Anna Mastroianni

Federal policies on human subjects research have undergone a progressive transformation. In the early decades of the twentieth century, federal policies largely relied on the discretion of investigators to decide when and how to conduct research. This approach gradually gave way to policies that augmented investigator discretion with externally imposed protections. We may now be entering an era of even more stringent external protections. Whether the new policies effectively absolve investigators of personal responsibility for conducting ethical research, and whether it is wise to do so, remains to be seen.

Beyond Consent examines the concept of justice, and its application to human subject research, through the different lenses of various research populations: children, the vulnerable sick, captive and convenient populations, women, people of colour, and subjects in international settings. Separate chapters address the evolution of research policies, implications of the concept of justice for the future of human subject research, and the ramifications of this concept throughout the research enterprise.

Federal policies on human subjects research have undergone a progressive transformation. In the early decades of the twentieth century, federal policies largely relied on the discretion of investigators to decide when and how to conduct research. This approach gradually gave way to policies that augmented investigator discretion with externally imposed protections. We may now be entering an era of even more stringent external protections. Whether the new policies effectively absolve investigators of personal responsibility for conducting ethical research, and whether it is wise to do so, remains to be seen.

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services’ regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision-making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions.

In lieu of an abstract, here is a brief excerpt of the content:Women and Health Research:A Report from the Institute of MedicineAnna C. Mastroianni (bio), Ruth Faden (bio), and Daniel Federman (bio)In recent years, claims have been made by segments of the research community and by women's health advocacy groups that clinical research practices and policies have not benefitted women's health to the same extent as men's health. Central to these claims has been an assertion that women have been inadequately represented as subjects of clinical studies and that as a result neither health conditions unique to women—e.g., menopause—nor women's manifestations of health problems affecting both sexes—e.g., heart disease—have been investigated sufficiently.The scientific community, including federal agencies that sponsor and regulate clinical studies, is increasingly responsive to these claims and is taking steps to raise the level of women's participation in clinical studies. Controversy and concern have surrounded these actions, however. Two of the claims that have been made are: (1) that women are more difficult to study than men because of their cyclical hormonal changes; and (2) that conducting gender-specific subgroup analyses would increase the size of study populations, raise the cost of studies, and thereby reduce the number of studies that could be performed with the limited resources available. In addition, controversy over the inclusion of women of childbearing potential and pregnant women has been particularly salient. Concerns have been expressed about avoiding potential harm to existing or potential fetuses and about the possible legal and financial ramifications of such harm. A further concern involves the perceived difficulties in enrolling women in studies and retaining them for the duration of the studies.Against this backdrop, the Office of Research on Women's Health at the National Institutes of Health (NIH) asked the Institute of Medicine (IOM) in October 1992 to establish the Committee on the Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies. The Committee's charge was to: (1) consider the ethical and legal implications of including women, particularly pregnant women and women of childbearing potential, in clinical studies; (2) examine known instances of litigation regarding injuries to research subjects [End Page 55] and describe existing legal liabilities and protections; and (3) provide practical advice on these issues for consideration by NIH, institutional review boards (IRBs), and clinical investigators.The 16 Committee members came from diverse backgrounds: bioethics, law, epidemiology and biostatistics, public health policy, obstetrics and gynecology, clinical research, pharmaceutical development, social and behavioral sciences, and clinical evaluative sciences.1 Chaired by two of the authors of this article, Ruth Faden and Daniel Federman, and coordinated by the third, IOM Study Director Anna Mastroianni, the Committee met five times over a fourteen-month period, convened a one-and-one-half day invitational workshop, and commissioned several background papers. The Committee's deliberations were complicated by the announcement of new federal policies late in its term. Specifically, the Food and Drug Administration (FDA) issued guidelines (FDA 1993) to replace its 1977 guidelines, which prohibited the inclusion of women of childbearing potential in early phases of most clinical drug trials. In addition, Congress passed the NIH Revitalization Act of 1993 (P.L. 103-43), which contains provisions mandating the inclusion of women and racial and ethnic minorities in NIH-sponsored clinical research. In February 1994, the IOM Committee publicly issued its final report and recommendations, Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, publishing the workshop presentations and commissioned papers in a separate volume.Deliberations of the CommitteeA number of issues arose at the outset as the Committee considered its charge. A few members initially believed that verification of the underrepresentation of women relative to men in clinical studies as a whole was a prerequisite to providing policy recommendations. Others believed that such an examination would be an important contribution to the knowledge base, but that it was not necessary for addressing the Committee's charge. As summarized in the Committee's report, the Committee's research indicated that firm conclusions about the relative underrepresentation of women could not be drawn from the available data because of the lack of systematic information...

Federal policies on human subjects research have undergone a progressive transformation. In the early decades of the twentieth century, federal policies largely relied on the discretion of investigators to decide when and how to conduct research. This approach gradually gave way to policies that augmented investigator discretion with externally imposed protections. We may now be entering an era of even more stringent external protections. Whether the new policies effectively absolve investigators of personal responsibility for conducting ethical research, and whether it is wise to do so, remains to be seen.

At a White House ceremony in October 1995, the Advisory Committee on Human Radiation Experiments presented its Final Report to President Bill Clinton. The 925-page report and the over 2,000 pages of supplemental volumes summarized eighteen months of investigative research, debate, and deliberation on historical and contemporary issues in human subjects research. The Advisory Committee's efforts were aided by unprecedented support from the highest levels of the executive branch, including the heads of eight cabinet-level agencies and their departments' resources. The presidentially appointed committee and its staff delved into long-forgotten Cold Warera government archives, listened to hours of public testimony, interviewed key players in the development of medical therapies and nuclear weapons, and studied ethical issues arising in today's research.In this article we focus on a critical, but narrowly defined, part of the Advisory Committee's Final Report: remedying harms or wrongs to subjects of human radiation experiments conducted or sponsored by the U.S. government between 1944 and 1974.

