The Institute of Medicine has called on health care leaders to transform their health systems into “learning health care systems,” capable of studying and continuously improving their practices. Learning health care systems commit to carrying out numerous kinds of investigations, ranging from clinical effectiveness studies to quality improvement research and implementation science. There has been progress in realizing the IOM's vision, but also many challenges. One of these challenges has been lingering uncertainty about whether the data collection and monitoring central (...) to learning health care systems is actually research and if so, what kind of ethical oversight it should have. This is not a new question. Yet so far, there has been no foundational analysis of the fit between the existing human subjects protection framework in use in the United States and the new kinds of data collection activities that are being, and increasingly will be, undertaken by learning health care systems. Two companion feature articles in this volume, by a team at Johns Hopkins, fill this void. (shrink)

The papers by Nancy Kass, Ruth Faden, and colleagues describe an ethical imperative to study clinical care as it is being delivered. The goal of learning from each patient is attractive, but integrating research and clinical practice is not easy. The authors suggest that the bioethical framework in use for the past forty years to oversee clinical research may be as much an impediment to the development of a learning health care system as a means of protecting the interests (...) of patients. This framework draws a bright line between clinical research and clinical care activities, subjecting clinical research to institutional review and ongoing oversight while assuming that clinical care is conducted primarily in the interests of patients and not in need of additional ethical oversight. The authors identify five characteristics that have been used to distinguish the two activities, and they conclude that none succeed. The practical implications of this conclusion are left unspecified, however. Should ethical oversight simply be eliminated for these kinds of research activities on the grounds that oversight is not mandated for clinical care and the two cannot be distinguished? (shrink)

Institutional review boards distinguish health care quality improvement and health care quality improvement research based primarily on the rigor of the methods used and the purported generalizability of the knowledge gained. Neither of these criteria holds up upon scrutiny. Rather, this apparently false dichotomy may foster under-protection of participants in QI projects and over-protection of participants within QIR.

We provide additional information relevant to our previous publication on the quality of reports of investigations of research integrity by academic institutions. Despite concerns being raised about ethical oversight of research published by a group of researchers, each of the four institutional investigations failed to determine and/or report whether ethics committee approval was obtained for the majority of publications assessed.

Researchers and others involved in the research enterprise from 12 African countries met with those working in ethics and oversight in the United States as part of an effort to develop research ethics capacity. Drawing on a wealth of experience among participants, discussions at the meeting revealed five categories of issues that warrant careful attention by those engaged in similar efforts as well as international policymakers and those charged with oversight of research. Principal investigators should build ‘true research (...) teams’ where members of the team are meaningfully involved in decisions regarding the protocol and its implementation. There should be explicit discussion about the ‘standard of care’ at the outset of project planning that includes clarification of the terminology that is being used. While internationally collaborative research may involve populations that have inherent vulnerabilities, it is important to recognize the limitations of host country solutions and look for means to negotiate appropriate protections for those willing to participate. In conducting research involving biological materials it would be prudent to develop material transfer agreements at the outset of the study to clarify expectations and to minimize the likelihood of harm. Those engaged in internationally collaborative research need to be alert to the potential conflicts of interests of host country ethics committees during the approval process and to take measures to manage them if they indeed exist. (shrink)

This paper argues that international development research should be submitted to the oversight of research ethics committees from the countries where data will be collected. This includes research conducted by individuals who may fall outside the jurisdictions of most ethics guidelines or policies, such as individuals contracted by non-governmental organizations. The argument is grounded in an understanding of social justice that recognizes that not seeking local ethics approval can be an affront to the decolonization movement, and may lead to (...) significant direct harms to participants. Local ethics oversight can help ensure projects appropriately take into consideration local laws, regulations, priorities and context. For example, a local research ethics committee may be in a better position than a foreign one to assess whether any given proposed project carries context-specific risks. In addition, submitting to a local research ethics committee is to acknowledge the legitimacy of local authorities, thereby taking a stance against the history of colonizing disempowerment. Local oversight is a mechanism to increase the accountability of researchers working abroad: if respect for local authority and tailoring to local context are to be upheld, there must be mechanisms to ensure that research that does not meet these requirements does not proceed. Objections based on the limited oversight capacity in some countries and on concerns related to the politicization of the review process are discussed. Finally, the roles and responsibilities of the various stakeholders in the implementation of greater local ethics oversight are laid out. (shrink)

