Identities ascribed to research staff in face-to-face encounters with participants have been raised as key ethical challenge in transnational health research. ‘Misattributed’ identities that do not just deviate from researchers' self-image, but obscure unequivocal aspects of researcher identity – e.g. that they are researchers – are a case of such ethical problem. Yet, the reasonable expectation of unconcealed identity can conflict with another ethical premise: confidentiality; this poses challenges to staff visiting participants at home. We explore these around a case (...) study of ‘follow-up’ staff, observed during an ethnographic study of a Kenyan HIV ‘trial community’, which included participant observation, conversations, and interviews with staff (n = 79) and participants (n = 89). We found that because of the need to maintain confidentiality and because of some suspicions towards researchers, research staff drew upon alternative identities – presenting themselves to non-participants as relatives or friends, rather than as researchers. Several staff experienced this as necessary but uncomfortable. Simultaneously, staff and participants forged close relations in line with their fictional identities, which however also posed challenges because they entailed personal responsibilities that were difficult to live up to, due to limited resources, and the trial's limited duration. Similar challenges may arise in transnational HIV treatment programmes and should be explored further in that context. (shrink)

This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are (...) not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions. (shrink)

Access to treatment, in HIV vaccine trials (HVTs), remains ethically controversial. In most prevention trials, including in South Africa, participants who seroconvert are referred to publicly funded programmes for treatment. This strategy is problematic when there is inadequate and uneven access to public sector antiretroviral therapy (ART) and support resources. The responsibilities, if any, of researchers, sponsors and public health authorities involved in HVTs has been hotly debated among academics, scholars, representatives of international organizations and sponsors. However, there (...) is little published on community perceptions. Recent guidance asserts that communities should make inputs into treatment and care decisions. This qualitative study explored a South African community's perceptions of who should provide what to HVT participants as well as how and why this should be done. Twenty-nine adults working at or attending five primary health care clinics in two rural areas in KwaZulu-Natal participated in in-depth interviews. Respondents expressed that researchers should ‘help participants to access’ treatment and care ‘because they are in a position to do so’ and ‘are in a relationship with’ trial participants. Respondents suggested that researchers could help by ‘facilitating referral’ until such time that participants can access care and treatment on their own. We highlight a series of implications for researchers in HVTs, including their need to be aware of prospective participants' considerable trust in and respect for researchers, the responsibility that this places on them, and the need for clear communication with communities so as not to erode community trust. (shrink)

Background The world has come closer than ever to discovering a viable HIV vaccine. However, it remains less certain whether HIV vaccines should be made available to participants and communities in which trials are run no or subsidized cost. Hence the essence of this inquiry.Methodology This is a case study design using in-depth interviews (IDI) and focus group discussions (FGD) with researchers of HIV vaccine trials, institutional review board (IRB) members, HIV advocates, a policy maker, and members of (...) community advisory board (CAB) in Tanzania. Participants were purposively selected and data thematically analyzed using MAXQDA software.Results Hosting a vaccine trial and the financial incapacity of individuals at increased risk of HIV were among the reasons in favor of free access to HIV vaccines. In contrast, the view that vaccines should be provided at a subsidized cost was related to high costs of vaccine development, financial return expectations by investors, and the fear of labeling the free vaccine as less important. Moreover, apart from governments and international organizations, well-off individuals could share the cost burden.Conclusion Stakeholders engaging in active discussion about sharing the viable vaccine ought to take the aforementioned concerns into account and ensure unhindered access to individuals and host communities in Tanzania and beyond. (shrink)

Trial participation in the proposed HIV Vaccine Trials in South Africa is discussed in the context of the ethical tension that exists between international ethical research standards and local standards of care and cultural norms in the Third World. The important concepts of informed consent, risk-benefit ratio and fair treatment of trial participants are interpreted differently in traditional, rural African communities, where a moderate form of communitarianism referred to as "Ubuntu" or "communalism" is still prevalent. Research is an altruistic (...) endeavor that benefits communities and societies as a result of risks taken by individuals. Universal ethical guidelines that are highly individualistic and fail to emphasize communalism may represent serious problems for the sort of research needed in Africa today. (shrink)

