Public domain human genomic resources are infrastructure: tools researchers use to ask basic biological questions whose answers are then translated into products and care. Translational science now asks them to support an expanding set of tasks, including clinical variant interpretation for diverse populations, pharmacogenomic prescribing, polygenic risk prediction, and the training of clinical artificial intelligence. The corpus of public domain genomes, due in large part to upstream recruitment choices, is not fit for these purposes, and the gap between discovery and translation is widening. This essay argues that closing the gap requires treating public domain genomic infrastructure as a particular object of translational bioethics rather than a technical precondition for it. The limited number of genomes in the public domain relative to the broader genomic record, and the typology-friendliness of how that record represents human variation, are two faces of the same set of upstream choices. Reversing them is not a matter of more sampling under existing terms; it is a matter of building infrastructure of a particular kind; infrastructure made from people. That category, common in genomics but absent from the rest of science, demands an ethical apparatus the field has not yet built. Here we consider the commitments such an apparatus requires, and argue that where, how, and with whom we build genomic infrastructure is itself an ethics question the field has largely declined to ask.
The rapid growth of artificial intelligence and automated systems has significantly impacted digital survey-based research, particularly when recruitment is conducted via social media platforms. This case study details the erosion of data integrity in a 2025 follow-up survey, originally designed to replicate a successful 2021 study. Despite implementing increasingly sophisticated antifraud mechanisms such as CAPTCHA, IP geo-restrictions, and behavioral validation, survey bots repeatedly infiltrated the study, rendering the dataset unusable. This highlights a critical tension between broad digital accessibility and the vulnerability of online research to fraud. Moreover, the use of financial incentives to participate in research, while effective in increasing response rates, was found to amplify bot activity and raise ethical dilemmas surrounding compensation and data quality. As automated deception continues to evolve, researchers must navigate a complex landscape where conventional protections are no longer sufficient. The authors call for the urgent development of fieldwide standards, institutional support, and robust fraud prevention strategies to preserve the methodological and ethical integrity of digital research. Without such measures, the viability of online recruitment and the trustworthiness of the resulting data remain at serious risk.
Human-in-the-loop (HITL) approaches are commonly proposed to address alignment challenges arising from the use of large language models in research ethics oversight. This paper argues that, paradoxically, a HITL can amplify the risk of misalignment. Using the example of protocol triage in research ethics oversight, I demonstrate how reliance on imperfect proxies (observable stand-ins for ethical principles) creates a fundamental proxy-target gap in ethics use-cases. While human ethics committee reviewers are intended to supply phenomenological and causal judgments necessary to bridge this gap, their involvement inadvertently introduces new vulnerabilities: hallucination, over-reliance, reward hacking, and sycophancy. Each vulnerability arises directly from the interaction between human feedback signals and model optimization strategies. I outline key mitigation techniques, including retrieval grounding, calibration drills, structured prompting, and adversarial debate, explaining their distinct costs and benefits. Effective HITL oversight therefore demands specialized ethics committee reviewer competencies. These reviewers must recognize model vulnerabilities, understand mitigation trade-offs, and strategically deploy mitigations to preserve justificational alignment without sacrificing efficiency gains.
Our study examines the perspectives of researchers and other research team members who conducted National Institutes of Health (NIH)-funded studies about their use of a single institutional review board (sIRB) review and onboarding process. More than 84% (n = 639) of respondents agreed that NIH-sponsored multisite clinical trials benefit from sIRB use. A higher proportion of super-users (>10 studies) of an sIRB than moderate users (1-10 studies) described the onboarding process positively (n = 119, 56% vs. n = 225, 42%, p = .01) and found sIRBs to be more cost-effective than a site-specific model (n = 113, 53.05% vs. n = 221, 41%, p <.01). Timeline delays were experienced by over 90% (n = 680) of respondents and an increased administrative burden was reported by almost half (n = 353, 47%) of respondents. Respondents described increased administrative burden for sIRB approvals when an institution-specific application was required (n = 299, 51% vs. n = 30, 29%, p <.01). Most researchers judged sIRBs to be beneficial. However, delays in approval, increased administrative burden, and associated compulsory institution-specific applications posed logistical challenges for researchers. Reform efforts must focus on aligning sIRB and local study site standards to optimize sIRB study review.
