Medical Research Ethics

Animal models have long been used to investigate human mental disorders, including depression, anxiety, and schizophrenia. This practice is usually justified in terms of the benefits (to humans) outweighing the costs (to the animals). I argue on utility maximization grounds that we should phase out animal models in neuropsychiatric research. Our leading theories of how human minds and behavior evolved invoke sociocultural factors whose relation to nonhuman minds, societies, and behavior has not been homologized. Thus it is not at all (...) clear that we are gaining the epistemic or clinical benefits we want from this animal-based research. (shrink)

En este trabajo se comparan dos representaciones en competencia sobre el origen de la bioética para llamar la atención sobre un posible cambio de marco teórico dentro de la disciplina. Por un lado, una representación parroquiana del origen de la bioética, centrada en problemas tecnológicos locales, y fundamentada en tradiciones culturales particulares. Por otro lado, una representación universal y pluralista, que enfrenta problemas de justicia y salud globales y que intenta buscar el fundamento normativo del discurso de la bioética en (...) los derechos humanos. Luego de compararlas, desarrollo algunas razones para mostrar por qué las relaciones entre bioética y derechos humanos están sólidamente justificadas. Por último, planteo dos observaciones críticas que deberían tenerse en cuenta al pensar la relación entre bioética y derechos humanos. (shrink)

A self-fulfilling prophecy (SFP) in neuroprognostication occurs when a patient in coma is predicted to have a poor outcome, and life-sustaining treatment is withdrawn on the basis of that prediction, thus directly bringing about a poor outcome (viz. death) for that patient. In contrast to the predominant emphasis in the bioethics literature, we look beyond the moral issues raised by the possibility that an erroneous prediction might lead to the death of a patient who otherwise would have lived. Instead, we (...) focus on the problematic epistemic consequences of neuroprognostic SFPs in settings where research and practice intersect. When this sort of SFP occurs, the problem is that physicians and researchers are never in a position to notice whether their original prognosis was correct or incorrect, since the patient dies anyway. Thus, SFPs keep us from discerning false positives from true positives, inhibiting proper assessment of novel prognostic tests. This epistemic problem of SFPs thus impedes learning, but ethical obligations of patient care make it difficult to avoid SFPs. We then show how the impediment to catching false positive indicators of poor outcome distorts research on novel techniques for neuroprognostication, allowing biases to persist in prognostic tests. We finally highlight a particular risk that a precautionary bias towards early withdrawal of life-sustaining treatment may be amplified. We conclude with guidelines about how researchers can mitigate the epistemic problems of SFPs, to achieve more responsible innovation of neuroprognostication for patients in coma. (shrink)

Reprint of an article that first appeared in Theoretical Medicine and Bioethics (2017).

Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the “gastruloid,” which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos. But fitting an ambiguous object into an existing category with well-worn pathways in research ethics, like the embryo, is only a (...) temporary fix. The bigger problem is that we no longer know what an embryo is. We haven’t had a non-absurd definition of ‘embryo’ for several decades and without a well-defined comparison class, asking whether gastruloids belong to the morally relevant class of things we call embryos is to ask a question without an answer. What’s the alternative? A better approach needs to avoid what I’ll refer to as “the potentiality trap” and, instead, rely on the emergence of morally salient facts about gastruloids and other synthetic embryos. (shrink)

Deep Brain Stimulation is currently being investigated as an experimental treatment for patients suffering from treatment-refractory AN, with an increasing number of case reports and small-scale trials published. Although still at an exploratory and experimental stage, initial results have been promising. Despite the risks associated with an invasive neurosurgical procedure and the long-term implantation of a foreign body, DBS has a number of advantageous features for patients with SE-AN. Stimulation can be fine-tuned to the specific needs of the particular patient, (...) is relatively reversible, and the technique also allows for the crucial issue of investigating and comparing the effects of different neural targets. However, at a time when DBS is emerging as a promising investigational treatment modality for AN, lesioning procedures in psychiatry are having a renaissance. Of concern it has been argued that the two kinds of interventions should instead be understood as rivaling, yet “mutually enriching paradigms” despite the fact that lesioning the brain is irreversible and there is no evidence base for an effective target in AN. We argue that lesioning procedures in AN are unethical at this stage of knowledge and seriously problematic for this patient group, for whom self-control is particularly central to wellbeing. They pose a greater risk of major harms that cannot justify ethical equipoise, despite the apparent superiority in reduced short term surgical harms and lower cost. (shrink)

