: The debate over when medical research may be performed in developing countries has steered clear of the broad issues of social justice in favor of what seem more tractable, practical issues. A better approach will reframe the question of justice in international research in a way that makes explicit the links between medical research, the social determinants of health, and global justice.

Advertising by health care institutions has increased steadily in recent years. While direct-to-consumer prescription drug advertising is subject to unique oversight by the Federal Drug Administration, advertisements for health care services are regulated by the Federal Trade Commission and treated no differently from advertisements for consumer goods. In this article, we argue that decisions about pursuing health care services are distinguished by informational asymmetries, high stakes, and patient vulnerabilities, grounding fiduciary responsibilities on the part of health care providers and health (...) care institutions. Using examples, we illustrate how common advertising techniques may mislead patients and compromise fiduciary relationships, thereby posing ethical risks to patients, providers, health care institutions, and society. We conclude by proposing that these risks justify new standards for advertising when considered as part of the moral obligation of health care institutions and suggest that mechanisms currently in place to regulate advertising for prescription pharmaceuticals should be applied to advertising for health care services more broadly. (shrink)

First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns on claims (...) about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs. Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will (...) be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world. (shrink)

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs. Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will (...) be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world. (shrink)

This paper offers a non-paternalistic justification for prospective research review as providing a credible social assurance that the institutions of scientific advancement respect and affirm the moral equality of all community members and as creating a “market” in which stakeholders working to advance diverse ends also advance the common good.

This paper examines the concept of a 'standard of care' as it has been used in recent arguments over the ethics of international human-subjects research. It argues that this concept is ambiguous along two different axes, with the result that there are at least four possible standard of care arguments that have not always been clearly distinguished. As a result, it has been difficult to assess the implications of opposing standard of care arguments, to recognize important differences in their supporting (...) rationales, and even to locate the crux of the disagreement in some instances. The goal of the present discussion, therefore, is to disambiguate the concept of a 'standard of care' and to highlight the areas of genuine disagreement among different standards. In the end it is argued that one standard of care argument in particular is more complex than either its proponents or its critics may have recognized and that understanding this possibility opens up a potentially promising avenue of inquiry that remains to be carefully explored. (shrink)

Patient-funded trials are gaining traction as a means of accelerating clinical translation. However, such trials sidestep mechanisms that promote rigor, relevance, efficiency, and fairness. We recommend that funding bodies or research institutions establish mechanisms for merit review of patient-funded trials, and we offer some basic criteria for evaluating PFT protocols.

Any view of equipoise faces perhaps the most radical and far-reaching objections from moral foundations. These objections hold that the equipoise requirement conflates the ethics of medical research and the ethics of clinical medicine. Once this conflation is recognized, this position holds, research can be given a new foundation on the imperative to avoid exploiting research participants. This article argues that what is novel in this critique is not as successful as its proponents claim and that the ultimate success of (...) this approach actually hinges on a version of the objection from utility. Nevertheless, this criticism highlights the limited scope of applicability of the equipoise requirement. The article concludes, therefore, by describing the outlines of what the article calls an ‘integrative approach’ to clinical trials. This approach represents one way in which the normative requirements of equipoise and the non-exploitation approach might be unified under a single, broad framework. (shrink)

This paper examines the role of equipoise in evaluating international research. It distinguishes two possible formulations of the equipoise requirement that license very different evaluations of international research proposals. The interpretation that adopts a narrow criterion of similarity between clinical contexts has played an important role in one recent controversy, but it suffers from a number of problems. An alternative interpretation that adopts a broader criterion of similarity does a better job of avoiding both exploitation of the brute fact of (...) social deprivation and the exploitation of needy populations for the benefit of more well-off populations. It also holds out the promise of reconciling the need to find interventions that can be employed in developing world contexts with the cluster of moral values that must constrain the way such research is carried out. (shrink)

This article argues that lingering uncertainty about the normative foundations of research ethics is perpetuated by two unfounded dogmas of research ethics. The first dogma is that clinical research, as a social activity, is an inherently utilitarian endeavor. The second dogma is that an acceptable framework for research ethics must impose constraints on this endeavor whose moral force is grounded in role-related obligations of either physicians or researchers. This article argues that these dogmas are common to traditional articulations of the (...) equipoise requirement and to recently articulated alternatives, such as the non-exploitation approach. Moreover, important shortcomings of these approaches can be traced to their acceptance of these dogmas. After highlighting these shortcomings, this article illustrates the benefits of rejecting these dogmas by sketching the broad outlines of an alternative called the "integrative approach" to clinical research. (shrink)

