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)

The ethical challenge is squarely focused on the question of what is owed to participants of vaccine trials who happen to become infected during the course of the trial. Not surprisingly, given the prominence of HIV/AIDS in many parts of the developing world, HIV vaccine trials have become the focal point of this debate. It is worth noting from the outset, however, that the same arguments that apply to HIV vaccines would apply to any number of (...) microbicide trials aimed at protecting women against a large variety of sexually transmitted illnesses.1 One of the controversial questions in this debate has been the issue of whether or not an infection acquired by vaccine trial participants during the course of the trial can reasonably be considered a trial related injury that ought to be subject to compensation (in the form of access to good quality AIDS treatments, including antiretrovirals). (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)

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)

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)

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)

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)

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)

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 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)

Objective Adolescents have had very limited access to research on biomedical prevention interventions despite high rates of HIV acquisition. One concern is that adolescents are a vulnerable population, and trials carry a possibility of harm, requiring investigators to take additional precautions. Of particular concern is preventive misconception, or the overestimation of personal protection that is afforded by enrolment in a prevention intervention trial. Methods As part of a larger study of preventive misconception in adolescent HIV vaccine trials, (...) we interviewed 33 male and female 16–19-year-olds who have sex with men. Participants underwent a simulated HIV vaccine trial consent process, and then completed a semistructured interview about their understanding and opinions related to enrolment in a HIV vaccine trial. A grounded theory analysis looked for shared concepts, and focused on the content and process of adolescent participants’ understanding of HIV vaccination and the components of preventive misconception, including experiment, placebo and randomisation. Results Across interviews, adolescents demonstrated active processing of information, in which they questioned the interviewer, verbally worked out their answers based upon information provided, and corrected themselves. We observed a wide variety of understanding of research concepts. While most understood experiment and placebo, fewer understood randomisation. All understood the need for safer sex even if they did not understand the more basic concepts. Conclusions Education about basic concepts related to clinical trials, time to absorb materials and assessment of understanding may be necessary in future biomedical prevention trials. (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)

South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders’ perspectives on ethical guidance related to prevention and care in HIV vaccine trials.

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)

The American Journal of Bioethics, Volume 11, Issue 6, Page 21-22, June 2011.

BackgroundFor over 35 years, Africa has continued to host HIV vaccine trials geared towards overturning the HIV/aids pandemic in the continent. However, the methods of sharing the vaccines, when available remain less certain. Therefore, the study aims to explore stakeholders’ perspectives in the global South, in this case, Tanzania, on how HIV vaccines ought to be fairly shared.MethodsThe study deployed a qualitative case study design. Data were collected through in-depth interviews and focus group discussions with a total of (...) 37 purposively selected participants. This included researchers, institutional review board members, a policymaker, HIV/aids advocates, and community advisory board members. The data obtained were inductively and deductively analyzed.Results Findings indicate that HIV vaccines can be shared fairly under the principles of distributive justice (contribution, need and equality). Thus, contribution-based sharing ought to be utilized upon the necessity to prioritize vaccine access or subsidized trial benefits to host communities. Need-based sharing ought to be considered for non-host communities that are at an increased risk of HIV infection. Lastly, equal-based sharing would be useful at later stages of vaccine distribution or when the aforementioned principles are deemed morally inappropriate. However, none of the benefit-sharing approaches is free of limitations and a counterbalancing sense of unfairness.ConclusionFair sharing of HIV vaccines, when available, ought to be informed by the contribution, need and equality principles of distributive justice. Countries in the global south including Tanzania are likely to be prioritized during the distribution of the HIV vaccines due to their participation in HIV vaccine trials and due to the disproportionate HIV burden evident in the region. (shrink)

BackgroundLittle is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate.MethodsObservation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews (...) were recorded, transcribed and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants’ stories to develop two ideal portraits based on "composite characters" based on study participants features. These provide ethnographically rich details of participants’ meaningful social worlds while protecting individual identities.ResultsTen of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation.ConclusionsOur findings support Fisher’s argument of “structural coercion” in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie “under consent” of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North. (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)

