One of the arguments against conducting human subject trials in the Third World adopts a distributive justice principle found in a commentary of the CIOM'S Eighth Guideline for international research on human subjects. Critics argue that non-participant members of the community in which the trials are conducted are exploited because sponsoring agencies do not ensure that the products developed have been made reasonably available to these individuals. I argue that the distributive principle's wording is too vague and ambiguous (...) to be used to criticize any trial. Furthermore, the mere fact that an experiment does not fulfill this particular distributive justice principle does not entail that it is unethical. (shrink)

In the first part of this article, we considered how Thandi, a 15-year-old girl, was treated when taken by her mother to their GP, Dr Randera. Dr Randera notified them that Thandi was pregnant, HIV positive, and had syphilis and herpes. Dr Randera also informed them that there was a substantial risk that the baby would be born HIV positive. Both Thandi and her mother wanted an abortion. However, Dr Randera, who was morally opposed to abortions, refused to provide the (...) service and did not refer Thandi to another doctor who would perform the abortion.The saga continues:. (shrink)

Socrates On Trial tells of Socrates's return to a modern city that is plagued by prejudice, privilege and populism. On resuming his questioning in the agora he is arrested, interrogated by his prosecutors, questioned by his Judge, and confessed to by his inquisitor. On a Festival Day, he explores a new model for the just city --a city based not on mastery but on learning --before offering a new apology to the court that will, once again, decide his fate. This (...) new/old Socrates offers the city a renewed vision of justice by reconceptualizing the meaning and significance of thinking and education. From the force of Socratic questioning, he unfolds a different logic of truth, freedom, and justice. His conversations exert a gravitational force that draws key cultural elements of the city -- property, wealth, money, family, essence, gendered and racialized identities, production, distribution and consumption -- into its educational orbit. At stake here is the vulnerability of modern democracy to authoritarian leaders and their sponsors. Influenced by sophisticated propaganda people's frustration with democracy is channeled into visceral anger on the one hand, and into disillusioned scepticism and cynicism on the other. Belief in truth and education collapses in exhaustion and fatigue, caught in the headlights of seemingly irresolvable and petrifying rational paradoxes that block all paths to social justice. Socrates On Trial, describing the return of Socrates to the modern city, heralds a new education for such a city. (shrink)

Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members of lower socio-economic groups (...) for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants. (shrink)

Successful clinical trials are important for all of us, but they can be extremely complicated to design and run, so work must be done to consider what commonly goes wrong and how these issues can be addressed. Gelinas et al suggest an ethical argument for institutional prioritisation of clinical trials conducted among limited populations. This is to ensure successful recruitment and prevent competing trials rendering each other irrelevant through lack of statistical power. But they overlook the fact (...) that effective prioritisation already occurs, and their suggestion produces yet another hurdle for researchers to overcome. Their argument hinges around the claim that allocation of participants to trials represents an inevitable rationing scenario and, like all rationing scenarios, the best methods should be used for objectively determining how limited resources are distributed to achieve the end goal.1 Although they acknowledge that both individuals and clinicians may have preferences as to which trial a patient participates in, trial interventions are by definition experimental, and therefore choosing between trials is not really analogous to choosing between alternative clinical interventions. Here it seems that although clinical instinct is important when determining treatment options, a clinical trial is a specific attempt to create systematic justified knowledge and thus individual patient/clinician autonomy …. (shrink)

The maternal‐fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki – the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against (...) the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow ‘local conditions’ to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta‐ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects. (shrink)

Stenography had been used for centuries to capture the words of orators, lecturers, and royals, but there was a significant expansion of the use of stenography in the eighteenth century. During the period when Samuel Richardson held the contract to report on decisions reached in the House of Commons, Thomas Gurney began transcribing the testimony of many speakers at trials in the Old Bailey. In this article, I suggest that Richardson, increasingly aware of stenography as a technology for capturing (...) many different speakers’ words verbatim, ratcheted up epistolarity to establish a high-water mark for the multivoiced novel. He depicted characters who weren’t merely using stenographic concisions to keep up with the pace of speech but were essentially taking dictation from themselves. In a final section I consider Edgar Allan Poe’s “The Gold-Bug” as a repudiation of the multivoiced novel as a literary form and an effort to humiliate its voice-centeredness. (shrink)