Given the sordid history of injustices linking genetics to race and ethnicity, considerations of justice are central to ensuring the responsible development of precision medicine programmes around the world. While considerations of justice may be in tension with other areas of concern, such as scientific value or privacy, there are also be tensions between different aspects of justice. This paper focuses on three particular aspects of justice relevant to this context: social justice, distributive justice and human rights. The implications of (...) each for the use of race and ethnicity in precision medicine is described, along with how they intersect and potentially conflict with one another. By attending to these intersections, we aim to enrich and add nuance to debates over how best to proceed with precision medicine initiatives. (shrink)

This article presents a quantitative way of modeling the interim decisions of clinical trials. While statistical approaches tend to focus on the epistemic aspects of statistical monitoring rules, often overlooking ethical considerations, ethical approaches tend to neglect key epistemic dimension. The proposal is a second-order decision theoretic framework. The framework provides means for retrospective assessment of interim decisions based on a clear and consistent set of criteria that combines both ethical and epistemic considerations. The framework is broadly Bayesian and addresses (...) a fundamental question behind many concerns about clinical trials: What does it take for an interim decision (e.g., whether to stop the trial, or continue) to be a good decision? I provide simulation illustrating the modeling of interim decisions counterfactually using the framework. (shrink)

Due to the intricate nature of its subject matter, medicine is always threatened by speculations and disagreements about which among its entities exist, e.g., any specific biological structures, substructures or substances, pathogenic agents, pathophysiological processes, diseases, psychosomatic relationships, therapeutic effects, and other possible and impossible things. To avoid confusion, and to determine what entities an item of medical knowledge presupposes to exist if it is to be true, we need medical ontology. The term “medical ontology” we understand to mean the (...) study that seeks to ascertain what entities exist in the world of medicine, which formal relations hold between them, and whether there are any relatioships between types of medical research and practice, on the one hand; and the new worlds they create, on the other. (shrink)

In debates over the regulation of communication related to dual-use research, the risks that such communication creates must be weighed against against the value of scientific autonomy. The censorship of such communication seems justifiable in certain cases, given the potentially catastrophic applications of some dual-use research. This conclusion however, gives rise to another kind of danger: that regulators will use overly simplistic cost-benefit analysis to rationalize excessive regulation of scientific research. In response to this, we show how institutional design principles (...) and normative frameworks from free speech theory can be used to help extend the argument for regulating dangerous dual-use research beyond overly simplistic cost-benefit reasoning, but without reverting to an implausibly absolutist view of scientific autonomy. (shrink)

In response to the COVID-19 pandemic, large-scale research and pharmaceutical regulatory processes have proceeded at a dramatically increased pace with new and effective, evidence-based COVID-19 interventions rapidly making their way into the clinic. However, the swift generation of high-quality evidence and the efficient processing of regulatory authorisation have given rise to more specific and complex versions of well-known research ethics issues. In this paper, we identify three such issues by focusing on the authorisation of Molnupiravir, a novel antiviral medicine aimed (...) at reducing the ability of SARS-CoV-2 to multiply in the body, for clinical use by the National Health Service in England and the concomitant testing of Molnupiravir through the large-scale PANORAMIC randomised control trial. By analysing the ways in which the authorisation and clinical use of Molnupiravir complicate standard approaches to clinical equipoise, standard of care, and participant consent in the PANORAMIC randomised control trial we will explain some of ethical implications for clinical trials that aim to study the efficacy and safety of new COVID-19 and other therapeutics when conditional authorisation has already been granted and when such treatments have already been made available to patients by national health providers. (shrink)

In the beginning of the COVID pandemic, researchers and bioethicists called for human challenge trials to hasten the development of a vaccine for COVID. However, the fact that we lacked a specific, highly effective treatment for COVID led many to argue that a COVID challenge trial would be unethical and we ought to pursue traditional phase III testing instead. These ethical objections to challenge trials may have slowed the progress of a COVID vaccine, so it is important to evaluate their (...) merit. One common way of doing so is to make an analogy to other social practices that are relevantly similar and which we currently sanction. We submit that non-directed live organ donation (NDLOD) is a promising analogy. After arguing that the risks to volunteers for each activity appear similar, we explore potential disanalogies that would undermine the comparison. We note that there are differences in both the kind and certainty of benefit secured by NDLOD compared to challenge trials. We conclude these differences are insufficient to make NDLOD permissible and challenge trials impermissible. Ultimately, if we think the risks associated with NDLOD are ethically permissible, then we should think the same of the risks associated with COVID challenge trials. (shrink)

