At least since the seminal work of the (US) National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in the 1970s, a fundamental distinction between research and practice has underwritten both conceptual work in research ethics and regulations governing research involving human subjects. Notwithstanding its undoubted historical importance, I believe the distinction is problematic because it misrepresents clinical inquiry. In this essay, I aim to clarify the character of clinical inquiry by identifying crucial contextual constraints on (...) justification constitutive of clinical science. This analysis shows that, from an epistemological point of view, clinical research and clinical practice are not sharply distinct but intimately intertwined. This result is important in its own right—an enriched understanding of the epistemology of clinical research is valuable in and of itself. But this result is also important because it has profound implications for the ethics of human subjects research. (shrink)

This Special Issue titled "Severe Uncertainty in Science, Medicine and Technology" aims to shed new light on the understanding of severe uncertainty and its multifaceted implications. The main idea of the papers of this collection is that, despite possible sophisticated statistical judgments towards future risks in science, medicine, and technology, severe forms of uncertainty still exist.While ignorance is usually assumed to be a total absence of knowledge, uncertainty often refers to the incompleteness of knowledge or information. In its extreme form, (...) this is called "severe uncertainty" but is also known as "fundamental," "radical," "deep," "great," or "genuine" uncertainty. A common characteristic of these... (shrink)

The bioethics literature has paid little attention to matters of informed reproductive decision-making among women of childbearing age who have chronic kidney disease (CKD), including women who are on dialysis or women who have had a kidney transplant. Women with CKD receive inconsistent and, sometimes, inadequate reproductive counseling, particularly with respect to information about pursuing pregnancy. We identify four factors that might contribute to inadequate and inconsistent reproductive counseling. We argue that women with CKD should receive comprehensive reproductive counseling, including (...) information about the possibility of pursuing pregnancy, and that more rigorous research on pregnancy in women with CKD, including women on dialysis or who have received a kidney transplant, is warranted to improve informed reproductive decision making in this population. (shrink)

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)

What proper role should considerations of risk, particularly to research subjects, play when it comes to conducting research on human enhancement in the military context? We introduce the currently visible military enhancement techniques (1) and the standard discussion of risk for these (2), in particular what we refer to as the ‘Assumption’, which states that the demands for risk-avoidance are higher for enhancement than for therapy. We challenge the Assumption through the introduction of three categories of enhancements (3): therapeutic, preventive, (...) and pure enhancements. This demands a revision of the Assumption (4), alongside which we propose some further general principles bearing on how to balance risks and benefits in the context of military enhancement research. We identify a particular type of therapeutic enhancements as providing a more responsible path to human trials of the relevant interventions than pure enhancement applications. Finally, we discuss some possible objections to our line of thought (5). While acknowledging their potential insights, we ultimately find them to be unpersuasive, at least provided that our proposal is understood as fully non-coercive towards the candidates for such therapeutic enhancement trials. (shrink)

Reasoning in medicine requires the critical use of a clinical methodology whose validity must be evaluated as well as its limits. In the last decade, an increasing amount of evidence has shown severe limitations and flaws in the conduct of prognostic studies. The main reason behind this fact is that prognostic judgments are at high risk of error. In this paper we investigate the pragmatic and illocutionary aspects of different forms of linguistic acts and judgments involved in clinical practice. More (...) specifically, we analyze the role of uncertainty with regard to ‘particular’ clinical judgments and its relation with ‘general’ evidence. Focusing on how prognostic judgments are formulated and justified, our main purpose is to highlight the explication, the structure and the limits of prognosis from a linguistic and epistemological perspective. (shrink)

It can be argued that there is an ethical requirement to classify correctly what is known and what is unknown in decision situations, especially in the context of biomedicine when risks and benefits have to be assessed. This is because other methods for assessing potential harms and benefits, decision logics and/or ethical principles may apply depending on the kind or degree of uncertainty. However, it is necessary to identify and describe the various epistemic states of uncertainty relevant to such estimates (...) in the first place. Therefore, this paper aims to develop a category system of different epistemic states of uncertainty which, although not exclusively, is primarily intended to be applied to early clinical trials. It is formed on the basis—and various combinations—of three dimensions of uncertainty that represent certain parts of incomplete knowledge: outcome (type of event), probability (of outcome) and evaluation (assessment of outcome). Furthermore, it is argued that uncertainty can arise from three different sources (the structure of the object of research, the state of the evidence, or individual handling of the research and already existing knowledge). The categories developed are applied to actual examples from gene therapy and genome editing to illustrate that they can be helpful for a more precise definition of the respective uncertainties, especially in the context of risk–benefit assessment. The categories allow a differentiated perspective of decision-making situations from the point of view of incomplete knowledge in general, but particularly, for example, in early clinical research, and may thereby support a more acceptable ethical assessment of potential harms and benefits. (shrink)

Background Randomized controlled trials are central to generating knowledge about effectiveness of interventions as well as risk, protective and prognostic factors related to diseases in emergency newborn care. Whether prospective participants understand the purpose of research, and what they perceive as the influence of the context on their understanding of the informed consent process for RCTs in emergency obstetric and newborn care are not well documented. Methods Conceptual review. Discussion Research is necessary to identify how the illnesses may be prevented, (...) to explore the causes, and to investigate what medications could be used to manage such illness. Voluntary informed consent requires that prospective participants understand the disclose information about the research, and use this to make autonomous informed decision about participation, in line with their preferences and values. Yet the emergency context affects how information may be disclosed to prospective research participants, how much participants may comprehend, and how participants may express their voluntary decision to participate, all of which pose a threat to the validity of the informed consent. I challenge the claim that the ‘understanding’ of research is always necessary for ethical informed consent for research during emergency care. I argue for reconceptualization of the value of understanding, through recognition of other values that may be equally important. I then present a reflective perspective that frames moral reflection about autonomy, beneficence and justice in research in emergency research. Conclusion While participant ‘understanding’ of research is important, it is neither necessary nor sufficient for a valid informed consent, and may compete with other values with which it needs to be considered. (shrink)

Recent progress in synthetic biology has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including ‘risk’ minimization. These concerns are associated with any FIH trial, however, due to the (...) novelty of the approach, they become more pronounced for medical applications of emerging technologies like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using ‘risk assessment’ as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as ‘risk’ and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue. (shrink)

Clinical equipoise has been proposed as an ethical principle relating uncertainty and moral leeway in clinical research. Although CE has traditionally been indicated as a necessary condition for a morally justified introduction of a new RCT, questions related to the interpretation of this principle remain woefully open. Recent proposals to rehabilitate CE have divided the bioethical community on its ethical merits. This paper presents a new argument that brings out the epistemological difficulties we encounter in justifying CE as a principle (...) to connect uncertainty and moral leeway in clinical ethics. The argument proposes, first, that the methodology of hypothetical retrospection is applicable to the RCT design and that it can accommodate uncertainty. As currently understood, however, HR should give up its reliance on the assumption of uncertainty transduction, because the latter assumes the principle of indifference, which does not accommodate uncertainty in the right way. The same principle is then seen to distort also the received interpretations of CE. (shrink)