Introduction

Although genetics and genomics research (GGR) is expected to be a public good that would contribute to improved health care and disease outcomes, a number of ethical, social and regulatory issues associated with this research remain unresolved. Aspects such as return of genetic information derived during research continue to be an issue globally and a topic of intense debate [1–3]. Although human GGR can yield information that may be of clinical relevance to the individuals who participate in research, there is not yet a consensus on the responsibilities of researchers to disclose individual research results to research participants [4, 5]. In many settings, there is no legal obligations for researchers to return genetic results to participants despite patient willingness to receive the results [6, 7]. Additionally, GGR testing has a potential for identifying incidental or secondary findings unrelated to the objective of the testing but of potential medical value for the individual being tested. Incidental findings (IFs) have been used in a variety of clinical and research contexts to indicate unexpected positive findings [8]. Incidental findings have further been defined as findings having potential health or reproductive importance for an individual, discovered during genetics and genomics testing but beyond the aims of the testing [7, 9]. Such incidental findings have been reported to occur at a rate of 0.9% to 8.8% in some populations [10].

While the global debate on IFs is taking shape, literature on the African perspective, Uganda inclusive, is still limited [1, 11]. Yet, African genomes have been characterized as having more variants than in any other population in the world. Thus, the need to address issues such as whether to, how and which IFs to share following testing in African populations [12].

The debate about the circumstances under which researchers are obliged to feedback IFs is ongoing with suggestions that such determination be made at an institutional level, on a case-by-case basis often by Research Ethics Committees (RECs). However, in many countries, nationally accepted or contextualized guidelines to direct researchers’ or REC members’ decisions about disclosure of IFs discovered during GGR and testing do not exist [13, 14].

In Uganda, the available national guidelines for conduct of research involving humans are silent about GGR including the sharing of IFs [15]. International guidelines such as those drafted by the H3Africa consortium stress clinical validity and relevance for the target population as important considerations [16]. However, determination of clinical validity and relevancy is often left to the discretion of researchers or attending doctors, leaving room for a significant degree of idiosyncrasy.

In the absence of specific guidelines, many researchers argue that only IFs with confirmed clinical utility; with a possibility of treatment or prevention should be disclosed [10, 14]. However, for many countries uncertainty remains regarding whether, when, how and to whom to offer IFs [6]. Other concerns include the relevance of IFs to the participants’ or patients’ family members and if researchers and clinicians should regard genetic information as confidential to individuals or to families [17]. This is because it’s still unresolved in many settings on whether clinicians/researchers have an obligation to warn family members of potential risk associate with a genetic disorder identified in a family member when such an individual is not willing to disclose their genetic information.

Since literature and debate on GGR and associated incidental findings has been evolving over the last decade, an updated discussion on this topical issue is necessary to provide updated information on the subject matter. This study explored researchers’ perspectives and experiences regarding feedback of incidental genetics and genomics research findings to participants.

Methods

This was a cross-sectional study that employed a qualitative exploratory approach. The study was conducted by a team of academics comprising of social scientists, bioethicists and medical scientists including both male and females with experience in qualitative research. Data was collected between 2019 and 2020 among researchers who were actively involved in GGR in Uganda. Respondents were recruited from institutions in the Central, Western, Eastern and Northern parts of the country. Data were collected using in-depth interviews that were guided by a semi-structured interview schedule adapted from a checklist for genetic and genomic testing of the Federal Code of Regulations which provides detailed information on the requirements for research participants to be respected throughout the research process [18]. Thirty researchers were identified with help of one of the leading GGR researcher in the country and purposively selected based on their being investigators on GGR projects.

Data collection entailed face to face in-depth interviews conducted in the English language privately conducted at the offices of the respondent and lasted 40–70 minutes. Responses were audio recorded which was complemented by notes taken by a research assistant. Recorded information was transcribed verbatim and checked for accuracy before analysis. Data were analysed through content analysis along the main themes of the study. Content analysis was conducted using a comprehensive thematic matrix that included codes, categories and themes to identify common patterns arising from the narratives. The coding was done both deductively and inductively. Transcripts were further reviewed for emerging themes which were integrated into the thematic matrix. Multiple people JO, BK, DES were involved in applying and confirming application of codes across all transcripts and disagreements were resolved by cross checking with the recorded data. NVivo software (QSR international 2020) was used to support data analysis and illustrative quotes were extracted.

