Research ethics committees (RECs) evaluate whether the risk-benefit ratio of a study is acceptable. Decentralized clinical trials (DCTs) are a novel approach for conducting clinical trials that potentially bring important benefits for research, including several collateral benefits. The position of collateral benefits in risk-benefit assessments is currently unclear. DCTs raise therefore questions about how these benefits should be assessed. This paper aims to reconsider the different types of research benefits, and their position in risk-benefit assessments. We first propose (...) a categorization of research benefits, based on the types of benefits that can be distinguished from the literature and ethical guidelines. Secondly, we will reconsider the position of collateral benefits. We argue that these benefits are not fundamentally different from other benefits of research and can therefore be included in risk-benefit assessments of DCTs. (shrink)

Scholars have debated the role that altruistic considerations play—and should play—in recruitment and decision-making processes for clinical trials. Little empirical data are available to support their various perspectives. We analyzed 140 audiotaped pediatric informed consent sessions, of which 95 (68%) included at least one discussion of how participation in a cancer clinical trial might benefit: 1) the pursuit of scientific knowledge generally; 2) other children with cancer specifically; and 3) “the future” and other vaguely defined recipients. Clinicians initiated most (...) (80%) of these discussions of altruism. The enrollment rate of children in the clinical trial was high (83%) overall, but not higher among children whose parents were involved in an altruism-oriented discussion. These findings suggest that: (1) clinicians invoke a spectrum of altruistic considerations rather than a single monothematic notion of altruism, and (2) the effect of altruistic considerations on subsequent enrollment decisions is marginal. While further research on this topic is warranted, bioethical debate should strive to reflect the diversity of altruistic discourse in clinical research encounters and to place this discourse in the context of other, including nonaltruistic, considerations. (shrink)

Our aims are to set forth a multiprinciple system for selecting among clinical trials competing for limited space in an immunotherapy production facility that supplies products under investigation by scientific investigators; defend this system by appealing to justice principles; and illustrate our proposal by showing how it might be implemented. Our overarching aim is to assist manufacturers of immunotherapeutic products and other potentially breakthrough experimental therapies with the ethical task of prioritizing requests from scientific investigators when production capacity is (...) limited. (shrink)

The robust design and conduct of pragmatic cluster randomised trials may be in tension with the ethical requirement to obtain written informed consent from prospective research participants. In our experience, researchers tend to focus on whether a waiver of consent is appropriate for their studies. However, pragmatic cluster randomised trials raise other important questions that have direct implications for determining when an alteration or waiver of consent is permissible. To assist those involved in the design, conduct and review (...) of pragmatic cluster randomised trials, we outline four critical questions to consider: (1) What is the nature of the intervention being evaluated? (2) Is the choice to use cluster randomisation justified? (3) Can the risk of recruitment bias be addressed? and (4) Is an alteration or waiver of consent appropriately justified? We recommend that researchers and research ethics committees conduct a stepwise analysis of a planned cluster randomised trial using these questions. To illustrate the application of this stepwise analysis, we use three pragmatic cluster randomised trials in the haemodialysis setting as case studies. (shrink)

After achieving sustained graft functioning in animal studies, the next step in the progression of xenotransplantation towards clinical application is the initiation of the first clinical trials. This raises the question according to which criteria patients shall be selected for these trials. While the discussion regarding medical criteria has already commenced, ethical considerations must also be taken into account. This is essential, first, to establish a procedure that is ethically reasonable and justified. Second, it is a prerequisite for (...) a publicly acceptable and comprehensible implementation. This paper outlines a multicriteria approach for the selection of patients in first-in-human clinical trials of cardiac xenotransplantation with four ethical criteria: medical need, capacity to benefit, patient choice and compliance (as an exclusion criterion). Consequently, these criteria identify a primary target group of patients who exhibit a high medical need for cardiac xenotransplantation, face a high risk of morbidity and mortality without an organ replcaement therapy, have a substantial chance of benefiting from xenotransplantation, thereby also enhancing the scientific value of the trial, and qualify for an allotransplant to have a real choice between participating in a first-in-human xenotransplantation trial and waiting for a human organ. A secondary group would include patients for whom only the first two criteria are met, that is, who have a high medical need and a good capacity to benefit from xenotransplantation but who have a restricted choice because they do not qualify for an allotransplant. (shrink)

In this issue of the American Journal of Bioethics, manuscripts focus on the obligations of clinicians and researchers in pragmatic clinical trials (Garland, Morain, and Sugarman 2023; Morain and L...