Disaster research has grown in scope and frequency. Research in the wake of disasters and during humanitarian crises – particularly in resource-poor settings – is likely to raise profound and unique ethical challenges for local communities, crisis responders, researchers, and research ethics committees. Given the ethical challenges, many have questioned how best to provide research ethics review and oversight. We contribute to the conversation concerning how best to ensure appropriate ethical oversight in disaster research and (...) argue that ethical disaster research requires of researchers and RECs a particular sort of ongoing, critical engagement which may not be warranted in less exceptional research. We present two cases that typify the concerns disaster researchers and RECs may confront, and elaborate upon what this ongoing engagement might look like – how it might be conceptualized and utilized – using the concept of real-time responsiveness. The central aim of RTR, understood here as both an ethical ideal and practice, is to lessen the potential for research conducted in the wake of disasters to create, perpetuate, or exacerbate vulnerabilities and contribute to injustices suffered by disaster-affected populations. Well cultivated and deployed, we believe that RTR may enhance the moral capacities of researchers and REC members, and RECs as institutions where moral agency is nurtured and sustained. (shrink)

Urban communities experiencing marginalization often disproportionately bear the risks and burdens of research and are left out of research ethics governance processes. To address this, many communities have created place-based and community-led research ethics governance initiatives to ensure that community voice is included in discussions surrounding research conduct. Place-based strategies in the Vancouver Downtown Eastside, the Bronx, and the Philadelphia Promise Zone successfully mobilize community perspectives in research ethics, filling in a significant gap in our current system of institutional research (...) ethics review and oversight. These cases demonstrate that place-based research ethics governance has the potential to account for the community-level risks posed by research projects and to ensure communities receive more felt benefits. Place-based communities sidestep simplistic notions of identity based on single shared features and make space for intersectional analyses and diverse community viewpoints to be considered. Such communities have a unique claim to expertise given their shared experience of place, which grants them the ability to see problematic assumptions embedded in scientific projects as well as community-level concerns within research. Despite this, many marginalized communities are excluded from current research ethics oversight processes. This exclusion demands critical examination and a way forward to facilitate the integration of place-based community oversight strategies within research ethics governance. (shrink)

Background. Africa has seen an increase in the number of health research projects being conducted on the continent, particularly clinical trials. Ideally, this should be accompanied by a commensurate improvement in research ethics review capacity to competently provide the much-required research ethics oversight. Unfortunately, this is not the case in many African countries, which are still grappling with weak research ethics oversight capacity, not only at national level but also at institutional level. Objectives. To describe the proposal by (...) Kenya’s national research ethics regulatory authority, the National Commission for Science Technology and Innovation (NACOSTI), to build the capacity of its National Scientific and Ethics Committee (NSEC), tasked with providing the required research ethics oversight in the country. Methods. This is the proposal submitted by NACOSTI to the European and Developing Countries Clinical Trials Partnership for funding of a project entitled ‘Strengthening Research Ethics and Oversight in Kenya’ (STReK). It describes the activities involved to strengthen the NSEC to provide the required research ethics in the country, and to build the research ethics capacity of research ethics committees (RECs) it has accredited, through training and mentorship programmes, to enable them to efficiently review research proposals. Results. Proposed activities of the project are presented. Implementation of the activities described is ongoing. Conclusion. Lessons learnt in this regard may be of benefit to other research ethics regulatory authorities in resource-constrained countries aiming to strengthen their research ethics oversight capacity. (shrink)

Cloning Trevor, a story about therapeutic cloning research, appeared in the June issue of The Atlantic Monthly. The story gives a human face to the people whom therapeutic cloning could benefit. It presents an argument for government funding and it puts the usual calls for a moratorium on embryonic stem cell research to allow for more debate, in a less favourable light. The story also highlights some problems with ethical oversight.