Results

Of the 30 study respondents, 23 were male. The mean age was 41 years (range, 29–65years). All were residents of Uganda and affiliated to one of five research institutions in the Central, Western, Eastern and Northern parts of the country. The participants’ main job roles included academic and researcher roles with most 24/30 (80%) having at least five years of GGR experience (see Table 1).

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Table 1. Demographic characteristics of respondents.

https://doi.org/10.1371/journal.pone.0273657.t001

Fields of specialization included molecular biology, immunology, microbiology, biochemistry, pharmacology, internal medicine, transfusion medicine, surgery, obstetrics, and gynaecology. Types of studies conducted by the respondents included molecular diagnostics, pharmaco-genetics, pharmaco-genomics, molecular genotyping, microbio-genotyping and haematological genomics. Content analysis identified five themes; a). On perspectives, sharing of incidental findings was acceptable and four themes emerged including; 1). role of professional judgement; 2). role of ethics committees and ethical guidelines; 3). optimal disclosure practices; 4). limits to professional duty and uncertainty and; b). on experiences, sharing had been carried out by some researchers and a theme on 1). experience emerged.

Discussion

We set out to explore genetics and genomics researchers’ perspectives and experiences regarding sharing incidental findings during the conduct of GGR in Uganda. Many of the respondents were agreeable to sharing incidental GGR findings with research participants giving a number of proposals on the nature of incidental findings and contexts/conditions under which incidental findings should be shared.

Emphasis was placed on sharing of beneficial, actionable, verified results, and results that are of public health interest. s Similar perceptions about sharing IFs have been documented where respondents from a population biobank study who were informed about an unexpected genetic finding evaluated this process as mainly positive. A cross-sectional, web-based survey investigated attitudes of 6944 individuals from 75 countries towards returning IFs from genome research and found that treatability and perceived utility of incidental results were deemed important with 98% of stakeholders [19, 20].

Genetic counselling was considered a crucial component of GGR. Counsellors are key players in facilitating participants’ comprehension of complex genomics language, implications of receipt of results, risks and benefits involved. Other aspects to be clarified by counsellors include address misconceptions and allaying anxiety especially during communication of incidental findings. Hence the recommendation that sharing of incidental GGR results should be done in the presence of a genetic counsellor. However, despite the emphasis on the importance of genetic counselling, none of the respondents reported participation of qualified genetic counsellors in the respective genetics’ studies. There is a capacity gap in this area. Our findings are similar to work reported in the USA where it has been observed that the genetic counsellors are important, their work is not well appreciated and may not be available for every research study [2, 21].

The need for regulation and ethical guidelines for conducting GGR including communicating incidental findings is key to setting ethical standards in practice. Although there are guidelines that regulate ethical conduct of research in Uganda, the existing guidelines do not address the unique challenges posed by GGR in this context [16]. Such context specific guidelines would provide a national framework for ethical oversight of GGR. The inadequacy of guidelines leaves unresolved the issues on whether or not to share incidental findings including what constitutes ethical practice. The need for ethical guidelines, including facilitation of research oversight by RECs, has been highlighted by other literature [15, 22]. Such oversight by RECs would mandate researchers to comply with the set standards and ethical obligation to “give back” to participants [3]. Although questions relating to how much, when and how information to give back including the fact that many have argued that there isn’t really a general moral duty, especially given that returning results can sometimes be unhelpful or possibly even unwanted. Many of our respondents have on the contrary highlighted the fact that it is morally right and professionally necessary to share incidental findings particularly those deemed beneficial. For such sharing of findings to be appropriately conducted, the need for context specific national ethical guidelines for GGR is a growing reality [15].

