“The keeping is the problem”: A qualitative study of IRB-member perspectives in Botswana on the collection, use, and storage of human biological samples for research

Advances in pharmacogenetics and genomics research and their potential to yield public health benefits have contributed to the growing use of human biological specimens (HBS) in research and the establishment, mainly in developed countries, of large-scale biorepositories. Samples from African populations have been included in several public genome reference collections, among them the International HapMap Project, The 1000 Genomes Project, and the Malaria Genomic Epidemiology Network [1–3]. In the past decade, several African biorepositories have been established, including The Gambia National DNA Bank, the African Institute of Biomedical Science and Technology (Zimbabwe) and the biobank at the University of Kwazulu-Natal’s African Centre for Health and Population Studies in South Africa [4–6].

Recently, international efforts to establish a number of regional pan-African biorepositories have gained momentum, largely under the aegis of the Human Heredity and Health in Africa Initiative (H3Africa) [7]. Four pilot regional biobanks are in development- two in South Africa and one each in Nigeria and Uganda. The H3Africa Initiative centers on a ‘hub-and-spoke’ model, with biobanks serving as regional biorepositories of specimens collected as part of research initiatives situated in universities and centers across Africa [8]. It is anticipated that all H3Africa research projects will begin to send a portion or all of their samples to one of these biobanks starting in 2014 [9].

Biobanking introduces highly complex ethical challenges, particularly in Africa where limited access toresearch ethics education and familiarity with drug/treatment development may make it difficult for research participants to understand the risks and the potential benefits associated with genetic research and where regulatory guidance on collection, use, export, ownership and storage of biospecimens is scant [10–12]. Ethics reviewers may lack sufficient understanding about these technologies or have limited access to accurate information on which to base their decisions. “Northern” conceptualizations of self, human origins, risks and potential benefits have shaped approaches to consent, specimen collection, ownership and information sharing — approaches that may be at odds with local meaning-making and therefore of limited value in determining what constitutes ethical practice in these communities [13].

Recent work by Staunton and Moodley identified five studies in the literature that have examined community perspectives on the storage and reuse of biospecimens in countries in Sub-Saharan Africa [12]. Less research has been done to date to gauge the knowledge and perspectives of local ethics committee members who have an essential role to play in protecting stakeholder interests. IRB members may require more information about the science and ethical use of biospecimens in research as well as better policy guidance at a national level if they are to strike the right balance between ensuring safeguards for subjects and their communities on the one hand and facilitating research with potential public health benefits on the other. As efforts to establish biobanks across the African continent expand, due consideration must be given to the extent to which ethics committees have the knowledge to serve as ethical gatekeepers, particularly in communities where local understanding of biomedicine may be rudimentary or at odds with cultural meanings traditionally ascribed to biological phenomena.

Botswana has attracted global attention over the past three decades as a hub for behavioral, epidemiological, and clinical research. A number of foreign academic research universities and NGOs have established study centers in Botswana, including Baylor International Pediatric AIDS, Botswana Harvard AIDS Institute Partnership, otswana-UPenn Partnership, BOTUSA Project, and I-TECH Botswana [14–18]. The University of Botswana opened the country’s first medical school and school of public health in 2009 and has a commitment to advance research and graduate studies as part of its current strategic plan [19]. A number of studies examining genetic attributes of particular sub-populations in Botswana have already begun [20, 21] and the creation of a biorepository at the University of Botswana with the eventual public release of data for future research activities is planned as part of the H3Africa initiative [22].

