A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations

In this paper, I interrogate an ethical obligation to participate in genomics research on the basis of solidarity. I explore two different ways in which solidarity is used to motivate participation in genomics research: as an appeal to participate in genomic research because it cultivates solidarity and as an appeal to participate in genomic research because it expresses solidarity. I critique those appeals and draw lessons from them for how we ought to understand solidarity. The working definition of solidarity that I defend is that solidarity involves recognizing another creature, person, or persons as, like ourselves, vulnerable to injustice and entails acting in ways that contribute to creating, reforming, and participating in institutions that are aimed at enhancing their flourishing. I argue that participating in genomics research is not an expression of solidarity. Participation in research may be praiseworthy, a "good thing to do," but actually cultivating and expressing solidarity requires much more of us.

BackgroundDisclosure of research results may impose undesirable responsibilities and consequences on the participants. Locally and culturally applicable guidelines for protection of research participants from negative consequences of genomic research results...

Introduction: Research advances on effective methods to prevent, diagnose and treat cancer continue to emerge through clinical and genomic research. To ensure the results from these research studies help those who need it most, a diverse population needs to enroll. Despite guidance from authorities, such as the National Institutes of Health, most clinical trial and genomic research participants identify as White. At the participant level, mistrust of research, unawareness of research opportunities and gaps in bioethical knowledge about clinical trials and genomic research remain proven barriers to participating, especially among African Americans (AA) and Hispanics. With the development and access to technology, digital delivery of salient and tailored health education may provide innovative pathways to increase representation of AA and Hispanics in research. Methods: Members from the NCI-funded Partnerships to Advance Cancer Health Equity (PACHE) including experts from the community, healthcare, biomedical research and public health, such as oncologists, cancer geneticists, behavioral scientists and bioethicists collaborated on all phases. A design lab with experience synthesizing complex health messages into brief animations was contracted. The goal was to utilize existing educational resources from the National Cancer Institute and the National Human Genome Research Institute to create a tailored message to address AA's and Hispanics’ beliefs, values and bioethical concerns related to participation in clinical and genomic research. Models of behavior change and communication theories were leveraged to frame key components of the message, which then informed the animated video. Results: Development of the video consisted of six iterative phases: 1) writing sessions; 2) storyboarding; 3) animating; 4) screening/revisions; 5) acceptability testing; 6) finalization. In the last two steps, the video was presented to family members of cancer patients, cancer survivors and community members who provided quantitative and qualitative feedback which informed further edits. The final animated video is approximately five minutes in length and covers several topics including the goal of clinical research, disparities in clinical trials and genomic research participation, genomic research regulations and the purpose of a biobank. Supporting imagery to emphasize specific concepts, such as racial disparities in research, was dispersed throughout the video. A voiceover emphasized key bioethical concepts, including how research participation is safe and voluntary. When possible, characters were designed to resemble the targeted viewing audience. Discussion: Increasing AA and Hispanic participation in clinical and genomic research is imperative to achieving health equity. Tailored messages via short videos may assist in addressing the barriers and facilitators towards research participation and increase intentions to enroll in trials. Future research will evaluate the efficacy of the video through a multi-level framework in real-world settings. Citation Format: Victoria Churchill, Yu-Mei Schoenberger, Vivian L Carter, Windy Dean-Colomb, Roland Matthews, Desiree Rivers, Stephen O Sodeke, Jamirah Chevrin, Brian Rivers. The development of a bioethically sensitive education video: Addressing the barriers to African Americans’ and Hispanics’ participation in clinical and genomic research through digital animation [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A005.