Many are calling for concrete mechanisms of oversight for health research involving artificial intelligence (AI). In response, institutional review boards (IRBs) are being turned to as a familiar model of governance. Here, we examine the IRB model as a form of ethics oversight for health research that uses AI. We consider the model's origins, analyze the challenges IRBs are facing in the contexts of both industry and academia, and offer concrete recommendations for how these committees might be adapted in order (...) to provide an effective mechanism of oversight for health‐related AI research. (shrink)

Many ethicists maintain that medical research on human subjects that presents no prospect of direct medical benefit must have a prospect of social benefit to be ethical. Payment is not the sort of benefit that justifies exposing subjects to risk. Alan Wertheimer has raised a serious challenge to this view, pointing out that in industry, social value is not considered necessary to make dangerous jobs ethical. This article argues that Wertheimer was correct to think that the ethics of hazard pay (...) should be the same in medical research and in business. Nevertheless, a qualified social benefit requirement should apply in both fields. For a study or a job with significant net physical risk to be ethical, it must have social value beyond the satisfaction of ordinary preferences, including the preference for money. The requirement derives from a non-absolutist version of the doctrine of double effect. If a risky study or a dangerous job has no distinctive social value, and hazard pay is subjects' or workers’ only reason to undergo risks, the very fact that they undergo risk is intended as a means to a financial end. Inviting people to enrol in such a study or to take such a job wrongfully treats people as mere means. By contrast, if a study or a job has social value, people can participate with a primary end other than money, even if they accept compensation. Researchers or employers do not intend but merely foresee risks to subjects or workers. There are no data in this work. (shrink)

Research Ethics, Volume 18, Issue 2, Page 132-150, April 2022. Limited research has been done among pregnant people participating in investigational drug trials. To enhance the ethical understanding of pregnant people’s perspectives on research participation, we sought to describe motives and risk perceptions of participants in a phase 1 trial of ledipasvir/sofosbuvir treatment for chronic Hepatitis C virus during pregnancy. Pregnant people with chronic HCV infection enrolled in an open-label, phase 1 study of LDV/SOF participated in semi-structured, in-depth interviews to (...) explore their reasons for participation and experiences within the study. Pregnant people took 12 weeks of LDV/SOF and were interviewed at enrollment and at the end of study. We recorded the interviews, transcribed them verbatim, coded them using NVivo software, and performed inductive thematic analysis. Nine women completed the study yielding 18 interview transcripts. We identified two themes regarding motives and one regarding risk perception. Motives— Women conceptualized study participation as part of the caregiving role they associate with motherhood; participating was viewed as an act of caregiving for their infants, their families, themselves, and other pregnant women with chronic HCV. Women also noted that they faced multiple barriers to treatment prior to pregnancy that created a desire to receive therapy through trial participation. Risk perception— Women acknowledged personal and fetal risk associated with participation. Acceptance of risk was influenced by women’s concepts of motherhood, preexisting knowledge of HCV and medical research, family members, intimate partners, or by the study design. Women enrolled in a phase 1 trial for chronic HCV therapy during pregnancy acknowledged risks of participation and were motivated by hopes for fetal and personal benefit and by lack of prenatal access to treatment. Ethical inclusion of pregnant people in research should acknowledge structural factors that contribute to vulnerability and data deficiencies for treatment in pregnancy. (shrink)

In “Obligations of the Gift” Sandra Lee (2021) suggests that social norms of reciprocity and the expectations and obligations associated with gift-giving afford a framework for addressing social justice considerations in precision medicine. Lee is particularly concerned with obligations to marginalized or oppressed racial and ethnic groups, which are also historically under-represented populations in precision medicine. Obligations arise, Lee argues, through the “gift” that research participants make when they contribute their data or biospecimens to precision medicine research. This conceptualization of (...) research participation is distinct from an altruistic donation model that explicitly precludes obligations of reciprocity. I agree with Lee’s overall project to support social justice aims by better recognizing responsibilities of researchers to their research participants, and increasing diverse participation in biomedical research. However, I am not convinced that the account of “the gift” she deploys can achieve the social justice goals she intends because it risks replicating rather than resisting problematic conceptions of labor, property, and ownership of selves and others. However, an alternate conceptualization of “the gift” found in the work of 20th century French philosopher Jacques Derrida recasts ethical obligations on the part of precision medicine to those who contribute their data and biospecimens for precision medicine research. (shrink)