The Botswana Anthropological Research Act of 1967 provides the basis for research regulation [23]. In 1984, a Health Research Unit (HRU) was created within the Ministry of Health (MoH) and a Health Research and Development Committee (HRDC) established to review, approve, and oversee all health-related research. An Institutional Review Board (IRB) has been in operation at the University of Botswana since 2004; it is responsible for the review and approval of all undergraduate and masters-level research permits and intramural faculty research. It is also tasked with the preliminary review and referral of all health-related PhD and international research to the HRDC for final approval. IRBs have also been in operation for some time at large referral hospitals in Gaborone, Francistown, and Maun. In 2010, the MoH launched a multi-year endeavor to create a country-wide system of local ethics committees to meet the growing demand for ethics review and the expansion of research activities to small communities outside the capital city. Frameworks now exist in a number of the district hospitals for ‘local’ IRBs to provide feedback to the HRDC on the feasibility of projects proposed for their facilities, although most lack infrastructure and research expertise (Kasule M 2014, personal communication). New ethics committees have also been established in various tertiary academic institutions throughout the country, but these are limited in their scope of authority to the review of research proposals by students at the masters level and below. Reviews conducted by this emergent ‘system’ of IRBs are submitted as recommendations to the HRDC, which operates as the national review body for Botswana and remains responsible for final review and monitoring of all health research in the country.

The HRDC is guided by principles articulated in the Declaration of Helsinki, and the Council for International Organizations of Medical Sciences’ International Ethical Guidelines for Biomedical Research involving Human Subjects [24, 25]. Until recently, regulatory guidance on HBS existed only for clinical trials relating to drug applications [26]. In 2011, the Ministry of Health issued Standard Operating Procedures intended to guide the structure and operation of the HRDC and the review of research protocols involving human subjects [27]. A National Health Research Bill remains under review at the parliamentary level.

To date, ethics training programs for IRB members in Botswana have focused on ethical principles and international guidelines rather than on ethical dimensions of specific medical technologies and research methodologies. Little is known about the knowledge, concerns, and training needs of IRB members in Botswana with respect to the use of biospecimens in biomedical research.

Members of the HRDC and all IRBs in Botswana at the time of the study were invited by letter with follow-up phone and email reminders to participate in one of several focus groups to be held at various locations in Botswana in March 2013. A total of 41 IRB members drawn from five different committees participated, a sample representing a majority of those members serving on committees tasked with review of protocols involving HBS. Sessions were designed to elicit IRB-member perceptions of common attitudes and beliefs of Batswana (the people of Botswana) towards the collection and use of HBS for research and to gauge member knowledge and attitudes about these issues. Additionally, the research team was interested in IRB-member awareness of existing national regulation regarding the collection and use of HBS, their confidence in its adequacy to guide review, and their perceived need for additional training.

Focus groups took place in Gaborone (two groups of 17 and six participants, respectively) and Francistown (one group of 10 participants), both urban centers in which biomedical research activity has to date been concentrated. One discussion group (eight participants) took place in Mahalapye, a major town to the northeast of Gaborone where the new District Hospital has recently appointed its first IRB. Approximately 70 % of the participants were female. All had received some training in research ethics, but none had received training specific to biospecimens, genetic or genome-based research, or bio-repositories. A number of the members from the HRDC and the University of Botswana were researchers and health professionals familiar with biomedical science. The remaining three committees represented were relatively new, tasked with ‘local’ review of protocols that will be situated in their hospitals and with evaluating their suitability given hospital capacity and local cultural norms and practices. Members of these committees tend to have received less training in ethics compared to their urban counterparts and are less familiar with health research in general. Ethical issues concerning the collection and use of HBS has not been a topic of focus in ethics training programs to date.

Each focus group discussion was guided by a study script. Study questions were chosen with the intention to stimulate a free-flowing conversation in English (the official language of Botswana) to explore IRB members’ own views on the collection and use of biospecimens, as well as what they perceived to be the views of local communities.

An informal training session about genetic and genomic research was offered at the end of each discussion group. These sessions, intended as a capacity-building effort, were not audiotaped nor were discussions that took place during them considered study data.

The project was reviewed and approved prior to its implementation by the Institutional Review Boards at Rutgers University, the University of Botswana and the University of Pennsylvania, as well as the Health Research and Development Committee at the Botswana Ministry of Health.

