This paper explores the convergence of two recent and growing streams of bioethical work and concern. Each has originated independently, but each arises from the fact that the Common Rule that has shaped medical research ethics, as institutionalized in the United States and also abroad, is largely silent about what needs to be done in response to researchers’ positive obligations. One stream concerns what to do about the sometimes vast range of findings that may arise incidentally to performing research procedures. (...) The other asks whether medical researchers owe their study participants any “ancillary care” — that is, medical care that their study participants need but that goes beyond what is required to do the science safely. (shrink)

The question of how to handle incidental findings has sparked a heated debate among neuroimaging researchers and medical ethicists, a debate whose urgency stems largely from the recent explosion in the number of imaging studies being conducted and in the sheer volume of scans being acquired. Perhaps the point of greatest controversy within this debate is whether the magnetic resonance imaging scans of all research participants should be reviewed in an active search for pathology and, moreover, whether this search should (...) be performed by a radiologist. Resistance to routine readings performed by radiologists, as opposed to selective review of those scans on which investigators have spotted a possible IF, has been fueled in part by the obvious and enormous cost — financial and logistical — of engaging radiologists to read massive numbers of scans. This cost would be especially burdensome, even prohibitive, to investigators who are not affiliated with a medical center, because of their limited access to radiologists and other medical expertise. (shrink)

This new edition of Charles Fried's Medical Experimentation includes a general introduction by Franklin Miller and the late Alan Wertheimer, a reprint of the 1974 text, an in-depth analysis by Harvard Law School scholars I. Glenn Cohen and D. James Greiner, and a new essay by Fried reflecting on the original text and how it applies to the contemporary landscape of medicine and medical experimentation.

A predominant ethical view holds that physician‐investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second‐rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.

Empirical studies and ethical-legal analyses have demonstrated that incidental fndings in the brain, most commonly vascular in origin, must be addressed in the current era of imaging research. The challenges, however, are substantial. The discovery and management of incidental fndings vary, at minimum, by institutional setting, professional background of investigators, and the inherent diferences between research and clinical protocols. In the context of human subjects protections, the challenges of disclosure of unexpected and potentially meaningful clinical information concern privacy and confdentiality, (...) communication, and responsibility for follow-up. Risks, including a blurring of boundaries between research and clinical practice, must be weighed against the possible beneft to subjects and a moral duty to inform. Identifcation and examination of these challenges have been met by scientifc interest and a robust, interdisciplinary response resulting in the pragmatic recommendations discussed here. (shrink)

The use of brain imaging technology as a common tool of research has spawned concern and debate over how investigators should respond to incidental fndings discovered in the course of research. In this article, we argue that investigators have an obligation to respond to incidental fndings in view of their entering into a professional relationship with research participants in which they are granted privileged access to private information with potential relevance to participants' health. We discuss the scope and limits of (...) this professional obligation to respond to incidental fndings, bearing in mind that the relationship between investigators and research participants differs fundamentally from the doctor-patient relationship. (shrink)

Recent work on incidental fndings, concentrating on the difcult problems posed by the ambiguous results often generated by high-tech medicine, has proceeded largely independently from recent work on medical researchers' ancillary-care obligations, the obligations that researchers have to deal with diseases or conditions besides the one(s) under study. This paper contends that the two topics are morally linked, and specifcally that a sound understanding of ancillary-care obligations will center them on incidental fndings. The paper sets out and defends an understanding (...) of ancillary-care obligations, which is based on the idea that when participants signed up for a study they may — independently of their beliefs and expectations and of those of the researchers — be taken to have partially entrusted certain aspects of their health into the researchers' hands. This partial-entrustment model of ancillary-care obligations, in turn, has substantive implications for how to deal ethically with incidental fndings; for instance, it suggests that researchers have no moral obligation to hunt for incidental fndings. (shrink)

We weigh the presumed benefts of routinely searching all research scans for incidental fndings against its substantial risks, including false-positive and false-negative fndings, and the possibility of triggering unnecessary, costly evaluations and perhaps harmful treatments. We argue that routinely searching for IFs may not maximize benefts and minimize risks to participants.

No consensus yet exists on how to handle incidental fnd-ings in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers (...) have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed. (shrink)

Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

One of the most important questions in the ethics of human clinical research asks what obligations investigators owe the people who enroll in their studies. Research differs in many ways from standard care - the added uncertainties, for instance, and the nontherapeutic interventions such as diagnostic tests whose only purpose is to measure the effects of the research intervention. Hence arises the question whether a physician engaged in clinical research has the same obligations toward research subjects that he owes his (...) medical patients, or whether they differ in any fundamental way.Perhaps the most common answer is that the relationship is the same. Investigators, like physicians, are said to be fiduciaries of the volunteers who enroll in research trials. Each owes the best available medical care, which means that a physician can only justify enrolling his patient in research if the study meets the requirements of clinical equipoise, namely, that there is legitimate disagreement within the medical community as to whether the standard treatment or the investigational intervention is superior. (shrink)

One of the most important questions in the ethics of human clinical research asks what obligations investigators owe the people who enroll in their studies. Research differs in many ways from standard care - the added uncertainties, for instance, and the nontherapeutic interventions such as diagnostic tests whose only purpose is to measure the effects of the research intervention. Hence arises the question whether a physician engaged in clinical research has the same obligations toward research subjects that he owes his (...) medical patients, or whether they differ in any fundamental way.Perhaps the most common answer is that the relationship is the same. Investigators, like physicians, are said to be fiduciaries of the volunteers who enroll in research trials. Each owes the best available medical care, which means that a physician can only justify enrolling his patient in research if the study meets the requirements of clinical equipoise, namely, that there is legitimate disagreement within the medical community as to whether the standard treatment or the investigational intervention is superior. (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 Phillip Kerr’s 1994 spellbinding novel A Philosophical Investigation, the medical test to which the protagonist refers is a functional brain scan based on positron emission tomography. It is used to run large studies of male and female brains and, following a lead suggested by animal studies, has been used to identify rare cases of human male subjects who lack the ventral medial nucleus. This nucleus, in the experiment, is hypothesized to inhibit the activity of the sexually dimorphic nucleus, a (...) preoptic area of the male brain believed to be a repository of male aggressive response. Prior research, we learn from the plot, shows that 3 in 100,000 human males are VMN-negative. Thirty percent of those affected are believed to be in prison or to have a criminal record; 70% are believed to stabilize levels of aggression by producing increased levels of estrogen. Identities of subjects participating in the brain scan studies are protected through the conversion of real names to those of famous figures of the past — Bertrand Russell, Charles Dickens. Those for whom results are unfavorable are recontacted, and they are offered counseling. (shrink)