The ethics of collaborative global health research: a network to build capacity in the United Kingdom and in Developing Countries

The Ethox Centre is funded by a major five year Wellcome Trust Enhancement Award (2009 - 2013) to establish an international research network on the ethics of collaborative global health research. The Network, which is a joint initiative of the Ethox Centre in Oxford and the Wellcome-KEMRI Unit in Kilifi, Kenya, will build ethics expertise and capacity both in the United Kingdom and in developing countries - with a particular emphasis on building capacity at the Wellcome Trust’s Major Overseas Programme sites.  The research activities of the network will focus on four themes: community engagement; global ethics governance; the ethics of research collaboration; and, the roles and responsibilities of research actors. The Award will fund DPhil studentships; the development of on-line resources; and a range of training activities. The Network will also act as a focus for the encouragement of local research initiatives in developing country sites. The Network’s Principal Investigator is Professor Michael Parker.

Background

Enormous global inequalities exist in health measures such as mortality, quality of life and disease. These persist despite increasing levels of overall wealth (Berlinguer, 2004; Farmer and Campos, 2004; Resnik, 2004). The global burden of disease is disproportionately large in developing countries. Malaria, for example, kills in the order of a million children and causes debilitating illness in over half a billion people each year (Snow, 2005). Despite this, only a very small proportion of medical research is focussed on the problems primarily affecting the world's poorest people. In 1990, the Commission on Research for Development estimated that about 5 percent of the world's medical research resources were being applied to health problems arising in developing countries where more than 90 percent of the global burden of preventable mortality was located (COHRED, 1990). In subsequent years, this disparity has come to be known as the 10/90 gap.

COHRED (1990) and the subsequent reports of the Ad Hoc Committee on Health Research (1996) and International Conference on Health Research for Development (COHRED, 2000) together established something of a consensus on five core recommendations for the action needed to move towards a more equitable distribution of medical research resources. The five recommendations comprised the need to: (i) correct the 10/90 gap and set priorities; (ii) build up the capacity of health research systems in developing countries; (iii) create international research networks and public-private partnerships; (iv) increase funding for health research by developing countries; and, (v) create health research forums to monitor progress in health research (Global Forum, 2004).

These recommendations, together with the United Nations’ Millennium Development Goals which included a commitment to work to eradicate infectious diseases such as malaria, have led to a number of important developments. The Global Forum for Health Research 10/90 Report on Health Research 2003-2004 found that the landscape of medical research funding had changed significantly between 1990 and 2003. It reported that there were now ‘many more actors engaged in funding or conducting health research relevant to the needs of developing countries’ than previously and estimated that global expenditure on research had ‘more than quadrupled’ by 2003. The Report noted that much of this new research takes the form of emerging international research networks. Among others, the Report identified: The Roll Back Malaria Partnership; the Global Alliance for TB Drug Development; and HIV/AIDS.

The developments identified by the Global Forum in 2004 continue (Global Forum, 2008). Both the scale of the research being carried out on global health, and the shift towards more collaborative, networked approaches to global health research, have been further encouraged by initiatives such as the Grand Challenges in Global Health Scheme launched in 2003.

The growth in collaborative global health science has also been driven by developments in science and technology. The rapid pace of development in technologies and statistical methods for analysing DNA sequence variation at the level of the whole genome has, for example, made it possible for the first time to contemplate genome-wide analysis of phenotypes such as human resistance to malaria. Such research requires very large sample sets of cases and controls because of the involvement of multiple environmental and genetic factors. The requirement for such large sample sets combined with the importance of cutting edge sequencing facilities and statistical expertise – to be found largely in developed country sites - means that such research networks are increasingly bringing together research groups in many countries across both the developed and developing worlds. An example is MalariaGEN which is a genomic epidemiology of malaria consortium funded by the Gates Grand Challenges Scheme and the Wellcome Trust. MalariaGEN involves 24 partners in 21 countries, 15 of which are malaria-endemic.

