Randomization is the “gold standard” design for clinical research trials and is accepted as the best way to reduce bias. Although some controversy remains over this matter, we believe equipoise is the fundamental ethical requirement for conducting a randomized clinical trial. Despite much attention to the ethics of randomization, the moral psychology of this study design has not been explored. This article analyzes the ethical tensions that arise from conducting these studies and examines the moral psychology of this design from (...) the perspectives of physician-investigators and patient-subjects. We conclude with a discussion of the practical implications of this analysis. (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed alternatives are. (...) In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

The foundations of research ethics are riven with fault lines emanating from a fear that if research is too closely connected to weighty social purposes an imperative to advance the common good through research will justify abrogating the rights and welfare of study participants. The result is an impoverished conception of the nature of research, an incomplete focus on actors who bear important moral responsibilities, and a system of ethics and oversight highly attuned to the dangers of research but largely (...) silent about threats of ineffective, inefficient, and inequitable medical practices and health systems. -/- In For the Common Good: Philosophical Foundations of Research Ethics, Alex John London defends a conception of the common good that grounds a moral imperative with two requirements. The first is to promote research that generates the information necessary to enable key social institutions to effectively, efficiently, and equitably safeguard the basic interests of individuals. The second is to ensure that research is organized as a voluntary scheme of social cooperation that respects its various contributors' moral claims to be treated as free and equal. Connecting research to the goals of a just social order grounds a framework for assessing and managing research risk that reconciles these requirements and justifies key oversight practices in non-paternalistic terms. Reconceiving research ethics as resolving coordination problems and providing credible assurance that these requirements are being met expands the issues and actors that fall within the purview of the field and provides the foundation for a more unified and coherent approach to domestic and international research. -/- This is an open access title available under the terms of a CC BY-NC-ND 4.0 license. It is free to read at Oxford Scholarship Online and offered as a free PDF download from OUP and selected open access locations. (shrink)

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use (...) and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand. (shrink)

The issue of benefits in international clinical research is highly controversial. Against the background of wide recognition of the need to share benefits of research, the nature of benefits remains strongly contested. Little is known about the perspectives of research populations on this issue and the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. This exploratory study contributes to filling this void by examining perspectives of people in low-income South (...) African communities on benefits in international clinical research. Twenty-four individuals with and without experience of being involved in clinical research participated in in-depth interviews. Respondents felt that ancillary care should be provided to clinical research participants, while a clinical study conducted in particular community should bring better health to its members through post-trial benefits. Respondents' perspectives were grounded in the perception that the ultimate goal of international clinical research is to improve local health. We argue that perspectives and understandings of the respondents are shaped by local moral traditions rather than clinical research specificities and require attention as valid moral claims. It is necessary to acknowledge such claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting expectations. (shrink)

There is substantial published evidence showing that countless people enroll each year in ethically deficient clinical trials. Many of the trials are problematic because the quality of the science used to justify their launch may not be sufficiently vetted while many other trials may lack requisite social value. This poses the question: why do people volunteer for them? The answer resides in large part in the fact that informed consent practices have historically masked, rather than disclosed, the information that would (...) alert research candidates to the ethically problematic nature of the trials. The “reasonable person” and “key information” provisions in the revised US Common Rule create the opportunity to correct this historical shortcoming. Two sources are employed to shed light on what the “key information” is that should be disclosed to a “reasonable person”: the original disclosure aims of the Nuremberg Code, as well as an extensive body of meta-research evidence. Those sources jointly support a range of new disclosures in the informed consent process that would unmask the heretofore undisclosed information. The resulting proposed new disclosures pertain to the overall success prospects of clinical trials, the quality of the prior research that both forms the basis of clinical trials and informs assessment of their risks and benefits, the potential social value of clinical trials, and the commercial purposes of clinical trials. (shrink)