The current system of ethical oversight in the United States is based on Institutional Review Board (IRB) review. The system was established in response to well-known and egregious mistreatment of subjects in both biomedical and social and behavioral research. In the decades since the research regulations were enacted, reaction to the burden of IRB oversight has led the system to focus on compliance and limit its active oversight disproportionately to studies that could present the risk of (...) physical harm. At the same time, the characteristics of the research enterprise have changed and methodologies now present novel risks that were not envisioned in the regulations. We convened a group of IRB professionals, academic leaders, and others to discuss limitations of the current system, how that system could be changed to recognize evolving risks and an increasing focus on participant and community voice, and how it could better serve the needs of researchers and support the societal project of science as a public good. Recommendations included a call to reexamine the academic incentive structure, to develop a system to support consideration of ethical principles from the time of study design, and to explicitly provide different ethical support and oversight for high-risk interventional trials and lower risk biomedical and social behavioral research. (shrink)

Developing countries face numerous barriers to conducting effective and efficient ethics reviews of international collaborative research. In addition to potentially overlooking important scientific and ethical considerations, inadequate or insufficiently trained ethics committees may insist on unwarranted changes to protocols that can impair a study's scientific or ethical validity. Moreover, poorly functioning review systems can impose substantial delays on the commencement of research, which needlessly undermine the development of new interventions for urgent medical needs. In response to these concerns, (...) the Drugs for Neglected Diseases Initiative, an independent nonprofit organization founded by a coalition of public sector and international organizations, developed a mechanism to facilitate more effective and efficient host country ethics review for a study of the use of fexinidazole for the treatment of late stage African Trypanosomiasis. The project involved the implementation of a novel ‘pre-review’ process of ethical oversight, conducted by an ad hoc committee of ethics committee representatives from African and European countries, in collaboration with internationally recognized scientific experts. This article examines the process and outcomes of this collaborative process. (shrink)

As biomedical citizen science initiatives become more prevalent, the unique ethical issues that they raise are attracting policy attention. One issue identified as a significant concern is the ethical oversight of bottom-up biomedical citizen science projects that are designed and executed primarily or solely by members of the public. That is because the federal rules that require ethical oversight of research by institutional review boards generally do not apply to such projects, creating what has been (...) called an ethics gap. -/- Working to close this gap, practitioners and scholars have considered new mechanisms of ethical oversight for biomedical citizen science. To date, however, participants’ attitudes about ethics and oversight preferences have not been systematically examined. This information is useful to efforts to develop ethical oversight mechanisms because it provides a basis for evaluating the likely effectiveness of specific features of such mechanisms and their acceptability from the perspective of biomedical citizen scientists. -/- Here, we report data from qualitative interviews with 35 stakeholders in bottom-up biomedical citizen science about their general ethics attitudes and preferences regarding ethical oversight. Interviewees described ten ethical priorities and endorsed oversight mechanisms that are voluntary, community-driven, and offer guidance. Conversely, interviewees rejected mechanisms that are mandatory, hierarchical, and inflexible. Applying these findings, we conclude that expert consultation and community review models appear to align well with ethical priorities and oversight preferences of many biomedical citizen scientists, although local conditions should guide the development and use of mechanisms in specific communities. (shrink)

Calls are increasing for American health care to be organized as a learning health care system, defined by the Institute of Medicine as a health care system “in which knowledge generation is so embedded into the core of the practice of medicine that it is a natural outgrowth and product of the healthcare delivery process and leads to continual improvement in care.” We applaud this conception, and in this paper, we put forward a new ethics framework for it. No such (...) framework has previously been articulated. The goals of our framework are twofold: to support the transformation to a learning health care system and to help ensure that learning activities carried out within such a system are conducted in an ethically acceptable fashion. (shrink)

Char and colleagues provide a useful conceptual framework for the proactive identification of ethical issues arising throughout the lifecycle of machine learning applications in healthcare. Th...

