If, as is alleged, challenge trials of vaccines against COVID-19 are likely to save thousands of lives and vastly diminish the economic and social harms of the pandemic while subjecting volunteers to risks that are comparable to kidney donation, then it would seem that the only sensible objection to such trials would be to deny that they have low risks or can be expected to have immense benefits. This essay searches for a philosophical rationale for rejecting challenge trials (...) while supposing that they have huge benefits and relatively low risks. Although it finds some force in objections to challenge trials grounded in the obligations of researchers to limit the harms imposed on some individuals for the benefit of others, it argues that there is no compelling objection to challenge trials of vaccines for COVID-19—if they have the benefits and risks that have been claimed. (shrink)

The world’s first COVID-19 human challenge trial using the D614G strain of SARS-CoV-2 is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta variant (B.1.351) for a follow-up human challenge trial, and researchers at Imperial College London are considering conducting that trial. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. While vaccine resistance as such (...) does not increase risks for volunteers in COVID-19 challenge trials, we explore two specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical. (shrink)

One way to test vaccines is through human challenge trials in which participants are intentionally infected with a contagious organism to expedite the process of assessing the vaccine’s effectiveness. Some experts believe challenge trials may play an important role in fighting COVID-19, especially if the vaccines under current study do not demonstrate sufficient efficacy, if spread of COVID-19 is controlled to a point that radically slows down traditional trials, or if new vaccines need to be rapidly developed for (...) specific subpopulations.1 Challenge trials involve significant time, burden and risk, requiring participants to spend 3–6 weeks in legal quarantine for 24 hours a day in a high-security facility. During this time, no inperson visitors will be allowed, except for very limited inperson contact from researchers collecting necessary data and checks. Following the quarantine period, participants will be asked to attend numerous outpatient follow-up visits over the course of months, to further monitor their response to the vaccine. Participation involves being away from family who may themselves become sick during the global pandemic, as well as potential fear and mental anguish around being a ‘first’ subject. Because there is no definitive treatment for COVID-19, participants could experience serious illness. But even with milder illness, medical experts know very little about the long-term consequences of COVID-19 infection. This raises the question of how much people should be paid for their participation in COVID-19 challenge trials. Most think participants should be paid something, but many contend that we should be …. (shrink)

The COVID-19 pandemic has necessitated rapid research to aid in the understanding of the disease and the development of novel therapeutics. One option is to conduct controlled human infection trials (CHITs). In this article I examine the history of deliberate human infection and CHITs and their utilization prior to the COVID-19 pandemic, key ethical considerations of CHITs in the COVID-19 setting, an analysis of the World Health Organization’s (WHO) Key criteria for the ethical acceptability of COVID-19 human challenge studies, (...) and a review of the two COVID-19 CHITs that have already commenced, their compliance with the WHO criteria and other ethical considerations. (shrink)

Notwithstanding the success of conventional field trials for vaccines against COVID-19, human challenge trials that could obtain more information about these and about other vaccines and further strategies against it are about to start in the UK. One critique of COVID-19 HCTs is their distinct paucity of information on crucial population groups. For safety reasons, these HCTs will exclude candidate participants of advanced age or with comorbidities that worsen COVID-19, yet a vaccine should protect such populations. We turn this (...) cliché on its head. The truth is that either an HCT or a field trial has intrinsic generalisability limitations, that an HCT can expedite protection of high-risk participants even without challenging them with the virus, and that an important route to obtaining results generalisable to high-risk groups under either strategy is facilitated by HCTs. There are no data in this work. (shrink)

To reduce the global burden of the COVID-19 pandemic, there is an urgent need to develop a safe vaccine. Vaccine development usually takes many years as it goes through several different phases. To hasten COVID-19 vaccine development, it has been suggested that the final stage could be replaced with a human challenge trial. Volunteers would be intentionally infected with SARS-CoV-2 to see how the vaccine candidate works. To intentionally infect a healthy human being with a potentially deadly virus (...) is contrary to the highest ethical standards in medical research. This article highlights the benefits and risks of COVID-19 HCTs and summarises what research ethics committees need to consider during the ethical assessment of such trials including risk reduction, strict containment measures, specific informed consent measures and avoiding high monetary inducements. (shrink)

