Until 1995 [Ref: Monitor], clinical trials were mainly conducted in the USA, Europe, and Japan, but in the era of globalisation drug companies have been steadily outsourcing their research enterprises to the developing world [Ref: Clinical Trials]. According to an article in the New England Journal of Medicine, approximately one third of the trials conducted by the 20 largest US-based pharmaceutical companies now take place in other countries [Ref: NEJM], ‘many in developing countries’ [Ref: NEJM]. Western research institutions also play a significant role in trialling drugs in the developing world, with particular emphasis on diseases such as HIV/AIDS, tuberculosis (TB) and malaria {Ref: BioMed Central]. This has led to the development of initiatives such as the European-Developing Countries Clinical Trials Programme (EDCTP), which intends to create a partnership between European member states, African countries and the pharmaceutical industry to find long term solutions to poverty-related diseases [Ref: THES].

Some argue that the globalisation of clinical research brings global benefits, enabling pharmaceutical companies to test new drugs more quickly and effectively than if trials were limited to the developed world [Ref: Medical Progress Today]. For example, the existence of a large and genetically diverse population in India is said to provide a ‘microcosm of the world’ and therefore opportunities to rigorously assess drugs more efficiently [Ref: The Indian]. Clinical trials also bring resources and expertise to resource-poor countries, and give trial participants access to treatment that they would otherwise be denied. Others argue that ‘Big Pharma’ is exploiting the poverty of ill people in the developing world, by taking advantage of their need for medical help in order to make the maximum profit from new drugs. There is a concern that powerful companies and research institutions cannot be held to account by the poor, illiterate, sick people who often become part of clinical trials, and that the pharmaceutical industry has used citizens of resource-poor countries as guinea pigs [Ref: Wired] for drugs which have more relevance for the West than for the country hosting the trial [Ref: Amnesty USA]. On the other hand, others point out the dangers of adopting patronising attitudes to countries such as India that are in a state of transition: where their populations are increasingly afflicted by diseases prevalent in the West (for example diabetes [Ref: Diabetes India] and heart disease [Ref: BBC News]) and where successful home grown companies (such as Ranbaxy [Ref: Ranbaxy] and Dr. Reddy’s [Ref: Dr. Reddy’s]) are conducting clinical trials of their own products.

Who benefits from clinical trials conducted in the developing world? Are current regulations and practices adequate to ensure that citizens of resource-poor countries are not exploited?

Are clinical trials in the developing world inherently exploitative?
Increasing global concern about unscrupulous trials has attracted adverse coverage in the media and medical journals. Some argue that the outsourcing of clinical trials amounts to the outsourcing of risk [Ref: Guardian], as individuals in the developed world are increasingly reluctant to take part in trials [Ref: Huliq]. As people in developing countries often participate in clinical trials as their only way to access effective medical treatment, it is argued that trials take advantage of the desperation of the poor and vulnerable, without providing the ongoing medical care that people need: for example, by ensuring that trial participants continue to receive medical care when the trial has finished.

On the other hand, some trials are designed to test the most effective ways to manage treatments in circumstances that are specific to developing countries, such as poor access to lab facilities in rural areas. For example, the DART trial of anti-retroviral therapy (ART) in Uganda and Zimbabwe [Ref: DART] seeks to test whether anti-HIV drugs can be provided more widely and cost-effectively, and this has already shown some benefit [Ref: MRC Clinical Trials Unit]: if the findings are correct the hope is that this will make AIDS treatment in Africa more available to more people. This trial tests whether anti-HIV drugs can be given in the absence of routine laboratory tests, relying on clinical assessments instead; critics argue that this sells patients short compared to the best available treatment globally.

More generally, it is important to note that clinical trials in the developing world are necessary if the effects of drugs designed to treat diseases such as malaria, which largely affect non-Western countries, are to be assessed. Additionally, as medical scientists become more aware of the impact of genetic differences on the way in which individuals respond to drugs, ensuring that tests are conducted on people with diverse genetic profiles becomes more important. For example, when AstraZeneca tested its lung cancer drug Iressa, it discovered its efficacy amongst Western populations was low [Ref: BBC News]. However, when tested in South East Asia, due to a prominent genetic mutation in the population, its success rate was twice as high and the drug is now licensed for treatment in the region.

