

It is obvious that research which carries significant risks as the cost for yielding important benefits is likely to pose the most complex ethical problems. HIV vaccine-related trials fall into this category. No one can deny the significant medical and social risks that these trials present for potential volunteers (Porter et al, 1989).

Firstly, such trials need to be conducted in regions of the world where large numbers of suitable participants, that is, individuals at high risk for HIV infection, are available, and where antiretroviral drugs which could interfere with the assessment of vaccine efficacy, are not widely available (Bloom, 1998). These individuals are, by definition, vulnerable to exploitation and stigmatisation. Currently, most of these individuals are in resource-poor countries which themselves are vulnerable to exploitative relationships with funding agencies and research groups from the West and from within their own countries (Barry, 1992; Benatar, 1998; Ijsselmuiden & Faden, 1992).

Secondly, participation in trials carry significant social risks for participants, including those that arise from vaccine-induced seropositivity. Social risks include confidentiality issues, stigma, violence and abandonment, occupational and social constraints, among others. Thirdly, exposure to a vaccine may enhance disease if the individual is subsequently exposed to HIV, and may affect a participant's capacity, through immune tolerance, to receive a vaccine developed in the future.

In addition, the risk-benefit ratio may be distorted by the type of vaccine being tested in particular community or amongst a particular group of volunteers. While the vaccinological implications of the different subtypes of HIV remain uncertain, there has been increasing concern about the ethics of testing a product that has been developed against a sub-type that is not prevalent in the population where the product is proposed to be tested. The rationale that high incidence rates justify such trials distorts the principle of justice - in that the risks and benefits are not equal for the host and donor countries or their citizens. Of equal importance in cost-benefit evaluations is the choice of vaccine design. The emphasis to date has been on designs that emphasise safety at the expense of immunogenicity, which has retarded the vaccine development agenda, thereby depriving potential beneficiaries earlier access to protection from developing products.

Informed consent procedures need to make risks clear to recruits, at the same time as indicating the potential benefits to society of producing an effective vaccine, together with any other benefits specific to a particular trial. This, together with the need to communicate the nature of the experimental design, creates a considerable communication challenge. It is likely that strong motivations on the part of volunteers will drive participation in vaccine trials, particularly the desire to avoid infection and/or seek treatment. These motivations will themselves complicate volunteers' interpretation of the purposes and methods of the trial. In order to understand the social processes governing recruitment and adherence, it will be necessary to have some understanding of volunteer motivations.

Several questions recur in the literature with respect to informed consent, among which are the following:

1. How can consent be truly informed when many laypersons cannot comprehend complex medical and scientific information?

2. How much disclosure of information is necessary and beneficial to informed decision making, and how much is harmful to the wellbeing of volunteers?

3. How can an investigator know how a volunteer interprets information about an experiment?

4. Is the consent form the appropriate instrument through which researchers may fulfill their obligations not to treat volunteers merely as a means to an end?

6. Are individuals free to participate under conditions of limited health care resources which coincide with research sites?

No clear answers exist to these questions. Christakis (1992) argues that final and transcendant resolution of ethical issues is not possible, apart from decisions made in particular local settings in which the problems are framed. We return to the assertion that the dilemmas of obtaining informed consent in any particular setting cannot be separated from the design and ethical intentions of the scientific team. It may be advisable, in addition to the requirement for signed informed consent by volunteers, for scientific teams to write ethical justifications for all aspects of the research design in terms of the fundamental principles of respect for persons, beneficence and justice.

1.2.8 VOLUNTARINESS AND FREEDOM FROM COERCION

Financial and other benefits offered to trial participants are regarded as inducements that impair voluntariness and act to influence participation. For example, Adityanjee (1982) argues that money offered to pay for transport for examinations and other procedures can function as an inducement in poor communities. He advocates that no benefits or potential benefits should be discussed until consent has been given.

On the other hand, it must be acknowledged that the communities likely to be targeted for trials, particularly in southern hemisphere countries, are generally poor. Individuals and families will not be easily persuaded to cover transport costs for visits to health centres with no apparent benefit to themselves, especially when they have other very pressing financial priorities. In addition, work and especially women's work in households, has economic value. Many women spend hours collecting water and fuel, washing clothes, preparing food, and caring for small children and dependent others. Time spent out of the household to attend to trial examinations is a spent resource, and other capital has to be found to compensate for them.

Research teams will have to struggle with issues concerned with compensation and benefits for trial participants. Simplistic either-or dichotomies, while morally comfortable, are not going to be adequate to deal with the complexities of motivations and expectations that potential trial participants bring to the informed consent process.

Ethical dilemmas, by their very nature, are often not amenable to solutions which can be shown to be unequivocally and substantively correct.

(Benatar, 1988; p. 222)

1.2.9 SUMMARY

In the preceding sections, a conceptual framework was created for the consideration of informed consent. This framework informs understanding of informed consent in the following ways:

1. Informed consent should not be seen merely as a technical requirement of ethical oversight bodies. Instead, informed consent procedures express researchers' commitment to respect for persons and the principle of autonomy.

