This paper targets an orphan topic in research ethics, namely the so called principle of the primacy of the human being, which states that the interests of the human subject should always take precedence over the interests of science and society. Although the principle occupies the central position in the majority of international ethical and legal standards for biomedical research, it has been commented in the literature mainly in passing. With a few notable exceptions, there is little in-depth discussion about (...) the meaning and role of the principle. Several authors note that the principle is vogue, ambiguous and apparently conflicting with the accepted practice of conducting non-beneficial research on individuals unable to give consent. There are opinions that it is just “a vacuous figure of speech” and should be abandoned. This paper argues that the primacy principle is far from being “a vacuous figure of speech”, rather it should be seen as a threefold concept: a fundamental interpretative rule, a procedural rule, and a substantive rule aimed at protecting research subjects from instrumental treatment and unacceptable risks. This interpretation tracks back to the principle regulatory and normative origins in the Declaration of Helsinki of 1975, but also acknowledges changes in research ethics and practice, which took place at the turn on the twentieth and twenty-first centuries. Thus, the proposed reading of the principle is not only original, but also historically grounded and normatively fruitful. It provides a fresh and ethically rich perspective on extensively debated, but still controversial problem of an upper limit of permissible risks in non-beneficial studies. (shrink)

Researchers are developing a fertility preservation technique?testicular tissue cryopreservation (TTCP)?for prepubescent boys who may become infertile as a result of their cancer treatment. Although this technique is still in development, some researchers are calling for its widespread use. They argue that if boys do not bank their tissue now, they will be unable to benefit from any therapies that might be developed in the future. There are, however, risks involved with increasing access to an investigational procedure. This article examines four (...) methods of expanding access to TTCP: (1) expansion of institutional review board (IRB)-approved research trials; (2) offering TTCP as an innovative procedure in hospitals; (3) offering TTCP as a standard practice in hospitals; and (4) commercialization of TTCP. The ethical and practical implications of each are evaluated through a comparison with umbilical cord blood banking (UCBB), a technology that has achieved widespread use based on similar claims of future benefit. (shrink)

In this article we attempt to answer the question of how the ethical and conceptual framework (ECF) for a learning health‐care system (LHS) affects some of the main controversies in research ethics by addressing five key problems of research ethics: (a) What is the difference between practice and research? (b) What is the relationship between research ethics and clinical ethics? (c) What is the ethical relevance of the principle of clinical equipoise? (d) Does participation in research require a higher standard (...) of informed consent than the practice of medicine? and (e) What ethical principle should take precedence in medicine? These questions allow us to construct two opposite idealized positions on the distinction between research and practice: the integration model and the segregation model of research and practice. We then compare the ECF for an LHS with these two idealized positions. We argue that the ECF for a LHS does not, in fact, solve these problems, but that it is a third, separate position in the relationship between research ethics and clinical ethics. Moreover, we suggest that the ECF for a LHS raises new ethical problems that require additional ethical analysis and justification. Our article contributes to the discussion on the relationship between research ethics and clinical ethics, revealing that although a learning health‐care system may significantly change the landscape of health care, some ethical dilemmas still require resolving on both theoretical and policy‐making levels. (shrink)

Human clinical research trials, by which corporations, universities, and research scientists bring new drugs, devices, and procedures into the practice and marketplace of medicine, have become a huge business. The National Institutes of Health doubled its spending over the past five years, while in the private sector the top twenty pharmaceutical companies have more than doubled their investment in research and development over a roughly comparable period. To date, some twenty million Americans have participated in clinical research trials that now (...) are as common in the private practice setting as in academia.For many years human clinical trials received relatively little public attention. In the wake of several well-publicized research abuses, Congress created in 1974 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to formulate recommendations to protect human research subjects. The Commission’s 1979 Belmont Report helped to guide the Institutional Review Boards that review the ethics of federally funded research. (shrink)

Human clinical research trials, by which corporations, universities, and research scientists bring new drugs, devices, and procedures into the practice and marketplace of medicine, have become a huge business. The National Institutes of Health doubled its spending over the past five years, while in the private sector the top twenty pharmaceutical companies have more than doubled their investment in research and development over a roughly comparable period. To date, some twenty million Americans have participated in clinical research trials that now (...) are as common in the private practice setting as in academia.For many years human clinical trials received relatively little public attention. In the wake of several well-publicized research abuses, Congress created in 1974 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to formulate recommendations to protect human research subjects. The Commission’s 1979 Belmont Report helped to guide the Institutional Review Boards that review the ethics of federally funded research. (shrink)

The National Commission for the Protection of Human Subjects of Bio-medical and Behavioral Research ended its work by substantially endorsing the status quo which places primary reliance on local Institutional Review Boards for subject protection. This was predictable because of the commission's researcher-dominated composition which permitted it to assume that(1) research is good;(2) experimentation is almost never harmful to subjects; and (3) researcher-dominated IRBs can adequately protect the interests of human subjects. The successor Presidential Commission can learn much by reexamining (...) these premises. (shrink)

The medical profession contains five “spheres of morality”: clinical care, clinical research, scientific knowledge, population health, and the market. These distinct sets of normative commitments require physicians to act in different ways depending on the ends of the activity in question. For example, a physician-scientist emphasizes patients’ well-being in clinic, prioritizes the scientific method in lab, and seeks to maximize shareholder returns as a board member of a pharmaceutical firm. Physicians increasingly occupy multiple roles in healthcare and move between them (...) frequently, creating the possibility of conflict between the ethical obligations of their various roles. This paper examines the entire moral landscape of medicine through the lens of role morality. It develops a novel framework that helps physicians recognize how their moral commitments depend on the nature and context of the situation, clarifies ethical conflicts that physicians face, and concludes with ideas for resolving these conflicts. (shrink)

