Conducting clinical genomics research during the COVID-19 pandemic: Lessons learned from the CSER consortium experience.

Clinical research studies have navigated many changes throughout the COVID-19 pandemic. We sought to describe the pandemic's impact on research operations in the context of a clinical genomics research consortium that aimed to enroll a majority of participants from underrepresented populations. We interviewed (July to November 2020) and surveyed (May to August 2021) representatives of six projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, which studies the implementation of genome sequencing in the clinical care of patients from populations that are underrepresented in genomics research or are medically underserved. Questions focused on COVID's impact on participant recruitment, enrollment, and engagement, and the transition to teleresearch. Responses were combined and thematically analyzed. Projects described factors at the project, institutional, and community levels that affected their experiences. Project factors included the project's progress at the pandemic's onset, the urgency of in-person clinical care for the disease being studied, and the degree to which teleresearch procedures were already incorporated. Institutional and community factors included institutional guidance for research and clinical care and the burden of COVID on the local community. Overall, being responsive to community experiences and values was essential to how CSER navigated evolving challenges during the COVID-19 pandemic.

Conducting inclusive research in genetics for transgender, gender-diverse, and sex-diverse individuals: Case analyses and recommendations from a clinical genomics study.

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex- and gender-related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex- and gender identity-related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD-inclusive genetics research design, data models, and processes.

Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study.

BACKGROUND: Standard interpretations of the ethical principle of respect for persons have not incorporated the views and values of patients, especially patients from groups underrepresented in research. This limits the ability of research ethics scholarship, guidance, and oversight to support inclusive, patient-centered research. This study aimed to identify the practical approaches that patients in community-based settings value most for conveying respect in genomics research. METHODS: We conducted a 3-round, web-based survey using the modified Delphi technique to identify areas of agreement among English-speaking patients at primary care clinics in Washington State and Idaho who had a personal or family history of cancer. In Round 1, respondents rated the importance of 17 items, identified in prior qualitative work, for feeling respected. In Round 2, respondents re-rated each item after reviewing overall group ratings. In Round 3, respondents ranked a subset of the 8 most highly rated items. We calculated each item's mean and median rankings in Round 3 to identify which approaches were most important for feeling respected in research. RESULTS: Forty-one patients consented to the survey, 21 (51%) completed Round 1, and 18 (86% of Round 1) completed each of Rounds 2 and 3. Two sets of rankings were excluded from analysis as speed of response suggested they had not completed the Round 3 ranking task. Respondents prioritized provision of study information to support decision-making (mean ranking 2.6 out of 8; median ranking 1.5) and interactions with research staff characterized by kindness, patience, and a lack of judgment (mean ranking 2.8; median ranking 2) as the most important approaches for conveying respect. CONCLUSIONS: Informed consent and interpersonal interactions are key ways that research participants experience respect. These can be supported by other approaches to respecting participants, especially when consent and/or direct interactions are infeasible. Future work should continue to engage with patients in community-based settings to identify best practices for research without consent and examine unique perspectives across clinical and demographic groups in different types of research.

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.

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.

Demonstrating 'respect for persons' in clinical research: findings from qualitative interviews with diverse genomics research participants.

The ethical principle of 'respect for persons' in clinical research has traditionally focused on protecting individuals' autonomy rights, but respect for participants also includes broader, although less well understood, ethical obligations to regard individuals' rights, needs, interests and feelings. However, there is little empirical evidence about how to effectively convey respect to potential and current participants. To fill this gap, we conducted exploratory, qualitative interviews with participants in a clinical genomics implementation study. We interviewed 40 participants in English (n=30) or Spanish (n=10) about their experiences with respect in the study and perceptions of how researchers in a hypothetical observational study could convey respect or a lack thereof. Most interviewees were female (93%), identified as Hispanic/Latino(a) (43%) or non-Hispanic white (38%), reported annual household income under US$60 000 (70%) and did not have a Bachelor's degree (65%); 30% had limited health literacy. We identified four key domains for demonstrating respect: (1) personal study team interactions, with an emphasis on empathy, appreciation and non-judgment; (2) study communication processes, including following up and sharing results with participants; (3) inclusion, particularly ensuring materials are understandable and procedures are accessible; and (4) consent and authorisation, including providing a neutral informed consent and keeping promises regarding privacy protections. While the experience of respect is inherently subjective, these findings highlight four key domains that may meaningfully demonstrate respect to potential and current research participants. Further empirical and normative work is needed to substantiate these domains and evaluate how best to incorporate them into the practice of research.