2. HIV vaccine-related trials will have to transcend technical approaches to informed consent and grapple with thorny issues of risks and benefits.

3. Culture is a complex concept that overlaps also with class and other power differentials. Considerable sensitivity is required both to accommodate cultural differences while at the same time recognising the fundamental nature of the ethical principles of biomedical research.

4. The ethical issues facing HIV vaccine-related trials will require that scientific teams create mechanisms for public discussion and debate amongst themselves on ethical issues to resolve matters concerning design as well as benefits for participants.

1.3 CONCEPTUAL FRAMEWORK FOR PROCEDURES TO OBTAIN INFORMED CONSENT:

The procedures recommended to obtain informed consent laid out in Part 2 of this document are based on the notion of informed consent as a shared decision making process between researcher and volunteer, aimed at optimizing the process of making this decision in the best interest of the volunteer. The following considerations form the basis of the approach to informed consent adopted in these guidelines.

1.3.1 THE DECISION MAKING PROCESS

One of the most important issues in informed consent is the question of how prospective participants come to make the decision whether or not to participate in a trial, and why they remain in the study.

Essentially, the informed consent process is concerned with assisting the volunteer to make a decision which is "truly" in their own best interest. Many of the standard procedures regarding informed consent are based on the assumption that the decision to participate in a research study is a rational decision made on the basis of the information presented to prospective participants. Yet a considerable proportion of the available research suggests that the information transmitted to potential research subjects has little impact on their decision to participate, and that the decision is often made before or independently of the technical information provided to participants (Faden & Beauchamp, 1980). There is evidence that personal and cultural values play a major role in coming to a decision about whether or not to participate in research (Parker, 1995; Weil, 1996), and that the decision making process involves cognitive, emotional, motivational and value-based components (Faden & Beauchamp, 1980; Kent, 1996; Weil, 1996). In developing the protocol proposed in this document, we have attempted to take account of the complexity of the decision making process, and to facilitate this process by incorporating the various factors likely to affect decisions.

1.3.2 SOCIAL DESIRABILITY

Social desirability refers to the tendency for research participants to behave in what they deem to be socially acceptable ways in order to win the favour, or avoid the displeasure, of the researcher.

It is likely that social desirability has a very strong influence on various aspects of biomedical research studies, as well as the informed consent process itself. The importance of social desirability becomes even more apparent when one considers the significant power and status differentials between medical researchers and research participants, especially in resource poor settings. Therefore, for the informed consent process to be truly ethical, the issue of social desirability needs to be carefully considered, including the issue of dependency of potential participants on health care provided through or alongside the research effort. In designing the protocol outlined in Part 2 of this document, the authors have attempted to consider ways in which the issue of social desirability may be addressed in the informed consent process. In the main, we recommend that advocacy-support staff be employed to assist volunteers in identifying and voicing their concerns.

1.3.3 UNDERSTANDING

Another central issue in considerations of informed consent is the question of understanding or comprehension. While it may be relatively easy to assess the adequacy of information disclosed and imparted, it is far more difficult to assessed whether the information is understood. This means that the legal requirement of disclosure of information may be satisfied, while the moral requirement of understanding in order to make decisions in one's own best interest may not. Further, expressed understanding on the part of research participants is not necessarily the same as true understanding (Meisel & Roth, 1983), so that opinions of participants regarding their understanding cannot be taken at face value.

The most common check on the adequacy of the understanding of the technical elements of a study is in the form of an information test for participants after the transmission of information, or at different stages of the research. However, there are a number of complications with such tests of understanding or comprehension. Numerous studies indicate that relatively few participants recall a large portion of information conveyed by researchers. But more important, such tests are actually assessments of short-term verbal memory rather than of understanding.

Further, the culturally or personally based value systems that enable prospective participants to evaluate information given to them with respect to its personal implications are largely unrecognized or ignored (Parker, 1995). To achieve understanding (as opposed to the repetition of facts following some delay) entails incorporating a recognition of these value systems. Finally, if informed consent is accepted to be a process of shared decision making, then understanding should always be a two way process. The researcher should comprehend the needs, values and motivations of the recruit, and how best to optimize their participation in the research study (Meisel & Kuczewski, 1996).

In the light if these considerations, a number of decisions have to be made in setting up the procedures for informed consent in a study: What kinds of information should be given to potential participants to optimize their understanding? For example, is it necessary for participants to understand the elements of randomization? How should this information be given so as to best facilitate an optimum decision-making process? And how can personal understanding of this information and its implications best be facilitated and assessed?

In preparing this protocol, the authors have operated from the assumption that for understanding to operate as an ethical and psychologically sound part of the informed consent process, it is essential that understanding is taken to be more than the short-term memory of technical facts. It is acknowledged that participants may require an understanding of certain basic technical issues (objective understanding) in order to indemnify the researchers. However, for informed consent by persons to be attained it is more important that participants understand the personal implications of participation in research (subjective understanding).

