美国联邦受试者保护通则最新修订述评

作为美国受试者保护基本的法律框架,联邦通则于2009年启动第一次大规模修订。历时近七年,两轮征求公众意见,最终规则于2017年1月正式发布。最终规则对知情同意过程、泛化知情同意、合作研究的单中心伦理审查、免除审查条款以及持续审查要求等做出了新的规定和要求。从分析通则修订背景入手,简要回顾修订历程,介绍通则主要的修订内容并予以评论,阐述其积极的影响及可能面临的挑战,强调及时学习借鉴美国经验对于推进我国受试者保护制度建设的指导意义,鼓励立足国情的研究探索与制度创新。     

注重全人群、全方位、全过程——论受试者知情同意伦理审查的强化

通过对医药学研究人体试验受试者知情同意的伦理审查发展现状的说明,分析现阶段知情同意伦理审查工作中存在流于形式,审查结果不够科学、客观和公正等问题。再结合医药学研究的发展需要,说明知情同意伦理审查的工作情况和不断发展的要求。提出对知情同意做到全人群、全方位、全过程的伦理审查的覆盖。并通过实施全人群、全方位、全过程的伦理审查的过程,提高人体试验受试者知情同意伦理审查水平,促进医药学研究和社会医学的发展。     

临床研究生科研人体试验的伦理审查状况调查

采用匿名问卷调查的方法对临床研究生进行关于科研人体试验的伦理审查状况的调查研究.研究表明,人体试验在临床科研中比重很大;伦理审查制度建设已初具规模,存在导师及研究生伦理意识的差距,接受伦理审查相关培训的需求强烈;要进一步正确认识知情同意的意义,应加强对安慰剂使用的严格监管.     

生物医学人体受试者研究未来面临的挑战

人体受试者研究的伦理问题在今后将会愈益引起关注,如何看待知情同意的代理权？如何处理不同文化背景下的知情同意原则？在商业利益诱惑下背离本人健康利益和知情同意是否有效？受试者的利益回报,以及体试验研究要求的双盲,随机、对照等原则可能面临的新问是,都是人体受试者研究未来面临的挑战。     

痛经临床科研中的伦理问题及措施

通过梳理痛经临床科研中的有关伦理问题,具体涉及受试者招募、知情同意、对照选择、患者依从性、研究人员资质和中医药研究特点等容易出现伦理问题的环节,进行探讨和分析其存在的原因,并提出相应防范和改进措施,加强伦理委员会参与临床研究过程管理的相关措施,如受试者招募环节的伦理监管;完善知情同意的过程,提高受试者的依从性;注重多部门协作,提高跟踪审查质量;伦理审查与科学审查相互配合;加强中医药伦理审查等,唯有这样才能更好地保护痛经临床科研中的受试者。     

生物医学研究的知情同意过程及知情同意豁免

知情同意并不仅仅是知情同意书签字,它是一个持续的决定过程,发挥着保护受试者权益的重要作用。对知情同意过程中的关键问题,包括谁可以获得知情同意、谁可以同意或授权参加研究、信息告知过程、受试者信息理解、受试者自愿选择过程、知情同意书签字及免除签字的情况进行了系统地介绍。知情同意是保护受试者的权利和自主性的基本原则,但在特殊情况下是可以豁免的,包括不具备获取知情同意可行性及急救研究两种特殊情况。     

美国与知情同意有关的一些问题

知情同意是医疗保健和医学研究的一个基本的伦理学要求。这两种情况中,当医学研究的知情同意标准比医疗保健要求更加严格时,知情同意包含了3种要素：（1）告知病人或受试者该研究的性质。包括益处,危险和其他有关内容;（2）确保病人受试者理解所提供的信息;（3）得到病人或受试者自愿的同意,没有能力参与知情同意的病人包括患痴呆和危重病等无决断 能力的病人,这些病人属弱势病人。如要获许对他们的疾病进行研究,我们必须制定保护弱势受试者有效的伦理政策,提出了关于对痴呆病人、危重病人,脑死亡病人研究的伦理学政策。     

国际合作中知情同意面临的难题及思考

目前在医学研究的国际合作中,知情同意原则在实施中出现了许多争议和难题.结合一些典型案例,对知情同意的跨文化研究、知情同意表格的误解以及保护受试者与自由研究之间的权衡等问题进行了深入地分析.指出:加强交流、相互尊重、求同存异是解决跨文化研究的必由之路;严格审查、加强监管是避免知情同意流于形式的重要手段;鼓励与防范并举才能达到双赢的局面.     

