Human capital is key to research ethics
If the US system of research ethics is close to “meltdown”, how can the developing world adequately regulate research with human subjects — an issue raised this week by the publication of the report of the Nuffield Council on Bioethics.
The answer lies in shifting primary emphasis from writing guidelines to training people to implement and monitor them. Another 10 revisions of the Declaration of Helsinki — a document originally developed by the World Medical Association as a set of principles to guide research involving human subjects — will not improve the ethical conduct of research in developing countries as much as training 1000 people from developing countries to implement systems to ensure that research is carried out in an ethical manner in their home countries.
We do not mean to set up a false dichotomy: both guidelines and people are needed. However, in the past, there has been undue emphasis on guidelines, and insufficient emphasis on people. Moreover, it is the people who contribute to the writing and implementation of the guidelines.
Between 1995 and 1999, the proportion of new drugs approved for use in the United States on the basis of trials carried out in foreign countries tripled, from 9 to 27 per cent. There are three reasons why this trend will continue under increasing pressure for more clinical research in developing countries.
First, there will be a growing need to test new preventive vaccines and drugs for diseases such as HIV, malaria, tuberculosis and dengue fever. Since the majority of people exposed to, or suffering from, these diseases live in developing countries, that is where many of the trials will need to take place.
Second, the revolution in genomics and its downstream technologies means that the number of potential new drugs that need testing is set to escalate rapidly. Already in the United States, millions of individuals participate in about 70,000 clinical trials each year. The need for even more research will add to the pressure to do research in developing countries, where in many instances the research may additionally be carried out at lower cost.
Third, there will be ongoing, appropriate pressure to correct the 10/90 gap — the fact that of the US$70 billion spent on health research annually, only 10 per cent is used for research into 90 per cent of the world’s health problems — by focusing research on diseases representing the heaviest burden.
For example, Isaakidis et al from the University of Ioannina and the South African Medical Research Council, found that only 1179 randomised controlled trials have been conducted in sub-Saharan Africa in the past 50 years, compared to almost a million worldwide .
Need for better research ethics systems
Partly as a result of these pressures, there is a growing awareness that research cannot progress without better research ethics systems in developing countries. The need was highlighted by a series of articles in the Washington Post 18 months ago entitled “The Body Hunters”, which detailed potential abuses in research in developing countries.
The response until recently has been in trying to develop ever more “aspirational” guidelines, such as the Council of International Organizations of Medical Sciences guidelines, the US National Bioethics Advisory Commission guidelines, UNAIDS guidelines, and so on.
However if the experience of the United States is anything to go by, these will have limited impact in ensuring research participants’ safety and their rights to be informed, to consent, to be cared for well, and to have their confidentiality protected because in developing countries the capacity to implement these guidelines is lacking.
Beyond these basic requirements is the bigger question of equity, involving issues such as sharing the benefits of research, intellectual property rights, and the subsequent availability of therapies for those engaged in the trials, and their access to them. These issues are not adequately dealt with in current guidelines, perhaps reflecting the fact that there are few participants from developing countries who play a role in shaping these documents.
Need for trained people
We are therefore convinced that what is needed is people trained to play a role in shaping these documents, and even more importantly, in implementing them in a way that will actually help protect subjects of clinical research. As we have previously noted what is needed now is an urgent focus on building human capacity in developing countries for research ethics .
The Fogarty International Center of the US National Institutes of Health has recently established a long-term programme which identified five centres in the North to train mid-career professionals in bioethics with a focus on research bioethics (more will be announced shortly and some of these may well be from developing countries).
The University of Toronto Joint Centre for Bioethics is one of these centres. Last year we received the first batch of students from India, Pakistan, Zimbabwe, Uganda and Chile to do a masters degree in bioethics with us.
The Fogarty programme will continue to support these scholars once they go back home, where they will conduct research projects to strengthen their understanding and application of bioethics. Ideally the Northern centres will train, over a number of years, several people from the same Southern centre so that they can form a nucleus to establish research and training programmes in bioethics in their own countries.
Efforts such as these, clearly thought out, well financed, and with clear long-term goals are the best way to ensure that the needed bioethics capacity is developed in a sustainable manner.
Value of networks
South-South networks such as the Pan-African Bioethics Initiative, which is meant to increase dialogue and flow of information amongst the few African bioethicists, will also help spur the development of bioethics capacity. The annual Global Forum on Bioethics in Research provides a venue where developing countries have significant input into the ethical debate on international collaborative research.
Some might argue that training professionals to have capacity in bioethics is something of a luxury in developing countries where millions are starving. Of course poverty needs to be reduced, effective public health measures need to be improved, and health care delivery systems need to be made more responsive to the actual needs of local populations.
However, as long as clinical research is to play an increasing role in developing countries, there will be a great need to train people to oversee the ethical implementation of that research. Furthermore, what we are talking about is not the training of philosophers to think abstractly about what is right or wrong (a few of those are needed too), but a core of professionals from the medical, public health, and paramedical professions who will, in addition to their already well-developed professional skills, be equipped to provide ethical oversight of clinical research.
The network of centres and trainees, with their newly acquired bioethical skills and sensitivity to wider social issues, might well make a positive contribution in ameliorating some of the other inequities that they and their countries face. In addition to research ethics, these trained professionals can assist with a variety of other ethical issues in their home countries including the coming challenges of the post genomics era.
Moreover, a network of ethics centres in developing countries may also be a mechanism to move towards the vision of a “global open society”, as described by George Soros in his recent book On Globalization.  Building upon the current global system, Soros’ vision involves “a change of emphasis, a better balance between competition and cooperation, a reassertion of morality amid our amoral preoccupations.”
A global public good
The goal here is to produce a parallel system for the provision of global public goods. The network could provide the human capital to help refine this concept, advocate for it, and assist with its implementation as it relates to global public goods for health. Indeed, health research itself, which is facilitated by the network of centres focussed on research ethics, is a global public good.
The way to train 100 people to monitor research ethics in Pakistan is not to send them all to Toronto or Boston, but rather after training their leadership core in the North, to help establish and fund a centre in Pakistan to train them at one-quarter the cost and greater sensitivity to the local environment and culture. The strategic role of North-South partnerships, which need continued support for this purpose, will be increasingly focused on the important task of training a critical mass of faculty to help launch these developing country centres.
The crucial step is for international organisations to provide direct support to a network of bioethics centres and training programs in developing countries. It is likely that the Fogarty programme will evolve in this important direction. Moreover, some of the costs of the centres can be borne locally. However, to accelerate the vision, and to broaden it beyond research ethics alone, what is needed is a philanthropic foundation (or consortium of philanthropies) to establish a major programme to complement the Fogarty initiative, with a focus on creating a network of developing country ethics centres.
Over the last 20 years, the Rockefeller Foundation has had a significant impact on health research in developing countries by launching the International Clinical Epidemiology Network, which now includes 64 medical institutions in 26 countries. Now there is an opportunity for a philanthropic foundation to have a major impact on ethics in the world. It will be interesting to see who has the vision to seize the opportunity.
 Michael Kranish. System for protecting humans in research faulted. The Boston Globe. March 25, 2002.
 Petros Isaakidis, George H Swingler, Elizabeth Pienaar, Jimmy Volmink, and John P A Ioannidis. Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research. BMJ 324, 702 (2002).
 Peter A Singer and Solomon R Benatar. Beyond Helsinki: a vision for global health ethics. BMJ 322, 747-748 (2001).
 George Soros. On Globalization (Public Affairs, New York, 2002).