Pregnant women have historically been excluded from clinical research, denying pregnant women the benefits of the societal investment in biomedical research and potential direct benefits from research participation. National and international guidance documents have called upon institutional review boards (IRBs) to institute policies to establish the expectation for inclusion of pregnant women in clinical research and require justification when pregnant women are excluded. However, only limited evidence exists regarding the extent to which IRBs have adopted policies consistent with these recommendations. We reviewed IRB policies and related guidance documents from the top 50 research institutions in the United States and the two largest independent IRBs. Four academic and one independent IRB included language that reinforced the view that pregnant women should not be included in research. Conversely, eight academic institutions included language that expressly fostered a culture of inclusion, and five academic institutions included language describing a requirement to justify decisions to exclude pregnant women. Neither independent IRB required justification for exclusion. While some institutions have implemented changes to advance the goal of ethical inclusion, considerable gaps remain between widely endorsed recommendations that IRBs contribute to facilitating appropriate inclusion of pregnant women in research and on-the-ground IRB policies.
It is important to know what motivates people, especially from groups underrepresented in biomedical research, to accept or decline participation in research studies. With this information, engagement strategies, incentives to participate, and benefits of participation can be aligned with what potential research participants value and expect from participating in research. Our project sought to identify what motivated people recruited at a Federally Qualified Health Center (FQHC) to enroll, or not, in the All of Us Research Program (AoU). Qualitative interviews revealed that the most common motivator was the prospect of learning information about their health, especially genetic information that might indicate inherited disease or disease risk, and opportunities for disease prevention. However, our research also revealed that the low-income, medically underserved people typically served by FQHCs face myriad financial, social, and political barriers to reaping the potential health benefits of knowing genetic health information. There is currently a misalignment between what motivates actual and potential research participants to enroll in AoU and the ability of low-income, medically underserved people to use genetic research results to benefit their health. Whether or not learning genetic research results leads to improved health outcomes should be approached as a question rather than an assumption. Embedding research within an unequal society remains a barrier to aligning research participants' motivations with the benefits that participation in research can deliver.
The aim of this paper is to discuss the ethical and legal justification of the broadly accepted ethical principle that researchers may not include adults without decision-making capacity to consent to participating in research studies if there are potential research participants with capacity who could be included instead. From the perspective of disability rights, the paper argues that this ethical principle is overprotective in its current form as it gives insufficient consideration to providing persons with disabilities the opportunity to participate in research on an equal basis with others. Nonetheless, the paper also argues that rather than rejecting this ethical principle entirely, it should be qualified to strike a better balance between protecting people without decisional capacity to consent to research and including them.
Organ chips, also known as organ-on-a-chip devices, tissue chips, or microphysiological systems, have emerged over the last decade as a promising translational technology amidst growing concern about the translational crisis between laboratory research and patient bedside. Pointing to high rates of failure between nonhuman animal models and safety and efficacy in humans, organ chips and similar new approach methods have attracted substantial public and private investment. As human-cell-based alternatives to animal models, organ chips promise more predictive, efficient, and ethical platforms for pharmaceutical and toxicity testing. Engineered cultivation systems that enable cells to assemble into tissue-like structures (e.g. kidney, brain, liver), organ chips mimic tissue architecture and function and live for extended periods of time. This essay considers the translational bioethics issues raised by organ chips, including those that arise early in development such as the obfuscation of cell-origin data, representation in design, and the normalization of conflicts of interest within commercialization-oriented translational science efforts. Integrating a translational bioethics lens from the outset, rather than deferring social and ethical implications analysis to downstream points in technology development and adoption, is essential to realizing the translational promise of organ chips while avoiding the reproduction of existing inequities and ethical conundrums.
Individuals with limited English proficiency (LEP) are a rapidly growing social group in the United States, yet they have been historically under-included in clinical research. This is partly due to the fact that research team members typically conduct the informed consent process in English. While some institutions have policies for how to conduct an informed consent process with individuals who have LEP, many lack structured instructions for consent of LEP participants. Our study investigated whether the human research protection programs and institutional review boards at the top 50 institutions that receive funding from the National Institutes of Health have policies about the inclusion of individuals with LEP in research. We investigated whether they have an inclusion statement, specifications around minimal risk and direct benefit studies, requirements regarding translation of study materials, and provisions for funding the translation of consent forms into non-English languages. We found variation in policies across institutions. Our findings serve as a benchmark to assess the changing landscape regarding the inclusion of individuals with LEP in clinical research, which has the potential to alter care for LEP patients.
The ethical challenges of enrolling critically ill patients into emergency care clinical trials without their consent remain, despite a 30-year regulatory framework for conducting research in the emergency setting. In this series introduction, we outline some suggestions to improve studies conducted under the regulatory framework involving an exception from informed consent for emergency care research. These suggestions were made at a recent workshop sponsored by the National of Institutes of Health.