Communication of incidental findings was considered acceptable provided informed consent had been sought. Such informed consent would best be obtained at the time of recruitment in the study; where participants are informed of the possibility of getting results that are outside the scope of the objectives of the current study. However, if consent was not obtained at recruitment, in case of incidental findings that are deemed beneficial, then re-consenting the participants should be done after seeking approval from the REC. This requirement for informed consent is an ethical standard for all research involving humans as participants. Although informed consent should ideally be obtained at recruitment, researchers are faced with a challenge of providing adequate information on incidental findings at the time of participant recruitment. Such dilemmas associated with informed consent for communicating incidental findings from genomic research have been highlighted by other scholars [7, 23]. The need to re-consent participants in order to share incidental genomics findings has also been discussed if such new information is to be released to research participants [14, 23].

A number of other ethical considerations for sharing incidental GGR findings were highlighted. These include proper evaluation of the risks and implications anticipated from sharing the results on the individual, family members and the entire community. This is attributed to the fact that genetic information though collected from a consenting individual, has potential to reveal information about the participant’s family and sometimes the whole community. Release of such findings can cause anxiety and distress to individuals, cause family breakups or provoke widespread stigmatization of the community. Ethical issues including violation of privacy and breach of confidentiality associated with sharing incidental findings have been observed elsewhere [7]. Consent is also challenging in clinical genetic practice as testing can generate ‘incidental findings’ with potential to reveal patient’s family members’ risk which may lead to breach of confidentiality [17]. Because of the potential risk associated with incidental findings, other commentators have discussed the consideration of the option of notifying participants about the right not to be re-contacted [24]. Feedback of incidental findings can sometimes be challenging if researchers discover sensitive information where test results could inadvertently reveal sensitive personal information particularly for vulnerable groups like children and fetuses. For example, during genetic testing for sickle cell disease, which is prevalent in Uganda, it’s not uncommon to reveal discordant genetic information between the child and the male parent. And if not properly handled, such information could have dire consequences for the child and the family.

Although the majority of the respondents had not found incidental findings that they felt were worth sharing, some of those who had what they considered clinically significant incidental findings shared the results with their research participants and or the attending clinicians. However, owing to lack of clear ethical guidelines such sharing did not follow any systematic approach, procedures or standards. The decision and procedures were at the discretion of the researcher. As a result, researchers in such contexts experienced challenges. Issues to do with what constitutes appropriate ethical conduct, pre-conditions and procedures for sharing incidental findings. The different approaches employed in returning incidental findings namely, sending results to the attending clinicians, communicating to individual participants or their representatives and use of community meetings may have lacked adequate preparation and clear processes necessary for sharing sensitive unanticipated findings. This discrepancy in handling and sharing incidental findings is attributed to the lack of policy and specific ethical guidelines on how genomics testing results should be appropriately communicated. The challenge of lack of context specific evidence to inform guideline development in the African setting is also highlighted by the H3Africa guidelines for sharing genomics findings which recommends clinically valid and actionable results, but with an additional task to researchers to determine relevance of information for the target population. Additionally, many considered clinical benefit or results being actionable as the main premises for sharing incidental findings although determination of clinical utility of the results was also subjectively made by the researchers using no context relevant specified or regulated criteria. Sharing of incidental genomics findings based on clinical benefit and actionability has been highlighted in related works [3, 20, 21, 25].

Finally, there is limited literature that addresses GGR in the Uganda setting with none focusing on incidental genomic findings [1, 11, 13, 26]. The research reported in this study provided insight on the issues affecting feedback of incidental findings in a Ugandan setting that has not been documented before. Findings of this study and other related literature [1, 11, 13, 26] can go a long way in addressing the current gaps in GGR including data for development of ethics guidelines that are currently unavailable in Uganda. Additionally, other related settings particularly those on the African continent can adopt the findings for use in their context for example in places where stakeholders in research have considered feedback of GGR results important and expressed interest in return of results [27]. Our work to a good extent confirms what is proposed by international guidelines like the H3Africa guidelines published by the African Academy of Sciences with recommendations similar to what the Ugandan researchers propose, and this makes adoption of the international guidelines to the Ugandan setting feasible [16, 28].

Supporting information

Acknowledgments

We are grateful to the researchers who participated in this study.