In their paper, “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care,” Stephanie Morain and Emily Largent (2023) argue that investigators, and poss...

The primary purpose of Institutional Review Boards (IRBs) is to protect the rights and welfare of human research participants. Evaluation and measurement of how IRBs satisfy this purpose and other important goals are open questions that demand empirical research. Research on IRBs, and the Human Research Protection Programs (HRPPs) of which they are often a part, is necessary to inform evidence-based practices, policies, and approaches to quality improvement in human research protections. However, to date, HRPP and IRB engagement in empirical (...) research about their own activities and performance has been limited. To promote engagement of HRPPs and IRBs in self-reflective research on HRPP and IRB quality and effectiveness, barriers to their participation need to be addressed. These include: extensive workloads, limited information technology systems, and few universally accepted or consistently measured metrics for HRPP/irb quality and effectiveness. Additionally, institutional leaders may have concerns about confidentiality. Professional norms around the value of participating in this type of research are lacking. Lastly, obtaining external funding for research on IRBs and HRPPs is challenging. As a group of HRPP professionals and researchers actively involved in a research consortium focused on IRB quality and effectiveness, we identify potential levers for supporting and encouraging HRPP and IRB engagement in research on quality and effectiveness. We maintain that this research should be informed by the core principles of patient- and community-engaged research, in which members and key stakeholders of the community to be studied are included as key informants and members of the research team. This ensures that relevant questions are asked and that data are interpreted to produce meaningful recommendations. As such, we offer several ways to increase the participation of HRPP professionals in research as participants, as data sharers, and as investigators. (shrink)

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System as an alternative pathway (...) based on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies. (shrink)

Board oversight of community benefit constitutes an ethical imperative for nonprofit health care organizations. By "ethical imperative" we mean a health care organization's duty to fulfill value-based obligations that transcend compliance requirements in order to be consistent with its basic sense of purpose. We consider three points here: the existence of a distinctively ethical imperative for board oversight, the fact that the imperative is organizational in nature, and practical ways to fulfill its obligations. To explain (...) the meaning of ethical imperative, offer analytical clarification, and provide evidence-based guidelines we adopt an organizational ethics paradigm. Because community benefit for tax-exempt .. (shrink)

In spite of many and varied concerns that the processes of institutional ethical review are flawed, cumbersome, and in need of reform, these processes do provide effective protection in certain sit...

The ethics research community has all but ignored issues of oversight ethics – the vices and virtues of overseers. This study develops a conceptual framework for exploring the ethics of oversight and provides insights into the design of codes of ethics for oversight institutions and for overseers. Analysis of business licensing in Israel reveals prospective and retrospective oversight ethics problems at the levels of national and local policy and implementation: Overseers failed to act on knowledge of (...) breaches of business licensing stipulations and took action known to be slow and ineffective; policymakers neglected their duty to enact significant policy change in an oversight system that was clearly not working. Partially as a result of these oversight failures, over one third of Israeli businesses are unlicensed, 23 people were killed in the collapse of an unlicensed banquet hall, 2 major fires erupted in the same shopping mall, and a fire in a fertilizer warehouse very nearly became a mega-disaster. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with (...) an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)

A robust measure of whether local oversight of human subjects research is achieving the ethical goals of research oversight has never been developed. Assessing whether the local review process is achieving the ethical goals of research oversight will allow institutions to monitor their own human subjects protection programs and guide the investment of funds to improve performance. Without a measure of ethical quality, institutions, institutional review boards, regulators, and the public have no way of (...) knowing if the intent of regulations is being realized. (shrink)