The COVID-19 pandemic touched off an unprecedented search for vaccines and treatments. Without question, the development of vaccines to prevent COVID-19 was an enormous scientific accomplishment. Further, the RECOVERY and Solidarity trials identified effective treatments for COVID-19. But all was not success. The urgent need for COVID-19 prevention and treatment fueled an embrace of risks—to research participants and to the reliability of the science itself—as allegedly necessary costs to speed scientific progress. Scientists and (even) ethicists supported overturning longstanding norms protecting (...) healthy volunteers in human challenge trials to speed vaccine development, but these trials led to no vaccines. Physicians, with the approval of research ethics committees, designed hundreds of unblinded, single-center clinical trials at high risk of bias to speed the identification of new treatments. But these clinical trials led to no treatments. The lesson for future pandemics is that the acceptance of greater risks to participants or science does not reliably lead to progress. We are better served by science that upholds the highest ethical and methodological standards. (shrink)

Ongoing and anticipated COVID-19 human challenge studies in the UK may advance our understanding of COVID-19 and facilitate the licensure of safe, effective, and easily deployable next-generation COVID-19 vaccines and boosters. We argue that international volunteer recruitment for COVID-19 human challenge trials can help promote diversity in these trials and ensure a sufficient number of eligible volunteers, both of which will increase the benefits of challenge research. We explore the ethical ramifications of dealing with unfair background conditions (...) of global vaccine injustice to expand medical research, and conclude that international recruitment for COVID-19 human challenge trials can be conducted ethically provided that several robust protections are in place for volunteers. (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)

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)

To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2, some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.

Sometimes doing what’s right depends on anticipating how people will react when you do the right thing. Consider two aspects of challenge trial payments discussed by Lynch and colleagues. Th...

In a recent article, Steel, Buchak and Eyal argue that current levels of uncertainty do not present a good reason to bar controlled human infection trials of COVID-19 vaccines from proceeding. We argue that their argumentation for this conclusion is flawed. SBE are mistaken about the effects which different forms of ignorance have on participants’ ability to provide valid informed consent. Decision-makers considering whether to allow such trials, we argue, must ultimately consider the likelihood that consent to participation in such (...) trials under current conditions would be valid, and whether this likelihood is high enough to permit such trials. This is a question that SBE completely ignore. We conclude that there indeed are valid concerns about conducting CHI trials given the current state of knowledge about COVID-19, concerns which SBE fail to address. (shrink)

Despite their clearly demonstrated safety and effectiveness, approved vaccines against COVID-19 are commonly mistrusted. Nations should find and implement effective ways to boost vaccine confidence. But the implications for ethical vaccine development are less straightforward than some have assumed. Opponents of COVID-19 vaccine challenge trials, in particular, made speculative or empirically implausible warnings on this matter, some of which, if applied consistently, would have ruled out most COVID-19 vaccine trials and many non-pharmaceutical responses.

Bioethicists broadly agree that there is a limit to the level of net risk that biomedical research may permissibly impose on participants, even in cases where the potential of that research to improve the health of the population health would be great. Although some may permissibly volunteer to take on some degree of pro‐social risk, no one, not even a willing volunteer, may ever be outright sacrificed for others. One might think this perspective, if correct, makes it effectively impossible to (...) study interventions with high intrinsic risks. But I describe a method – risk dilution – by which an extremely high‐risk intervention can nonetheless be effectively studied in the context of an acceptably low‐risk trial. I then defend risk dilution from objections. (shrink)

