The authors respond to four JME commentaries on their Feature Article, ‘Autonomy-based criticisms of the patient preference predictor’.

There has been long-standing, albeit largely implicit, debate over whether investigator intentions are relevant to the ethical appropriateness of clinical research. Some commentators argue that whether investigators intend to collect generalizable knowledge or to benefit subjects is central to the ethics of clinical research. Others do not even mention investigator intentions when evaluating what makes clinical research ethical. To shed light on this debate, the present paper considers the reasons why investigator intentions might be ethically relevant. This analysis reveals that (...) investigator intentions are related to, but distinct from three ethical requirements: whether subjects understand that they are contributing to a project to help others, whether the included interventions have an appropriate risk/benefit ratio, and whether subjects’ interests are adequately protected. Provided these three requirements are satisfied, the ethical appropriateness of clinical research does not depend on what intentions investigators have in conducting it. (shrink)

The patient preference predictor is a proposed computer-based algorithm that would predict the treatment preferences of decisionally incapacitated patients. Incorporation of a PPP into the decision-making process has the potential to improve implementation of the substituted judgement standard by providing more accurate predictions of patients’ treatment preferences than reliance on surrogates alone. Yet, critics argue that methods for making treatment decisions for incapacitated patients should be judged on a number of factors beyond simply providing them with the treatments they would (...) have chosen for themselves. These factors include the extent to which the decision-making process recognises patients’ freedom to choose and relies on evidence the patient themselves would take into account when making treatment decisions. These critics conclude that use of a PPP should be rejected on the grounds that it is inconsistent with these factors, especially as they relate to proper respect for patient autonomy. In this paper, we review and evaluate these criticisms. We argue that they do not provide reason to reject use of a PPP, thus supporting efforts to develop a full-scale PPP and to evaluate it in practice. There are no data in this work. (shrink)

Net‐risk pediatric research encompasses interventions and studies that pose risks and do not offer a compensating potential for clinical benefit. These interventions and studies are central to efforts to improve pediatric clinical care. Yet critics argue that it is unethical to expose children to research risks for the benefit of unrelated others. While a number of ethical justifications have been proposed, none have received widespread acceptance. This leaves funders with uncertainty over whether they should support and institutional review boards with (...) uncertainty over whether they should approve net‐risk pediatric research. To try to answer these questions, this article describes a justification that I previously proposed and considers two objections to it. This analysis reveals that the opportunity to contribute to a valuable project can justify exposing children to risks even though some trials turn out to be valueless and others turn out to be harmful. It follows that, to protect pediatric participants, institutional review boards need to assess whether trials have the potential to collect socially valuable information and whether they are likely to enroll and retain a sufficient number of participants. (shrink)

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. (...) Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research. Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable. (shrink)

Background: Ethical issues related to comparative effectiveness research, or research that compares existing standards of care, have recently received considerable attention. In this paper we focus on how Ethics Review Committees should evaluate the risks of comparative effectiveness research. Main text: We discuss what has been a prominent focus in the debate about comparative effectiveness research, namely that it is justified when “nothing is known” about the comparative effectiveness of the available alternatives. We argue that this focus may be misleading. (...) Rather, we should focus on the fact that some experts believe that the evidence points in favor of one intervention, whereas other experts believe that the evidence favors the alternative. We will then introduce a case that illustrates this point, and based on that, discuss how ERCs should deal with such cases of expert disagreement. Conclusion: We argue that ERCs have a duty to assess the range of expert opinions and based on that assessment arrive at a risk judgment about the study under consideration. We also argue that assessment of expert disagreement is important for the assignment of risk level to a clinical trial: what is the basis for expert opinions, how strong is the evidence appealed to by various experts, and how can clinical trial monitoring affect the possible increased risk of clinical trial participation. (shrink)

In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in a given study (the subjective interpretation). (...) The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this (...) gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present article assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. (shrink)

Guidelines for health research focus on protecting individual research subjects. It is also vital to protect the communities involved in health research. In particular, a number of studies have been criticized on the grounds that they exploited host communities. The present paper attempts to address these concerns by providing an analysis of community exploitation and, based on this analysis, determining what safeguards are needed to protect communities in health research against exploitation. (edited).

The U.S. federal regulations require investigators conducting nonbeneficial research to obtain the assent of children who are capable of providing it. Unfortunately, there has been no analysis of which children are capable of assent or even what abilities ground the capacity to give assent. Why should investigators be required to obtain the positive agreement of some children, but not others, before enrolling them in research that does not offer a compensating potential for direct benefit? We argue that the scope of (...) children's research decision making should be based on the principles of respect for autonomy and nonmaleficence. These principles imply that the threshold for assent should be fixed at 14 years of age, and a dissent requirement should be adopted for all children in the context of nonbeneficial research. (shrink)

Background -- Evaluating the worry -- Proposed justifications -- Human interests and human causes -- Our connection to our contribution -- The value of passive contributions -- Implications -- Objections and the potential for abuse.

