The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment

Sylvia Nabukenya; David Kyaddondo; Ian Guyton Munabi; Catriona Waitt; Adelline Twimukye; Erisa S Mwaka

doi:10.1371/journal.pone.0299081

. 2024 Apr 2;19(4):e0299081. doi: 10.1371/journal.pone.0299081

The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment

Sylvia Nabukenya ^1,^3,^*,^#, David Kyaddondo ^2,^#, Ian Guyton Munabi ^1,^#, Catriona Waitt ^3,^4,^#, Adelline Twimukye ^3,^#, Erisa S Mwaka ^1,^#

Editor: Tahir Turk⁵

PMCID: PMC10986979 PMID: 38564575

Abstract

Community engagement (CE) is praised to be a powerful vehicle in empowering communities with knowledge and skills to make informed decisions for better health care. Several CE approaches have been proposed to improve participants’ and research communities’ understanding of genomic research including pharmacogenomic information and results. However, there is limited literature on how these approaches can be used to communicate findings of pharmacogenomic research to communities of people living with HIV. This study explored stakeholders’ perspectives on the role of community engagement in promoting understanding of pharmacogenomic research results among people living with HIV. We adopted a qualitative approach that involved 54 stakeholders between September 2021 and February 2022. We held five focus group discussions among 30 community representatives from five research institutions, 12 key informant interviews among researchers, and 12 in-depth interviews among ethics committee members. A thematic approach was used to analyze the results. Five themes merged from this data and these included (i) benefits of engaging communities prior to returning individual pharmacogenomic research results to participants. (ii) Obtaining community consensus on the kinds of pharmacogenomic results to be returned. (iii) Opinions on how pharmacogenomic research information and results should be communicated at community and individual levels. (iv) Perceived roles of community stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results. (v) Perceived challenges of engaging communities when returning individual results to research participants. Stakeholders opined that CE facilitates co-learning between researchers and research communities. Researchers can adapt existing CE approaches that are culturally acceptable for meaningful engagement with minimal ethical and social risks when communicating pharmacogenomic research results. CE approaches can facilitate understanding of pharmacogenomic research and findings among research participants and communities. Therefore, if creatively adapted, existing and new CE approaches can enable researchers to communicate simple and understandable results of pharmacogenomic research.

Introduction

There is an increase in pharmacogenomic research in sub-Saharan Africa aimed at improving HIV treatment [1–5]. In Uganda, there are about 1.5 million people living with HIV (PLHIV) and 28,000 dying of AIDS-related illnesses annually [6]. Pharmacogenomic research involves studying how an individual’s genes precisely influence their response to a given medication including drug efficacy, adverse events, and dosing requirements [7]. Pharmacogenomic research can present a vast amount of information [8, 9], some of which may be pleiotropic, where a single gene can contain information about several phenotypes, resulting into potential incidental findings [10, 11], in addition to primary results. Primary results are defined as findings responding to a well-defined research question, while incidental findings are any results discovered unintentionally and are not related to the primary research question, but may have significant implications for the health or well-being of the participant and family members [12].

Researchers and clinicians may use results from pharmacogenomic research analyses to determine the most appropriate drug and dosing requirements for an individual. Similarly, these results are equally important to research participants and communities involved in pharmacogenomic and other genomic research studies in determining their best treatment options. Studies have reported a high demand from research participants for their individual results from pharmacogenomic and genomic research [13, 14]. A recent study that explored the factors influencing the preferences and reasons for the desire to receive individual results from pharmacogenomic research among people living with HIV showed that 98% wanted to receive all their primary results [15]. However, several studies have reported participants’ inadequate understanding of genomic and pharmacogenomic research information including results across the globe [16–20]. This has been attributed to the complexity of genomic terms and the absence of direct translations of genomic terms in many African local languages where genomic studies are being conducted [21–23]. A study conducted among PLHIV reported that only 23% of the participants enrolled in clinical trials that included a pharmacogenomic component had adequate understanding of the information disclosed to them during the consenting process [24].

Inadequate understanding of research information is a barrier to participants’ informed decision-making for participation, and determining the kind of results they would like to receive. To promote adequate understanding of genomic and pharmacogenomic research information and findings, CE has been proposed by several researchers [25–28]. They suggested that communities should be actively engaged in research activities right from proposal development to result dissemination. CE is considered one of the platforms where research participants can learn more about how individuals’ genes interact with drugs, an opportunity to clarify the research goal and objectives, and understand the appropriate CE approaches and strategies specific to a given research project [25, 29]. CE also facilitates co-learning between the researchers and research communities promoting transparency and free sharing, hence building long-term relationships based on mutual respect and trust [28, 30, 31]. The Uganda National Council for Science and Technology (UNCST) guidelines for Community Engagement in Research recommend using one or more approaches, for example, formative consultations, existing structures and groups, community leaders, community events, mass media, and community advisory boards (CABs) when engaging research communities [29]. In addition, the H3Africa guidelines of community engagement for genomic research and biobanking in Africa recommend adopting responsive and flexible CE strategies that are shaped by the participants and their communities’ experiences [25]. These guidelines emphasize that communities are not homogeneous, so researchers ought to employ creative approaches that minimize the potential risks to participants and research communities when communicating pharmacogenomic and genomic information. It is important to note that individual pharmacogenomic and genomic research results may present findings with ethical, legal and social implications that may not only affect research participants but also extend to families and research communities [32]. Therefore, inappropriate approaches of communicating pharmacogenomic research results at community and individual levels might raise concerns such as loss of privacy and breach of confidentiality, which may stigmatize research participants and their family members. Yet, there is limited literature on the suitable CE approaches for communicating simple and understandable pharmacogenomic information including results at community level. Therefore, this study explored stakeholders’ perspectives on the role of CE in promoting understanding of pharmacogenomic research results among PLHIV. We present findings on CE approaches that can enhance participants’ understanding of pharmacogenomic information and findings. We hope that findings from this study might inform institutional and national guidelines for returning genomic and genetic research results to people living with HIV, their families and communities.

Materials and methods

Study design and setting

This cross-sectional study used a qualitative exploratory approach [33–35]. The study was conducted at Makerere University College of Health Sciences (MakCHS) and five affiliated research institutions located on Mulago Hill. College of Health Sciences is one of the nine constituent colleges of Makerere University, with vast experience in HIV/AIDS research, including pharmacogenomics. We also considered three of the five accredited research ethics committees (RECs), housed at MakCHS, that had experience reviewing pharmacogenomic research specifically, for HIV treatment. In addition, we included three Ugandan RECs with prior experience in reviewing pharmacogenomic research in HIV.

Research team

The research team comprised of a social scientist, bioethicists, a medical anthropologist, and medical scientists with experience in conducting and analyzing qualitative data.

Study participants

In this study, we selected three categories of stakeholders in pharmacogenomic research for HIV treatment who were researchers, members of research ethics committees and community representatives. We purposively selected 15 researchers involved in pharmacogenomics research for HIV treatment for the period 2018–2021 and based at MakCHS or affiliate research institutes as eligible for enrolment in this study. Of these, 12 consented to participate, while three declined, citing inadequate time to participate in our study. We selected 12 REC members with experience in reviewing proposals for pharmacogenomic research in HIV treatment. Six were REC chairpersons and the rest were members of the RECs representing the research communities. Three of the REC chairpersons preferred to nominate a member of their REC who was more knowledgeable in the field of study. We also conducted five deliberative focus group discussions (dFGDs), each comprising of six community representatives from the five HIV research institutions affiliated with MakCHS. This study was conducted between September 2021 and February 2022. All participants were purposively selected and were above 18 years of age. Before conducting the study interviews, the research team was trained on the protocol to ensure that they understood the study well.

Study procedure

Considering the restrictions that prevailed during the COVID-19 pandemic, some data collection activities were conducted virtually. Researchers and REC members who were involved in or had reviewed HIV pharmacogenomic research respectively, were contacted by email, which contained a brief description of the study and a request to schedule an appointment for the interview. Expression of interest to participate was recorded by a positive response to the email, followed by sharing the consent form. The consent forms were either signed electronically or by a written email notification of acceptance to participate in this study. Appointments were scheduled and conducted virtually via Zoom at the participants’ convenience. Interviews were audio-recorded and lasted between 30 and 40 minutes.

Five dFGDs were conducted with community representatives. The community representatives were contacted through their respective leaders. The dFGDs were conducted in two languages, English and Luganda, the commonly spoken language in Central Uganda. The dFGDs were conducted through face-to-face interactions after the national lockdown was lifted during the COVID-19 pandemic, with appropriate mitigation measures in place. Prior to the dFGDs, each community representative received a consent form document in the language of their choice. One of the research team members obtained written consent from each community representative after discussions on the various components of the study. At the beginning of each dFGD, participants were provided with an overview of how antiretroviral drugs interact with human genes. This was followed by a vignette describing a hypothetical scenario of the possible results that could be generated from pharmacogenomic research, and these included primary results and incidental findings. Prior information helped participants to gain an understanding of pharmacogenomic research and the different kinds of results that could emerge from it. Clarifications were offered prior to and during the discussions. A team of four researchers (SN, AT, CW and ESM) conducted all interviews to ensure consistency. A note-taker was present throughout the discussions to back up the electronic recording. The dFGDs were audio-recorded and lasted about 60–90 minutes. Both dFGD and interview guides were developed from the literature [36–43] and subsequently revised to capture new emerging topics. The topics of discussion included questions related to the potential benefits of community engagement, how to effectively communicate pharmacogenomic research information including primary results and incidental findings at community level, how to achieve community consensus when determining the kind of results to be returned, perceived challenges of enganging communities in the feedback process of results, and the perceived roles of each stakeholder in promoting research participants’ understanding of pharmacogenomic research results. The guides were first piloted on three genomic researchers, two REC members and three HIV peer support members who were excluded from the study. However, their feedback was used to improve the interview guides. The research team held debriefing meetings at the end of each interview to identify new perspectives that were not initially captured by the tool. Data were collected until no new information or insights were being revealed.