What Does the Word "Treatable" Mean? Implications for Communication and Decision-Making in Critical Illness.

OBJECTIVES: To explore how nonphysicians and physicians interpret the word "treatable" in the context of critical illness. DESIGN: Qualitative study using in-depth interviews. SETTING: One academic medical center. SUBJECTS: Twenty-four nonphysicians (patients and community members) purposively sampled for variation in demographic characteristics and 24 physicians (attending physicians and trainees) purposively sampled from four specialties (critical care, palliative care, oncology, and surgery). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified two distinct concepts that participants used to interpret the word "treatable": 1) a "good news" concept, in which the word "treatable" conveys a positive message about a patient's future, thereby inspiring hope and encouraging further treatment and 2) an "action-oriented" concept, in which the word "treatable" conveys that physicians have an action or intervention available, but does not necessarily imply an improved prognosis or quality of life. The overwhelming majority of nonphysicians adopted the "good news" concept, whereas physicians almost exclusively adopted the "action-oriented" concept. For some nonphysicians, the word "treatable" conveyed a positive message about prognosis and/or further treatment, even when this contradicted previously stated negative information. CONCLUSIONS: Physician use of the word "treatable" may lead patients or surrogates to derive unwarranted good news and false encouragement to pursue treatment, even when physicians have explicitly stated information to the contrary. Further work is needed to determine the extent to which the word "treatable" and its cognates contribute to widespread decision-making and communication challenges in critical care, including discordance about prognosis, misconceptions that palliative treatments are curative, and disputes about potentially inappropriate or futile treatment.

The evolving landscape of expanded carrier screening: challenges and opportunities.

Carrier screening allows individuals to learn their chance of passing on an autosomal or X-linked condition to their offspring. Initially introduced as single-disease, ancestry-based screening, technological advances now allow for the possibility of multi-disease, pan-ethnic carrier screening, which we refer to as "expanded carrier screening." There are numerous potential benefits to expanded carrier screening, including maximizing the opportunity for couples to make autonomous reproductive decisions, and efficiency and marginal additional costs of including more conditions if the test is already being offered. While numerous laboratories currently offer expanded carrier screening services, it is not yet commonly used in clinical practice, and there is a lack of consensus among experts about the service, including whether this should be offered to individuals and couples, whether this should be offered preconception or prenatally, and what conditions to include in screening programs. Challenges for expanded carrier screening programs include a lack of demand from the public, low prioritization by health systems, the potential for pressure to undergo screening, the possibility of disability-based discrimination, needed adaptations to pre- and post-test counseling, technical limitations, and the evolving technological and socio-political landscape.

"I don't want to be Henrietta Lacks": diverse patient perspectives on donating biospecimens for precision medicine research.

PURPOSE: To determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections. METHODS: We conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research. RESULTS: Our study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data. CONCLUSION: Considering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.

Engaging populations underrepresented in research through novel approaches to consent.

The lack of diversity of populations included in genomics databases is an important inhibitor of genomic discovery from bench to bedside. One way to increase the diversity of participants is to ensure that informed consent processes are designed for cultural and linguistic concordance for non-majority populations. This article describes two case studies of genomics research studies that are using novel approaches to informed consent to increase recruitment and retention of participants from traditionally underrepresented populations: The Cancer Health Assessments Reaching Many (CHARM) study, part of the Clinical Sequencing Evidence-Generating Research (CSER) consortium, and the All of Us Research Program, part of the Precision Medicine Initiative. We conclude by proposing a community of practice among researchers seeking to improve informed consent to increase diversity in genomics research.

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.

Beyond Consent: Building Trusting Relationships With Diverse Populations in Precision Medicine Research.

With the growth of precision medicine research on health data and biospecimens, research institutions will need to build and maintain long-term, trusting relationships with patient-participants. While trust is important for all research relationships, the longitudinal nature of precision medicine research raises particular challenges for facilitating trust when the specifics of future studies are unknown. Based on focus groups with racially and ethnically diverse patients, we describe several factors that influence patient trust and potential institutional approaches to building trustworthiness. Drawing on these findings, we suggest several considerations for research institutions seeking to cultivate long-term, trusting relationships with patients: (1) Address the role of history and experience on trust, (2) engage concerns about potential group harm, (3) address cultural values and communication barriers, and (4) integrate patient values and expectations into oversight and governance structures.

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.