A primary goal of clinical practice is to respect patient autonomy. To promote this goal for patients who have lost the ability to make their own decisions, commentators recommend that surrogates make their treatment decisions based on the substituted judgment standard. This standard is commonly interpreted as directing surrogates to make the decision the patient would have made in the circumstances, if the patient were competent. However, recent commentators have argued that this approach—attempting to make the decision the patient would (...) have made if competent—is theoretically problematic, practically infeasible, and ignores the interests of the patient9s family and loved ones. These commentators conclude that the substituted judgment standard should be revised significantly, or abandoned altogether. While this response would avoid the cited problems, it also would require substantial changes to clinical practice and would raise significant problems of its own. The present paper thus considers the possibility that the criticisms do not point to problems with the substituted judgment standard itself; instead, they point to problems with the way it is most commonly interpreted. This analysis suggests that the substituted judgment standard need not be dramatically revised or abandoned. Instead, it should be interpreted in a way that effectively promotes respect for the autonomy of incompetent patients. The ‘endorsed life’ interpretation described here helps clinicians and surrogates to achieve this important goal. To clarify this approach, we explain how it differs from three other recently proposed alternatives to the standard interpretation of the substituted judgment standard. (shrink)

Pediatric research without the potential for clinical benefit is vital to improving pediatric medical care. This research also raises ethical concern and is regarded by courts and commentators as unethical. While at least 10 justifications have been proposed in response, all have fundamental limitations. This article describes and defends a new justification based on the fact that enrollment in clinical research offers children the opportunity to contribute to a valuable project. Contributing as children to valuable projects can benefit individuals in (...) two ways. First, individuals may come to ?embrace? the contributions they made as children. Second, contributing to valuable projects can lead to a better overall life. Because these potential benefits can outweigh small research risks, they provide a justification for pediatric research without the potential for clinical benefit, when it poses low risks and has the potential to benefit others in important ways. (shrink)

Debate surrounding the SUPPORT study highlights the absence of consensus regarding what information should be disclosed to potential research participants. Some commentators endorse the view that clinical research should be subject to high disclosure standards, even when it is testing standard-of-care interventions. Others argue that trials assessing standard-of-care interventions need to disclose only the information that is disclosed in the clinical care setting. To resolve this debate, it is important to identify the ethical concerns raised by clinical research and determine (...) what consent process is needed to address them. (shrink)

It has recently been proposed to incorporate the use of a “Patient Preference Predictor” (PPP) into the process of making treatment decisions for incapacitated patients. A PPP would predict which treatment option a given incapacitated patient would most likely prefer, based on the individual’s characteristics and information on what treatment preferences are correlated with these characteristics. Including a PPP in the shared decision-making process between clinicians and surrogates has the potential to better realize important ethical goals for making treatment decisions (...) for incapacitated patients. However, developing and implementing a PPP poses significant practical challenges. The present paper discusses these practical challenges and considers ways to address them. (shrink)

Research studies and interventions sometimes offer potential benefits to subjects that compensate for the risks they face. Other studies and interventions, which I refer to as “nonbeneficial” research, do not offer subjects a compensating potential for benefit. These studies and interventions have the potential to exploit subjects for the benefit of others, a concern that is especially acute when investigators enroll individuals who are unable to give informed consent. US regulations for research with human subjects attempt to address this concern (...) by mandating strict protections for nonbeneficial research with subjects who cannot consent. Typically, humans who cannot consent, such as children, may be enrolled in nonbeneficial research only when it poses low risks and has the potential to gather information of sufficient value to justify the risks, an appropriate surrogate gives permission on the individual’s behalf and the individual agrees (assents). In contrast, US regulations for nonbeneficial research with nonhuman primates do not include these protections, even though it too involves subjects who cannot consent and who face risks for the benefit of others. Is this difference in regulatory protections justified? Or does the principle of fairness—treat like cases alike—imply that regulations for nonbeneficial research with nonhuman primates should include protections similar to those that apply to nonbeneficial research with humans who cannot consent? (shrink)

: When children and incapacitated adults are enrolled in research that cannot directly benefit them, they can be exposed to no more than "minimal" risks, according to guidelines accepted around the world. We need a new standard for what "minimal" risks are, howeve--one that recognizes that participating in nonbeneficial research is like participating in a charitable activity. Such a standard appears likely to provide more stringent protections for these vulnerable populations.