The exclusion of the elderly and people with disabilities from cancer clinical research without appropriate justification is discriminatory and is at odds with the ethos of EU principles, laws and research regulations. It further limits study generalizability. Several primary EU laws fronted by the European Charter prohibit engaging in disparate impact discrimination on the grounds of age and disability in all of EU tasks.

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating (...) in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. (shrink)

The concept of practical, or pragmatic, clinical trials was introduced in the early 2000s, in parallel with the growing availability and use of electronic health data. Researchers and policymakers...

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet (...) platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease , debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for (...) in-depth analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned.. (shrink)

First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns (...) on claims about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

Monitoring of clinical trials is important to ensure adherence to protocol, to safeguard the rights of research participants and to achieve compliance with principles of good clinical practice. Recent regulatory changes in India require Ethics Committees to keep an oversight of ongoing clinical trials including on-site monitoring. In this article, we share the experience of on-site monitoring of clinical trials by the Ethics Committee of a tertiary care, academic and research centre in India. We found a large (...) number of shortcomings in the areas of informed consent, adverse events, insurance and reimbursement, which would not have been detected by off-site document review. Interestingly, many shortcomings were also not detected by on-site monitoring arranged by clinical trial sponsors. We therefore conclude that on-site monitoring of ongoing clinical trials is a highly important activity for Indian Ethics Committees. (shrink)

Effective community engagement is an important legal, ethical, and practical prerequisite for conducting field trials of genetically modified mosquitoes, because these studies can substantially impact communities and it is usually not possible to obtain informed consent from each community member. Researchers who are planning to conduct field trials should develop a robust community engagement strategy that meets widely recognized standards for seeking approval from the affected population, such as timeliness, consent, information sharing, transparency, understanding, responsiveness, mutual understanding, inclusiveness, (...) and respectfulness. Additional research is needed on the effectiveness of different methods of engaging communities in field trials of genetically modified mosquitoes and how to respond to public opposition to genetically modified organisms. For research programs involving the genetic modification of disease vectors to move forward, they must have public acceptance and support, which cannot be achieved without effective community engagement. (shrink)

Given the past two decades of over 40 failed trials of amyloid-lowering therapies in Alzheimer’s Disease (AD), many of which succeeded in lowering amyloid as designed, we present an ethical argument for emptying the drug pipeline of tests of amyloid-lowering agents so as to end the historical dominance of the amyloid-reducing therapeutic approach in AD.

Unrealistic therapeutic beliefs are very common—the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such (...) therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant’s primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects’ appreciation as a component of informed consent—it is already an established component of decision-making capacity assessments—can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual’s understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, ‘Why do you want to participate in this trial?’, all potential participants should be asked the question: ‘What are you giving up by participating in this trial?’ and (2) researchers should consider the settings in which it may be possible and practical to obtain ‘two-point consent’. (shrink)

Unrealistic optimism is a bias that leads people to believe, with respect to a specific event or hazard, that they are more likely to experience positive outcomes and/or less likely to experience negative outcomes than similar others. The phenomenon has been seen in a range of health-related contexts—including when prospective participants are presented with the risks and benefits of participating in a clinical trial. In order to test for the prevalence of unrealistic optimism among participants of early-phase oncology trials, (...) we conducted a survey with patients over 18 years of age who were enrolled in a phase I, phase I/II, or phase II clinical cancer trial in the New York City area between August 2008 and October 2009. Participants in our study were asked to compare their own chances of experiencing a range of risks and benefits related to the trial they were enrolled in with the chances of the other trial participants. We found a significant optimistic bias in their responses. Respondents tended to overestimate the benefits of the trial they were enrolled in and underestimate its risks. In addition, we found no significant relationship between respondents’ understanding of the trial’s purpose and how susceptible they were to unrealistic optimism. Our findings suggest that improving the consent process for oncology studies requires more than addressing deficits in understanding. (shrink)

Smajdor addresses the problem of inferior clinical outcomes among adults with impairments of capacity to give informed consent (AWIC). She notes that AWIC are generally excluded from clinical trials to protect them against harms and avoid exploitation and claims there is a causal link between involvement in clinical trials and favourable outcomes. She argues, given this link, that we should increase AWIC representation in clinical trials and can justifiably do so by recognising the capacity of AWIC to (...) assent. AWIC form a diverse group, with multiple aetiologies, including, for example, Down syndrome, traumatic brain injury and dementia. In some cases, the inability to consent may fluctuate so that the same person could be AWIC only at certain times. Yet despite these differences, the group has a shared unmet need. We agree with Smajdor that AWIC outcomes should be improved, but question whether simply increasing representation in clinical trials is sufficient to achieve this. We identify the following points: 1. AWIC are under-represented in clinical trials. There is evidence of widespread exclusion of AWIC in clinical trials within the UK and abroad and it is often a specific exclusion criterion.1 2. AWIC have worse clinical outcomes and a lower life expectancy. The life expectancy …. (shrink)