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)

While the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, markers measuring immune response to vaccination were strongly correlated with infection. This finding generated the hypothesis that some marker-defined vaccinated subgroups were partially protected whereas others had their risk increased. This hypothesis can be assessed using the principal stratification framework (Frangakis and Rubin, 2002) for studying treatment effect modification by an intermediate response variable, using methods in the sub-field of principal (...) surrogate (PS) analysis that studies multiple principal strata. Unfortunately, available methods for PS analysis require an augmented study design not available in HVTN 505, and make untestable structural risk assumptions, motivating a need for more robust PS methods. Fortunately, another sub-field of principal stratification, survivor average causal effect (SACE) analysis (Rubin, 2006) – which studies effects in a single principal stratum – provides many methods not requiring an augmented design and making fewer assumptions. We show how, for a binary intermediate response variable, methods developed for SACE analysis can be adapted to PS analysis, providing new and more robust PS methods. Application to HVTN 505 supports that the vaccine partially protected individuals with vaccine-induced T-cells expressing certain combinations of functions. (shrink)

An amendment to this paper has been published and can be accessed via the original article.

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)

A group of activist clinicians have offered to volunteer for clinical trials of live attenuated HIV vaccines. This has provided an important conceptual challenge to medical ethics, and to work on the development of HIV vaccines. In exploring these issues, this article highlights how the HIV field has altered the content as well as the tone of ethical discourse. The balance of expertise and authority between research subjects and triallists is profoundly changed, raising questions about the limits of voluntarism (...) and differing perspectives on risk-benefit analysis. Care is needed to ensure that the novelty of the situation does not confuse the central ethical and scientific issues. (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)

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 study reports on the results of an empirical investigation of the education and recruitment processes used in HIV vaccine trials conducted in South Africa. Interviews were conducted with 21 key informants involved in HIV vaccine research in South Africa and three focus groups of community advisory board members. Data analysis identified seven major themes on the relationship between education and recruitment: the process of recruitment, the combined dual role of educators and recruiters, conflicts perceived by field (...) staff, pressure to achieve recruitment targets, problems in achieving comprehension, accountability and education as capacity building. The results raise ethical concerns about the adequacy of current informed consent processes in these settings. The study findings bear directly on current debates about issues of exploitation and the scope of moral responsibilities of researchers and funding agencies to assure that HIV clinical prevention research is conducted ethically. (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)

Proper conduct of an AIDS vaccine trial in Africa must be informed not only by the epidemiology and biology of HIV infection in African settings, but also by the ethical norms and cultural constraints prevailing in African settings.

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)

Introduction Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. Methods Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. Results 123 youth completed (...) the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. Conclusions Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking. (shrink)

This dissertation explores the ethics of human subjects research with particular attention to how clinical research on vaccines differs from research on therapies. The major differences are rooted in the fact that the benefits of vaccines and vaccine research accrue to the community to which vaccines belong by inducing herd immunity and thereby protecting both vaccinated and unvaccinated individuals. Therapeutics have no corresponding benefit to the community, the primary beneficiary is the individual. The ethical justification for conducting vaccine (...) research in a given community therefore should include an evaluation of the risks and benefits to the community as well as to involved individuals. Respect for individuals extends to respect for communities and for individuals as members of communities. A three way partnership between investigators, the community, and the community members is suggested as an ethical foundation for vaccine research. ;This model is then applied to the particular and complex case of testing a preventive HIV vaccine. HIV is an unique virus which continues to cause extraordinary devastation worldwide. The characteristics of HIV, its transmission and epidemiology, along with unprecedented scientific possibilities present a formidable challenge to the development and testing of an HIV vaccine. Using the community model, specific suggestions are made for the ethical conduct of clinical efficacy trials of HIV preventive vaccines. (shrink)