Some participants will get HIV-infected in HIV prevention trials, despite risk reduction measures. The subsequent treatment responsibilities of sponsor-investigators have been widely debated, especially where access to antiretroviral therapy (ART) is not available. In this paper, we explore two accounts of beneficence to establish whether they can shed light on sponsor-investigator responsibilities. We find the notion of general beneficence helpful insofar as it clarifies that some beneficent actions will be obligatory where they can be dispensed without scuppering the trial. (...) We find the notion of specific beneficence helpful insofar as it directs investigators to attend to the needs of trial participants; however the range of interventions that could be provided remains unhelpfully broad. We then examine accounts of the investigator-participant relationship to narrow the range of interventions that investigators should provide, concluding that health-care, and HIV infection, are appropriate foci. We conclude that when investigators are able to meet the ART needs of their participants (e.g. referral, assisted referral or direct provision) without sacrificing trial quality, they must do so. However, there is little of this explicit direction to be found in the account of specific beneficence itself, but rather it is found in accounts of the relationship that are compatible with beneficence. (shrink)

BackgroundThe prevention of HIV remains an ongoing global concern. The safety and welfare of participants in these trials are imperative. Research Ethics Committees (RECs) review all reports of serious adverse events, adverse events and social harms arising in the course of such trials. There is little guidance for RECs on how to respond appropriately to social harm reports.MethodologyThis paper reviews the literature on social harms in HIV prevention trials and offers suggestions for RECs on how to respond (...) appropriately to such reports.ResultsThis review confirms that social harms are reported in clinical trials in South Africa and that specific guidance on managing these is minimal.ConclusionSocial harms in South African HIV prevention trials need to be more systematically researched so that ethical evidence‐based prevention, care and treatment strategies can be developed. This review makes specific suggestions for further research on social harms that can inform further consultations to develop more specific guidance for stakeholders on appropriate responses to such social harms. Such future work may also inform future versions of relevant local and international ethics guidance on HIV prevention trials. (shrink)

The maternal‐fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki – the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against (...) the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow ‘local conditions’ to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta‐ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects. (shrink)

BackgroundAfrica continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges.MethodsIn order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and (...) Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009.ResultsKey cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing.ConclusionThe consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields. (shrink)

In 2004, the first ever multi‐sited clinical trials studied the prospect of HIV biomedical prevention (referred to as pre‐exposure prophylaxis—‘PrEP’). The trials were implemented at several international sites, but many officially closed down before they completed. At most sites, both scientists and community AIDS advocates raised concerns over the ethics and scientific rationales of the trial. Focusing on the Nigerian trial site, we detail the controversy that emerged among mostly Nigerian research scientists who scrutinized the research design and (...) protocol. While some of the disputes, especially those pertaining to community engagement mechanisms, were ultimately resolved in international fora and implemented in later PrEP trials, concerns over science rationales and assumptions were never addressed. We argue that scientific rationales should be treated as ethical concerns and suggest that such concerns should be deliberated at host sites before the trial protocol is finalized. (shrink)

The Declaration of Helsinki and the Council of the International Organization of Medical Sciences provide guidance on standards of care and prevention in clinical trials. In the current and increasingly challenging research environment, the ethical status of a trial design depends not only on protection of participants, but also on social value, feasibility, and scientific validity. Using the example of a study assessing efficacy of a vaccine to prevent human papilloma virus in HIV-1 infected adolescent girls in low resource (...) countries without access to the vaccine, we compare several trial designs which rank lower on some criteria and higher on others, giving rise to difficult trade-offs. This case demonstrates the need for developing more nuanced guidance documents to help researchers balance these often conflicting criteria. (shrink)