The COVID-19 pandemic led to significant changes of the usual procedures in the clinical trials conduct, as well as to modifications of the relevant study documentation, which also affected regular quality assurance activities ensuring the safety of clinical trial participants, compliance with good clinical practice, and the integrity and validity of the clinical trial data collected during the COVID-19 pandemic. The paper deals with the ethical guidelines and legal regulations that govern the conduct of clinical trials and discusses (...) the ethical implications that arose from the forced adjustments of routine processes and procedures in the clinical trial conduct during the COVID-19 public health emergency. The paper also reflects on the ethical consequences of conducting clinical trials during the public health emergency, as well as on means of performing quality assurance activities and a regular oversight of clinical research. (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.

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

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)

Informed consent may be seriously compromised if patients fail to understand the experimental nature of the trial in which they are participating. Using focus groups, the authors explored how prospective trial participants interpret and understand the science of clinical trials by using patient information sheets relative to their medical condition. An opportunity was provided to hear in the patients’ own words how they interpret the information and why there is variable understanding. Respondents struggled to comprehend the meaning and purpose (...) of concepts such as randomisation and double blinding, and found them threatening to their ideas of medical care. Suggestions are made about how to improve the national guidelines on written information for trial participants and pretesting of the information sheets is advocated. (shrink)

In Italy, a judge reduced the sentence of a defendant by 1 year in response to evidence for a genetic predisposition to violence. The best characterized of these genetic differences, those in the monoamine oxidase A (MAOA), were cited as especially relevant. Several months previously in the USA, MAOA data contributed to a jury reducing charges from 1st degree murder (a capital offence) to voluntary manslaughter. Is there a rational basis for this type of use of MAOA evidence in criminal (...) court? This paper will review in context recent work on the MAOA gene–environment interaction in predisposing individuals to violence and address the relevance of such findings to murder trials. Interestingly, the MAOA genetic variants impact future violence and aggression only when combined with the adverse environmental stimuli of childhood maltreatment. Thus nature and nurture interact to determine the individual’s risk. Based on current evidence, I argue there is a weak case for mitigation. But should future experiments confirm the hypothesis that individual differences in impulse control and response to provocation found in MAOA-L men (without abuse) are significantly magnified when combined with childhood maltreatment, the case could turn into a stronger one. (shrink)

Much has changed in maternal-fetal medicine since the early 2000s, when the previous ethical frameworks for fetal therapy trials were established. We applaud Hendriks and colleagues for taking on t...

Objective: To assess whether continuous consent, a process in which information is given to research participants at different stages in a trial, and clinician training in that process were effective when used by clinicians while gaining consent to the Total Body Hypothermia (TOBY) trial. The TOBY trial is a randomised controlled trial (RCT) investigating the use of whole-body cooling for neonates with evidence of perinatal asphyxia. Obtaining valid informed consent for the TOBY trial is difficult, but is a good test (...) of the effectiveness of continuous consent. Methods: Semistructured interviews were conducted with 30 sets of parents who consented to the TOBY trial and with 10 clinicians who sought it by the continuous consent process. Analysis was focused on the validity of parental consent based on the consent components of competence, information, understanding and voluntariness. Results: No marked problems with consent validity at the point of signature were observed in 19 of 27 (70%) couples. Problems were found mainly to lie with the competence and understanding of the parents: mothers, particularly, had problems with competence in the early stages of consent. Problems in understanding were primarily to do with side effects. Problems in both competence and understanding were observed to reduce markedly, particularly for mothers, in the post-signature phase, when further discussion took place. Randomisation was generally understood but unpopular. Information was not always given by clinicians in stages during the short period available before parents gave consent. Most clinicians, however, were able to give follow-up information. Discussion: Consent validity was found to compare favourably with similar trials examined in the Euricon study. Conclusion: Adopting the elements of the continuous consent process and clinician training in RCTs should be considered by researchers, particularly when they have concerns about the quality of consent they are likely to obtain by using a conventional process. (shrink)

