A qualitative interview study to determine barriers and facilitators of implementing automated decision support tools for genomic data access.

Data access committees (DAC) gatekeep access to secured genomic and related health datasets yet are challenged to keep pace with the rising volume and complexity of data generation. Automated decision support (ADS) systems have been shown to support consistency, compliance, and coordination of data access review decisions. However, we lack understanding of how DAC members perceive the value add of ADS, if any, on the quality and effectiveness of their reviews. In this qualitative study, we report findings from 13 semi-structured interviews with DAC members from around the world to identify relevant barriers and facilitators to implementing ADS for genomic data access management. Participants generally supported pilot studies that test ADS performance, for example in cataloging data types, verifying user credentials and tagging datasets for use terms. Concerns related to over-automation, lack of human oversight, low prioritization, and misalignment with institutional missions tempered enthusiasm for ADS among the DAC members we engaged. Tensions for change in institutional settings within which DACs operated was a powerful motivator for why DAC members considered the implementation of ADS into their access workflows, as well as perceptions of the relative advantage of ADS over the status quo. Future research is needed to build the evidence base around the comparative effectiveness and decisional outcomes of institutions that do/not use ADS into their workflows.

Investigating the Roles and Responsibilities of Institutional Signing Officials After Data Sharing Policy Reform for Federally Funded Research in the United States: National Survey.

BACKGROUND: New federal policies along with rapid growth in data generation, storage, and analysis tools are together driving scientific data sharing in the United States. At the same, triangulating human research data from diverse sources can also create situations where data are used for future research in ways that individuals and communities may consider objectionable. Institutional gatekeepers, namely, signing officials (SOs), are therefore at the helm of compliant management and sharing of human data for research. Of those with data governance responsibilities, SOs most often serve as signatories for investigators who deposit, access, and share research data between institutions. Although SOs play important leadership roles in compliant data sharing, we know surprisingly little about their scope of work, roles, and oversight responsibilities. OBJECTIVE: The purpose of this study was to describe existing institutional policies and practices of US SOs who manage human genomic data access, as well as how these may change in the wake of new Data Management and Sharing requirements for National Institutes of Health-funded research in the United States. METHODS: We administered an anonymous survey to institutional SOs recruited from biomedical research institutions across the United States. Survey items probed where data generated from extramurally funded research are deposited, how researchers outside the institution access these data, and what happens to these data after extramural funding ends. RESULTS: In total, 56 institutional SOs participated in the survey. We found that SOs frequently approve duplicate data deposits and impose stricter access controls when data use limitations are unclear or unspecified. In addition, 21% (n=12) of SOs knew where data from federally funded projects are deposited after project funding sunsets. As a consequence, most investigators deposit their scientific data into "a National Institutes of Health-funded repository" to meet the Data Management and Sharing requirements but also within the "institution's own repository" or a third-party repository. CONCLUSIONS: Our findings inform 5 policy recommendations and best practices for US SOs to improve coordination and develop comprehensive and consistent data governance policies that balance the need for scientific progress with effective human data protections.

Should secondary pharmacogenomic variants be actively screened and reported when diagnostic genome-wide sequencing is performed in a child?

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over time, decision supports to assist using pharmacogenetic results in future treatment decisions, and sharing information in public databases to improve the clinical interpretation of pharmacogenetic variants identified in other children. We conclude by presenting a series of points to consider for clinicians and policymakers regarding whether, and under what circumstances, routine screening and return of pharmacogenomic variants unrelated to the indications for testing is appropriate in children who are undergoing genome-wide sequencing to assist in the diagnosis of a suspected genetic disease.

Achieving Procedural Parity in Managing Access to Genomic and Related Health Data: A Global Survey of Data Access Committee Members.

Data access committees (DACs) are critical players in the data sharing ecosystem. DACs review requests for access to data held in one or more repositories and where specific constraints determine how the data may be used and by whom. Our team surveyed DAC members affiliated with genomic data repositories worldwide to understand standard processes and procedures, operational metrics, bottlenecks, and efficiencies, as well as their perspectives on possible improvements to quality review. We found that DAC operations and systemic issues were common across repositories globally. In general, DAC members endeavored to achieve an appropriate balance of review efficiency, quality, and compliance. Our results suggest a similarly proportionate path forward that helps DACs pursue mutual improvements to efficiency and compliance without sacrificing review quality.

Benefits of sharing neurophysiology data from the BRAIN Initiative Research Opportunities in Humans Consortium.

Sharing human brain data can yield scientific benefits, but because of various disincentives, only a fraction of these data is currently shared. We profile three successful data-sharing experiences from the NIH BRAIN Initiative Research Opportunities in Humans (ROH) Consortium and demonstrate benefits to data producers and to users.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

Enhancing Reciprocity, Equity and Quality of Ethics Review for Multisite Research During Public Health Crises: The Experience of the COVID-19 Clinical Research Coalition Ethics Working Group.