: In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in a given study (the subjective (...) interpretation). The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)

When patients cannot make their own treatment decisions, surrogates typically step in to do it for them. Surrogate decision‐making is far from ideal, of course, as the surrogate may not know what the patient prefers or what best promotes her interests. One way to improve it would be to arm surrogates with information about what patients in similar circumstances tend to prefer, allowing them to make empirically grounded predictions about what their patient would want.

To give valid informed consent to participate in clinical research, potential participants should understand the risks, potential benefits, procedures, and alternatives. Potential participants also should understand that they are being invited to participate in research. Yet it is unclear what potential participants need to understand to satisfy this particular requirement. As a result, it is unclear what additional information investigators should disclose about the research; and it is also unclear when failures of understanding in this respect undermine the validity of (...) potential participants' informed consent. An analysis of individuals' interests suggests that potential participants need to understand three additional facts to understand that they are being invited to participate in research: 1) research contribution: those who enroll in the study will be contributing to a project designed to gather generalizable knowledge to benefit others in the future; 2) research relationship: the investigators will rely on participants' efforts to gather the generalizable knowledge to benefit others; and 3) research impact: the extent to which participating in the study will alter what participants do and what happens to them. (shrink)

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial (...) concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research. (shrink)

In standard medical care, physicians select treatments for patients based on clinical judgment, considering which treatment is best for the individual patient, given the patient's history and circumstances. In contrast, investigators conducting randomized clinical trials select treatments for participants based on a random selection process. Because this process represents a significant departure from the norms of standard medical care, it is widely assumed that potential research participants must understand randomization to give valid informed consent. This assumption, together with data that (...) many research participants do not understand randomization, implies that randomized clinical trials often fail to obtain adequately informed consent. Before accepting this conclusion, and before initiating extensive efforts to improve research participants' understanding of randomization, we should assess the plausible, but rarely analyzed assumption that participants need to understand randomization to give valid informed consent for randomized clinical trials. (shrink)

The first of two commentaries on "Respecting Donors to Biobank Research," from the January-February 2013 issue. © 2013 by The Hasti.

When children and incapacitated adults are enrolled in research that cannot directly benefit them, they can be exposed to no more than “minimal” risks, according to guidelines accepted around the world. We need a new standard for what “minimal” risks are, however—one that recognizes that participating in nonbeneficial research is like participating in a charitable activity. Such a standard appears likely to provide more stringent protections for these vulnerable populations.

There is wide agreement that communities in lower-income countries should benefit when they participate in multinational research. Debate now focuses on how and to what extent these communities should benefit. This debate has identified compelling reasons to reject the claim that whatever benefits a community agrees to accept are necessarily fair. Yet, those who conduct clinical research may conclude from this rejection that there is no reason to involve communities in the process of deciding how they benefit. Against this possibility, (...) the present manuscript argues that involving host communities in this process helps to promote four important goals: protecting host communities, respecting host communities, promoting transparency, and enhancing social value. (shrink)

There is widespread discussion concerning the safeguards appropriate for human research subjects. Less discussed is the fact that the safeguards one deems appropriate depend, in large part, on the model of research participation that one assumes. Therefore, to determine what safeguards are appropriate, it is necessary first to clarify the competing models of research participation. The ostensibly obscure debate over informed consent for research on stored biological samples is of particular interest in this regard because such research can involve varying (...) subsets of the three central elements of research involvement. As a result, analysis of this debate provides an opportunity to identify the competing models of research participation. Based on this analysis, this paper describes a new model of research participation that is emerging, and considers its implications for clinical research. (shrink)

ABSTRACT:Guidelines and regulations for medical research recognize that the experiences of humans and animals both matter morally. They thus set a presumption against harming research subjects, whether humans or animals, and mandate that the harms subjects experience should be the minimal necessary for achieving the scientific aims of the study. Beyond this, guidelines and regulations place upper limits on the extent to which human, but not animal, subjects may be harmed. They also mandate that human, but not animal, subjects should (...) be compensated for the harms they experience. In this article, I argue that this common approach to regulating medical research is mistaken. In particular, there are upper limits on the extent to which animals may ethically be harmed in order to collect data to benefit others, and there are moral reasons to compensate them for the harms they experience. I conclude that guidelines and regulations for research with animals should be revised accordingly. (shrink)