Artificial Intelligence (AI), especially of the machine learning (ML) variety, is used by health care organizations to assist with a number of tasks, including diagnosing patients and optimizing operational workflows. AI products already proliferate the health care market, with usage increasing as the technology matures. Although AI may potentially revolutionize health care, the use of AI in health settings also leads to risks ranging from violating patient privacy to implementing a biased algorithm. This chapter begins with a broad overview of (...) health care AI and how it is currently used. We then adopt a “lifecycle” approach to discussing issues with health care AI. We start by discussing the legal and ethical issues pertaining to how data to build AI are gathered in health care settings, focusing on privacy. Next, we turn to issues in algorithm development, especially algorithmic bias. We then discuss AI deployment to treat patients, focusing on informed consent. Finally, we will discuss existing oversight mechanisms for health AI in the United States: liability and regulation. (shrink)

To judge from the rash of recent law review articles, it is a miracle that research with human subjects in the U.S. continues to draw breath under the asphyxiating heel of the rent-seeking, creativity-stifling, jack-booted bureaucrethics that is the current system of research ethics oversight and review. Institutional Review Boards, sometimes called Research Ethics Committees, have been accused of perpetrating “probably the most widespread violation of the First Amendment in our nation's history,” resulting in a “disaster, not only for (...) academics, but for the whole nation.” One member of the President's Council on Bioethics went so far as to assert, “There has been no greater damage to academic freedom in the United States in my lifetime. And my lifetime encompasses McCarthy and it encompasses political correctness, both.” Locked in the bureaucratic “iron cage” of IRB oversight, critics charge that researchers have been transformed into a vulnerable, exposed population, subject to domination, that has been likened in one case to a kind of “Tuskegee in reverse.”. (shrink)

Medical research saves lives--yet all too often, it is thwarted by a review system supposed to safeguard patients that instead creates needless delays and expense. Institutional Review Boards, which exist at every hospital and medical school that conducts medical research, have ended up imposing such complex, draconian conditions that research is frequently damaged, delayed, and distorted. This is why medical miracles like the COVID-19 vaccines, which were developed at warp speed, are far too rare. Instead, medical research in countless areas (...) is kept at a horse-and-buggy pace. The result: unnecessary suffering and avoidable deaths. From Oversight to Overkill vividly recounts the story behind this crisis, one that remains unknown to the general public. Family physician and ethicist Simon Whitney shows how the IRB system was launched in response to scandals like the notorious Tuskegee syphilis study--and how, in recent decades, this well-intentioned program has become increasingly bureaucratic, convoluted, and stifling. Readers will learn how vital breakthroughs in treating conditions from kidney stones to heart attacks and premature birth have been delayed by IRB red tape, forcing doctors and patients to settle for less-effective treatments. They'll see how ill-informed demands from Congressional leaders that regulators "get tough" on scientists have caused respected research institutions to be shut down-with no benefit to the public. And they'll learn about a balanced, common-sense approach to reforming the system that can free scientists from pointless wheel-spinning while still protecting the public from the risks of unethical or careless experimentation. Until now, the debate about the IRB system's failures has been confined to specialty journals in medicine, law, and ethics. From Oversight to Overkill will finally alert citizens about this little-known crisis with America's medical research system-and what can be done about it. (shrink)

The U.S. oversight system for genetically engineered organisms was evaluated to develop hypotheses and derive lessons for oversight of other emerging technologies, such as nanotechnology. Evaluation was based upon quantitative expert elicitation, semi-standardized interviews, and historical literature analysis. Through an interdisciplinary policy analysis approach, blending legal, ethical, risk analysis, and policy sciences viewpoints, criteria were used to identify strengths and weaknesses of GEOs oversight and explore correlations among its attributes and outcomes. From the three sources of (...) data, hypotheses and broader conclusions for oversight were developed. Our analysis suggests several lessons for oversight of emerging technologies: the importance of reducing complexity and uncertainty in oversight for minimizing financial burdens on small product developers; consolidating multi-agency jurisdictions to avoid gaps and redundancies in safety reviews; consumer benefits for advancing acceptance of GEO products; rigorous and independent pre- and post-market assessment for environmental safety; early public input and transparency for ensuring public confidence; and the positive role of public input in system development, informed consent, capacity, compliance, incentives, and data requirements and stringency in promoting health and environmental safety outcomes, as well as the equitable distribution of health impacts. Our integrated approach is instructive for more comprehensive analyses of oversight systems, developing hypotheses for how features of oversight systems affect outcomes, and formulating policy options for oversight of future technological products, especially nanotechnology products. (shrink)

