Introduction

Although the expanding applicability of knowledge generated from (GGR) holds great promise for discoveries in the biomedical and socio-behavioural sciences, it also raises challenging ethical and societal issues. Such challenges include, but are not limited to, implications of sharing research findings with participants and their family members, issues of confidentiality and determining appropriate strategies for providing information to individuals tested [1–3]. Furthermore, GGR has significant potential risk for social and psychological harms. For example, studies that generate information about an individual’s health risks can provoke anxiety and confusion, damage familial relationships due to misaligned paternity, and/or compromise the individual’s future financial status [4–7]. Results could also possibly be used as a basis for ethnic/racial segregation or discrimination such as denial of insurance coverage or employment [8].

A significant amount of research has been conducted in the fields of genetics and genomics. Associated findings have contributed to the global debate on return of GGR results [9–14]. Although international policies for return of individual genetic research findings are still evolving, there is general consensus for feedback of results. A number of criteria need to be met including 1) the ability to assess the evidence base for potentially disease-causing genetic variants in relation to the concerned population(s); 2) assessment of whether the particular finding is beneficial to the individual; and 3) ensuring that patients are appropriately informed of the implications of the findings for their disease or treatment, and referral for follow-up care while seeking guidance of the Research Ethics Committee (REC) [15]. However, debate addressing similar issues of relevance to the African setting [1, 2, 16–20], and Uganda in particular is still limited. This situation is exacerbated by the fact that many countries in the African region including Uganda lack ethics guidance on return of results [21].

GGR has been conducted for about 20 years in the Ugandan setting and is expected to continue to increase owing to its potential for advancing targeted disease detection and interventions for both communicable and non-communicable diseases in this resource-limited setting [22]. However, there is a paucity of knowledge on the ethical, legal and social challenges that accompany GGR in the country [23–26]. There are few publications on perspectives of researchers [24, 26] and research participants [25]. This literature highlighted the need for adequate informed consent, community engagement, genetic counselling, feedback of beneficial/actionable GGR findings and ethics guidance for research. In addition to this list, research participants expressed the need for more effective support during and after participation and as well as feedback of all findings since consideration of beneficial/actionable findings to a good extent is individual based. Published literature on perspectives of grassroots communities is lacking. These communities are based in rural, communal settings with limited interaction with the outside world, are less formally educated and represent lower socio-economic groups. Adding the views of grassroots communities to those of other stakeholders will provide a more comprehensive context for guideline development and conduct of GGR in Uganda.

We set out to assess the perceptions of grassroots communities on feedback of individual GGR results in Uganda to inform development of contextualized research ethics guidelines.

Methods

Findings

Five deliberative FGDs involving 42 participants were conducted across the three regions of the country. Over half of the FGD participants were male and aged between 18–77 years. The majority were small scale farmers, Christians, married and had children. They all lived in rural communities.

All the participants were willing to participate in GGR and receive feedback of genetic results. The main reasons for receiving genetic results were the need to know one’s health status and to seek care or to plan for one’s future and the future of their families. However, the willingness to participate in GGR was conditional based on the expectation that feedback of results would occur. Other expectations included adequate informed consent, genetic counselling, implications of testing, privacy and confidentiality.

Thematic analysis identified four themes and a number of sub-themes including 1) the need to know one’s health status; with subthemes of therapeutic and/ or diagnostic misconception, as well as concerns, challenges and implications for sharing; 2) paternity information as a benefit and risk; 3) ethical considerations for feedback of findings, with sub-themes of adequate informed consent, genetic counselling as well as privacy and confidentiality; and 4) extending feedback of genetics findings to family and community, (Table 1).

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 1. Summary of the identified themes.

https://doi.org/10.1371/journal.pone.0267375.t001

Although the respondents were agreeable to feedback of all GGR results including aggregate results, individual results, incidental findings and secondary findings, for this paper, we focused on perspectives regarding feedback of individual genetics results.

Discussion

We set out to assess the views of grassroots communities in Uganda on if and how feedback of hypothetical genetics results should occur and if they were willing to participate in GGR. Our study findings show that such feedback of results was acceptable to all respondents conditional upon receiving health status information. Several reasons for needing feedback of results were identified including and especially, the need to know one’s health status and planning for the future. Several strategies were proposed if such feedback was to be conducted appropriately.