1.3.4 FREEDOM FROM COERCION

An essential component of the informed consent process is respect for the autonomy of volunteers and their right to decide about their participation in research studies without coercion of any sort. The research team needs to be especially aware of subtle coercive pressures arising from various sources. The issue of social desirability is again relevant here, as the significant power differential between researchers and volunteers in resource poor settings may exert considerable social pressure on volunteers to conform to the wishes of services providers and health care professionals. In addition, the research team needs to give careful attention to understanding the motivations of volunteers for participating in research trials as these may, at times, exert pressures to participate. This is especially important if the volunteer's motivations are based on misunderstanding or assumed benefits.

1.4 REFERENCES

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Appelbaum, P. & Grisso, T. (1988). Assessing patient's capacities to consent to treatment. The New England Journal of Medicine, 319, 1635-1638.

Appelbaum, P., Lidz, C. & Meisel, A. (1987). Informed consent: Legal theory and clinical practice. New York: Oxford University Press.

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PART 2: PRACTICAL GUIDE

2.1 PREPARATION FOR INFORMED CONSENT:

2.1.1 COMMUNITY PREPARATION

It is suggested that all research trials should be jointly developed by researchers and the communities in which they are carried out, with volunteers as active participants rather than passively complying with institutional demands. All decisions regarding participation should be shared decisions of the research team and volunteers, and their representatives. In addition to broad education of the community regarding the nature of the research project, full consultation should take place with the community and with key informants in the community, in order to foster a sense of partnership with respect to the research project. Early in the research, the research team should establish a community advisory board (CAB) which can represent the interests of the community, and advise the research team on matters relating to cultural expectations and others issues of local importance which need to be considered in setting up the research.

These considerations apply also to trials being conducted in facilities in addition to communities.

2.1.2 PREPARATION OF THE SCIENTIFIC TEAM

If informed consent is to be a mutual decision making process then it is essential that researchers and volunteers establish a relationship of mutual understanding before and during the introduction and execution of the study. The research team also needs to maintain an attitude of respect towards the notion of partnerships in research projects carried out in particular communities, as well as the active participation of the community in the research process. Further, researchers need to acquire information about the motivations and expectations of volunteers.

2.1.3 RESEARCHER UNDERSTANDING

While the community and research participants will obviously need to be educated and informed about various elements of the research, it is as essential that the research team has an understanding of various issues affecting volunteers in the research project. Amongst the issues to be understood by the research team are: the socio-cultural and personal values which impact on the decision to participate in the research; the psychosocial implications of participating; and the expectations and motivations of volunteers. Community representatives and a community advisory board play a vital role in fostering this understanding early in the research process. It is suggested that once the research is underway there should be constant monitoring and feedback to the research team about the expectations, implications and effects of participation in the study. Given that informed consent is best enacted as a shared decision making process, mutual understanding rather than unilateral understanding of the research by volunteers, is an essential pre-requisite

2.1.4 STAFF PREPARATION

In order to foster the informed consent process, it is recommended that particular attention be given to the training and supervision of two types of participant counsellors: research counsellors and advocacy/support counsellors. Both types of participant counsellors should be thoroughly trained, supervised and monitored in basic counselling skills. The task of research counsellors is to counsel volunteers regarding the necessary technical and personal information in order to make the decision about participation in the project. These counsellors should be in a position to understand and counsel volunteers about personal concerns they might have. They would also be responsible for ongoing monitoring of the social and personal effects of participation and for providing feedback to the research team. These counsellors would effectively be part of the research team. In addition, it is recommended that advocacy/support counsellors be employed to assist volunteers in identifying issues of personal concern and in voicing these concerns from an advocacy perspective. Parallel to union representatives, these support counsellors would assume the responsibility of protecting the interests of volunteers (e.g. freedom from coercion), and would be primarily responsible to volunteers, CABs and other community representatives rather than to the research team. It is suggested that early on in the research process they be publically established with an advocacy role.

2.1.5 PREPARATION OF POTENTIAL VOLUNTEERS AND SIGNIFICANT OTHERS

Especially in cultural contexts where the value of individual autonomy is balanced by the importance attached to community allegiance and interpersonal relationships, it is important that the research team give special attention to various people to whom potential volunteers are connected by blood relationship or community membership. Reference has already been made to the preparation of the broader community for participation in research trials. With the consent of potential volunteers, family and significant others need to be offered the possibility of active incorporation into the various stages and aspects of the informed consent process. Further reference to these components is made below.

2.2 INFORMED CONSENT MATERIAL PREPARATION:

2.2.1 PREPARATION OF INFORMATION FOR EDUCATION OF VOLUNTEERS

Informed consent traditionally requires the transmission of information regarding the project's aims, methods and procedures, and expected benefits or risks/hazards. Disclosure of all information is seen as an essential aspect of risk management for legal protection of researchers. But insofar as informed consent is driven by moral as well as legal concerns, careful attention needs to be given to the nature, amount and method of information disclosure and its effects on the decision making process (Lantos, 1993). We recommend that the research team also needs to consult with the community on the nature of information required by volunteers in order to decide in their own best interests whether to participate in the project or not. It is also recommended that rather than viewing information giving as a once-off activity, the research team should make ongoing counselling (incorporating information) available to all volunteers.