Data analysis

Data were analysed continuously throughout the study using a thematic approach [44, 45]. All audio recordings were transcribed verbatim. Transcripts of the community representatives were translated from Luganda to English. All transcripts were verified for accuracy by reading word by word while listening to the audio recordings for quality checks and spelling errors. This step helped the authors to familiarize, mark and memo the data. Transcripts were initially analyzed separately based on the three participant categories: researchers, REC members and community representatives, in order to gain a deeper understanding of each category’s perceptions on the subject matter. Three authors (SN, AT, and ESM) selected three transcripts from each participant category for open coding. These scripts were read line by line to generate the first set of codes. Synthesis of codes from the independent reading were iteratively discussed among the three authors and codes of similar ideas were merged. Differences in coding among the independent coders were resolved by consensus. A hierarchal codebook and coding framework was developed for each participant category by the three authors to guide the analysis of the data. The hierarchy of codes was then sorted into categories based on how themes were related and linked. We then deductively generated themes using our pre-existing analytic framework, which we developed from the literature on the role of community engagement in genomic research, as represented in the interview guides. We also inductively considered new themes that merged from the transcripts. All the transcripts were then imported into Nvivo version 12 [46] and coded by three authors (SN, AT, and EMS). Three authors DK, IM and CW examined the themes for patterns consistency until consensus was achieved on the final themes. All the authors compared the emergent themes with the existing literature to confirm that the final themes accurately represented the stakeholders’ perspectives on the role of community engagement in promoting participants’ understanding of pharmacogenomic research results. We also returned some transripts to the stakeholders to verify whether the data collected was a true reflection of their statements on the subject matter. This ensured that the data can be transferable to similar settings and enhanced the credibility of the study findings [25, 47]. The key findings were summarized and the overlapping themes across the three categories of participants were merged as presented in Table 2. The final codebook included the merged themes and codes from all three categories of participants. It was continuously refined to establish the themes presented in the results section.

Regarding research reflexivity, the research team was aware that we needed to remain neutral throughout the interviews and focus group discussions. We acknowledge our potential biases based on the prior knowledge about the research institutions where we recruited the research stakeholders and the existing relationships between the interviewees and the research team through prioritizing listening from the interviewees’ perspective.

Ethical consideration

This study obtained ethics approval from the Makerere University School of Biomedical Sciences Higher Degrees and Research Ethics Committee (SBS- 855) and Uganda National Council for Science and Technology (SS 735ES). Written informed consent was obtained from all stakeholders, and they were assured of confidentiality.

Results

The demographic characteristics of stakeholders are presented in Table 1. A total of 54 participants participated in this study. The majority had more than five years’ experience in pharmacogenomic research and HIV care and treatment.

Table 1. Stakeholders’ demographic characteristics.

Participants	Researchers	REC members	Community Representatives
N = 54	12	12	30
Sex
Men	07	05	16
Women	05	07	14
Highest level of Education
Primary			02
Secondary			07
Diploma			13
Bachelor	02		07
Master	08	07	01
PhD	02	05
^* Research Experience in PGx research and HIV treatment and care
< 5 years	02	02	07
5–10 years	06	04	12
>10 years	04	06	11

Open in a new tab

*PGx stands for Pharmacogenomic research

Summary of the themes and key findings

A summary of the key themes that emerged from the data collected as described in Table 2.

Table 2. Emergent themes.

Theme	A summary of findings from various stakeholders
1. Benefits of engaging communities prior to returning individual pharmacogenomic research results	Facilitates cross-learning between researchers and community members. Fosters long-term relationships between researchers and community members. Promotes ownership of results and solidarity. Overcomes societal stigma and misconceptions.
2. Obtaining community consensus on the kinds of pharmacogenomic results to be returned.	First, define the community with a likelihood to benefit from these results. Provide generalized and understandable information about pharmacogenomic research, kinds of results that can be returned and their ethical, legal and social implications. The need to balance community and individual interests. Obtaining consent from family members before sharing information and results of pharmacogenomic research.
3. Opinions on how pharmacogenomic information and research results should be communicated at community and individual levels.	Using a language preferred by the community members Employing a genetic counselor to aid the research team in determining the appropriate communication strategies and tools. Training peer-clients with skills in explaining and communicating certain genomic terms to research communities. Using institutional music and drama clubs to communicate pharmacogenomic research information and results Group education to promote participants’ learning from each other
4. Perceived roles of community stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results.	Researchers: Provide basic, adequate, and understandable information, Ought to be knowledgeable about the implications of the results, Encourage public sensitization and community education about the role of genes in the human body. Provide a well-explained action plan after returning results, and Report study outcomes to RECs & regulators. Community members: Identifies potential social harms from the results, Use familiar/ relatable life stories to facilitate understanding of genomic terms, Provide accurate information to overcome societal misconceptions. REC members: Identify potential ethical issues that may arise from returning results, Ensure that information provided to participants and communities is sufficient and understandable. Research participants: Raise questions and concerns about unclear concepts for clarification, Express their interest either to receive or not to receive results. Research institutions: Put measures in place to protect participants and research communities from possible social harm after learning about these results. Facilitate a smooth referral to health facilities offering various genetic services. National research regulators: Develop contextualized guidelines for returning individual and aggregate genomic research results. Develop a framework to address the need to balance community interests and individual interests when selecting the kinds of results to be returned to research communities.
5. Perceived challenges of engaging communities when returning individual results to research participants.	Difficult and time consuming to determine the most suitable CE approach and language to use when interacting with multilingual communities. Fear of losing the scientific meaning when translating genomic information into drama and songs. Absence of genetic counselors in Uganda.

Open in a new tab

I
Benefits of engaging communities prior to returning individual pharmacogenomic research results
II
Obtaining community consensus on the kinds of pharmacogenomic results to be returned.
III
Opinions on how pharmacogenomic research information and results should be communicated at community and individual levels
IV
Perceived roles of community stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results
V
Perceived challenges of engaging communities when returning individual results to research participants

Benefits of engaging communities prior to returning individual pharmacogenomic research results to participants

Majority of the stakeholders (47) lauded CE for promoting understanding of individual pharmacogenomic results, but emphasized the need to engage community members right from proposal development. Stakeholders considered CE an opportunity to create platforms where participants and community members can freely interact with researchers throughout the research period. In addition, engaging communities was recognized for enabling researchers to learn about communities’ cultural values and local explanations of disease experiences. In return, participants and communities also learn about the individual variability of drug response, thus promoting adequate understanding of pharmacogenomic research and the implications of research results. The continuous interactions between researchers, participants and communities were also said to foster lasting relationships based on mutual respect and trust, and eliminate misconceptions about genomics research.

[……]As long as you keep giving information to people about unclear things…they can easily trust you. This will help reduce on many community misunderstandings and misconceptions about genomic research.

(KII_Male_Researcher_12)

You see, you need to engage the communities early enough. When you do so, many will be given an opportunity to understand the goal of pharmacogenomic research and its implications even if they may not necessarily participate, but they will have learnt about these genetics hard concepts. So here, you see, these results do not necessarily help the participants alone but the whole community who have very many questions about this topic…

(FGD 2_Male_Community representative 3)

One community representative mentioned that community engagement can promote ownership of findings of pharmacogenomic research and foster community solidarity, where community members may contribute to the financial and social support for the less privileged individuals.

When they receive the research information and results as a family or as community, they will be more willing to learn more about genes and drug interactions…and then take necessary action. I have even seen sometimes, people in communities come together to collect finances for their friends to go abroad for expensive medications which they [patients] cannot afford on their own.

(FGD 1_Female_Community representative 4)

Majority of the stakeholders across the different participant categories (38) acknowledged community engagement as an important strategy to overcome societal stigmatization of individuals or families who may not respond well to the available HIV treatment regimen provided by the Government of Uganda.

Most of the time people in communities believe that individuals or families that are different from the majority of the population are cursed or are being punished by God. But when you discuss these [genetics] issues together with them [community members] as a group, many will appreciate the importance of having a genetically diverse population

(KII_Male_Researcher_6).

Obtaining community consensus on the kinds of pharmacogenomic results to be returned

We asked stakeholders about the various ways of obtaining community consensus on the kinds of results they would wish to learn from pharmacogenomic research. All stakeholders across the different participant categories (54) agreed that a community is a complex group of people with varying values, beliefs and interests. Therefore, stakeholders emphasized the need to first define the specific groups of people within the community that have potential to benefit from the genomic research study, and later, identify the key gatekeepers prior to accessing the potential beneficiaries.

I think in this case, it would be important to first define a community based on the disease and subject at hand, if we want them [communities] to appreciate the benefits of research. Research targets a particular population and not the whole community, so we should be able to engage with people who have been infected and/ or affected by HIV/AIDS and see how these results can be returned them.

(KII_Female_Researcher_5).

Almost all of the stakeholders (50) agreed that before selecting the kinds of results from pharmacogenomic research, community members should be provided with adequate information about the nature of the results and their implications. One REC member emphasized that researchers and community representatives should provide generalized but appropriate and understandable information about the role of genes in the treatment of HIV/AIDS to minimize raising ethical issues in communities, such as stigmatization.