Medical practice is ideally based on robust, relevant research. However, the lack of disease-modifying treatments for Alzheimer’s disease has motivated “innovative practice” to improve patients’ well-being despite insufficient evidence for the regular use of such interventions in health systems treating millions of patients. Innovative or new non-validated practice poses at least three distinct ethical questions: first, about the responsible application of new non-validated practice to individual patients ; second, about the way in which data from new non-validated practice are communicated (...) via the scientific and lay press ; and third, about the prospect of making new non-validated interventions widely available before more definitive testing. We argue that the authors of metabolic enhancement protocols for Alzheimer’s disease have overstated the evidence in favor of these interventions within the scientific and lay press, failing to communicate weaknesses in their data and uncertainty about their conclusions. Such unmeasured language may create false hope, cause financial harm, undermine informed consent, and frustrate the production of generalizable knowledge necessary to face the societal problems posed by this devastating disease. We therefore offer more stringent guidelines for responsible innovation in the treatment of Alzheimer’s disease. (shrink)

A special report of The Hastings Center and the Association of American Medical Colleges addressed the ethical oversight of learning health systems, which seek to combine high‐quality patient care with routine data collection aimed at improving patient outcomes. The report contained two position papers, authored by a number of distinguished bioethicists, and several commentaries. The position papers urged two changes. First, they urged a rethinking of our approach to the regulation of human subjects research, so as to make it easier (...) in the future for learning health systems to function well. Second, they argued that the rethinking required dispensing with a strict distinction between research and therapy, which has been a major tenet of bioethics since the Belmont Report, which explicated basic ethical principles governing human subjects research. We fully support the objectives of the authors, and we agree that the learning health system is an important advance that serves patients well. Unnecessary regulatory burden ought not impede this progress. We disagree, however, that the best way to bring about these needed changes in the regulatory environment is to reject the basic distinction between research and treatment. Unfortunately, we find the arguments in favor of that strategy to be, in places, reminiscent of what we take to be basic conceptual errors that hampered the ethical understanding of human subjects research prior to adoption of the Belmont Report. To see why one need not reject the research‐treatment distinction in order to promote learning health systems, we first investigate in some detail the arguments offered for eliminating the distinction. We next turn to an issue not addressed by those authors, namely, the relationship between the physician or investigator and the patient or subject, to illustrate why the distinction is important and what is lost if it is jettisoned. (shrink)

One of the founding principles of research ethics is that subjects should be treated equally. In the words of the Belmont Report, “equals ought to be treated equally.” This principle does not imply that all subjects should be treated exactly the same. Rather, subjects who are similar in relevant respects should receive similar treatment. Clinical status is clearly relevant to determining how subjects should be treated. Greater resources should be devoted to subjects who have worse diseases. In contrast, fame is (...) irrelevant. Subjects should not receive greater resources simply because they are famous. A more challenging question, one that pervades clinical research yet has received almost no attention in the literature, is whether subjects' level of scientific importance is relevant to determining how much support they should receive. (shrink)

The distinction between clinical research and clinical practice directs how we partition medicine and biomedical science. Reasons for a sharp distinction date historically to the work of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, especially to its analysis of the “boundaries” between research and practice in the Belmont Report (1978). Belmont presents a segregation model of the research-practice distinction, according to which research and practice form conceptually exclusive sets of activities and interventions. This (...) model is still the standard in federal regulations today. However, the Commission’s deliberations and conclusions about the boundaries are more complicated, nuanced, and instructive than has generally been appreciated. The National Commission did not conclude that practice needs no oversight comparable to the regulation of research. It debated the matter and inclined to the view that the oversight of practice needed to be upgraded, though the Commission stopped short of proposing new regulations for its oversight, largely for prudential political reasons. (shrink)

Discussions about the merits and shortcomings of non-inferiority trials are becoming increasingly common in the medical community and among regulatory agencies. However, criticisms targeting the ethical standing of non-inferiority trials have often been mistargeted. In this article we review the ethical standing of trials of non-inferiority. In the first part of the article, we outline a consequentialist position according to which clinical trials are best conceived as epistemic tools aimed at fostering the proper ends of medicine. According to this view, (...) clinical trials are means to ends, and thus their moral status depends both on how well they perform as means to reach desired ends and on which ends they are meant to achieve. Building upon this normative framework in the next two sections we analyze the specific ethical issues raised by non-inferiority trials. By making it clear that clinical trials are just epistemic tools – i.e. means to certain ends – it is possible not only to clarify the conceptual debate over a fundamental issue in clinical research, but also to identify which ethically relevant considerations ought to be addressed in setting up a non-inferiority trial. (shrink)

Experimental design is one aspect of a scientific method. A well-designed, properly conducted experiment aims to control variables in order to isolate and manipulate causal effects and thereby maximize internal validity, support causal inferences, and guarantee reliable results. Traditionally employed in the natural sciences, experimental design has become an important part of research in the social and behavioral sciences. Experimental methods are also endorsed as the most reliable guides to policy effectiveness. Through a discussion of some of the central concepts (...) associated with experimental design, including controlled variation and randomization, this chapter will provide a summary of key ethical issues that tend to arise in experimental contexts. In addition, by exploring assumptions about the nature of causation and by analyzing features of causal relationships, systems, and inferences in social contexts, this chapter will summarize the ways in which experimental design can undermine the integrity of not only social and behavioral research but policies implemented on the basis of such research. (shrink)