The following specific recommendations are made regarding preparation of information:

All aspects of the study should be discussed with key community representatives, in order to decide on issues such as: what cultural values need to be considered in implementing the research; which information should be transmitted to participants; how could such information best be transmitted; who should share the information with potential participants; how can potential participants best be assisted in the decision process.
Researchers should attempt to establish a network of participants, linking potential participants with others already in the study (with the agreement of both parties) with similar demographic characteristics and values, in order to better understand the personal implications of participation.
The research team should decide on the minimal technical information that is essential to be given to participants for legal indemnity of researchers.
Informational counselling sessions with participants should be repeated at different stages of the research.
The right of volunteers to withdraw from the study at any stage should be emphasized during initial and subsequent informational counselling sessions.

2.2.2 SELECTION AND TRAINING OF STAFF FOR EDUCATION AND COUNSELLING

Reference has already been made to the training of research counsellors for the transmission of information. These research counsellors should include people who share the values and world-view of potential research participants.

2.2.3 METHODS OF INFORMATION TRANSMISSION

The research team, in collaboration with the community advisory board, should decide on the most effective and most acceptable medium of information transmission. It is recommended that video-taped presentations be prepared for transmission of information. These should also incorporate material relating to the personal implications of participation for volunteers.

2.2.4 INTERACTIONAL ASPECTS OF EDUCATION

Careful attention should be given to the establishment of rapport between researchers and participants in order to facilitate an optimal emotional context for the transmission and understanding of information. In order to facilitate understanding through the asking of questions or discussion of personal concerns, research counsellors should attend to process aspects of information counselling. The following are important to achieving these aims:

Ensure that all research assistants are trained to take account of the process/interactional aspects of information provision.
Request volunteer evaluation of satisfaction with information-giving interviews. These evaluations should not be conducted by researchers or persons who gave the information, but by a support/advocate staff member.
Do a full assessment of a random sample of interviews recorded on audio- or video-tape in order to assess the adequacy of the informed consent process using, for example, the Meerwein model. This model looks at three dimensions of information: i) the information dimension, concerned with the content and technique of disclosure; adequacy of description; technical terms and jargon used; appropriateness of information disclosed; ii) the emotional dimension, concerned with the rapport between researcher and subject; and iii) the interactional dimension, concerned with the capacity and willingness of the researcher to perceive and discuss the emotional needs, concerns and complaints of the subject, and to deal with these concerns.
Test beliefs about volunteers' perceptions of the trustworthiness of researchers, through the support/advocate person.

2.2.5 ONGOING MONITORING OF INFORMATION PROVIDED

There should be ongoing monitoring of information provided to volunteers. Regular feedback interviews with participants should be done by research counsellors in order to ascertain what kind of information participants would have found helpful at the start of the project which can be used for new recruits into the project; as well as what kinds of issues are emerging that participants would have liked to consider in deciding whether or not to participate in the project, and which they would like to now discuss.

2.3 UNDERSTANDING AND DECISION MAKING:

Adequate understanding is an essential aspect of informed consent. It is recommended that this understanding goes beyond short-term recall of technical information. It should include understanding of personal implications of participation. Assessment of understanding should be an ongoing part of information counselling.

To facilitate understanding it is recommended that:

The video tape should include clips illustrating one participant explaining the research to another person, and telling the story of their participation.
Following the screening of a video tape as described above, allow interactive discussion to improve and assess understanding.
Researchers should apprise themselves of the life circumstances of potential participants, with the assistance of community representatives and a community advisory board, in order to identify which personal implications of participation it is important for participants to understand.
That the right to withdraw from the study at any stage without prejudice is fully understood by volunteers and ensured.
An advocacy/support counsellor should assist volunteers in identifying desired benefits and potential risks, and in reminding volunteers of their right to withdraw.

Follow-up visits should be scheduled at which participants can raise personal questions.
Family and friends should be allowed and encouraged to attend a follow-up visit to raise questions.
Time is allowed for further discussion of issues after talking with family, friends and support persons.

2.3.1 ASSESSMENT OF UNDERSTANDING BY VOLUNTEERS

In order to assess various facets of understanding, it is recommended that:

The research team, in collaboration with the community advisory board, establish a list of essential technical issues which require understanding, e.g. that the vaccine being tested cannot be assumed to provide protection.
Understanding of these essential technical issues should be assessed through specific questions, but also through discussion of typical scenarios from volunteers' lives.
Volunteers should be asked to explain in their own words what the research is about and its implications for themselves and significant others.
Understanding should be checked at different stages of the study.

2.3.2 RESEARCH TEAM UNDERSTANDING OF VOLUNTEERS' MOTIVATIONS

From the outset, researchers should view the transmission of information as a two-way process, and set in place processes for researchers to obtain necessary information from the community and participants about the implications of participation in the project. Arrangements should be made for mutual informational exchange during the course of the research project, with the researchers viewed as recipients of information as much as potential participants. Research counsellors should provide constant feedback to researchers about the kind of information that they need in order to better comprehend the position of participants.

