‘It is an entrustment’: Broad consent for genomic research and biobanks in sub‐Saharan Africa

Abstract In recent years, there has been an increase in the establishment of biobanks for genetic and genomic studies around the globe. One example of this is the Human Heredity and Health in Africa Initiative (H3Africa), which has established biobanks in the sub‐region to facilitate future indigenous genomic studies. The concept of ‘broad consent’ has been proposed as a mechanism to enable potential research participants in biobanks to give permission for their samples to be used in future research studies. However, questions remain about the acceptability of this model of consent. Drawing on findings from empirical research about the role of trust in decision‐making, we argue that an account of entrustment may be an appropriate way of addressing current challenges of seeking consent for biobank research in Africa. We propose a set of key points to consider that can support the proposed entrustment framework.

debated of these issues is the concept and practice of 'broad consent' for biobanks and future uses of samples. 8,9,10 In this paper, we review the concept and practice of broad consent and the various alternative models proposed in the literature. In light of an examination from empirical studies on attitudes to biobanking in Africa, we argue that an account of entrustment may be an appropriate way of addressing current challenges of seeking consent for biobank research in Africa.

| WHAT IS BROAD CONSENT?
Broad consent for biobanking is usually taken to refer to consent that allows the use of human biological samples both in immediate primary research and for future as yet unknown research purposes. Broad consent might be said to fall somewhere between specific consent (for a defined research study) and blanket consent (with no restrictions on the future use of samples). 11 Table 1 presents an overview of the different consent models proposed in the literature for genomics and biobanking research.
It has been argued that broad consent is legitimate because it is consistent with current practices, it respects the autonomy of participants and the risks involved are minimal. 11,12,13,14,15 Some studies have also suggested that insisting on informed consent in its strict sense would be burdensome to participants, particularly in LMICs and could undermine important research. 16,17 Broad consent has recently been endorsed by some international guidelines and regulations such as the recent revisions of the CIOMS guidelines 18 and the US Code of Federal Regulations also support the concept of broad consent for future uses of samples and tissues. 19 A recent review by Tindana and de Vries suggests that there is a growing acceptance of the use of broad consent, although some research participants say that they would like to receive some information on the range of studies that their samples will be used for. 20 The concept of broad consent and alternative approaches to consent for biobanks have been widely discussed in high-incomecountries (HICs). 21,22,23,24,25 Although there has been recent attention to this discourse in Africa within the context of international collaborative studies, questions remain about what the key elements of broad consent should be. 26

Specific informed consent
Allows the use of biological samples and associated data only in immediate research: forbids any future research that is not foreseen at the time of the original consent Partially restricted consent Allows the use of biological samples and associated data in specific immediate research and associated future research Generic /Broad Consent Allows the use of biological samples and associated data in specific immediate research and future research of any kind at any time, with appropriate governance processes in place.

Multi-layered consent
Requires several options to be explained to the research subjects in a detailed form to allow opt in and out options.

| What is entrustment?
Entrustment is broadly defined as the act of 'assigning the responsibility for doing something to someone'. In the context of research involving human biological samples, entrustment will mean participants/ communities giving over (entrusting) samples to research institutions to advance scientific research. But this act involves not just handing over samples but also assigning or establishing responsibilities.
Entrustment requires that the one to whom responsibility is entrusted is trustworthy. 35 According to Valerie Braithwaite, when citizens and clients say they trust an institution, 'they are declaring a belief that on average, its agents will prove to be trustworthy and that they will live up to the trust placed in them'. 36 Thus, the key requirement here for valid entrustment is trustworthiness. To some extent we can relate this to researcher-participant relationships in scientific research, at least in Kilifi and Navrongo, our study sites. Our study suggested that there is an 'unspoken' understanding that when research participants consent to blood sampling in research, they also entrust researchers with the responsibility of using samples wisely. In return, research institutions have a moral obligation to ensure that they use these

| DISCUSSION
In what follows, we highlight the practical ways in which an entrustment framework can support current models of broad consent for biobanks. These include: promoting institutional trustworthiness; establishing clear institutional guidelines; strengthening consent and community engagement practices; strengthening ethics review processes; and promoting trust building as illustrated in Table 2 below.
Based on our analysis of empirical research and other related studies in the African context, we believe that a viable model of entrustment would need to have the following features:

| PROMOTING INSTITUTIONAL TRUSTWORTHINESS
In empirical studies conducted in Kilifi and Navrongo, many researchers reported that they have been able to earn the trust of the host community by being consistent in their behaviour, being open and not going contrary to promises made to the community. 42,43 They suggested that their closeness to local communities and their knowledge that community members have put their trust in them should motivate researchers to 'do the right thing'. Some suggested that losing the trust of the community and access to samples -which biomedical research depends on -would be at huge cost to the research institution; even a threat to its survival. It is therefore important for host institutions to promote a culture of research integrity.
The key principles that could promote institutional trustworthiness include: good motives and intent, scientific integrity, honesty, transparency and openness, and minimizing harm and risks associated with uses of samples and data. Host research institutions should therefore establish effective mechanisms for promoting these values such as regular meetings between research teams, including field staff, and local training workshops. The research institutions and their agents (researchers, laboratory and field staff) must recognize that their trustworthiness is essential to their ability to work at all.