Background Genomic research on neurodevelopmental disorders (NDDs), particularly involving minors, combines and amplifies existing research ethics issues for biomedical research. We performed a review of the literature on the ethical issues associated with genomic research involving children affected by NDDs as an aid to researchers to better anticipate and address ethical concerns. Results Qualitative thematic analysis of the included articles revealed themes in three main areas: research design and ethics review, inclusion of research participants, and communication of research results. Ethical (...) issues known to be associated with genomic research in general, such as privacy risks and informed consent/assent, seem especially pressing for NDD participants because of their potentially decreased cognitive abilities, increased vulnerability, and stigma associated with mental health problems. Additionally, there are informational risks: learning genetic information about NDD may have psychological and social impact, not only for the research participant but also for family members. However, there are potential benefits associated with research participation, too: by enrolling in research, the participants may access genetic testing and thus increase their chances of receiving a (genetic) diagnosis for their neurodevelopmental symptoms, prognostic or predictive information about disease progression or the risk of concurrent future disorders. Based on the results of our review, we developed an ethics checklist for genomic research involving children affected by NDDs. Conclusions In setting up and designing genomic research efforts in NDD, researchers should partner with communities of persons with NDDs. Particular attention should be paid to preventing disproportional burdens of research participation of children with NDDs and their siblings, parents and other family members. Researchers should carefully tailor the information and informed consent procedures to avoid therapeutic and diagnostic misconception in NDD research. To better anticipate and address ethical issues in specific NDD studies, we suggest researchers to use the ethics checklist for genomic research involving children affected by NDDs presented in this paper. (shrink)

Most technology is used properly for their intended purpose, but certain technological breakthroughs have a dual-use nature, pose risks or lead to unintended consequences when applied in some areas...

Background: Biomedical research nowadays is increasingly carried out in multinational and multicenter settings. Due to disparate national regulations on various ethical aspects, such as informed consent, there is the risk of ethical compromises when involving human subjects in research. Although the Declaration of Helsinki is the point of reference for ethical conduct of research on humans, national normative requirements may diverge from its provisions. The aim of this research is to examine requirements on informed consent in biomedical research in Germany, (...) Poland, and Russia to determine how each national regulatory framework relates to the provisions of the Declaration of Helsinki. Methods: For this analysis, we conducted a search of the legal databases “Gesetze im Internet” for Germany, “Internetowy System Aktow Prawnych” for Poland, and “ГAPAHT – Garant” for Russia. The search was complemented by a review of secondary literature contained in the databases Google Scholar, PubMed, Polish National Library, and eLibrary ru. We have identified 21 normative regulations containing provisions on informed consent in clinical research in all three countries. The content of these documents was systematically categorized and analyzed. Results: The normative framework in all three countries shows a strong commitment towards the core ethical principles of research envisaged in the Declaration of Helsinki. Nevertheless, provisions on informed consent vary between these three countries. The differences range from the method and language in which information should be provided, through the amount of information required to be disclosed, to the form of documenting consent or withdrawal. In the case of research on vulnerable groups, these differences are particularly visible. Conclusions: The identified differences can negatively impact the ethical conduct of international clinical studies. Attention needs to be paid that flexibilities within national regulations are not misused to undermine the protection of research subjects. Achieving global or regional legislative harmonization might prove impossible. Such lack of legal consensus reinforces the significance of the international ethical agreements. (shrink)

Consistent and well-designed frameworks for ethical oversight enable socially valuable research while forestalling harmful or poorly designed studies. I suggest some alterations that might strengthen the valuable checklist Rattani & Hyder propose for the ethical review of health policy and systems research (HPSR), or prompt future work in the area.

Psychiatric research often poses special ethical concerns. This chapter first provides historical context, including scandals that stoked public concern about psychiatric research and led to the promulgation of canonical documents and bioethics scholarship, and then explores issues related to the decision-making capacity and safety of participants—including the use of placebos and washout periods, the design of suicide prevention studies, and research in emergency psychiatry. The chapter then describes how shifting models of psychiatric nosology have precipitated conflicts in the determination of (...) research priorities. Finally, the chapter attends to emerging issues related to research in psychedelic psychiatry and the use of artificial intelligence and social media by investigators. (shrink)

The biopsychosocial model, which was deeply influential on psychiatry following its introduction by George L. Engel in 1977, has recently made a comeback. Derek Bolton and Grant Gillett have argued that Engel’s original formulation offered a promising general framework for thinking about health and disease, but that this promise requires new empirical and philosophical tools in order to be realized. In particular, Bolton and Gillett offer an original analysis of the ontological relations between Engel’s biological, social, and psychological levels of (...) analysis. I argue that Bolton and Gillett’s updated model, while providing an intriguing new metaphysical framework for medicine, cannot resolve some of the most vexing problems facing psychiatry, which have to do with how to prioritize different sorts of research. These problems are fundamentally ethical, rather than ontological. Without the right prudential motivation, in other words, the unification of psychiatry under a single conceptual framework seems doubtful, no matter how compelling the model. An updated biopsychosocial model should include explicit normative commitments about the aims of medicine that can give guidance about the sorts of causal connections to be prioritized as research and clinical targets. (shrink)