These forms of collaborative global health research are leading to the parallel emergence of complex ethical issues arising out of the interplay between globalised research collaborations and the ways in which such research is manifested locally. These issues are complementary to and interwoven with the well-described ethical issues arising out of global health inequalities (Benatar and Singer, 2000; Pogge, 2002; Nuffield, 2002; Daniels, 2008; Brock and Wikler, 2005), but present qualitatively new challenges. While some issues, such as the standards of care to be provided to control groups, and post-trial responsibilities to participants, have been the subject of debate for over a decade (Lurie and Wolfe, 1997; Angell, 1997; Editorial, 1997) and remain the subject of conflicting guidance to date (CIOMS, 2002; Helsinki [1964] 2000, 2002, 2004; ICH GCP, 1996), others arising in the building and maintenance of global research collaborations have received less attention. These include those relating to the importance of achieving shared good practice across the network whilst remaining sensitive to local variation (Chokshi et al, 2007) and reaching agreement about data-sharing and the sharing of biological materials between partners with different values, practices and priorities (Chokshi et al, 2006). Collaborative global research also has implications for the development of appropriate and effective community engagement (Molyneux et al, 2004; Marsh et al, 2008); for the question of what are to count as appropriate and culturally sensitive modes of obtaining valid consent in the context of complex global collaborations (Chokshi et al, 2007; Bull et al, 2008); and for the collection, storage and distribution of biological samples. An ethics capable of making sense of these emerging and interdependent phenomena will itself need to be collaborative and multi-sited if it is to be capable of grasping the implications of both global collaboration and the manifestation of the global in the local, where the ‘local’ is to be found both in developed and developing country sites (Marcus and Fischer, 1999). Such research will necessarily have a strong empirical component and the issues arising also present new theoretical challenges (Molyneux and Geissler, 2008; Parker, 2007; Hayden, 2007).

Research Themes:

A key aim of the network will be to carry out and facilitate primary research on four key themes: community engagement; global ethics governance; the ethics of research collaboration; and the roles and responsibilities of research actors.

1.Community engagement

Why is this theme important?

Community engagement and accountability are increasingly promoted in developing countries and by medical research funders. This is driven by recognition of the need for locally relevant health research i.e. research with ‘social value’, by awareness of the potential for exploitation in contexts of vulnerability and inequality, and by the need to develop appropriate methods for seeking consent to specific studies.  Despite the growing emphasis on the importance of community engagement, there is relatively little published experience of community engagement in practice and there have been a number of recent calls for further research.

What are the issues?

Successful and appropriate community engagement presents a number of practical and ethical challenges. Some of these challenges relate to the question of how the relevant community to be engaged with is to be identified. Other challenges concern the question of identifying and establishing procedures, principles and mechanisms of engagement that are fair, inclusive, accountable and appropriate. A related issue concerns the relationship between community engagement and community consent, and the extent to which valid community engagement and consent require community involvement in the setting of research agendas, priorities and methods. This presents real challenges both for engagement and consent, particularly in scientific contexts in which many of the investigators have expertise in only some aspects of the research programme and few people understand the collaborative enterprise as a whole. Such research also presents challenges for community engagement arising out of the complexity of concepts and practices such as ‘data-sharing’. It also presents challenges because the harms and benefits of such research may relate to populations rather than to individuals.

2.Global ethics governance

Why is this theme important?

Ensuring that collaborative global health research meets the needs of people in developing countries requires the development of effective and appropriate models of governance. The governance environment within which such research takes place is highly complex. The US Office for Human Research Protections currently lists more than 1,100 international, regional and national examples of guidance and regulation on the ethical conduct of research. Not only are researchers in collaborative studies sometimes faced with applying multiple and conflicting forms of guidance; some documents, such as the Declaration of Helsinki, have also been criticised as being internally inconsistent. Given the volume of international guidance and regulation currently available, it is important for collaborative international research consortia to develop rigorous and transparent procedures to inform the movement from theory to practice when determining best practice in conducting research at specific sites.

It is widely accepted that decisions about the appropriate conduct of research require independent, competent and transparent ethical review. In practice however, the effective and appropriate functioning of research ethics review in developing country settings is frequently undermined not only by the complexity of the guidance but also by inadequate training and resources. In response to limited capacity to conduct ethical review, a number of collaborative groups have been established to develop expertise in such review. The emergence of collaborative forms of often highly sophisticated global health research presents significant governance challenges. In  both developed and developing countries ethics committees have often had little or no relevant training for reviewing protocols concerning research for complex networked science to be carried out across multiple sites in both developed and developing countries.

What are the issues?

Collaborative global health research presents a range of important new governance challenges, some of which are not clearly addressed in current guidance and regulation. Some of these challenges emerge out of the distribution of scientific and technological expertise across the diverse and multiple sites of ‘the project’ in developed and developing countries. This can present particular challenges for investigators and research ethics committees because the nature of the research enterprise only makes sense in the context of activities going on in a number of distant socially, technologically and scientifically diverse locations. Developing protocols for research ethics committees and reviewing such research often requires expertise not available locally. Other governance challenges arise out of the shipping of large numbers of blood or DNA samples and data between different sites and the distributed nature of the intellectual property in such research. These may be further complicated by increasing moves to ‘open access’ which may have significant implications for developing country partners unless adequate protections are put in place.  Against this background, a further issue concerns the extent to which major scientific consortia, and those who fund them, have a responsibility to build capacity of research ethics review in the countries in which they carry out their research. If such a responsibility exists, how can it be met such that such review remains appropriately independent and rigorous?