In this paper we report findings from a commissioned report to the COVID-19 Clinical Research Coalition on approaches to streamline multinational REC review/approval during public health emergencies. As currently envisioned in the literature, a system of REC mutual recognition is theoretically possible based on shared procedural REC standards, but raises numerous concerns about perceived inequities and mistrust.

Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi.

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.

Ethics Education for Healthcare Professionals in the Era of ChatGPT and Other Large Language Models: Do We Still Need It?

In this paper, we contend with whether we still need traditional ethics education as part of healthcare professional training given the abilities of chatGPT (generative pre-trained transformer) and other large language models (LLM). We reflect on common programmatic goals to assess the current strengths and limitations of LLMs in helping to build ethics competencies among future clinicians. Through an actual case analysis, we highlight areas in which chatGPT and other LLMs are conducive to common bioethics education goals. We also comment on where such technologies remain an imperfect substitute for human-led ethics teaching and learning. Finally, we conclude that the relative strengths of chatGPT warrant its consideration as a teaching and learning tool in ethics education in ways that account for current limitations and build in flexibility as the technology evolves.

Ethical hazards of health data governance in the metaverse.

Metaverse-enabled healthcare is no longer hypothetical. Developers must now contend with ethical, legal and social hazards if they are to overcome the systematic inefficiencies and inequities that exist for patients who seek care in the real world.

Passive monitoring by smart toilets for precision health.

Smart toilets are a key tool for enabling precision health monitoring in the home, but such passive monitoring has ethical considerations.

A mixed-methods protocol to develop and validate a stewardship maturity matrix for human genomic data in the cloud.

This article describes a mixed-methods protocol to develop and test the implementation of a stewardship maturity matrix (SMM) for repositories which govern access to human genomic data in the cloud. It is anticipated that the cloud will host most human genomic and related health datasets generated as part of publicly funded research in the coming years. However, repository managers lack practical tools for identifying what stewardship outcomes matter most to key stakeholders as well as how to track progress on their stewardship goals over time. In this article we describe a protocol that combines Delphi survey methods with SMM modeling first introduced in the earth and planetary sciences to develop a stewardship impact assessment tool for repositories that manage access to human genomic data. We discuss the strengths and limitations of this mixed-methods design and offer points to consider for wrangling both quantitative and qualitative data to enhance rigor and representativeness. We conclude with how the empirical methods bridged in this protocol have potential to improve evaluation of data stewardship systems and better align them with diverse stakeholder values in genomic data science.

Exome/Genome-Wide Testing in Newborn Screening: A Proportionate Path Forward.

Population-based newborn screening (NBS) is among the most effective public health programs ever launched, improving health outcomes for newborns who screen positive worldwide through early detection and clinical intervention for genetic disorders discovered in the earliest hours of life. Key to the success of newborn screening programs has been near universal accessibility and participation. Interest has been building to expand newborn screening programs to also include many rare genetic diseases that can now be identified by exome or genome sequencing (ES/GS). Significant declines in sequencing costs as well as improvements to sequencing technologies have enabled researchers to elucidate novel gene-disease associations that motivate possible expansion of newborn screening programs. In this paper we consider recommendations from professional genetic societies in Europe and North America in light of scientific advances in ES/GS and our current understanding of the limitations of ES/GS approaches in the NBS context. We invoke the principle of proportionality-that benefits clearly outweigh associated risks-and the human right to benefit from science to argue that rigorous evidence is still needed for ES/GS that demonstrates clinical utility, accurate genomic variant interpretation, cost effectiveness and universal accessibility of testing and necessary follow-up care and treatment. Confirmatory or second-tier testing using ES/GS may be appropriate as an adjunct to conventional newborn screening in some circumstances. Such cases could serve as important testbeds from which to gather data on relevant programmatic barriers and facilitators to wider ES/GS implementation.

Institutional Review Board Use of Outside Experts: A National Survey.