It is widely assumed that the use of deception in research is always inconsistent with obtaining valid consent. In addition, guidelines and regulations permit research without valid consent only when it poses no greater than minimal risk. Current practice thus prohibits studies that use deception and pose greater than minimal risk, including studies that rely on deceptive methods to evaluate experimental treatments. To assess whether these prohibitions are justified, the present paper evaluates five arguments that might be thought to support (...) the assumption that deception is always inconsistent with valid consent. Analysis of these arguments reveals that deception is frequently, but not always, inconsistent with obtaining valid consent for research. This conclusion suggests that, in order to avoid unnecessarily blocking valuable research, current policies and practice should be revised to recognize the conditions under which the use of deception can be consistent with obtaining research participants’ valid consent. (shrink)

When a patient lacks decision-making capacity and has not left a clear advance directive, there is now widespread agreement that patient-designated and next-of-kin surrogates should implement substituted judgment within a process of shared decision-making. Specifically, after discussing the “best scientific evidence available, as well as the patient's values, goals, and preferences” with the patient's clinicians, the patient-designated or next-of-kin surrogate should attempt to determine what decision the patient would have made in the circumstances. To the extent that this approach works, (...) it seems to provide about as much respect for the autonomy of incapacitated patients as we could ask for. But, as articles in this issue of the Report by Jeffrey Berger and by Ellen Robinson and colleagues emphasize, reality presents challenges. (shrink)

A good deal has been written on the ethics of peer review, especially in the scientific and medical literatures. In contrast, we are unaware of any articles on the ethics of peer review in bioethics. Recognising this gap, we evaluate the extant proposals regarding ethical standards for peer review in general and consider how they apply to bioethics. We argue that scholars have an obligation to perform peer review based on the extent to which they personally benefit from the peer (...) review process. We also argue, contrary to existing proposals and guidelines, that it can be appropriate for peer reviewers to benefit in their own scholarship from the manuscripts they review. With respect to bioethics in particular, we endorse double-blind review and suggest several ways in which the peer review process might be improved. (shrink)

The U.S. Federal regulations allow institutional review boards (IRBs) to approve non-beneficial pediatric research when the risks are a minor increase over minimal, provided that the research is likely to develop generalizable knowledge about the subjects' disorder or condition. This “subjects' condition” requirement is quite controversial; commentators have argued for a variety of interpretations. Despite this considerable disagreement in the literature, there have not been any attempts to apply principles of legal interpretation to determine how the subjects' condition requirement should (...) be understood. (shrink)

Although many of the issues surrounding innateness have received a good deal of attention lately, the basic concept of token innateness has been largely ignored. In the present paper, I try to correct this imbalance by offering an account of the innateness of token traits. I begin by explaining Stephen Stich's account of token innateness and offering a counterexample to that account. I then clarify why the contemporary biological approaches to innateness will not be able to resolve the problems that (...) beset Stich's account. From there, I develop an alternative understanding of the innateness of token traits, what I call a causal/explanatory account. The argument to be made is that token innateness is both a causal, and an explanatory, concept. After clarifying this understanding of innateness, and showing how it handles several counterexamples to other accounts, I end with some comments on what the causal/explanatory account suggests for our understanding of innateness in general. (shrink)

Identifying which subjects are vulnerable, and implementing safeguards to protect them, is widely regarded as essential to clinical research. Commentators have endorsed a number of responses to these challenges and have thereby made significant progress in understanding vulnerability in clinical research. At the same time, this literature points to a central contradiction which calls into question its potential to protect vulnerable subjects in practice. Specifically, analysis suggests that all human subjects are vulnerable and vulnerability in clinical research is comparative and (...) context dependent, in the sense that individuals are vulnerable relative to others and in some contexts only. Yet, if everyone is vulnerable, there seems to be no point in citing the vulnerability of some individuals. Moreover, the conclusion that everyone is vulnerable seems inconsistent with the claims that vulnerability is comparative and context dependent, raising concern over whether it will be possible to develop a comprehensive account of vulnerability that is internally consistent. The solution to this dilemma lies in recognition of the fact that the practical significance of claims regarding vulnerability depends on the context in which they are used. The claims that appear to lead to the central contradiction are in fact accurate conclusions that follow from different uses of the term ‘vulnerability’. The present manuscript describes this ‘pragmatic’ approach to vulnerability in clinical research and considers its implications for ensuring that subjects receive appropriate protection. (shrink)