Research that is initiated, designed or funded by sponsor agencies based in countries with relatively high social and economic development, and conducted in countries that are relatively less developed, gives rise to many important ethical challenges. Although clinical trials of HIV vaccines began ten years ago in the US and Europe, an increasing number of trials are now being conducted or planned in other countries, including several that are considered “developing” countries. Safeguarding the rights and welfare of individuals (...) participating as research subjects in developing countries is a priority. In September, 1997, the Joint United Nations Programme on HIV/AIDS embarked on a process of international consultation; its purpose was further to define the important ethical issues and to formulate guidance that might facilitate the ethical design and conduct of HIV vaccine trials in international contexts. This paper summarises the major outcomes of the UNAIDS consultative process. (shrink)

More than 25 years into the HIV epidemic, in excess of 2 million new infections continue to occur each year. HIV prevention research is crucial for groups at heightened risk for HIV, but the design and conduct of HIV prevention research with vulnerable populations worldwide raises considerable ethical challenges. The HIV Prevention Trials Network (HPTN) is a global collaborative network that conducts clinical and behavioural studies on non-vaccine interventions to reduce the transmission of HIV. In 2003, the HPTN developed (...) ethical guidance to enhance the responsible conduct of its research activities and as a distinctive contribution to global research ethics. In what follows, the developments that motivated the drafting of a revised ethics document in 2009 are described, including the process by which that revision took place and some of the key differences between the HPTN ethics guidance and other relevant guidelines in the field. (shrink)

Objectives: To describe the concerns and priorities of key stakeholders in a developing country regarding ethical obligations held by researchers and perceptions of equity or “what is fair” for study participants in an HIV/AIDS clinical drug trial. Design: Qualitative study with focus groups. Setting: Teaching and referral hospital and rural health centre in western Kenya. Participants: Potential HIV/AIDS clinical trial participants, clinician researchers, and administrators. Results: Eighty nine individuals participated in a total of 11 focus groups over a four month (...) period. The desire for continued drug therapy, most often life long, following an HIV/AIDS clinical trial was the most common priority expressed in all focus groups. Patients with and without HIV/AIDS also thought subsidisation of drug therapies and education were critical forms of compensation for clinical trial participation. Financial incentives were considered important primarily for purchasing drug therapy as well as obtaining food. Patients noted a concern for the potential mismanagement of any money offered. Clinician researchers and administrators felt strongly that researchers have a moral obligation to participants following a trial to provide continued drug therapy, adverse event monitoring, and primary care. Finally, clinician researchers and administrators stressed the need for thorough informed consent to avoid coercion of study participants. Conclusions: Kenyan patients, clinician researchers, and administrators believe that it would be unfair to stop antiretroviral therapy following an HIV/AIDS clinical trial and that researchers have a long term obligation to participants. (shrink)

Debates about what constitutes benefits in human research continue to be less informed due to a lack of empirical evidence from the developing world. This study aimed to explore what constitutes benefits in HIV vaccine trials in Tanzania and examine inherent ethical implications. A qualitative case study design was deployed and a total of 29 purposively selected study participants comprising of experienced researchers, institutional review board members and community advisory board members were included. Collected data were analyzed by thematic (...) analysis aided by computer software: MAXQDA version 20.4.0. The study findings indicate that there is a growing appreciation of benefits beyond actual vaccines to include 1) capacity building at individual, community, institutional and regulatory levels; and 2) non‐capacity building related benefits such as strengthened collaborations, ancillary care and employment opportunities. So, as the struggle for viable HIV vaccines continues, other benefits that have accrued from such trials are not to be blindsided especially for developing countries like Tanzania. (shrink)

Background South Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality. Discussion This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent (...) requirements, child protection laws, and processes for the ethical and regulatory approval of research. Summary This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trig mandatory reporting response; networking among relevant ethics commitees; and lobbying the National Regulatory Authority for guidance. (shrink)