Effective pain management in prehospital settings remains a significant challenge, particularly for patients with acute trauma. This report examines the complexities of conducting prehospital pain studies, focusing on two clinical trials as case studies. The first trial implemented a novel two-step informed consent process, which, despite its innovation, faced logistical challenges and introduced biases favoring the enrollment of less severely injured patients. The second study, conducted under the federal regulatory pathway for Exception from Informed Consent (EFIC), successfully addressed consent challenges but restricted enrollment to severely injured patients to meet EFIC regulatory requirements. Both studies excluded women of childbearing age due to concerns about fetal safety. These limitations underscore the urgent need for regulatory revisions to expand research with alteration of informed consent, enabling the development of new interventions for prehospital pain management.
Leading medical organizations have called for advancement of pregnancy-specific research to reduce harmful evidence gaps. However, meeting this objective poses ethical, legal, and policy dilemmas for investigators, oversight committees, academic institutions, and sponsors. To better understand the extent to which policies may facilitate or hinder the inclusion of pregnant women in research, we conducted two studies: an international study of laws, regulations, and ethical guidelines from a diverse sample of 59 countries and a study of policies from 84 top-funded US research institutions. We found that most policies use risk-based criteria for determining whether pregnant women should be included in research. Among countries with inclusion policies for pregnant women, 76% had risk-based policies (i.e., inclusion is based on risks and benefits to the pregnant woman and/or fetus), 13% had inclusionary policies (i.e., pregnant women should or must be included in research unless there is a valid scientific or ethical reason for exclusion), and 11% had exclusionary policies (i.e., pregnant women should or must be excluded from research unless there is a valid scientific or ethical reason for inclusion). In the US study, 96% of institutions had risk-based policies, 3% had exclusionary policies, and 1% had inclusionary policies. We also found that many policies referred to pregnant women as vulnerable. To promote fair and responsible inclusion of pregnant women in research, academic institutions, sponsors, and oversight agencies should adopt and implement policies with inclusionary language and refrain from referring to pregnant women as vulnerable.
Evidence-based informed consent practices—such as writing in plain language, formatting for readability, and assessing understanding using validated instruments—are underutilized in research practice. Yet the Common Rule does not specifically require the use of evidence-based informed consent practices. In this paper, we explore the wisdom of mandating evidence-based informed consent practices either at the institutional or federal level. In the first part, we share findings from a series of six focus groups with leaders of institutional review boards (IRBs) about mandating evidence-based informed consent practice. In general, IRB leaders had positive views toward plain language and optimal document formatting but were skeptical about validated assessments of participant comprehension of consent information. They generally opposed federal and institutional mandates, preferring an educational approach to promoting evidence-based informed consent practices. In the second part of the paper, we draw upon data from several of our studies and the literature to defend the conclusion that IRBs should experiment with mandates for evidence-based informed consent practices. We accept that federal regulations may be insufficiently flexible. However, educational efforts alone have not sufficed and are not likely to increase adoption of evidence-based informed consent practices. We believe institutional mandates will not actually lead to greater delays in review of research protocols or investigator burden if rolled out with sufficient guidance and resources, which are readily available.
For many of the decisions made in the clinical care setting, clinicians lack evidence to inform which treatment would result in the best patient outcomes. This problem is particularly common in emergency care, a field in which the condition of the patient and the urgent nature of the treatment often preclude research conducted using prospective informed consent. Large-scale comparative effectiveness clinical trials could address the evidence gaps in clinical medicine and improve patient outcomes but are hindered by the lack of a clear regulatory framework in the United States for low-to-minimal risk trials comparing commonly used treatments. In this paper, we summarize a presentation and discussion that took place at a workshop held by the National Institutes of Health that focused on the issue of informed consent and the appropriate regulatory pathway for comparative effectiveness trials conducted in the emergency care setting. A key insight of this workshop is that generating the comparative effectiveness data needed to improve clinical care will require revising ethical and regulatory oversight practices and related guidance to support the conduct of this socially valuable research.
Much of the discussion of hope in oncology research ethics literature raises concern that hope is problematic because it indicates irrationality or misunderstanding, which makes potential research participants vulnerable to exploitation. If hope is rooted in ignorance, exploitation, or a failure to appreciate risks, then consent is not voluntary. Some argue that research participants who hope for benefit should be rejected from phase I oncology trials because they lack capacity to consent. This article considers how hope relates to rationality and voluntary decision-making, especially in the context of religious faith and terminal illness, and shows that the issue causing concern is not necessarily due to decision-making capacity. Potential participants who hope for medical benefit from a trial should not be rejected on the grounds that they lack capacity; rather, they should be admitted and provided support for moral deliberation, especially when relying on religious reasons for participating in a trial.