Debate over the relationship of law and bioethics is growing - what the relationship has been and what it should be in the future. While George Annas has praised law and rights-talk for creating modern bioethics, Carl Schneider has instead blamed law for hijacking bioethics and stunting moral reflection. Indeed, as modern bioethics approaches the 40-year mark, historians of bioethics are presenting divergent accounts. In one account, typified by Albert Jonsen, bioethics largely grew out of philosophy and theology, not law. (...) In another account, law has deeply shaped bioethics from the start, forging its central commitment to the rights of patients and research subjects and the fields imposition of broad fiduciary responsibilities on health care professionals and researchers.In addition to debating how to properly describe laws historical relationship to bioethics, commentators have argued over whether laws influence in bioethics is now good or bad. (shrink)

In many cases, the “therapeutic misconception” may be an unavoidable part of the imperfect process of recruitment and consent in medical researchPaul Appelbaum, Loren Roth, and Charles Lidz coined the term “therapeutic misconception” in 1982.1 They described it as the misconception that participating in research is the same as receiving individualised treatment from a physician. It referred to the research subject’s failure to appreciate that the aim of research is to obtain scientific knowledge, and that any benefit to the subject (...) is a by-product of that knowledge. More recent studies by Appelbaum and Lidz have shown that this phenomenon is just as pervasive now as it was twenty four years ago.2 The problem pertains not to any duty of care for researchers but to participants’ unfounded belief in the therapeutic potential of research.3 It is especially acute in phase I oncology trials, which aim to test the toxicity and highest tolerable dose of anticancer drugs.To remedy this situation, many have argued that both clinicians and researchers need to do more in explaining to subjects the differences between experimental research and standard care. Clinicians and researchers recruiting potential subjects for research must present information about the expected risks and benefits of participation in research in a more realistic and straightforward way.4 In one recent examination of consent forms for phase I oncology trials, Sam Horng et al found that, in the section on “benefit”, only one of 272 forms stated that the subjects were expected to benefit. They also found that 11 consent forms stated clearly that subjects would not benefit, 25 forms communicated uncertainty about benefit, and 5 forms said nothing about the chance of benefit. Interestingly, 139 forms alluded to the …. (shrink)

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)

One of the key ethical requirements for biomedical research is that it have an acceptable risk-benefit profile (Emanuel, Wendler, and Grady 2000). The International Conference of Harmonization guidelines mandate that clinical trials should be initiated and continued only if “the anticipated benefits justify the risks” (1996). Guidelines from the Council for International Organizations of Medical Sciences state that biomedical research is acceptable only if the “potential benefits and risks are reasonably balanced” (2002). U.S. federal regulations require that the “risks to (...) subjects” be “reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge” to be gained from the .. (shrink)

Earlier in the pages of this journal (p 481), Wendler and Miller offered the "net risks test" as an alternative approach to the ethical analysis of benefits and harms in research. They have been vocal critics of the dominant view of benefit-harm analysis in research ethics, which encompasses core concepts of duty of care, clinical equipoise and component analysis. They had been challenged to come up with a viable alternative to component analysis which meets five criteria. The alternative must (1) (...) protect research subjects; (2) allow clinical research to proceed; (3) explain how physicians may offer trial enrolment to their patients; (4) address the challenges posed by research containing a mixture of interventions and (5) define ethical standards according to which the risks and potential benefits of research may be consistently evaluated. This response argues that the net risks test meets none of these criteria and concludes that it is not a viable alternative to component analysis. (shrink)

Clinical trials in emergency situations present unique challenges, because they involve enrolling individuals who lack capacity to consent in the context of acute illness or injury. The US Department of Health and Human Services and Food and Drug Administration regulations allowing an Exception from Informed Consent in these circumstances contain requirements for community consultation, public disclosure and restrictions on study risks and benefits. In this paper, we analyse an issue raised in the regulations that has received little attention or analysis (...) but is ethically complex. This challenge is when to solicit and honour objections to EFIC trial enrolment, including from non-legally appointed representatives. We address novel questions involving whose objections should be honoured, what level of understanding is necessary for objections to be considered valid and how hard investigators should work to offer an opportunity to object. We present a set of criteria that provide conceptual and practical guidance. We argue that objections should be honoured if they undermine one of the key assumptions that allows for the permissibility of EFIC trials: that individuals would likely not object to enrolment based on their values or preferences. We then clarify the practical implications of this approach through examination of three cases of refusal in an EFIC study. (shrink)

