The Wellcome Trust has traditionally been a significant funder of research overseas, and has well-established centres of research based in the developing world. Much of this work is clinically oriented, focusing on health problems in the developing world, and addressing a very serious burden of disease (see Clinical issues worldwide below). Research in developing countries raises many of the same ethical issues as in developed countries. However, there are a number of additional issues, driven by cultural, economic and socio-political factors, which are specific to particular regions or countries. The presence of researchers from rich countries carrying out research in poor countries also raises important questions even if, as in the case of Wellcome Trust-funded research, it is being carried out for the benefit of the poor countries.

One of these issues was highlighted in the recent debate surrounding trials of zidovudine (AZT) treatments. In many developing countries, there is no prospect of widespread anti-HIV drug treatment. US-sponsored trials of restricted courses of zidovudine treatment were carried out in countries that could not afford full courses, to see if a reduced dose was better than no dose at all in prevention of perinatal transmission in HIV-infected pregnant women. Some US experts subsequently argued that these trials were unethical, as no patient taking part in a trial sponsored by US funds should have been denied the ‘standard of care’ available in the USA.

There are some well-established guidelines for researchers. The Council for International Organizations of Medical Sciences (CIOMS) produced guidelines on ethical research in developing countries (see Biomedical research guidelines: A brief history below). These state, for example, that people in developing countries should not ordinarily be involved in research funded from developed countries if it could be carried out in those developed countries, and that research should be responsive to the health needs of the host country, not the sponsoring one.

Valuable though these guidelines are, difficulties can arise when it comes to their application in local settings. Indeed, weighing up local circumstances and general guidelines is one of the most testing challenges facing researchers working overseas. The issue of ‘universal standard of care’, exemplified by the HIV/zidovudine trial, is just one amongst several. Should people in developing countries be asked to take part in trials that may expose them to risk and offer them little benefit? The question of consent is also a vexed one. ‘Informed consent’ is a fundamental principle in any research involving human participants. However, it may be difficult to ensure that participants truly understand the nature of what they are consenting to. Translation into local languages may cause problems, and concepts such as placebo may be difficult to explain or be culturally unacceptable. In addition, ideas of individual autonomy are not universal – in some cultures, consent may be given by a spouse or a community leader, which may be considered unacceptable by the sponsoring country.

In countries where healthcare is very poor, the improved access to medical services that may come with research participation may be very hard to refuse. At what point does this constitute an inappropriate inducement and compromise the consent procedures? In addition, is there an ethical obligation on those conducting trials to ensure that improvements in healthcare as a result of the trial are maintained after the trials have finished?

These are just some of the very difficult issues that have to be addressed. In many cases the answers are unlikely to be clearcut; moreover, ethics are rarely set in stone: what was acceptable, say 20 years ago, may not be today. Many groups around the world are wrestling with the issues, and in the UK, the Nuffield Council on Bioethics – an independent body that receives financial support from the Wellcome Trust and others – has been running a consultation exercise and will be reporting in 2001 (see Nuffield Council on Bioethics below).

As well as contributing to the international debate, the Trust is also willing to support research projects on ethical issues in international biomedical research. Its Overseas Research Unit in Kenya, for example, is undertaking a project on informed consent. In its review procedures for overseas research grant applications, it has strict guidelines (for example, that research has approval from local bodies with authority for ethical approval, as well as the go-ahead from UK ethical committees if UK centres are involved). These are supported by a number of general principles underpinning its research (for example, that UK researchers should develop local collaborations at an institutional or individual level).

On the ground

While funding agencies such as the Wellcome Trust are well aware of their global responsibilities, the issues are an everyday fact of life for locations such as the Wellcome Trust’s International Centre in Population Studies and Reproductive Health in South Africa, colloquially referred to as the ‘Africa Centre’. It hosted and organised a workshop entitled ‘Ethical Issues in International Health Research’, after the World AIDS Congress, which was held in South Africa in July 2000. The workshop was funded by the Wellcome Trust and the US National Institutes of Health.

The Africa Centre, says Wendy Ewart of the Trust’s Population Studies Programme, has three main aims: “To be a world-class centre of excellence in research in population studies and reproductive health, to capacity build and create researchers for the future, and to act as a magnet for existing researchers.” The Centre was established in KwaZulu Natal, a rural area outside Durban with few healthcare resources.

According to the Centre’s Director, Michael Bennish, there has been ongoing debate about the ethical dilemmas triggered by the Centre’s creation: “There are those who say that we should focus on the primary mission, our research, and there are those who say that you have a special responsibility to help this community, that you cannot just go in and conduct research without looking at other ways to help. We are really wrestling with the question of the extent of our obligation to improve the quality of life across the district.”

Difficulties also arise because of the huge disparity between the Centre’s resources and the local health services. For example, the Centre has five paediatricians at its disposal, while local health services have none. The Director of Health services in the local area, Sean Drysdale, feels that the Africa Centre “has an obligation to at least facilitate local service development”. Some researchers and members of the community liaison team at the Centre agree with this assessment.

But the issue is not clearcut. For example, as part of one research project into sexually transmitted diseases (STDs), an STD reference centre was built that served the entire district. This seemed to benefit both sides: the researchers have access to a high quality research facility, and local health providers get better STD services. However, what happens after the study is finished? Willem Sturm, principal investigator at the Centre, felt there was a real dilemma: “We are not service providers, but researchers. How far can we go in providing services during the research project if we cannot sustain them afterwards? This is an ethical issue that really needs attention.”

Another issue highlighted by Wendy Ewart of the Trust is that of equity between researchers and participants. “In South Africa most especially, because of its political and social history, the need for the community to be an active and equal partner is paramount.” But there is debate over the terms of the partnership, with some researchers feeling that the main objective is clarity about the Centre’s established research aims, and others feeling the local community should be involved much earlier in the process, at the stage of formulating the research questions themselves.

Director Michael Bennish is sanguine about the Centre’s ability to navigate these conflicting currents: “Guidelines on research as it affects individuals are reasonably well established. But there are far fewer guidelines dealing with obligations researchers have to entire communities. We are trying to chart the water. We would like to be able to establish guidelines that are not unique to this programme, but have practical relevance for other researchers working in developing countries.”

See also

• Science, medicine and society: Article describing the programme on biomedical ethics at the Trust

Related links

• Council for International Organizations of Medical Sciences (CIOMS)
• Nuffield Council on Bioethics
• US National Institutes of Health
• The Nuremberg Code: Defines the ‘permissible medical experiments’ on human beings and focuses on voluntary consent and protection from harm
• United Nations: Details the Universal declaration of Human Rights by the UN General Assembly
• World Medical Association: Details the Declaration of Helsinki
• World Health Organization

Further reading

Lurie P, Wolfe S M (1997). Unethical trials of interventions to reduce perinatal transmission of HIV in developing countries. New England Journal of Medicine 337: 883-5

Angell M (1997). The ethics of clinical research in the developing world. New England Journal of Medicine 337: 847-9

Editorial (1997). The ethics industry. The Lancet 350: 897