Enhanced protection for research participants is often stated as a goal and potential benefit of engaging community partners in research. However, many community-engaged research teams report challenges in completing human research protection (HRP) training. Some human research protection programs (HRPPs) require community researchers to complete the same training that university faculty and staff members are required to do, while others allow alternatives that are more accessible and appropriately suited to community researchers' background and roles. To learn more about general HRPP requirements for training and alternatives for community researchers, we surveyed 163 research institutions funded by the National Institutes of Health's Clinical and Translational Science Award program. Out of 55 respondents, 34 HRPPs (61.8%) allow community researchers to complete different HRP training from that required for faculty/staff. Reasons for allowing or denying alternative training vary, and some institutions that currently do not allow alternatives report that they are reconsidering their policy. The fact that some institutions do not allow alternatives and are not considering changing their policies, even when requested by the principal investigators of studies, may pose significant barriers to community-engaged research. Effort is needed to increase awareness about alternatives as well as their acceptability in meeting training requirements of federal funding agencies.
Navigating the complexities of institutional review board (IRB) determinations in participatory research with transgender youth is essential for prioritizing youth voices and establishing equitable opportunities for research participation. We codesigned an online interactive sexual education tool with an advisory board of transgender youth as lived-experience experts. Early codesign efforts revealed challenges in classifying advisory board members as either research participants or study team members and highlight the frequent irreconcilability between participatory approaches and IRB standards. We describe challenges our research team encountered in the IRB review process and discuss lessons learned, emphasizing the need for flexible IRB guidelines, ongoing consent practices, greater attention to power dynamics, and enhanced IRB education on participatory research, particularly with transgender youth. These lessons highlight critical insights regarding youth involvement in participatory research that are essential for prioritizing youth voices in the creation of effective, youth-led interventions.
Institutional review boards (IRBs) are charged with conducting risk-benefit analysis for early phase clinical trials that often involve high levels of uncertainty regarding a trial's potential risks and benefits. Our study used a survey of IRB chairs to explore how IRBs conduct risk-benefit analysis, the unique facets of risk-benefit analysis for early phase clinical trials and specifically for early phase neurology trials, and what facilitates high-quality risk-benefit analysis. The survey measured IRB chairs' perceived difficulty, preparedness, processes, and satisfaction with risk-benefit analysis for early phase trials. The survey was completed by 148 of the 259 eligible IRB chairs for a response rate of 64.6%. Two-thirds of respondents found risk-benefit analysis for early phase clinical trials more challenging than for later phase trials. Ninety-one percent of respondents felt that their IRB did an "excellent" or "very good" job conducting risk-benefit analysis, but more than one-third of respondents did not feel "very prepared" to conduct key aspects of risk-benefit analysis. Over two-thirds of respondents reported that additional resources, like a standardized process for conducting risk-benefit analysis, would be mostly or very valuable. Our results suggest that conducting risk-benefit analysis for early phase clinical trials generally and early phase neurology trials specifically is challenging for IRBs. One-third of respondents reported that they lack preparation for assessing the scientific value of these types of trials and the risks and benefits to research participants, and a majority desire additional support.
Drawing from a 2023 symposium panel that focused on conducting health equity research with Black communities, we propose to expand our interpretation of core research ethics principles. In light of a surge of research conducted in Black diasporic communities since the 2020 killing of George Floyd, the symposium sought to enhance the quality and impact of research involving Black Canadians. We contend that by broadening the interpretation and application of respect for persons, beneficence, and justice, researchers will conduct impactful and transformative research projects that foster health equity. We emphasize the importance of not limiting the core principle of respect for persons to individual participants but to extend it to communities throughout the research process. Furthermore, we suggest that researchers can deepen their commitment to the core principle of beneficence or concern for welfare and design relevant and empowering research projects through meaningful community involvement. We highlight that to further the implementation of the core principle of justice, scholars should adopt a human development approach and mobilize innovative outreach recruitment strategies to ensure that Black communities have the opportunity to participate in biomedical and public health research while also benefiting from the knowledge produced.
Increasingly, new legal measures are restricting the use of gender-affirming care, raising challenges not only for the medical care of transgender/gender-nonbinary individuals, but also for medical research and research ethics. These restrictions may discourage researchers from conducting various types of research with transgender/gender-nonbinary individuals, such as asking about sexual behavior and gender identity or related issues in studies of adolescents and young adults more broadly. Researchers and institutions may also face professional risks in pursuing such research. Thus, restrictions on the use of gender-affirming care have important implications for researchers, institutional review boards (IRBs), institutional officials, policy-makers, and others. Restrictions could have an impact on the design, implementation, and management of research studies, potentially requiring consent form modifications, reconsent of participants, and asking participants about possible resulting physical/legal/social problems. Researchers and IRBs need to carefully assess these shifting legal restrictions. Input from legal experts may be needed concerning the interpretation, implementation, and enforcement of local and federal legal measures for initial and continuing IRB review of research protocols and the assessment of any changes to relevant legal measures. Researchers, IRBs, and others thus need to recognize, address, and develop "best practices" regarding these new restrictions.
