Bioethics of public commenting: Manipulation,data risk,and public participation in E-Rulemaking

Little scholarly attention has been given to the ethics of public commenting as part of the online federal rule-making process. This essay argues the process of public commenting on federal regulations in the digital era threatens both the integrity of those regulations and the integrity of the individuals they are meant to protect. The ongoing risk is anonymous public commenting is open to manipulation. This risk is particularly salient for eRulemaking with implications for human subjects as was shown in the completed revision process to the Common Rule. Guarding against physical and informational harms requires at least some verification of the identities of public commenters. The burdens of verification access are outweighed by the benefits to authentic participation in e-Rulemaking.     

Harmonizing regulations for biomedical research: a critical analysis of the US and Venezuelan systems

This article aims to compare the national legal systems that regulate biomedical research in an industrialized country (United States) and a developing country (Venezuela). A new international order is emerging in which Europe, Japan and the United States (US) are revising common guidelines and harmonizing standards. In this article, we analyze - as an example - the US system. This system is controlled by a federal agency structured to regulate research funded by the federal government uniformly, either in the US or abroad. In contrast, in Venezuela, a developing country, the creation of a centralized system is a slow process. Different types of ethical committees review research projects using non-uniform criteria. Consequently, various parallel organizations that conduct biomedical research, such as universities, research institutes and private hospitals have diverse regulations operating at a local level. Thus, the most relevant difference between the Venezuelan and the US systems is the degree of standardization. In the US, the review process is performed by institutional review boards (IRBs), which have a similar organization and maintain relationships with a centralized agency, following standard regulations. Although new proposals for establishing national regulations are currently being considered in Venezuela, the success of these initiatives will depend on promoting governmental efforts to create a more structured centralized system supported by a national regulatory framework. This system will need governmental financial support at all levels. This article proposes an integrated system to regulate research with human participants in Venezuela and other developing countries.     

AGAINST RISK-BENEFIT REVIEW OF PRISONER RESEARCH

The 2006 Institute of Medicine (IOM) report, 'Ethical Considerations for Research Involving Prisoners', recommended five main changes to current US Common Rule regulations on prisoner research. Their third recommendation was to shift from a category-based to a risk-benefit approach to research review, similar to current guidelines on pediatric research. However, prisoners are not children, so risk-benefit constraints on prisoner research must be justified in a different way from those on pediatric research. In this paper I argue that additional risk-benefit constraints on prisoner research are unnecessary: the current Common Rule regulations, omitting category-based restrictions but conjoined with the IOM report's other four main recommendations, ensure that prisoner research is as ethical as non-prisoner research is. I explain why four problems which which may be more prevalent in prisons and which risk-benefit constraints may seem to address – coercion, undue inducements, exploitation, and protection from harm – are in fact not solved by adding further risk-benefit constraints on prisoner research.     

Xenotransplantation: a problematic world behind a glamorous facade

The discussion about the ethics of xenotransplantation seems to focus upon the benefits for individual patients and the potential risks for human society, in general, to contract a newly emerging retrovirus. In these risk-benefit considerations, the moral concern for the research animals involved appears to be absent. This is remarkable, because the presumed successful xenograft is not expected very soon. A lot of basic problems in pig and primate xenotransplantations still need solving. These new experiments in our own biomedical laboratories raise questions regarding animal welfare and ethical justification in the light of possible alternative strategies. In this article, I discuss some of the moral issues related to preclinical, fundamental xenotransplantation research.     

Xenotransplantation: A Problematic World Behind a Glamorous Facade

The discussion about the ethics of xenotransplantation seems to focus upon the benefits for individual patients and the potential risks for human society, in general, to contract a newly emerging retrovirus. In these risk-benefit considerations, the moral concern for the research animals involved appears to be absent. This is remarkable, because the presumed successful xenograft is not expected very soon. A lot of basic problems in pig and primate xenotransplantations still need solving. These new experiments in our own biomedical laboratories raise questions regarding animal welfare and ethical justification in the light of possible alternative strategies. In this article, I discuss some of the moral issues related to preclinical, fundamental xenotransplantation research.     