BackgroundResearch has been an essential part of the COVID-19 pandemic response, including in Latin American (LA) countries. However, implementing research in emergency settings poses the challenge of producing valuable knowledge rapidly while upholding research ethical standards. Research ethics committees (RECs) therefore must conduct timely and rigorous ethics reviews and oversight of COVID-19 research. In the LA region, there is limited knowledge on how countries have responded to this need. To address this gap, the objective of our project is (...) to explore if LA countries developed policies to streamline ethics review and oversight of research in response to the pandemic while ensuring its adherence to ethical standards, and to analyze to what extent these governance frameworks are in accordance with international guidance.MethodsWe conducted a descriptive and exploratory study assessing the COVID-19 research ethics governance frameworks of 19 LA countries, considering 4 dimensions based on international COVID-19 ethics guidance documents: (i) ethics review organizational model adopted, (ii) measures to coordinate between RECs and other research stakeholders, (iii) operational guidance for RECs, and (iv) key ethical issues for review and oversight of COVID-19 research.Results10 out of 19 LA countries have some policy to streamline ethics review of COVID-19 research. Of these countries only 6 issued comprehensive documents following international guidance that contemplate strategies with recommendations for concrete actions for a timely and rigorous review.ConclusionLA countries adopted partial strategies and operational guidance that may demonstrate a lack of a comprehensive view of research ethics for the review and oversight of COVID-19 research. Continuing efforts should be directed to strengthen LA countries' research capacity to respond timely and ethically to future health emergencies. Past lessons and the ones from this pandemic should be the basis to develop international standards and operational guidelines for ethics review and oversight of any research for public health emergencies. (shrink)