Recent changes to the Common Rule have helped reduce regulatory burden on researchers conducting minimal risk research. However, in this paper, I propose a way of minimizing burden further within the existing confines of the current regulations. I focus my discussion on the newly created “benign behavioral interventions” category of exempt research, arguing that this exemption from the federal regulations governing research with human subjects should be more expansively interpreted by the Secretary's Advisory Committee on Human Research Protections (SACHRP) than (...) is currently the case. Specifically, I argue against the restriction, advocated by SACHRP, that the exemption exclude “physical (bodily) tasks” unless they are “incidental to the behavioral intervention.” This restriction, I argue, is problematically vague and does no significant moral work. Acceptance of my proposed reinterpretation of “benign behavioral interventions” would, I hope, result in a significant reduction in regulatory burden for minimal risk research. -/- . (shrink)

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

As governments around the world imposed lockdowns or stay-at-home measures, people began to feel the stress as time dragged on. There were already reports on some individuals committing suicide. How do governments respond to such a phenomenon? Our main focus is the Philippine government and how it responded to the COVID-19 pandemic. In this paper, we argue that the problem with COVID-19 went forth just dealing with physical health. First, people suffer not just from being infected but the psychological stress (...) of possibly getting the virus and the toll of the government lockdown or quarantine. Second, the Philippine Bayanihan ‘We Heal As One Act’ lacks focus on mental health issues while the government's response seemed to focus on security issues. Third, there are countries around the world that have acted effectively in protecting people’s mental health. Lastly, we propose appropriate measures to help address the people's mental health while still in the pandemic and for a future one. (shrink)

There is too much that we do not know about COVID-19. The longer we take to find it out, the more lives will be lost. In this paper, we will defend a principle of risk parity: if it is permissible to expose some members of society (e.g. health workers or the economically vulnerable) to a certain level of ex ante risk in order to minimize overall harm from the virus, then it is permissible to expose fully informed volunteers to a (...) comparable level of risk in the context of promising research into the virus. We apply this principle to three examples of risky research: skipping animal trials for promising treatments, human challenge trials to speed up vaccine development, and low-dose controlled infection or “variolation.” We conclude that if volunteers, fully informed about the risks, are willing to help fight the pandemic by aiding promising research, there are strong moral reasons to gratefully accept their help. To refuse it would implicitly subject others to still graver risks. (shrink)

This book offers a philosophically-based, yet clinically-oriented perspective on current medical reasoning aiming at 1) identifying important forms of uncertainty permeating current clinical reasoning and practice 2) promoting the application of an abductive methodology in the health context in order to deal with those clinical uncertainties 3) bridging the gap between biomedical knowledge, clinical practice, and research and values in both clinical and philosophical literature. With a clear philosophical emphasis, the book investigates themes lying at the border between several disciplines, (...) such as medicine, nursing, logic, epistemology, and philosophy of science; but also ethics, epidemiology, and statistics. At the same time, it critically discusses and compares several professional approaches to clinical practice such as the one of medical doctors, nurses and other clinical practitioners, showing the need for developing a unified framework of reasoning, which merges methods and resources from many different clinical but also non-clinical disciplines. In particular, this book shows how to leverage nursing knowledge and practice, which has been considerably neglected so far, to further shape the interdisciplinary nature of clinical reasoning. Furthermore, a thorough philosophical investigation on the values involved in health care is provided, based on both the clinical and philosophical literature. The book concludes by proposing an integrative approach to health and disease going beyond the so-called “classical biomedical model of care”. (shrink)

Eyal et al have recently argued that researchers should consider conducting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human challenge studies to hasten vaccine development. We have conducted (J. L.) and overseen (L. D.) human challenge studies and agree that they can be useful in developing anti-infective agents. We also agree that adults can autonomously choose to undergo risks with no prospect of direct benefit to themselves. However, we disagree that SARS-CoV-2 challenge studies are ethically appropriate at this time, for (...) 3 reasons: (1) current scientific knowledge of SARS-CoV-2 infection is insufficient to manage risks; (2) autonomous decision making, while necessary, does not override concerns about risk; and (3) undertaking challenge studies now would imperil confidence in the research enterprise, potentially undermining the global response to the coronavirus disease 2019 (COVID-19) pandemic. (shrink)

