Imagine a study in which HIV-infected pregnant women are given antiretroviral treatment to determine how effectively it will prevent HIV transmission during childbirth. Each mother’s involvement in this study ends with the birth of her child, at which time her access to antiretrovirals provided by the study also ceases. At the outset of the study, the investigator and sponsor agree that after the child’s birth, they will refer mothers who require treatment for their HIV to a national program that provides (...) antiretroviral treatment and care. Assuming the Institutional Review Board raises no objections to this plan, should the research team consider their ethical obligations to participants fulfilled? If the investigator and sponsor were to consult the Common Rule, they would find little to suggest that there are any further ethical issues to address. (shrink)

Biomedical research is increasingly carried out in low- and middle-income countries. International consensus has largely been achieved around the importance of valid consent and protecting research participants from harm. But what are the responsibilities of researchers and funders to share the benefits of their research with research participants and their communities? After setting out the legal, ethical and conceptual frameworks for benefit sharing, this collection analyses seven historical cases to identify the ethical and policy challenges that arise in relation to (...) benefit sharing. A series of recommendations address possible ways forward to achieve justice for research participants in low- and middle-income countries. (shrink)

Objective: Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting. Methods: We selected global randomized trials registered on http://www.clinicaltrials.gov and http://www.controlled-trials.com. We searched for intervention (...) trials of HIV/AIDS, malaria, and tuberculosis from 9 October 2004, the date of the most recent version of the Helsinki Declaration, to 10 April 2007. Results: We collected data from 312 trials. Fifty-eight percent (58%, 95% CI = 53 to 64) of trial protocols report informed consent. Fifty-eight percent (58%, 95% CI = 53 to 64) of trials report active controls. Almost no trials (1%, 95% CI = 0.5 to 3) mention post-trial provisions. Most trials measure surrogate outcomes. Twenty percent (20%, 95% CI = 16 to 25) of trials measure patient-important outcomes, such as death; and the odds that these outcomes are in a low income country are five times greater than for a developed country (odds ratio (OR) 5.03, 95% CI = 2.70 to 9.35, p = < 0.001). Pharmaceutical companies are involved in 28% (CI = 23 to 33) of trials and measure surrogate outcomes more often than nonpharmaceutical companies (OR 2.45, 95% CI = 1.18 to 5.09, p = 0.31). Conclusion: We found a large discrepancy in the quality of reporting and approaches used in trials in developing settings compared to wealthier settings. (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)

The acceleration of the market globalisation process over the last three decades has internationalised clinical research and influenced both the way in which it is funded and the development and application of research practices. In addition, in recent years international multicentre randomised clinical trials have become the model par excellence for research on new medicines. The neoliberal model of globalisation has induced a decline in state power, both with regard to establishing national research for health priorities and to influencing the (...) development of adequate ethical guidelines to protect human beings that participate in multinational research. In this respect, poor and low-income countries, which lack sustainable control and review systems to deal with the ethical and methodological challenges of complex studies conducted by researchers from affluent countries and funded by large multinational pharmaceutical companies, are particularly vulnerable. The aim of the present paper is to explore critically some of the actual and possible ethical pitfalls of globalisation of clinical research and propose mechanisms for turning transnational clinical research into a more cooperative and fairer enterprise. (shrink)

BackgroundHIV prevention research in resource-limited countries is associated with a variety of ethical dilemmas. Key amongst these is the question of what constitutes an appropriate standard of health care (SoC) for participants in HIV prevention trials. This paper describes a community-focused approach to develop a locally-appropriate SoC in the context of a phase III vaginal microbicide trial in Mwanza City, northwest Tanzania.MethodsA mobile community-based sexual and reproductive health service for women working as informal food vendors or in traditional and modern (...) bars, restaurants, hotels and guesthouses has been established in 10 city wards. Wards were divided into geographical clusters and community representatives elected at cluster and ward level. A city-level Community Advisory Committee (CAC) with representatives from each ward has been established. Workshops and community meetings at ward and city-level have explored project-related concerns using tools adapted from participatory learning and action techniques e.g. chapati diagrams, pair-wise ranking. Secondary stakeholders representing local public-sector and non-governmental health and social care providers have formed a trial Stakeholders' Advisory Group (SAG), which includes two CAC representatives.ResultsKey recommendations from participatory community workshops, CAC and SAG meetings conducted in the first year of the trial relate to the quality and range of clinic services provided at study clinics as well as broader standard of care issues. Recommendations have included streamlining clinic services to reduce waiting times, expanding services to include the children and spouses of participants and providing care for common local conditions such as malaria. Participants, community representatives and stakeholders felt there was an ethical obligation to ensure effective access to antiretroviral drugs and to provide supportive community-based care for women identified as HIV positive during the trial. This obligation includes ensuring sustainable, post-trial access to these services. Post-trial access to an effective vaginal microbicide was also felt to be a moral imperative.ConclusionParticipatory methodologies enabled effective partnerships between researchers, participant representatives and community stakeholders to be developed and facilitated local dialogue and consensus on what constitutes a locally-appropriate standard of care in the context of a vaginal microbicide trial in this setting.Trial registrationCurrent Controlled Trials ISRCTN64716212. (shrink)