For the purposes of the study, a number of words whose conceptual meanings did not directly translate into English were left in Setswana, the recognized local language of Botswana. Batswana is the collective noun used to describe the people of Botswana. Go rupa and bogwera, once terms in Setswana (the local language of Botswana) used to describe traditional initiation ceremonies for adolescent boys, is now used by the Botswana MoH to refer to medical male circumcision. Muti is the Setswana term used to refer to objects of witchcraft. In describing the ethics system in Botswana, the study used terms commonly used in that country. Ethics research committees in Botswana are referred to as ‘IRBs’ and its members as ‘IRB members’. The IRB at the Ministry of Health is called the Health Research and Development Committee (HRDC).

A number of the issues raised by study participants echo findings from other studies in developing countries that examined community attitudes and norms towards biomedical research. Similar concerns about the use of human ‘parts’ for sorcery or witchcraft have previously been reported in the academic literature as has the attribution of cultural meaning to parts of the human body [29–33].

Bodily integrity, particularly at death, has been identified as a critical value in various cultural and religious traditions and one with significant ramifications for research [34, 35]. To what extent the meaning given to bodily integrity might cause communities to resist the donation of biospecimens for future research and storage is new to considerations about biobanking in Africa and warrants further study, particularly in the context of genetic and genomic research involving biosamples in Botswana.

Trust has also been identified elsewhere as central to the research subject–researcher relationship and in the willingness of individuals to participate in research [31, 32, 36, 37]. IRB members in Botswana emphasized the absence of trust as a significant problem, attributing this in part to lack of understanding on the part of Batswana and lack of adequate explanation and study feedback on the part of researchers. This failure to engage with communities adequately has been cited previously as a cause for erosion of trust in researchers in developing countries [38]. De Vries and colleagues observed that trust between researchers and research subjects may be further diluted when samples are exported for use by strangers in foreign countries [10].

IRB-member views that Batswana are likely to be resistant to the reuse of their specimens is in sharp contrast with earlier findings from Uganda that 95 % of research subjects interviewed would be comfortable with the reuse of their biospecimens contingent on IRB review [39]. A recent study by Igbe and Adebamowo also found that lay persons in Nigeria, once biobanking was explained to them, felt that storage and reuse was a ‘worthwhile’ activity [40].

Donor consent or local approval for reuse was preferred by the majority of IRB members in this study, a point of view they felt accurately represented how Batswana in general would feel and how they themselves felt as members of the IRB. Most agreed that review and decision-making could be delegated to a knowledgeable IRB or other regulatory body in Botswana. Review and approval by bodies outside the country was generally not considered adequate protection for the interests of the individuals and communities from whom the biospecimens had been collected.

Ownership was a particularly contentious topic in this study, reflecting a consensus that samples ultimately belonged to the people of Botswana and by extension should be under the care and protection of the national government. Similarly, Moodley and colleagues found that most of the perspectives voiced by research subjects in South Africa regarding sample storage, export, reuse, and benefit-sharing ultimately had to do with ownership [32]. Participants in that study, despite discussions about ‘donations’, persisted in referring to ‘my blood’ or ‘my child’s blood’ just as IRB members in this study repeatedly emphasized “my specimen”, “my samples”, or commented “if I donate a sample for research as a participant, that sample is mine”.

The expectation that an individual’s samples will be used up in the course of his or her own care may be viewed by Batswana as a fair exchange — the ‘giving up’ of a specimen in exchange for treatment or return to health — that is absent when they are asked to provide a specimen for the purposes of research. Certainly there is concern among IRB members that societal benefits may be absent if specimens are taken outside the country or if decisions as to their future use do not remain in the hands of the donors themselves or the government of Botswana. IRB members in Botswana discussed benefits both in very basic terms of compensation to research subjects themselves and in broader language suggesting that they view biosamples as a collective resource that should be used primarily for the benefit of the country and all its citizens.