SIDCER、AAHRPP认证和CAP认证的比较研究

目前常见的伦理审查认证体系包括:亚太地区伦理审查委员会论坛组织的"伦理审查委员会能力拓展战略方案"(SIDCER认证)、美国人体研究保护体系认证协会的认证(AAHRPP认证)和我国的中医药研究伦理审查体系认证(CAP认证)。通过对这三种体系进行多方面的深入比较,说明SIDCER认证关注的重点是伦理委员会(IRB)的标准操作规程(SOP)规范性,要求实际操作与SOP保持一致;AAHRPP认证强调的是机构、IRB、研究者等共同建立有效的受试者保护体系,其标准主要依据美国法规体系;CAP认证是个新生事物,依据我国现行法规制度建立,也强调建立受试者保护体系,更有利于指导我国一般机构建立伦理审查体系。     

儿童临床试验伦理要素与受试者保护机制研究

国家卫生健康委员会2016年5月、2017年5月公布71种药物纳入鼓励研发申报儿童药品清单,以儿童为受试者的临床试验迎来巨大的机会,给儿童受试者保护带来巨大的挑战。通过探讨儿童临床试验方案设计、儿童及家庭知情同意、儿童受试者风险-受益评估及伦理委员会审查程序等与儿童临床试验特殊伦理问题相关的伦理审查体系,以期构建以临床试验方案为依据,受试者安全为核心,知情同意为底线,兼顾公平原则,研究者-监护人-伦理委员会-行政管理部门-社会各方协同配合的儿童受试者保护机制。     

Oversight framework over oocyte procurement for somatic cell nuclear transfer: comparative analysis of the Hwang Woo Suk case under South Korean bioethics law and U.S. guidelines for human embryonic stem cell research

We examine whether the current regulatory regime instituted in South Korea and the United States would have prevented Hwang’s potential transgressions in oocyte procurement for somatic cell nuclear transfer, we compare the general aspects and oversight framework of the Bioethics and Biosafety Act in South Korea and the US National Academies’ Guidelines for Human Embryonic Stem Cell Research, and apply the relevant provisions and recommendations to each transgression. We conclude that the Act would institute centralized oversight under governmental auspices while the Guidelines recommend politically-independent, decentralized oversight bodies including a special review body for human embryonic stem cell research at an institutional level and that the Guidelines would have provided more vigorous protection for the women who had undergone oocyte procurement for Hwang’s research than the Act. We also suggest additional regulations to protect those who provide oocytes for research in South Korea.     

Determining risk in pediatric research with no prospect of direct benefit: time for a national consensus on the interpretation of federal regulations

United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" ( section sign 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition ( section sign 45CFR46.406) (DHHS 2001). During the 25 years since their adoption, these regulations have helped IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations section sign section sign 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria.     

IRB and Research Regulatory Delays Within the Military Health System: Do They Really Matter? And If So,Why and for Whom?

Institutional review board (IRB) delays may hinder the successful completion of federally funded research in the U.S. military. When this happens, time-sensitive, mission-relevant questions go unanswered. Research participants face unnecessary burdens and risks if delays squeeze recruitment timelines, resulting in inadequate sample sizes for definitive analyses. More broadly, military members are exposed to untested or undertested interventions, implemented by well-intentioned leaders who bypass the research process altogether. To illustrate, we offer two case examples. We posit that IRB delays often appear in the service of managing institutional risk, rather than protecting research participants. Regulators may see more risk associated with moving quickly than risk related to delay, choosing to err on the side of bureaucracy. The authors of this article, all of whom are military-funded researchers, government stakeholders, and/or human subject protection experts, offer feasible recommendations to improve the IRB system and, ultimately, research within military, veteran, and civilian populations.     