BACKGROUND Return of research results and ownership of data and biospecimens are ethically complex issues in genomic research. This study explored perspectives on ROR and data/specimen ownership among individuals affected by low-grade glioma (LGG) and other community representatives. METHODS In 2022, we conducted 11 community-engaged facilitated discussions using three platforms: a Research Advisory Council (RAC), Twitter (now X), and a private LGG Facebook group. Participants included individuals with brain cancer (including LGG), care partners, clinicians, researchers, and regulatory experts. Discussions focused on strategies for enhancing trust and participation in brain cancer genomic research and were guided by ethical principles—autonomy, ownership, privacy, and relevance. Transcripts were analyzed using qualitative content analysis. RESULTS 352 unique participants contributed to discussions. Across platforms, participants perceived continued ownership over their data and biospecimens and emphasized a strong expectation of reciprocity: contributing data and biospecimens should be met with access to both individual and aggregate research findings. Individuals with LGG viewed return of individual and overall research results as a means of maintaining autonomy; they saw individual results as highly relevant for making informed medical decisions, even when results lacked clinical validation. Trust in researchers to protect privacy was high. While researchers and clinicians also acknowledged the value of returning results, they expressed concerns about returning results prematurely, especially when clinical significance was unknown. CONCLUSIONS As part of an ethical research partnership, participants in LGG genomic research have an expectation of reciprocity: in return for sharing their health information and biospecimens, they expect access to both individual and research results. Despite limitations in clinical validity and contradictory policy, return of results is seen as empowering, personally relevant, and a way of recognizing participants’ contributions to scientific advancement. Addressing these expectations may enhance trust and participation in genomic research.

BACKGROUND The International Low Grade Glioma (LGG) Registry is a community of people with LGGs who have contributed data and specimens to facilitate genomic research. The Registry aims to discover the roles genetics and the environment play in glioma risk factors and treatment response. To ensure findings apply to a range of diverse populations and settings, it is crucial to build trust and encourage representative participation in the Registry. METHODS Three engagement strategies were used to gather recommendations for improving trust and participation in LGG genomic research. We established a Research Advisory Council (RAC) consisting of 25 members, including people with LGG, care partners, clinicians, researchers, advocates, and genomics and ethics experts. Additionally, we engaged two existing social media communities (the #BTSM community on Twitter, the Oligodendroglioma/LGG Warriors Facebook group) through separate discussions with each group over four months. Topics included: 1) Trust and benefits of genomic research; 2) Registry recruitment; 3) Registry data collection; and 4) Return of results. We used qualitative methods to summarize recommendations. RESULTS Feedback received from community members indicated a willingness to share information with the Registry. Recommendations related to recruitment message content and packaging, communication channels, data security, and conveying the individual- and population-level impacts of genomic research. The Registry’s messages should include clear information about how data and specimens are being used. Both research and individual-level findings should be shared back with participants and the broader community using accessible language, but without being paternalistic or promising cures or “miracles.” CONCLUSIONS Engaging an advisory council and existing social media communities were effective approaches for identifying recommendations for enhancing trust and participation in genomic research. Regular, consistent, transparent communication with participants throughout the research process is key. Future efforts will operationalize and evaluate the impact of these recommendations on equity and representativeness of Registry participants.

BackgroundIt is important for researchers to understand the motivations and decision-making processes of participants who take part in their research. This enables robust informed consent and promotes research that meets the needs and expectations of the community. It is particularly vital when working with Indigenous communities, where there is a history of exploitative research practices. In this paper, we examine the accounts of Australian Indigenous and non-Indigenous research participants in terms of how and why they agree to take part in research.MethodsA qualitative research approach was employed to undertake individual interviews with 36 research participants in Victoria, Australia. Eight participants identified as Indigenous and 28 were non-Indigenous. Thematic analysis was used to interpret the data.ResultsThere were stark differences between Indigenous and non-Indigenous research participants in terms of why and how they decided to participate in research. For Indigenous participants, taking part in research was primarily to benefit their communities rather than for personal interests. Indigenous participants often started from a position of caution, and showed a considered and deliberate process of decision making. In weighing up their decision to participate, some Indigenous participants clearly articulated what was valued in conducting research with Indigenous communities, for example, honesty, reciprocity, and respect; these values were explicitly used to assist their decision whether or not to participate. This was in contrast to non-Indigenous participants who took researchers’ claims on face value, and for whom deciding to participate in research was relatively straightforward. The motivations to participate of non-Indigenous participants were due to personal interests, a desire to help others, or trust in the medical practitioner who recruited them for the research project.ConclusionUnderstanding research participants’ motivations about taking part in research is important. This is particularly relevant for Indigenous communities where there is a reported history of research abuse leading to mistrust. This understanding can lead to research practice that is more respectful and responsive to the needs of Indigenous communities and abides by the values of Indigenous communities. Moreover it can lead to more ethical and respectful research practice for all.