An Exploration of the Protective Effects of Investigators’ Ethical Awareness upon Subjects of Drug Clinical Trials in China

Up till now, China has not enacted any legal mechanisms governing certification or supervision for ethics committees. This article analyses deficiencies in the protection of subjects in clinical drug trials under China’s current laws and regulations; it emphasizes that investigators, as practitioners who have direct contact with subjects, play significant roles in protecting and safeguarding subjects’ rights and interests. The paper compares the status quo in China in this area to that of other countries and discusses ways China might enhance the protection of rights and interests of trial subjects, such as enhancing the ethical awareness of investigators through training, improving laws and regulations, and strengthening the communication between investigators and ethics committees.     

STAKEHOLDER PERSPECTIVES ON ETHICAL CHALLENGES IN HIV VACCINE TRIALS IN SOUTH AFRICA

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

Faith-based perspectives on the use of chimeric organisms for medical research

Efforts to advance our understanding of neurodegenerative diseases involve the creation chimeric organisms from human neural stem cells and primate embryos—known as prenatal chimeras. The existence of potential mentally complex beings with human and non-human neural apparatus raises fundamental questions as to the ethical permissibility of chimeric research and the moral status of the creatures it creates. Even as bioethicists find fewer reasons to be troubled by most types of chimeric organisms, social attitudes towards the non-human world are often influenced by religious beliefs. In this paper scholars representing eight major religious traditions provide a brief commentary on a hypothetical case concerning the development and use of prenatal human–animal chimeric primates in medical research. These commentaries reflect the plurality and complexity within and between religious discourses of our relationships with other species. Views on the moral status and permissibility of research on neural human animal chimeras vary. The authors provide an introduction to those who seek a better understanding of how faith-based perspectives might enter into biomedical ethics and public discourse towards forms of biomedical research that involves chimeric organisms.     

Protecting subjects' interests in genetics research

Biomedical researchers often assume that sponsors, subjects, families, and disease-associated advocacy groups contribute to research solely because of altruism. This view fails to capture the diverse interests of many participants in the emerging research enterprise. In the past two decades, patient groups have become increasingly active in the promotion and facilitation of genetics research. Simultaneously, a significant shift of academic biomedical science toward commercialization has occurred, spurred by U.S. federal policy changes. The concurrent rise in both the roles that subjects play and the commercial interests they have presents numerous ethical challenges. We examine the interests of different research participants, finding that these interests are not addressed by current policies and practices. We conclude that all participants should be given a voice in decisions affecting ownership, access to, and use of commercialized products and services, and that researchers and institutions should negotiate issues relating to control of research results and the sharing of benefits before the research is performed.     

Bystanders and ethical review of research: Proceed with caution

Scientists seeking to conduct research with human subjects must first submit their proposals to research ethics committees (Institutional Review Boards [IRBs], in the United States). Some of these studies pose risks to “bystanders,” i.e., people who may be affected by the research but who are not enrolled as study subjects. Should IRBs expand their scope to include oversight over possible harms to bystanders as well as research subjects? This paper presents arguments against this step. Prior review of research with human subjects, despite its evident burden on the research enterprise, is a necessary caution, because the tension between the objectives of humane treatment of research subjects and sound scientific design and procedure has in the past led to serious abuses. This rationale is inapplicable in the case of bystanders. Moreover, in view of the many and varied effects of both research practices and scientific advances on the broader public over time, those who may be considered to be “bystanders” may potentially expand without limit; requiring IRBs to anticipate these distant and long-term effects as part of prior ethical review could greatly increase its burden and its deterrent effect on research. While conducting research without concern for serious potential harm to bystanders may be irresponsible and unethical, expanding the scope of prior review by IRBs to include risks to bystanders is not required by the principles governing human subjects research, and the costs and burdens of this expansion may outweigh any expected gains.     

