Research ethics committees in a tight spot: Approving consent strategies for child research that are prima facie illegal but are ethical in terms of national guidelines.

It is an internationally accepted principle that ethics norms should be applied and enforced in research with humans through ethics review by research ethics committees (RECs). This places RECs at the very heart of the system for protecting participants and enforcing their rights. In the South African ethical-legal framework for child research, there are divergent approaches to consent. That is, section 71 of the National Health Act (No. 61 of 2003) (NHA) requires mandatory parental consent for child research, and limits the authority for proxy consent to parents and legal guardians. However, national ethics guidelines authorised by section 72 of the NHA and issued by the National Health Research Ethics Council (NHREC) acting in terms of its mandate (National Department of Health, 2015) allow a more nuanced approach - i.e. self-consent by older adolescents, provided certain conditions are met, and consent by a range of parental substitutes where there are no available parents or legal guardians. We have argued elsewhere that the consent approach in section 71 is inappropriately restrictive and are of the view that the consent approach endorsed in national ethics guidelines is more defensible. An REC that elects to approve a consent strategy allowable in ethics guidelines is effectively electing to not follow section 71, which raises the question of what the consequences might be for that REC. This article examines the legal liability of RECs through three 'threads' of accountability: the NHREC, the institutions hosting RECs, and the courts. We conclude that: (i) if an REC approves a child protocol with consent strategies allowable in terms of national ethics guidelinesbut not in terms of section 71, it is unlikely that the NHREC would discipline the REC in the face of a complaint - provided the REC acted within national ethics guidelines issued by the NHREC in terms of the latter's section 72 mandate to set national norms and standards; (ii) if an REC approves a consent approach allowed for in ethics guidance, it is also unlikely that the host institution would discipline the REC in the face of a complaint - especially if the institution is aware of the REC's explicit decision to follow national ethics guidelines that are authorised by section 72 of the NHA; and (iii) an REC could only be sued by a participant in terms of the law of delict (and be liable for damages) if several demanding components are proven, such as that the harm suffered by the participant resulted directly from the REC's actions in approving a particular consent strategy for that research. Furthermore, the court may well look to national ethics guidelines in making determinations about whether an REC's conduct was wrongful for the purposes of liability in civil law. RECs are protected from being collectively liable by insurance taken out by their host institutions. We make a series of recommendations to address this issue.

Obtaining informed consent for a sterilisation in the light of recent case law.

The need to obtain informed consent prior to any sterilisation is a very well-established ethical and legal obligation. South African law, however, does not specifically state who is responsible for obtaining informed consent before performing a sterilisation. This has implications for the liability of a surgeon or gynaecologist in circumstances where the informed consent is defective. Due to the vagueness of the applicable law, a surgeon or gynaecologist might be held liable, even in situations where he/she did not obtain the consent and relied on a nurse or assistant to procure the relevant informed consent. This article explores the relevant statutory law and canvasses two legal cases that came before the court regarding defective informed consent and the resultant liability for damages. We also make recommendations for proposed amendments to the current law to provide further clarity.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation.

BACKGROUND: HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues. OBJECTIVES: To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA). METHOD: A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4. RESULTS: The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit. CONCLUSIONS: This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation

Background. HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues.Objectives. To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA).Method. A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4.Results. The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit.Conclusions. This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required

Facilitating access to adolescent sexual and reproductive health services through legislative reform: Lessons from the South African experience.

South Africa (SA) has progressive legislation enabling adolescents to access various sexual- and reproductive-health services (SRH) independently, without consent from parents or legal guardians. This article reviews the SA legislative framework for adolescent access to SRH interventions. It outlines the five approaches adopted in current legislation to address adolescents' capacity to independently consent to specified health interventions, based on age, capacity and public policy requirements, or combinations thereof. Rather than subsume various health interventions under the umbrella of medical treatment, SA has separately legislated on many SRH interventions (e.g. HIV testing, contraceptives and terminations of pregnancy, among others). We identify strengths and weaknesses of the SA approach, and conclude with lessons learned from the SA experience which could inform discussion and debate on the most appropriate ways for countries to consider law reform that facilitates adolescent access to SRH services.

Addressing legal and policy barriers to male circumcision for adolescent boys in South Africa.

With millions of adolescents becoming infected with HIV globally, it is essential that barriers to much-needed interventions are reduced for at-risk adolescents. In this article we review the legal and policy framework in South Africa for adolescent access to male circumcision. We are of the view that the framework does confer protection for adolescent boys while enabling access to male circumcision; however, we identify ambiguities and tensions that exist between the Children's Act, regulations and national guidelines. We recommend reform to further enable access by this vulnerable group to this prevention modality.

