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Ethical Inquiry: September 2010

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Is it ethical to conduct medical trials among poor and uneducated populations in developing countries?




Over the last ten years the volume of medical trials sponsored by drug companies from wealthy countries conducted among poor populations in developing countries has risen dramatically. This has led to increased scrutiny of the ethical standards employed in these trials.

Some question the morality of conducting clinical trials on people who understand very little of what they are all about. Other critics of such trials, including Médecins Sans Frontières (Doctors Without Borders) have suggested that it is “…critical that research be conducted in Africa and the developing countries to test new drugs for malaria, sleeping sickness and Chagas disease that sick people in poor countries need [rather than on diseases of interest primarily to developed nations] and these tests should always be conducted in an ethical way.”

Others believe “it is virtually impossible to conduct medical research ethically in poor countries, because it is inherently exploitative.”

Proponents argue that these trials are necessary for the good of society, and have direct benefits for those participating as well.

For some additional background, see a six-part Washington Post series from 2000, “The Body Hunters,” which explores the context for these questions in depth, including recent updates.

In this installment of "Ethical Inquiry" we explore some of the ethical challenges of conducting these trials, note some of the benefits, and begin a consideration of constructive approaches to the situation.


The Ethical Challenges

There are a number of challenges often identified as concerns with regard to conducting clinical trials in the developing world.

Informed consent

Obtaining proper consent from participants according to the standards of the World Medical Association's “Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects” poses a great challenge. Poverty and lack of education among the participants may make it difficult to obtain proper informed consent.

The New York Times reported in 2009 on a New England Journal of Medicine article, “Ethical and Scientific Implications of the Globalization of Clinical Research”, in which the authors “…suggest that human volunteers in foreign countries may be unduly influenced with the promise of financial compensation or free medical care to participate in clinical trials.”

The Montreal Gazette recently reported that “the meaning of something like 'informed consent' might not be clear in a different cultural context” such as in a region where patients have “blind trust” in their doctors.

In countries where people are struggling daily to get sufficient food and health care both doctors and patient are unduly influenced to sign on clinical trials suggests Dr. Marcia Angell, who teaches social medicine at Harvard Medical School: “doctors can multiply their income tenfold or more…” while patients “…are readily enticed by small amounts of money and promises of free care.”

In Global Medicine, the magazine of the International Federation of Medical Students' Association - The Netherlands, Emmaline Brouwer highlights the Helsinki Declaration’s concern that “poverty and dependency on treatment offered in the trial make informed consent a matter of discussion and question on the volunteerism of the participants.”

In the Journal of Postgraduate Medicine, B. Gitanjali, R. Raveendran, D.G. Pandian, and S. Sujindra observed from their study in India that none of the participants who consented to their study scored all the five points of understanding informed consent. In “Obtaining informed consent: observations from community research with refugee and impoverished youth” in the Journal of Medical Ethics, the authors discuss “…cultural and social challenges to adherence to the elements of informed consent: disclosure, comprehension, capacity, voluntariness and consent….” A British Medical Journal “Ethical Debate” further explores the issue of informed consent. 

Lack of formal training and education among researchers in the developing world

The Journal of the National Cancer Institute estimates that “only about a third of oncologists in low income countries have had a real research training". Glickman et al. in the New England Journal of Medicine state that investigators in the developing countries are generally untrained and inexperienced which may hinder them from fully knowing all the aspects of the trial. This concern is echoed by Brouwer and Barr. They point out the shortage of  educated health personnel in developing countries leads to overworking of the few who are educated.

The subjects of the trials since rarely fully benefit from the research

The New York Times article mentioned above references a report, "Ethical and Scientific Implications of the Globalization of Clinical Research," which questions whether  “drug research conducted in developing countries is relevant to the treatment of American patients” and if  “lower-income countries are the clinical trial mill for higher-income countries.” Glickman et al., in the New England Journal of Medicine, argue that the developing countries do not enjoy the benefits of the trial since the drugs may not be available to them as most of the drugs are sold to the wealthy countries. They also point out that drug companies do not readily sponsor trials to address diseases that affect the poor.

Some disagree with the notion that drug companies intend to respond to market needs in the developing countries, and contend that drug companies are primarily interested in the developed world. Brouwer observes that most of the drugs tested in developing countries are meant to treat diseases that are more profitable than those the local people suffer from. Dr. Angell insists that “relatively few studies are devoted to finding treatments for the diseases that plague poor countries, such as malaria, sleeping sickness, and schistosomiasis. The big companies are more interested in the usual first-world conditions, like high cholesterol, obesity, and arthritis.” She adds that clinical trials in developing countries are “using vulnerable people in vulnerable countries as drug laboratories….It is all about dollars and cents.”

Lack of oversight bodies and transparency

While there are clear guidelines for clinical trials, Glickman et al. point out that 90% of published clinical studies conducted in China did not report ethical review of the protocol and only 18% adequately discussed informed consent. They continue to say that researchers in developing countries are not familiar with the clinical trial regulations. Fewer than 6 out of 10 trial protocols are reviewed. Even though there are international standards governing clinical research, there is no “global cop” to enforce these standards. Developing nations do not have the capacity to create regulatory bodies or they may not find it necessary. Lack of resources in developing countries is a huge obstacle to successfully establish regulatory structures. Although the West has well developed regulatory systems, it is hard for regulatory bodies, which are structured to monitor safety of drugs domestically, to have full information on all aspects of research conducted outside their jurisdiction.

Dr. Angell speculates that the “most important reason for conducting human research in Africa and other poor regions outside the US is that it is a way of circumventing FDA regulations.”