Regulators rely on clinical trials for drug approval and labeling decisions. Health systems and clinicians rely on the evidence from trials to determine treatment, and patients rely on it to decide which courses of care to undertake. Many of these stakeholders presume that the careful review of individual studies is enough to address the ethical and scientific questions that arise in clinical trials. In what follows, however, we demonstrate that explicit consideration of trial portfolios—series of trials that are interrelated (...) by a common set of objectives—is crucial. the ethical acceptability and evidentiary probity of individual trials can change depending on the characteristics of the portfolios in which they are embedded. Second, how trial portfolios are composed, how well they are coordinated, and how efficiently they use information determines the balance of risks and benefits they present as well as their different prospects for generating socially valuable information; these three factors also raise distinct questions of justice. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 10.2 (2000) 171-174 [Access article in PDF] Bioethics Inside the Beltway The Oversight of Human Gene Transfer Research LeRoy Walters Jesse Gelsinger's death last September in a gene transfer study being conducted at the University of Pennsylvania has helped to spark a national debate. In part, this debate parallels the broader discussion of how human subjects research should be reviewed and regulated in (...) the United States. However, human gene transfer research is one of a handful of biomedical technologies that seem to deserve special attention, at least in the early years of their development.The major participants in the national debate on human gene transfer include the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the National Bioethics Advisory Commission, members of Congress, biotechnology and pharmaceutical companies, disease-oriented advocacy groups, reporters, and academics. At the December 1999 meeting of the NIH Recombinant DNA Advisory Committee (RAC), the protocol that involved Jesse Gelsinger was a central focus of discussion, but other topics emerged as well. One ad hoc panel reviewed adverse events that had occurred in other research protocols using adenovirus vectors, while a second proposed changes in the general system for reporting adverse events to NIH and the RAC.During the first several months of the year 2000, the United States Congress also became involved in the human gene transfer debate. In February, Senator Bill Frist (R-TN) convened a hearing to which Jesse Gelsinger's father, representatives of NIH and FDA, and several other witnesses were invited. At approximately the same time, the House Commerce Committee and its Subcommittee on Oversight and Investigations initiated their own inquiries, asking the Office of Inspector General at the Department of Health and Human Services to review the oversight roles of NIH and FDA. In March and April, the House committee also wrote directly to the NIH Director, the FDA Commissioner, and the President of the University of Pennsylvania, requesting extensive documentation on gene transfer, in general, and the trial in which Jesse Gelsinger was involved, in particular. Congressman Henry Waxman (D-CA) and Senator Edward Kennedy (D-MA) have also raised questions and proposed solutions in multiple letters to the NIH Director and the Secretary of Health and Human Services. [End Page 171]The major general questions that have emerged from this discussion are the following:(1) What kinds of information about adverse events should be reported by researchers or sponsors during the course of human gene transfer trials?(2) To what group or groups should adverse-event information be reported? How often and in what ways should the information be analyzed?(3) Should the information about adverse events remain confidential, or should it be discussed publicly?(4) How can the disclosure and consent process in gene transfer trials be improved?(5) Which federal agency should have primary responsibility for overseeing human gene transfer research, and how can it best fulfill its oversight role?How these questions are answered will have immediate relevance to the field of human gene transfer research as it enters into its next phase. At the same time, the models that are created for this important cutting-edge field also may be useful in other complex or controversial arenas of biomedical research, for example, xenotransplantation or human embryonic stem-cell research. In addition, the lessons learned from this one important area of human subjects research may suggest ways to improve protections for all the volunteers who make clinical research--and medical progress--possible.In the remainder of this article, I will turn from reporting, in as objective a way as possible, on the status of the public policy debate about human gene transfer research to suggesting measures for improving the current oversight system for such research. My initial general recommendation is that we should not expect a single regulatory agency to be solely responsible for a field as large and dynamic as human gene transfer research. Rather, there should be some helpful redundancy or, to change the metaphor, checks and balances in the public oversight of this field. Thus, an... (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section (...) I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight. (shrink)

U.S. approaches to oversight of research and technological products have developed over time in an effort to ensure safety to humans, animals, and the environment and to control use in a social context. In modern times, regulatory and oversight tools have evolved to include diverse approaches such as performance standards, tradable allowances, consultations between government and industry, and pre-market safety and efficacy reviews. The decision whether to impose an oversight system, the oversight elements, the level of (...) oversight, the choice of approach, and its execution can profoundly affect technological development, individual and collective interests, and public confidence in technological products. Oversight is conducted by a range of institutions with various capabilities, cultures, and motives. Avenues for disputing oversight decisions are also important, and some argue that the U.S. operates in an adversarial regulatory culture in which Congress, the media, and stakeholders regularly contest the decisions of federal agencies. (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Throughout, assessments employing both the multiple criteria and a method of expert elicitation are combined with the existing literature, case law, and regulations providing an integrative historical case study approach. The goal is to provide useful information from multiple disciplines and perspectives (...) to guide discussions regarding appropriate oversight frameworks for nanobiotechnology applications under the FDA’s purview. (shrink)

Clinical gene transfer research has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee. This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.Clinical GTR is governed by (...) the same oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration. (shrink)

In vitro fertilization using donated oocytes is an important medical technique that provides the only option for some infertile patients to have children. The technique remains ethically contentious, however, and, as a result of this controversy, different oversight approaches have been developed in countries around the world. This paper examines the oversight and practice of oocyte donation in Canada, the United Kingdom and the United States to examine how policy choices have influenced the development and use of this (...) medical technology. Examining per capita utilization of oocyte donation in these three countries provides evidence that supply-side policies—specifically policies affecting the compensation of potential oocyte donors—have substantially influenced the use of this technology. These results should provide useful insight for policymakers developing or revising oocyte donation policies. (shrink)