Receiving genetics results that impact on one’s health condition can be a benefit to research participants particularly in an African rural setting where genetic testing is out of reach of almost all individuals and access to general public health services is limited. Feedback to research participants is a growing reality and an ethical obligation that should be incorporated in the research processes as highlighted by several ethics guidelines [15, 29, 30]. Although the usual call for feedback of research findings has been focussed on other fields of research, the need for return of results is emerging in genetics research because of the anticipated implications such as fear and anxiety related to uncertainty around impact of findings on future health or other family members.

The fears associated with findings of genetics research can be appropriately addressed via mechanisms like adequate consent processes and genetic counselling. However, qualified genetic counsellors are an extremely limited resource in Uganda and in most African countries [26]. Other mechanisms to address the fears include observance of privacy and confidentiality as well as only sharing results that are potentially beneficial or actionable. Related work among genomics research participants and genomics researchers in Uganda has also highlighted the need for feedback of GGR results [25, 26].

Although researchers in Uganda are supportive of return of individual genetics results, they were hesitant to share results due to complexity of the science and lack of staff to accurately communicate the meaning of results, the lack of context specific guidelines as well as the challenges of accurate interpretation of the findings [26]. This dilemma faced by researchers is worsened by the desire of grassroots communities to receive feedback of all their GGR findings with clear interpretation whether beneficial/actionable or not. Participants in this study conflated genetics and genomics results even though it was explained that only significant and actionable genetics results could be returned in the information session prior to the FGDs. The need for feedback of genetics results has been described as a form of solidarity by research participants in Botswana and as a reciprocity obligation of researchers who can make participants feel valued as part of a mutual relationship [19]. Dissemination, beneficence and reciprocity have been considered as essential components of a framework for enhancing ethical genetics research with indigenous communities in the USA [31]. It should be noted that, the hypothetical research scenario the participants are responding to in this study may not correspond to the reality of feedback, and this should be borne in mind when extrapolating on the basis of these study findings.

Participants felt that knowing the outcome of GGR testing would help them seek early treatment or prevention, creating the impression that genetic testing results were reliably associated with causality of disease and that treatment is available for all conditions caused by a genetic predisposition. Likewise, there was an expectation that genomics results would confer individual benefit. Although this was a rural non-research setting, it is important to note that therapeutic and diagnostic misconception where participants perceive research as diagnosis or care rather than experimentation are very common [32–40]. Such misconception may lead individuals to participate in research with diagnostic or therapeutic expectations as has been observed among tuberculosis genetic study participants in Cameroon [32]. Yet most genetic studies may not yield results that can benefit health or predict risk of disease [41]. But even in cases where accurate diagnosis can be made, many diseases identified may not be treatable.

For feedback of genetics results to be conducted appropriately, several strategies were proposed by the respondents including adequate consent processes, genetic counselling as well as privacy and confidentiality. Informed consent for research participation is an ethical requirement that should be carried out as a continuous process starting before recruitment, through implementation to the post study period. Such consent processes should be suitable for participants and be provided in a language that is easily understandable to the participant. And for feedback of genetics findings, consent should be done at different levels including before recruitment of the participant, and at return of results for those who chose to receive results. The need for meaningful informed consent has been highlighted by participants of a genomics research study in Uganda [25]. However, the referenced study also revealed participants’ recall bias about their participation in the concerned study that affected their shared experience on the informed consent process. GGR has been challenged by the fact that genetics and genomics terminology and associated vocabulary may be difficult to translate into many of the local languages in Uganda. Hence making it difficult to achieve adequate and meaningful consent.

Recent work that reviewed consent documents for 13 H3Africa genomics projects observed that genetics was mostly explained in terms of inherited characteristics, heredity and health, genes and disease causation, or disease susceptibility and only one project made provisions for the feedback of individual genetic results [42]. However, it is important to note that not all GGR can return individual results for example genetic epidemiology of complex disorders or population genetics results which focus on the population overall. Challenges regarding meaningful informed consent for GGR have been observed particularly when it comes to sharing of human biological samples and data in the context of international collaborative research [43, 44]. In order to address the challenges associated with informed consent in GGR, some commentators have proposed tailoring the informed consent process based on a ten-point framework. The framework includes among others the study design, data and biological sample sharing, reporting study results to participants, cultural context, language and literacy and potential for stigmatization of study populations [45]. However, this proposed framework needs to be clearly interpreted and studied if it is to be meaningfully applied.