Familiarity with pharmacogenetics and genomic research was limited in IRB members participating in this study. Participants on the two most active IRBs – the national HRDC and the IRB at the University of Botswana – were more comfortable discussing the scientific aspects of research and more likely to consider the potential benefits of genetic- and genomic-based research than their counterparts in the newer and less active IRBs. There was a uniform call from all IRB members for more training in these areas, a need that has been expressed by similar constituencies in other African countries [41–44].

Uniformly absent from the discussions in all groups, regardless of their familiarity with research or their experience as IRB members, were several topics of particular relevance to biomedical research in Botswana. First, the concept of ‘benefit’ was narrowly viewed by IRB members only within the context of individual, community, and national interests of Botswana. Little, if any, consideration was given to the potential benefits that genetic- and genomic-based research using biospecimens from Botswana could offer other peoples in Africa or other populations worldwide sharing common traits, risk-profiles or diseases despite follow-on questions on this issue from the study team. This consideration of benefit only within the geographic boundaries of their country may simply reflect what IRB member participants perceived as the ‘local’ focus of this current study. However, if the discussants’ comments are symptomatic of a broader territorial protectionism, it suggests that there may be some resistance to proposals that call for export of biospecimens to regional or non-African biorepositories located outside of Botswana. Concerns such as these, for example, have been noted previously in South Africa [45]. In particular, it may reflect a negative view of management and reuse of such specimens by foreign investigators without local oversight. Such attitudes could be directly at odds with the ‘common heritage’ approach that underpins many international and regional strategies for biobanking, including the current H3Africa initiatives [7, 46].

Second, despite the near unanimity of IRB members as to the lack of understanding on the part of research subjects in Botswana and the particularly disturbing reports that participants are frequently unaware that they are subjects of research or that their specimens are not exhausted in their own care, the IRB members participating in this study did not evidence any sense of personal responsibility as ‘gatekeepers’ to address such concerns. Despite the national mandate to its IRBs to “ensure that the dignity, rights, safety and well-being of research subjects are protected” [27], and the IRB members’ uniform call for more ethics training, there was little evidence that the IRB members at present saw their boards accountable for the remediation of ethical ‘gaps’ in how studies are actually taking place on the ground. Training requirements for new IRB members, combined with continuing professional development opportunities for current members, can certainly help. The success of such efforts, however, will depend on the existence of clear regulatory guidance as well as adequate investment in research governance and support structures. All IRB members need to be given access to training, time-off from other responsibilities, and recognition for the value of their service if they are to function as effective, meaningful stewards of citizen safety, rights, and dignity in research.

A number of IRB-member concerns identified in this study may well be addressed through education and capacity-building efforts. Greater investment on the part of the Botswana health system as well as the international research community in community-level education could reduce misconceptions about how biospecimens are used, sharpen the distinction in patient understanding between clinical care and medical research, and engender a greater appreciation for the potential benefits afforded their communities by new advances in research. Opportunities for community engagement, both pre- and post-research, should be addressed in all study protocols, with clearly articulated plans for community feedback. Future education and training activities for IRB members can address the current knowledge gap on genetic- and genomic-based research, the risks and benefits of specimen reuse, regional biobanks, shared bioinformatics, and the current regulatory guidance for review of related protocols. Capacity-building programs are needed to develop local expertise in Botswana’s own growing research community and to create the necessary physical and professional infrastructure to manage the safe and ethical collection, utilization, and storage of biospecimens. Once developed and enacted, clear national policy on the export, ownership, and terms of use for biospecimens in research can provide a guide for research priority-setting, partnerships, review, and oversight.

This study also identified some areas that may prove less malleable to change. These include indigenous meanings ascribed to the human body and its parts that seem to be at odds with ‘western’ scientific knowledge and practice. Engagement by the international research community with local stakeholders will be needed to harmonize these fundamentally different ways of understanding the human body and community identity with the aims of contemporary biomedicine.