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I (...) examine two types of institutional contexts: (1) public research agencies – agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private‐for‐profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private‐for‐profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice‐based account of standard of care. (shrink)

The large scale, time varying, and diversification of physically coupled networked infrastructures such as power grid and transportation system lead to the complexity of their controller design, implementation, and expansion. For tackling these challenges, we suggest an online distributed reinforcement learning control algorithm with the one-layer neural network for each subsystem or called agents to adapt the variation of the networked infrastructures. Each controller includes a critic network and action network for approximating strategy utility function and desired control law, (...) respectively. For avoiding a large number of trials and improving the stability, the training of action network introduces supervised learning mechanisms into reduction of long-term cost. The stability of the control system with learning algorithm is analyzed; the upper bound of the tracking error and neural network weights are also estimated. The effectiveness of our proposed controller is illustrated in the simulation; the results indicate the stability under communication delay and disturbances as well. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative (...) entities of the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

Until a few years ago, the prevailing view was that children should not be participants in clinical research trials because children were incapable of consenting to such nontherapeutic interventions and are particularly vulnerable to abuse. That view has undergone a significant shift in the last few years, particularly in the context of trials to test the safety and effectiveness of drugs. A number of events facilitated this change, including the widespread off-label distribution of drugs to children and developments (...) in the AIDS epidemic. These social forces have shifted the core ethical question from whether children should be research subjects to when children should be research subjects.The presumption in favor of including children as research subjects for drug trials has manifested itself primarily through two different reforms: a 1997 federal statute and a set of regulations promulgated by the Food and Drug Administration that recently became effective. Together they reflect the view that children deserve the same access to safe and effective therapies as adults. (shrink)

A probabilistic explication is offered of equipoise and uncertainty in clinical trials. In order to be useful in the justification of clinical trials, equipoise has to be interpreted in terms of overlapping probability distributions of possible treatment outcomes, rather than point estimates representing expectation values. Uncertainty about treatment outcomes is shown to be a necessary but insufficient condition for the ethical defensibility of clinical trials. Additional requirements are proposed for the nature of that uncertainty. The indecisiveness of (...) our criteria for cautious decision-making under uncertainty creates the leeway that makes clinical trials defensible. (shrink)

Clinical trials emerged in rapid succession as the COVID-19 pandemic created an unprecedented need for life-saving therapies. Fair and equitable subject selection in clinical trials offering investigational therapies ought to be an urgent moral concern. Subject selection determines the distribution of risks and benefits, and impacts the applicability of the study results for the larger population. While Research Ethics Committees monitor fair subject selection within each trial, no standard oversight exists for subject selection across multiple trials for (...) the same disease. Drawing on the experience of multiple clinical trials at a single academic medical centre in the USA, we posit that concurrent COVID-19 trials are liable to unfair and inequitable subject selection on account of scientific uncertainty, lack of transparency, scarcity and, lastly, structural barriers to equity compounded by implicit bias. To address the critical gap in the current literature and international regulation, we propose new ethical guidelines for research design and conduct that bolsters fair and equitable subject selection. Although the proposed guidelines are tailored to the research design and protocol of concurrent trials in the COVID-19 pandemic, they may have broader relevance to single COVID-19 trials. (shrink)

Reducing inequalities in health and the determinants of health is a widely acknowledged health policy goal, and methods for measuring inequalities and inequities in health are well developed. Yet, the evidence base is weak for how to achieve these goals. There is a lack of high-quality randomised controlled trials reporting impact on the distribution of health and non-health benefits and lack of methodological rigour in how to design, power, measure, analyse and interpret distributional impact in RCTs. Our overarching aim (...) in this paper is to contribute to the emerging effort to improve transparency and coherence in the theoretical and conceptual basis for RCTs on effective interventions to reduce health inequity. We endeavour to achieve this aim by pursuing two more specific objectives. First, we propose an overview of three broader health equity frameworks and clarify their implications for the measurement of health inequality in RCTs. Second, we seek to clarify the relationship between theory and translational challenges that researchers would need to attend to, in order to ensure that equity-relevant RCTs are coherently grounded in theory. (shrink)