But is this really the 'parent' or 'guardian'? Practical strategies for consent to child research in South Africa.

Research ethics committees (RECs) in South Africa may require consent from a parent or legal guardian for child research. In instances where an REC determines that parental or guardianship consent is required, how far should researchers go to establish if the accompanying adult is in fact the parent or guardian? Should researchers accept disclosures at face value, probe assertions that are made, or even call for supporting documentation? In this article we set out the facts research staff should possess, propose key questions they could ask, and recommend practical steps for uncertain cases. We recognise that a parental/guardianship consent strategy may not be appropriate in all instances, but do not debate that issue in this article. This article is confined to practical advice for researchers wishing to implement a parental or guardianship consent approach.

Boni mores and consent for child research in South Africa.

Consent is required for almost all health research. In order for consent to be valid a number of requirements must be met including that the consent cannot be contra bonos mores or contrary to public policy. This principle has its roots in the common law and it is used to ensure that the consent to harm, or the risk of harm, is permitted or ought to be permitted by the legal order. Recently, it has also become a statutory requirement embedded in the consent obligations relating to non-therapeutic health research with minors. Section 71 of the National Health Act provides that the Minister of Health (or potentially his or her delegated authority) must provide consent to non-therapeutic research with minors. However, such consent may not be granted if 'the reasons for the consent to the research or experimentation are contrary to public policy'. Limited work has been done on how to determine when consent to health research with children would be contrary to public policy. This article attempts to begin the debate by describing the boni mores principle, setting out some of the general factors that could be used to assess whether consent is consistent with it and suggesting how they could be applied to health research. The article concludes by stating that simply requiring proxy consent for non-therapeutic health research with children is insufficient as it cannot always be assumed that proxy consenters will act in the best interests of the child. Thus the boni mores principle acts as a limit on autonomy in order to protect the child participant. It is further submitted that establishing when consent to health research is consistent with public policy requires an assessment of whether the research is consistent with constitutional values, prevailing legal norms regarding children, and an assessment of the legal convictions of the community.

Compensation for research-related harm: the implications of Venter v Roche Products (Pty) Limited and Others for research ethics committees.

BACKGROUND: The issue of what type of compensation a research participant would be entitled to in a clinical trial when they have signed an informed consent document excluding certain forms of compensation recently came before our courts in the matter of Venter v Roche Products (Pty) Limited and Others (Case No. 12285/08). In this case, the court had to consider whether the plaintiff, Mr Venter, was entitled to claim for non-medical costs such as pain and suffering, loss of income and general damages, even though the informed-consent document expressly excluded such claims. OBJECTIVES: To set out the facts, issues and judgment in the case, concluding with a discussion of the implications of the judgment for research ethics committees (RECs). METHODS: Critical review of a judgment of the Western Cape High Court. RESULTS: The court concluded that Mr Venter's application for damages should be dismissed because he had voluntarily agreed to the limited compensation as set out in the informed consent form that had been approved by both the local RECs and the Medicines Control Council. CONCLUSIONS: The Venter case has shown that delictual claims for research-related injuries will not be successful if plaintiffs have agreed to limit their own rights through signing an informed-consent form that limits compensation. This places an important obligation on RECs to ensure that they carefully review compensation clauses in informed-consent documents and that these are made clear to potential research participants.

Provision of HIV treatment in HIV preventive vaccine trials: a developing country perspective.

HIV treatment for participants who become infected during HIV vaccine trials has been the focus of ethical controversy. The obligations of sponsors to ensure that participants have access to antiretrovirals have been a particular focus of this debate. This paper presents three arguments that have been made in this regard, and some of their limitations, in anticipation of HIV vaccine trials in South Africa. The first argument is that HIV risk behaviour increases in such trials, and HIV infection can be viewed as a research-related injury, justifying sponsor provision of treatment on grounds of compensation for harm. We conclude that risk-behaviour studies to date do not show general increases in risk behaviour that could constitute the basis for a general obligation. Participation may well adversely impact on risk behaviour for some individuals, and conceivably this could be demonstrated. This argument may, therefore, have merit at the individual level; however, it seems a weak platform from which to argue that sponsors should treat all HIV infections acquired during trials. The second argument is that treatment should be provided based on distributive justice. We conclude that traditional concepts of "distributive justice" in research appear limited in justifying obligations of sponsors to ensure access to antiretrovirals. Further, using research initiatives to reduce global health care inequities is controversial, and even proponents may disagree about the fairest use of finite resources. The third argument is that sponsors should ensure antiretroviral access on grounds of beneficence; namely, the maxim that if one can do something beneficial without sacrificing anything of comparable significance, it ought to be done. Thus, sponsors should provide more interventions than those minimally required to conduct the research. However, beneficence may demand levels of altruism that exceeds what is reasonable. While the latter arguments may provide stronger justifications than the first, it is difficult to use these arguments to establish that sponsor provision of antiretrovirals to infected individuals is obligatory.