Researchers' ethical concerns regarding habituating wild-nonhuman primates and perceived ethical duties to their subjects: Results of an online survey

While the process of habituation is essential for researchers to observe primates in their natural habitats, ethical dilemmas may arise from its consequences. We collected data from 286 participants via an online survey to investigate: (a) how primatologists perceive their ethical duties toward their subjects; (b) the extent to which primatologists are concerned about the potential ethical consequences of habituation; and (c) the methods primatologists use to reduce potential harms caused by habituation. Overall, primatologists felt an extremely strong duty to mitigate harms that they may cause (e.g., to not stress individuals during observation, treat injuries, and reunite separated individuals) and expressed very high concern for habituation's potential to increase the vulnerability of their subjects to poaching and disease transfer. Ratings for those items were so high that they could not be included in subsequent exploratory factor analyses that were designed to reveal constructs underlying respondents’ ratings of their ethical duties and concerns. Factor analysis of ratings of ethical duties revealed that primatologists reported a strong duty to mitigate harms caused by other humans and a lower perceived duty to mitigate naturally occurring harmful events. Factor analysis on ethical concern ratings revealed that respondents were concerned about harms during the habituation process, the presence of unhabituated behavior after habituation had been established, and indirect harms of habituation. Concerns for unhabituated behavior and indirect harms were rated slightly higher than concern for harms during the habituation process. To mitigate potential harms, primatologists primarily reported engaging in strategies to reduce stress in their subjects. Our findings reveal a disconnect between primatologists' ratings of their ethical concerns and their reported mitigation practices that may, in part, stem from gaps in knowledge about the true impacts of habituation. We suggest areas of discussion and research in the field necessary to address those gaps.     

The Concept of Risk in Biomedical Research Involving Human Subjects

An established ethical principle of biomedical research involving human subjects stipulates that risk to subjects should be proportionate to an experiment's potential benefits. Sometimes this principle is imprecisely stated as a requirement that 'risks and benefits' be balanced. First, it is noted why this language is imprecise. Second, the persistence of such language is attributed to how it functions as a rhetorical trope. Finally, an argument is made that such a trope is infelicitous because it may not achieve its intended persuasive purposes. More importantly, it should be avoided because it masks the important role that chance plays in clinical research. Risk is the possibility of harm. As a precondition of harm it is unintended and undesirable in projects of biomedical research. It requires ethical vigilance. As a vehicle of chance, however, it is both intended and desirable. It requires methodological appreciation.     

Sentience and sensation

When animals are used in a biomedical research activity that may result in more than mild or momentary pain or distress, humanity, federal regulations and common sense direct us to use the least sentient species that can fulfill the aims of the research. The use of a less-sentient species is in line with the concept of Replacement, one of the well-known 3Rs of laboratory animal use. But what is a less-sentient species? Is a chimpanzee less sentient than a human; is a dog less sentient than a chimpanzee; and is a mouse less sentient than a dog? Does 'less sentient' imply that a species is less able to experience pain, is less intelligent or has less self-awareness? This essay will explore some of the relationships between sentience, pain and vertebrate phylogeny.     

医学研究伦理学的发展现状与前景

创新技术的开展和转化医学的注重给医学的发展注入了新的活力,但同时,也带来了一系列社会伦理问题和法律问题。生命医学伦理学的兴起和发展催生了医学研究伦理学分支学科形成,目的在于推进解决涉及人体的医学研究的伦理问题。当前,面临的最突出的伦理问题在于,对医学研究合法性、先进性及伦理性的把握,对医学研究伦理审查必要性的认知,对医学研究方案设计与伦理道德的匹配,对医学研究知情同意的告知,对医学研究风险与受益的平衡。逐步与国际接轨,加强伦理委员会制度建设;提高伦理审查能力建设,形成高水平的伦理审查队伍;学术组织和团体共同努力,推进医学研究伦理学的发展,这将助推医学研究伦理学的发展。     