ABSTRACTGiven the ethical controversies concerning HIV vaccine trials , we aimed to understand through an exploratory study how members of institutional review boards in the United States and research ethics committees in South Africa view issues concerning the process and content of reviews of these studies. We mailed packets of 20 questionnaires to 12 US IRB chairs and administrators and seven REC chairs to distribute to their members. We received 113 questionnaires . In both countries, members tended to be (...) white males with advanced academic degrees. Compared to the US, SA members called for ‘major changes’ in HVT protocols more frequently , and were less likely to think that HVT participants understood risks and benefits or informed consent forms . In both countries, members were divided on several critical issues , but agreed that they needed more training. Of the SA respondents, 40% reported that they were ‘self‐taught’ in ethics. This study, the first we know of to offer quantitative data comparing US vs. non‐US IRBs/RECs, thus suggests key similarities and differences , along with needs for education. These initial exploratory data in this area have important implications for IRBs, RECs, policy‐makers and scholars concerning future practice, training, policy, and investigations in research ethics, and prevention and treatment of HIV and other diseases in the developing world and elsewhere. (shrink)

The European Clinical Trials Directive (EU 2001; 2001/20/EC) was introduced to improve the efficiency of commercial and academic clinical trials. Concerns have been raised by interested organizations and institutions regarding the potential for negative impact of the Directive on non-commercial European clinical research. Interested researchers within the European Group for Blood and Marrow Transplantation (EBMT) were surveyed to determine whether researcher experiences confirmed this view. Following a pilot study, an internet-based questionnaire was distributed to individuals in key (...) research positions in the European haemopoietic SCT community. Seventy-one usable questionnaires were returned from participants in different EU member states. The results indicate that the perceived impact of the European Clinical Trials Directive has been negative, at least in the research areas of interest to the EBMT. (shrink)

In October 2013, the Declaration of Helsinki was revised a seventh time in its 50 year history. While it is the most widely accepted set of ethical principles for the protection of patients participating in medical research, the Declaration of Helsinki has also been subject of constant controversy. In particular, its paragraph on the use of placebo controls in clinical trials divides the research community into active-control and placebo orthodox proponents, both continuously demanding revisions of the Declaration of Helsinki (...) in favour of their position. The goal of the present project is to compare the mainly theoretical controversy with regulatory implementation. We distributed a questionnaire to national drug regulatory authorities from different countries to collect information on the authorities’ respective approaches to interpretation and implementation of the Declarations’ placebo paragraph in the conduct of medical research. Our findings suggest that the majority of drug regulatory authorities have established a practice of a middle ground, allowing placebo controls in some instances. Various interpretations of “serious harm” and “methodological reasons” are proposed as well as safeguards to avoid abuse of the option to use placebo-controls. Leaving the placebo paragraph open to various interpretation is a result of the Declaration of Helsinki’s character as a guidance document. With the current version controversy will continue. The Declaration should be continued to be strengthened to enforce the appreciation of conducting medical research with the highest ethical standard. (shrink)

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I (...) examine two types of institutional contexts: (1) public research agencies – agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care. (shrink)

It is a commonplace of the critical innovation literature that experiment has replaced mass production as the driving force of accumulation. But while many theorists have explored the politics and dynamics of such economies of experiment under the rubric of ‘immaterial’, cognitive or affective labour, few have examined the intersection of labour, experiment and the speculative in the clinic. Taking the clinic as representative of contemporary transformations in the commodity-form, labour and innovation, this article will look at recent attempts to (...) reform the clinical trial, arguing that these developments represent a far-reaching shift in our understanding of medicine. First, I investigate recent efforts (associated with the discourse of ‘translational medicine’) to rethink the interface between experimental lab-based science and the clinic. I also look at closely associated efforts to reintroduce an element of experimental surprise into the clinical trial process itself, through the adoption of novel trial designs. If the randomized controlled trial was conceived essentially along the lines of a product testing procedure, recent efforts have attempted to reintroduce surprise into the testing process itself – in other words, to invent a trial process capable of producing unexpected events as leads for further innovation. I then move from the experimental clinic to what I call the distributed experiment. Here I focus on efforts to outsource pharmacological innovation to a distributed public of patients through the use of social networking software. These platforms allow drug developers to escape the limits of the conventional clinical trial by tracking the experimental practices taking place in the distributed clinic of unregulated drug consumption. (shrink)

: Some commentators have recently proposed that "clinical equipoise," although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects--bad deal trials--could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