Background A topic of great concern in bioethics is the medical research conducted in poor countries sponsored by wealthy nations. Western drug companies increasingly view Latin America as a proper place for clinical research trials. The region combines a large population, modern medical facilities, and low per capita incomes. Participants from developing countries may have little or non alternative means of treatment other than that offered through clinical trials. Therefore, the provision of a valid informed consent is important. Methods To (...) gain insight about some aspects of the informed consent procedure in a major cancer centre in Mexico, we conducted a three-step evaluation process: 1) a ten point multiple choice survey questionnaires, was used to explore some aspects of the patients' experiences during the informed consent process, 2) researchers' knowledge about specific aspects of the informed consent was evaluated in this study using survey questionnaires; and 3) the comprehensibility, readability and number of pages of the consent forms were analysed. The socioeconomic and educational level of the patients, were also considered. Results were reported using a numerical scale. Results Thirty five patients, 20 doctors, and 10 individuals working at the hospital agreed to participate in the study. Eighty three percent of the patients in the study were classified as living in poverty; education level was poor or non existent, and 31% of the patients were illiterate. The consent forms were difficult to understand according to 49% of the patients, most doctors agreed that the forms were not comprehensible to the patients. The average length of the IC documents analysed was 14 pages, and the readability average score was equivalent to 8TH Grade. Conclusion The results presented in this work describe some relevant characteristics of the population seen at public health care institutions in Mexico. Poverty, limited or no education, and the complexity of the information provided to the patients may question the validity of the informed consent procedure in this group of patients. (shrink)

The acceptance of military directives violating medical ethics and international covenants encouraged by the demonisation of the enemy by the US president in 2002 has effectively removed the right of medical personnel to refuse participation in internationally proscribed actionsMedicine and its traditional ethic of care is today a victim of the current conflict in Iraq and Afghanistan, its uniquely humanising mission rejected by US President George W Bush and his advisors. In denying the applicability of international agreements guaranteeing medicine’s ecumenical (...) role in this conflict they have transformed medicine into just another weapon of tactical significance. The result, predictable in retrospect, has been to make military physicians and nurses complicit—actively or passively—in what Litton calls an “atrocity-producing situation”, resulting in detainee or prisoner abuse.1From the first revelations of detainee torture in US detention camps to recent allegations of continued abuse , the focus of international attention has shifted from the US prosecution of low ranking, non-commissioned military personnel to the context in which the atrocities they committed occurred. “No one up the chain of command has ever been held accountable for what is in these horrifying images,” Center for Constitutional Rights Director Bill Goodman said of recently published photographs of 2004 prisoner torture and abuse.2 “The situation in several areas violates international law and conventions on human rights and torture,” said the UN Special Rapporteur on Torture following a 2006 investigation.3The denial of international law and convention involved the overt disavowal of covenants and conventions that for almost 150 years required medical personnel in the US military to act within the guidelines of a Hippocratic vision of medicine. To understand how fundamental this change has been requires a brief review of the history of medicine’s previously protected status and then a description of …. (shrink)

BackgroundThe pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.MethodsWe conducted a scoping review of the growing HIV cure (...) research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.DiscussionDespite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).ConclusionHIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time. (shrink)