The trial of Jean-Paul Akayesu is by far the most well known and widely discussed case at the International Criminal Tribunal for Rwanda, a distinction that can be attributed to the fact that it was groundbreaking for several reasons. However, with regard to the importance of this trial both as a precedent for subsequent ICTR cases and within the broader context of international jurisprudence, its most significant contribution has undoubtedly been the recognition and prosecution of rape as a (...) means of perpetrating genocide. The task of collecting admissible evidence to that end was heavily impacted by the necessity of interpreting and translating witness testimonies from their original language of expression, Kinyarwanda, into the working languages of the Tribunal, French and English. The multiple challenges associated with this translation process concerned not only questions of semantic equivalence of specific lexical terms. They also highlighted the considerable ‘cultural collision’ that occurred in the courtroom between the Rwandan witnesses and the international judiciary. This article elucidates the complex task faced by the courtroom interpreters in navigating these linguistic and sociocultural considerations underpinning the evocations of rape within the evidentiary framework of the Akayesu trial. (shrink)

This methodological discussion invites critical reflection about the procedures used to analyze the contribution of qualitative and mixed methods research to nursing trials by mounting an argument that these should rest on multiple publications produced about a project, rather than a single article. We illustrate the value‐added of this approach with findings from a qualitative, cross‐case analysis of three critical case exemplars from nursing researchers that each used a qualitative approach with a mixed method phase. The holistic lens afforded by (...) a case‐based approach informs nursing inquiry by documenting that the critical case exemplars presented evidence of (a) a sustained commitment of resources and expertise for the qualitative methods that extended across more than one phase of the trial, (b) the impact of the qualitative methods on the trial or its aftermath, (c) deploying a theoretical or conceptual framework for a variety of purposes, and (d) integrating qualitative and quantitative data for purposes of extending explanatory power. Findings challenge the practice of linking purposes served by qualitative and mixed methods to a single trial phase. (shrink)

Clinical trial recruitment is ripe for innovation. The current model is costly, often results in poor recruitment and offers inequitable access. To improve this system, we envision a peer-to-peer blockchain platform where patients control the depth and breadth of how their medical information is shared.

The paper seeks to analyse how two domestic courts decided criminal trials under circumstances of emotional mobilisation and political stress. Decisions from Argentina after 1983 and Romania after Ceausescu’s dictatorship illustrate how citizens’ affects influence courts’ choices within penal cases. Both cases show how the judiciary had to enter a dialogue with resentful and indignant claims for redress. However, while the Argentinean court filtered emotions through the strainer of equal respect and thus pushed the cause of democratic justice ahead, the (...) Romanian case serves as a cautionary tale about how not to correct injustices through criminal law. These two cases provide us with important lessons about the obstacles, but also the opportunities associated with public emotions during periods of radical political transformation. (shrink)

BackgroundImplementation of recommendations from clinical practice guidelines is essential for evidence based clinical practice. However, the most effective methods of implementation are unclear. We conducted a national, cluster-randomised, blinded implementation trial to determine if midwife or doctor local implementation leaders are more effective in implementing a guideline for use of oral dextrose gel to treat hypoglycaemic babies on postnatal wards. To prevent any conscious or unconscious performance bias both the doctor and midwife local implementation leaders were kept unaware of (...) the trial. This paper reports the ethical dilemmas and practical challenges of ensuring clinicians remained unaware of their involvement in an implementation trial.MethodsWe sought approval from the National Health and Disability Ethics committee to keep clinicians unaware of the trial by waiving the standard requirement for locality approval usually required for each district health board. The ethics committee did not approve a waiver of consent but advised that we approach the chief executive of each district health board to ask for provisional locality approval. Ultimately it was necessary to seek ethics approval for three separate study designs to keep clinicians unaware of the trial.ResultsThe median time for chief executive approval was 16 days and for locality approval was 57 days. We completed 21 different locality approval forms for 27 hospitals.ConclusionsKeeping clinicians unaware of their involvement in a national implementation cluster-randomised trial is feasible. However, despite a national ethics committee, significant logistical challenges were time consuming and delayed trial completion. Co-ordination of the locality approval process would help facilitate multi-centre trials. (shrink)