Researchers and sponsors are required to assist HIV prevention trial participants to remain HIV-uninfected by ensuring access to prevention services. Ethics guidelines require that these HIV risk-reduction services be state of the art. This and related ethics recommendations have been intensely debated. This descriptive study aimed to identify actual HIV prevention practices for two HIV vaccine trials at five South African sites, to explore whether actual practices meet guideline recommendations and to discuss implications for practices and ethics guidelines. Practices (...) were examined through a review of site documents and interviews with site staff and network representatives, as well as community advisory board and research ethics committee representatives. A thematic analysis of HIV prevention practices, perspectives and perceived challenges was undertaken. Findings indicated that there was a high degree of correspondence between actual practices in South African HIV vaccine trials and guideline recommendations. Key challenges for implementing prevention services were identified as partnerships, provider-promotion of services and participant uptake of services. Practices deviated most from guidelines with regard to the description of prevention plans in informed consent forms. Recommendations are made for both practices and ethics guidelines. (shrink)

Controversy persists over the ethics of compensating research participants and providing posttrial benefits to communities in developing countries. Little is known about residents' views on these subjects. In this study, interviews about compensation and posttrial benefits from a hypothetical HIV vaccine trial were conducted in Uganda’s Rakai District. Most respondents said researchers owed the community posttrial benefits and research compensation, but opinions differed as to what these should be. Debates about posttrial benefits and compensation rarely include residents' views like these, (...) but future ones should. (shrink)

The massive growth in global health research in past decades has posed many challenges for its effective ethical oversight, not least of which is how best to provide effective protection of research participants. The extent of the HIV epidemic in sub-Saharan Africa in particular makes research into prevention technologies for HIV, including HIV vaccine research, a global priority. However, the need for vaccine research must be considered in conjunction with the individual's right to informed consent, which is based on the (...) principle of respect for autonomy. One of the primary human rights violations likely to occur in the context of HIV vaccine research is that potential research participants may not fully understand what participation in research studies entails. People who elect to enrol in HIV vaccine trials are required to understand both the potential negative effects of participation (eg, discrimination) as well as complex scientific concepts such as randomisation and prophylaxis in order to be ethically enrolled. In this study, two vignettes are presented to illustrate two core issues in conducting phase III HIV vaccine trials in low-income countries—namely, (1) from the perspective of participants, the extent to which understanding is a prerequisite for consenting to participate in a trial, and (2) from the perspective of trial investigators, whether it is appropriate to persuade eligible people to enrol in a trial, even though their initial reaction is to decline to participate. These vignettes are used to analyse these issues through the prisms of research ethics and human rights in order to identify helpful synergies. It is argued that the human rights perspective provides a helpful lens on ethical issues. (shrink)

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption, involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal (...) decision-making study nested in a Thai acute HIV research cohort. In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks. These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. (shrink)

ABSTRACTGiven the ethical controversies concerning HIV vaccine trials , we aimed to understand through an exploratory study how members of institutional review boards in the United States and research ethics committees in South Africa view issues concerning the process and content of reviews of these studies. We mailed packets of 20 questionnaires to 12 US IRB chairs and administrators and seven REC chairs to distribute to their members. We received 113 questionnaires . In both countries, members tended to be (...) white males with advanced academic degrees. Compared to the US, SA members called for ‘major changes’ in HVT protocols more frequently , and were less likely to think that HVT participants understood risks and benefits or informed consent forms . In both countries, members were divided on several critical issues , but agreed that they needed more training. Of the SA respondents, 40% reported that they were ‘self‐taught’ in ethics. This study, the first we know of to offer quantitative data comparing US vs. non‐US IRBs/RECs, thus suggests key similarities and differences , along with needs for education. These initial exploratory data in this area have important implications for IRBs, RECs, policy‐makers and scholars concerning future practice, training, policy, and investigations in research ethics, and prevention and treatment of HIV and other diseases in the developing world and elsewhere. (shrink)