In additional, for consent to be meaningful it should be coupled with relevant information on the proposed genetics testing and associated implication. Such genetic counselling is essential and should be provided before testing and during feedback of results. It should be noted that although genetic counselling is a developing field in emerging economies like South Africa [46], there is a relative lack of qualified genetic counsellors and the associated counselling in many of the low resource settings in Africa including Uganda [26, 47]. Yet such genetic counselling would go a long way in addressing issues like implications of GGR and feedback of results to the individual, the family and the community. Other issues that can be addressed by counselling include aspects like therapeutic misconception, privacy and confidentiality as well as the common beliefs in the Ugandan setting of genetic testing being associated primarily with paternity testing. Since the concept of genetic counselling is relatively new in our setting and virtually non-existent in the rural communities, respondents felt that the doctor who is most knowledgeable should be the one to conduct the counselling. The lack of genetic counsellors can be addressed by capacity building for genetic counselling.

Furthermore, consent forms should be explicit on aspects like who would have access to genetic results and whether return of results concerning paternity information would be done. If so, this should be approved by the REC before data collection is initiated. Otherwise, it is always a dilemma when researchers discover sensitive information after running the tests and seek guidance from an equally unprepared REC. For example, during genetic testing for sickle cell disease, which is prevalent in Uganda, it’s not uncommon to discover discordant genetic information between the child and the male parent. Similar findings emerged in a study in Kenya that discussed challenges associated with paternity mal-alignment [48]. It would be good if consent documents provided by researchers and approved by RECs clearly state if such paternity information including misaligned paternity will be provided to both parents.

Our study findings highlight a situation where participants stress the need for privacy and confidentiality of their participation in GGR and return of results. However, despite the call for privacy and confidentiality, most of the respondents preferred the presence of a family member during feedback of results, hinting that such feedback could as well be done at participants’ homes. Hence the concept of confidentiality in these communities needs to be clarified and could imply keeping information not only to the individual tested but within their close family. The nature of confidentiality proposed by our respondents is quite different from the model practiced in the western world where private information usually remains with the individual tested. Additionally, the privacy and confidentiality mandated in the research ethics guidelines and some laws like the Data Protection and Privacy Act of 2019 in Uganda [29, 30, 49], employ the western approach that focuses on individual privacy and not the family as a whole. Hence the need for adaptation to fit the local setting. However, it should be noted that anonymisation of genomics data may not always be possible.

Other considerations to facilitate understanding of the GGR concepts include meaningful community engagement (CE). Such engagement would help researchers understand community-based practices for example the meaning of privacy and confidentiality, and whether it should be handled at the individual level or family level. Some commentators have proposed the Tygerberg Research Ubuntu-Inspired Community Engagement Model. This model would require RECs/IRBs to play a role in requiring a CE plan for every study that is community based, and scientific journals to require a paragraph on CE in publication of relevant research projects. This would ensure moving CE from a guidance requirement to a regulatory requirement, emphasizing that it is a critical component of a robust consent process in research and that it ought to be embedded within research projects, where applicable [50]. However, for such community engagement to be effective in facilitating research that is responsive to community needs, it has to be meaningful and collaborative. Such collaboration may extend to levels like community involvement, community empowerment and community participation. The collaboration can facilitate applicable benefit sharing models, developing capacity for genetic testing, counselling, technology transfer and translation of vocabulary.

Many respondents were agreeable to extending feedback of genetics testing results to family because genetics information was considered to belong to the whole family since it is inherited. The need for extending feedback to family and sometimes the wider community could be explained by the fact that most of the individuals in the Ugandan rural setting live in communities, often share health information and support each other during times of sickness. It is also important because family and community members play an important role in the provision of health care to patients. However, despite the fact that most of the respondents were agreeable to extending feedback of GGR results to family, fewer respondents supported such feedback to the wider community and only for particular health conditions. Sharing of genetics results with family and community was assumed to have a potential to benefit the individual tested in terms of social and financial support in case the individual became unwell, but would also act as an early warning to others at risk. Extending feedback should depend on the willingness of the individual tested, nature of the genetic condition, adequate genetic counselling and appreciation of the implications and, if there is likelihood of the tested individual to benefit from such disclosure.