We need to strike a balance regarding the information researchers communicate at community level and individual level. People living with HIV still suffer stigmatization, even among themselves. Just telling someone that your body cannot respond to first-line ARVs [Antiretroviral drugs], you need to move to second line may make one feel stigmatized. So, I feel we should provide general information about pharmacogenomic research at community level and then get into the specifics at individual level.

(IDI_Male_REC member_5).

Another REC member cited concerns about balancing community and individual interests when selecting the kinds of results to be returned from pharmacogenomic analyses. Since community choices are made based on a majority decision, sometimes the voices of the minority may be ignored, yet individuals’ rights should be respected. He suggested that research institutions and regulators should develop a framework for building community consensus on the kind of results to be discussed at community level while considering the interests of the individuals participating in pharmacogenomic research.

….. As communities are pushing to be involved in the process of returning these results, we need a framework and guidance from regulators and RECs on how to balance participants’ interests at individual level and communities’ interests at community level.

(KII_Male REC member #12)

Several REC members (06) emphasized the need to seek consent from the family head and individual consent from each family member who wishes to learn about their pharmacogenomic research results. They emphasized the need to provide adequate information and time to the family members to understand the results’ implications fully, before soliciting their choices of the kinds of results they wish to receive.

These family members should be first prepared by providing them with detailed information about genes and their role in their bodies just like how you have prepared the participant throughout the study. In fact, these people [family members] should first consent to either accept to know this information or not. Some family members may not want to know about these results. No one should decide for them, not even the participant’s decision to share his/ her results with family members. They [family members] should also be autonomous because the results will be affecting their lives as individuals…..

(KII_Male_REC member # 6)

Opinions on how pharmacogenomic research information and results should be communicated at community and individual level

In order to build community trust and promote ownership of these results, stakeholders suggested that a healthcare provider knowledgeable and experienced in genetics should provide the pharmacogenomic information and results to communities. Eight community representatives emphasized the need to provide genomic information in local languages that local communities can understand.

The language researchers use to communicate this information matters. Researchers should consider translating this information into local languages and consult community representatives on the appropriate local words to be used when explaining genomic terms.

(FGD 5_Male_Community representative 5).

Majority of the researchers (10) emphasized the role of genetic counselors in the feedback process of pharmacogenomic research results. One researcher mentioned that genetic counselors should work with the research team to devise appropriate tools for communicating pharmacogenomic information and results, and guide on the strategies for engaging communities throughout the research project.

Sharing this genetics information with community members can sometimes be tricky. Many of them [community members] are illiterate and do not know much about genes. Therefore, the research team needs to be very creative and probably work with genetic counselors who understand both the scientific information and societal norms.

(KII_Female_Researcher_2)

Another researcher mentioned that the research team usually trains peer clients to communicate pharmacogenomic research information to fellow participants. She hoped this strategy would enhance participants’ understanding of individual pharmacogenomic research results, since some participants may be more willing to open up to their peers than healthcare workers.

I think we can also utilize our peer-clients to explain these results to their fellow participants. From the time we started these PG [pharmacogenomic research] studies, we have trained our expert patients how to explain and break down these terms. They even share with us some of the concerns that some participants tell them….

(KII_Female_Researcher_8)

Some researchers (04) suggested using music, dance and drama to convey information about pharmacogenomic research and the implications of its results to participants.

Another way we can communicate these results to participants and community members is utilizing the creativity of our drama club here at the Institute. They usually come up with skits and songs to communicate HIV-related information at least once in two weeks. So we can give them scripts to act out something about the role of genes in breaking down the ARVs [Antiretroviral drugs].

(KII_Male_Researcher_11)

One researcher suggested using group education as another way of promoting participants’ understanding of pharmacogenomic research information including results.

I would think about holding group discussions among the potential participants who may be attending the ART [Antiretroviral treatment] clinic on a given day. For example, I could plan a session on one Tuesday, the day when many patients come in, then I give them some information about the study and encourage them to ask questions. This way, some other potential participants can learn from others’ questions but can ask more questions when they choose to join the study

(KII_Female_Researcher _2)

One community representative emphasized the need to identify a family elder or an influential member of a particular family to communicate these results at the family level.

If you want participants and families to own and utilize these results, you may need to identify a key person in that family, someone that is respected and can be listened to by most family members…. If one of their own can describe a given condition, while citing familiar stories, it will be easy for other family members to appreciate the results and own them…

(FGD 1_Male_Community representative 5).

Perceived roles of community stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results

Stakeholders made several suggestions on what they perceived as the roles of the different stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results. They highlighted the contribution of participants, community representatives, researchers, research institutions and research regulators to enhancing community understanding of pharmacogenomic research results.

Researchers asserted that adequate and relevant information about pharmacogenomic research should be clearly provided to research participants and communities throughout the study. However, one researcher emphasized the need to avoid redundant information that may not have meaning to research participants and the community members. Furthermore, they indicated that researchers ought to be knowledgeable and competent to interpret pharmacogenomic results, fully understand their implications and provide a well-explained action plan following the return of results to participants and their communities. Two researchers mentioned that it is their responsibility to share study findings with the national regulatory agencies and RECs to maximize utilization of research findings. They emphasized working together with the Ministry of Health to educate the public about the different roles of genes in the human body.

“What we [researchers] should do is to understand the implications of these results first, before presenting them to the participants, or to their family members. This way, we shall be able to provide answers and appropriate solutions to participants and their family members.

(KII_Male_Researcher_6)

“We have the moral obligation to share all these findings with the Regulatory Authorities and ethics committees, whether primary results information or incidental findings. This information can help guide policy makers on what they may think is crucial to consider about pharmacogenomics in HIV treatment or other genomic studies.

(KII_Male_Researcher_12)

Community representatives indicated that its is their responsibility to guide the research team when assessing the potential social harm and other risks of returning individual pharmacogenomic research results to participants, their families, and community members. They mentioned that it was their responsibility to enhance community members’ understanding of research findings by explaining complex genomic terms using relatable and relevant life stories. They also felt that it was their responsibility to create awareness about pharmacogenomic research and the implications of research findings through sensitization and health campaigns. They argued that health campaigns would help to provide accurate information about pharmacogenomic research and minimize misinformation and misperceptions.

…. You know genetics is a very sensitive topic and many communities have not appreciated these studies right now. There are many incorrect stories and myths about HIV drugs that come up because people respond differently to the ARVs [Antiretroviral drugs]… And some people take their ARVs [Antiretroviral drugs] along with some traditional herbs, which may also affect how their bodies react to the ARVs [Antiretroviral drugs]… so the community representatives should come out and provide accurate information to nullify the myths about how different human bodies respond to ARVs [Antiretroviral drugs]….

(FGD 5_Female_Community representative 1)

REC members highlighted some of their responsibilities in promoting participants’ understanding of pharmacogenomic research results. They stated that it is their role to review research protocols and identify the possible ethical, social, and legal implications of sharing individual pharmacogenomic research results with research participants and their communities. They also pointed out the importance of ensuring that the informed consent documents have accurate information, are simple and written in a language that is easily understandable. They further suggested that researchers should put in place measures to protect participants and families from social harms that may be associated with the results feedback process. REC members also emphasized the need for researchers to submit study-specific dissemination plans for review and approval prior to the commencement of study activities.

“.. The REC’s primary role is to protect participants and their communities from research related harm….. for example we need to ensure that the information given to them is simple, clear and easy to understand because the results can be misinterpreted and cause psychological harm to participants…

(KII_Male_REC Participant #10)

In addition, RECs should provide standardized protocol templates for genetic and genomic studies to guide researchers on the critical ethical aspects of genomic and genetics studies when developing research protocols.

RECs have a role of reviewing and advising investigators how to design informed consent processes and how these results can be safely returned. We can achieve this by standardizing genetics protocol templates for genetics and genomic studies..

(KII_Male_REC Participant #12)

Regarding the role of research participants and community members, stakeholders said that research participants and members of research communities should raise questions and concerns about unclear concepts for clarification during their interactions with research teams. They said that research participants have a role of selecting the kind of results they would wish to receive after full comprehension of the implications of their choices.

We try our level best to build a good relationship with our participants so that they can freely and openly tell us their concerns and aspects they might not have understood. So we expect them to ask questions and also tell us truthful information during our discussions with them

(KII_Female_Researcher_3)

I think research participants have the responsibility to clearly inform the researchers whether they want to receive their results or not. They should also specify the kind of results they would like to receive. They should also let us know whether it is okay to share their results with family members or not

(KII_Male_Researcher_10)

Stakeholders asserted that research institutions should put in place measures to protect research participants and communities from possible social harm that may arise from the result feedback process.

Research institutions should come up with structures and systems that protect participants and communities from possible harm. These institutions should employ full-time genetic counselors to address genetics related questions and concerns to both individual participants and communities, even when the research project has ended.

(IDI_Female_REC member_6)

Stakeholders also felt that research institutions should encourage continuous feedback from research participants and communities even after the study closure, for example using suggestion boxes at the facilities. Further, stakeholders indicated that institutions should engage and /or collaborate with health facilities offering genetic services for a smooth referral of participants and building new relationships at these facilities.

