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.

Stem Cell Transplant Experiences Among Hispanic/Latinx Patients: A Qualitative Analysis.

BACKGROUND: Hispanic/Latinx (H/L) patients with cancer treated with stem cell transplant are vulnerable to adverse outcomes, including higher mortality. This study explored their unmet transplant needs, barriers, and facilitators. METHODS: Eighteen English- or Spanish-speaking H/L patients (M age = 59.2) who had a transplant in the past year were interviewed about their transplant experience and rated their interest in receiving information about transplant topics (0 = not at all to 10 = extremely). RESULTS: Content analysis revealed five main themes: (1) pre-transplant barriers and concerns; (2) complex relationships with medical teams; (3) informational mismatch; (4) impacts on daily life after transplant; and (5) methods of coping. Participants were most interested in information about ways of coping with transplant (M = 9.11, SD = 1.45) and words of hope and encouragement (M = 9.05, SD = 1.80). At just above the scale's midpoint, they were least interested in information about side effects and unintended consequences of transplant (M = 5.61, SD = 3.85). CONCLUSIONS: Cultural factors, social determinants, and structural inequalities give rise to unique needs in this growing patient population. Healthcare team members and researchers can better meet the needs of H/L transplant recipients through attention to described considerations, such as financial barriers, communication difficulties, family dynamics, and coping styles.

The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research.

This paper analyses the activities of five organizations shaping the debate over the global governance of genome editing in order to assess current approaches to public engagement (PE). We compare the recommendations of each group with its own practices. All recommend broad engagement with the general public, but their practices vary from expert-driven models dominated by scientists, experts, and civil society groups to citizen deliberation-driven models that feature bidirectional consultation with local citizens, as well as hybrid models that combine elements of both approaches. Only one group practices PE that seeks community perspectives to advance equity. In most cases, PE does little more than record already well-known views held by the most vocal groups, and thus is unlikely to produce more just or equitable processes or policy outcomes. Our exploration of the strengths, weaknesses, and possibilities of current forms of PE suggests a need to rethink both "public" and "engagement."

The Burden of COVID-19 on Caregivers of Children with Suspected Genetic Conditions: A Therapeutic Odyssey.

AIMS: Children with disabilities and rare or undiagnosed conditions and their families have faced numerous hardships of living during the COVID-19 pandemic. For those with undiagnosed conditions, the diagnostic odyssey can be long, expensive, and marked by uncertainty. We, therefore, sought to understand whether and how COVID-19 impacted the trajectory of children's care. METHODS: We conducted semi-structured qualitative interviews with 25 caregivers who, prior to the pandemic, were on a diagnostic odyssey for their children. RESULTS: Most caregivers did not report any interruptions to their child's diagnostic odyssey. The greatest impact was access to therapy services, including the suspension or loss of their child's in-person therapeutic care and difficulties with virtual therapies. This therapy gap caused caregivers to fear that their children were not making progress. CONCLUSION: Although much has been written about the challenges of diagnostic odysseys for children and their families, this study illustrates the importance of expanding the focus of these studies to include therapeutic odysseys. Because therapeutic odysseys continue regardless of whether diagnoses are made, future research should investigate how to support caregivers through children's therapies within and outside of the COVID-19 context.

Optimizing use of written peer support as a supportive resource in cancer: Focus group insights.

PURPOSE: Cancer survivors frequently describe wanting to learn from others who have had similar diagnoses or treatments (peer support). We conducted focus groups to investigate hematopoietic stem cell transplant survivors' attitudes and preferences regarding accessing written peer support through a website. Although written peer support does not allow for interpersonal interactions with peers, it could increase transplant recipients' access to evidence-based benefits of informational and emotional peer support. METHODS: We conducted four videoconference focus groups with 34 adult transplant survivors who were diverse in their medical and sociodemographic characteristics and geographic location. Discussions were recorded, transcribed, and content analyzed. RESULTS: Many participants reported need for information about transplant beyond what they received from their healthcare providers. Needs varied across participants, as did preferences for characteristics and timing of information optimally provided through peer support. Participants were enthusiastic about the value of written peer support but emphasized that it should be delivered in a way that accommodates variation in transplant experiences, underscores its trustworthiness, and pairs it with useful psychoeducational content. CONCLUSIONS: Findings provide guidance for making written peer support an accessible, supportive resource for transplant survivors. Future research should evaluate personalized online delivery of written peer support paired with psychoeducational content that enhances its benefits. IMPLICATIONS FOR CANCER SURVIVORS: Written peer support delivered online could be a useful, valued resource for transplant survivors.

Hospital Policies During COVID-19: An Analysis of Visitor Restrictions.