Corrupt systems and governments in developing countries

Due to corrupt systems and governments in some developing countries, “using poor people as guinea pigs for the clinical trials goes on with impunity,” according to the Tribune of India. Dr. Angell suggests that it is easy to get willing participants on board in developing countries “where authoritarian regimes and corrupt local government officials and health authorities are eager to be paid off by first-world organizations and to have good relations with them. They 'encourage' entire villages or provinces to enroll in research programs, while local doctors enrich themselves by providing human subjects.” 

Improperly Designed Trials

Barr, in the Journal of the National Cancer Institute, notes that many of these trials are designed for the researchers to parachute in and out. He argues that such a design rarely produces good results.

Basic Medical Care: A Competing Need

Barr also points out that there are other priority needs that people should first address before doing clinical trials in the name of helping the poor, such as basic medical needs.


Benefits

The proponents of conducting clinical trials in developing countries argue that the globalization of clinical trials has tremendous global benefits, while critics note some of these benefits may serve as incentives for unethical conduct.

Faster Drug Development

It is argued that these trials enable drug companies to test new products effectively within a shorter period than would be possible in the developed world. Philip Stevens, director of the health program at International Policy Network in London, believes “humanity as a whole stands to benefit from the faster, cheaper clinical trials offered by India. Simply put, it will eventually mean a greater range of cheaper drugs to tackle an ever wider spread of diseases.” He also argues that “although there might be isolated cases of exploitation of trial participants, the arrival of clinical trials in the subcontinent stands to benefit both Indian and Western patients alike.”

Acute Need for New Drugs in the Developing World

Availability of the trial participants is mostly in the developing world where certain diseases are rampant. In support of HIV vaccine trial in Africa, globe with stethescope imageBernstein and Kagame state that “any of these studies should be conducted in Africa, where the disease is most widespread, and where a vaccine is most urgently needed.”

Choudhary and Knapp point out that developed country-sponsored research in developing world has “contributed to the understanding, prevention and treatment of disease.” Karen Politis adds that “large populations devastated by infectious diseases such as HIV, TB, and malaria may greatly benefit from recent drug developments and clinical research being conducted in South Africa.”

Availability of Good Research Subjects

The lack of healthcare in many developing countries provides greater opportunity to recruit participants who have untreated disease. This enables more effective research about the effectiveness of particular drugs on trial. Huge samples are easily available within a short time frame to support large scale testing, due to more willing people and higher rate of disease incidence than in the West.

Karen Politis notes that with a “… large and diverse number of subjects that can be recruited for clinical trials in South Africa, it is understandably becoming an important research location.”

Healthcare is provided to participants with little to no access to medical care

Some proponents argue that clinical trials are the only way that some of the patients can get any form of healthcare at all. They assert that even though the treatments given are of low quality than in the developed world, it is better than the baseline outcomes for that country.

Jill A. Fisher, PhD, assistant professor at the Vanderbilt University Center for Biomedical Ethics and Society notes "…clinical trials are a problematic kind of care, because it comes in the context of a study intervention. But people are ready to enroll, because they see it as such an incredible advantage over basically nothing."

Financial Benefits for Host Countries

Clinical trials provide tremendous economic benefit to the host governments. Steven observes that conducting trials in developing countries such as India, provides a “much needed foreign exchange.” He adds that conducting trials in developing countries attempts to reverse brain drain.

Cost Savings

Low costs of human labor is another benefit to drug companies that conduct medical trials in developing countries as this is done at a fraction of cost of conducting them in developed countries. The savings can be passed to the patients in developing countries. According to Mark Henderson, most of savings are invested back to research and development.


Constructive approaches to dealing with the ethical challenges

While the belief that “it is virtually impossible to conduct medical research ethically in poor countries, because it is inherently exploitative,” may sound too sweepingly broad, Dr. Angell calls for a sharp curtailing of amount of research in the developing world sponsored by wealthier nations. She suggests that “research should not be done in the third world unless it concerns diseases that are virtually confined to those regions” and with rules as stringent as those in place in the developed world.

Informed Consent

Informed consent is perhaps the most challenging ethical requirement to fulfill in the developing countries. Dr Angell insists that “consent should be truly informed, and there should be no penalties for refusing to participate or undue inducements to do so.” She goes on to say that consent should be documented, with claims of oral consent not being acceptable.

Gitanjali et al. suggest that “a more focused standard of uncoerced and undeceived consent” ought to replace the standard of voluntary and informed consent. Lackey echoes this suggestion saying that it is a “focused attempt to captures what morally matters in consent process [PDF].” Dangayach and Joshi conclude that consent should be individualized for every case rather than employing a universal consent for all patients. Gitanjali et al. advocate for an adaptable template that can be localized to meet the needs to the local participants.

Partnering With Host Communities

To gain support and trust with the participants of the clinical trial, the researchers need to partner with the local communities as equal partners. The developing countries should be fully involved in the efforts of clinical trials for new drugs. Bernstein and Kagame observe that “Africa seeks, and rightly so, to be a full partner in these efforts. The days in which Africa’s only role was to provide volunteers or samples for researchers in the developed world are over.

A Comprehensive Approach

Glickman et al. call for multiple approaches in addressing ethical issues regarding clinical trial globalization. They point out that while the goal should be “to foster innovation and access to therapy” by the participants after the drugs have been approved, it is important to put in place structures that ensure “integrity of research wherever it takes place.”



pillsFinal Thoughts

The need for new and better treatment options continues unabated. As long as that need persists, medical trials are likely to continue. We invite you to continue exploring the ethical issues that arise in this context, and to share your thoughts with us on our Facebook page.

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This installment of "Ethical Inquiry" was researched and written by Esther Kamau, Masters candidate in the Programs in Sustainable International Development at the Heller School for Social Policy and Management, Brandeis University.