One thing I would request research institutions to do, is to establish collaborations with other health facilities or NGOs that can provide extra support to our participants and their family members after we share these results. You may find that some participants need extra psychological support than just the counseling services we offer here [HIV/AIDS research clinics]

(KII_Female_Researcher_5)

Regarding the role of national research regulators for example the Ministry of Health, UNCST and NDA, stakeholders asserted that the regulators should amplify the need to provide individual results of genomic analyses particularly those that are of clinical significance. Stakeholders also suggested that the national research regulators should develop contextualized guidelines to facilitate a safe return of individual genomic and genetic research results to participants, family members, and research communities.

We currently do not have national guidelines on returning genomic and genetics research results to participants and community members…. Therefore, it is sometimes hard for us REC members to advise researchers on some ethical aspects that may affect participants in any way. So our regulators need to develop these guidelines as soon as possible

(IDI_Male_REC member_12)

Perceived challenges of engaging communities when returning individual results to research participants

Two researchers observed that it might be difficult to determine the most suitable CE approach when engaging community members. They advised that sometimes, the research team needs to be flexible to accommodate more than one approach. This may require a lot of time and financial resources to creatively adapt more than one approach when engaging and communicating pharmacogenomic related -information appropriately without losing scientific meaning.

[….] pharmacogenomic research is already difficult to understand. So the team [research team members] need to be careful when translating this information in plays and songs not to lose the scientific meaning of this research [pharmacogenomic research]….

(KII_Female_Researcher_8)

[….] Sometimes deciding on what language to use when speaking to a group of people is very hard. In Kampala, people speak more than three common languages so the researchers may even get confused on the most suitable language to choose over others.

(FGD 1_Female_Community representative 4)

One third of the community representatives raised concerns about diagnostic misconceptions of genetics and genomics studies.

Right now, there is a lot of ‘noise’ about paternity testing in our communities. Even many labs (laboratories) are making adverts for people to go for paternity testing. Now, when you talk about anything concerning genes, many people’s minds run to testing their children’s paternity….

(FGD 5_Female_Community representative 1)

One REC member said that prioritizing certain kinds of results over others could be challenging to communicate at community level compared to individual level. He felt that it is sometimes difficult to give an answer regarding why emphasis is placed on certain kinds of results while leaving out others.

[.….] I can see it being difficult to explain why researchers are concentrating on certain kinds of results and missing others [results]. They [participants] might think that other results are not important. And, you see, our people are shy. They will fear to ask questions in a group of people.

(KII_Male REC member #12)

Many researchers (08) were concerned about the absence of genetic counselors at their institutions who are skilled in communicating genomic/ genetic information while respecting the community values and beliefs.

I worry about if we [researchers] can communicate these results to our participants effectively. We don’t have genetics counselors in my institution….And I think we may ignore some ethical and social challenges that may affect our people.

(KII_Male_Researcher_6)

Discussion

This study explored the role of community engagement in promoting understanding of individual pharmacogenomic research results among PLHIV. Pharmacogenomic research is paving way for the future of personalized medicine [48, 49], where tailor-made treatment strategies are defined for groups of individuals based on their genetic make-up. Results from pharmacogenomic research may be used to guide clinicians and researchers’ decisions on the appropriate drug and drug dosage required to produce a desirable effect for an individual or groups of people based on their genetic makeup [4]. Similarly, returning these results to PLHIV could help them understand why some people respond to the same drugs differently from others. Participants’ understanding of their genetic make-up encourages adherence to the prescribed treatment, especially among PLHIV with long treatment periods [50, 51]. However, it is imperative that PLHIV attain full understanding of the ethical, legal and social implications before receiving individual results of pharmacogenomic research. This is because these results can lead to social and psychological harm to participants and their family members [32]. Studies have reported the complex nature of genomic terms that are difficult to understand even among the literate populations, low literacy levels in many resource limited settings, and community misconception of linking participation and receiving results from genomic and genetic results to establishing the paternity of children and other family members as contributing factors to participants’ inadequate understanding of pharmacogenomic and genomic information [32, 52–54]. To overcome these challenges, it is important that communities likely to benefit from a genetic or genomic study are actively engaged throughout the study. Respondents agreed that determining a culturally acceptable approach or approaches is an essential step to achieve effective CE. Research teams should select an approach that is creative, flexible and sensitive to participants’ values, beliefs and education levels. Their views are consistent with a study that explored perspectives on returning individual and aggregate genomic research results to study participants and communities in Kenya [55]. Researchers suggested using music, dance and drama as an approach that could enhance communication of understandable information about pharmacogenomic research and results at community level. A study conducted in South Africa used the drama of DNA approach to engage communities reported that drama can be a relatively effective approach in engaging community members when conveying information about ethical and social challenges related to the return of individual genetic research results [56]. Music and drama has been used to convey information related to HIV prevention, and adherence to ARV treatment in Uganda and many parts of sub-Saharan Africa [57–60]. Therefore, research teams might adapt the music and drama approach to communicate understandable information about the implications of findings from pharmacogenomic research since communities of PLHIV are familiar with. However, caution is necessary during the development of music and drama scripts and translation of research information from English to local languages. This is to avoid losing the scientific meaning of how genes interact with medicines. Therefore, the research teams should work together with drama teams in the development of drama scripts to ensure communication of accurate information in a simple manner that is understandable by community members.

Respect for individual’s privacy and confidentiality should be paramount when communicating information about pharmacogenomic research results through music and drama at community level. Upholding participants’ privacy and confidentiality when communicating results from genomic and pharmacogenomic research prevents risks of stigmatizing participants and their families, discrimination, and lack of interest in participating in future genomic and genetic research [61–64]. In order to maintain participants’ privacy and confidentitality, stakeholders mentioned that relatively general but understandable information about pharmacogenomic research results should be provided at the community level, while providing individualized information about the results to participants during one-on-one discussions with the participants.

Researchers also suggested training peer clients to provide additional explanation to participants on how an individual’s genes interact with drugs in a layman’s language. Empowering community members as vessels to explain genomic and genetics to their fellow peers might encourage free and open sharing of feelings about these results. Trained peer-clients also provide social support to fellow peers to overcome fears and misconceptions about findings from genomic and pharmacogenomic research, hence promoting participants’ understanding and ownership of the results. Group education is also another approach that was suggested by researchers to promote participants’ understanding. This approach might provide an opportunity for potential participants to ask questions based on the background information given during the group discussions thus enabling their fellow peers to learn from the explanations provided by the researchers. It is important to note that participants who might not be comfortable raising certain questions during the group discussion are still able to ask their questions during their individual meetings with the research teams.

Respondents also suggested the need to engage genetic counselors when determining an appropriate communication method of returning these results to communities. Currently, there are few genetic counselors in some sub-Saharan African countries while others do not have any genetic cousellor, yet genomic research in rapidly increasing in Sub-Saharan Africa [65, 66]. Genetic counselors are skilled professionals in providing scientific information about genomic and genetics and social support to participants involved in genomic research. Therefore, research institutions should develop capacity of genetic counselors to support the process of returning individual pharmacogenomic research results.

Respondents also suggested that research insitutions should hold regular and ongoing discussions about genomic and genetic research. The institutions may develop a consistent schedule for discussions about genomic research as an opportunity for participants to appreciate the relevance of genes in an individual’s body and implications of receiving individual pharmacogenomic research results. However, some research institutions in developing countries might face challenges with limited funding to achieve effective community engagement. Therefore, research institutions may solicit financial support from the government and non-government agencies to achieve effective community engagement.

Lastly, key stakeholders for example researchers, REC members, and community representatives involved in pharmacogenomic research have a role in ensuring that participants adequately understand the implication of genomic and pharmacogenomic research results before they are returned to them. Researchers should report study findings to the national research regulators and policy-makers to jointly develop appropriate strategies of sensitizing communities about the various roles of genes in the human body, thus promoting participants’ understanding of geneomic and pharmacogenomic research. Researchers, together with other stakeholders should protect participants and research communities from possible harm that might arise from returning individual pharmacogenomic research results to participants. In addition, researchers should sensitize communities about the various functions of genes in an individual’s body. This may help community members to overcome misconceptions about of receiving results from genomic and pharmacogenomic research studies. Similarly, community representatives should also encourage sharing of correct information about genomic research to demistify the existing diagnostic misconceptions in communities. Community representatives and research participants should raise concerns or questions on unclear information about genomic and pharmacogenomic research and the implications of the results on their lives. Research regulators should develop guidelines and frameworks that facilitate adequate understanding of genomic and pharmacogenomic results at the individual and community levels.

Our study had some limititations. Some interviews were conducted virtually via Zoom due to the COVID-19 pandemic, whose mitigation measures restricted face-to-face interactions. Thus, the authors were not able to capture non-verbal communication for some respondents. Sometimes, the research team experienced challenges with network connectivity. However, zoom interviews were substituted with telephone calls and respondents were encouraged to share additional information via email after the interviews.

Conclusion

Our findings show that there is a consensus among the different stakeholders that CE can play a vital role in promoting research participants’ understanding of individual pharmacogenomic research results. Respondents mentioned several CE approaches including adapting existing music, dance and drama clubs, group education and training peer clients to communicate understandable information about pharmacogenomic research and the implications of its results to research communities. However, these approaches should comply to the ethical standards of conducting research such as respect of participants’ privacy and confidentiality. We recommend further research to explore the feasibility of using the existing CE approaches to communicate simple and understandable information and the implications of the results to research participants at community level. Of concern, respondents emphasized the need to engage genetic counselors when determining the suitable approach or approaches to achieve meaningful community engagement, yet many research instititutions conducting genomic research do not have genetic counselors. We recommend building capacity for genetic counselors in Uganda and other sub-Saharan countries where genomic and genetics research is conducted. We also recommend developing a framework that respects individuals and community interests, values and literacy levels when communicating the pharmacogenomic research information and results at individual and community levels.