In recent years, there has been a particular emphasis placed on conducting randomized controlled trials (RCTs) that compare the relative efficacy of psychosocial and pharmacological interventions. This article addresses relevant ethical considerations in the conduct of these treatment trials, with a focus on RCTs with children. Ethical concerns, including therapeutic misconception, treatment preference, therapeutic equipoise, structure of treatments, and balancing risks versus benefits, are introduced through a clinical scenario and discussed as they relate to psychotherapy versus medication RCTs. In each (...) case, suggestions are made for researchers seeking to minimize the impact of these ethical concerns on research participants. (shrink)

In this article, the question is discussed if and how Healthcare Ethics Committees (HECs) should be regulated. The paper consists of two parts. First, authors from eight EC member countries describe the status quo in their respective countries, and give reasons as to the form of regulation they consider most adequate. In the second part, the country reports are analysed. It is suggested that regulation of HECs should be central and weak. Central regulation is argued to be apt to improve (...) HECs’ accountability, relevance and comparability. To facilitate biomedical citizenship and ethical reflection, regulation should at the same time be weak rather than strict. Independence of HECs to deliberate about ethical questions, and to give solicited and unsolicited advice, should be supported and only interfered with by way of exception. One exception is when circumstances become temporary adversarial to ethical deliberation in healthcare institutions. In view of European unification, steps should be taken to develop consistent policies for both Eastern and Western European countries. (shrink)

The use of foster children as subjects in the pediatric HIV/AIDS clinical trials has been the subject of media controversy, raising a range of ethical and social dimensions. Several unsettled issues and debates in research ethics underlie the controversy and the lack of consensus among professional researchers on these issues was neither adequately appreciated nor presented in media reports. These issues include (1) the tension between protecting subjects from research risk while allowing them access to the possible benefits of research; (...) (2) the blurring of the potentially conflicting roles of investigator and physician and the boundaries between research and therapy; (3) the adequacy of Institutional Review Board oversight; and (4) trust and the relationships among physicians, investigators and industry. The media controversy about the pediatric HIV/AIDS clinical trials can be seen as a means of “manufacturing mistrust” in health care, research and social services that have not always met the needs and expectations of the public. In an era of emerging infections, it is critical to the public’s health that people understand the role of rigorous and ethical research in the development of safe and effective care. Investigators, journalists and the public need to become knowledgeable about major ethical issues in the conduct of research in order to engage in dialogue about balancing research risks and benefits and to be able to distinguish fact from distortion in an era of multiple and rapid transmission of information. (shrink)

Hastings Center Report, Volume 52, Issue 5, Page 32-42, September–October 2022.

Randomized trials depend on clinicians feeling that they are morally justified in allowing their patients to be randomized across treatment arms. Typically such justification rides on what has been called “clinical equipoise”—when there is disagreement of opinion among the community of experts about whether one treatment is better than another, then physicians can ethically enter their patients into a clinical trial, even if individual physicians are not at equipoise. Recent debates over prominent studies, however, illustrate that controversy can be easily (...) created rather than dispelled by trials, with many clinicians choosing not to use the proven therapy until they receive more convincing evidence of its superiority. In such situations, we propose that a new standard of equipoise be used to guide decisions about the ethical justifications for research trials—a standard of behavioral equipoise. Under behavioral equipoise, a trial is potentially justifiable if it addresses behavioral resistance to prior scientific evidence. (shrink)

Surveys and routine clinical procedures applied in research protocols are typically considered only minimally risky to participants. The apparent benign nature of "minimal risk" tasks increases the chance that investigators and Institutional Review Boards (IRBs) will overlook the probability that clinical tools will identify signs, symptoms, or definitive test results that are clinically-relevant to subjects' welfare. "Minimal risk" procedures may also pose a particular hazard to participants in clinical research by increasing the therapeutic misconception because the tasks mimic clinical care (...) and are often conducted in clinical settings. Investigators should anticipate which measures could yield clinically-important findings and should describe explicit plans for data monitoring, disclosure, and follow-up. Protocols that include reliable and valid clinical measures should prompt a more detailed risk assessment by the IRB, even when the tasks meet the regulatory criteria for minimal physical, psychological, or emotional risk. (shrink)