Offering aggregate results to participants in genomic research: opportunities and challenges

Although genomic research offering next-generation sequencing (NGS) has increased the diagnoses of rare/ultra-rare disorders, populations experiencing health disparities infrequently participate in these studies. The factors underlying non-participation would most reliably be ascertained from individuals who have had the opportunity to participate, but decline. We thus enrolled parents of children and adult probands with undiagnosed disorders who had declined genomic research offering NGS with return of results with undiagnosed disorders (Decliners, n = 21) and compared their data to those who participated (Participants, n = 31). We assessed: (1) practical barriers and facilitators, (2) sociocultural factors-genomic knowledge and distrust, and (3) the value placed upon a diagnosis by those who declined participation. The primary findings were that residence in rural and medically underserved areas (MUA) and higher number of barriers were significantly associated with declining participation in the study. Exploratory analyses revealed multiple co-occurring practical barriers, greater emotional exhaustion and research hesitancy in the parents in the Decliner group compared to the Participants, with both groups identifying a similar number of facilitators. The parents in the Decliner group also had lower genomic knowledge, but distrust of clinical research was not different between the groups. Importantly, despite their non-participation, those in the Decliner group indicated an interest in obtaining a diagnosis and expressed confidence in being able to emotionally manage the ensuing results. Study findings support the concept that some families who decline participation in diagnostic genomic research may be experiencing pile-up with exhaustion of family resources - making participation in the genomic research difficult. This study highlights the complexity of the factors that underlie non-participation in clinically relevant NGS research. Thus, approaches to mitigating barriers to NGS research participation by populations experiencing health disparities need to be multi-pronged and tailored so that they can benefit from state-of -the art genomic technologies.

Nowadays, new technologies, like genomics, cannot be developed without the support of the public. However, although interested, the public does not always actively participate in science issues when offered the opportunity via public participation activities. In a study aimed at validating a measurement scale, first, we investigated if public participation existed, and, secondly, we investigated how levels of public participation in genomics research varied among groups. Finally, we studied which factors predicted public participation. Results were based on a questionnaire with four subsamples. Results confirmed, first of all, the internal consistency of the measurement scale to assess levels of public participation. Secondly, the groups differed significantly with regard to their levels of participation in genomics research. Finally, the findings revealed that information-seeking behaviour, knowledge and education were main predictors of public participation, while interest, social involvement, and trust and influence had some influence together with age and gender.

With widespread genomic sequencing research efforts, there is increasing impetus to return results to participants. Parents of healthy children are increasingly asked to participate in genomic research, yet there are limited studies of parental expectations for the return of results amongst healthy children. We explored parental attitudes towards their healthy children's participation in genomic research and expectations for return of results. Data collection involved semi-structured telephone interviews with parents of healthy children participating in a primary care research network. Transcripts were analyzed thematically using constant comparison. A total of 26 parents were interviewed: 22 were female, 19 self-reported as White/European, and 20 were aged 30-39. Three themes emerged: (1) Reciprocity; Parents preferred to receive medically actionable, childhood-onset results and expected recontact overtime in exchange for their research participation. (2) Downstream impacts of testing; Parents expected future clinical benefits but were concerned about the risk of genetic discrimination. (3) Power and empowerment; Some parents felt empowered to take preventative action for their child and relatives, while others did not want to limit their child's autonomy. Considering these tensions may help to inform participant-centered approaches to optimize parental decision-making and participation, as well as maximize the utility of results.