BackgroundVast sums are distributed based on grant peer review, but studies show that interrater reliability is often low. In this study, we tested the effect of receiving two short individual feedback reports compared to one short general feedback report on the agreement between reviewers.MethodsA total of 42 reviewers at the Norwegian Foundation Dam were randomly assigned to receive either a general feedback report or an individual feedback report. The general feedback group received one report before the start of the (...) reviews that contained general information about the previous call in which the reviewers participated. In the individual feedback group, the reviewers received two reports, one before the review period and one during the period. In the individual feedback group, the reviewers were presented with detailed information on their scoring compared with the review committee as a whole, both before and during the review period. The main outcomes were the proportion of agreement in the eligibility assessment and the average difference in scores between pairs of reviewers assessing the same proposal. The outcomes were measured in 2017 and after the feedback was provided in 2018.ResultsA total of 2398 paired reviews were included in the analysis. There was a significant difference between the two groups in the proportion of absolute agreement on whether the proposal was eligible for the funding programme, with the general feedback group demonstrating a higher rate of agreement. There was no difference between the two groups in terms of the average score difference. However, the agreement regarding the proposal score remained critically low for both groups.ConclusionsWe did not observe changes in proposal score agreement between 2017 and 2018 in reviewers receiving different feedback. The low levels of agreement remain a major concern in grant peer review, and research to identify contributing factors as well as the development and testing of interventions to increase agreement rates are still needed.Trial registrationThe study was preregistered at OSF.io/n4fq3. (shrink)

The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, especially where government bodies, sponsors, and (...) regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. (shrink)

BackgroundPatient skepticism concerning medical innovations can have major consequences for current public health and may threaten future progress, which greatly relies on clinical research.The primary objective of this study is to determine the variables associated with patient acceptation or refusal to participate in clinical research. Specifically, we sought to evaluate if distrust in pharmaceutical companies and associated psychosocial factors could represent a recruitment bias in clinical trials and thus threaten the applicability of their results.MethodsThis prospective, multicenter survey consisted in (...) the administration of a self-questionnaire to patients during a pulmonology consultation. The 1025 questionnaires distributed collected demographics, socio-professional and basic health literacy characteristics. Patients were asked to rank their level of trust for pharmaceutical companies and indicate their willingness to participate in different categories of research.Logistic regression was used to determine factors contributing to “trust” versus “distrust” group membership and willingness to participate in each category of research.ResultsOne thousand patients completed the survey, corresponding to a response rate of 97.5%. Data from 838 patients were analyzed in this study.48.3% of respondents declared that they trusted pharmaceutical companies, while 35.5% declared distrust. Being female, inactive in the employment market, and not-knowing the name of one’s disease are factors related to declared distrust. Distrust-group membership is associated with unwillingness to participate in certain categories of trials such as pre-marketing and industry-sponsored trials.ConclusionDistrust in pharmaceutical companies is associated with a specific patient profile and with refusal to participate in certain subcategories of trials. This potential recruitment bias may explain the under-representation of certain categories of patients such as women in pre-marketing drug trials. (shrink)

Some commentators have recently proposed that “clinical equipoise,” although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects—”bad deal trials”—could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

The outsourcing and offshoring of clinical trials has expanded a global field of experimental activity. This essay addresses the competitive logic and social norms by which a field of human subjects research for drug development has taken form. The clinical trials industry and its move to low- and middle-income countries serve as a telescope into the global clinical trial and how it is crafted and made to work in different locales. Lives often depend on new medical commodities as (...) they enter the value chains of transnational medicine and capital. Transparency remains a key problem. The essay explores the politics of creating centralized registries through which the scope of this experimental enterprise might be known. As the engine of pharmaceutical research molds itself to international and national regulatory norms, detection of adverse risk can be deferred or minimized. The essay also points to policy gaps with respect to how the benefits and insecurities of global experiments are distributed as well as to emergent political practices of care and accountability. (shrink)

