Widening the Lens
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The inaugural issue of Ethics & Human Research (E&HR) marks an exciting milestone in The Hastings Centers’ 40‐year history of publishing a journal that focuses on the ethical, regulatory, and policy issues related to research with humans. Like its predecessor, IRB: Ethics & Human Research, E&HR will publish conceptual and empirical analyses on a wide range of topics related to the human research enterprise.
The journal’s name change conveys to the global community of authors and readers that E&HR is not solely about issues related to institutional review boards (IRBs) in the United States. The title shift provides an opportunity to identify new ethical, policy, and regulatory challenges that rapid developments in science, medicine, and regulatory frameworks bring to the conduct and oversight of human subjects research in the United States and elsewhere. Along with publishing work that investigates new challenges, E&HR aims not only to draw attention to unresolved issues but also to broaden the scope of issues for investigation and analysis in the field of human research ethics. The pieces in this inaugural issue identify several new challenges and hint at some of the unresolved issues and broader topics that merit further attention.
In the lead article, about phase I clinical trials with healthy volunteers, Jill Fisher and Rebecca Walker propose adapting the ethical concepts and oversight mechanisms that are applied to research with nonhuman animals to enhance the welfare of healthy human volunteers in such trials, improve oversight of the trials, and more critically assess their scientific value. For example, using a “model‐organism” approach to advance the ethical framework for phase I healthy‐volunteer trials would draw attention to shared structural features of animal and human research. As is the case with animal subjects, human participants in healthy‐volunteer trials are typically confined at a research facility. Participants in these trials cannot leave the study site during the duration of the trial—which can last 24 hours or more—unless they withdraw from the study. While animal research regulations require adherence to specific health and welfare conditions for the confinement of animals used in research, the authors point to gaps in ethics and regulatory standards on these matters for the confinement of healthy human volunteers in phase I trials.
Articles by Holly Taylor et al. and Robert Klitzman et al. address new challenges with respect to IRB review and oversight of protocols for multisite studies. In response to two new federal policies, the protocols for most federally funded multisite studies must be reviewed and approved by a single IRB of record, rather than the IRB at each research site. Taylor and Klitzman and their respective colleagues show that concerns have been raised about whether the single IRB of record will have access to the local knowledge each research site’s IRB would have taken into consideration in reviewing a protocol for a multisite study. Klitzman et al. identify an empirical research agenda to foster “learning single IRBs,” yet note that some IRBs have been reluctant to participate in empirical and observational studies about IRB processes and decision‐making. What obligation do IRBs and other types of research ethics committees have to participate in empirical studies of policies and practices regarding ethics review of research protocols and ongoing oversight of research studies? How transparent should they be about the outcomes of their protocol decisions, particularly if their institutions receive federal funding for such research?
In the case study about Costa Rica’s moratorium on human research, Michael Householder et al. highlight the challenges countries face in adhering to international ethical standards for human subjects research when they have a weak regulatory and ethics oversight infrastructure, particularly when studies are sponsored by foreign pharmaceutical companies. Although these issues are not new, the case study is a reminder that research ethics capacity building does not happen overnight and that a country’s cultural values and existing health, social, and regulatory infrastructures play important roles in how capacity building moves forward. With industry‐funded trials on the rise and the more and more frequent exportation of trial sites to countries that may have weak regulatory infrastructures, additional case studies along with empirical investigations are needed to identify ethical, regulatory, and policy gaps regarding human subjects protections that exist in those countries.
E&HR also aims to expand the boundaries of inquiry by publishing conceptual and empirical studies that examine the ethical, policy, and regulatory implications of some research that does not directly involve humans as research participants. For example, research with humans’ digital data from social media and other “big data” collections and platforms is advancing at a rapid pace, yet it is unclear whether and the extent to which such research has implications for the privacy and confidentiality interests of the individuals from whom the data were obtained. And the scientific value of preclinical studies involving animals and other nonhuman models (such as in vitro assays, epidemiological studies, and computer simulations) has ethical implications for the translation of such research to human trials. Asking healthy individuals or patients to volunteer for phase I studies designed on the basis of unreliable safety or efficacy data from animal and other preclinical research raises issues about informed consent and ethics committee approval and oversight of phase I trials, as well as for later‐phase efficacy trials that recruit hundreds of patients. Given the increasing concerns about the irreproducibility of preclinical studies, what questions about relevant preclinical studies should IRBs and other research ethics committees be asking when reviewing protocols for human studies, especially for first‐in‐human trials? How vigilant should they be in determining whether the protocols they review accurately report both negative and positive results from preclinical studies?
Other important issues E&HR will address include research with humans that involves novel biotechnologies such as genome‐editing techniques; cell‐, gene‐, and tissue‐based interventions; and preventive and therapeutic neurological drug and device interventions. Are there new or unresolved issues about existing ethics oversight mechanisms and regulatory frameworks that these new technologies raise when tested in humans? What ethical obligations, if any, do funders, researchers, or their institutions have to longitudinally study the benefits or harms to research participants whose cells were modified by complex genetic or tissue‐engineering applications or whose neural implants can never be removed? Does the answer differ if the participant is a child, an adolescent, or an adult?
These questions, along with those raised by the authors in this issue, are just a few of the important topics in human research ethics that E&HR will cover in traditional articles, case studies, commentaries, and book reviews. And E&HR stands ready to give voice to new ethical, regulatory, and policy challenges that may emerge as 21st‐century science and medicine continue to move into unchartered territories.