This paper explores three selected issues which present ethical challenges unique to the development and testing of preventive HIV vaccines. The issues are: when to move forward with large scale efficacy testing of vaccines, how to incorporate behavioral interventions into the study of vaccine efficacy, and how to plan for and mitigate social harms associated with participation in an HIV vaccine trial. Careful and ongoing consideration must be given to the ethical implications of these decisions. Proposed solutions include (...) planning for a more complex prevention trial which would integrate the evaluation of behavioral interventions and vaccine efficacy; scrupulous attention to the process of individual informed consent and community participation; and serious and deliberate attempts to plan for, educate about, and minimize the social harms. Keywords: behavioral interventions, HIV, subject protection, trial design, vaccines CiteULike Connotea Del.icio.us What's this? (shrink)

This study examined female sex workers’ evaluation of ethically relevant experiences of participating in an HPV4 vaccine clinical trial conducted in Lima, Peru. The Sunflower Study provided all participants with HPV testing, treatment for those testing positive, and access to the vaccine for all testing negative. Themes that emerged from content analysis of interviews with 16 former participants included the importance of respectful treatment and access to healthcare not otherwise available and concerns about privacy protections, the potential for (...) HIV stigma, and poststudy abandonment. (shrink)

Before sailing past the sirens' “flowery meadow,” Ulysses instructed his sailors to lash him to the mast so that he would not succumb to the siren's singing. His advance directive demonstrated that he valued his dispositional or long-term autonomy over his unquestioned right to make decisions. He also indicated to his oarsmen that he understood the nature of temptation and his inability to resist it. Ideas of autonomy and sexual choice are central to this discussion of new AIDS treatments, especially (...) the trials of preventative vaccines. Questions arise over the rights of individuals and the extent that these should be limited by concerns of the gay community. Should the gay community intervene in the risky decisions of individuals if no explicit advance directive exists? If so, how do they justify their paternalism? Could their aims not be better served through strengthening the individual dispositional autonomy of trial participants rather than making specific claims about the common good? (shrink)