Drug repurposing is a strategy of identifying new potential uses for already existing drugs. Many researchers adopted this method to identify treatment or prevention during the COVID-19 pandemic. However, despite the considerable number of repurposed drugs that were evaluated, only some of them were labeled for new indications. In this article, we present the case of amantadine, a drug commonly used in neurology that attracted new attention during the COVID-19 outbreak. This example illustrates some of the ethical challenges associated with (...) the launch of clinical trials to evaluate already approved drugs. In our discussion, we follow the ethics framework for prioritization of COVID-19 clinical trials proposed by Michelle N Meyer and colleagues (2021). We focus on four criteria: social value, scientific validity, feasibility, and consolidation/collaboration. We claim that launching amantadine trials was ethically justified. Although the scientific value was anticipated to be low, unusually, the social value was expected to be high. This was because of significant social interest in the drug. In our view, this strongly supports the need for evidence to justify why the drug should not be prescribed or privately accessed by interested parties. Otherwise, a lack of evidence-based argument could enhance its uncontrolled use. With this paper, we join the discussion on the lessons learned from the pandemic. Our findings will help to improve future efforts to decide on the launch of clinical trials on approved drugs when dealing with the widespread off-label use of the drug. (shrink)

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, (...) the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment. While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research. (shrink)

Volume 20, Issue 2, February 2020, Page 35-38.

Novel precision oncology trial designs, such as basket and umbrella trials, are designed to test new anticancer agents in more effective and affordable ways. However, they present some ethical concerns referred to scientific validity, risk-benefit balance and informed consent. Our aim is to discuss these issues in basket and umbrella trials, giving examples of two ongoing cancer trials: NCI-MATCH (National Cancer Institute – Molecular Analysis for Therapy Choice) and Lung-MAP (Lung Cancer Master Protocol) study. We discuss three ethical requirements (...) for clinical trials which may be challenged in basket and umbrella trial designs. Firstly, we consider scientific validity. Thanks to the new trial designs, patients with rare malignancies have the opportunity to be enrolled and benefit from the trial, but due to insufficient accrual, the trial may generate clinically insignificant findings. Inadequate sample size in study arms and the use of surrogate endpoints may result in a drug approval without confirmed efficacy. Moreover, complexity, limited quality and availability of tumor samples may not only introduce bias and result in unreliable and unrepresentative findings, but also can potentially harm patients and assign them to an inappropriate therapy arm. Secondly, we refer to benefits and risks. Novel clinical trials can gain important knowledge on the variety of tumors, which can be used in future trials to develop effective therapies. However, they offer limited direct benefits to patients. All potential participants must wait about 2 weeks for the results of the genetic screening, which may be stressful and produce anxiety. The enrollment of patients whose tumors harbor multiple mutations in treatments matching a single mutation may be controversial. As to informed consent – the third requirement we discuss, the excessive use of phrases like “personalized medicine”, “tailored therapy” or “precision oncology” might be misleading and cause personal convictions that the study protocol is designed to fulfill the individual health-related needs of participants. We suggest that further approaches should be implemented to enhance scientific validity, reduce misunderstandings and risks, thus maximizing the benefits to society and to trial participants. (shrink)

Advances in neuromodulation and an improved understanding of the anatomy and circuitry of psychopathology have led to a resurgence of interest in surgery for psychiatric disease. Clinical trials exploring deep brain stimulation (DBS), a focally targeted, adjustable and reversible form of neurosurgery, are being developed to address the use of this technology in highly selected patient populations. Psychiatric patients deemed eligible for surgical intervention, such as DBS, typically meet stringent inclusion criteria, including demonstrated severity, chronicity and a failure of conventional (...) therapy. Although a humanitarian device exemption by the US Food and Drug Administration exists for its use in obsessive-compulsive disorder, DBS remains a largely experimental treatment in the psychiatric context, with its use currently limited to clinical trials and investigative studies. The combination of a patient population at the limits of conventional therapy and a novel technology in a new indication poses interesting challenges to the informed consent process as it relates to clinical trial enrollment. These challenges can be divided into those that relate to the patient, their disease and the technology, with each illustrating how traditional conceptualisations of research consent may be inadequate in the surgical psychiatry context. With specific reference to risk analysis, patient autonomy, voluntariness and the duty of the clinician-researcher, this paper will discuss the unique challenges that clinical trials of surgery for refractory psychiatric disease present to the consent process. Recommendations are also made for an ethical approach to clinical trial consent acquisition in this unique patient population. (shrink)

Although the use of the cluster randomized trial (CRT) design to evaluate vaccines, public health interventions or health systems is increasing, the ethical issues posed by the design are not adequately addressed, especially in low- and middle-income country settings (LMICs). To help reveal ethical challenges, qualitative interviews were conducted with key stakeholders experienced in designing and conducting two selected CRTs in Malawi. The 18 interviewed stakeholders included investigators, clinicians, nurses, data management personnel and community workers who were invited to (...) share their experiences related to implementation of CRTs. Data analysis revealed five major themes with ethical implications: (1) The moral obligation for health care providers to participate in health research and its compensation; (2) Suboptimal care services compromising the integrity of CRT; (3) Ensuring scientific validity and withholding care service; (4) Obtaining valid consent and permission for waiver of consent; and (5) Inadequate risk assessment for trial participation. Understanding key ethical issues posed by CRTs in Malawi could improve ethical review and research oversight of this particular study design. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a (...) criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

As new HIV prevention tools are developed, researchers face a number of ethical and logistic questions about how and when to include novel HIV prevention strategies and tools in the standard prevention package of ongoing and future HIV prevention trials. Current Joint United Nations Programme on HIV/AIDS /World Health Organization guidance recommends that participants in prevention trials receive ‘access to all state of the art HIV risk reduction methods’, and that decisions about adding new tools to the prevention package be (...) made in consultation with ‘all relevant stakeholders’. The guidance, however, leaves open questions of both process and implementation. In March 2009, the Global Campaign for Microbicides, UNAIDS and the Centers for Disease Control and Prevention convened a consultation to develop practical answers to these questions. Fifty-nine diverse participants, including researchers, ethicists, advocates and policymakers, worked to develop consensus criteria on when to include new HIV prevention tools in future trials. Participants developed a set of questions to guide decision-making, including: whether the method has been recommended by international bodies or adopted at a national level; the size of the effect and weight of the evidence; relevance to the trial population; whether the tool has been approved or introduced in the trial country; whether adding the tool might lead to trial futility; outstanding safety issues and status of the trial. Further work is needed to develop, implement and evaluate approaches to facilitate meaningful stakeholder participation in this deliberative process. (shrink)

Economists are often called upon as expert witnesses by the parties involved in antitrust litigation. One challenge they may face in US federal courts is compliance with the Daubert standard of admissibility of expert testimony. The interplay between model applicability and the Daubert standard is analyzed, suggesting the importance of distinguishing between weak applicability claims, those that state that a model’s critical assumptions are shared by the target, and strong applicability claims, those that connect empirical models and quantitative market (...) features. Recent antitrust cases in which expert testimonies based on economic models have been assessed following the Daubert standard are examined using this framework. Some normative implications are drawn concerning how to improve judges’ assessment of model-based arguments. (shrink)

Volume 20, Issue 5, June 2020, Page 38-40.

BackgroundThe contemporary frameworks for clinical research require informed consent for research participation that includes disclosure of material information, comprehension of disclosed information and voluntary consent to research participation. There is thus an urgent need to test, and an ethical imperative, to test, modify or refine medications or healthcare plans that could reduce patient morbidity, lower healthcare costs or strengthen healthcare systems.MethodsConceptual review.DiscussionAlthough some allocation principles seem better than others, no single moral principle allocates interventions justly, necessitating combining the moral principles (...) into multiprinciple allocation systems. The urgency notwithstanding, navigating ethical challenges related to conducting corona virus disease (COVID-19) clinical trials is mandatory, in order to safeguard the safety and welfare of research participants, ensure autonomy of participants, reduce possibilities for exploitation and ensure opportunities for research participation. The ethical challenges to can be categorized as challenges in allocation of resources for research; challenges of clinical equipoise in relation to the research questions; challenges of understanding disclosed information in potential participants; and challenges in obtaining informed consent.ConclusionTo navigate these challenges, stakeholders need a delicate balance of moral principles during allocation of resources for research. Investigators need to apply information processing theories to aid decision-making about research participation or employ acceptable modifications to improve the informed consent process. Research and ethics committees should strengthen research review and oversight to ensure rigor, responsiveness and transparency. (shrink)