At its core, public health introduces tensions between individuals' autonomy and the need to account for the perspectives and needs of communities and populations. It further raises social justice issues, including fair allocation of limited resources. This article examines and elaborates on these tensions and their resolutions using specific public health examples. Experiences in the 1980s and 1990s with HIV/AIDS provide a particularly rich collection of issues that brought ethical issues in public health to the public's attention, and in so doing challenged previously held assumptions about the appropriate consideration of individual rights in the context of population health objectives. Lastly, the article examines some of the ethical challenges arising in public health applications of recent science and technology advances, specifically the emerging area of public health genomics and the large scale collection and analysis of health information.

: During the nearly 10 years since its introduction, preimplantation genetic diagnosis (PGD) has been used predominantly to avoid giving birth to a child with identified genetic disease. Recently, PGD was used by a couple not only to test IVF-created embryos for genetic disease, but also to test for a nondisease trait related to immune compatibility with a child in the family in need of an hematopoetic stem cell transplant. This article describes the case, raises some ethical and policy issues, highlights gaps in U.S. policy, and finally makes some recommendations for addressing advancing genetic and reproductive technologies

In lieu of an abstract, here is a brief excerpt of the content:IntroductionAnna Mastroianni (bio) and Jeffrey Kahn (bio)In this issue of the Kennedy Institute of Ethics Journal, we subject the work of the Advisory Committee on Human Radiation Experiments to examination from many angles. Nearly one year has passed since the release of the Committee’s final report and recommendations, and it seems an appropriate time to invite discourse and reflection on the influence and impact of the Committee and its efforts. Our intent is to advance understanding of the Committee and its work, its place in the evolution of bioethics and public policy, as well as the broader legacy of restoring trust in the conduct of human subjects research.In 1993, President Clinton and Secretary of Energy Hazel O’Leary initiated an investigation of America’s involvement in radiation experiments on its citizens during the Cold War. The investigation resulted in the appointment of the Committee in January 1994. Some issues raised by these radiation experiments were brought to the attention of the nation by revelations contained in a Pulitzer Prize-winning series of newspaper stories about plutonium injections carried out by the government on allegedly unsuspecting subjects during the Cold War. The Committee faced a broad mandate, which included piecing together the history of Cold War radiation experiments and human subjects research, as well as recommending remedies for past wrongs and mechanisms to ensure that such wrongs could not be repeated in the future.This issue of the Journal consists of articles and accompanying commentaries on historical, philosophical, policy, and political aspects of the Committee’s work that are important to bioethics. This collection of articles, authored by Committee members, staff, and leading scholars, is designed to paint a picture of the breadth and complexity of the Committee’s efforts and to provide context and to stimulate discussion of significant issues.In the first article, Ruth Faden provides her unique perspective as chair of the Committee. She goes beyond the necessary overview and background of the Committee to reflect on the impact and meaning of the Committee’s work to bioethics and public policy.Much of the Committee’s effort was directed at gathering and uncovering information about the history of Cold War radiation experiments, an endeavor fairly foreign to bioethics but critically important to understanding the context in which to make moral judgments about the past. Jonathan Moreno and Susan Lederer discuss how the Committee’s work changed some of the traditional views of the history of research ethics. The commentary by Allan Brandt and Lara Freidenfelds further illuminates the value of understanding this recovered history. [End Page ix]In making moral judgments about the past, the Committee confronted complex questions about how to assess wrongdoing and the culpability of the government and its agents. Allen Buchanan explains why this was such a difficult but crucial task and how the Committee worked through some of the answers to these questions. His discussion illustrates the challenges to consensus in the committee decision-making process described in Ruth Macklin’s article in this issue on committees and consensus. Tom Beauchamp analyzes the frameworks for making retrospective moral judgments developed by two committees, the Advisory Committee and the University of California at San Francisco Ad Hoc Fact Finding Committee on World War II Human Radiation Experiments, and critiques their applications of the frameworks in the case of the plutonium injection experiments.The Committee recognized that in order to prevent wrongs seen in the past from occurring in the future, it would be necessary to understand the human subjects protections now in place. Nancy Kass and Jeremy Sugarman discuss the results of the Committee’s attempts to measure the operation and effectiveness of the current system for protection of human subjects. Paul Appelbaum comments on the relevance and value of the Committee’s empirical projects to contemporary human subjects research.The Committee’s work, and the products of any commission’s work, must be viewed partly in light of the place of commissions in bioethics scholarship and policymaking. Appointed commissions can have significant impacts on scholarly and public thinking, policymaking, and future direction, and bring high visibility to issues. It is important to realize that the conclusions of the Committee...

Public health ethics, like the field of public health it addresses, traditionally has focused more on practice and particular cases than on theory, with the result that some concepts, methods, and boundaries remain largely undefined. This paper attempts to provide a rough conceptual map of the terrain of public health ethics. We begin by briefly defining public health and identifying general features of the field that are particularly relevant for a discussion of public health ethics.Public health is primarily concerned with the health of the entire population, rather than the health of individuals. Its features include an emphasis on the promotion of health and the prevention of disease and disability; the collection and use of epidemiological data, population surveillance, and other forms of empirical quantitative assessment; a recognition of the multidimensional nature of the determinants of health; and a focus on the complex interactions of many factors—biological, behavioral, social, and environmental—in developing effective interventions.