Problems posed by HIV/AIDS differ from those ofpast epidemics by virtue of unique propertiesof the causative agent, dramatic societalchanges of the late 20th century, and thetransition of medical practice from aprofessional ethic to a technology-dependentbusiness ethic. HIV/AIDS struck during thecoming-of-age of molecular biology and also ofbioethics, and the epidemic stimulated thegrowth of both disciplines. The number ofarticles published about AIDS and ethics (asidentified by a MEDLINE search) peaked in 1990,just before the peak incidence of AIDS in theUnited States. The character (...) of ethicaldialogue has now shifted from familiar moralquandaries such as civil liberty versus publicwelfare to concerns about vaccine trials andpublic policy toward the developing world.Physicians and other health care workers whowere involved from the onset endured somethingof an emotional roller coaster. Theircompassion-based work ethic was to a largeextent replaced by a competence-based workethic after the introduction in 1996 of highlyactive antiretroviral therapy. The abundantrecent literature on ``professionalism'' inmedicine makes scant mention of AIDS/HIV. Thedisruptive effect of AIDS/HIV on society wouldhave been substantially greater had relevanttechnology such as the ability to isolateretroviruses and potent therapy againsttuberculosis not been in place. This soberingconsideration, along with such recent events asthe use of bioterrorism against civilianpopulations, suggests new relevance forPotter's definition of ``bioethics'' as a scienceof survival in which the biology of ecosystemsmust be taken into account. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Closing the Gaps in Pediatric HIV/AIDS Care, One Step at a TimeLisa V. Adams, Helga Naburi, Goodluck Lyatuu, Paul Palumbo, and C. Fordham von ReynFatuma's* doctors were completely perplexed. It was 2003 and she had returned to the DARDAR clinic in her hometown of Dar es Salaam, Tanzania three times that week with vague complaints of various pains and aches. Her doctors were considering whether these symptoms were due (...) to the initiation of her recent treatment with antiretroviral medications for her HIV infection or related to the last administration of the investigational tuberculosis (TB) vaccine that the DARDAR Health Study was evaluating. Fatuma's doctor, Dr. Lillian Mtei, consulted with Dartmouth's chief of Infectious Disease, Dr. Ford von Reyn, who happened to be in Dar that week on a site visit. Neither physician could determine the basis for her symptoms. Dr. Mtei returned to the exam room once more and this time emerged with the answer: Fatuma had just learned that her three year old daughter was HIV-infected, likely contracted from Fatuma during or shortly after she gave birth to her daughter. Fatuma believed that her HIV diagnosis was a death sentence for her daughter since antiretroviral therapy was not widely available for children.Dr. von Reyn, Dartmouth's lead clinical researcher in Africa and a father, knew too well the harsh reality of inequities in a resource-limited country. He turned to Dr. Mtei and said decidedly, "we need to do something about this."Thus the DARDAR Pediatric Program was born.Pediatric HIV: A Neglected DiseaseThe need for HIV treatment among children in Tanzania, as in most of sub-Saharan Africa, is compelling. At the end of 2009, approximately 160,000 children aged zero to fourteen in Tanzania were living with HIV (Joint United Nations Programme on HIV/AIDS [UNAIDS], 2011). Even with successful roll out of prevention of mother to child transmission programs in Tanzania, there were nearly 29,000 perinatal infections in 2009. As of December 2010, only 18% of these were enrolled in HIV treatment programs (UNAIDS, 2011; World Health Organization [WHO], 2011). Without antiretroviral therapy (ART), one-half of HIV-infected children will die before their second birthday. Since clinical research to determine efficacy and safety of new medical treatments is conducted almost exclusively in adults, provision of new medical treatments to [End Page 75] children always lags behind advances for adults. Furthermore, children are often underrepresented in programs for antiretroviral drugs for the following reasons: 1) they are not prioritized for care; 2) facilities lack infant diagnostic capabilities; 3) there is limited pediatric HIV training and consequently, a shortage of pediatric providers; and 4) pediatric antiretroviral formulations are frequently unavailable. The unacceptable delays in pediatric HIV drug development and treatment access led the international organization Drugs for Neglected Diseases initiative to publish an editorial in which they referred to pediatric HIV as a "neglected disease" (Lallemant, Chang, Cohen, & Pecoul, 2011).The Tip of the Iceberg: More than Just MedicinesWith a grant from the New York-based Foundation for the Treatment of Children with AIDS, the DARDAR Pediatric Program, a joint collaboration between Geisel School of Medicine at Dartmouth and Muhimbili University of Health and Allied Sciences, began seeing patients in May 2006. It was the first dedicated pediatric HIV Care and Treatment Center in Tanzania and operates in accordance with Tanzania's National AIDS Control Programme's guidance. Testing for both children and infants (the latter of which requires a more sophisticated assay) is available.The day the clinic opened we celebrated this collaborative effort that would provide HIV-infected children in Dar es Salaam access to antiretroviral treatment. One of our first patients was a six-year-old boy whose mother, like Fatuma, was a participant in our TB vaccine trial. She had been advised to bring her son to us for HIV screening. Her son looked healthy so she was surprised and understandably distraught when his test results indicated that not only was he HIV-infected, but his CD4 percentage was very low. His mother was reluctant to have him started on antiretrovirals given his general appearance and young age—and that he was... (shrink)

Developing a vaccine against HIV is one of the greatest challenges the scientific community faces today. Several vaccine candidates have undergone preliminary safety and immunogenicity studies in humans. Research teams are ready to test these vaccines in the field, yet the scientific community is divided as to whether efficacy trial should begin. This paper addresses the complex scientific and ethical issues raised by clinical trials. Considering the pressure to act rapidly to solve the crisis, scientists need to (...) hold to the fundamental principles that guide decisions in biomedical research: respect for persons, beneficence and justice. Because these studies need to enroll a large number of subjects, prospective vaccines will need to be tested in developing, as well as industrial countries. The international community needs to work to ensure that the populations that accept the risk of the research receive the full benefit of that research and, that the vaccine proven successful, be made accessible and affordable to people in less economically developed situation. (shrink)