Background A morally sound framework for benefit-sharing is crucial to minimize research exploitation for research conducted in developing countries. However, in practice, it remains uncertain which stakeholders should be involved in the decision-making process regarding benefit-sharing and what the implications might be. Therefore the study aimed to empirically propose a framework for benefit-sharing negotiations in research by taking HIV vaccine trials as a case. Methods The study was conducted in Tanzania using a case study design and qualitative approaches. Data (...) were collected using in-depth interviews (IDI) and focus group discussions (FGD). A total of 37 study participants were selected purposively comprising institutional review board (IRB) members, researchers, community advisory board (CAB) members, a policymaker, and HIV/AIDS advocates. Deductive and inductive thematic analysis approaches were deployed to analyze collected data with the aid of MAXQDA version 20.4.0 software. Results The findings indicate a triangular relationship between the research community, researched community and intermediaries. However, the relationship ought to take into consideration the timing of negotiations, the level of understanding between parties and the phase of the clinical trial. The proposed framework operationalize partnership interactions in community-based participatory research. Conclusion In the context of this study, the suggested framework incorporates the research community, the community being researched, and intermediary parties. The framework would guarantee well-informed and inclusive decision-making regarding benefit-sharing in HIV vaccine trials and other health-related research conducted in resource-limited settings. (shrink)

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale multicentre HIV (...) prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA. (shrink)

Volume 31, Issue 1, December 2020, Page 47-66.

Clinical trials in developing countries are often beset by ethical problems that would be considered unresolvable in countries like Australia and the U.S. Nevertheless, such trials continue to go ahead throughout Asia, Africa and South America, and are often conducted in ways that could be considered to be unethical. In this article I discuss two issues, focussing on an HIV preventative trial of a vaginal gel, the Nonoxynol 9 phase three trial being held in Kenya. The first of (...) these is what makes such a trial unethical given that it has approval from the WHO and seemingly conforms with acceptable standards of consent. The second issue involves using material from such trials, if we accept that they were conducted unethically. (shrink)

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from (...) South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. (shrink)

The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, especially where government bodies, sponsors, and (...) regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. (shrink)

The aims of this study were to measure the readability of Australian based informed consent documents and determine whether informed consent readability guidelines have been established by Australian human research ethics committees (HRECs). A total of 20 informed consent documents, 10 HIV/AIDS and 10 type 2 diabetes, were measured for readability using the Simple Measure of Gobbledygook (SMOG) and Gunning Fog Index (Fog). Published guidelines and policy statements of the two local HREC who approved the 20 clinical trials under (...) study where examined to identify whether they had any formal policies/guidelines on the readability of informed consent documents. The two HRECs were contacted via e-mail to also determine whether they utilised any informal readability standards or “rules of thumb” that may not have been mentioned in the published documents. The HIV/AIDS and type 2 diabetes informed consent documents were, on average, written at a grade 13 reading level. Formal readability standards had not been established by the two local HRECs, however, they did verify the use of informal rules for assessing readability of informed consent documents. Based on Australian literacy data, the majority of informed consent documents were written well beyond the reading ability of many Australians. Unreadable informed consent documents may result in patients rejecting trial participation altogether or conversely may result in their participating in a trial with inadequate consent. Therefore, a step toward reducing the complexity of informed consent documents may be to implement objective readability assessments into the human research ethics application and review process. (shrink)

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research (...) stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment. While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research. (shrink)

This pilot randomized controlled trial explored the feasibility, acceptability, and potential utility of an intervention to improve the decisional capacity (DC) for research consent/assent among youth living with HIV (YLWH). We randomly assigned 30 YLWH aged 13–24 to a control (paper-based) or intervention (multimedia) consent/assent condition. Using a between- and within-subjects design, participants completed a demographic questionnaire and measures of DC, acceptability/feasibility, and voluntary self-consent perceptions after undergoing a hypothetical consent/assent process for a biomedical HIV study. Findings suggest participants found (...) the intervention feasible and acceptable. Participants in the intervention condition scored higher on a DC measure; however, scores did not meet the predetermined cutoff score for adequate DC in either group. The potential implications of these findings for research with youth, including YLWH, are discussed. (shrink)