The Interface Between the Practice of Medical Genetics and Human Genetic Research: What Every Genetic Counselor Needs to Know

Genetic counselors have historically used human genetic research as an advanced information resource for their patients. Most commonly, this has been via access to information provided by gene identification studies in advance of commercial testing. More recently genetic counselors have been participating in human genetic research studies as part of the investigative team. This review provides a framework to help genetic counselors in research and clinical practice understand the historical perspectives, ethical principles, and federal regulations that govern the current practice of human subject research. Special consideration is given to the IRB process and unique issues in human genetic research. This overview is intended to help improve the ability of genetic counselors to act as advocates for their patients.     

The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.     

A commentary on Dr. Kennedy's perception of the impact of Institutional Review Boards on cancer research

The Institutional Review Board is a committee of the institution responsible for carrying out the institution's responsibilities for the protection of human research subjects. Since it is a local committee, most of the complaints about the IRB can be resolved locally provided it is borne in mind that the IRB is the champion not only of the human research subject but also of the investigator. National or regional cooperative research protocols present problems that are not insurmountable.     

Utilitarianism and the Ethics of Professional Psychologists

Evidence exists that behavioral and social science researchers have been frustrated with regulations and institutional review boards (IRBs) from the 1970s through today. Making matters worse, many human participants protection instruction programs—now mandated by IRBs—offer inadequate reasons why researchers should comply with regulations and IRBs. Promoting compliance either for its own sake or to avoid penalties is contrary to the developmental aims of moral education and may be ineffective in fostering the responsible conduct of research. This article explores the concept of professional virtue and argues that compliance is capable of becoming a professional virtue like scientific honesty. This requires, however, that regulatory and IRB demands contribute to human well-being and to the aims of research as a profession and that researchers, therefore, internalize the norms that underlie regulatory and IRB demands. This, in turn, requires a series of changes in the way society develops, promulgates, and enforces regulatory and IRB rules. The challenge is, simply put, to embed compliance into the world of living morality.     

Human and Animal Subjects of Research: The Moral Significance of Respect versus Welfare

Human beings with diminished decision-making capacities are usually thought to require greater protections from the potential harms of research than fully autonomous persons. Animal subjects of research receive lesser protections than any human beings regardless of decision-making capacity. Paradoxically, however, it is precisely animals’ lack of some characteristic human capacities that is commonly invoked to justify using them for human purposes. In other words, for humans lesser capacities correspond to greater protections but for animals the opposite is true. Without explicit justification, it is not clear why or whether this should be the case. Ethics regulations guiding human subject research include principles such as respect for persons—and related duties—that are required as a matter of justice while regulations guiding animal subject research attend only to highly circumscribed considerations of welfare. Further, the regulations guiding research on animals discount any consideration of animal welfare relative to comparable human welfare. This paper explores two of the most promising justifications for these differences␣between the two sets of regulations. The first potential justification points to lesser moral status for animals on the basis of their lesser capacities. The second potential justification relies on a claim about the permissibility of moral partiality as␣found in common morality. While neither potential justification is sufficient to justify the regulatory difference as it stands, there is possible common ground between supporters of some regulatory difference and those rejecting the current difference.     

Is compliance a professional virtue of researchers? Reflections on promoting the responsible conduct of research

Evidence exists that behavioral and social science researchers have been frustrated with regulations and institutional review boards (IRBs) from the 1970s through today. Making matters worse, many human participants protection instruction programs--now mandated by IRBs--offer inadequate reasons why researchers should comply with regulations and IRBs. Promoting compliance either for its own sake or to avoid penalties is contrary to the developmental aims of moral education and may be ineffective in fostering the responsible conduct of research. This article explores the concept of professional virtue and argues that compliance is capable of becoming a professional virtue like scientific honesty. This requires, however, that regulatory and IRB demands contribute to human well-being and to the aims of research as a profession and that researchers, therefore, internalize the norms that underlie regulatory and IRB demands. This, in turn, requires a series of changes in the way society develops, promulgates, and enforces regulatory and IRB rules. The challenge is, simply put, to embed compliance into the world of living morality.