Ethics and biomedical research

Ethics in biomedical research took off from the 1947 Nuremberg Code to its own right in the wake of the Declaration of Helsinki in 1964. Since then, (inter)national regulations and guidelines providing a framework for clinical studies and protection for study participants have been drafted and implemented, while ethics committees and drug evaluation agencies have sprung up throughout the world. These two developments were crucial in bringing about the protection of rights and safety of the participants and harmonization of the conduct of biomedical research. Ethics committees and drug evaluation agencies deliver ethical and scientific assessments on the quality and safety of the projects submitted to them and issue respectively approvals and authorizations to carry out clinical trials, while ensuring that they comply with regulatory requirements, ethical principles, and scientific guidelines. The advent of biomedical ethics, together with the responsible commitment of clinical investigators and of the pharmaceutical industry, has guaranteed respect for the patient, for whom and with whom research is conducted. Just as importantly, it has also ensured that patients reap the benefit of what is the primary objective of biomedical research: greater life expectancy, well-being, and quality of life.     

The Social Value of Knowledge and International Clinical Research

In light of the growth in the conduct of international clinical research in developing populations, this paper seeks to explore what is owed to developing world communities who host international clinical research. Although existing paradigms for assigning and assessing benefits to host communities offer valuable insight, I criticize their failure to distinguish between those benefits which can justify the conduct of research in a developing world setting and those which cannot. I argue that the justification for human subjects research is fundamentally grounded in the social value of knowledge, and that this value is context‐dependent in a manner which should inform our ethical evaluation of the conduct of research in specific settings. I propose a new framework for the assessment of research benefits assigned to developing world host communities, a natural implication of which is to limit the types of research projects which may permissibly be conducted in developing world settings.     

Research misconduct--an indictment and possible solution

The core problems of scientific misconduct are systemic to the infrastructure of the conduct of scientific research itself, and therefore are probably immune to any short-term solutions. Renaming federal agencies, reorganizing monitoring activities, appointing new personnel, and other similar proposed remedies are necessary but insufficient measures. Indeed, the etiological factors in misconduct include an erosion of trust that stands in the way of the ethical integrity flowing from the major ethical principles identified in the Belmont Report. To make those principles applicable and useful to meet the challenges of current research activities, especially those involving human subjects, depends on our ability to foster an unprecedented cooperation of community resources.     

CRISPR Ethics: Moral Considerations for Applications of a Powerful Tool

With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to CRISPR applications; 3) whether a regulatory framework(s) for clinical research involving human subjects might accommodate all types of human genome editing, including editing of the germline; and 4) whether international regulations governing inappropriate CRISPR utilization should be crafted and publicized. We conclude that moral decision making should evolve as the science of genomic engineering advances and hold that it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress.     

Maintaining Research Integrity While Balancing Cultural Sensitivity: A Case Study and Lessons From the Field

Contemporary emphasis on creating culturally relevant and context specific knowledge increasingly drives researchers to conduct their work in settings outside their home country. This often requires researchers to build relationships with various stakeholders who may have a vested interest in the research. This case study examines the tension between relationship development with stakeholders and maintaining study integrity, in the context of potential harms, data credibility and cultural sensitivity. We describe an ethical breach in the conduct of global health research by a arising from the ad‐hoc participation of a community stakeholder external to the visiting research group. A framework for reflection is developed from a careful examination of underlying factors and presented with a discussion of consequences and mitigation measures. This framework aims to present lessons learned for researchers working abroad who might face similar situations in their work.     

Solidarity and equity: new ethical frameworks for genetic databases

Genetic database initiatives have given rise to considerable debate about their potential harms and benefits. The question arises as to whether existing ethical frameworks are sufficient to mediate between the competing interests at stake. One approach is to strengthen mechanisms for obtaining informed consent and for protecting confidentiality. However, there is increasing interest in other ethical frameworks, involving solidarity--participation in research for the common good--and the sharing of the benefits of research.