BackgroundFew studies have examined factors associated with willingness of people living with HIV to participate in HIV treatment clinical trials in Sub-Saharan Africa. We assessed the factors associated with participation of PLHIV in HIV treatment clinical trials research at a large urban clinical and research facility in Uganda.MethodsA mixed methods study was conducted at the Infectious Diseases Institute, adult HIV clinic between July 2016 and January 2017. Data were collected using structured questionnaires, focused group discussions with respondents categorised as either (...) participated or never participated in clinical trials and key informant interviews with IDI staff. A generalized linear model with a logit link function was used for multivariate analyses while the qualitative data were summarized using a thematic approach.ResultsWe enrolled a total of 202 and analysed 151 participants, 77 of whom were male with mean age of 41 years. The majority 127 expressed willingness to participate in treatment clinical trials if given an opportunity. At bivariate analysis, willingness to participate was significantly associated with respondents’ perception of a satisfactory compensation package, special status accorded and belief that their health status would improve while on the clinical trial. At multivariate analysis, a satisfactory compensation package and special status accorded in clinical trials remained significant. The qualitative data analysis confirmed these findings as participants valued the privilege of jumping the clinic waiting queues and spending less time in clinic, the wide range of free tests offered to trial participants, unrestricted access to senior physicians and regular communication from study team. Additionally, free meals offered during clinic visits meant that participants were not in a hurry to go back home. Barriers to participation included the perception that new drugs were being tested on them, fear of side effects like treatment failure and the uncertainty about privacy of their data.ConclusionWe found overwhelming willingness to participate in HIV treatment clinical trials. This was largely extrinsically influenced by the perceived material and health-related benefits. Investigators should pay attention to participants’ concerns for benefits which may override the need to understand study procedures and risks. (shrink)

In few other areas of bioethical inquiry exists as close a connection between bioethical professional advice and policy development as is the case with HIV and AIDS. Historically, the reasons for this have much to do with one of the groups initially affected most severely by HIV and AIDS, namely well-educated middle-class gay men in developed countries. This particular group of people, highly sophisticated and used to political activism in its pursuit of civil rights-related objectives, engaged the medical profession as (...) well as regulatory agencies such as the US Food and Drug Administration, and legislators (more so in the USA than in other countries) in a number of bioethically interesting policy areas. Many of the controversies of the times were framed as civil rights and/or ethical disputes. The initial areas of concern and inquiry focused on: informed consent to HIV testing and trial participation, the confidentiality of HIV test results, access to trials as a means of access to experimental drugs, the length of time it took to get an experimental drug to the market approval stage, and end-of-life decision-making. This line-up of issues explains why AIDS has become such an interesting topic for bioethicists. Bioethicists concerned about the traditional breadand- butter themes of medical ethics themes of the doctor - patient relationship (e.g., Daniels, 1991; Boyd, 1992), as well as bioethicists more concerned about policy and regulatory issues in the drug research and approval process (e.g., Edgar & Rothman, 1990; Salisbury & Schechter, 1990), found research topics worthy of vigorous pursuit. No surprise, then, that HIV/AIDS led to a probably unprecedented number of books and articles in professional journals (Manuel et al., 1990). HIV/AIDS has become a permanent fixture in all major mainstream bioethics textbooks (e.g., Kuhse & Singer, 1998; Arras & Steinbock, 1999). Reference series in medicine, ethics and law provide for dedicated volumes on AIDS.1 Even specialist bioethics textbooks, for instance those directed at dentistry students, carry chapters on HIV/AIDS (Ozar & Sokol, 2002). 128 Udo Schuklenk AIDS, designated by the medical profession a pandemic lives up to its classification. It did not stop at the borders of developed countries. As one would expect of a primarily sexually transmitted illness in the age of globalisation, it spread rapidly across the globe. Indeed, in many countries it has become one of the main causes of death, as in sub- Saharan Africa (Shisana & Simbayi, 2002). Dramatic increases in the number of AIDS cases are predicted for many Eastern European countries as well as for the two most populous nations on earth, India and China. Some of the HIV/AIDS-related bioethical and policy issues of concern to developed countries remain the same for developing countries. However, in ethically important ways they are dwarfed by concerns over drug prices, intellectual property rights, and affordable access to essential AIDS drugs for the impoverished masses of infected people in such countries. Of increasing importance have become ethical issues pertaining to the ever-growing research industry associated with clinical trials undertaken in developing countries. Indeed, major funding initiatives both in the USA and UK have brought clinical research in developing countries into focus. Some have questioned whether this attention is appropriate, considering other bioethical problems of arguably greater importance to developing countries (Chadwick & Schuklenk, 2003). Standards of clinical care in a study, and after a trial has concluded, as well as community benefits and access to the trial regime after the trial’s conclusion remain contentious issues. It is worth noting that more often than not it was an AIDS-related trial or policy decision that led to a great deal of bioethical analysis, yet the issues discussed almost always have ramifications far beyond AIDS. For instance, decisions about the question of what (if any) standards of care failures in preventive trials (of HIV vaccines or microbicides) ought to receive have important implications for non-AIDS prevention trials. (shrink)

