Genetic research within Indigenous communities: Engagement opportunities and pathways forward.

PURPOSE: Against a historical backdrop of researchers who violated trust through lack of benefit sharing, transparency, and engagement, efforts are underway to develop better approaches for genetic and genomic research with Indigenous communities. To increase engagement, there is a need to understand factors that affect researcher and community collaborations. This study aimed to understand the barriers, challenges, and facilitators of Indigenous Peoples in the United States participating in genetic research. METHODS: We conducted 42 semistructured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members across the United States to explore perceived risks, benefits, barriers, and facilitators of genetic research participation. RESULTS: Participants, identifying as Indigenous (88%) or non-Indigenous allies (12%), described their concerns, hesitancy, and fears about genetic research, as well as the roles of trust, transparency, and respect for culture in facilitating partnerships. Previous harms-such as sample and data misuse, stigmatization, or misrepresentation by researchers-revealed strategies for building trust to create more equitable and reciprocal research partnerships. CONCLUSION: Participants in this study offered strategies for increasing genetic research engagement. The pathway forward should foster transparent research policies and practices to facilitate informed research that supports the needs and priorities of participants, communities, and researchers.

Motivations for and against Participation in Neonatal Research: Insights from Interviews of Diverse Parents Approached for Neonatal Research in the US.

OBJECTIVE: To describe parents' motivations for and against participation in neonatal research, including the views of those who declined participation. STUDY DESIGN: We performed 44 semi-structured, qualitative interviews of parents approached for neonatal research. Here we describe their motivations for and against participation. RESULTS: Altruism was an important reason parents chose to participate. Some hoped participation in research would benefit their infant. Burdens of participation to the family, such as transportation to follow up (distinct from risks/burdens to the infant), were often deciding factors among those who declined participation. Perceived risks to the infant were reasons against participation, but parents often did not differentiate between baseline risks and incremental risk of study participation. Concerns regarding their infant being treated like a "guinea pig" were common among those who declined. Finally, historical abuses and institutional racism were reported as important concerns by some research decliners from minoritized populations. CONCLUSIONS: Within a diverse sample of parents approached to enroll their infant in neonatal research, motivations for and against participation emerged, which may be targets of future interventions. These motivations included reasons for participation which we may hope to encourage, such as altruism. They also included reasons against participation, which we may hope to, as feasible, eliminate, mitigate, or at least acknowledge. These findings can help clinical trialists, regulators, and funders attempting to improve neonatal research recruitment processes.

Motivations and concerns of patients considering participation in an implementation study of a hereditary cancer risk assessment program in diverse primary care settings.

PURPOSE: Understanding the motivations and concerns of patients from diverse populations regarding participation in implementation research provides the needed evidence about how to design and conduct studies for facilitating access to genetics services. Within a hereditary cancer screening study assessing a multifaceted intervention, we examined primary care patients' motivations and concerns about participation. METHODS: We surveyed and interviewed study participants after they enrolled, surveyed those who did not complete enrollment, and used descriptive qualitative and quantitative methods to identify motivations and concerns regarding participation. RESULTS: Survey respondents' most common motivations included a desire to learn about their future risk (81%), receiving information that may help family (58%), and a desire to advance research (34%). Interviews revealed 3 additional important factors: affordability of testing, convenience of participation, and clinical relationships supporting research decision-making. Survey data of those who declined enrollment showed that the reasons for declining included concerns about privacy (38%), burdens of the research (19%), and their fear of not being able to cope with the genetic information (19%). CONCLUSION: Understanding the facilitating factors and concerns that contribute to decisions about research may reveal ways to improve equity in access to care and research that could lead to greater uptake of genomic medicine across diverse primary care patient populations.

ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial.

PURPOSE: Individuals having genomic sequencing can choose to be notified about pathogenic variants in genes unrelated to the testing indication. A decision aid can facilitate weighing one's values before making a choice about these additional results. METHODS: We conducted a randomized trial (N = 231) comparing informed values-choice congruence among adults at risk for a hereditary cancer syndrome who viewed either the Optional Results Choice Aid (ORCA) or web-based additional findings information alone. ORCA is values-focused with a low-literacy design. RESULTS: Individuals in both arms had informed values-choice congruence (75% and 73% in the decision aid and web-based groups, respectively; odds ratio [OR] = 1.10, 95% CI = 0.58-2.08). Most participants had adequate knowledge (79% and 76% in the decision aid and web-based groups, respectively; OR = 1.20, 95% CI = 0.61-2.34), with no significant difference between groups. Most had information-seeking values (97% and 98% in the decision aid and web-based groups, respectively; OR = 0.59, 95% CI = 0.10-3.61) and chose to receive additional findings. CONCLUSION: The ORCA decision aid did not significantly improve informed values-choice congruence over web-based information in this cohort of adults deciding about genomic results. Both web-based approaches may be effective for adults to decide about receiving medically actionable additional results.