OBJECTIVE: In response to the COVID-19 pandemic, hospitals have developed visitor restriction policies in order to mitigate spread of infection. We reviewed hospital visitor restriction policies for consistency and to develop recommendations to highlight fair and transparent restrictions, exceptions, and appeals in policy development and implementation. DESIGN: Collection and analysis of public-facing visitor restriction policies during the first 3 months of the pandemic. SETTING: General acute care hospitals representing 23 states across all 4 major regions of the United States. PARTICIPANTS: A cohort of the 70 largest hospitals by total bed capacity. MEASUREMENTS: Characteristics of visitor restriction policies including general visitor restriction statement, changes/updates to policies over time, exceptions to policies, and restrictions specific to COVID-19-positive patients. RESULTS: Sixty-five of the 70 hospitals reviewed had public-facing visitor restriction policies. Forty-nine of these 65 policies had general "no-visitor" statements, whereas 16 allowed at least 1 visitor to accompany all patients. Sixty-three of 65 hospitals included exceptions to their visitor restriction policies. Setting-specific exceptions included pediatrics, obstetrics/gynecology, emergency department, behavioral health, inpatient rehabilitation, surgery, and outpatient clinics. Exceptions that applied across settings included patients at end of life and patients with disabilities. CONCLUSION: Visitor restriction policies varied significantly among hospitals in this review. These variances create challenges in that their fair application may be problematic and ethical issues related to allocation may arise. Five recommendations are offered for hospitals revising or creating such policies, including that offering transparent, accessible, public-facing policies can minimize ethical dilemmas. In addition, hospitals would benefit from communicating with each other in the development of visitor policies to ensure uniformity and support patients and family members as they navigate hospital visitation.

Genomic knowledge in the context of diagnostic exome sequencing: changes over time, persistent subgroup differences, and associations with psychological sequencing outcomes.

PURPOSE: People undergoing diagnostic genome-scale sequencing are expected to have better psychological outcomes when they can incorporate and act on accurate, relevant knowledge that supports informed decision making. METHODS: This longitudinal study used data from the North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing Study (NCGENES) of diagnostic exome sequencing to evaluate associations between factual genomic knowledge (measured with the University of North Carolina Genomic Knowledge Scale at three assessments from baseline to after return of results) and sequencing outcomes that reflected participants' perceived understanding of the study and sequencing, regret for joining the study, and responses to learning sequencing results. It also investigated differences in genomic knowledge associated with subgroups differing in race/ethnicity, income, education, health literacy, English proficiency, and prior genetic testing. RESULTS: Multivariate models revealed higher genomic knowledge at baseline for non-Hispanic Whites and those with higher income, education, and health literacy (p values < 0.001). These subgroup differences persisted across study assessments despite a general increase in knowledge among all groups. Greater baseline genomic knowledge was associated with lower test-related distress (p = 0.047) and greater perceived understanding of diagnostic genomic sequencing (p values 0.04 to <0.001). CONCLUSION: Findings extend understanding of the role of genomic knowledge in psychological outcomes of diagnostic exome sequencing, providing guidance for additional research and interventions.

Referencing BRCA in hereditary cancer risk discussions: In search of an anchor in a sea of uncertainty.

As panel testing and exome sequencing are increasingly incorporated into clinical care, clinicians must grapple with how to communicate the risks and treatment decisions surrounding breast cancer genes beyond BRCA1 and BRCA2. In this paper, we examine clinicians' practice of employing BRCA1 and BRCA2 to help contextualize less certain genetic information regarding cancer risk and the possible implications of this practice for patients within the context of an exome sequencing study, NCGENES. We audio-recorded return of results appointments for 14 women who participated in NCGENES, previously had breast cancer, and were suspected of having a hereditary cancer predisposition. These patients were also interviewed four weeks later regarding their understanding of their results. We found that BRCA1 and BRCA2 were held as the gold standard, where clinicians compared what is known about BRCA to the limited understanding of other breast cancer-related genes. BRCA1 and BRCA2 were used as anchors to shape patients' understandings of genetic knowledge, risk, and management, illustrating how the information clinicians provide to patients may work as an external anchor. Yet, presenting BRCA1 and BRCA2 as a means of scientific reassurance can run the risk of patients conflating knowledge about certainty of risk with degree of risk after receiving a result for a moderate penetrance gene. This can be further complicated by misperceptions of the precision of cancer predictability attributed to these or other described 'cancer genes' in public media.

Returning negative results to individuals in a genomic screening program: lessons learned.