In contrast to most publications on the ethics of paying research subjects, which start by identifying and analyzing major ethical concerns raised by the practice (in particular, risks of undue inducement and exploitation) and end with a set of—more or less well-justified—ethical recommendations for using payment schemes immune to these problems, this paper offers a systematic, principle-based ethical analysis of the practice. It argues that researchers have aprima faciemoral obligation to offer payment to research subjects, which stems from the principle (...) of social beneficence. This principle constitutes an ethical “spine” of the practice. Other ethical principles of research ethics (respect for autonomy, individual beneficence, and justice/fairness) make up an ethical “skeleton” of morally sound payment schemes by providing additional moral reasons for offering participants (1) recompense for reasonable expenses; and (2a) remuneration conceptualized as a reward for their valuable contribution, provided (i) it meets standards of equality, adequacy and non-exploitation, and (ii) it is not overly attractive (i.e., it does not constitute undue inducement for participation or retention, and does not encourage deceptive behaviors); or (2b) remuneration conceptualized as a market-driven price, provided (i) it is necessary and designed to help the study achieve its social and scientific goals, (ii) it does not reinforce wider social injustices and inequalities; (iii) it meets the requirement of non-exploitation; and (iv) it is not overly attractive. The principle of justice provides a strong ethical reason for not offering recompenses for lost wages (or loss of other reasonably expected profits). (shrink)

This paper targets an orphan topic in research ethics, namely the so called principle of the primacy of the human being, which states that the interests of the human subject should always take precedence over the interests of science and society. Although the principle occupies the central position in the majority of international ethical and legal standards for biomedical research, it has been commented in the literature mainly in passing. With a few notable exceptions, there is little in-depth discussion about (...) the meaning and role of the principle. Several authors note that the principle is vogue, ambiguous and apparently conflicting with the accepted practice of conducting non-beneficial research on individuals unable to give consent. There are opinions that it is just “a vacuous figure of speech” and should be abandoned. This paper argues that the primacy principle is far from being “a vacuous figure of speech”, rather it should be seen as a threefold concept: a fundamental interpretative rule, a procedural rule, and a substantive rule aimed at protecting research subjects from instrumental treatment and unacceptable risks. This interpretation tracks back to the principle regulatory and normative origins in the Declaration of Helsinki of 1975, but also acknowledges changes in research ethics and practice, which took place at the turn on the twentieth and twenty-first centuries. Thus, the proposed reading of the principle is not only original, but also historically grounded and normatively fruitful. It provides a fresh and ethically rich perspective on extensively debated, but still controversial problem of an upper limit of permissible risks in non-beneficial studies. (shrink)

