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ABSTRACTOver 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.

Background: Since the National Institutes of Health (NIH) Revitalization Act of 1993, focus on the equitable inclusion of women in clinical research has been ongoing. NIH's 2015 sex as a biological variable (SABV) policy aims to transform research design, analysis, and reporting in the preclinical sphere by including male and female organisms in vertebrate animal research as well as human studies. However, questions remain regarding how researchers and members of research oversight committees perceive the value and need of the SABV policy. Materials and Methods: Based on 62 interviews with animal researchers and oversight personnel, we analyze what the animal research community knows about the policy and sees as the benefits and challenges of implementation. Results: We found that the 62 interviewees disagreed about the need for the policy, with some being supportive and others questioning whether the policy is based on science or is politically motivated. There were also tensions in how interviewees conceptualized the challenges to and resources needed for implementing the SABV policy. For instance, while some thought implementation would require a significant increase in numbers of animals used for each study, others explicitly rejected this claim. Conclusions: We conclude by discussing the practical and social implications of our findings about the views of members of the animal research community regarding the SABV policy.

ABSTRACTPhase I healthy volunteer trials test the safety and tolerability of investigational pharmaceuticals. In them, participants are exposed to study‐drug risks without the possibility of direct medical benefit and typically must spend days or weeks in a residential research facility. Monetary payments are used to incentivize enrollment and compensate participants for their time. Together, these features of phase I healthy volunteer trials create a research context that differs markedly from most other clinical research, including by enrolling disproportionate numbers of economically disadvantaged people of color as participants. Due to these unique trial features and participation patterns, traditional biomedical research oversight offers inadequate ethical and policy guidance for phase I healthy volunteer research. This article details five ethical criteria crafted to be responsive to the particularities of this type of research: translational science value, fair opportunity and burden sharing, fair compensation for service, experiential welfare, and enhanced voice and recourse.

<b><i>Background:</i></b> Online study recruitment is increasingly popular, but we know little about the decision making that goes into joining studies in this manner. In GeneScreen, a genomic screening study that utilized online education and consent, we investigated participants' perceived ease when deciding to join and their understanding of key study features. <b><i>Methods:</i></b> Individuals were recruited via mailings that directed them to a website where they could learn more about GeneScreen, consent to participate, and complete a survey. <b><i>Results:</i></b> Participants found it easy to decide to join GeneScreen and had a good understanding of study features. Multiple regression analyses revealed that ease of deciding to join was related to confidence in one's genetic self-efficacy, limited concerns about genetic screening, trust in and lack of frustration using the website, and the ability to spend a limited time on the website. Understanding of study features was related to using the Internet more frequently and attaining more information about GeneScreen conditions. <b><i>Conclusions:</i></b> The ease of deciding to join a genomic screening study and comprehension of its key features should be treated as different phenomena in research and practice. There is a need for a more nuanced understanding of how individuals respond to web-based consent information.

The advent of human gene editing has stimulated international interest in how best to govern this research. However, research on stakeholder views has neglected scientists themselves. We surveyed 212 scientists who use gene editing in their work. Questions captured views on oversight and use of somatic and germline human gene editing for treatment, prevention, and enhancement. More respondents were supportive of somatic than germline editing, and more supported gene editing for treatment compared to prevention. Few supported its use for enhancement. When presented with specific conditions, levels of support for somatic editing differed by type of condition. Almost all respondents said scientists and national government representatives should be involved in oversight, but only 28% said scientists are best positioned to oversee gene-editing research. These results can inform the development of sound approaches to research governance, demonstrating the importance of identifying specific gene-editing uses when considering oversight.

For years, genomic medicine—medicine based on the growing understanding of the genetic contribution to many diseases and conditions—has been hailed as the future of medical treatment, but it has thus far had limited effect on day-to-day medical practice. The ultimate goal of genomic medicine has always been the ability not just to identify dangerous gene mutations, but to fix them. Now CRISPR and related genome-editing technologies may have the potential to provide a safe and effective way to repair dangerous mutations. In the wake of ethically dubious experiments with human embryos in China, the international governance of human genome editing is emerging as an urgent topic for scientists, regulators, and the public. Efforts to develop a governance model are underway at national and international levels. These efforts are the subject of multiple initiatives by national and international health and science organizations and are topics of discussion at scientific conferences, summits, and meetings. This Article reports on the Authors' multi-year, interdisciplinary project to identify and investigate the practical, ethical, and policy considerations that are emerging as the greatest concerns about human genome editing, and ultimately to develop policy options. The project involves monitoring the discussions of groups, both government-sponsored and private, that are considering how genome editing should be governed; observing conferences where the topic is discussed; analyzing emerging policy reports by national and international bodies; and interviewing a wide range of stakeholders, including scientists, ethicists, and those who make and comment on public policy. The Article identifies several stakeholder concerns that are especially prominent in the research to date and begins to explore the implications of these concerns for alternative models of governance. There are current indications that, for practical purposes, a focus on "soft," hybrid forms of governance based on networks of multiple public and private ...

AbstractIntroductionThe South East Asia Research Collaboration in HIV (SEARCH) RV411 clinical trial in Thailand was a systematic investigation of analytic treatment interruption (ATI) in individuals diagnosed and treated since Fiebig stage I acute HIV infection. Here, we explore decision‐making processes and perceptions of trial participation in a phase I trial that raised important ethical considerations, to identify potential areas of improvement in this relatively new field of HIV research. Similar considerations apply to other HIV phase I trials, especially those involving ATI, making this trial a model to identify challenges and opportunities in promoting informed choice.MethodsUsing longitudinal semi‐structured interviews and a validated questionnaire, we examined how decisions to join or decline the trial were made, whether there was evidence of decisional conflict, and reactions to the trial outcomes. We also explored contrasting views and experiences in this small trial cohort. We report analyses of data from these questionnaires and interviews, conducted from February through December of 2016 with the 14 SEARCH cohort participants who either joined (n = 8) or declined (n = 6) participation in RV411.ResultsThe eight participants and six decliners had low overall decisional conflict, which remained low over time. Decision making was more difficult for decliners than participants, at least initially. While all interviewees described being satisfied with their decisions, our study identified important negative consequences for a few individuals, including seroconversion, negative experiences with optional procedures and disappointment due to rapid viral rebound.ConclusionsAlthough our results reflect the experiences of a small group invited to join this trial, our overall finding of low decisional conflict even while some individuals reported negative experiences provides lessons for clinical trial investigators. We developed points‐to‐consider in helping participants make informed choices, to support participants during the trial and to support decliners in their decisions.

INTRODUCTION: Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium. METHODS: A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing. RESULTS: Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects. CONCLUSIONS: In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.