The Ebola epidemic that broke out inWest Africa West AfricaAfrica towards the end of 2013 had been brought under reasonable control by 2015. The epidemic had severely affected three countries. This case study is about a phase I/II clinical trial Phase I/II clinical trial of a candidate Ebola virus vaccine in 2015 in a sub-Saharan AfricanSub-Saharan Africa country which had not registered any cases of the Ebola virus disease. The study was designed as a randomized double-blinded trialRandomized double blinded (...) trial. It was sponsored and funded by one of the biggest Northern multinational pharmaceutical companiesPharmaceutical companies. The protocol received ethics clearance from the relevantNational Ethics Committee national ethics committeeEthics committee. The study was coordinated and managed at the local branch of a big Northern diagnostic laboratoryDiagnostic laboratory and a laboratory of a local regional hospital. The overall study was a multi-countryMulti-country, multi-siteMulti-site trial aimed at recruiting a total of 3,000 research participantsResearch participants across four or five sub-Saharan African countries. For this country, the recruitmentRecruitment sites were two big cities, each aiming to recruit 200 participants: adults at the first site and childrenChildren at the second. The target sampleSample size was almost achieved at the first site but, before the study commenced at the second site, some members of raised the alarm that the governmentGovernment was carelessly risking the health, safetySafety and lives of citizens in the cause of an unproven vaccine that could precipitate a public health disaster. The trial was immediately suspended. A commentary on this case, and on the importance of trustTrust, is provided by Katharine Browne and Doris Schroeder at the end of this chapter. It highlights differences between this case and a phase I Ebola vaccine trial in CanadaCanada in 2014. (shrink)

Retroviruses replicate by inserting their proviral DNA into host cell chromosomes, usually in cells of the immune system. Nevertheless, an efficacious and safe subunit recombinant vaccine has been prepared against the feline leukemia retrovirus of cats. Because of high rates of morbidity and mortality, particularly in the developing world, the development of a vaccine against human immunodeficiency virus type I (HIV-I) has become very important. The very high rate of mutation or variation of lentiviruses, such as HIV-I, makes (...) a vaccine against this virus particularly difficult. Active research must be encouraged to design a modified envelope vaccine molecule of gp120 subtype E or C for trials in appropriate developing country settings. (shrink)

This paper discusses how to apply a collective decision model of the principle of voluntary informed consent in African communitarian culture, in a culturally sensitive way, in order to protect research candidates from potential exploitations and abuses. Dismissing cultural and ethical skepticism surrounding the global application of the principle of voluntary informed consent, the paper ultimately concludes that international collaboration on diagnostic and therapeutic medical research in Africa, especially HIV vaccine trials, is a moral imperative.

It has been proposed that the urgency of having a vaccine as a response to SARS-CoV-2 is so great, given the potential health, economic and social benefits that we should override the established s...

Vaccines are a powerful measure to protect the health of individuals and to combat outbreaks such as the COVID-19 pandemic. An ethical dilemma arises when one effective vaccine has been successfully developed against an epidemic disease and researchers seek to test the efficacy of another vaccine for the same pathogen in clinical trials involving human subjects. On the one hand, there are compelling reasons why it would be unethical to trial a novel vaccine when an effective (...) product exists already. First, it is a firm principle of medical ethics that an effective treatment or vaccine should not be withheld from patients if their life may depend on it. Second, since epidemic outbreaks often emerge in settings with less-resourced health systems, there is a pronounced risk that any trial withholding an effective vaccine would disproportionately affect the vulnerable populations that historically have been exploited for biomedical research. Third, clinical trials for novel vaccines may be at odds with efforts to control active outbreaks. On the other hand, it may be justified to conduct a trial for a candidate vaccine if it is expected to have certain advantages compared with the existing product. This essay discusses key factors for comparing vaccines against epidemic pathogens, including immunological, logistical and economic considerations. Alongside a case study of the development of vaccines for Ebola, the essay seeks to establish a general framework that should be expanded and populated by immunologists, epidemiologists, economists and bioethicists, and ultimately could be applied to the case of COVID-19 vaccines. (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)