Between December 2020 and March 2021, the US Food and Drug Administration and the European Medicines Agency issued Emergency Use Authorizations and Conditional Marketing Authorizations for the distribution of the first COVID-19 vaccines. Although these vaccines were thoroughly assessed before their approval, regulators required companies to continue ongoing placebo-controlled clinical trials in order to gather further reliable scientific information on their safety and efficacy, as well as to start new studies to evaluate additional candidates. The aim of this paper (...) is to present and discuss the ethical issues raised by the tension between the need to continue these types of clinical trials and the obligations related to the protection of the rights and well-being of research participants. Specifically, we question whether—how, and to what extent—fundamental principles governing research involving human beings can be applied to the current pandemic situation. We argue that continuing ongoing placebo-controlled clinical trials can be considered ethically justifiable only if all participants are adequately informed of any developments that may affect their willingness to remain enrolled, including the current situation of resource scarcity and the prioritization criteria established for vaccination. However, we also argue that currently approved vaccines, which are considered safe and effective enough to be administered to millions of people as part of the vaccination campaign, necessarily represent the “best proven intervention” currently available and, therefore, should be used as comparators in future studies instead of placebo. (shrink)

The Clauser–Horne–Shimony–Holt (CHSH) inequality is a constraint that local hidden variable theories must obey. Quantum Mechanics predicts a violation of this inequality in certain experimental settings. Treatments of this subject frequently make simplifying assumptions about the probability spaces available to a local hidden variable theory, such as assuming the state of the system is a discrete or absolutely continuous random variable, or assuming that repeated experimental trials are independent and identically distributed. In this paper, we do two things: (...) first, show that the CHSH inequality holds even for completely general state variables in the measure-theoretic setting, and second, demonstrate how to drop the assumption of independence of subsequent trials while still being able to perform a hypothesis test that will distinguish Quantum Mechanics from local theories. The statistical strength of such a test is computed. (shrink)

While most of the mortality associated with severe acute respiratory syndrome coronavirus 2 has been in elderly populations and adults with significant medical comorbidities, there has been death and morbidity in paediatric populations. As vaccine trial data is released to the public, many people look to the future with hope ; with good vaccine uptake there is the opportunity to reduce the spread of infectious pandemics. Initial vaccine trials were completed with adults and were expanded to include paediatric populations (...) delaying paediatric COVID-19 vaccine initiatives. The exclusion of children from initial vaccine trials during a pandemic is not morally justifiable and fosters distrust with the pharmaceutical and medical industries and inevitably postpones vaccinating children when there is a surplus of available vaccines. The delayed vaccination of children under twelve may have significant public health and economic consequences as there may be ongoing viral transmission in the context of reopening strategies. The safety and efficacy of these candidate vaccines in children should be assessed expeditiously so that distribution to vulnerable paediatric populations is not impacted. Vaccine uptake compliance in the general population is important in establishing herd immunity and ensuring that there is thorough scientific evidence to support vaccination for children is important in establishing community trust. (shrink)

Shortages of generic, injectable chemotherapeutics have been increasing in prevalence since 2006. Due to the lack of access to first-line, lifesaving treatments, physicians have been forced to ration chemotherapy between patients. Although the scarcity has been managed with good intentions, it has been done in an ad hoc manner, without the benefit of an ethically grounded and standardized schema. Using an approach based on the “accountability for reasonableness” method by Daniel and Sabin, I establish a framework and protocol for rationing (...) that is specific to chemotherapy. Prior to the state of true shortage, I present guidelines for the use of an adequate supply of chemotherapy with knowledge of upcoming scarcity. Within the rationing framework itself, I first prioritize emergency use of chemotherapeutics and those already receiving treatment at the time of shortage. I advocate for stratifying patients based on the prognostic indicators of their cancer type, using a combination of clinical-trial-based initial response and longer term survival, followed by the patients’ line of treatment. All patients who are not able to receive their “best” treatment must receive a sequent, next-best treatment, and their treatment team must have the ability to appeal to a rationing committee in special circumstances. I reject the ideas of stratification based on the intention of the treatment, perceived quality of life, pre-existing condition not impacting performance status, the classical “sickest first” argument, and giving preference to pediatric cases. Lastly, I advocate for any system of rationing to be transparent to those it affects and acknowledge the difficulties it presents to patients and physicians alike. (shrink)

This article draws on ethnographic field data collected during an investigation of the informed consent process and AIDS clinical trials. It describes the involvement of care providers (physicians, nurse practitioners, physician assistants) during the enlistment, or recruitment, phase of the informed consent process. It shows that sometimes care providers are involved in the receipt, evaluation and distribution of information on clinical trials through their interactions with research professionals and patients. It suggests that the involvement of care providers has (...) the potential to influence the informed consent process. Some of the ethical and practice considerations of this are discussed. (shrink)