Specific recommendations regarding research team understanding include:

A sample of interviews with volunteers should be evaluated to assess the extent to which research counsellors understand the issues facing participants.
Request ratings by volunteers, with the help of the advocacy/support counsellor, of volunteers' perceptions of researcher understanding.
Research counsellors should monitor the ongoing experiences of participants. Regular feedback to researchers about experiences of participants should be arranged, in order that researchers can provide more helpful information to other participants.

2.4 VOLUNTARINESS AND FREEDOM FROM COERCION:

An essential component of informed consent is the freedom to make the decision to participate or not, in one's own best interest, without coercion of any nature.

Specific recommendations to facilitate freedom from coercion are:

Researchers need to explore potential recruits' motivations to participate with the help of a community advisory group.
The provision of information about expectations and motivations, and the extent to which they will be met in the study or not, should be facilitated by an advocate/support person.
Sufficient time should be allowed before participants are required to commit themselves to participation. This should be at least enough time to discuss the matter with people at home and in the community if they so choose.
Require the advocacy/support counsellor to identify and voice any aspect of coercion to participate. This counsellor can especially assist in overcoming obstacles created by social desirability pressures.

2.5 CONSENT:

Informed consent requires that participants have the capacity to decide about participation in research; that is, potential recruits have the legal status of adults and are not mentally impaired. It is assumed that participants are in a position to make decision for themselves. Consent refers to the autonomous and explicit agreement by individuals to participate in a research project based on their informed understanding of what it entails.

In order to foster free consent the following recommendations are made:

Advocacy/support counsellors should assist volunteers in identifying and voicing reservations about consent, to overcome social desirability pressures.
Potential participants should be allowed time before requiring them to commit themselves to participate, as well as a "cooling off" period before participation commences.
The bilateral nature of consent should be recognized. The implicit hopes and expectations of individuals, families and community should be encouraged to be voiced, with a commitment, following negotiation, to meeting or not meeting these expectations on the part of the scientific team. It is the responsibility of the scientific team, through advocacy/support counsellors and the community advisory board, to introduce important issues, such as provisions for participants at the end of the trial, as communities and volunteers may not have sufficient grasp of the implications of the trial to raise them.
The willingness of people to continue to participate should be checked at different stages of the project.
Advocacy/support counsellors should assist in the drafting of consent forms, and assist volunteers in understanding and signing them.
Family, friends and advocacy/support counsellors should be invited to witness the consenting process (with the agreement of the volunteer), especially where volunteers are illiterate.

2.5.1 PHASED CONSENT

The ongoing research project is likely to involve a series of distinct stages. Each stage of the volunteer's participation should be spelled out, and explicit consent should be obtained for each stage, in addition to consent to participate in the project as a whole. For example, volunteers will need to consent to HIV-testing, to being vaccinated or to receive other treatment, to being examined, to give biological samples at various stages, and so on. It is also important that the consent of the community, via the community advisory board, be obtained for processes such as the public release of information derived from the study.

2.5.2 ONGOING RIGHT TO WITHDRAW

The research team and volunteers need to bear in mind the ongoing right of volunteers to withdraw from the study. In this connection:

Advocacy/support staff should frequently review with volunteers their right to withdraw from the study without prejudice.
Researchers should regularly assess willingness for ongoing participation in the research project, rather than assume that participants are aware of the right to withdraw at any time.
Where possible, ambivalent participants should be introduced to other participants who have remained in the study, and to some who have chosen to withdraw from the study and have done so without prejudice. If, and where possible, incorporate an interview with such participants should be presented on videotape.

2.5.3. MULTI-PERSON CONSENT

Most informed consent considerations are founded upon philosophical assumptions of rugged individualism, which may not be shared by all cultural groups and communities. Certain cultural views may define the meaning of persons in relationships with others, and this may affect how individual informed consent is understood. There may be explicit community norms regarding who should be consulted for agreement that any particular individual can be approached to participate in research trials; for example, parents, community leaders etc.

It is recommended that the principle of respect for individual autonomy is preserved as a universal principle in research trials, not being substituted by any other principle. But it is also important that the research team identify, understand and respect other cultural norms pertaining to individual participation in research trials. Therefore, it is recommended that in addition to always seeking individual consent, other family and community members should be incorporated into various stages and aspects of the informed consent process, but only with the explicit consent of the volunteer concerned.

Specific recommendations regarding whose consent to seek include:

Community partnerships on the project should be facilitates, and community groups should be consulted regarding general principles of who should be approached about consent procedures.
All parties that need to be consulted and whose cooperation should be obtained in the case of each potential participant should be identified. Participants should be invited and encouraged to involve these people in the informed consent process if they so choose, and such people should be invited to attend information sessions.
Where participants decline opportunities for other family or community members to be involved in their recruitment into the study, or where such involvement is difficult or inappropriate, the wishes of the individual person should be respected.
Researchers should ascertain if there are any community-based constraints to particular volunteers participating in the research.