Objective Adolescents have had very limited access to research on biomedical prevention interventions despite high rates of HIV acquisition. One concern is that adolescents are a vulnerable population, and trials carry a possibility of harm, requiring investigators to take additional precautions. Of particular concern is preventive misconception, or the overestimation of personal protection that is afforded by enrolment in a prevention intervention trial. Methods As part of a larger study of preventive misconception in adolescent HIV vaccine trials, we (...) interviewed 33 male and female 16–19-year-olds who have sex with men. Participants underwent a simulated HIV vaccine trial consent process, and then completed a semistructured interview about their understanding and opinions related to enrolment in a HIV vaccine trial. A grounded theory analysis looked for shared concepts, and focused on the content and process of adolescent participants’ understanding of HIV vaccination and the components of preventive misconception, including experiment, placebo and randomisation. Results Across interviews, adolescents demonstrated active processing of information, in which they questioned the interviewer, verbally worked out their answers based upon information provided, and corrected themselves. We observed a wide variety of understanding of research concepts. While most understood experiment and placebo, fewer understood randomisation. All understood the need for safer sex even if they did not understand the more basic concepts. Conclusions Education about basic concepts related to clinical trials, time to absorb materials and assessment of understanding may be necessary in future biomedical prevention trials. (shrink)

Background Ethically, informed consent regarding randomised controlled trials (RCTs) should be understandable to patients. The patients can then give free consent or decline to participate in a RCT. Little is known about what patients really understand in consultations about RCTs. Methods Cancer patients who were asked to participate in a randomised trial were surveyed using a semi-standardised interview developed by the authors. The interview addresses understanding, satisfaction and needs of the patients. The sample included eight patients who participated in (...) a trial and two who declined. The data were analysed on the basis of Mayring's qualitative analysis. Results Patients' understanding of informed consent was less developed than anticipated, especially concerning key elements such as randomisation, content and procedure of RCTs. Analysing the result about satisfaction of the patients, most of the patients described their consultations as hectic and without advance notice. Health limitations due to cancer played a decisive role. However, most of the patients perceived their physician to be sympathetic. Analysing the needs of patients, they ask for a clear informed consent consultation with enough time and adequate advance notice. Conclusion This study fills an important empirical research gap of what is ethically demanded in an RCT consultation and what is really understood by patients. The qualitative approach enabled us to obtain new results about cancer patients' understanding of informed consent, to clarify patients' needs and to develop new ideas to optimise the informed consent. (shrink)

The temptation to use prospective observational studies (POS) instead of conducting difficult trials (RCTs) has always existed, but with the advent of powerful computers and large databases, it can become almost irresistible. We examine the potential consequences, were this to occur, by comparing two hypothetical studies of a new treatment: one RCT, and one POS. The POS inevitably submits more patients to inferior research methodology. In RCTs, patients are clearly informed of the research context, and 1:1 randomized allocation between (...) experimental and validated treatment balances risks for each patient. In POS, for each patient, the risks of receiving inferior treatment are impossible to estimate. The research context and the uncertainty are down-played, and patients and clinicians are at risk of becoming passive research subjects in studies performed from an outsider’s view, which potentially has extraneous objectives, and is conducted without their explicit, autonomous, and voluntary involvement and consent. (shrink)

Is there no balm in Gilead; is there no physician there? Why then is not the health of the daughter of my people recovered?In July of 2004, Cambodian sex workers staged a protest of an HIV prevention trial set to enroll 900 sex workers in Phnom Penh, charging the study planners with exploitation. The Cambodian study was one of a series of international clinical trials sponsored by the U.S. National Institutes of Health, U.S. Centers for Disease Control and Prevention, (...) and the Bill and Melinda Gates Foundation testing the safety and efficacy of tenofovir, an antiretroviral drug produced by Gilead Sciences, Inc., to prevent HIV transmission. To date, two of these international studies have been closed and one is suspended, prompting calls for re-examination of the ethics of HIV prevention trials. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods (...) will favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

The academic literature in research ethics has been marked in the past decade by a much broader focus on the need for the protection of developing communities subjected to international clinical trials. Because of the proximity of the revision of the Declaration of Helsinki, completed in October 2008, most papers have addressed the issue of a double standard of care following the use of placebo. However, other no less important issues, such as interactions between the lifestyles structures of low-income (...) communities and the efficiency of risk-minimising procedures also deserve attention. The purpose of this paper is to discuss forms of uncertainty involved in clinical trials in poor and low-income countries that are not addressed by conventional methods of risk assessment. Furthermore, the increase in size of risks that are identified by conventional assessment methods will be addressed. Besides, the difficulty in properly applying risk-minimising procedures will be discussed. Finally, this paper proposes the involvement of research ethics committees in the risk evaluation process and the establishment of national ethics evaluation systems. (shrink)

