Guidance notes on research involving human participants living in low- and middle-income countries.
These guidance notes should be read in conjunction with our research involving human participants policy.
We have produced these guidance notes to:
We believe it is important to make a clear statement of its position in these areas to assist the researchers it funds and the people they work with. This is particularly important as various international guidelines address these issues but sometimes differ in their recommendations and conclusions; there is no one set of guidelines that Wellcome feels deals with these issues in a way that is consistent with its own approach.
In these guidance notes, we use the World Bank definitions of LMICs, which are based on gross national income per capita. See a list of low- and middle-income countries, as defined by the Organisation for Economic Co-operation and Development (OECD).
These guidance notes do not form part of our grant conditions, but are intended to inform and guide applicants who are applying for Wellcome funding to support research involving people living in low- and middle-income countries. Such applicants are advised to demonstrate within their grant applications that they have taken these guidance notes into consideration in developing their research proposal, by referencing them where relevant.
Investigators conducting Wellcome-funded research involving people living in LMICs must demonstrate that their research is responsive to the healthcare needs or priorities within that country. Examples include research that addresses diseases that are prominent in low and middle income countries, such as malaria, tuberculosis and HIV/AIDS.
The outcomes of such research should be likely to lead to relevant and sustainable health benefits to people in those areas where the research is undertaken.
Where research may lead to a new health intervention or treatment, such as a clinical trial for a new drug, we will consider such research to have local applicability where:
One aspect of making research locally applicable is the subsequent communication of research findings. Grant applicants should demonstrate that consideration has been given as to how research results will be disseminated, locally and globally. We will fund reasonable requests to cover the costs of such activities.
We will, in special circumstances, fund certain types of basic, non-therapeutic research that involves people living in LMICs but are not obviously or immediately responsive to local health care needs. Such research must be able to demonstrate a potential benefit to the health of people wherever they may live in the world, ie the research must have a potential 'global public benefit'.
'Global public benefit' research could include basic research into human biology, human genetic variation and the development of research tools (such as genetic maps or databases). There may not necessarily be any direct benefit from research outcomes to the participants themselves, particularly in non-therapeutic research.
People involved in Wellcome-funded research in LMICs should only be chosen to take part in research on the basis of being appropriate individuals to answer the research question.
Participants must not be enrolled in a research project if this would:
In all research involving people, an appropriate balance must be struck between the interests of participants (and, where relevant, the communities to which they belong) and the interests of society or the advancement of knowledge.
In planning any research a careful risk-benefit assessment should always be carried out so that participants or communities are not exploited or disadvantaged by their inclusion in the research. The risk assessment exercise should include a comparison of the degree of risk (if any) with the anticipated benefits of the research to the participants or communities involved.
Community engagement is increasingly seen as a key benchmark of ethically conducted research in LMIC settings. Such engagement should be proportionate to the scale and impact of the study being undertaken.
Community consultation or engagement prior to and/or during the course of research studies may be appropriate in many settings.
The use of community consultation can play a role in:
Consultation may be carried out by various means, including focus groups and public meetings.
It is important to note that the legal age of adulthood in certain LMICs can be different to high-income countries. Principal investigators should also be aware of any relevant issues surrounding consent and confidentiality for 'mature' or 'emancipated' minors, who may be able to freely consent to participate in research. We expect that such issues would normally be considered by ethics committees in approving research protocols.
We require that ethical review should be undertaken in all countries where any part of the research is to take place. Where research is undertaken wholly in an LMIC and an independent and properly constituted research ethics committee exists in that country, we do not require additional review in the UK.
If no independent and properly constituted research ethics committee exists in the country where the research is being carried out, review should be sought from an alternative source. We will accept ethical approval from an alternative source such as an inter-governmental organisation, for example, the Science and Ethical Review Group (SERG) at the World Health Organization.
The employing institution of the principal investigator is responsible for ensuring that it is satisfied with the procedures and quality of the ethical review. Accordingly, principal investigators should comply with any obligations their own employing institution might place on them regarding ethical review. This may well require dual (or even multiple) ethics review of the research.
For advice, see 'Examples of national and international guidance on the composition of research ethics committees', Nuffield Council on Bioethics report: 'The Ethics of Research Related to Healthcare in Developing Countries', April 2002.
If research is taking place partly in the UK, UK review is required and should be carried out, as a matter of routine, by institutional or NHS research ethics committees.
If ethical review is being undertaken by more than one ethics committee, and they have any disagreements, they should attempt to resolve these through dialogue. The Trust will not fund research where there are intractable disagreements between ethics committees. It is the responsibility of principal investigators to inform the Trust of any such disagreements.
Collateral benefits may arise as a by-product of carrying out research, whether or not they are necessary for the research design. Examples include the provision of healthcare benefits to communities during a research study, strengthening local research capacity and providing research-related technical or clinical equipment. Thus, local clinics associated with a research project may benefit from improved diagnostic, medical and scientific expertise.
We will consider supporting the provision of collateral benefits as part of a research programme, where they are not of such a degree that they could have an adverse effect on the local research environment or could create an undue influence to participate in research. The principal investigator must fully explain the nature and sustainability of any collateral benefits as part of the research proposal, and these must form part of the grant application and be approved by relevant ethics committees.
Where recompense for participating in research is offered, either financial or in kind, it should be set at an appropriate level to cover, for example, reasonable expenses and subsistence costs. Where it is proposed to offer healthcare unrelated to the specific research question, we recommend that this should usually be the standard treatment that is available locally.
In order to be locally applicable, any successful interventions arising from Wellcome-funded research must be capable of being made available to patients in those areas and of being deliverable within existing structures (or structures which are to be or could readily be developed).
Principal investigators must indicate in their application forms how any post-research access needs will be addressed. We will consider funding requests for activities and processes that relate to ensuring post-research access (for example, meetings and discussions with relevant health authorities, government bodies, non-governmental organisations, pharmaceutical companies, bilateral organisations or any other appropriate organisation).
We will also provide assistance to these processes (for example, in the form of letters of support), where it deems this appropriate to its role as a research funder.