2.5.4 AGREEMENT ABOUT COMPENSATION

This document has recommended that research trials be seen as involving partnerships between researchers and the community participating in research. Further, it has been recommended that informed consent should always be seen as a mutual decision making process. Giving that there is always likely to be some degree of expectation from communities and individuals regarding the benefits to be derived from participation in research trials, it is recommended that consent should be seen as a two-way process. In addition to volunteers consenting to various aspects of participation in the research trial, it is recommended that researchers also indicate their explicit consent to meeting negotiated expectations of communities and volunteers. These may include expectations about employment and economic investment in the community, upgrading of health facilities, financial compensation for time lost to do household work, access to treatments, and so on.

Other recommendations include:

Specific expectations of community, volunteers and families should be identified early in the research trial.
Motivations for participation should be identified with the help of the community advisory board, advocacy/support counsellors and others.
The research team should explicitly address expectations of the community and volunteers, by making clear which expectations can be met and to what extent.
The motivations and expectations of individual volunteers should be carefully monitored by research counsellors. Where these are substantially different from those negotiated and consented to with community representatives, they should be brought to the attention of the research team before acceptance of particular volunteers into the research trial.

2.6 EVALUATION OF THE CONSENT PROCESS AND CONDITIONS:

It is recommended that there should be ongoing evaluation of the consent process and conditions in order to monitor and improve on various aspects of consent. Reference has already been made to various ongoing evaluation procedures and includes:

Evaluation of the process/interactional aspects of informational counselling, through the application of evaluation measures, such as those of Meerwein, to samples of interviews observed or videotaped.
With the assistance of advocacy/support staff, there should be ongoing evaluation of the research team's understanding of the situations and experiences of volunteers.
There should be regular monitoring of the experience of volunteers and feedback to the research team in order to improve the quality of information and understanding early in the research trial.
There should be ongoing monitoring and feedback regarding understanding of various issues by volunteers at different stages of the research trial.
Advocacy/support staff should be requested to monitor and offer regular feedback regarding protection of the autonomy of volunteers at different stages of the research trial, e.g. regarding the right to withdraw without prejudice or disadvantage.

2.7 PROTOCOL FOR IMPLEMENTING A CULTURALLY SENSITIVE INFORMED CONSENT PROCESS

2.7.1 PRE-RECRUITMENT STAGE

-The scientific team needs to discuss and reach consensus on ethical issues implied by the research design. Commitments to uphold ethical standards with respect to all features of the study should be made explicit and incorporated into the training of all staff.
-Community leaders and representatives need to be identified.
-Explicit agreements should be reached regarding (joint) project ownership, including terms and conditions.
-Advocacy/support counsellors need to be selected and trained, and their conditions of operation clarified.
-Facilitate the establishment of a community advisory board consisting of people known for their leadership and independence.
-A strategy should be developed to ensure that all members of the scientific team are acquainted with the necessary anthropological knowledge of people in the community to be able to relate to them in culturally sensitive ways.

2.7.2 PREPARATION FOR INFORMED CONSENT

-Detailed and repeated discussions of the project need to be held with community leaders and the community advisory board to ensure that the purposes and methods of the study are understood.
-Ethnographic research needs to be conducted among potential volunteers in order to identify attitudes towards the study and potential barriers and obstacles to participation.
-Together the scientific team and the community advisory board need to identify the major issues and values of likely concern to the community and potential participants regarding the project.
-The scientific team and the community advisory board need to identify the major motivations, advantages and disadvantages of participation to community members.
-Expectations about individual and community benefits need to be made explicit as well as agreements regarding meeting expectations.
-The scientific team needs to identify major components of information about the study thought to be necessary for transmission to potential participants.
-These informational components should be discussed with community advisors in order to decide what information potential participants should have in order to make an informed decision to participate in the study, who would best convey this information to potential participants, when, where and how.
-The scientific team and the community advisory group should establish a check list of essential components to be understood for participation.
-The community advisory board should establish a list of essential issues about the local community that need to be understood and taken into account by the scientific team before commencing the research.
-Community education through meetings should be undertaken to facilitate general understanding of the essential components identified;
-A videotape recording should be prepared, with the assistance of educational experts and community representatives, conveying all the information identified, including hypothetical questions by participants and some case illustrations of different scenarios.
-Structures and functions for research counsellors and advocacy/support counsellors should be set in place.

2.7.3 RECRUITMENT

-Initial contacts should be made with potential participants once significant progress has been made with community preparation.
-Following preliminary interest, research staff should arrange for a meeting and screening of the videotape, followed by discussion and counselling around personal issues.
-The support/advocacy staff should meet independently with potential participants to explain their advocacy role and function.

-Individual interviews should be arranged with potential participants. In the interviews attempt should be made to identify the person's expectations of benefit from participation, as well as likely personal implications of participation.