There is near universal agreement within the scientific and ethics communities that a necessary condition for the moral permissibility of cross-national, collaborative research is that it be responsive to the health needs of the host community. It has proven difficult, however, to leverage or capitalize on this consensus in order to resolve lingering disputes about the ethics of international medical research. This is largely because different sides in these debates have sometimes provided different interpretations of what this requirement amounts to (...) in actual practice. The goal of the discussion that follows is to clarify the nature of this important moral requirement. The first section explains the requirement for responsiveness to host community health needs in the context of international medical research. The second section examines various formulations of this requirement as they are enunciated in some of the core consensus documents in research ethics. The third section then defends a particular interpretation of this requirement, and the final sections examine more liberal alternatives with the aim of highlighting points of agreement and assessing the significance of areas of disagreement. (shrink)

Before participants can be enrolled in a clinical trial, an institutional review board must determine that the risks that the research poses to participants are ‘reasonable.’ This paper examines the two dominant frameworks for assessing research risks and argues that each approach suffers from significant shortcomings. It then considers what issues must be addressed in order to construct a framework for risk assessment that is grounded in a compelling normative foundation and might provide more operationally precise guidance to the deliberations (...) of various stakeholders. The paper concludes by sketching the outlines of what is referred to as the ‘Integrative Approach’ to risk assessment and by highlighting some of the ways in which this approach may be more promising than current alternatives. (shrink)

Little research has explored the possible effects of government institutions in emerging economies on ethical reviews of multinational research. We conducted semi-structured, in-depth telephone interviews with 15 researchers, Research Ethics Committees personnel, and a government agency member involved in multinational HIV Prevention Trials Network research in emerging economies. Ministries of Health or other government agencies often play pivotal roles as facilitators or barriers in the research ethics approval process. Government agency RECs reviewing protocols may face particular challenges, as they can (...) lack resources, be poorly organized, have inconsistent review processes and limited expertise, and use differing definitions of national interests, including upholding national reputation and avoiding potential exploitation and stigma of the country's population. The MOH/governmental review body may be affected by power dynamics and politics in study reviews; may consider issues both related and unrelated to research ethics as understood elsewhere; and may prioritize particular diseases, treatments, or interventions over other topics/types of research. Poor communication and deeply-rooted tensions may exist between sponsor and host countries, impeding optimal interactions and reviews. Investigators must understand and plan for the potential effects of governmental agencies on multinational collaborative research, including preserving adequate time for agency review, and contacting these agencies beforehand to address issues that may arise. Better understanding of these issues can aid and advance appropriate global scientific collaboration. (shrink)

To give substance to the rhetoric of ‘learning health systems’, a variety of novel trial designs are being explored to more seamlessly integrate research with medical practice, reduce study duration and reduce the number of participants allocated to ineffective interventions. Many of these designs rely on response adaptive randomisation. However, critics charge that RAR is unethical on the grounds that it violates the principle of equipoise. In this paper, I reconstruct critiques of RAR as holding that it is inconsistent with (...) five important ethical principles. I then argue that these criticisms rest on a faulty view of equipoise encouraged by the idea that a RAR study models the beliefs of a single rational agent about the relative merits of the interventions being studied. I outline a view in which RAR models an idealised health system in which diverse communities of fully informed experts shrink or grow as their constituent members update their expert opinions in light of reliable medical evidence. I show how a proper understanding of clinical equipoise can reconcile this conception of RAR with these five ethical principles. This analysis removes an in-principle objection to RAR and sheds important light on the relationship between clinical equipoise and transient diversity in the scientific community. (shrink)

After criticizing three common conceptions of therelationship between practical ethics and ethical theory, analternative modeled on Aristotle's conception of the relationshipbetween rhetoric and philosophical ethics is explored. Thisaccount is unique in that it neither denigrates the project ofsearching for an adequate comprehensive ethical theory norsubordinates practical ethics to that project. Because the purpose of practical ethics, on this view, is tosecure the cooperation of other persons in a way that respectstheir status as free and equal, it seeks to influence thejudgments (...) of others by providing them with reasons that areaccessible to their own understanding. On this account, theindependence of practical ethics is rooted in an appreciation ofthe constraints that non-ideal circumstances place on the rolethat the philosophically refined premises of moral theory canplay in such public deliberations. Practical and philosophicalethics are united, not by shared theoretical frameworks orprinciples, but by the need to exercise intelligently the sameintellectual and affective capacities. They are separated, notby the particularity or generality of their starting points, butby their responsiveness to the practical problem of facilitatingsound normative deliberations among persons as we find them,under non-ideal circumstances. (shrink)