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

BACKGROUND: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study. METHODS: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool. RESULTS: Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history. CONCLUSIONS: Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool. TRIAL REGISTRATION: This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.

Integrating stakeholder feedback in translational genomics research: an ethnographic analysis of a study protocol's evolution.

PURPOSE: This study describes challenges faced while incorporating sometimes conflicting stakeholder feedback into study design and development of patient-facing materials for a translational genomics study aiming to reduce health disparities among diverse populations. METHODS: We conducted an ethnographic analysis of study documents including summaries of patient advisory committee meetings and interviews, reflective field notes written by study team members, and correspondence with our institutional review board (IRB). Through this analysis, we identified cross-cutting challenges for incorporating stakeholder feedback into development of our recruitment, risk assessment, and informed consent processes and materials. RESULTS: Our analysis revealed three key challenges: (1) balancing precision and simplicity in the design of study materials, (2) providing clinical care within the research context, and (3) emphasizing potential study benefits versus risks and limitations. CONCLUSIONS: While involving patient stakeholders in study design and materials development can increase inclusivity and responsiveness to patient needs, patient feedback may conflict with that of content area experts on the research team and IRBs who are tasked with overseeing the research. Our analysis highlights the need for further empirical research about ethical challenges when incorporating patient feedback into study design, and for dialogue with genomic researchers and IRB representatives about these issues.

Patient perspectives on the use of categories of conditions for decision making about genomic carrier screening results.

As expanded genome-scale carrier screening becomes increasingly prevalent, patients will face decisions about whether to receive results about a vast number of genetic conditions. Understanding patient preferences is important to meaningfully demonstrate the ethical goal of respect and support patient autonomy. We explore one possible way to elicit preferences by sorting conditions into categories, which may support patient decision making, but the extent to which categories are helpful is unknown. In the context of a randomized trial of genome sequencing for preconception carrier screening compared to usual care (single disease carrier testing), we interviewed 41 participants who had genome sequencing about their experience using a taxonomy of conditions to select categories of results to receive. We then conducted interviews with an additional 10 participants who were not randomized to genome sequencing, asking them about the taxonomy, their reasons for selecting categories, and alternative ways of presenting information about potential results to receive. Participants in both groups found the categories helpful and valued having a meaningful opportunity to choose which results to receive, regardless of whether they opted to receive all or only certain categories of results. Additionally, participants who received usual care highlighted preparedness as a primary motivation for receiving results, and they indicated that being presented with possible reasons for receiving or declining results for each category could be helpful. Our findings can be used to develop approaches, including the use of categories, to support patient choices in expanded carrier screening. Further research should evaluate and optimize these approaches.

The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative.

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.

A randomized study of multimedia informational aids for research on medical practices: Implications for informed consent.

BACKGROUND/AIMS: Participant understanding is a key element of informed consent for enrollment in research. However, participants often do not understand the nature, risks, benefits, or design of the studies in which they take part. Research on medical practices, which studies standard interventions rather than new treatments, has the potential to be especially confusing to participants because it is embedded within usual clinical care. Our objective in this randomized study was to compare the ability of a range of multimedia informational aids to improve participant understanding in the context of research on medical practices. METHODS: We administered a web-based survey to members of a proprietary online panel sample selected to match national US demographics. Respondents were randomized to one of five arms: four content-equivalent informational aids (animated videos, slideshows with voice-over, comics, and text) and one no-intervention control. We measured knowledge of research on medical practices using a summary knowledge score from 10 questions based on the content of the informational aids. We used analysis of variance and paired t-tests to compare knowledge scores between arms. RESULTS: There were 1500 completed surveys (300 in each arm). Mean knowledge scores were highest for the slideshows with voice-over (65.7%), followed by the animated videos (62.7%), comics (60.7%), text (57.2%), and control (50.3%). Differences between arms were statistically significant except between the slideshows with voice-over and animated videos and between the animated videos and comics. Informational aids that included an audio component (animated videos and slideshows with voice-over) had higher knowledge scores than those without an audio component (64.2% vs 59.0%, p < .0001). There was no difference between informational aids with a character-driven story component (animated videos and comics) and those without. CONCLUSION: Our results show that simple multimedia aids that use a dual-channel approach, such as voice-over with visual reinforcement, can improve participant knowledge more effectively than text alone. However, the relatively low knowledge scores suggest that targeted informational aids may be needed to teach some particularly challenging concepts. Nonetheless, our results demonstrate the potential to improve informed consent for research on medical practices using multimedia aids that include simplified language and visual metaphors.

Experiences and preferences for learning about neonatal research: insights from parent interviews.

