Description of the guidelines reviewed
The research ethics guidelines that were reviewed and a brief contextual background on their jurisdiction are presented in Additional file 1
. The general guidelines with a global jurisdiction that were reviewed include; i) the Declaration of Helsinki by the World Medical Association (WMA), ii) the international guidelines for biomedical research involving human subjects by the International Organisation for Medical Sciences (CIOMS), iii) the guidelines for good clinical practice (GCP) promulgated by the International Conference on Harmonisation (ICH), iv) the Report on the Ethical and Policy Issues relating to the conduct of Research Involving Human Participants by the US National Bioethics Advisory Committee (NBAC), v) the statement on benefit sharing by the Human Genome Organisation (HUGO), vi) the report on the Ethical Aspects of Clinical Research in Developing Countries by the European Group on Ethics (EGE), vii) the Universal Declaration on Bioethics and Human Rights (UDBHR) by United Nations Educational Social and Cultural Organisation (UNESCO), viii) the Report on the Ethics of Research Related to health care in developing countries by the Nuffield Council on Bioethics (NCOB) and the guidance document on Ethical Considerations in biomedical HIV prevention trial by the UNAIDS/WHO. Country-specific guidelines that were included are those from Kenya, Uganda, South Africa, Nigeria, Sudan, Zimbabwe, Ethiopia, India and Brazil.
The need to consider benefit sharing
Close to half of the guidelines reviewed have specific articles/clauses recommending consideration of the value of research, or pointing to the need to engage with such a consideration in general terms. Guidelines were examined for particular clauses that made specific mention of the responsibilities of researchers in relation to the benefits, the beneficiaries, obligations and the mechanisms through which such decisions should be made. Table shows the specific clauses identified within all the guidelines that address such responsibilities.
Exemplars of clauses supporting the need to consider research benefits1.
What forms of benefit sharing are recommended?
In most cases, the guidance relating to what benefits can potentially be provided are articulated within a continuum of time when research is being undertaken. Accordingly, research benefits are articulated as either those that are concurrent to the conduct of research or those that are expected after the research is complete. Table presents the forms of benefits that are recommended by international and regional specific research guidelines.
Classification of forms of benefit sharing.
Table presents examples of benefits which may be considered while negotiating benefit sharing both during and after research is complete. In the case of benefits while research is on-going, access to interventions being researched is recommended by most guidelines as a key benefit by most of the guidelines. Other forms of benefits include provision of unavailable health care, capacity building for individuals and institutions, support to health care systems and access to medical and public health interventions once they are proven effective.
Class of beneficiaries within research ethics guidelines.
The provision of unavailable health care services and the support to local health care systems were not given as key benefits especially among the international guidelines such as DoH and CIOMS. Where these are recommended, provision of healthcare services encompasses gaining regular contact with health care workers and other measures that facilitate access to existing health care services. In addition, the benefits that are expected after research is complete mainly focus on the application of generalisable knowledge from proven interventions in their broadest sense. This can for instance be seen in the tone of Article 33 of the DoH (2008)3, Article 8 of CIOMS (2002) and UDBHR (2005) among others. It should however be noted that in most cases, the benefits in question are rather aspirational in the sense that they comprise the expected outcome of research, including generalisable knowledge.
Who is the target beneficiary?
Three categories of beneficiaries are clearly evident from the guidelines. The first category comprises research participants; whether in the intervention or control group. Research participants are mainly expected to benefit from the intervention under investigation, and in some cases, they are assumed to be the bona fide beneficiaries of such interventions once they are proven to be effective as exemplified by the tone of some guidelines including the DoH, CIOMS, NBAC, NCOB and HUGO. The second category of beneficiaries is the community where research studies are undertaken or from which the participants are drawn. Special groups such as People Living with HIV and Aids (PLWHAs) or Men who have Sex with Men (MSM) are also included in this category. Guidelines that advocate for benefitting the host community and other special groups include; CIOMS (Epidemiology), HUGO, NBAC, and country specific guidelines such as those by India, Nigeria, Uganda and Brazil. Interestingly, guidelines by most developing countries focus on benefits to the community as opposed to the individuals, perhaps, pointing to the preferred category of beneficiaries in these settings. Such are likely to be in tension with most prominent international guidelines like the DoH, CIOMS, UNAIDS and to some extent the NCOB do not feature in this category.
The last group among beneficiaries is what might be referred to as the international community or society more generally. Often, this group is considered in relation to aspirational benefits that may accrue from accumulated generalisable knowledge. Such benefits include improved health and lifestyles resulting from a robust body of knowledge or availability of medicines to treat diseases afflicting the society. Table shows the party (ies) expected to benefit by guideline.
Obligation for providing benefits and mechanisms for making these decisions
There is little agreement amongst guidelines on how responsibility for providing benefits should be apportioned. Nonetheless, determination of responsibility appears to be based on how potential benefits are framed. For instance, when research benefits are seen as a compensation for risk assumed by participating in research, investigators and research sponsors are held responsible. This compensatory approach to delineation of responsibilities is mainly articulated by guidelines such as the CIOMS, NCOB, and the UNAIDS. Other guidelines that place responsibility on investigators and sponsors include the Declaration of Helsinki, the Indian Council for Medical Research, the Council of Europe (CoE) and the Ugandan national guidelines for medical research.
The scope of these obligations in terms of the beneficiaries and the period is however limited to those participating in research, and for the period before interventions are proven to be effective or introduced into the health care system. Some guidelines in this category especially those by Uganda and India, however, stretch this responsibility beyond benefits to individuals, to include provision of benefits to the host community. The Ugandan guideline for instance requires that investigators provide benefits while research is ongoing and that research should assist in securing access of proven interventions for the community. In both cases, the responsibilities of the sponsor are confined to financial support to aspects of the project and the provision of indemnity in the event of research related injuries.
On the other hand, when potential benefits are conceived from a social justice perspective including the duty not to exploit the vulnerable, responsibility for making them available is placed on all stakeholders involved in the research enterprise including communities, researchers, the host government and sponsors. Both the UNESCO declaration on human rights, the NCOB and the Nigerian Research Ethics Committee for instance place the responsibility to provide benefits on all stakeholders involved in the research enterprise, by emphasizing the importance of prior engagement among stakeholders to identify and apportion responsibility. Other guidelines that hold governments accountable for providing proven interventions into the healthcare system include the NCOB report, and the UNESCO declaration on bioethics and human rights.
Prior consultation among parties to be involved in research is the commonly recommended mechanism through which the extent and scope of researcher's responsibilities are to be determined. Most guidelines have specific clauses that point to the importance of prior engagement. Guideline 10 of the CIOMS 2002 for instance states that "before undertaking a study in a population or community with limited resources, the sponsor and the investigator must make every effort to ensure that first, the research is responsive to the health needs and priorities of the population or community in which it is to be carried out". Similarly, chapter 4.2 of the report by the NBAC 20014 recommend that "whenever possible, preceding the start of research, agreements should be negotiated by the relevant parties to make the effective interventions or other research benefits available to the host country after the study is completed". Other guidelines including the HUGO statement on benefit sharing, the NCOB report, and the DoH similarly recommend prior consultation among stakeholders to establish and agree on the benefits, who to benefit and the nature and extent of stakeholder responsibilities.