Critics of clinical equipoise have long argued that it represents an overly permissive, and therefore morally unacceptable, mechanism for resolving the tensions inherent in clinical research. In particular, the equipoise requirement is often attacked on the grounds that it is not sufficiently responsive to the interests of individual patients. In this paper, we outline a view of equipoise that not only withstands a stronger version of this objection, which was recently articulated by Deborah Hellman, but also plays important roles in (...) clarifying the discussion. (shrink)

When the benefits of surgery do not outweigh the harms or where they do not clearly do so, surgical interventions become morally contested. Cutting to the Core examines a number of such surgeries, including infant male circumcision and cutting the genitals of female children, the separation of conjoined twins, surgical sex assignment of intersex children and the surgical re-assignment of transsexuals, limb and face transplantation, cosmetic surgery, and placebo surgery.

: An Aristotelian conception of practical ethics can be derived from the account of practical reasoning that Aristotle articulates in his Rhetoric and this has important implications for the way we understand the nature and limits of practical ethics. An important feature of this conception of practical ethics is its responsiveness to the complex ways in which agents form and maintain moral commitments, and this has important implications for the debate concerning methods of ethics in applied ethics. In particular, this (...) feature enables us to understand casuistry, narrative, and principlism as mutually supportive modes of moral inquiry, rather than divergent and mutually exclusive methods of ethics. As a result, an Aristotelian conception of practical ethics clears the conceptual common ground upon which practical ethicists can forge a stable and realistic self-understanding. (shrink)

In crafting our paper on addressing the ethical challenges in HIV prevention research with people who inject drugs, 1 we had hoped to stimulate further discussion and deliberation about the topic. We are pleased that three commentaries on our paper have begun this process. 2 3 4 The commentaries rightly bring up important issues relating to community engagement and problems in translating research into practice in the fraught environments in which PWID face multiple risks. These risks include acquisition of HIV (...) as well as criminalisation, stigma and lack of access to needed healthcare, prevention and social services. We take this opportunity to respond to the excellent points raised by the commentators. All of the commentaries support our emphasis on robust community engagement with PWID and other stakeholders in designing and conducting HIV prevention research, but urge us to go farther. Wolfe highlights the... (shrink)

Within international development [1], public health [2], and clinical medicine [3]–[5], there is increasing interest in determining whether cash payments or other economic incentives can be used to influence the choices and behavior of individuals and groups in order to promote desired health goals. However, a number of complex issues affect the review and approval by research ethics committees of research studying the effectiveness of using financial incentives to promote desired health goals. Current ethical and regulatory frameworks regard the provision (...) of gifts or cash payments to participants in human research as potentially problematic. Specifically, these frameworks imply that such incentives may undermine the autonomy of participant choice, hinder the disclosure of medical information, exacerbate social inequalities, or result in the exploitation or degradation of vulnerable populations [6]–[9]. Typically, these frameworks provide guidance about payment to research participants to reimburse expenses, to compensate for time and effort, to provide insurance coverage, or as an incentive to participate in the research itself. However, the issue of payment as a component of the research intervention is relatively new. RECs thus lack explicit guidance about ethical issues surrounding research that evaluates the use of financial incentives as an intervention to promote health. (shrink)

Advance care planning refers to the process of determining how one wants to be cared for in the event that one is no longer competent to make one's own medical decisions. Some have argued that advance care plans often fail to be normatively binding on caretakers because those plans do not reflect the interests of patients once they enter an incompetent state. In this article, we argue that when the core medical ethical principles of respect for patient autonomy, honest and (...) adequate disclosure of information, institutional transparency, and concern for patient welfare are upheld, a policy that would allow for the disregard of advance care plans is self-defeating. This is because when the four principles are upheld, a patient's willingness to undergo treatment depends critically on the willingness of her caretakers to honor the wishes she has outlined in her advance care plan. A patient who fears that her caretakers will not honor her wishes may choose to avoid medical care so as to limit the influence of her caretakers in the future, which may lead to worse medical outcomes than if she had undergone care. In order to avoid worse medical outcomes and uphold the four core principles, caregivers who are concerned about the future welfare of their patients should focus on improving advance care planning and commit to honoring their patients’ advance care plans. (shrink)