INTRODUCTION: Parents struggle with being asked to participate in neonatal research. Past work has largely failed to include views of minoritized parents, low-socioeconomic status parents, and those who declined research. We aimed to describe parents' preferences related to learning about eligibility for neonatal research. METHODS: Qualitative interviews of parents who were asked to enroll their infant in neonatal research. Themes related to parental experiences and preferences for learning about neonatal research were identified using content analysis. RESULTS: Many parents desired greater involvement of their clinical team. Emotions at the time of recruitment were critically important to parents' experience, where were deeply impacted by interpersonal relationships with research staff. DISCUSSION: Increased involvement of the clinical team and greater sensitivity to the stressors around parent and infant conditions at the time of recruitment for neonatal research should be considered by those attempting to improve recruitment for neonatal research.

Equity Concerns Across Pediatric Research Recruitment: An Analysis of Research Staff Interviews.

BACKGROUND AND OBJECTIVES: Difficulty recruiting individuals from minoritized and underserved populations for clinical research is well documented and has health equity implications. Previously, we reported findings from interviews with research staff about pediatric research recruitment processes. Respondents raised equity concerns related to recruitment and enrollment of participants from minoritized, low resourced, and underserved populations. We therefore decided to perform a secondary coding of the transcripts to examine equity-related issues systematically. METHODS: We conducted a process of secondary coding and analysis of interviews with research staff involved in recruitment for pediatric clinical research. Through consensus we identified codes relevant to equity and developed a conceptual framework including 5 stages of research. RESULTS: We analyzed 28 interviews and coded equity-related items. We report 6 implications of our findings. First, inequitable access to clinical care is an upstream barrier to research participation. Second, there is a need to increase research opportunities where underserved and under-represented populations receive care. Third, increasing research team diversity can build trust with patients and families, but teams must ensure adequate support of all research team members. Fourth, issues related to consent processes raise institutional-level opportunities for improvement. Fifth, there are numerous study procedure-related barriers to participation. Sixth, our analysis illustrates that individuals who speak languages other than English face barriers across multiple stages. CONCLUSIONS: Research staff members identified equity-related concerns and recommended potential solutions across 5 stages of the research process, which may guide those endeavoring to improve research recruitment for pediatric patients from minoritized and underserved populations.

Current landscape of research ethics consultation services: National survey results.

Introduction: The goal of a research ethics consultation service (RECS) is to assist relevant parties in navigating the ethical issues they encounter in conduct of research. The goal of this survey was to describe the current landscape of research ethics consultation and document if and how it has changed over the last decade. Methods: The survey instrument was based on the survey previously circulated. We included a number of survey domains from the previous survey with the goal of direct comparison of outcomes. The survey was sent to 57 RECS in the USA and Canada. Results: Forty-nine surveys were completed for an overall response rate of 86%. With the passing of 10 years, the volume of consults received by RECS surveyed has increased. The number of consults received by a subset of RECS remains low. RECS continues to receive requests for consults from a wide range of stakeholders. About a quarter of RECS surveyed actively evaluate their services, primarily through satisfaction surveys routinely shared with requestors. The number of RECS evaluating their services has increased. We identified a group of eight key competencies respondents find as key to providing RECS. Conclusions: The findings from our survey demonstrate that there have been growth and development of RECS since 2010. Further developing evaluation and competency guidelines will help existing RECS continue to grow and facilitate newly established RECS maturation. Both will allow RECS personnel to better serve their institutions and add value to the research conducted.

Research recruitment through the patient portal: perspectives of community focus groups in Seattle and Atlanta.

Objective: Research recruitment through patient portals (ie, patient-facing, web-based clinical interfaces) has the potential to be effective, efficient, and inclusive, but best practices remain undefined. We sought to better understand how patients view this recruitment approach. Materials and Methods: We conducted 6 focus groups in Atlanta, GA and Seattle, WA with members of patient advisory committees and the general public. Discussions addressed acceptability of patient portal recruitment and communication preferences. Focus groups were audio-recorded, transcribed, and analyzed using deductive and inductive codes. Iterative team discussions identified major themes. Results: Of 49 total participants, 20 were patient advisory committee members. Participants' mean age was 49 (range 18-74); 59% identified as non-Hispanic White and 31% as Black/African American. Participants were supportive of patient portal recruitment and confident that messages were private and legitimate. Participants identified transparency and patient control over whether and how to participate as essential features. Concerns included the frequency of research messages and the ability to distinguish between research and clinical messages. Participants also discussed how patient portal recruitment might affect diversity and inclusion. Discussion: Focus group participants generally found patient portal recruitment acceptable and perceived it as secure and trustworthy. Transparency, control, and attention to inclusiveness were identified as key considerations for developing best practices. Conclusion: For institutions implementing patient portal recruitment programs, continued engagement with patient populations can help facilitate translation of these findings into best practices and ensure that implemented strategies accomplish intended goals.