Clinicians and health researchers frequently encounter opportunities to rescue people. Rescue cases can generate a moral duty to aid those in peril. As such, bioethicists have leveraged a duty to rescue for a variety of purposes. Yet, despite its broad application, the duty to rescue is under-analyzed. In this paper, we assess the state of theorizing about the duty to rescue. There are large gaps in bioethicists’ understanding of the force, scope, and justification of the two most cited duties to (...) rescue—the individual duty of easy rescue and the institutional rule of rescue. We argue that the duty of easy rescue faces unresolved challenges regarding its force and scope, and the rule of rescue is indefensible. If the duty to rescue is to help solve ethical problems, these theoretical gaps must be addressed. We identify two further conceptions of the duty to rescue that have received less attention—an institutional duty of easy rescue and the professional duty to rescue. Both provide guidance in addressing force and scope concerns and, thereby, traction in answering the outstanding problems with the duty to rescue. We conclude by proposing and propose research priorities for developing accounts of duties to rescue in bioethics. (shrink)

Many in the international development community have embraced the randomized controlled field experiment, akin to a biomedical clinical trial for social interventions, as the new “gold evidential standard” in program impact evaluation. In response, critics have called upon the method’s advocates to consider the moral dimensions of randomization, leading to a debate about the method’s ethics. My research intervenes in this debate by empirically investigating how researchers manage the perception of randomization in the field. Without the possibility of a placebo, (...) researchers rhetorically and materially frame the experiment differently for the control and treatment groups. Three technologies allow for this differential framing: geographic separation, temporal delay, and public randomization ceremonies. Geographic separation is a “technology of opacity” designed to obscure unequal resource distribution by disentangling the intervention and research components of the experiment for the control group. The latter two are technologies of transparency designed to expose the element of randomization but downplay conditions that may affect participant buy in. All three technologies work to preclude collective definitions of fair resource allocation, yet they are not fully successful in preventing modes of confrontation and resistance that lie outside of the experiment’s framing. (shrink)

With improved diagnostic capability and accuracy, the fields of medicine, neuroscience, psychiatry, and psychology have benefitted remarkably from the dramatic advancements in neuroimaging technology. Not only can surface and subsurface structures of the brain be mapped with incredible anatomical detail, now neural activity can be imaged across time as the brain responds to different stimuli. These sophisticated techniques have been a vital element in the recent increase in neuroimaging-based research. This increase, while producing new diagnostic techniques and improved treatment mechanisms (...) for neurological disease, has also led to a new dilemma for human subjects researchers: how should incidental findings be managed? An incidental finding is a finding concerning an individual research participant that has potential health or reproductive importance and is discovered in the course of conducting research but is beyond the aims of this study. (shrink)

This paper addresses the question of how incidental findings in clinical research should be managed by researchers, focusing in detail on IFs discovered in neuroimaging research. It begins by engaging the larger research ethics issue of whether researchers have any obligations of clinical care to participants, and assesses the content and merits of one particular framework for answering this question, Richardson and Belsky's ancillary care model. From here the paper develops an organizational structure for integrating the ancillary care model with (...) existing research ethics standards, with the aim of better understanding their respective domains. It makes a distinction between incidental findings that are anticipated by informed consent documents, and those that are unanticipated, arguing that this distinction is critical for evaluating researcher obligations. Finally, it takes on the issue of incidental findings in neuroimaging research, translating the standards discussed into recommendations for both unanticipated and anticipated findings. (shrink)

Novel immune therapies are increasingly based on the molecular differentiation of disease patterns. The related clinical studies are thus more often characterized by the so-called adaptive study designs (umbrella or basket studies including platform studies), which are continuously adjusted based on novel results. This paper analyses new study designs beyond the often-postulated need for regulation in order to identify ethical problems based on typical structural features and to—whenever possible—suggest solutions. To do so, it addresses the following topics: the relationship between (...) social and scientific values of a study as well as aspects of the scientific validity of new forms of evidence; the inclusion of study subjects under the condition of relative uncertainty; specific challenges in the process of ethical approval, and ethical and practical challenges in the process of informing patients and receiving informed consent. Additionally, the topic of a potential risk–benefit assessment of such therapies is addressed. (shrink)