Supporting information

S1 Dataset

(DOCX)

pone.0299081.s001.docx^{(85.9KB, docx)}

S2 Dataset

(DOCX)

pone.0299081.s002.docx^{(24.6KB, docx)}

S3 Dataset

(DOCX)

pone.0299081.s003.docx^{(40KB, docx)}

Acknowledgments

The authors would like to acknowledge the assistance offered by the Faculty at Berman Institute of Bioethics, Johns Hopkins University and the Faculty of Makerere University International Bioethics who contributed to the study design and interpretation of the results.

Data Availability

All relevant data are within the manuscript and its Supporting information files.

Funding Statement

This study was funded by the Fogarty International Center of the National Institute of Health through the Makerere University International Bioethics Research Training Program Grant Number D43TW010892. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

1.Aminkeng F., et al., Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent. 2014. 14(2): p. 160–170. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Dandara C., et al., African pharmacogenomics consortium: consolidating pharmacogenomics knowledge, capacity development and translation in Africa. 2019. 2(19): p. 19. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Calcagno A., et al., The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study. 2019. 106(2): p. 450–457. [DOI] [PubMed] [Google Scholar]
4.Mukonzo J.K., et al., Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes. 2014. 9(1): p. e86919. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Ngaimisi E., et al., Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations. 2013. 8(7): p. e67946. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Loarec A., et al., Extremely low hepatitis C prevalence among HIV co-infected individuals in four countries in sub-Saharan Africa. AIDS (London, England), 2019. 33(2): p. 353–355. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Korol S., et al., Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants. 2013. 14(6): p. 675–688. [DOI] [PubMed] [Google Scholar]
8.Cassa C.A., et al., Disclosing pathogenic genetic variants to research participants: quantifying an emerging ethical responsibility. 2012. 22(3): p. 421–428. [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Tabor H.K., et al., Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. 2011, Wiley Online Library. p. 2916–2924. [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Meacham M.C., et al., Researcher perspectives on disclosure of incidental findings in genetic research. 2010. 5(3): p. 31–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Barrio-Hernandez I., et al., Network expansion of genetic associations defines a pleiotropy map of human cell biology. 2023: p. 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Middleton A., et al., Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research. 2016. 24(1): p. 21–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Ralefala D., et al., Participants’ Preferences and Reasons for Wanting Feedback of Individual Genetic Research Results From an HIV-TB Genomic Study: A Case Study From Botswana. 2021. 16(5): p. 525–536. [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Matshabane O.P., et al., Preferences and expectations of feedback of individual genetic research results in African genomics: Views of South African parents of children with neurodevelopmental disorders. 2022. 5(41): p. 41. [Google Scholar]
15.Nabukenya S., et al., Research Participants’ Preferences for Individual Results of Pharmacogenomics Research: A Case of a Ugandan HIV Research Institute. 2023: p. 15562646231187434. [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Just K.S., et al., Medical education in pharmacogenomics—results from a survey on pharmacogenetic knowledge in healthcare professionals within the European pharmacogenomics clinical implementation project Ubiquitous Pharmacogenomics (U-PGx). 2017. 73: p. 1247–1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Moaddeb J., Mills R., and Haga S.B. J.J.o.t.A.P.A., Community pharmacists’ experience with pharmacogenetic testing. 2015. 55(6): p. 587–594. doi: 10.1331/JAPhA.2015.15017 [DOI] [PubMed] [Google Scholar]
18.Haga S.B., et al., Primary care providers’ use of pharmacist support for delivery of pharmacogenetic testing. 2017. 18(4): p. 359–367. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Haga S.B., et al., Incorporation of pharmacogenetic testing into medication therapy management. 2015. 16(17): p. 1931–1941. [DOI] [PubMed] [Google Scholar]
20.Lee Y.M., et al., Assessment of patient perceptions of genomic testing to inform pharmacogenomic implementation. 2017. 27(5): p. 179. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Van Der Merwe N., Ramesar R., and De Vries J. J.F.i.G., Whole exome sequencing in South Africa: Stakeholder views on return of individual research results and incidental findings. 2022. 13: p. 912. doi: 10.3389/fgene.2022.864822 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Mwaka E.S., et al., Researchers’ perspectives on return of individual genetics results to research participants: a qualitative study. 2021. 32(1): p. 15–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Middleton A., et al., ‘Your DNA, Your Say’: global survey gathering attitudes toward genomics: design, delivery and methods. 2018. 15(04): p. 311–318. [DOI] [PubMed] [Google Scholar]
24.Nabukenya S., An assessment of understanding of information provided in genetic research among people living with HIV at the Infectious Diseases Institute (IDI). 2019, Makerere University. [Google Scholar]
25.Tindana P., et al., Developing the science and methods of community engagement for genomic research and biobanking in Africa. 2017. 2: p. e13. [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Molyneux S. and Bull S.J. J.o.E.R.o.H.R.E., Consent and community engagement in diverse research contexts: Reviewing and developing research and practice: Participants in the community engagement and consent workshop, Kilifi, Kenya, March 2011. 2013. 8(4): p. 1–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Mashinya F., et al., Community engagement in Genomics research; Challenges and lessons learnt in the AWI-Gen study at Dikgale Health and Demographic Surveillance System (HDSS) Site, South Africa. 2020. 3(38): p. 38. [Google Scholar]
28.Tindana P., et al., Community engagement strategies for genomic studies in Africa: a review of the literature. 2015. 16: p. 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.UNCST, Uganda National Council for Science and Technology: National Guidelines for Community Engagement in Research. https://www.uncst.go.ug/details.php?option=smenu&id=6&Research%20Management%20Policies,%20Guidelines%20and%20Regulations.html, 2022.
30.Heredia N.I., et al., Community perceptions of biobanking participation: a qualitative study among Mexican-Americans in three Texas cities. 2017. 20(1): p. 46–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Lemke A.A., et al., Addressing underrepresentation in genomics research through community engagement. 2022. 109(9): p. 1563–1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
32.Ochieng J., et al., Feedback of individual genetic and genomics research results: A qualitative study involving grassroots communities in Uganda. 2022. 17(11): p. e0267375. [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Butterfield P., Qualitative research strategies and methods in health care settings. Journal of healthcare education and training: the journal of the American Society for Healthcare Education and Training, 1989. 4(2): p. 15–21. [PubMed] [Google Scholar]
34.Mays N. and Pope C., Assessing quality in qualitative research. Bmj, 2000. 320(7226): p. 50–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Pope C., et al., Qualitative methods in research on healthcare quality. 2002. 11(2): p. 148–152. [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Godard B., et al., Ethnocultural community leaders’ views and perceptions on biobanks and population specific genomic research: a qualitative research study. Public Understanding of Science, 2009. 19(4): p. 469–485. [DOI] [PubMed] [Google Scholar]
37.Haga S.B., et al., Public attitudes toward ancillary information revealed by pharmacogenetic testing under limited information conditions. 2011. 13(8): p. 723–728. [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Bollinger J.M., et al., Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. 2012. 14(4): p. 451–457. [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Fernandez C.V., et al., Attitudes of parents toward the return of targeted and incidental genomic research findings in children. 2014. 16(8): p. 633–640. [DOI] [PubMed] [Google Scholar]
40.Ramoni R.B., et al., Experiences and attitudes of genome investigators regarding return of individual genetic test results. 2013. 15(11): p. 882–887. [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Lohn Z., et al., Genetics professionals’ perspectives on reporting incidental findings from clinical genome‐wide sequencing. 2013. 161(3): p. 542–549. [DOI] [PubMed] [Google Scholar]
42.Heaney C., et al., Researcher practices on returning genetic research results. 2010. 14(6): p. 821–827. [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Klitzman R., et al., Researchers’ views on return of incidental genomic research results: qualitative and quantitative findings. 2013. 15(11): p. 888–895. [DOI] [PMC free article] [PubMed] [Google Scholar]
44.Fereday J. and Muir-Cochrane E., Demonstrating rigor using thematic analysis: A hybrid approach of inductive and deductive coding and theme development. International journal of qualitative methods, 2006. 5(1): p. 80–92. [Google Scholar]
45.Braun V. and Clarke V., Using thematic analysis in psychology. Qualitative research in psychology, 2006. 3(2): p. 77–101. [Google Scholar]
46.International-Pty-Ltd, Q., NVivo qualitative data analysis software (Version 12) [Computer software]. 2018. [Google Scholar]
47.Kaplan B., et al., A culture of understanding: reflections and suggestions from a genomics research community board. 2017. 11(2): p. 161. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Gemmati D., et al., “Bridging the gap” everything that could have been avoided if we had applied gender medicine, pharmacogenetics and personalized medicine in the gender-omics and sex-omics era. 2019. 21(1): p. 296. [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Vizirianakis I.S.J.D.D. and T.V.I.P.S. Publishing, Advancement of pharmacogenomics toward pharmacotyping in drug prescription: Concepts, challenges, and perspectives for personalized medicine. 2014: p. 893–952. [Google Scholar]
50.Tostmann A., et al., Antituberculosis drug‐induced hepatotoxicity: concise up‐to‐date review. 2008. 23(2): p. 192–202. [DOI] [PubMed] [Google Scholar]
51.Hosseinipour M.C., et al., Emergence of HIV drug resistance during first-and second-line antiretroviral therapy in resource-limited settings. 2013. 207(suppl_2): p. S49–S56. [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Kampourakis K., et al., Key challenges for next‐generation pharmacogenomics: Science & Society series on Science and Drugs. 2014. 15(5): p. 472–476. [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Veilleux S., Bouffard M., and Bourque Bouliane M.J.Q.H.R., Patient and health care provider needs and preferences in understanding pharmacogenomic and genomic testing: a meta-data analysis. 2020. 30(1): p. 43–59. [DOI] [PubMed] [Google Scholar]
54.Determeyer P., et al., Application of the community dialogues method to identify ethical values and priorities related to pharmacogenomics. 2021. 22(11): p. 693–701. [DOI] [PubMed] [Google Scholar]
55.Kisiangani I., et al., Perspectives on returning individual and aggregate genomic research results to study participants and communities in Kenya: a qualitative study. 2022. 23(1): p. 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
56.Faure M.C., Wonkam A., and De Vries J.J.O.R.A., Using the drama of DNA approach to community engagement in genomic research in South Africa: experiences and lessons learnt. 2020. 3(1): p. 1. [Google Scholar]
57.Bogart L.M., et al., A pilot test of game changers, a social network intervention to empower people with HIV to be prevention advocates in Uganda. 2020. 24: p. 2490–2508. [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Mendelsohn J.B., et al., Reducing HIV-related stigma among young people attending school in Northern Uganda: study protocol for a participatory arts-based population health intervention and stepped-wedge cluster-randomized trial. 2022. 23(1): p. 1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Uwah C. J.S.-J.J.o.S.A.o.H.A., The role of culture in effective HIV/AIDS communication by theatre in South Africa. 2013. 10(3–4): p. 140–149. doi: 10.1080/17290376.2014.903809 [DOI] [PMC free article] [PubMed] [Google Scholar]
60.Robert Walker G., Pulsing bodies and embodying pulse: musical effervescence in a South African HIV/AIDS community outreach program. Anthropology & Medicine, 2022. 29(3): p. 289–304. [DOI] [PubMed] [Google Scholar]
61.Millum J., et al., Ethical challenges in global health-related stigma research. 2019. 17: p. 1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
62.Shabani M., et al., Oversight of genomic data sharing: what roles for ethics and data access committees? 2017. 15(5): p. 469–474. [DOI] [PubMed] [Google Scholar]
63.Shabani M., Bezuidenhout L., and Borry P. J.E.r.o.m.d., Attitudes of research participants and the general public towards genomic data sharing: a systematic literature review. 2014. 14(8): p. 1053–1065. doi: 10.1586/14737159.2014.961917 [DOI] [PubMed] [Google Scholar]
64.Beaton A., et al., Engaging Māori in biobanking and genomic research: a model for biobanks to guide culturally informed governance, operational, and community engagement activities. 2017. 19(3): p. 345–351. [DOI] [PubMed] [Google Scholar]
65.Kasule M., et al., Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana. 2022. 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
66.Ochieng J., et al., Perspectives and experiences of researchers regarding feedback of incidental genomic research findings: A qualitative study. 2022. 17(8): p. e0273657. [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0299081.r001