One of the Belmont Report’s most important contributions was the clear and serviceable distinction it drew between standard medical practice and biomedical research. A less well-known achievement of the Report was its conceptualization of innovative practice, a type of medical practice that is often mistaken for research because it is new, untested, or experimental. Although the discussion of innovative practice in Belmont is brief and somewhat cryptic, this does not reflect the significant progress its authors made in understanding innovative practice (...) and the distinctive ethical issues it raises. This article explores the history and broader context of Belmont’s conception of innovative practice, its strengths and weaknesses, and its contemporary relevance for scholars working in bioethics and health policy. While this conception of innovative practice deserves our attention, it is inherently limited in some important ways. (shrink)

Innovative practice involves medical interventions that deviate from standard practice in significant ways. For many patients, innovative practice offers the best chance of successful treatment. Because little is known about most innovative treatments, clinicians who engage in innovative practice might consider including extra procedures, such as scans or blood draws, to gather information about the innovation. Such information-gathering interventions can yield valuable information for modifying the innovation to benefit future patients and for designing scientific studies of the innovation. However, existing (...) guidelines do not say when or whether it is appropriate to add potentially risky information-gathering interventions for these purposes. As a result, clinicians may assume that information-gathering interventions are ethically inappropriate and should not be used in innovative practice. This assumption can lead to seriously negative consequences, such as increasing the likelihood that harmful or ineffective innovations will be adopted and creating new barriers to the development of genuinely beneficial treatments. We argue that health care institutions need to promote the responsible use of information-gathering interventions as an adjunct to innovative practice, and that these interventions are not clinical research and should not be subject to research oversight. (shrink)

Unlike its friendly cousin the placebo effect, the nocebo effect (the effect of expecting a negative outcome) has been almost ignored. Epistemic and ethical confusions related to its existence have gone all but unnoticed. Contrary to what is often asserted, adverse events following from taking placebo interventions are not necessarily nocebo effects; they could have arisen due to natural history. Meanwhile, ethical informed consent (in clinical trials and clinical practice) has centred almost exclusively on the need to inform patients about (...) intervention risks with patients to preserve their autonomy. Researchers have failed to consider the harm caused by the way in which the information is conveyed. In this paper, I argue that the magnitude of nocebo effects must be measured using control groups consisting of untreated patients. And, because the nocebo effect can produce harm, the principle of non-maleficence must be taken into account alongside autonomy when obtaining (ethical) informed consent and communicating intervention risks with patients. (shrink)

The burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research. We conducted a systematic review of (...) the ethical literature concerning human-animal chimeras based on the research question: “What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?” Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected. Four hundred and thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types.15% of the retrieved passages contained reasons in favor of conducting chimera research, while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera, its treatment, reasons referring to metaphysical or social issues resulting from its existence and to potential downstream effects of chimera research. A significant proportion of identified passages fell under Category C. We hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation. (shrink)

Experimental design is one aspect of a scientific method. A well-designed, properly conducted experiment aims to control variables in order to isolate and manipulate causal effects and thereby maximize internal validity, support causal inferences, and guarantee reliable results. Traditionally employed in the natural sciences, experimental design has become an important part of research in the social and behavioral sciences. Experimental methods are also endorsed as the most reliable guides to policy effectiveness. Through a discussion of some of the central concepts (...) associated with experimental design, including controlled variation and randomization, this chapter will provide a summary of key ethical issues that tend to arise in experimental contexts. In addition, by exploring assumptions about the nature of causation and by analyzing features of causal relationships, systems, and inferences in social contexts, this chapter will summarize the ways in which experimental design can undermine the integrity of not only social and behavioral research but policies implemented on the basis of such research. (shrink)

Background Several jurisdictions, including Singapore, Australia, New Zealand and most recently Ireland, have a public interest or public good criterion for granting waivers of consent in biomedical research using secondary health data or tissue. However, the concept of the public interest is not well defined in this context, which creates difficulties for institutions, institutional review boards and regulators trying to implement the criterion. Main text This paper clarifies how the public interest criterion can be defensibly deployed. We first explain the (...) ethical basis for requiring waivers to only be granted to studies meeting the public interest criterion, then explore how further criteria may be set to determine the extent to which a given study can legitimately claim to be in the public interest. We propose an approach that does not attempt to measure magnitude of benefit directly, but rather takes into account metrics that are more straightforward to apply. To ensure consistent and justifiable interpretation, research institutions and IRBs should also incorporate procedural features such as transparency and public engagement in determining which studies satisfy the public interest requirement. Conclusion The requirement of public interest for consent waivers in secondary biomedical research should be guided by well-defined criteria for systematic evaluation. Such a criteria and its application need to be periodically subject to intra-committee and intra-institution review, reflection, deliberation and amendment. (shrink)