This response addresses criticisms in this journal of an Editorial written by Willem Landman and Udo Schuklenk. I demonstrate that the UNESCO Declaration on Bioethics and Human Rights is in crucial aspects deficient, despite attempts in this journal to defend the Declaration against its critics. I focus on individual versus societal interests, research ethics, informed consent and the use of “human dignity” to illustrate the weaknesses of the UNESCO Declaration on Bioethics and Human Rights. This article concludes with reflections on (...) what documents such as the UNESCO Declaration on Bioethics and Human Rights ought to be called to avoid the mislabelling of what essentially are policy documents. (shrink)

The conduct of clinical trials involving placebo in developing countries in the presence of an existing effective treatment triggered an intense debate on the standard of care to be provided to those populations. Charges of exploitation of vulnerable groups and double standards have been raised by several scholars. In response to these concerns, the Declaration of Helsinki was revised in 2000, 2008 and 2013, eventually endorsing the golden standard instead of the local standard of care. The European Union adopted a (...) strategy on the Marketing Authorization of medicinal products tested in third countries, improved with Regulation 536/2014 on clinical trials on medicinal products for human use. Additional rules have been enacted by other international organizations. The present paper has the aim of analyzing scope and content of existing international and regional standards on placebo. (shrink)

HIV prevention is a critical health issue in Nigeria; a country that has one of the worst HIV epidemic profiles in the world. With 270,000 new infections in 2012, Nigeria is a prime site for HIV prevention research. One effect of the HIV epidemic has been to revolutionalise ethical norms for the conduct of research: it is now considered unethical to design and implement HIV related studies without community engagement. Unfortunately, there is very little commensurate effort in building the capacity (...) of local persons to engage actively with researchers, and there is no existing platform to facilitate dialogue between researchers and communities engaged in research in Nigeria. In an effort to address this gap, we undertook a series of three community dialogues and two community-researcher interface meetings in Nigeria. This paper aims to give an empirical account of the dialogue from these community engagement processes and provide a resulting critique of the implementation of research ethics practices in Nigeria. It is anticipated that the outputs will: support researchers in designing community-based research protocols; inform ethics committees of key considerations during research protocol reviews from a community perspective; and inform policy makers and research sponsors about issues of primary concern to communities with respect to HIV research. (shrink)

At the end of a paper on international research ethics published in the July-August 2010 issue of the Hastings Center Report, London and Zollman argue the need for grounding our duties in international medical and health-related research within a broader normative framework of social, distributive, and rectificatory justice. The same goes for Thomas Pogge, who, in a whole range of publications during the past years, has argued for a human-rights-based approach to international research. In a thought-provoking paper in the June (...) 2010 issue of the American Journal of Bioethics, Angela J. Ballantyne argues that “the global bioethics priority” in medical and health-related research ethics today is how to do research fairly in an unjust world. (shrink)

In rapidly evolving medical fields where the standard of care or prevention changes frequently, guidelines are increasingly likely to conflict with what participants receive in research. Although guidelines typically set the standard of care, there are some cases in which research can justifiably deviate from guidelines. When guidelines conflict with research, an ethical issue only arises if guidelines are rigorous and should be followed. Next, it is important that the cumulative evidence and the conclusions reached by the guidelines do not (...) eliminate the need for further research. Even when guidelines are rigorous and the study still asks an important question, we argue that there may be good reasons for deviations in three cases: (1) when research poses no greater net risk than the standard of care; (2) when there is a continued need for additional evidence, for example, when subpopulations are not covered by the guidelines; and (3) less frequently, when clinical practice guidelines can be justified by the evidence, but practitioners disagree about the guidelines, and the guidelines are not consistently followed as a result. We suggest that procedural protections may be especially useful in deciding when studies in the third category can proceed. (shrink)

(2010). For-Profit Clinical Trials in Developing Countries—Those Troublesome Patient Benefits. The American Journal of Bioethics: Vol. 10, No. 6, pp. 52-54.

There are now at least two different views that fall under the heading of the “fair benefits” approach (FBA) to international research. These views share a number of important commitments, such as...