BACKGROUND: Institutional review board (IRB) expertise is necessarily limited by maintaining a manageable board size. IRBs are therefore permitted by regulation to rely on outside experts for review. However, little is known about whether, when, why, and how IRBs use outside experts. METHODS: We conducted a national survey of U.S. IRBs to characterize utilization of outside experts. Our study uses a descriptive, cross-sectional design to understand how IRBs engage with such experts and to identify areas where outside expertise is most frequently requested. RESULTS: The survey response rate was 18.4%, with 55.4% of respondents reporting their institution's IRB uses outside experts. Nearly all respondents who reported using outside experts indicated they do so less than once a month, but occasionally each year (95%). The most common method of identifying an outside expert was securing a previously known subject matter expert (83.3%). Most frequently, respondents sought consultation for scientific expertise not held by current members (69.6%). Almost all respondents whose IRBs had used outside experts reported an overall positive impact on the IRB review process (91.5%). CONCLUSIONS: Just over half of the IRBs in our sample report use of outside experts; among them, outside experts were described as helpful, but their use was infrequent overall. Many IRBs report not relying on outside experts at all. This raises important questions about what type of engagement with outside experts should be viewed as optimal to promote the highest quality review. For example, few respondents sought assistance from a Community Advisory Board, which could address expertise gaps in community perspectives. Further exploration is needed to understand how to optimize IRB use of outside experts, including how to recognize when expertise is lacking, what barriers IRBs face in using outside experts, and perspectives on how outside expert review impacts IRB decision-making and review quality.

Leveraging Algorithms to Improve Decision-Making Workflows for Genomic Data Access and Management.

Studies on the ethics of automating clinical or research decision making using artificial intelligence and other algorithmic tools abound. Less attention has been paid, however, to the scope for, and ethics of, automating decision making within regulatory apparatuses governing the access, use, and exchange of data involving humans for research. In this article, we map how the binary logic flows and real-time capabilities of automated decision support (ADS) systems may be leveraged to accelerate one rate-limiting step in scientific discovery: data access management. We contend that improved auditability, consistency, and efficiency of the data access request process using ADS systems have the potential to yield fairer outcomes in requests for data largely sourced from biospecimens and biobanked samples. This procedural justice rationale reinforces a broader set of participant and data subject rights that data access committees (DACs) indirectly protect. DACs protect the rights of citizens to benefit from science by bringing researchers closer to the data they need to advance that science. DACs also protect the informational dignities of individuals and communities by ensuring the data being accessed are used in ways consistent with participant values. We discuss the development of the Global Alliance for Genomics and Health Data Use Ontology standard as a test case of ADS for genomic data access management specifically, and we synthesize relevant ethical, legal, and social challenges to its implementation in practice. We conclude with an agenda of future research needed to thoughtfully advance strategies for computational governance that endeavor to instill public trust in, and maximize the scientific value of, health-related human data across data types, environments, and user communities.

A systematic literature review to identify ethical, legal, and social responsibilities of nonprofit organizations when funding clinical trials in pediatric cancer.

Nonprofit organizations (NPOs) play critical roles as funding sources, research partners, and disseminators of drug developments in pediatric cancer. Yet the literature provides limited guidance about ethical best practices when NPOs make trial funding decisions in this space. We conducted a systematic review of the literature indexed in PubMed and Web of Science to identify the ethical, legal, and social responsibilities of NPOs to four key stakeholder groups in funding pediatric cancer trials: (i) patients/families, (ii) researchers, (iii) industry sponsors, and (iv) donors. We applied the lifecycle framework for patient engagement in drug research and development proposed by Geissler and colleagues to analyze themes related to NPOs' responsibilities across 54 articles that met our inclusion criteria. Emergent themes included transparency surrounding conflicts of interest, the rigor of scientific review, and communication with patients/communities about trial progress. Our research identified critical gaps in best practices for negotiating research partnerships, managing competing research priorities, and pursuing alternative financing models including venture philanthropy. Results from our review informed a set of best practices to guide NPOs in making trial funding decisions that align with stakeholder values and interests.

Insights for Teaching During a Pandemic: Lessons From a Pre-COVID-19 International Synchronous Hybrid Learning Experience.

BACKGROUND AND OBJECTIVES: Medical educators and researchers have increasingly sought to embed online educational modalities into graduate medical education, albeit with limited empirical evidence of how trainees perceive the value and experience of online learning in this context. The purpose of this study was to explore the experiences of hybrid learning in a graduate research methods course in a family medicine and primary care research graduate program. METHODS: This qualitative description study recruited 28 graduate students during the fall 2016 academic term. Data sources included qualitative group discussions and a 76-item online survey collected between March and September 2017. We used thematic analysis and descriptive statistics to analyze each data set. RESULTS: Nine students took part in three group discussions, and completed an online survey. While students reported positive learning experiences overall, those attending virtually struggled with the synchronous elements of the hybrid model. Virtual students reported developing research skills not offered through courses at their home institution, and students attending the course in person benefited from the diverse perspectives of distance learners. All stressed the need to foster a sense of community. CONCLUSIONS: Quality delivery of online graduate education in family medicine research requires optimizing social exchanges among virtual and in-person learners, ensuring equitable engagement among all students, and leveraging the unique tools afforded by online platforms to create a shared sense of a learning community.