IN BOTH THE EUDEMIAN ETHICS AND THE NICOMACHEAN ETHICS, Aristotle says that the aim of ethical inquiry is a practical one; we want to know what virtue is so that we may become good ourselves and thereby do well and be happy. By classifying ethical inquiry as a practical endeavor, Aristotle is rejecting a view that he attributes to Socrates according to which ethics is a kind of theoretical science. In theoretical sciences, such as geometry or astronomy, the knowledge of (...) a particular subject matter is sought as an end in itself, and the possession of such knowledge is sufficient to make one a geometer or an astronomer. In rejecting this model Aristotle argues that the knowledge of virtue is sought not solely for itself but in order to inform praxis and in order that we become virtuous and good, not by knowing what the virtues are but by cultivating them in practice. (shrink)

The extant clinical literature indicates profound problems in the assessment, monitoring, and documentation of care in long-term care facilities. The lack of adequate resources to accommodate higher staff-to-resident ratios adds additional urgency to the goal of identifying more costeffective mechanisms to provide care oversight. The ever expanding array of electronic monitoring technologies in the clinical research arena demands a conceptual and pragmatic framework for the resolution of ethical tensions inherent in the use of such innovative tools. CareMedia is a project (...) that explores the utility of video, audio and sensor technologies as a continuous real-time assessment and outcomes measurement tool. In this paper, the authors describe the seminal ethical challenges encountered during the implementation phase of this project, namely privacy and confidentiality protection, and the strategies employed to resolve the ethical tensions by applying principles of the interest theory of rights. (shrink)

In crafting our paper on addressing the ethical challenges in HIV prevention research with people who inject drugs,1 we had hoped to stimulate further discussion and deliberation about the topic. We are pleased that three commentaries on our paper have begun this process.2 3 4 The commentaries rightly bring up important issues relating to community engagement and problems in translating research into practice in the fraught environments in which PWID face multiple risks. These risks include acquisition of HIV as well (...) as criminalisation, stigma and lack of access to needed healthcare, prevention and social services. We take this opportunity to respond to the excellent points raised by the commentators. All of the commentaries support our emphasis on robust community engagement with PWID and other stakeholders in designing and conducting HIV prevention research, but urge us to go farther. Wolfe highlights the difficulty of even engaging with community members in oppressive settings, where authorities severely restrict civil liberties of PWID so that even discussing issues related to drug use and enforcement may place individuals at risk. To overcome such limitations, he appropriately suggests interviewing confidentially those who have previously been detained in closed settings as part of the community engagement process. Similarly, Wolfe observes that critical issues can be overlooked with a narrow focus on study procedures if contextual factors before, during or after a study are ignored. For example, he cites the risk of overdose for study participants who have been abstinent during a study and subsequently resume injecting when the study concludes. These kinds of risks may not be obvious …. (shrink)

International non-governmental organisations face a dilemma when deciding whether to intervene in crisis situations where their efforts can be exploited or co-opted by others: intervene and risk becoming complicit with wrongdoing or sit on the sidelines and consign vulnerable people to the ravages of neglect or oppression. In “‘ He who helps the guilty, shares the crime’? INGOs, moral narcissism and complicity in wrongdoing,” Buth et al argue that concerns about complicity often stifle ethical debate and encourage moral narcissism. We (...) argue that neglecting concerns about complicity can foster a different form of moral narcissism and that where worries of complicity are present, aid efforts face three types of risk: risks to others created by contributing to wrongful acts or bad outcomes; risks to the moral integrity of the INGO and its personnel; and risks to social trust in the INGO. In the end, we challenge the assumption that there is a unique, ethically best way to reconcile these values. We suggest that the causes of justice and humanity might be better served by a diverse community of INGOs who each gives different weight to these concerns, than if each INGO adopts the same framework for reconciling these competing demands. (shrink)

This paper presents a proof of concept for a graphical models approach to assessing the moral coherence and moral robustness of systems of social interactions. “Moral coherence” refers to the degree to which the rights and duties of agents within a system are effectively respected when agents in the system comply with the rights and duties that are recognized as in force for the relevant context of interaction. “Moral robustness” refers to the degree to which a system of social interaction (...) is configured to ensure that the interests of agents are effectively respected even in the face of noncompliance. Using the case of conscientious objection of pharmacists to filling prescriptions for emergency contraception as an example, we illustrate how a graphical models approach can help stakeholders identify structural weaknesses in systems of social interaction and evaluate the relative merits of alternate organizational structures. By illustrating the merits of a graphical models approach we hope to spur further developments in this area. (shrink)

The decision to initiate invasive, first-in-human trials involving Parkinson’s disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable riskbenefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close (...) with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies. (shrink)