First-in-human research has several characteristics that require special attention with respect to ethics and human subjects protections. At least some nanomedical technologies may also have characteristics that merit special attention in clinical research, as other papers in this symposium show. This paper considers how to address these characteristics in the consent form and process for FIH nanomedicine research, focusing principally on experimental nanotherapeutic interventions but also considering nanodiagnostic interventions.It is essential, as a starting point, to recognize that the consent form (...) and process are by no means the primary protectors of human subjects. Instead, consideration of the form and content of informed consent becomes relevant only after a clinical trial has been reviewed and deemed scientifically and ethically acceptable.Two convergent types of challenges to informed consent are posed by nanomedicine FIH research. First, some issues appear generally applicable to FIH research, but have specific nanomedicine implications. (shrink)

It has become evident that neuroimaging raises new normative questions that cannot be addressed adequately within the (in this regard unspecific) frameworks of existing research ethics. Questions that are especially troubling are, among others, provoked by incidental findings. Two questions are particularly intricate in view of incidental findings: (1) How can the research subject’s right not to know be guaranteed? And (2) should a diagnostic check of scans by a neuroradiologist become an obligatory part of neuroscientific research protocols? The present (...) paper examines these question against the background of two recent recommendations. The differentiation between difference position and similarity position serves as an analytic tool to further investigate the issue and to develop a distinct proposal for answering the questions. (shrink)

In line with recent proposals for experimental philosophy and philosophy of science in practice, we propose that the philosophy of medicine could benefit from incorporating empirical research, just as bioethics has. In this paper, we therefore take first steps towards the development of an empirical philosophy of medicine, that includes investigating practical and moral dimensions. This qualitative study gives insight into the views and experiences of a group of various medical professionals and patient representatives regarding the conceptualization of health and (...) disease concepts in practice and the possible problems that surround them. This includes clinical, epistemological, and ethical issues. We have conducted qualitative interviews with a broad range of participants (n = 17), working in various health-related disciplines, fields and organizations. From the interviews, we highlight several different practical functions of definitions of health and disease. Furthermore, we discuss 5 types of problematic situations that emerged from the interviews and analyze the underlying conceptual issues. By providing theoretical frameworks and conceptual tools, and by suggesting conceptual changes or adaptations, philosophers might be able to help solve some of these problems. This empirical-philosophical study contributes to a more pragmatic way of understanding the relevance of conceptualizing health and disease by connecting the participants’ views and experiences to the theoretical debate. Going back and forth between theory and practice will likely result in a more complex but hopefully also better and more fruitful understanding of health and disease concepts. (shrink)

Over the past decade, there has been an extensive debate about whether researchers have an obligation to disclose genetic research findings, including primary and secondary findings. There appears to be an emerging (but disputed) view that researchers have some obligation to disclose some genetic findings to some research participants. The contours of this obligation, however, remain unclear. -/- As this paper will explore, much of this confusion is definitional or conceptual in nature. The extent of a researcher’s obligation to return (...) secondary and other research findings is often limited by reference to terms and concepts like “incidental,” “analytic validity,” “clinical validity,” “clinical relevance,” “clinical utility,” “clinical significance,” “actionability,” and “desirability.” These terms are used in different ways by different writers to describe obligations in different sorts of cases. -/- Underneath this definitional confusion is a general notion, supported by much of the literature, that findings only need to be disclosed when they surpass certain presumably objective or measureable thresholds, such as medical importance or scientific reproducibility. The problem is that there is significant variability in the way that these terms and concepts are used in the literature and, as such, in defining the scope of an obligation to return findings that surpasses the relevant thresholds. -/- The goal of this paper is to analyze the definitional muddle underlying the debate about returning genetic research findings, with the hope of answering a few questions. First, what is the range of definitions being used in this debate? Based on an extensive literature review, Part 1 will lay out a range of articulated definitions for each relevant term, with the goal of categorizing them into a handful of distinct types. Part 2 explains the definitional redundancy and confusion in the current literature, and, drawing from the terminological patterns identified in Part 1, outlines more cohesive building blocks to inform the development of future disclosure frameworks.Our minimum goal in articulating these conceptual building blocks is to promote clearer articulations of, and distinctions between, future disclosure frameworks. More ambitiously, we suggest which definitions and conceptualizations we consider most appropriate to use in future disclosure frameworks. Here, we seek to balance benefits to participants through the disclosure of important information with the minimization of undue burdens on individual researchers and the research enterprise more generally. -/- Our analysis builds upon the central philosophical distinction between concepts and conceptions. The basic idea is that the “concept” of X refers to the general (and relatively uncontroversial) structure/shape of X, while various “conceptions” of X are more particular, filled out, and controversial elaborations of the concept. In other words, “concepts” of X will be formal representations of X, while “conceptions” of X will be substantive interpretations of the key elements and relationships operating within that formal framework. (Implicit in this distinction is an important point about the nature of disagreement – namely, that in order for two or more parties to “disagree” about X as opposed to simply talk past one another, there must be at least enough shared agreement about X to know that the parties are referring to the same thing. A concept of X provides this point of common agreement, while competing conceptions of X mark the areas where disagreement arises.) In this paper, we will employ this distinction in a fundamental way to clarify exactly where the primary disagreements arise in the debate over disclosing genetic research findings. -/- We propose that, underlying all the seeming confusion and disagreement, there are three central and widely agreed upon concepts at work in this debate—validity, value, and volition. The first two concepts concern the nature of the information itself. An obligation to disclose only exists when findings are valid and have value but there are competing conceptions of how to determine or define validity and valuableness. The third concept—volition—pertains not to the information but rather to the person to whom it will be disclosed. Does that person want or not want the information, and what is the best way of determining this? Here, too, competing conceptions arise. Our key point, though, is that almost all of the ethical disagreement arises because of competing conceptions of these three concepts. Understanding and appreciating this key point can help to refocus the substantive debate by providing some common ground to start from in determining how best to interpret these shared concepts. This refocusing can, ideally, produce more productive debate and facilitate some progress in resolving it. (shrink)