Cross-situational learning has recently gained attention as a plausible candidate for the mechanism that underlies the learning of word-meaning mappings. In a recent study, Blythe and colleagues have studied how many trials are theoretically required to learn a human-sized lexicon using cross-situational learning. They show that the level of referential uncertainty exposed to learners could be relatively large. However, one of the assumptions they made in designing their mathematical model is questionable. Although they rightfully assumed that words are (...) class='Hi'>distributed according to Zipf's law, they applied a uniform distribution of meanings. In this article, Zipf's law is also applied to the distribution of meanings, and it is shown that under this condition, cross-situational learning can only be plausible when referential uncertainty is sufficiently small. It is concluded that cross-situational learning is a plausible learning mechanism but needs to be guided by heuristics that aid word learners with reducing referential uncertainty. (shrink)

Based on anthropological fieldwork among protesters against the Covid policy in Germany, this paper elaborates the symmetry of accusations made against each other by proponents and opponents of the state-imposed protection measures against the backdrop of an asymmetrical distribution of power. The social dynamics that emerged during the pandemic are often understood as the result of a knowledge controversy that most participants thus categorize as a media problem. A key finding of my research on protests against the German Covid policy (...) is that, as in my research on the controversy over mediumism, the controversy is about the agency of human and nonhuman actors and carried out to a great extent based on the same values on both sides, which at the same time accuse each other of not conforming to these values. The protesters are part of a heterogeneous minority that in large parts embodies the values of the majority and, in a way, exceeds them, i.e., a minority that is hypercritical and has extreme expectations about the values of the majority society – in this case: of solidarity, science, transparency, rationality, and coherence. From its marginal position, the minority develops a canny eye for the unfulfilled promises of the majority: its contradictions and conscious or unconscious double standards are perceived as bigotry against the backdrop of the aspiration to absence of contradiction. Therefore, this minority suspects that the motivations and goals behind the measures taken are other than just the protection of health, while the majority in turn see the minority’s commitment to society and democracy as (self-)deception and also suspect hidden motives and actors behind it. This mutual suspicion leads to a hysterical state of doubt and distrust, which is rooted in the nature of mediality. (shrink)

Ethical issues relating to the use of the injectable contraceptive in developed and developing countries alike involve public policy decisions concerning both criteria for testing a new drug and individual choices about using a specific form of contraception approved for national distribution. Drug testing consists of an important but still evolving set of procedures. Depo-Provera is not qualitatively different from any other drug and some unpredictable risks are inevitable, even after extensive animal experiments and clinical trials. In assessing the (...) risks and benefits of Depo-Provera use, epidemiological data from large-scale human use is now beginning to become more important than data from animal experiments and clinical trials. The consumer's best interest is central to any ethically responsible system of drug distribution. Systems of informed choice are needed, even in societies where illiteracy remains common and medical services are weak. In the case of a contraceptive, the risks of non-use leading to unintended pregnancy, which can result in high mortality, are relevant as well as the side-effects of the method. An attempt, therefore, is made here to categorise those issues which are universal and those which are country-specific. (shrink)

BackgroundAfrica continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges.MethodsIn order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and (...) Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009.ResultsKey cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing.ConclusionThe consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields. (shrink)

Little is known about how bow mechanical characteristics objectively and quantitatively influence violinists' preferences and performance. Hypothesizing that the bow shape and mass distribution modifications would alter both violinists' appreciations of a bow and objective assessments of their performance, we recruited 10 professional violinists to play their own violin using 18 versions of a single bow, modified by combining three cambers and six mass distributions, in random order. A musical phrase, composed for this study, was played legato and spiccato at (...) three octaves and two tempi. Each violinist scored all 18 bows. Then, experts assessed the recorded performances according to criteria inspired by basic musical analysis. Finally, 12 audio-descriptors were calculated on the same note from each trial, to objectivise potential acoustic differences. Statistical analysis reveals that bow camber impacted the violinists' appreciations, and that heavier bow tips gave lower scores for spiccato playing. The expert evaluations reveal that playing with a lighter bow, or with a bow whose camber's maximum curvature is close to the frog, had a positive impact on some violinists' performance. The “camber-participant” interaction had significant effects on the violinists' appreciations, on the expert's evaluation and on almost all the audio-descriptors. While trends were identified, multiple camber-participant interactions suggest that bow makers should provide a variety of cambers to satisfy different violinists. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)