| Strengthen institutional leadership
A key ingredient in sustaining scientific research in SSA is strong scientific leadership. Leadership is not only required in the technical aspects of research but also in managing human relationships within the institution and keeping members of the team motivated. In an increasingly competitive scientific environment, good leadership includes ensuring that key members of the institution at different levels have good connections with the national and international scientific community, including a strong reputation for quality work and attracting funding. These will contribute to promote trustworthiness within the research institution.

| ESTABLISHING CLEAR AND TRANSPARENT INSTITUTIONAL GUIDELINES AND POLICIES
Because there is some sense of community trust in the host re-   And as widely recommended in the literature, all future research should be approved by relevant RECs.

| Seek entrustment for sample export and sample sharing with external collaborators
As much as possible, and taking cost implications into consideration, the host institution should build the necessary capacity to store all samples in locally established biobanks. However, sample export should not be ruled out because this practice is likely to remain a key part of research collaborations-because of scientific rationales such as the requirements for uniformity of analysis, a potential lack of local expertise. Material transfer agreements should accompany sample export and such agreements should be mutually agreed on. Secondary users of samples and data should also regard samples in their care as an entrustment, which means they have an obligation to provide appropriate updates to host institutions on the status of exported samples and ensure that they are only used for studies and analysis that have been mutually agreed upon. The MalariaGEN data release policy, which encourages local capacity building of data-fellows in malariaendemic countries to enable them to use samples and data locally, is an example. 58 Institutions should also encourage the transfer of knowledge by ensuring that local scientists get the opportunity to participate in analyses conducted abroad. There should also be appropriate recognition of local contributions in scientific publications and presentations and authorship issues should be discussed upfront to avoid any future tensions.

| Develop effective communication strategies
RECs should also develop effective communication strategies to engage with researchers and understand the practical challenges encountered in the field. This could be done through periodic joint meetings and workshops within the institution or host country. Such communication will ensure that participants' interests are respected when biorepository resources are shared. It can also facilitate the effective conduct of research for which there are plans to share data and samples, but avoiding unnecessary delays and ambiguities for researchers. RECs should also work together with the local institution to develop appropriate mechanisms for engaging with local communities as well.
In international research collaborations, multiple REC review is inevitable. Effective communication between RECs is very important to streamline the review process and avoid unnecessary delays. One approach may also be to explore joint reviews in multicentre studies to improve the efficiency of the review process.

| Actively monitor approved research
RECs should develop effective mechanisms for actively monitoring the sharing of samples and data This could involve requesting for periodic updates from the institution on the status and use of archived samples. Observing consent processes in the field would enable RECs to understand the practical challenges being faced and take them into account in their review requirements. It is also important for RECs to be given adequate regulatory backing and power to hold institutions to account for meeting -or failing to meet -their obligations to host communities.

| ACTIVE TRUST-BUILDING AND GENUINE COMMUNITY INVOLVEMENT
Responding to the ethical issues arising from sample use in research requires genuine community involvement, especially in deciding what is culturally acceptable for future use of samples stored in biobanks.
Currently, the practice is to relegate this decision to the research ethics committee or a data access committee. While RECs, as independent review bodies, are appropriate for making these decisions, they could also face limitations such as the lack of expertise on genetics and genomics.
Therefore, it is important for research institutions to consider setting up a board/committee of trustees to protect the interests of participants and communities. This independent advisory committee could also provide opportunities for genuine community involvement in deciding acceptable future uses of samples. Membership of this committee could include scientists, field staff, laboratory personnel and well-informed community representatives. This committee would be responsible for advising the institution on acceptable uses of samples in research. in determining the appropriate use of archived human biological samples.

| CONCLUSION
We have argued that given the lack of consensus on the best approach to achieving high ethical standards in research using broad consent for biobanks, an approach grounded in principles of 'entrustment' offers a good way of establishing and maintaining trust for such research and embedding high ethical standards. We have suggested practical ways in which this entrustment framework can inform policy and practice. These include establishing trustworthy institutions, clear and transparent institutional guidelines and policies, strengthening consent and community engagement practices, strengthening ethics review and active trust building.

ACKNOWLEDGMENT
We are extremely grateful to all the key stakeholders who took part in our empirical study in in Accra and Navrongo in Ghana and Kilifi and Nairobi, Kenya. We also acknowledge the support of the Director  (096527).

CONFLICT OF INTEREST
No conflicts Declared.