-People whose agreement is important to the potential participant, should be identified and invited to see the video, if and when explicit agreement for this has been obtained from the participant.

-The possible participation of these people and their role in the informed consent process should be discussed.
-A further screening of the videotape and discussion of issues should be offered to family and others whom the potential participant wishes to consult about involvement in the study.

-Advocacy/support counsellors should meet with volunteers and family/friends to identify and articulate possible concerns to be considered and discussed before deciding about participation.
-An information sheet and informed consent form, prepared with the help of educational experts and advocacy counsellors, should be given to the potential participant to take home and discuss with significant others.

-The potential participant should be put in contact with other volunteers, or people already participating in the study, as they become available.

2.7.4 EVALUATION OF RECRUITMENT PROCEDURES, INCLUDING UNDERSTANDING

-Potential participants who have been exposed to the initial contact procedures should be interviewed by advocacy/support counsellors to evaluate the quality of the initial procedures using a multi-level model such as that of Meerwein, as well as their degree of satisfaction with these interviews and procedures.

-Advocacy/support counsellors should summarise potential participants' fears and concerns to the scientific team.
-Strategies should be devised to address these concerns and fears.
-Random recordings or observation of initial interviews should be evaluated for process/interactive aspects of effective communication, and staff feedback and further training should follow.

-Potential participants should be interviewed to assess their understanding.
-In addition to assessment of the specific understanding of some of the core technical issues, participants' understanding of the personal implications of participation in the research should be assessed through discussion of vignettes.
-Specific questions should be addressed to participants to assess understanding of essential technical issues.
-In interviews, potential participants should be asked to give their understanding of the aims and procedures of the research.
-Motivations, expectations and concerns of potential participants should be discussed.
-Individual descriptions and responses need to be evaluated according to criteria established by the research team, to assess adequacy of understanding of key components identified to be essential to informed decision making. When required, remedial steps need to be taken to improve understanding.
-If desired by potential participants, the process should be repeated with family or friends.
-If requested by the potential participant, the advocacy/support counsellor should be present to speak on behalf of the participant and to assist with the estimation of the level of understanding obtained.
-Assessment of understanding should be repeated at all identified stages of the research process.

2.7.5 OBTAINING CONSENT

-Family and other people whose support or agreement is regarded as desirable should be identified with the volunteer, if s/he provides consent for this.
-Following exposure to information, videotape and discussion, a meeting should be held with these people together with the potential participant.
-Opportunity should be provided for further questions or discussion about participation in the research.
-Expectations of the participant and family/community should be discussed and, where necessary, corrected.
-An advocacy/support counsellor and/or a community representative may be present for the discussion if the participant prefers this.
-The volunteer is invited to sign the agreement or offer verbal consent (if illiterate) in the presence of witnesses.
-Where family or community members have been involved in the informed consent process, they are invited to indicate their support (as opposed to consent) for the person participating in the research process.

-A written copy of the obligations of the research team is made available to the volunteer.
-At any stage where particular steps are to be taken which may affect the community, e.g. the public release of information from the research, this should only be with the written consent of the community advisory board.

2.7.6 ONGOING COUNSELLING AND EVALUATION

-At regular intervals, research counsellors should approach participants to assess ongoing willingness to participate in the research.

-Interviews with participants should be held in order to obtain feedback on their experience of the research, factors affecting their participation, their understanding of the process, the effects and implications of the study, as well as feedback about the most suitable information to be imparted to new recruits into the research project.
-Research counsellors and advocacy/support counsellors should be available to volunteers and their families throughout the project, and for a time period following termination of their participation in the project in order to enable them to deal with the issues and implications arising from participation in the project.
-Regular report backs and meetings should be held with the research team to keep them informed of the processes and evaluation of participation by individuals and the community.

2.8 TASKS AND RESPONSIBILITIES FOR IMPLEMENTATION OF INFORMED CONSENT PROCEDURES:

Scientific Team (including Director of Community Liason and Researcher)

Identify major ethical issues emerging from study
Articulate a commitment to ethical standards
Identify community leaders and representatives; arrange discussions regarding implementation of the project in the local community
Draw up agreement regarding partnership for the project
Establish terms of reference for research counsellors and support/advocacy counsellors.
Identify, select and train research counsellors
Identify, select and train support/advocacy counsellors
Facilitate selection and establishment of community advisory board (CAB)
Establish strategy to ensure that members of scientific team are acquainted with local and cultural issue of relevance to the project
Identify major components of information which need to be transmitted to subjects; discuss components with CAB; finalize components to be included in information to participants.
Arrange community meetings to facilitate understanding of components identified
Arrange preparation of informational video for participants in collaboration with research counsellors and CAB.
Prepare informed consent forms
Oversee informed consent procedures with potential participants
Receive feedback from research and support/advocacy counsellors regarding informed consent procedures and modification thereof
Ensure evaluation of ongoing willingness to participate