Over the past decade AIDS research has turned toward the use of pharmacology in HIV prevention, including pre-exposure prophylaxis (PrEP): the use of HIV medication as a means of preventing HIV acquisition in those who do not have it. This paper explores the contradictory reasons offered in support of PrEP—to empower women, to provide another risk-reduction option for gay men—as the context for understanding the social meaning of the experimental trials that appear to show that PrEP works in gay (...) men and heterosexual couples but not single women. The PrEP debates reveal the different ideas about “demedicalization” in the earlier gay health and women’s health movements and highlight the relationship between health activism and critique of research ethics in the context of a global pharmaceutical market. (shrink)

There is a gap in evidence regarding how research trial closure processes are managed to ensure continuity of HIV care for HIV positive participants following trial closure within low income settin...

All international codes of research ethics and virtually all national legislation and regulation in the field of research involving human subjects project an attitude of protectionism. Written with the aim of avoiding a repetition of atrocities like those committed by the Nazi physician-researchers, calamities like the thalidomide experience, or ethical violations like those of the Tuskegee syphilis study, their dominant concerns are the protection of individuals from injury and from exploitation. In recent years, however, society's perception of clinical research has (...) shifted dramatically. Now, largely as a consequence of the efforts of the AIDS activists, clinical research is widely perceived as benign and beneficial. Although this shift in attitude has resulted in some important improvements in research policies and practices, this new perception is just as wrong-headed as was the earlier excessive protectionism. It is necessary to maintain a balanced perspective; our policies should encourage the conduct of ethical research while maintaining the vigilance necessary to safeguard the rights and welfare of the subjects. (shrink)

The successful demonstration that antiretroviral (ARV) drugs can be used in diverse ways to reduce HIV acquisition or transmission risks – either taken as pre-exposure prophylaxis (PrEP) by those who are uninfected or as early treatment for prevention (T4P) by those living with HIV – expands the armamentarium of existing HIV prevention tools. These findings have implications for the design of future HIV prevention research trials. With the advent of multiple effective HIV prevention tools, discussions about the ethics and (...) the feasibility of future HIV prevention trial designs have intensified. This article outlines arguments concerning the inclusion of newly established ARV-based HIV prevention interventions as standard of prevention in HIV prevention trials from multiple perspectives. Ultimately, there is a clear need to incorporate stakeholders in a robust discussion to determine the appropriate trial design for each study population. (shrink)

BackgroundInformed consent as stipulated in regulatory human research guidelines requires that a volunteer is well-informed about what will happen to them in a trial. However researchers are faced with a challenge of how to ensure that a volunteer agreeing to take part in a clinical trial is truly informed. We conducted a qualitative study among volunteers taking part in two HIV clinical trials in Uganda to find out how they defined informed consent and their perceptions of the trial procedures, (...) study information and interactions with the research team.MethodsBetween January and December 2012, 23 volunteers who had been in the two trials for over 6 months, consented to be interviewed about their experience in the trial three times over a period of nine months. They also took part in focus group discussions. Themes informed by study research questions and emerging findings were used for content analysis.ResultsVolunteers defined the informed consent process in terms of their individual welfare. Only two of the volunteers reported having referred during the trial to the participant information sheets given at the start of the trial. Volunteers remembered the information they had been given at the start of the trial on procedures that involved drawing blood and urine samples but not information about study design and randomisation. Volunteers said that they had understood the purpose of the trial. They said that signing a consent form showed that they had consented to take part in the trial but they also described it as being done to protect the researcher in case a volunteer later experienced side effects.ConclusionVolunteers pay more attention during the consent process to procedures requiring biological tests than to study design issues. Trust built between volunteers and the research team could enhance the successful conduct of clinical trials by allowing for informal discussions to identify and review volunteers’ perceptions. These results point to the need for researchers to view informed consent as a process rather than an event. (shrink)