Decision Letter 0

Tahir Turk

11 Oct 2023

PONE-D-23-22714The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatmentPLOS ONE

Dear Dr. Nabukenya,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

hank you for the opportunity to review your study. We see this as an important area of investigation for dealing with a major pandemic threat. in this regard the manuscript was reviewed by an expert in the area who has provided comprehensive feedback, to which l concur, on a number of issues that will need to be addressed if the manuscript will be accepted for publishing at PLOS ONE. If you choose to resubmit we request that you carefully note the comments by the reviewer below, and address each issue in your resubmission. Alternatively, you may consider submitting to another journal. If you choose to resubmit, please submit your revised manuscript by Nov 25 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tahir Turk, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.

Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services. If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

Upon resubmission, please provide the following:

The name of the colleague or the details of the professional service that edited your manuscript

A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

"This study was funded by the Fogarty International Center of the National Institute of Health through the Makerere University International Bioethics Research Training Program Grant Number D43TW010892. The authors would like to acknowledge the assistance offered by the Faculty at Berman Institute of Bioethics, Johns Hopkins University and the Faculty of Makerere University International Bioethics who contributed to the study design and interpretation of the results. Waitt C is funded by Wellcome Trust Clinical Research Career Development Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."

We note that you have provided funding information that is currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

"This study was funded by the Fogarty International Center of the National Institute of Health through the Makerere University International Bioethics Research Training Program Grant Number D43TW010892. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

5. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to review your study. I welcome more literature to bolster Community Engagement practices in different parts of public health and the HIV response.

The study design is adequate, as are the data collection and analysis sections. I do have some recommendations that might increase the study's impact.

#1) Differentiate with responses. When I conduct focus groups, I usually have a design that differentiates people's roles to different focus groups. This way I can look at comparisons across groups with norms and concerns. You've presented the data as if all respondents - researchers, ethics committee members, and community members - all agree across every issue.

#2) Identify what is important in the study and lean into it. You're providing stories on how various actors feel about concepts of community engagement. The report back on findings seems dry, and basically is reduced to "Community Engagement is important." Why and how are key questions that you do not approach directly.

#3) Avoid jargon. While you discuss pharmacogenomic research, it is often jargon. What makes this kind of research important for people living with HIV and who decides it's important? What are the ramifications of the research? There are times when you seem to conflate research with clinical practice (e.g. the individual wants their data from research). How is this possible? You make an assumption that all readers are up to date in this part of the field.

#4) Barriers to Community Engagement are not identified. This is odd, as most researchers will discuss their frustrations openly (e.g. funding requirements, time, lack of expertise) yet there was little of that here (outside of language). Other barriers could be highlighted more.

Thank you for the opportunity to review your study.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 Apr 2;19(4):e0299081. doi: 10.1371/journal.pone.0299081.r002

Author response to Decision Letter 0

3 Dec 2023

22 November 2023

Academic Editor,

PLOS ONE Journal

Dear Dr Tahir Turk,

RE: Response to reviewers’ comments.

On behalf of the authors, I take this opportunity to appreciate you and the reviewers for sparing time to review and provide insightful feedback to improve the quality of our manuscript entitled “The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment” PONE-D-23-22714 for consideration by the PLOS ONE journal.

I hereby submit a point-by-point response to the peer review comments of the above named manuscript (attached).

We have positively responded to all the concerns raised by the reviewers and we believe that their feedback has greatly improved the quality of our work and readability of our manuscript.

Yours sincerely,

Sylvia Nabukenya

Email: nabukenyas89@gmail.com

RESPONSE TO ADDITIONAL JOURNAL REQUIREMENTS

ID COMMENTS RESPONSES

01 Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Thank you very much for raising this comment and providing the links to the style templates. We have revised the format of the manuscript as guided.

02 We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.

Upon resubmission, please provide the following:

The name of the colleague or the details of the professional service that edited your manuscript Thank you very much for raising this comment. We acknowledge that the version of the manuscript that was initially submitted had several spelling and grammatical errors. However, the authors have proof-read the revised manuscript and also sought an independent review from a colleague, Dr. Jerome Roy Semakula who recently excelled in his IELTS exam.

03 We note that you have provided funding information that is currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Thank you very much for raising this comment. We have deleted the funding information from the acknowledgment section in the revised manuscript. Thank you once again for the correction.

We request to maintain the funding information in the Funding Statement section of the online submission form

04 In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. Thank you for raising this comment. We appreciate the spirit of sharing data for replication of the reported study findings and other benefits of data sharing. The data has been reported as quotes in the results section of the manuscript. This is the minimal data set used to reach the conclusions described in the manuscript.

05 We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Thank you very much for raising this concern. I have provided the minimal data set as quotes reported in the results section of the manuscript.

RESPONSES TO PEER REVIEW COMMENTS

ID COMMENT RESPONSES Page Line

01 Differentiate with responses. When I conduct focus groups, I usually have a design that differentiates people's roles to different focus groups. This way I can look at comparisons across groups with norms and concerns. You've presented the data as if all respondents - researchers, ethics committee members, and community members - all agree across every issue.

Thank you very for raising this comment. This comment has helped us realize that we needed to clarify how the data were collected across the different study populations. We conducted focus group discussions with community representatives from five research institutions offering care and treatment to people living with HI. We also conducted key informant interviews with researchers involved in pharmacogenomic research and HIV treatment and in-depth interviews with members of research ethics committees who had prior experience in reviewing pharmacogenomic research for HIV treatment. We do agree with you that all the above categories of respondents have different roles and that their feedback has been presented with their roles. We have followed your recommendation on how to present the results and the discussion of our findings. The contributions from each category of the respondents have been well labelled at the end of each quote in the results section. 16 -29 NA

02 Identify what is important in the study and lean into it. You're providing stories on how various actors feel about concepts of community engagement. The report back on findings seems dry, and basically is reduced to "Community Engagement is important." Why and how are key questions that you do not approach directly. Thank you very much for raising this comment. We have followed your recommendation to focus on the research question when discussing our findings. We have provided detailed information to why and how community engagement plays an important role in promoting participants’ understanding of pharmacogenomic research results. 29-33 N/A

03 Avoid jargon. While you discuss pharmacogenomic research, it is often jargon. What makes this kind of research important for people living with HIV and who decides it's important? What are the ramifications of the research? There are times when you seem to conflate research with clinical practice (e.g. the individual wants their data from research). How is this possible? You make an assumption that all readers are up to date in this part of the field. Thank you very much for raising this comment. This comment has helped us realize that we needed to revise our discussion section. We have provided more detail about the importance of pharmacogenomic research to PLHIV and the researchers involved in the treatment of HIV/AIDS. We have also provided details on the ramifications of this research and tried to explain what pharmacogenomic research is to avoid jargon. 29-33 N/A