Community Advisory Board: CAB

Accepting joint responsibility for the study
Assist with identifying major issues affecting the local community
Assist with initial research into attitudes of potential participants to the study
Assist with identification of motivations and expectations of participants
Assist with identifying components of information which need to be transmitted to subjects and how best to do this
Assist with the preparation of informed consent forms
Assume responsibility for establishing understanding of cultural and local issues by scientific team
Receive ongoing feedback from support/advocacy counsellors, who are answerable to the CAB

Research Counsellors

Assist with research into attitudes of potential participants to the study
Assist with establishing motivations and expectations of participants
Assist with identifying components of information which need to be transmitted to subjects and how best to do this
Identify major components of information which need to be transmitted to subjects; discuss components with CAB; finalize components to be included in information to participants; establish checklist of items
Assist with preparation of informed consent forms
Establish network of community links for referral, where necessary
Make preliminary contact with potential participants
Arrange screening of video recording
Arrange preliminary interviews with potential participants
Identify family/community members to be incorporated into informed consent procedures
Arrange to see family/community members, plus video screening
Arrange contact with other willing participants
Interview and assessment of understanding by participants, and follow up to improve understanding, if necessary
Spell out expectations and motivations of participants
Arrange signing of informed consent forms, incorporating family/community members, where acceptable
Make written obligations of research team available to participants
Arrange regular follow up with participants regarding informed consent process and current participation
Feedback to scientific team to modify informed consent or participant processes, where necessary
Re-assess understanding and ongoing willingness to participate at different stages of the research project
Ongoing availability to participants to deal with their concerns or questions during the project
Assist with debriefing and follow-up of participants after leaving project

Support/Advocacy Counsellors

Establish terms of reference
Support/advocacy staff should be directly answerable to CAB
Assist in identifying components of the trial about which participants should be informed
Assist with preparation of informed consent forms
Meet with prospective participants after seeing video and after initial interviews, to identify issues of personal concern
Assist at signing of informed consent forms, where desired
Regular follow up with participants regarding informed consent processes and current participation
Ongoing availability to participants to deal with their concerns or questions during the project
Feedback to CAB and/or scientific team to modify informed consent and participation processes, where necessary
Re-assess understanding and ongoing willingness to participate at different stages of the research project
Assist with debriefing and follow-up of participants after leaving project

2.9 TIME LINE:

The time line given below is a rough estimate of the time required to prepare a community or facility and obtain the necessary agreement and consent from all involved. Some procedures, such as recruitment, obtaining consent, and ongoing counselling and evaluation, will continue for the duration of the trial.

Activity outlined in protocol (2.7)

Months ->

PRE-RECRUITMENT STAGE (2.7.1)

xxxx

PREPARATION FOR INFORMED CONSENT (2.7.2)

xxxx

RECRUITMENT (2.7.3)

xxxx

EVALUATION OF RECRUITMENT

PROCEDURES (2.7.4)

xxxx

OBTAINING CONSENT (2.7.5)

xxxx

ONGOING COUNSELLING AND EVALUATION (2.7.6)

xxxx

2.10 BUDGET

This proposal is based on the assumption that full-time staff will be available to develop, institute and monitor the informed consent process, and potentially other ethical issues in the trial as well - including a senior person at an equivalent level to other principal investigators. This is necessary to give credibility and influence to the activities and processes outlined.

The budget has been calculated at local costs in South Africa in mid-1999, and then converted into US dollars at the current rate of exchange. The actual amounts should therefore be regarded as a rough estimate. The amounts indicated refer to per annum costs except in the case of capital equipment.

STAFF

Director of community liason 30 000

Researcher 17 000

CAB facilitator 12 000

2 * Research counsellors (8 500 each) 17 000

2* Support counsellors (8 500 each) 17 000

Administrative/secretarial assistant 8 000

Sub-total 101 000

TRAVEL AND SUBSISTENCELocal travel 2 000

International, regional meetings 3 500

Sub-total 5 500

OFFICE INFRASTRUCTURE

Running expenses (1 500 per month) 18 000

Consummables (500 per month) 6 000

Sub-total 24 000

MEETINGS / INFORMATION DISSEMINATION

CAB activities 17 000

Workshops / meetings 8 500

Printing 7 000

Film production 8 000

Sub-total 40 500

Sub-total per annum 171 000

CAPITAL EQUIPMENT

Office furniture 8 000

Telephone/fax 500

2 * Computer/printer 3 500

Photocopier 5 000

Videotape and audiotape equipment 5 000

Sub-total once-off 22 000

APPROXIMATE 200 000 pa

1. The terms "scientific team" and volunteer" remind us of the reality of roles in trials. In most clinical trials, and certainly in vaccine-related trials, there will be a scientific team, headed by a director, rather than an individual physician-scientist. This influences the locus and nature of responsibilities for scientific and ethical issues. In turn, persons who enter trials are volunteers, not subjects which, as Stark (1998) asserts, carries unacceptable connotations of objectification.

2. There is no agreed upon terminology for what are called "developed" and "developing" countries, but these terms are recognised to refer to the division between rich countries, largely in the northern hemisphere, and poor countries, largely in the southern hemisphere.