The perception regarding extending feedback of genetics research results needs to be studied further and should be done on a case-by-case basis because the implications may vary amongst individual patients and from one family to the next. If genetics research results point to a particular predisposition that may affect the health of an individual, their family or community, extending feedback to family and community may be done at the discretion of the individual tested based on a clear appreciation of the implications. And such sharing may involve general information not specific personal information. This is in line with recommendations from a USA consultative team involving an ELSI working group of national experts which, among other recommendations, suggested that researchers should elicit participants’ preferences on such extension of feedback to family but also recommended further research on the subject matter [51]. Other countries like Australia, Britain and France have legislation that allows healthcare professionals to disclose genetic information considered beneficial to family members in case the individual tested is not willing to do so [52–54]. While current Belgian legislation coupled, with international precedent, may provide sufficient justification to establish a duty to inform relatives of their genetic risk in some cases [55].

It is imperative that the privacy and confidentiality of the person enrolling in the study be respected. But in cases where there is benefit in sharing results with family members, the original participant should grant permission because just like feedback to individuals, feedback should not be imposed on family members, but should be based on their voluntary consent [14]. A study involving REC chairpersons in the USA showed that 62% of the REC chairs agreed that participants should be informed that their results could be offered to family members and asked to indicate their choice, but such a statement may not be adequate informed consent [56]. Keeping genetic information and associated diseases confidential may be very difficult particularly in the Ugandan setting where the costs of medical treatment to a great extent are met by the relatives and sometimes the wider community who may inadvertently learn of the patients’ genetic condition. Since individuals in the communities are agreeable to extending feedback of GGR results to family members, it’s up to the research regulators with the oversight mandate to devise appropriate frameworks and guidelines to guide the process while respecting the participants’ preferences, privacy and confidentiality.

Although feedback of results is generally acceptable by grassroots communities, it is necessary to adequately evaluate and address the implications associated with such testing and feedback of results. Implications may include psychological and socio-economic aspects such as family disruption, a feeling of low self-esteem, stigma and discrimination, denial of insurance or increased premiums. Such effects may affect the individual tested, their family or the wider community. Yet familial implications of genomics contribute to the need for extending feedback to family. Hence adequate genetic counselling both before testing and at feedback of results, appropriate consent as well as maintenance of privacy and confidentiality are necessary for GGR.

Other challenges associated with return of GGR results include lack of appreciation of the information due to unfamiliarity with genetics and genomics vocabulary as well as affordability of the testing services to the community post the research period. Hence the need for appropriate translation of the information to a language understandable by the participant, use of visual aids to support information delivery as well as use of non-technical terminology. Additionally, the lack of availability or affordability of genetic testing facilities to the community post study, lack of a clear interpretation of the results and meaning of the findings may cause confusion. The researchers should therefore build meaningful collaboration with communities where research is conducted, and share only confirmed results and information with participants. This will avoid the negative implications of such research and enable research communities to benefit from the results of research.

Finally, most GGR conducted in Uganda to address ethical, social and legal issues has been carried out in well-established research settings, and the views that have informed debate on ethical conduct of GGR in the country are mainly those of research participants, researchers and research regulators [23–26, 57]. Our addition of the grassroots communities will contribute a new dimension with an additional group of stakeholders whose views will enrich the literature as well as the targeted ethics guidelines for conduct of GGR in Uganda. The acceptability of grassroots communities to participated in GGR as well as receive feedback of results whether beneficial/actionable or not goes beyond the protective recommendation by researchers and research regulators of sharing only beneficial/actionable findings. We believe the ethics guidelines for conduct of GGR informed by our study findings will go a long way in informing regulation and oversight of GGR in the country.

Conclusion

Participation in hypothetical GGR as well as feedback of genetic testing results is acceptable to individuals in grassroots communities conditional upon receiving health status information, to establish paternity in some cases and to plan for the future. The strong diagnostic and therapeutic misconception linked to GGR is concerning and has significant implications for consent processes, community engagement, genetic counselling and research ethics guidance. Furthermore, the expectation of paternity testing results being embedded in all GGR needs to be managed appropriately. Given the misperceptions and unrealistic expectations expressed, it is an ethical imperative to build meaningful collaboration with research communities for appropriate genomic language/vocabulary translation, benefit sharing, capacity development and knowledge translation. Finally, the willingness of grassroots communities to participate in GGR as well as receive feedback of genetics results whether beneficial/actionable or not goes beyond the protective recommendation by researchers and research regulators of sharing only beneficial/actionable findings and should be further evaluated. While extending feedback of genetic research results to close family members was generally acceptable, concern was expressed in extending feedback to the community.

Supporting information

Acknowledgments

We are grateful to all the individuals in the various communities who participated in this study.