The concept of minimal risk has been used to regulate and limit participation by adolescents in clinical trials. It can be understood as setting an absolute standard of what risks are considered minimal or it can be interpreted as relative to the actual risks faced by members of the host community for the trial. While commentators have almost universally opposed a relative interpretation of the environmental risks faced by potential adolescent trial participants, we argue that the ethical concerns against (...) the relative standard may not be as convincing as these commentators believe. Our aim is to present the case for a relative standard of environmental risk in order to open a debate on this subject. We conclude by discussing how a relative standard of environmental risk could be defended in the specific case of an HIV vaccine trial among adolescents in South Africa. (shrink)

Interdisciplinary essays on the ethical issues which encompassed the trials and Code of Nuremberg have been collated from researchers from various countries in fields as diverse as medicine, bioethics, psychoanalysis, history, philosophy, Jewish thought, law, and ethics. The book focuses on five main areas: the juridical originality of the Nuremberg trials; the scientific, epistemological, and psychoanalytic backgrounds of racism and anti-Semitism; the biomedical and bioethical issues of the Nuremberg Code; a post-Nuremberg historical, ethical, and philosophical study of the (...) notion of a 'crime against humanity'; and the Jewish perspective on purity, impurity, race, and the universal ethical expectations of mankind. The goal of the interdisciplinary study is to outline the necessary components of a bridge between science ethics, and ethics and law. (shrink)

The paper investigates how field experimentation of genetically modified crops became central to the French controversy on genetically modified organisms in recent years. Initially constructed in the 1980s as a cognitive endeavor to be preserved from lay interference, field trials of genetically modified crops were reconceived as “an intrusion in the social space,” which had to be negotiated with actors from that space. In order to analyze this transformation, the authors suggest that it is necessary to develop an interpretive (...) framework that combines theoretical perspectives from science and technology studies and the sociology of social problems, and emphasizes the importance of the way in which actors compete in a heterogeneous public space, to put forward alternative framings of problems. The authors present a detailed analysis of the interactions and conflicts between actors in diverse social arenas in order to better understand the dynamics of this sociotechnical controversy. (shrink)

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized (...) clinical trials.1-10 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials. (shrink)

The increasing use of cluster randomised trials in low-resource settings raises unique ethical issues. TheOttawa Statement on the Ethical Design and Conduct of Cluster Randomised Trialsis the first international ethical guidance document specific to cluster trials, but it is unknown if it adequately addresses issues in low-resource settings. In this paper, we seek to identify any gaps in theOttawa Statementrelevant to cluster trials conducted in low-resource settings. Our method is (1) to analyse a prototypical cluster trial conducted (...) in a low-resource setting (PURE Malawi trial) with theOttawa Statement; (2) to identify ethical issues in the design or conduct of the trial not captured adequately and (3) to make recommendations for issues needing attention in forthcoming revisions to theOttawa Statement. Our analysis identified six ethical aspects of cluster randomised trials in low-resource settings that require further guidance. The forthcoming revision of theOttawa Statementshould provide additional guidance on these issues: (1) streamlining research ethics committee review for collaborating investigators who are affiliated with other institutions; (2) the classification of lay health workers who deliver study interventions as health providers or research participants; (3) the dilemma experienced by investigators when national standards seem to prohibit waivers of consent; (4) the timing of gatekeeper engagement, particularly when researchers face funding constraints; (5) providing ancillary care in health services or implementation trials when a routine care control arm is known to fall below national standards and (6) defining vulnerable participants needing protection in low-resource settings. (shrink)

Recruitment processes for clinical trials are governed by guidelines and regulatory systems intended to ensure participation is informed and voluntary. Although the guidelines and systems provide some protection to potential participants, current recruitment processes often result in limited understanding and experiences of inadequate decision support. Many trials also have high drop-out rates among participants, which are ethically troubling because they can be indicative of poor experiences and they limit the usefulness of the knowledge the trials were designed (...) to generate. Drawing on recent social-psychological and philosophical-ethical research on trial recruitment and patient participation in treatment decision-making, this paper identifies possibilities for improving communicative support for both initial decisions and ongoing participation in clinical trials. It highlights the potential of a shift in thinking about ‘voluntariness’, underpinned by relational understandings of autonomy, to encourage more nuanced judgements about the ethics of communication between trial staff and (potential) participants. The paper suggests that the idea of responsively enabling people to consider invitations or requests to participate in particular trials could serve as a general guide to communication. This might help ensure decisions about trial participation are meaningfully informed and voluntary, and that relationships between trial staff and participants contribute to positive experiences of trial participation and ultimately to the generation of the robust knowledge. (shrink)