04 Barriers to Community Engagement are not identified. This is odd, as most researchers will discuss their frustrations openly (e.g. funding requirements, time, lack of expertise) yet there was little of that here (outside of language). Other barriers could be highlighted more. We have also provided information about other challenges that researchers experience when engaging communities in addition to some of them that were already mentioned. For example the absence of genetic counsellors who may be the most suitable professionals to determine the safe approaches and methods of communicating genomic and pharmacogenomic research information in different communities. In addition, we have added information about the limited funding for community engagement activities in some research institutions. 32 624-625

05 Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement Thank you very much for your feedback. We have revised the acknowledgment section as advised. 34 670-672

Attachment

Submitted filename: Responses to reviewers.docx

pone.0299081.s004.docx^{(19.5KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0299081.r003

Decision Letter 1

Tahir Turk

13 Dec 2023

PONE-D-23-22714R1The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatmentPLOS ONE

Dear Dr. Nabukenya,

Please submit your revised manuscript by Jan 27 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Tahir Turk, PhD

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Dr Nabukenya

Thank-you for addressing the reviewer feedback on your manuscript and making amendments on the funding statement and acknowledgements. However, when submitting a manuscript, authors must provide a Data Availability Statement describing compliance with PLOS' data policy. If the article is accepted for publication, the Data Availability Statement will be published as part of the article. PLOS believes that sharing data fosters scientific progress. Data availability allows and facilitates:

- Validation, replication, reanalysis, new analysis, reinterpretation or inclusion into meta-analyses;

- Reproducibility of research;

- Efforts to ensure data are archived, increasing the value of the investment made in funding scientific research;

- Reduction of the burden on authors in preserving and finding old data, and managing data access requests;

- Citation and linking of research data and their associated articles, enhancing visibility and ensuring recognition for authors, data producers and curators.

Acceptable data sharing methods are listed in PLSO ONE's Data Availability information section https://journals.plos.org/plosone/s/data-availability, which provides guidance for authors as to what must be included in their Data Availability Statement and how to follow best practices in research reporting. Publication is conditional on compliance with this policy. Therefore, PLOS strongly recommends sharing data in a repository whenever possible. Data repositories improve discoverability and accessibility, ensure long-term preservation, and lead to increased attention for the research. The Minimal Data Set Definition consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods. Additionally, PLOS requires that authors comply with field-specific standards for preparation, recording, and deposition of data when applicable.

Given these requirements we believe the dFGD data-set and the KIIs and IDI datasets from your study should be provided in a public data repository with relevant DOI identifiers. Failing compliance with the minimal dat set requirements, will mean your manuscript cannot be accepted for publishing by our Journal.

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

PLoS One. 2024 Apr 2;19(4):e0299081. doi: 10.1371/journal.pone.0299081.r004

Author response to Decision Letter 1

4 Jan 2024

2 January 2024

Academic Editor,

PLOS ONE Journal

Dear Dr Tahir Turk,

RE: Response to reviewers’ comments.

I hereby submit a point-by-point response to the peer review comments of the above named manuscript (attached).

We have positively responded to all the concerns raised by the reviewers and we believe that their feedback has greatly improved the quality and readability of our manuscript.

Yours sincerely,

Sylvia Nabukenya

Email: nabukenyas89@gmail.com

RESPONSE TO ADDITIONAL JOURNAL REQUIREMENTS

ID COMMENTS RESPONSES

01 Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Thank you very much for raising this comment and providing the links to the style templates. We have revised the format of the manuscript as guided.

Upon resubmission, please provide the following:

We request to maintain the funding information in the Funding Statement section of the online submission form

04 In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. Thank you for raising this comment. We appreciate the spirit of sharing data for replication of the reported study findings and other benefits of data sharing. The minimal data sets used to reach the conclusions described in the manuscript will be provided once accepted for publication.

05 We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Thank you very much for raising this comment. Once the manuscript is accepted for publication, we shall provide the dFGD, KIIs and IDI data sets.

RESPONSES TO PEER REVIEW COMMENTS

ID COMMENT RESPONSES Page Line

Attachment

Submitted filename: Responses to reviewers.docx

pone.0299081.s005.docx^{(19.6KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0299081.r005

Decision Letter 2

Tahir Turk

6 Feb 2024

The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment

PONE-D-23-22714R2

Dear Dr.Nabukenya,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tahir Turk, PhD

Academic Editor

PLOS ONE

Additional Editor Comments

Thank-you for addressing the concerns of the reviewer in the revised manuscript. Although we note that the authors have not included a COREQ or similar qualitative research checklist with the manuscript we note that a number of the checklist requirements have been addressed through the revision. We are also pleased to see practical and pragmatic recommendations emanating from the study.

Reviewers' Comments to the Author

Reviewer #1: Thank you for addressing my concerns in my review. I found the current version of the study to be interesting and compelling. All comments have been addressed

**********

PLoS One. doi: 10.1371/journal.pone.0299081.r006

Acceptance letter

Tahir Turk

22 Mar 2024

PONE-D-23-22714R2

PLOS ONE

Dear Dr. Nabukenya,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Tahir Turk

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Dataset

(DOCX)

pone.0299081.s001.docx^{(85.9KB, docx)}

S2 Dataset

(DOCX)

pone.0299081.s002.docx^{(24.6KB, docx)}

S3 Dataset

(DOCX)

pone.0299081.s003.docx^{(40KB, docx)}

Attachment

Submitted filename: Responses to reviewers.docx

pone.0299081.s004.docx^{(19.5KB, docx)}

Attachment

Submitted filename: Responses to reviewers.docx

pone.0299081.s005.docx^{(19.6KB, docx)}

Data Availability Statement

All relevant data are within the manuscript and its Supporting information files.

[pone.0299081.ref001] 1.Aminkeng F., et al., Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent. 2014. 14(2): p. 160–170. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref002] 2.Dandara C., et al., African pharmacogenomics consortium: consolidating pharmacogenomics knowledge, capacity development and translation in Africa. 2019. 2(19): p. 19. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref003] 3.Calcagno A., et al., The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study. 2019. 106(2): p. 450–457. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref004] 4.Mukonzo J.K., et al., Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes. 2014. 9(1): p. e86919. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref005] 5.Ngaimisi E., et al., Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations. 2013. 8(7): p. e67946. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref006] 6.Loarec A., et al., Extremely low hepatitis C prevalence among HIV co-infected individuals in four countries in sub-Saharan Africa. AIDS (London, England), 2019. 33(2): p. 353–355. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref007] 7.Korol S., et al., Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants. 2013. 14(6): p. 675–688. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref008] 8.Cassa C.A., et al., Disclosing pathogenic genetic variants to research participants: quantifying an emerging ethical responsibility. 2012. 22(3): p. 421–428. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref009] 9.Tabor H.K., et al., Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. 2011, Wiley Online Library. p. 2916–2924. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref010] 10.Meacham M.C., et al., Researcher perspectives on disclosure of incidental findings in genetic research. 2010. 5(3): p. 31–41. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref011] 11.Barrio-Hernandez I., et al., Network expansion of genetic associations defines a pleiotropy map of human cell biology. 2023: p. 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref012] 12.Middleton A., et al., Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research. 2016. 24(1): p. 21–29. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref013] 13.Ralefala D., et al., Participants’ Preferences and Reasons for Wanting Feedback of Individual Genetic Research Results From an HIV-TB Genomic Study: A Case Study From Botswana. 2021. 16(5): p. 525–536. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref014] 14.Matshabane O.P., et al., Preferences and expectations of feedback of individual genetic research results in African genomics: Views of South African parents of children with neurodevelopmental disorders. 2022. 5(41): p. 41. [Google Scholar]

[pone.0299081.ref015] 15.Nabukenya S., et al., Research Participants’ Preferences for Individual Results of Pharmacogenomics Research: A Case of a Ugandan HIV Research Institute. 2023: p. 15562646231187434. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref016] 16.Just K.S., et al., Medical education in pharmacogenomics—results from a survey on pharmacogenetic knowledge in healthcare professionals within the European pharmacogenomics clinical implementation project Ubiquitous Pharmacogenomics (U-PGx). 2017. 73: p. 1247–1252. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref017] 17.Moaddeb J., Mills R., and Haga S.B. J.J.o.t.A.P.A., Community pharmacists’ experience with pharmacogenetic testing. 2015. 55(6): p. 587–594. doi: 10.1331/JAPhA.2015.15017 [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref018] 18.Haga S.B., et al., Primary care providers’ use of pharmacist support for delivery of pharmacogenetic testing. 2017. 18(4): p. 359–367. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref019] 19.Haga S.B., et al., Incorporation of pharmacogenetic testing into medication therapy management. 2015. 16(17): p. 1931–1941. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref020] 20.Lee Y.M., et al., Assessment of patient perceptions of genomic testing to inform pharmacogenomic implementation. 2017. 27(5): p. 179. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref021] 21.Van Der Merwe N., Ramesar R., and De Vries J. J.F.i.G., Whole exome sequencing in South Africa: Stakeholder views on return of individual research results and incidental findings. 2022. 13: p. 912. doi: 10.3389/fgene.2022.864822 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref022] 22.Mwaka E.S., et al., Researchers’ perspectives on return of individual genetics results to research participants: a qualitative study. 2021. 32(1): p. 15–33. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref023] 23.Middleton A., et al., ‘Your DNA, Your Say’: global survey gathering attitudes toward genomics: design, delivery and methods. 2018. 15(04): p. 311–318. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref024] 24.Nabukenya S., An assessment of understanding of information provided in genetic research among people living with HIV at the Infectious Diseases Institute (IDI). 2019, Makerere University. [Google Scholar]