Do clinical trials in resource-poor countries cause harm?
With all clinical trials, wherever they take place, there is some risk to the health of the participant: as was graphically illustrated in the UK in 2006, when six men suffered multiple organ failure during a trial of an anti-inflammatory drug at Northwick Park Hospital [Ref: BBC News]. However, a distinction must be made [Ref: Clinical Trials] between Phase I clinical trials [Ref: Clinical Trials] – which are conducted upon small numbers of healthy people to test for safety, rarely have the averse consequences that occurred at Northwick Park and are rarely conducted in the developing world – and Phase III trials, designed to test for side-effects and efficacy [Ref: Clinical Trials].

Some recent clinical trials in developing countries have been dogged by controversy over ethical procedures, with accusations of misconduct being levelled at studies funded by a wide range of bodies: from leading philanthropic organizations, to research institutions and the pharmaceutical industry [Ref: SOMO]. It is generally known that some trials can be badly designed and some drugs can cause problems. However, this is different from arguing that outsourcing clinical trials is itself a problem. The potential for harm needs to be balanced against the potential benefits afforded by new drugs, both for the trial participants and for human health in general [Ref: The Times]. Do current regulations and practices achieve this end?

How are regulatory concerns being addressed?
The broad principles governing clinical trials were laid out in the 1964 Declaration of Helsinki [Ref: CIRP], which has been revised several times [Ref: WMO]. The World Medical Association’s fifth revision of the Declaration of Helsinki strove to strike a balance between ensuring high ethical standards and retaining sufficient sensitivity to local circumstances, especially in developing world research, to avoid thwarting research with bureaucracy [Ref: BMJ]. Two key principles for regulating clinical trials are that the participants must give their informed consent [Ref: Cancer.gov] to take part and that the study should be approved by an ethical review committee [Ref: WHO].

Critics of clinical trials in developing countries point out that the vulnerability caused by poverty and illiteracy make it difficult to ensure that participants fully understand the risks and consequences of trials in which they become involved [Ref: NEJM]. Few would deny that both the pharmaceutical industry and research institutions have taken steps to establish stronger procedures to secure [Ref: ReachoutHyderabad.com] informed consent and greater ethical oversight [Ref: ETHOX Centre]. However, for some, the simple lack of resources in poor countries, generate substantial obstacles to achieving appropriate levels of regulatory checks and ethical oversight [Ref: SciDev.net] . Another perspective is that adherence to a ‘one size fits all’ ethical standard can amount to a paper approval which distracts researchers from taking on board their own responsibilities for developing an ethical approach that is appropriate to the context in which they are working. Additionally, some scientists working in the West have begun to question the merit of burgeoning regulations which they argue are prohibitively restrictive [Ref: The Times], and do not necessarily advance the relationship of trust between investigator and volunteer that is vital to good research [Ref: spiked].

Are international regulations enough to ensure decent treatment of trial participants? To what extent can national regulations in resource-poor countries protect their citizens’ interests in relation to clinical trials? [Ref: Issues in Medical Ethics]

Who benefits?
Conducted appropriately, clinical trials themselves can provide several benefits. The participating physicians get first-hand experience of new drugs as well as extensive training. Resource-starved public hospitals see trials as a source of funds for much-needed improvements in infrastructure, and it is argued that the diseased benefit since they get free, focused and more frequent medical supervision for the duration of the trial. New drugs and treatments can be trialled that are of direct importance to the health of people in participating countries, whilst involvement in international trials is beneficial for the science base and, in some places such as India and South Africa, the economy of the country involved. Advocates argue that much has been done to improve ethics procedures in developing countries and that exploitation of people can be avoided through strategies that emphasise capacity building [Ref: Wikipedia] and through developing appropriate forms of ethical regulation [Ref: Nuffield Bioethics].

Others argue that a clinical trial, which provides resources for a limited time that may disappear after the trial is over and which is primarily concerned with experimenting upon a small number of people rather than treating a population, takes advantage of the gap left by a decent healthcare infrastructure. There also exists a wider cultural context of unease about the motivations [Ref: The Times], actions and accountability of the global pharmaceutical industry [Ref: The Nation]. Can an appropriate balance be struck between the demands of Western pharmaceutical companies and research institutions and the needs of those involved in clinical trials?