Randomised controlled trials (RCTs) sometimes recruit participants who are desperate to receive the experimental treatment. This paper defends the practice against three arguements that suggest it is unethical first, desperate volunteers are not in equipoise. Second clinicians, entering patients onto trials are disavowing their therapeutic obligation to deliver the best treatment; they are following trial protocols rather than delivering individualised care. Research is not treatment; its ethical justification is different. Consent is crucial. Third, desperate volunteers do not give proper consent: (...) effectively, they are coerced. This paper responds by advocating a notion of equipoise based on expert knowledge and widely shared values. Where such collective, expert equipoise exists there is a prima facie case for an RCT. Next the paper argues that trial entry does not involve clinicians disavowing their therapeutic obligation; individualised care based on insufficient evidence is not in patients best interest. Finally, it argues that where equipoise exists it is acceptable to limit access to experimental agents; desperate volunteers are not coerced because their desperation does not translate into a right to receive what they desire. (shrink)

This paper advances a new criterion of a vulnerable population in research. According to this criterion, there are consent-based and fairness-based reasons for calling a group vulnerable. The criterion is then applied to the case of people with serious illnesses. It is argued that people with serious illnesses meet this criterion for reasons related to consent. Seriously ill people have a susceptibility to “enticing offers” that hold out the prospect of removing or alleviating illness, and this susceptibility reduces their ability (...) to safeguard their own interests. This explains the inclusion of people with serious illnesses in the Belmont Report’s list of populations needing special protections, and supports the claim that vulnerability is the rule, rather than the exception, in biomedical research. (shrink)

When may a physician enroll a patient in clinical research? An adequate answer to this question requires clarification of trust-based obligations of the state and the physician-researcher respectively to the patient-subject. The state relies on the voluntarism of patient-subjects to advance the public interest in science. Accordingly, it is obligated to protect the agent-neutral interests of patient-subjects through promulgating standards that secure these interests. Component analysis is the only comprehensive and systematic specification of regulatory standards for benefit-harm evaluation by research (...) ethics committees (RECs). Clinical equipoise, a standard in component analysis, ensures the treatment arms of a randomised control trial are consistent with competent medical care. It thus serves to protect agent-neutral welfare interests of the patient-subject. But REC review occurs prior to enrolment, highlighting the independent responsibility of the physician-researcher to protect the agent-relative welfare interests of the patient-subject. In a novel interpretation of the duty of care, we argue for a “clinical judgment principle” which requires the physician-researcher to exercise judgment in the interests of the patient-subject taking into account evidence on treatments and the patient-subject‘s circumstances. (shrink)

Risk–benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible (...) research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm. (shrink)

Heated debate surrounds the question whether the relationship between physician-researcher and patient-subject is governed by a duty of care. Miller and Weijer argue that fiduciary law provides a strong legal foundation for this duty, and for articulating the terms of the relationship between physician-researcher and patient-subject.

Bioethics is currently witnessing unprecedented debate over the moral and legal norms governing the conduct of clinical research. At the center of this debate is the duty of care in clinical research, and its most widely accepted specification, clinical equipoise. In recent work, we have argued that equipoise and cognate concepts central to the ethics of clinical research have been left unnecessarily vulnerable to criticism. We have suggested that the vulnerability lies in the conspicuous absence of an articulated foundation in (...) moral and legal theory of the physician-researcher's duty of care to the patient-subject. We have repeatedly suggested that the requisite foundation is in the ethics of trust and the law of fiduciaries.Curiously, despite the absence of a published thorough exposition of our position, some have preemptively criticized our suggestion that the relationship between physician-researcher and patient-subject is fiduciary. Others have offered their own accounts of the implications of fiduciary law for the relationship. (shrink)