An alliance of established experts on critical care, Front Line COVID-19 Critical Care Alliance (FLCCC), has published two protocols for treatment of COVID-19. The first one, methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+), is intended for hospital and intensive care unit treatment of pulmonary phases of the disease. It is based on affordable, commonly available components: anti-inflammatory corticosteroids (methylprednisolone, "M"), high-dose vitamin C infusion (ascorbic acid, "A"), vitamin B1 (thiamine, "T"), anticoagulant heparin ("H"), antiparasitic agent ivermectin, and supplemental components ("+") (...) including melatonin, vitamin D, elemental zinc, and magnesium. -/- The MATH+ protocol has received scarce attention due to the World Health Organization (WHO) advising against the use of corticosteroids in the beginning of the pandemic. In addition, randomized controlled clinical trials were required as a condition for adoption of the protocol. As the hospital mortality rate of MATH+ treated patients was approximately a quarter of the rate of patients receiving a standard of care, the authors of the protocol considered performing such trials unethical. Other parties have later performed clinical trials with corticosteroids and anticoagulants, which has led to a more widespread adoption of these components. -/- In October 2020, ivermectin was upgraded from an optional component to an essential component of the protocol. According to the authors, ivermectin is considered the first agent effective for both prophylaxis (prevention) of COVID-19 and for treatment of all phases of COVID-19 including outpatient treatment of the early symptomatic phase. Therefore, at the end of October 2020, a separate ivermectin-based I-MASK+ protocol for prophylaxis and early outpatient treatment of COVID-19 was published. (shrink)

The article by MacKay and Saylor (2020) claims that the principle of fair subject selection yields conflicting imperatives (e.g. in the case of pregnant women) and should be understood as “a bundle of four distinct sub-principles” (i.e. fair inclusion, burden sharing, opportunity, distribution of third-party risks), each having conflicting normative recommendations (MacKay and Saylor 2020). The authors also offer guidance as to how we should navigate between subprinciples that may conflict with each other. The problem is a crucial one since (...) fair subject selection is one of the principles regulating clinical research that produces generalizable knowledge with the potential of improving people’s health. Therefore, there may be cases where the way in which participants are selected directly influences the generalizability (or its lack) of the clinically relevant knowledge and its value (if any) to different groups. In my commentary article, written from the philosophical perspective, I notice a number of interrelated problems which I believe have not been discussed thoroughly in the target article: (1) the precise way in which health care priority setting should influence the content of health research priority setting and fair inclusion principles; (2) the distinction between group and individual benefits and burdens from clinical research; (3) the reference class problem in medical research. (shrink)

This commentary explores the notion of vulnerability applied to pregnant women in clinical research. The use of this notion, related to a semantic problem, raises an ethical issue and participates in the quasi-systematic exclusion of this sub-population from the research process.

This paper discusses the criminalization of scientific misconduct, as discussed and defended in the bioethics literature. In doing so it argues against the claim that fabrication, falsification and plagiarism (FFP) together identify the most serious forms of misconduct, which hence ought to be criminalized, whereas other forms of misconduct should not. Drawing the line strictly at FFP is problematic both in terms of what is included and what is excluded. It is also argued that the criminalization of scientific misconduct, despite (...) its anticipated benefits, is at risk of giving the false impression that dubious practices falling outside the legal regulation “do not count”. Some doubts are also raised concerning whether criminalization of the most serious forms of misconduct will lower the burdens for universities or successfully increase research integrity. Rather, with or without criminalization, other measures must be taken and are probably more important in order to foster a more healthy research environment. (shrink)

Innovative practice occurs when a clinician provides something new, untested, or nonstandard to a patient in the course of clinical care, rather than as part of a research study. Commentators have noted that patients engaged in innovative practice are at significant risk of suffering harm, exploitation, or autonomy violations. By creating a pathway for harmful or nonbeneficial interventions to spread within medical practice without being subjected to rigorous scientific evaluation, innovative practice poses similar risks to the wider community of patients (...) and society as a whole. Given these concerns, how should we control and oversee innovative practice, and in particular, how should we coordinate innovative practice and clinical research? In this article, I argue that an ethical approach to overseeing innovative practice must encourage the early transition to rigorous clinical research without delaying or deferring the development of beneficial innovations or violating the autonomy rights of clinicians and their patients. (shrink)