[pone.0299081.ref025] 25.Tindana P., et al., Developing the science and methods of community engagement for genomic research and biobanking in Africa. 2017. 2: p. e13. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref026] 26.Molyneux S. and Bull S.J. J.o.E.R.o.H.R.E., Consent and community engagement in diverse research contexts: Reviewing and developing research and practice: Participants in the community engagement and consent workshop, Kilifi, Kenya, March 2011. 2013. 8(4): p. 1–18. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref027] 27.Mashinya F., et al., Community engagement in Genomics research; Challenges and lessons learnt in the AWI-Gen study at Dikgale Health and Demographic Surveillance System (HDSS) Site, South Africa. 2020. 3(38): p. 38. [Google Scholar]

[pone.0299081.ref028] 28.Tindana P., et al., Community engagement strategies for genomic studies in Africa: a review of the literature. 2015. 16: p. 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref029] 29.UNCST, Uganda National Council for Science and Technology: National Guidelines for Community Engagement in Research. https://www.uncst.go.ug/details.php?option=smenu&id=6&Research%20Management%20Policies,%20Guidelines%20and%20Regulations.html, 2022.

[pone.0299081.ref030] 30.Heredia N.I., et al., Community perceptions of biobanking participation: a qualitative study among Mexican-Americans in three Texas cities. 2017. 20(1): p. 46–57. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref031] 31.Lemke A.A., et al., Addressing underrepresentation in genomics research through community engagement. 2022. 109(9): p. 1563–1571. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref032] 32.Ochieng J., et al., Feedback of individual genetic and genomics research results: A qualitative study involving grassroots communities in Uganda. 2022. 17(11): p. e0267375. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref033] 33.Butterfield P., Qualitative research strategies and methods in health care settings. Journal of healthcare education and training: the journal of the American Society for Healthcare Education and Training, 1989. 4(2): p. 15–21. [PubMed] [Google Scholar]

[pone.0299081.ref034] 34.Mays N. and Pope C., Assessing quality in qualitative research. Bmj, 2000. 320(7226): p. 50–52. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref035] 35.Pope C., et al., Qualitative methods in research on healthcare quality. 2002. 11(2): p. 148–152. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref036] 36.Godard B., et al., Ethnocultural community leaders’ views and perceptions on biobanks and population specific genomic research: a qualitative research study. Public Understanding of Science, 2009. 19(4): p. 469–485. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref037] 37.Haga S.B., et al., Public attitudes toward ancillary information revealed by pharmacogenetic testing under limited information conditions. 2011. 13(8): p. 723–728. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref038] 38.Bollinger J.M., et al., Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. 2012. 14(4): p. 451–457. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref039] 39.Fernandez C.V., et al., Attitudes of parents toward the return of targeted and incidental genomic research findings in children. 2014. 16(8): p. 633–640. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref040] 40.Ramoni R.B., et al., Experiences and attitudes of genome investigators regarding return of individual genetic test results. 2013. 15(11): p. 882–887. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref041] 41.Lohn Z., et al., Genetics professionals’ perspectives on reporting incidental findings from clinical genome‐wide sequencing. 2013. 161(3): p. 542–549. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref042] 42.Heaney C., et al., Researcher practices on returning genetic research results. 2010. 14(6): p. 821–827. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref043] 43.Klitzman R., et al., Researchers’ views on return of incidental genomic research results: qualitative and quantitative findings. 2013. 15(11): p. 888–895. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref044] 44.Fereday J. and Muir-Cochrane E., Demonstrating rigor using thematic analysis: A hybrid approach of inductive and deductive coding and theme development. International journal of qualitative methods, 2006. 5(1): p. 80–92. [Google Scholar]

[pone.0299081.ref045] 45.Braun V. and Clarke V., Using thematic analysis in psychology. Qualitative research in psychology, 2006. 3(2): p. 77–101. [Google Scholar]

[pone.0299081.ref046] 46.International-Pty-Ltd, Q., NVivo qualitative data analysis software (Version 12) [Computer software]. 2018. [Google Scholar]

[pone.0299081.ref047] 47.Kaplan B., et al., A culture of understanding: reflections and suggestions from a genomics research community board. 2017. 11(2): p. 161. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref048] 48.Gemmati D., et al., “Bridging the gap” everything that could have been avoided if we had applied gender medicine, pharmacogenetics and personalized medicine in the gender-omics and sex-omics era. 2019. 21(1): p. 296. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref049] 49.Vizirianakis I.S.J.D.D. and T.V.I.P.S. Publishing, Advancement of pharmacogenomics toward pharmacotyping in drug prescription: Concepts, challenges, and perspectives for personalized medicine. 2014: p. 893–952. [Google Scholar]

[pone.0299081.ref050] 50.Tostmann A., et al., Antituberculosis drug‐induced hepatotoxicity: concise up‐to‐date review. 2008. 23(2): p. 192–202. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref051] 51.Hosseinipour M.C., et al., Emergence of HIV drug resistance during first-and second-line antiretroviral therapy in resource-limited settings. 2013. 207(suppl_2): p. S49–S56. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref052] 52.Kampourakis K., et al., Key challenges for next‐generation pharmacogenomics: Science & Society series on Science and Drugs. 2014. 15(5): p. 472–476. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref053] 53.Veilleux S., Bouffard M., and Bourque Bouliane M.J.Q.H.R., Patient and health care provider needs and preferences in understanding pharmacogenomic and genomic testing: a meta-data analysis. 2020. 30(1): p. 43–59. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref054] 54.Determeyer P., et al., Application of the community dialogues method to identify ethical values and priorities related to pharmacogenomics. 2021. 22(11): p. 693–701. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref055] 55.Kisiangani I., et al., Perspectives on returning individual and aggregate genomic research results to study participants and communities in Kenya: a qualitative study. 2022. 23(1): p. 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref056] 56.Faure M.C., Wonkam A., and De Vries J.J.O.R.A., Using the drama of DNA approach to community engagement in genomic research in South Africa: experiences and lessons learnt. 2020. 3(1): p. 1. [Google Scholar]

[pone.0299081.ref057] 57.Bogart L.M., et al., A pilot test of game changers, a social network intervention to empower people with HIV to be prevention advocates in Uganda. 2020. 24: p. 2490–2508. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref058] 58.Mendelsohn J.B., et al., Reducing HIV-related stigma among young people attending school in Northern Uganda: study protocol for a participatory arts-based population health intervention and stepped-wedge cluster-randomized trial. 2022. 23(1): p. 1043. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref059] 59.Uwah C. J.S.-J.J.o.S.A.o.H.A., The role of culture in effective HIV/AIDS communication by theatre in South Africa. 2013. 10(3–4): p. 140–149. doi: 10.1080/17290376.2014.903809 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref060] 60.Robert Walker G., Pulsing bodies and embodying pulse: musical effervescence in a South African HIV/AIDS community outreach program. Anthropology & Medicine, 2022. 29(3): p. 289–304. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref061] 61.Millum J., et al., Ethical challenges in global health-related stigma research. 2019. 17: p. 1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref062] 62.Shabani M., et al., Oversight of genomic data sharing: what roles for ethics and data access committees? 2017. 15(5): p. 469–474. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref063] 63.Shabani M., Bezuidenhout L., and Borry P. J.E.r.o.m.d., Attitudes of research participants and the general public towards genomic data sharing: a systematic literature review. 2014. 14(8): p. 1053–1065. doi: 10.1586/14737159.2014.961917 [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref064] 64.Beaton A., et al., Engaging Māori in biobanking and genomic research: a model for biobanks to guide culturally informed governance, operational, and community engagement activities. 2017. 19(3): p. 345–351. [DOI] [PubMed] [Google Scholar]

[pone.0299081.ref065] 65.Kasule M., et al., Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana. 2022. 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0299081.ref066] 66.Ochieng J., et al., Perspectives and experiences of researchers regarding feedback of incidental genomic research findings: A qualitative study. 2022. 17(8): p. e0273657. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

The role of community engagement in promoting research participants’ understanding of pharmacogenomic research results: Perspectives of stakeholders involved in HIV/AIDS research and treatment

Sylvia Nabukenya

David Kyaddondo

Ian Guyton Munabi

Catriona Waitt

Adelline Twimukye

Erisa S Mwaka

Roles

Abstract

Introduction

Materials and methods

Study design and setting

Research team

Study participants

Study procedure

Data analysis

Ethical consideration

Results

Table 1. Stakeholders’ demographic characteristics.

Summary of the themes and key findings

Table 2. Emergent themes.

Benefits of engaging communities prior to returning individual pharmacogenomic research results to participants

Obtaining community consensus on the kinds of pharmacogenomic results to be returned

Opinions on how pharmacogenomic research information and results should be communicated at community and individual level

Perceived roles of community stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results

Perceived challenges of engaging communities when returning individual results to research participants

Discussion

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Tahir Turk

Roles

Author response to Decision Letter 0

Decision Letter 1

Tahir Turk

Roles

Author response to Decision Letter 1

Decision Letter 2

Tahir Turk

Roles

Acceptance letter

Tahir Turk

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases