In this paper, we discuss challenges associated with implementing a policy for Ancillary Care (AC) for related and unrelated (serious) adverse events during an Ebola vaccine trial conducted in a remote area of the Democratic Republic of the Congo. Conducting clinical trials in resourceconstrained settings can raise context-related challenges that have implications for study participants’ health and wellbeing. During the Ebola vaccine study, three participants were injured in road traffic accidents, but there were unexpected difficulties when trying to apply (...) the AC policy. First, because of the nature of the adverse events, the insurer refused to cover the costs. Second, the AC policy did not address treatments by traditional medicine, even though traditional medicines are frequently used and highly trusted in the study community. This highlighted a contrast between the researchers’ well-intentioned AC approach and the participants’ legitimate preferences. The way in which researchers should address their responsibility to provide AC is not straightforward; it requires contextualization. Our experience highlights the importance of involving community representatives and the local ethics committee to ensure development of an AC policy that is culturally and ethically appropriate. Additionally, the insurance contract should clearly stipulate which adverse events are linked to the trial participation, and thus eligible for coverage, to avoid controversies when claims are made. (shrink)

We very much appreciate the helpful and generous commentaries in response to “Do Clinicians have a Duty to Participate in Pragmatic Clinical Trials?” (Garland, Morain, and Sugarman 2023). In that a...

Responsible research and good science are concepts with various meanings depending on one’s perspective and assumptions. Fellow researchers, research participants, policy makers and the general public also have differing expectations of the benefits of research ranging from accurate and reliable data that extend the body of knowledge, to solutions to societal concerns. Unless these differing constituencies articulate their differing views they may fail to communicate and undermine the value of research to society.

When it comes to how to hold people responsible for wrongdoing, much of the African philosophical tradition focuses on reconciliation as a final aim. This essay expounds an interpretation of reconciliation meant to have broad appeal, and then draws out its implications for responsibility in respect to three matters. First, when it comes to criminal justice, prizing reconciliation entails that offenders should be held responsible to “clean up their own mess,” i.e., to reform their characters and compensate victims in ways (...) they find burdensome, an approach to punishment that differs from deterrence and desert theories. Second, regarding civil justice, reconciliation means that holding responsible to compensate wrongful harm means improving victims’ quality of life in ways they accept, which contrasts with a common prescription to put victims in the condition they would have been in had the wrong not occurred. Third, reconciliation can involve putting on trial more than just the direct offender, for instance family members who had been able to influence his behavior and were allied with him. The chapter provides reason to take the reconciliatory approaches seriously that will be found prima facie attractive by those from a variety of backgrounds. (shrink)

In this commentary on the previous paper it is explained that screen-detected Duct Carcinoma In Situ is effectively a new disease of unknown natural history. It is therefore impossible that 'the doctor knows best' and it is therefore both in the patient and the public's best interests that such cases are submitted to the rigours of the randomised controlled trial. Inevitably this brings the ethical dilemma of how to explain to patients the uncertainty and how to involve them in a (...) rational decision to take part in the randomised controlled trial. It is argued that as well as there being a collective benefit for future generations of women, that we should resolve this problem now, the individual woman is likely to benefit from being treated according to a strict protocol. Nevertheless the time of diagnosis is paradoxically not the best time for a patient to become aware of these matters and it is about time that the lay public and the opinion formers recognized their responsibility to become acquainted with the benefits and the needs of the randomised controlled trial in anticipation of the day when they themselves will be patients. (shrink)

Memory Detection Tests (MDTs) are a general class of psychophysiological tests that can be used to determine whether someone remembers a particular fact or datum. The P300 MDT is a type of MDT that relies on a presumed correlation between the presence of a detectable neural signal (the P300 “brainwave”) in a test subject, and the recognition of those facts in the subject’s mind. As such, the P300 MDT belongs to a class of brain-based forensic technologies which have proved popular (...) and controversial in recent years. With such tests increasingly being proffered for use in the courtroom — to either support or call into question testimony — it would behoove the legal system to have some systematic framework for ensuring that they are used responsibly. In this paper, I defend one such framework for ensuring that this is the case: the legitimacy enhancing test. According to this test, it is appropriate to make use of technologies such as the P300 MDT whenever doing so would (probably) enhance the legitimacy of the trial. I argue that this test addresses tensions between scientific and legal norms of evidence, and exhibits a number of additional virtues including unification, simplicity and flexibility. Although the test is defended by considering the example of the P300 MDT, its significance is much broader than that. If it has the virtues I claim for it, it should provide a general framework for the responsible use of technologies, and the responsible innovation of social epistemic systems. (shrink)

This article analyzes the origins of the “responsible corporate officer” doctrine: the trial of Joseph Dotterweich. That doctrine holds that an officer may be personally liable for the criminal act of a subordinate if the officer was, in some indefinite way, able to prevent the violation. Applying this doctrine, the prosecution of Dotterweich entailed strict liability for a strict liability offense. The underlying offenses—the interstate sale of one misbranded and adulterated drug and one misbranded drug—were said to be strict liability (...) offenses. And then, with respect to Dotterweich as the corporation’s general manager, the government argued that he was strictly liable because he stood in “responsible relation” to the company’s acts. The government never tried to prove that the company, Buffalo Pharmacal, was negligent, nor did it try to prove that Dotterweich was negligent in his supervision of the employees of Buffalo Pharmacal. The prosecutor and judge were candid about this theory throughout the trial, although the judge conceded that it seemed bizarre and unfair. The defense lawyer repeatedly sought to inject what became known throughout the trial as the “question of good faith,” but was circumvented at almost every turn. What would thus seem to be the crux of any criminal trial—the personal fault of the defendant—was carefully shorn from the jury’s consideration. The government’s theory was so at odds with intuitive notions of liability and blame that, as one probes into the case, and looks at the language used in the government’s appellate briefs, imputations of moral fault inevitably crept in. Yet the government was not entitled to make such accusations, as it had pruned moral considerations from the trial. The article argues that the responsible corporate officer doctrine can never enjoy a secure place in our legal system. First, the doctrine is at a minimum in tension with, and often in direct opposition to, basic principles of the criminal law; and second, the doctrine fails, when followed to its logical conclusions, to accord with basic notions of fair play. The article concludes that the responsible corporate officer doctrine is either unnecessary, in cases in which the evidence establishes personal fault, or unjust, in cases in which it creates liability in the absence of personal fault through the unspecified notion of “responsibility.” The Dotterweich case illustrates what is contemplated by the latter possibility, and why it is problematic in any judicial system that purports, in the words of the Model Penal Code, “to safeguard conduct that is without fault from condemnation as criminal.”. (shrink)

“Responsible research” and “good science” are concepts with various meanings depending on one’s perspective and assumptions. Fellow researchers, research participants, policy makers and the general public also have differing expectations of the benefits of research ranging from accurate and reliable data that extend the body of knowledge, to solutions to societal concerns. Unless these differing constituencies articulate their differing views they may fail to communicate and undermine the value of research to society.

I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (...) University (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

ObjectiveCo-morbid insomnia and sleep apnea is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with (...) COMISA. We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA.MethodsOne hundred and forty five participants with insomnia and sleep apnea [apnea-hypopnea index ≥ 15] were randomized to CBTi or no-treatment control. Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional, and novel [quantitative electroencephalography ] polysomnographic predictors of between-group changes in Insomnia Severity Index scores from pre-treatment to post-treatment.ResultsCompared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI, less wake after sleep onset, and less N3 sleep. No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change.DiscussionAmong participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance. (shrink)

_Clinical Trials and the African Person_ offers an account of the African notion of the self/person within the clinical trials context. As opposed to autonomy-based principlism, this other-regarding/communalist perspective is touted as the preferred alternative model particularly in multicultural settings.

The American Journal of Bioethics, Volume 11, Issue 6, Page W1-W3, June 2011.

HIV intervention trials being conducted in developing countries continue to raise questions of ethics in clinical research. Most recently these questions have arisen because of a prospective study reporting the rate of transmission in discordant couples that was conducted in Uganda. The study raises serious questions about the minimum ethical standards required for this kind of research and the responsibilities of the researchers. We re-examine that research particularly focusing on issues of informed consent and duty of care, and place (...) this trial in the context of the broader debate. (shrink)

The term ‘locked-in’ syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain–computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, (...) sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow–based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants’ capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level–dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, realtime data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method.. (shrink)

Clinical trials in developing countries are often beset by ethical problems that would be considered unresolvable in countries like Australia and the U.S. Nevertheless, such trials continue to go ahead throughout Asia, Africa and South America, and are often conducted in ways that could be considered to be unethical. In this article I discuss two issues, focussing on an HIV preventative trial of a vaginal gel, the Nonoxynol 9 phase three trial being held in Kenya. The first of (...) these is what makes such a trial unethical given that it has approval from the WHO and seemingly conforms with acceptable standards of consent. The second issue involves using material from such trials, if we accept that they were conducted unethically. (shrink)

ABSTRACTDespite being held in something approaching universal esteem for its capacity to promote prosocial behavior and inhibit antisocial behavior, empathy has recently become the recipient of strong criticism from some of today’s leading academics. Two of the more high-profile criticisms of empathy have come from philosopher Jesse Prinz and psychologist Paul Bloom, each of whom challenges the view that empathy has an overall beneficial influence on human behavior. In this essay, I discuss the basis of their criticisms as well as (...) why I am not compelled by their arguments to believe that empathy does more harm than good. In the process of responding to empathy’s critics, I discuss the important role that empathy plays in our moral lives. I argue that, rather than employing rational considerations to minimize the role that empathy plays in our moral and political judgments, such considerations are put to better use by expanding empathy when conducive to the common good and suppressing it when it opposes th... (shrink)

BackgroundA recent paper presents an argument and mechanism for the possible stopping of clinical trials early based on opportunity costs.DiscussionAlthough we agree that the costs and opportunity costs of clinical trials need to be reduced wherever possible, we raise concerns about the motivation and mechanism for stopping clinical trials early raised by Lavery et al.SummaryWe argue that there are already enough acceptable criteria and actors in the clinical trials arena to justify early stoppage of clinical (...) class='Hi'>trials, and argue that factors other than efficacy need to be carefully considered, especially in developing country contexts. (shrink)

We argue that in implanted neurotechnology research, participants and researchers experience what Henry Richardson has called “moral entanglement.” Participants partially entrust researchers with access to their brains and thus to information that would otherwise be private, leading to created intimacies and special obligations of beneficence for researchers and research funding agencies. One of these obligations, we argue, is about continued access to beneficial technology once a trial ends. We make the case for moral entanglement in this context through exploration of (...) participants’ vulnerability, uncompensated risks and burdens, depth of relationship with the research team, and dependence on researchers in implanted neurotechnology trials. (shrink)

Because we are often nagged by the thought that we might not have behaved any differently than those good citizens whose respect for the law and fear of punishment led them to support the Nazi regime, we are fascinated with the behavior of ordinary Germans. Careful to first strip away the pathological explanations of German behavior, Pellegrino and Thomasma ask simply whether ordinary Germans could have reasoned and, by implication, acted differently. Although their affirmative answer is consistent with the activism (...) we have all come to demand of the Germans, it is not clear whether we, ourselves, can lay full claim to the moral high ground. (shrink)

BackgroundA recent paper presents an argument and mechanism for the possible stopping of clinical trials early based on opportunity costs.DiscussionAlthough we agree that the costs and opportunity costs of clinical trials need to be reduced wherever possible, we raise concerns about the motivation and mechanism for stopping clinical trials early raised by Lavery et al.SummaryWe argue that there are already enough acceptable criteria and actors in the clinical trials arena to justify early stoppage of clinical (...) class='Hi'>trials, and argue that factors other than efficacy need to be carefully considered, especially in developing country contexts. (shrink)

Some participants will get HIV-infected in HIV prevention trials, despite risk reduction measures. The subsequent treatment responsibilities of sponsor-investigators have been widely debated, especially where access to antiretroviral therapy (ART) is not available. In this paper, we explore two accounts of beneficence to establish whether they can shed light on sponsor-investigator responsibilities. We find the notion of general beneficence helpful insofar as it clarifies that some beneficent actions will be obligatory where they can be dispensed without scuppering the trial. (...) We find the notion of specific beneficence helpful insofar as it directs investigators to attend to the needs of trial participants; however the range of interventions that could be provided remains unhelpfully broad. We then examine accounts of the investigator-participant relationship to narrow the range of interventions that investigators should provide, concluding that health-care, and HIV infection, are appropriate foci. We conclude that when investigators are able to meet the ART needs of their participants (e.g. referral, assisted referral or direct provision) without sacrificing trial quality, they must do so. However, there is little of this explicit direction to be found in the account of specific beneficence itself, but rather it is found in accounts of the relationship that are compatible with beneficence. (shrink)

Volume 19, Issue 10, October 2019, Page 105-107.