PURPOSE: In genomics, the return of negative screening results for rare, medically actionable conditions in large unselected populations with low prior risk of disease is novel and may involve important and nuanced concerns for communicating their meaning. Recruitment may result in self-selection because of participants' personal or family history, changing the characteristics of the screened population and interpretation of both positive and negative findings; prior motivations may also affect responses to results. METHODS: Using data from GeneScreen, an exploratory adult screening project that targets 17 genes related to 11 medically actionable conditions, we address four questions: (1) Do participants self-select based on actual or perceived risk for one of the conditions? (2) Do participants understand negative results? (3) What are their psychosocial responses? (4) Are negative results related to changes in reported health-related behaviors? RESULTS: We found disproportionate enrollment of individuals at elevated prior risk for conditions being screened, and a need to improve communication about the nature of screening and meaning of negative screening results. Participants expressed no decision regret and did not report intention to change health-related behaviors. CONCLUSION: This study illuminates critical challenges to overcome if genomic screening is to benefit the general population.

Correction: Genomic knowledge in the context of diagnostic exome sequencing: changes over time, persistent subgroup differences, and associations with psychological sequencing outcomes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Perils of the Hidden Curriculum: Emotional Labor and "Bad" Pediatric Proxies.

Today's medical training environment exposes medical trainees to many aspects of what has been called "the hidden curriculum." In this article, we examine the relationship between two aspects of the hidden curriculum, the performance of emotional labor and the characterization of patients and proxies as "bad," by analyzing clinical ethics discussions with resident trainees at an academic medical center. We argue that clinicians' characterization of certain patients and proxies as "bad," when they are not, can take an unnecessary toll on trainees' emotions. We conclude with a discussion of how training in ethics may help uncover and examine these aspects of the hidden curriculum.

Age and perceived risks and benefits of preventive genomic screening.

PURPOSE: As genome sequencing moves from research to clinical practice, sequencing technologies focused on "medically actionable" targets are being promoted for preventive screening despite the dearth of systematic evidence of risks and benefits and of criteria for selection of screening subjects. This study investigates researchers' and research participants' perceptions of these issues within the context of a preventive genomic screening study, GeneScreen. METHODS: We recorded researcher deliberations regarding age eligibility criteria and the risks and benefits of screening, and conducted interviews with 50 GeneScreen participants about their motivations for joining and their perceptions of risks and benefits. RESULTS: Researchers made assumptions about who would want and benefit from screening based on age. After discussion, researchers opted not to have an upper age limit for enrollment. Participants of all ages perceived similar benefits, including prevention, treatment, and cascade testing, and similar risks, such as insurance discrimination and worry. CONCLUSION: While clinical benefits of preventive genomic screening for older adults are debatable, our respondents perceived a range of benefits of screening in both clinical and research settings. Researchers and clinicians should carefully consider decisions about whether to exclude older adults and whether to provide information about benefits and risks across age groups.

Public participation in human genome editing research governance: what do scientists think?

Within the numerous policy and governance recommendations for human genome editing research, anticipatory public engagement seems universally agreed upon as a vital endeavor. Yet it is unclear whether and how scientists whose research involves genome editing see value in engaging the public in discussions of genome editing research governance. To address this question, we interviewed 81 international scientists who use genome editing in their research. The views of our scientist interviewees about public engagement occupied a broad spectrum from enthusiastic support to strong skepticism. But most scientists' views landed somewhere in the middle, seeing public engagement as merely informing the public about the science of genome editing. We argue that such a stance reflects the traditional "knowledge-deficit model." Beyond addressing the operational difficulties of public engagement, many scientists' adherence to the deficit model is a deeper barrier that needs to be addressed if public engagement is to occur and be successful.

Reflections on 'common' genetic medical history questions: Time to examine the what, why, and how.

OBJECTIVE: A central goal of patient-centered care is to establish a therapeutic relationship. While remaining in tune with patient emotions, genetics providers must ask questions to understand medical histories that will inform the differential diagnosis, evaluation plan, and potential treatments. METHODS: 195 audio-recorded conversations between providers and caregivers of pediatric patients with suspected genetic conditions were coded and analyzed. Coders identified sensitive history-taking questions asked by providers related to exposures and complications during pregnancy; ancestry and consanguinity; educational attainment of the caregiver; and family structure. RESULTS: We highlight examples of providers: using stigmatizing language about conception or consanguinity; not clarifying the intent behind questions related to caregivers' educational attainment and work history; and making presumptions or assumptions about caregivers' race and ethnicity, family structure, and exposures during pregnancy. CONCLUSION: Some questions and phrasing considered routine by genetics providers may interfere with patient-centered care by straining attempts to establish a therapeutic, trusting relationship. Additional research is needed to assess how question asking and phrasing impact rapport building and patient experience during genetics encounters. PRACTICE IMPLICATIONS: Review of the purpose and need for medical history questions common to genetics practice could serve to improve patient-centered care.