The use of foster children as subjects in the pediatric HIV/AIDS clinical trials has been the subject of media controversy, raising a range of ethical and social dimensions. Several unsettled issues and debates in research ethics underlie the controversy and the lack of consensus among professional researchers on these issues was neither adequately appreciated nor presented in media reports. These issues include (1) the tension between protecting subjects from research risk while allowing them access to the possible benefits of (...) research; (2) the blurring of the potentially conflicting roles of investigator and physician and the boundaries between research and therapy; (3) the adequacy of Institutional Review Board oversight; and (4) trust and the relationships among physicians, investigators and industry. The media controversy about the pediatric HIV/AIDS clinical trials can be seen as a means of “manufacturing mistrust” in health care, research and social services that have not always met the needs and expectations of the public. In an era of emerging infections, it is critical to the public’s health that people understand the role of rigorous and ethical research in the development of safe and effective care. Investigators, journalists and the public need to become knowledgeable about major ethical issues in the conduct of research in order to engage in dialogue about balancing research risks and benefits and to be able to distinguish fact from distortion in an era of multiple and rapid transmission of information. (shrink)

Background: Clinical trials involving children previously considered unethical are now considered a necessity because of the inherent physiological differences between children and adults. An integral part of research ethics is the informed consent, which for children is obtained by proxy from a consenting parent or guardian. The informed consent process is governed by international ethical codes that are interpreted in accordance with local laws and procedures raising the importance of contextualizing their implementation.DiscussionThe Zimbabwean parental informed consent document for children (...) participating in clinical research is modeled along western laws of ethics and requires that the parent or legally authorized representative provide consent on behalf of a minor. This article highlights the experiences and lessons learnt by Zimbabwean researchers in interpreting and obtaining informed consent for orphaned children participating in a collaborative HIV clinical trial involving the Medical Research Council, United Kingdom and four centers, three of which are in Uganda. Researchers were faced with a situation where caregivers of orphaned children were not permitted to provide informed consent for trial participation if the Zimbabwean courts had not legally appointed them. The situation contrasted with general clinical practice where legal papers where not required for providing consent for surgical procedures for example.SummaryExperiences gained from this clinical trial revealed that while there may be internationally established guidelines governing the process of obtaining informed consent for children participating in research, there may be need to be cognizant of the culture within which the research is taking place. This may call for the development of an ethico-legal framework that governs research-involving children in Zimbabwe that would facilitate their participation in clinical research, while ensuring that they are protected from exploitation. The Medical Research Council of Zimbabwe has since started developing that framework in a process that is expected to involve critical stakeholders namely the community including children, ethicists, the legal fraternity and researchers. (shrink)

BackgroundInformed consent as stipulated in regulatory human research guidelines requires volunteers to be well-informed about what will happen to them in a trial. However, researchers may be faced with the challenge of how to ensure that a volunteer agreeing to take part in a clinical trial is truly informed. This study aimed to find out volunteers’ comprehension of informed consent and voluntary participation in Human Immunodeficiency Virus (HIV) clinical trials during the registration cohort.MethodsWe conducted a qualitative study among volunteers (...) who were enrolled in the registration cohort of HIV clinical trials in Dar es Salaam, Tanzania. A purposive sampling strategy was used to obtain twenty study participants. The data were collected between June and September 2020 using a semi-structured interview guide. In-depth interviews were used to collect the data to obtain deep insights of the individual study participants on the comprehension of informed consent and participation in the clinical trial. A thematic analysis approach was used to analyze the data. Themes and subthemes were supported by the quotes from the participants.ResultsVolunteers described comprehension of informed consent from different perspectives. They reported that various components of the informed consent such as study procedure, confidentiality, risk and benefits were grasped during engagement meetings. Furthermore, the volunteers’ decision to participate in the registration cohort was voluntary. However, trial aspects such as health insurance, free condoms, and medical checkups could have indirectly influenced their reluctance to withdraw from the study.ConclusionEngagement meetings may increase the comprehension of informed consent among potential participants for HIV clinical trials. However, trial incentives may influence participation, and thus future research should focus on the challenges of giving incentives in the study. This will ensure comprehension and voluntary participation in the context of HIV clinical trials. (shrink)