Many research studies conducted today in critical care have a genomics component. Patients' surrogates asked to authorize participation in genomics research for a loved one in the intensive care unit may not be prepared to make informed decisions about a patient's participation in the research. To examine the effectiveness of a new, computer-based education module on surrogates' understanding of the process of informed consent for genomics research. A pilot study was conducted with visitors in the waiting rooms of 2 intensive care units in a Midwestern tertiary care medical center. Visitors were randomly assigned to the experimental (education module plus a sample genomics consent form; n = 65) or the control (sample genomics consent form only; n = 69) group. Participants later completed a test on informed genomics consent. Understanding the process of informed consent was greater (P = .001) in the experimental group than in the control group. Specifically, compared with the control group, the experimental group had a greater understanding of 8 of 13 elements of informed consent: intended benefits of research (P = .02), definition of surrogate consenter (P= .001), withdrawal from the study (P = .001), explanation of risk (P = .002), purpose of the institutional review board (P = .001), definition of substituted judgment (P = .03), compensation for harm (P = .001), and alternative treatments (P = .004). Computer-based education modules may be an important addition to conventional approaches for obtaining informed consent in the intensive care unit. Preparing patients' family members who may consider serving as surrogate consenters is critical to facilitating genomics research in critical care.

Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants, revealing personal genomic information and data misuse might increase. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. For this purpose, we conducted a qualitative focus group study at the National Center for Tumor Diseases (NCT). Patients and oncologists assessed the informational risks either as minimal or as greater than minimal, depending on the context factors of occupational status, age, and patients’ prognosis. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational and institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. These results suggest (1) comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, (2) establishing independent governance entities in order to minimize the informational risks of genomic research, and (3) implementing data sharing policies which offer guidance for physicians and researchers involved in genomic research.

[This corrects the article DOI: 10.1371/journal.pone.0195171.].

BackgroundGenomic research advances the understanding of human health and disease. It also drives both the discovery of salient genetic association(s) as well as targeted screening, diagnostic and therapeutic strategies. Human subject participation is crucial for the success of genomic research.MethodsThis is a cross sectional analytical study conducted at two tertiary centers in Enugu Southeast Nigeria. Semi structured questionnaires were administered to eligible consenting participants. Data on their demographics, willingness to participate in genomic research and motivation for participation were obtained. Data was analyzed using Stata version 17 and summarized using median, frequencies and interquartile range(IQR). Associations between covariates were evaluated with Chi square test and multivariable logistic regression.ResultsAmong 228 glaucoma subjects who participated in our study,119(52.2%) were female and 109(47.8%) were male. The median age was 64 years(IQR = 50–76). Although 219 (96.0%) participants expressed willingness to participate in a glaucoma genetic study, only 27(11.9%) of them will be willing to participate if there will not be feedback of results to participants (χ2 = 18.59, P<0.001). No participant expressed willingness to submit ocular tissue samples. Majority (96.2%) of subjects will not participate if the intended research required submission of body samples after death. Desire to know more about glaucoma (63%) was the most common reason for participation. In a multivariable logistic model, subjects between 61–90 years (p = 0.004, OR = 7.2) were 7 times more likely to express willingness to participate in glaucoma genetic research after adjusting for other covariates when compared to subjects aged 41–60 years. Other covariates did not influence participants’ willingness.ConclusionGlaucoma subjects are more likely to be willing to participate in genetic research, if they would receive feedback of results. Willingness to participate in genetic research is significantly associated with age.LimitationsWe did not evaluate the salient options for feedback of results to participants in our study.

Moving beyond good intentions: Indigenous participation in Aboriginal and Torres Strait Islander health research