HIV vaccine research - South Africa's ethical-legal framework and its ability to promote the welfare of trial participants

An effective ethical-legal framework for the conduct of research is critical. We describe five essential components of such a system; review the extent to which these components have been realised in South Africa; present brief implications for the ethical conduct of clinical trials of HIV vaccines in South Africa and make recommendations. The components of an effective ethical-legal system that we propose are the existence of scientific ethical and policy-making structures that regulate research; research ethics committees (RECs) that ethically review research; national ethical guidelines and standards; laws protecting research participants; and mechanisms to enforce and monitor legal rights and ethical standards. We conclude that the ethical-legal framework has; for the most part; the necessary institutions; and certain necessary guidelines but does not have many of the laws needed to protect and promote the rights of persons participating in research; including HIV vaccine trials. Recommendations made include advocacy measures to finalise and implement legislation; development of regulations; analysis and comparison of ethical guidelines; and the development of measures to monitor ethical-legal rights at trial sites

Ethical issues in HIV vaccine trials in South Africa.

In this review we describe the ethical issues central to local and international debates about HIV vaccine trials. These issues include the physiological and psycho-social risks of trial participation, the preventative interventions to be provided to participants, access to treatment for participants who seroconvert, access to an effective vaccine after the trial, the role of placebo-controlled trials, and obtaining informed consent.

South African labour law and HIV / AIDS.

PIP: This article contains five key pieces of labor legislation in South Africa, including one applying specifically to the mining industry which protect the rights of employees. These laws include: the Employment Equity Act, No. 55 of 1998; the Labour Relations Act, No. 66 of 1995; the Occupational Health and Safety Act, No. 85 of 1993; the Compensation for Occupational Injuries and Diseases Act No. 130 of 1993; the Mines Health and Safety Act, No. 29 of 1996; and the Basic Conditions of Employment Act, No. 75 of 1997. This paper further presents the Medical Schemes Act, No. 131 of 1998 and the protection of the right to privacy and dignity. Although HIV/AIDS was expressly referred to only in the Employment Equity Act, there are provisions in all the other Acts, which have relevance to HIV/AIDS.^ieng

Workplace AIDS programmes. Why employers should get involved: the example of South Africa.

PIP: While employers are not required by law to implement workplace AIDS programs, doing so contributes positively to labor relations and can result in considerable saving to the company over the long term. The National HIV/AIDS and STD Directorate of the South African Department of Health argues that it makes economic sense to develop such programs. Addressing the impact of HIV/AIDS upon production and staff will help to minimize the impact of the epidemic upon a given company, department, or organization, protect benefit schemes and productivity, and help to prevent possible workplace disruptions. A study of the economic costs of HIV/AIDS upon businesses conducted in Kenya in 1992 also concluded that investing in HIV/AIDS prevention programs can result in considerable savings to companies at a later stage. The development of an AIDS policy and HIV/AIDS intervention programs, as well as the role of the government, are discussed.^ieng

The criminalisation of HIV transmission: what purpose does it serve?

PIP: Zimbabwe's Minister of Justice has proposed legislation which makes it a criminal offence for a person who knows that he or she is infected with HIV or any other sexually transmitted disease to have a sexual relationship. The proposed legislation also heightens liability for convicted rapists who are HIV-seropositive. The Criminal Law Amendment Act would make it so that boys under age 12 cannot be charged or convicted of a sex crime; anyone, except in the case of married couples, intentionally infecting someone with HIV will be liable to a prison sentence not exceeding 15 years; a person convicted of rape, having sex with a girl under age 16 years, or having sex with an imbecile while being HIV-positive will be sentenced to prison for no more than 20 years, regardless of whether the person was aware he or she was infected; and all people charged with sex offenses will be tested for infection with HIV. The South African AIDS Legal Network opposes legislation which criminalizes the transmission of HIV. Such legislation will not help check the spread of HIV. Furthermore, criminalizing the transmission of HIV will discourage people from seeking education, counseling, and treatment, further stigmatizing HIV and AIDS, dividing communities and households, and violating basic human rights. The network urges all opposed to the introduction of such criminal legislation to respond to Zimbabwe's proposal.^ieng