There is much philosophical literature on the duty to rescue. Individuals who encounter and could save, at relatively little cost to themselves, a person at risk of losing life or limb are morally obligated to do so. Yet little has been said about the other side of the issue. There are cases in which the need for rescue could have been reasonably avoided by the rescuee. We argue for a duty to take rescue precautions, providing an account of the circumstances (...) in which it arises. This novel duty has important implications for public policy. We apply it to the situation of some of the uninsured in the United States. Given the US clinician's duty to provide emergency care to all people regardless of ability to pay, some of the uninsured have a moral duty to purchase health insurance. We defend the duty against objections, including the possibility that a right to rescue can be waived, thus undermining a duty to take rescue precautions, that the duty of many professionals is voluntarily incurred, and that a distinction between actively assumed and passively assumed risks matters morally. (shrink)

The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease , debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for in-depth (...) analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned.. (shrink)

Martin Luther King, Jr., quoting the 19th-century clergyman Theodore Parker, claimed that the arc of the moral universe “bends toward justice.” One hopes he is right, perhaps especially at times when history appears to have taken something of a detour. The 40th anniversary of the Belmont Report offers the opportunity to evaluate the arc of research ethics, to assess where it is going and whether it too is bending toward justice.The Belmont Report is the work of the National Commission, which (...) was charged with identifying “the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects.” The Commission first considered the possibility of deriving these... (shrink)

Work on the therapeutic misconception suggests that investigators should ensure that potential research subjects understand the fundamental differences between clinical research and clinical care. Yet, what potential research subjects should understand depends on their circumstances and the study in question. This analysis implies that researchers and review committees should stop attempting to define, measure, and dispel the therapeutic misconception, and instead should focus on what potential subjects should understand to participate in individual studies.

The prevailing “segregated model” for understanding clinical research sharply separates it from clinical care and subjects it to extensive regulations and guidelines. This approach is based on the fact that clinical research relies on procedures and methods—research biopsies, blinding, randomization, fixed treatment protocols, placebos—that pose risks and burdens to participants in order to collect data that might benefit all patients. Reliance on these methods raises the potential for exploitation and unfairness, and thus points to the need for independent ethical review (...) and more extensive informed consent. In contrast, it is widely assumed that clinical care does not raise these ethical concerns because it is designed to promote the best interests of individual patients. The segregation of clinical research from clinical care has been largely effective at protecting research participants. At the same time, this approach ignores the fact that several aspects of standard clinical care, such as clinician training and scheduling, also pose some risks and burdens to present patients for the benefit of all patients. We argue that recently proposed learning health care systems offer a way to address this concern, and better protect patients, by developing integrated review and consent procedures. Specifically, current approaches base the need for independent ethical review and more extensive informed consent on whether an activity is categorized as clinical research or clinical care. An ethically sounder approach, which could be incorporated into learning health care systems, would be to base the need for independent ethical review and more extensive informed consent on the extent to which an activity poses risks to present patients for the benefit of all patients. (shrink)

Clinical research is thought to be ethically problematic and is subject to extensive regulation and oversight. Despite frequent endorsement of this view, there has been almost no systematic evaluation of why clinical research might be ethically problematic. As a result, it is difficult to determine whether the regulations to which clinical research is subject address the ethical concerns it raises. Commentators who consider this question at all tend to assume that clinical research is ethically problematic because it exposes some individuals (...) to risks for the benefit of others. Yet, many other activities that expose some individuals to risks for the benefit of others are not subject to extensive regulation and oversight. This difference raises the question of whether clinical research is distinct from these activities in normatively relevant ways and, if so, what implications this difference (or differences) has for how clinical research should be regulated and conducted. The present manuscript attempts to answer this question by comparing clinical research to two other activities that expose some individuals to risks for the benefit of others. This comparison highlights an aspect of clinical research which has received relatively little attention, namely, the active role investigators play in exposing subjects to risks. I argue that this aspect explains much of the ethical concern expressed regarding clinical research. I end by considering the normative significance of this feature and the implications it has for how clinical research should be regulated and conducted. (shrink)

To provide a theoretical basis for the common view that moral status comes in degrees, many philosophers endorse ‘two-factor’ accounts of the foundations of moral status. These accounts postulate one or more properties which endow individuals with moral status, and one or more other properties which increase the moral status of those who possess them. Critical assessment of two-factor accounts has focused on their implications, especially for humans who lack the properties thought to increase individuals’ moral status. Unfortunately, this approach (...) has led to an impasse. To try to break it, the present manuscript instead assesses the assumption on which two-factor accounts are based, namely, possession of one or more properties, what I call ‘moral status enhancing’ properties, increases their possessors’ moral status. I argue that two challenges, the problem of relevance and the need for a threshold, reveal that there are no moral status enhancing properties, hence, no degrees of moral status among those who matter morally. (shrink)

Some placebo-controlled trials can continue ethically after a candidate vaccine is found to be safe and efficacious.