3. The ethics of research collaboration

Why is this theme important?

Collaborative global health research increasingly involves the establishment of large and diverse multinational scientific networks. In many cases these require the development and maintenance of network-like partnerships involving a range of diverse yet interdependent forms of expertise such as: clinicians, epidemiologists; statisticians, database managers; fieldworkers; specialists in information technology, geneticists, cutting-edge laboratory facilities; multiple funding agencies; and communities. The networks also bring together diverse institutions both in developed and developing countries which may in other respects be in competition both for scientific prestige and resources. The dependence of successful science upon the building and maintenance of such consortia means that one of the key potential roadblocks to such research is the building and maintenance of the relationships, shared values and practices underpinning collaborative science, and the mechanisms for working in the context of different ethical values and commitments. Such relationships can generate important ethical issues about, for example, the appropriate and fair use of data and samples. Such networks will also need to reach agreement on particular occasions about important ethical principles relating to their relationship with ‘their’ research participants. This may involve negotiating the appropriate balance between the need for standardisation and shared ethical practices across the consortium on the one hand, and for diversity and appropriateness to local settings on the other.

What are the issues?

Collaborative global health research generates a number of ethical issues ‘internal’ to such collaborations such as those arising in the fair sharing of data and samples, the development of scientific capacity across the network, the allocation of scientific resources, decisions about authorship and ownership of intellectual property. This suggests that the building of sustainable relationships, shared practices and values, and ways of working within the broader diversity of practice and values are essential to successful and appropriate science. This suggests too the importance of building and maintaining both ‘trust’ and ‘confidence’. A key roadblock in the future development of collaborative global health research can be the need to reach agreement about the development of appropriate mechanisms for the oversight of data-release and data-sharing. This is an especially pressing issue in the context of the pressures for open access, and in relation to the responsibility for such consortia to protect the emerging scientific capacity in developing countries, and in particular that of their partners. If the data produced by the network on the basis of samples and data collected by partners in developing countries is exploited by institutions in the North at the expense of emergent capacity in the South, this has the potential to undermine long term trust. It may also undermine the emergence of the kind of networked science that is currently seen to be essential to understanding disease and addressing the health care needs of the poorest people.

4. Roles and responsibilities of research actors

Why is this theme important?

Collaborative global health research brings together diverse and distributed groups of ‘actors’ in formations which may be temporary and partial, or long-term, substantial and interdependent. These include: researchers, institutions such as universities and research institutes in both developed and developing countries, funders (increasingly including philanthropic initiatives such as the Bill and Melinda Gates Foundation), research ethics committees, national ethics advisory bodies, health professionals, and local community advisory boards. It has sometimes been argued that investigators and funding agencies have an obligation to promote equity in health in developing countries. But how should such responsibilities and related roles be understood in the context of collaborative global health research? These are important questions about the moral responsibilities arising during research in developing countries and raise important questions about how such responsibilities and roles are to be identified and negotiated in the context of collaborative global health research and what forms of accountability might be appropriate. International debate about the regulation of research also addresses key obligations arising in research in developing countries and, in particular, the ‘standards of care’ appropriate during research and the obligations of researchers to communities and participants when the research is completed.

What are the issues?

The fact that collaborative global health research involves multiple relationships and communities suggests the importance of negotiating and reaching clarity about roles and responsibilities before research begins, and as it proceeds. There may be particular advantages in this regard to the development of long-term community engagement. This suggests the possibility, and perhaps desirability (given concerns about 'one-size-fits-all' approaches), of the emergence of different solutions in different sites. Where this is the case, who will be responsible for achieving good practice across the network? What will this mean and how will it be achieved?

A key cluster of issues relating to the roles and responsibilities of research actors, and their negotiation, will inevitably be those related to questions of benefit-sharing; social value; intellectual property; appropriate standards of care; locally-appropriate consent processes and the identification of post research responsibilities. Similar issues arise in relation to capacity-building. To what extent is capacity-building a responsibility of research networks and their funders and what forms might it be appropriate for such capacity building to take?

For more information about this project contact  michael.parker@ethox.ox.ac.uk or  sjbull@well.ox.ac.uk