Mission Creep or Mission Lapse? Scientific Review in Research Oversight.

BACKGROUND: The ethical use both of human and non-human animals in research is predicated on the assumption that it is of a high quality and its projected benefits are more significant than the risks and harms imposed on subjects. Yet questions remain about whether and how IRBs and IACUCs should consider the scientific value of proposed research studies. METHODS: We draw upon 45 interviews with IRB and IACUC members and researchers with oversight experience about their perceptions of their own roles in reviewing the quality and value of scientific protocols. Interview transcripts were memoed to highlight specific findings, which were then used to identify key themes through an iterative process. RESULTS: IRB and IACUC members expressed broad trust in the need for and value of research, and they often assumed that protocols had social value or that prior review, especially when associated with funding, affirmed both the rigor and merit of those protocols. Some oversight members also took an explicit stance against scientific review by stating that such review is not within the regulatory mandates governing their parts in the oversight system. Yet other interviewees expressed uneasiness about the current paradigm for evaluating the quality and overall value of science, suggesting that IRB and IACUC members perceive gaps in the oversight systems. CONCLUSIONS: These findings reveal many similarities in how IRB and IACUC members understand the roles and limitations of their respective oversight committees. We conclude with a discussion of how the lack of a clear mandate regarding scientific review within US federal regulations may undermine ethical engagement of whether human and animal research is scientifically justified, resulting in a "mission lapse" wherein no organizational body is clearly responsible for ensuring that the research being conducted has the potential to advance science and benefit society.

"Death and Taxes": Why Financial Compensation for Research Participants is an Economic and Legal Risk.

In the US, research payments are technically taxable income. This article argues that tax liability is a form of possible economic and legal risk of paid research participation. Findings are presented from empirical research on Phase I healthy volunteer trials. The article concludes by discussing the implications of these findings for the informed consent process, as well as for broader ethical issues in whether and how payments for research participation should be regulated.

Exclusion of Women from Phase I Trials: Perspectives from Investigators and Research Oversight Officials.

Over the past 30 years, progress has been made in increasing women's representation in clinical research. However, women continue to be underrepresented in phase I clinical trials-those trials that test the safety and tolerability of investigational drugs, often on healthy individuals. As sex-based differences in adverse drug reactions are often linked to drug dose, pivotal safety information in phase I trials is often insufficiently-and inequitably-captured for females. Yet there has been little attention to how clinical investigators and those charged with overseeing the ethical conduct of these trials perceive the barriers to women's inclusion in phase I trials. To address this gap, we report on 22 interviews with U.S. phase I investigators and institutional review board (IRB) members. Our findings indicate that although these investigators and IRB members acknowledged the importance of including women in clinical trials, they justified women's exclusion from phase I trials by citing the need to manage their reproductive potential. In particular, we identified four key themes that informants used to warrant women's exclusion from phase I trials: the structure of the drug-development system itself, fears about risks to potential fetuses, distrust of women to prevent pregnancy, and concerns about risks and burdens to institutions from resulting pregnancies. We argue that these rationales reflect structural and cultural barriers to women's inclusion in clinical research that ultimately fail to respect female research participants as persons, highlighting the need for broad-based solutions.

Question prompt lists and caregiver question asking in pediatric specialty appointments: A randomized controlled trial.

OBJECTIVE: Question prompt lists (QPLs) have been effective at increasing patient involvement and question asking in medical appointments, which is critical for shared decision making. We investigated whether pre-visit preparation (PVP), including a QPL, would increase question asking among caregivers of pediatric patients with undiagnosed, suspected genetic conditions. METHODS: Caregivers were randomized to receive the PVP before their appointment (n = 59) or not (control, n = 53). Appointments were audio-recorded. Transcripts were analyzed to determine questions asked. RESULTS: Caregivers in the PVP group asked more questions (MeanPVP = 4.36, SDPVP = 4.66 vs. Meancontrol = 2.83, SDcontrol = 3.03, p = 0.045), including QPL questions (MeanPVP = 1.05, SDPVP = 1.39 vs. Meancontrol = 0.36, SDcontrol = 0.81, p = 0.002). Caregivers whose child had insurance other than Medicaid in the PVP group asked more total and QPL questions than their counterparts in the control group (ps = 0.005 and 0.002); there was no intervention effect among caregivers of children with Medicaid or no insurance (ps = 0.775 and 0.166). CONCLUSION: The PVP increased question asking but worked less effectively among traditionally underserved groups. Additional interventions, including provider-focused efforts, may be needed to promote engagement of underserved patients. PRACTICE IMPLICATIONS: Patient/family-focused interventions may not be beneficial for all populations. Providers should be aware of potential implicit and explicit biases and encourage question asking to promote patient/family engagement.