BackgroundCommunity Advisory Boards (CAB) have become essential organs of involving communities in HIV clinical trials especially in developing countries. However, limited empirical evidence exists on the role of CABs in low and middle-income countries including Tanzania. This study aims at exploring the role of CABs in community-based HIV clinical trials conducted in Tanzania.MethodologyWe adopted a phenomenological approach to purposefully select HIV clinical trial stakeholders. These included CAB members, researchers and Institutional Review Board (IRB) members in Tanzania. We conducted (...) In-depth Interviews (IDIs) with ten participants and three Focus Group Discussions (FGDs) with eighteen participants. The data were thematically analyzed with the aid of MAXQDA software version 20.2.1.ResultsThe findings indicate that at every stage of implementation of a community-based HIV clinical trial, a functioning CAB is important for its success. This importance is based on contextualization of the informed consent process and protocol, managing rumours in the community, weighing trial risks and benefits, sensitizing the community, assisting participant recruitment, tracing and retention. However, being perceived as financial beneficiaries than community representatives emerged as a challenge to CAB members. ConclusionThe study empirically indicates the need for functioning CABs in every stage of implementation of community-based HIV clinical trials. The roles of which are interwoven in serving research goals and protecting the interests of the community and that of trial participants. (shrink)

Is there no balm in Gilead; is there no physician there? Why then is not the health of the daughter of my people recovered?In July of 2004, Cambodian sex workers staged a protest of an HIV prevention trial set to enroll 900 sex workers in Phnom Penh, charging the study planners with exploitation. The Cambodian study was one of a series of international clinical trials sponsored by the U.S. National Institutes of Health, U.S. Centers for Disease Control and Prevention, (...) and the Bill and Melinda Gates Foundation testing the safety and efficacy of tenofovir, an antiretroviral drug produced by Gilead Sciences, Inc., to prevent HIV transmission. To date, two of these international studies have been closed and one is suspended, prompting calls for re-examination of the ethics of HIV prevention trials. (shrink)

The concept of minimal risk has been used to regulate and limit participation by adolescents in clinical trials. It can be understood as setting an absolute standard of what risks are considered minimal or it can be interpreted as relative to the actual risks faced by members of the host community for the trial. While commentators have almost universally opposed a relative interpretation of the environmental risks faced by potential adolescent trial participants, we argue that the ethical concerns against (...) the relative standard may not be as convincing as these commentators believe. Our aim is to present the case for a relative standard of environmental risk in order to open a debate on this subject. We conclude by discussing how a relative standard of environmental risk could be defended in the specific case of an HIV vaccine trial among adolescents in South Africa. (shrink)

BackgroundClinical trials involving children previously considered unethical are now considered essential because of the inherent physiological differences between children and adults. An integral part of research ethics is the informed consent, which for children is obtained by proxy from a consenting parent or guardian. The informed consent process is governed by international ethical codes that are interpreted in accordance with local laws and procedures raising the importance of contextualizing their implementation.FindingsIn Zimbabwe the parental informed consent document for children participating (...) in clinical research is modeled along western laws of ethics and requires that the parent or legally authorized representative provide consent on behalf of a minor. This article highlights the experiences and lessons learnt by Zimbabwean researchers in obtaining informed consent from guardians of orphaned children participating in a collaborative HIV clinical trial involving the Medical Research Council, United Kingdom and four centers, three of which are in Uganda. Researchers were faced with a situation where caregivers of orphaned children were not permitted to provide informed consent for trial participation. The situation contrasted with general clinical practice where consent for procedures on orphans is obtained from their caregivers who are not legal guardians.ConclusionThe challenges faced in obtaining informed consent for orphans in this clinical trial underscores the need for the Zimbabwe ethics committee to develop an ethical and legal framework for pediatric research that is based on international guidelines while taking into account the cultural context. The Medical Research Council of Zimbabwe has since started the process that is expected to involve critical stakeholders namely the community including children, ethicists, the legal fraternity and researchers. (shrink)