Ethically permissible clinical trials must not expose subjects to risks that are unreasonable in relation to anticipated benefits. In the research ethics literature, this moral requirement is typically understood in one of two different ways: as requiring the existence of a state of clinical equipoise, meaning a state of honest, professional disagreement among the community of experts about the preferred treatment; or as requiring an equilibrium between individual and collective ethics. It has been maintained that this second interpretation makes it (...) mandatory to minimize the number of patients receiving the treatment that will eventually be shown to be inferior by the trial. This requirement has led to the development of adaptive trials, i.e., trials in which treatment allocation is determined by data accumulated during interim analysis. Many statisticians argue that in some circumstances—typically with potentially high benefits, as in the much discussed ECMO trial—adaptive design is the only ethically permissible experimental design. Nevertheless, some proponents of clinical equipoise argue that adaptive trials are neither ethically required nor permissible. More specifically, they argue that clinical trials using adaptive designs fail to meet the moral requirement of clinical equipoise, since these trials presuppose an epistemic state that is incompatible with a physician’s duty of care to her subjects. This paper emphasizes that the debate is to a large extent resting on an epistemological confusion. Specifically, I argue that this response conflates two different conceptions of statistical evidence, and that recognizing this distinction elucidates an epistemological framework in which adaptive trials are both consistent with and recommended by the moral requirement of clinical equipoise. (shrink)

This book makes an important contribution to ongoing efforts in the fields of medical law and bioethics to answer the challenges posed by the limitations of the principle of respect for autonomy, especially as these pertain to human research ethics. The principle of respect for autonomy seems to have become firmly embedded in human research ethics since its inclusion in the 1947 Nuremberg Code, which was a response to atrocities committed by Nazi doctors. Nonetheless, there is an increasing awareness of (...) the limitations of the principle of respect for autonomy and the underlying conceptualisations of human autonomy. (shrink)

This book makes an important contribution to ongoing efforts in the fields of medical law and bioethics to answer the challenges posed by the limitations of the principle of respect for autonomy, especially as these pertain to human research ethics. The principle of respect for autonomy seems to have become firmly embedded in human research ethics since its inclusion in the 1947 Nuremberg Code, which was a response to atrocities committed by Nazi doctors. Nonetheless, there is an increasing awareness of (...) the limitations of the principle of respect for autonomy and the underlying conceptualisations of human autonomy. (shrink)

Since the end of World War II, most guidelines governing human research seem to have relied on the principle of respect for autonomy as a key, though not sole, criterion in assessing the moral validity of research involving human participants.1 One explanation for this apparent reliance on respect for autonomy may be that respect for autonomy, made effective through the practice of obtaining informed consent, functions as a useful proxy when dealing with competent adults for the more complex principle of (...) respect for human dignity that underpins much of the moral discourse in this area. If this explanation holds, then assessment of the moral licitness of research involving human individuals whose autonomy is limited in some way requires a deeper analysis of the ‘thicker’ concepts of human dignity, since we cannot rely on respect for autonomy to do the work of respect for human dignity where autonomy (understood as a capacity to consent based on adequate information) is not present, is limited or is compromised. (shrink)

This chapter examines the explicit and implicit roles that the concept of beneficence plays in the guidelines that govern biomedical research involving humans. We suggest that the role beneficence is actually playing in the guidelines is more comprehensive than is commonly assumed. The broader conceptualisation of beneficence proposed here clarifies the relationship of beneficence to respect for autonomy. It does this by showing how respect for autonomy is at the service of beneficence rather than in tension with it.

Respect for autonomy has become a fundamental principle in human research ethics. Nonetheless, this principle and the associated process of obtaining informed consent do have limitations. This can lead to some groups, many of them vulnerable, being left understudied. This book considers these limitations and contributes through legal and philosophical analyses to the search for viable approaches to human research ethics. It explores the limitations of respect for autonomy and informed consent both in law and through the examination of cases (...) where autonomy is lacking (infants), diminished (addicts), and compromised (low socio-economic status). It examines alternative and complementary concepts to overcome the limits of respect for autonomy, including beneficence, dignity, virtue, solidarity, non-exploitation, vulnerability and self-ownership. It takes seriously the importance of human relationality and community in qualifying, tempering and complementing autonomy to achieve the ultimate end of human research - the good of humankind. (shrink)