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

In this paper we argue that the consensus around normative standards for the ethics of research in clinical trials, strongly influenced by the Declaration of Helsinki, is perceived from various quarters as too conservative and potentially restrictive of research that is seen as urgent and necessary. We examine this problem from the perspective of various challengers who argue for alternative approaches to what ought or ought not to be permitted. Key themes within this analysis will examine these claims and argue (...) they have implications for the interests of the research subject, research governance and regulation. Using our work with TREAT-NMD, the neuromuscular clinical trials network, we posit that there is a place for advancing the discourse of moral rights and moral duties in the context of research, especially from the perspective of patients and their families, and for including the politics of patient activism and empowerment. At the same time we remain vigilant to the danger that the therapeutic misconception and other serious vulnerabilities for the patient population in clinical trials, are at risk of being overlooked. (shrink)

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, (...) in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. (shrink)

Identities ascribed to research staff in face-to-face encounters with participants have been raised as key ethical challenge in transnational health research. ‘Misattributed’ identities that do not just deviate from researchers' self-image, but obscure unequivocal aspects of researcher identity – e.g. that they are researchers – are a case of such ethical problem. Yet, the reasonable expectation of unconcealed identity can conflict with another ethical premise: confidentiality; this poses challenges to staff visiting participants at home. We explore these around a (...) case study of ‘follow-up’ staff, observed during an ethnographic study of a Kenyan HIV ‘trial community’, which included participant observation, conversations, and interviews with staff (n = 79) and participants (n = 89). We found that because of the need to maintain confidentiality and because of some suspicions towards researchers, research staff drew upon alternative identities – presenting themselves to non-participants as relatives or friends, rather than as researchers. Several staff experienced this as necessary but uncomfortable. Simultaneously, staff and participants forged close relations in line with their fictional identities, which however also posed challenges because they entailed personal responsibilities that were difficult to live up to, due to limited resources, and the trial's limited duration. Similar challenges may arise in transnational HIV treatment programmes and should be explored further in that context. (shrink)

While an ethical obligation to report findings of clinical research to trial participants is increasingly recognised, the academic debate is often vague about what kinds of data should be fed back and how such a process should be organised. In this article, we present a classification of different actors, processes and data involved in the feedback of research results pertaining to an individual. In a second step, we reflect on circumstances requiring further ethical consideration. In regard to a concrete (...) research setting—the one of clinico-genomic research—we discuss what kinds of difficulties have to be faced when returning individual research results to trial participants. In a last step, we elaborate on a stepwise model to trigger the individual feedback process. Hence, this paper gives guidance on how to feedback individual research results in a specific research setting and responds at the same time to new challenges in the debate on the duty to return individual research findings. (shrink)

Cluster randomised trials are an increasingly important methodological tool in health research but they present challenges to the informed consent requirement. In the relatively limited literature on the ethics of cluster research there is not much clarity about the reasons for which seeking informed consent in cluster randomised trials may be morally challenging. In this paper, I distinguish between the cases where informed consent in cluster trials may be problematic due to the distinct features of ‘population-based’ interventions, which have not (...) been adequately discussed in the research ethics literature, and the cases where informed consent may be problematic for reasons that investigators also encounter in other research designs. I claim that informed consent requirements in cluster trials should be adjusted to the level of risk involved, arguing for a more comprehensive notion of research risk than that currently found in the research ethics guidelines, and the amount of freedom to be sacrificed in relation to a particular research aim. I conclude that these two factors are the most important to consider when assessing whether a cluster study should proceed when informed consent is infeasible or difficult to obtain. (shrink)

Pragmatic comparative effectiveness randomized controlled trials evaluate the effectiveness of one interventions under real-world clinical conditions. The results of ceRCTs are often directly generalizable to everyday clinical practice, providing information critical to decision-making by patients, clinicians, and healthcare policymakers. The PRECIS-2 framework identifies nine domains that serve to score a trial on a continuum between very explanatory to very pragmatic. According to the framework, pragmatic trials may have one or more of the following features: there are fewer eligibility criteria (...) for participants, in an... (shrink)