This paper argues against considering incidental fndings as potential benefts of research when assessing the social value of proposed research, determining the appropriateness of a study's risk/beneft ratio, and identifying and disclosing the risks and benefts of participation during informed consent. The possibility of generating IFs should be disclosed during informed consent as neither a risk nor beneft, but as a possible outcome collateral to participation. Whether specifc IFs will be disclosed when identifed is a separate question whose answer is (...) material to determining whether IFs constitute a risk or a potential indirect beneft of participation. Finally, three types of IF should be distinguished and treated diferently during informed consent: those that will be routinely generated , those that can reasonably be characterized in terms of their nature and frequency of generation , and those of unpredictable nature and frequency that can be characterized only in general terms. Research protocols should provide a rationale for sharing or not sharing IFs of these three types with participants. Regulatory review of such plans should not, however, be confused with regarding IFs as potential benefts when assessing the study's risk/beneft ratio or merit. (shrink)

In much the same way that genomic technologies are changing the complexion of biomedical research, the issues they generate are changing the agenda of IRBs and research ethics. Many of the biggest challenges facing traditional research ethics today — privacy and confidentiality of research subjects; ownership, control, and sharing of research data; return of results and incidental findings; the relevance of group interests and harms; the scope of informed consent; and the relative importance of the therapeutic misconception — have become (...) important policy issues over the last 20 years because of the ways they have been magnified by genomic research efforts. Research that examines the ethical, legal, and social implications of human genomics research has become a burgeoning international field of scholarship over the last 20 years, thanks in part to its support first by the genome research funding bodies in the U.S. and then by national science agencies in other countries. (shrink)

Incidental fndings of potential medical signifcance are seen in approximately 5-8 percent of asymptomatic subjects and 16 percent of symptomatic subjects participating in large computed tomography colonography studies, with the incidence varying further by CT acquisition technique. While most CTC research programs have a well-defned plan to detect and disclose IFs, such plans are largely communicated only verbally. Written consent documents should also inform subjects of how IFs of potential medical signifcance will be detected and reported in CTC research studies.

While ethical and empirical interest in so-called secondary variants and incidental findings in clinical genetics contexts is growing, critical reflection on the ethical foundations of the various recommendations proposed is thus far largely lacking. We examine and critique the ethical justifications of the three most prominent disclosure positions: briefly, the clinical geneticist decides, a joint decision, and the patient decides. Subsequently, instead of immediately developing a new disclosure option, we explore relevant foundational ethical values and norms, drawing on the normative (...) and empirical ethical literature. Four ethical signposts are thereby developed to help guide disclosure discussions. These are: respectful sharing of the clinician’s expertise; transparent communication; epistemic modesty; and respect for the embedded nature of the patient. We conclude by considering the most common current disclosure positions in the light of the four ethical signposts. (shrink)